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Paroxysmal kinesigenic choreoathetosis	Paroxysmal kinesigenic choreoathetosis (PKC) also called paroxysmal kinesigenic dyskinesia (PKD) is a hyperkinetic movement disorder characterized by attacks of involuntary movements, which are triggered by sudden voluntary movements. The number of attacks can increase during puberty and decrease in a persons 20s to 30s. Involuntary movements can take many forms such as ballism, chorea or dystonia and usually only affect one side of the body or one limb in particular. This rare disorder only affects about 1 in 150,000 people, with PKD accounting for 86.8% of all the types of paroxysmal dyskinesias, and occurs more often in males than females. There are two types of PKD, primary and secondary. Primary PKD can be further broken down into familial and sporadic. Familial PKD, which means the individual has a family history of the disorder, is more common, but sporadic cases are also seen. Secondary PKD can be caused by many other medical conditions such as multiple sclerosis (MS), stroke, pseudohypoparathyroidism, hypocalcemia, hypoglycemia, hyperglycemia, central nervous system trauma, or peripheral nervous system trauma. PKD has also been linked with infantile convulsions and choreoathetosis (ICCA) syndrome, in which patients have afebrile seizures during infancy (benign familial infantile epilepsy) and then develop paroxysmal choreoathetosis later in life. This phenomenon is actually quite common, with about 42% of individuals with PKD reporting a history of afebrile seizures as a child. Genetics Paroxysmal kinesigenic dyskinesias are often inherited in an autosomal dominant fashion and several genes have now been identified where mutations can cause this disease. The genes typically code for proteins known to be involved in synaptic transmission, ion channels or ion transporters. The first gene to be identified was the PRRT2 gene on chromosome 16, found in 2011 to be the cause of the disease in some patients. The mutations in this gene included a nonsense mutation identified in the genome of one family and an insertion mutation identified in the genome of another family. Researchers found PRRT2 mutations in 10 of 29 sporadic cases affected with PKD, thus suggests PRRT2 is the gene mutated in a subset of PKD and PKD is genetically heterogeneous. Later reports have identified the genes SCN8A, CHRNA4, and SLC16A2 as further causes of PKD. Pathophysiology The pathophysiology of PKD is not fully explained. A few mechanisms have been suggested thus far: GABA dysregulation Abnormal breakdown of dopamine in the basal ganglia Dysfunction of the substantia nigra A form of epilepsyMultiple methods are being used to study the potential brain abnormalities of individuals with PKD compared with “normal” individuals. These methods include SPECT studies, fMRI studies, and diffusion tensor imaging. The main problem with many of the studies concerned with the pathophysiology of the disorder is the small sample size. Because the studies normally only include about 7-10 patients with PKD, the results cannot be generalized to the entire population of patients. However, the studies do bring up possibilities for further study. SPECT studies In a study by Joo et al., the researchers performed interictal studies, meaning they scanned the patients brain between attacks to find an underlying abnormality, rather than ictal scans, which look at the abnormalities that present themselves during an attack. The researchers found interictally decreased cerebral blood flow in the posterior parts of the bilateral caudate nucleus. However, the literature does state that although this could be a cause of PKD, it could also be a result of PKD. Another SPECT study showed an increase in the cerebral blood flow in the left posterior thalamus in a PKD patient during an attack. The researchers also subtracted the ictal from the postictal scans, and saw increased blood flow in the thalamus. They ultimately suggested that hyperactive blood flow in this area could be causing the pathophysiology of PKD. This study, however, was only performed on one patient, and would need to be replicated many more times in order to be generalized to the population of PKD patients. Other SPECT studies have been cited showing hyperactivity in the basal ganglia. fMRI studies In a study by Zhou et al., the researchers performed fMRI studies on PKD patients, and analyzed the differences between the amplitude low frequency fluctuations (ALFF) of the patients. They found that the left postcentral gyrus and the bilateral putamen had increased ALFF in PKD patients. The researchers concluded that the hyperactivity in these regions suggested that there is a dysfunction in the basal ganglia-thalamo-cortical circuit in PKD. This circuit is part of the motor control circuit in the brain, making it a reasonable place for abnormality in a movement disorder, but again, researchers are still unsure of the role these differences they found play in the disease pathology. Diffusion tensor imaging Diffusion tensor imaging (DTI) displays physical alterations in the brain that may not be seen on regular MRI. In one study researchers found that some of the patients had abnormalities in their thalamus. However, this does not prove that all patients have abnormalities in their thalamus. Other cases are cited, including a patient who developed a similar paroxysmal dyskinesia after a thalamic infarction, implicating that an abnormality in the thalamus of individuals could contribute to PKD. It is not fully known, however, what role a thalamic abnormality plays in the disease pathophysiology. Diagnosis Paroxysmal kinesigenic dyskinesia is diagnosed using a strict set of guidelines. These criteria were studied and confirmed by Bruno et al. in a study of 121 individuals with PKD. The age at onset is between 1 and 20 years old. The attacks of involuntary movements last less than one minute and have a known trigger, usually a sudden voluntary movement. For example, if a PKD patient stands up or begins walking after being sedentary for a period of time, or a person goes from a walk to a run, it can trigger an attack. Persons with PKD do not lose consciousness during attacks and have a full memory of the entire attack. Lastly, people with the disorder have a good response to medication and are usually prescribed anticonvulsants. The study also found that patients with familial PKD exhibit symptoms that follow the diagnostic criteria closely, while sporadic PKD individuals may deviate slightly. Prior to criteria for diagnosis being set out, many patients with PKD were often diagnosed with some form of epilepsy. Many patients also experience an aura, similar to those experienced with epilepsy, preceding their attacks. Some patients describe it as a tingling sensation in the affected limb or “butterflies in their stomach.” Some individuals also have precipitants, such as stress and anxiety, that make it more likely for attacks to occur. The above diagnostic criteria also set PKD apart from the other paroxysmal dyskinesias, which include paroxysmal nonkinesigenic dyskinesia (PNKD) and paroxysmal exercise-induced dyskinesia (PED). While PKD attacks last less than one minute, PNKD attacks last a few minutes to a few hours, and as the name suggests, the attacks do not occur because of a sudden voluntary movement like PKD. Additionally, PKD can almost always be managed with drug therapy, while PNKD is not as responsive to anticonvulsants. PED, on the other hand, separates itself from PKD in that it is caused by prolonged exercise. Attacks from PED will cease soon after exercise is stopped. Treatment Almost all patients respond positively to antiepileptic (anticonvulsant) drugs. One of the drugs most often mentioned in the literature is carbamazepine, and is the most widely used drug for treating PKD. Other anticonvulsants like valproic acid, phenytoin and clonazepam are common alternatives. Other categories of drugs have also been used, such as dopamine affecting drugs like Levodopa or Tetrabenazine. Individuals with the disorder can also modify their behavior to lessen their attacks without the influence of drug therapy. For example, decreasing stress to avoid precipitants can help patients decrease the number of attacks. In addition, avoiding any sudden movements can also prevent an attack. In order to prevent an attack, some individuals use their auras as a warning, while others purposefully perform slow gestures or movements prior to a triggering movement. Many, if not most, individuals end up growing out of the attacks with age, even without medicinal therapy, but some patients will go back to having attacks after a period of remission. In regards to secondary PKD, treatment of the primary condition can lessen the PKD attacks in those individuals. History A movement disorder similar to PKD was first mentioned in research literature in 1940 by Mount and Reback. They described a disorder consisting of attacks of involuntary movements but unlike PKD, the attacks lasted minutes to hours and were found to be caused by alcohol or caffeine intake. They named it paroxysmal dystonic choreoathetosis. Kertesz later described another new movement disorder in 1967. He described a disorder that was induced by sudden movements, and responded to anticonvulsants, naming it paroxysmal kinesigenic choreoathetosis. Finally in a review in 1995 Demirkiran and Jankovic stated the disease should be called paroxysmal kinesigenic dyskinesia instead, pointing out that the attacks could manifest as any form of dyskinesia, not just choreoathetosis. See also Paroxysmal dyskinesia Paroxysmal nonkinesogenic dyskinesia Paroxysmal exercise-induced dystonia References External links GeneReviews/NIH/NCBI/UW entry on Familial Paroxysmal Kinesigenic Dyskinesia OMIM entries on Familial Paroxysmal Kinesigenic Dyskinesia
Grocers itch	Grocers itch is a cutaneous condition characterized by a pruritic dermatitis that occurs from coming into contact with mites such as Carpoglyphus passularum (a fruit mite) or Glycyphagus domesticus (a common house mite). Contact usually occurs when handling food with mites in it, such as figs, dates, prunes, grain, cheese, or other dried foods.: 454 See also Grain itch Gamasoidosis List of mites associated with cutaneous reactions == References ==
Saber shin	Saber shin is a malformation of the tibia. It presents as a sharp anterior bowing, or convexity, of the tibia. Causes Periosteal reaction along the shaft of the tibia. It can result from congenital syphilis, yaws, Pagets disease of bone, vitamin D deficiency or Weismann-Netter–Stuhl syndrome. It can be due to osteomalacia. Prognosis Etymology Saber refers to the tibias resemblance to the curve of a saber sword. See also Saddle nose List of cutaneous conditions Rickets References Bibliography Mosbys Medical, Nursing, & Allied Health Dictionary. Edition 5, 1998 p7B49.
Nipple adenoma	A nipple adenoma is a rare benign tumour of the breast. The condition may also be known as : Florid papillomatosis of the nipple Florid adenomatosis Subareolar duct papillomatosis Erosive adenomatosis Signs and symptoms Nipple adenomas may be felt as a lump under the nipple or areola. They may come to attention because of nipple pain, ulceration, swelling or discharge. Diagnosis Definition A nipple adenoma is a type of intraductal papilloma that arises within the lactiferous ducts that are located within the nipple. Differential diagnosis The microscopic appearance of a nipple adenoma can be mistaken for carcinoma. Other conditions that have similar symptoms and signs as nipple adenoma include Pagets disease of the breast, other intraductal papillomas, ductal carcinoma in situ (DCIS), syringomatous adenoma of the nipple and subareolar sclerosing duct hyperplasia. Imaging Lesions of the nipple and areola, such as nipple adenoma, may be difficult to image clearly on routine mammogram or ultrasonography. Nipple adenomas can be imaged using magnetic resonance imaging (MRI) and conventional or MR ductogram. Biopsy Once excised, the macroscopic appearance of nipple adenomas is of a poorly defined nodular mass. The microscopic appearance can be quite bizarre, and may be misinterpreted as a carcinoma. Nipple adenomas usually have a rounded outline at low magnification, and at higher magnification can be seen to consist of a haphazardly arranged mass of proliferating tubular structures composed of epithelial and myoepithelial cells within varying amounts of fibrous stroma. The epithelial cells are usually columnar, but the columnar epithelial cells can undergo apocrine or squamous metaplasia. Mitotic figures and necrosis are not commonly seen. Treatment The appropriate treatment in contemporary western medicine is complete surgical excision of the abnormal growth with a small amount of normal surrounding breast tissue. Prognosis Nipple adenomas are non-cancerous growths, which can recur if not completely surgically removed. There are reported cases of cancers arising within nipple adenomas, and following excision of nipple adenomas, but these are rare occurrences. Epidemiology Nipple adenomas most commonly occur in 30- to 40-year-old women, but can also occur in men. They can also occur at any age, including in the elderly, in adolescence, and in infants. References == External links ==
Argininemia	Argininemia is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high; the nervous system is especially sensitive to the effects of excess ammonia. Signs and symptoms The presentation of argininemia, in those that are affected, is consistent with the following: Genetics Mutations in the ARG1 gene cause argininemia, which belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells (hepatocytes). This cycle processes excess nitrogen, generated when protein is used by the body, making urea that is excreted via the kidneys.The ARG1 gene provides instructions for making an enzyme called arginase, this enzyme controls the last steps of the urea cycle, which produces urea by extracting nitrogen from arginine. In people with arginase deficiency, arginase is missing, and arginine is not broken down properly. consequently, urea cannot be produced and excess nitrogen accumulates in the blood in the form of ammonia. Ammonia and arginine are thought to cause neurological problems and other symptoms of arginase deficiency.This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene are required to inherit the disorder. Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder. Diagnosis The diagnosis for argininemia can usually be done using fetal blood sample. One can look for the following indicators as to the presence of the condition: Plasma ammonia concentration. Urinary orotic acid concentration Red blood cell arginase enzyme activity (measurement) Treatment The treatment for infants (individuals) with argininemia is the following, including medications: References Further reading (editors), Jean-Marie Saudubray, Georges van den Berghe, John H. Walter; Berghe, Georges van den; Walter, John H. (2012). Inborn metabolic diseases diagnosis and treatment (5th ed.). Berlin: Springer. ISBN 9783642157202. Retrieved 28 November 2016. {{cite book}}: \|last1= has generic name (help) Piña-Garza, J. Eric (2013). Fenichels Clinical pediatric neurology a signs and symptoms approach (7th ed.). Oxford: Saunders. ISBN 978-1455748129. Retrieved 28 November 2016. == External links ==
Osteosclerosis	Osteosclerosis is a disorder that is characterized by abnormal hardening of bone and an elevation in bone density. It may predominantly affect the medullary portion and/or cortex of bone. Plain radiographs are a valuable tool for detecting and classifying osteosclerotic disorders. It can manifest in localized or generalized osteosclerosis. Localized osteosclerosis can be caused by Legg–Calvé–Perthes disease, sickle-cell disease and osteoarthritis among others. Osteosclerosis can be classified in accordance with the causative factor into acquired and hereditary. Types Acquired osteosclerosis Osteogenic bone metastasis caused by carcinoma of prostate and breast Pagets disease of bone Myelofibrosis (primary disorder or secondary to intoxication or malignancy) Osteosclerosing types of chronic osteomyelitis Hypervitaminosis D hyperparathyroidism Schnitzler syndrome MastocytosisSkeletal fluorosis Monoclonal IgM Kappa cryoglobulinemia Hepatitis C. Hereditary osteosclerosis Malignant infantile osteopetrosis Neuropathic infantile osteopetrosis Infantile osteopetrosis with renal tubular acidosis Infantile osteopetrosis with immunodeficiency IO with leukocyte adhesion deficiency syndrome (LAD-III) Intermediate osteopetrosis Autosomal dominant osteopetrosis (Albers-Schonberg) Pyknodysostosis (osteopetrosis acro-osteolytica) Osteopoikilosis (Buschke–Ollendorff syndrome) Osteopathia striata with cranial sclerosis Mixed sclerosing bone dysplasia Progressive diaphyseal dysplasia (Camurati–Engelmann disease) SOST-related sclerosing bone dysplasias Diagnosis Osteosclerosis can be detected with a simple radiography. There are white portions of the bone which appear due to the increased number of bone trabeculae. Animals In the animal kingdom, there also exists a non-pathological form of osteosclerosis, resulting in unusually solid bone structure with little to no marrow. It is often seen in aquatic vertebrates, especially those living in shallow waters, providing ballast as an adaptation for an aquatic lifestyle. It makes bones heavier, but also more fragile. In those animal groups, osteosclerosis often occurs together with bone thickening (pachyostosis). This joint occurrence is called pachyosteosclerosis. See also Pachyostosis Pachyosteosclerosis Heinrich Albers-Schönberg References == External links ==
Cryptococcosis	Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and brain, where it appears as a meningitis. Cough, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity and confusion or changes in behaviour. It can also affect other parts of the body including skin, where it may appear as several fluid-filled nodules with dead tissue.It is caused by the fungi Cryptococcus neoformans or less commonly Cryptococcus gattii, and is acquired by breathing in the spores from the air. These fungi are found around the world in soil, decaying wood, pigeon droppings, and in the hollows of some species of trees. Whereas C. neoformans infects generally people with HIV/AIDS and those on immunosuppressant drugs and does not usually affect fit and healthy people, C. gattii (found in some parts of Canada and the US) does. Once breathed in, the dried yeast cells colonize the lungs, where they are either cleared by immune cells, lie dormant, or cause infection and spread.Diagnosis is by isolating Cryptococcus from a sample of affected tissue or direct observation of the fungus by using staining of body fluids. It can be cultured from a cerebrospinal fluid, sputum, and skin biopsy. Treatment is with fluconazole or amphotericin B.Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died. Cryptococcosis was rare before the 1970s which saw an increase in at-risk groups such as people with organ transplant or on immunosuppressant medications. The number of cases escalated in the mid-1980s with over 80% occurring in people with HIV/AIDS. Pigeon breeders (or fanciers) are known to have a high incidence of cryptococcal infections including PCC due to Cryptococcus association with pigeon droppings. Classification Cryptococcus is generally classified according to how it is acquired and its site. It typically begins in the lungs before spreading to other parts of the body, particularly the brain and nervous system. The skin type is less common. Signs and symptoms Cough, shortness of breath, chest pain and fever are seen when the lungs are infected, appearing like a pneumonia. There may also be feeling of tiredness. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity, confusion or changes in behaviour. It can also affect other parts of the body including skin, eyes, bones and prostate. In the skin, it may appear as several fluid-filled nodules with dead tissue. Depending on the site of infection, other features may include loss of vision, blurred vision, inability to move an eye and memory loss.Symptom onset is often sudden when lungs are infected and gradual over several weeks when the central nervous system is affected. Cause Cryptococcosis is a common opportunistic infection for AIDS, and is particularly common among people living with AIDS in Africa. Other conditions that pose an increased risk include certain malignancies (such as lymphoma), liver cirrhosis, organ transplants, and long-term corticosteroid therapy.Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 50 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.In humans, C. neoformans chiefly infects the skin, lungs, and central nervous system (causing meningitis). Less commonly it may affect other organs such as the eye or prostate. Primary Cutaneous Cryptococcosis Primary Cutaneous Cryptococcosis (PCC) is a distinct clinical diagnosis separate from the secondary cutaneous cryptococcosis that is spread from systematic infection. Males are more likely to develop the infection and a 2020 study showed that the sex bias may be due to a growth hormone, produced by C. neoformans called gibberellic acid (GA) that is upregulated by testosterone. The upper limbs account for a majority of infections. Isolates found in PCC include Cryptococcus neoformans (most common), Cryptococcus gattii, and Cryptococcus laurentii. Prognosis for PCC is generally good outside of disseminated infection.Morphologic description of the lesions show umbilicated papules, nodules, and violaceous plaques that can mimic other cutaneous diseases like molluscum contagiosum and Kaposis sarcoma. These lesions may be present months before other signs of system infection in patients with AIDS. Pulmonary Cryptococcosis Cryptococcus (both C. neoformans and C. gattii) plays a common role in pulmonary invasive mycosis seen in adults with HIV and other immunocompromised conditions. It also affects healthy adults at a much lower frequency and severity as healthy hosts may have no or mild symptoms. Immune-competent hosts may not seek or require treatment, but careful observation may be important. Cryptococcal pneumonia has a potential to disseminate to the central nervous system (CNS) especially in immunocompromised individuals.Pulmonary cryptococcosis has a worldwide distribution and is commonly underdiagnosed due to limitations in diagnostic capabilities. Since pulmonary nodules are its most common radiological feature, it can clinically and radiologically mimic lung cancer, TB, and other pulmonary mycoses. The sensitivity of cultures and the Cryptococcal (CrAg) antigen with lateral flow device on serum are rarely positive in the absence of disseminated disease. Moreover, pulmonary cryptococcosis worsen the prognosis of cryptococcal meningitis. Cryptococcal meningitis Cryptococcal meningitis (infection of the meninges, the tissue covering the brain) is believed to result from dissemination of the fungus from either an observed or unappreciated pulmonary infection. Often there is also silent dissemination throughout the brain when meningitis is present. People with defects in their cell-mediated immunity, for example, people with AIDS, are especially susceptible to disseminated cryptococcosis. Cryptococcosis is often fatal, even if treated. It is estimated that the three-month case-fatality rate is 9% in high-income regions, 55% in low/middle-income regions, and 70% in sub-Saharan Africa. As of 2009 there were globally approximately 958,000 annual cases and 625,000 deaths within three months after infection.Although C. neoformans infection most commonly occurs as an opportunistic infection in immunocompromised people (such as those living with AIDS), C. gattii often infects immunocompetent people as well.Cryptococcus (both C. neoformans and C. gattii) is the dominant and leading etiologic agent of meningitis in adults with HIV and is considered an "emerging" disease in healthy adults. Though the rate of infection is clearly higher with immunocompromised individuals, some studies suggest a higher mortality rate in patients with non-HIV cryptococcal meningitis secondary to the role of T-cell mediated reaction and injury. CD4+ T cells have proven roles in the defense against Cryptococcus, but it can also contribute to clinical deterioration due its inflammatory response. Diagnosis Dependent on the infectious syndrome, symptoms include fever, fatigue, dry cough, headache, blurred vision, and confusion. Symptom onset is often subacute, progressively worsened over several weeks. The two most common presentations are meningitis (an infection in and around the brain) and pulmonary (lung) infection.Any person who is found to have cryptococcosis at a site outside of the central nervous system (e.g., pulmonary cryptococcosis), a lumbar puncture is indicated to evaluate the cerebrospinal fluid (CSF) for evidence of cryptococcal meningitis, even if they do not have signs or symptoms of CNS disease. Detection of cryptococcal antigen (capsular material) by culture of CSF, sputum and urine provides definitive diagnosis. Blood cultures may be positive in heavy infections. India ink of the CSF is a traditional microscopic method of diagnosis, although the sensitivity is poor in early infection, and may miss 15–20% of patients with culture-positive cryptococcal meningitis. Unusual morphological forms are rarely seen. Cryptococcal antigen from cerebrospinal fluid is the best test for diagnosis of cryptococcal meningitis in terms of sensitivity. Apart from conventional methods of detection like direct microscopy and culture, rapid diagnostic methods to detect cryptococcal antigen by latex agglutination test, lateral flow immunochromatographic assay (LFA), or enzyme immunoassay (EIA). A new cryptococcal antigen LFA was FDA approved in July 2011. Polymerase chain reaction (PCR) has been used on tissue specimens. Cryptococcosis can rarely occur in the non-immunosuppressed people, particularly with Cryptococcus gattii. Prevention Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL. Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.Antifungal prophylaxis such as fluconazole and itraconazole reduces the risk of contracting cryptococcosis in those with low CD4 cell count and high risk of developing such disease in a setting of cryptococcal antigen screening tests are not available. Treatment Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended for initial treatment (induction therapy).People living with AIDS often have a greater burden of disease and higher mortality (30–70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin. Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks. Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole. After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A 2018 Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment. IRIS The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by C. gattii and C. grubii. The increasing inflammation can cause brain injury or be fatal. Epidemiology Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died. Other animals Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLV infection in cats. Cryptococcosis is most common in dogs and cats but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and pigeon droppings are among the sources of infection. References Further reading Perfect JR, et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases. 50 (3): 291–322. doi:10.1086/649858. PMC 5826644. PMID 20047480. Gullo FP, et al. (2013). "Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment". European Journal of Clinical Microbiology & Infectious Diseases. 32 (11): 1377–1391. doi:10.1007/s10096-013-1915-8. PMID 24141976. S2CID 11317427. Perfect JR, et al. (2005). "Cryptococcus neoformans: a sugar-coated killer with designer genes". FEMS Immunology and Medical Microbiology. 45 (11): 395–404. doi:10.1016/j.femsim.2005.06.005. PMID 16055314. (Review) External links Medscape entry on cryptococcosis
Disseminated coccidioidomycosis	Disseminated coccidioidomycosis is a systemic infection with Coccidioides immitis, in which 15-20% of people develop skin lesions.: 315 See also Coccidioidomycosis List of cutaneous conditions == References ==
Dementia	Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affects a persons ability to function and carry out everyday activities. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Consciousness is not affected. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a persons usual mental functioning, and a greater cognitive decline than what is caused by normal aging. Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, the most common cause is Alzheimers disease, a neurodegenerative disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), has re-described dementia as a major neurocognitive disorder with varying degrees of severity and many causative subtypes. The International Classification of Diseases (ICD-11) also classes dementia as a neurocognitive disorder with many forms or subclasses. Dementia is listed as an acquired brain syndrome, marked by a decline in cognitive function, and is contrasted with neurodevelopmental disorders. Causative subtypes of dementia may be based on a known disorder, such as Parkinsons disease, for Parkinsons disease dementia; Huntingtons disease, for Huntingtons disease dementia; vascular disease, for vascular dementia – as vascular brain injury, including stroke, often results in vascular dementia; or many other medical conditions, including HIV infection, causing HIV dementia; and prion diseases. Subtypes may be based on various symptoms, possibly due to a neurodegenerative disorder: frontotemporal lobar degeneration for frontotemporal dementia, or Lewy body disease for dementia with Lewy bodies. More than one type of dementia, known as mixed dementia, may exist together. Diagnosis is usually based on history of the illness and cognitive testing with imaging. Blood tests may be taken to rule out other possible causes that may be reversible, such as an underactive thyroid, and to determine the subtype. One commonly used cognitive test is the Mini–Mental State Examination. The greatest risk factor for developing dementia is aging, however dementia is not a normal part of aging. Several risk factors for dementia, such as smoking and obesity, are preventable by lifestyle changes. Screening the general older population for the disorder is not seen to affect the outcome.Dementia is currently the seventh leading cause of death worldwide, with 10 million cases reported every year. That is about one new case every 7 seconds a day. There is no known cure for dementia. Acetylcholinesterase inhibitors such as donepezil are often used and may be beneficial in mild to moderate disorder. The overall benefit, however, may be minor. There are many measures that can improve the quality of life of people with dementia and their caregivers. Cognitive and behavioral interventions may be appropriate for treating associated symptoms of depression. Signs and symptoms The signs and symptoms of dementia are termed as the neuropsychiatric symptoms, also known as the behavioral and psychological symptoms of dementia. Behavioral symptoms can include agitation, restlessness, inappropriate behavior, sexual disinhibition, and aggression, which can be verbal or physical. These symptoms may result from impairments in cognitive inhibition. Psychological symptoms can include depression, psychotic hallucinations and delusions, apathy, and anxiety. The most commonly affected areas include memory, visuospatial function affecting perception and orientation, language, attention and problem solving. The rate at which symptoms progress occurs on a continuum over several stages, and they vary across the dementia subtypes. Most types of dementia are slowly progressive with some deterioration of the brain well established before signs of the disorder become apparent. Often there are other conditions present such as high blood pressure, or diabetes, and there can sometimes be as many as four of these comorbidities.People with dementia are also more likely to have problems with incontinence: they are three times more likely to have urinary and four times more likely to have fecal incontinence compared to people of similar ages.Dementia symptoms can vary widely from person to person. It affects memory, attention span, communication, reasoning, judgement, problem solving and visual perception, etc. Signs that may point to dementia include getting lost in a familiar neighborhood, using unusual words to refer to familiar objects, forgetting the name of a close family member or friend, forgetting old memories, not being able to complete tasks independently, etc. Stages The course of dementia is often described in four stages that show a pattern of progressive cognitive and functional impairment. However, the use of numeric scales allows for more detailed descriptions. These scales include the Global Deterioration Scale for Assessment of Primary Degenerative Dementia (GDS or Reisberg Scale), the Functional Assessment Staging Test (FAST), and the Clinical Dementia Rating (CDR). Using the GDS, which more accurately identifies each stage of the disease progression, a more detailed course is described in seven stages – two of which are broken down further into five and six degrees. Stage 7(f) is the final stage. Pre-dementia Pre-dementia states include pre-clinical and prodromal stages. The prodromal stages includes (1) mild cognitive impairment (MCI), (2) delirium-onset, and psychiatric-onset presentations. Pre-clinical Sensory dysfunction is claimed for this stage which may precede the first clinical signs of dementia by up to ten years. Most notably the sense of smell is lost. The loss of the sense of smell is associated with depression and loss of appetite leading to poor nutrition. It is suggested that this dysfunction may come about because the olfactory epithelium is exposed to the environment. The lack of blood–brain barrier protection here means that toxic elements can enter and cause damage to the chemosensory networks. Prodromal Pre-dementia states considered as prodromal are mild cognitive impairment (MCI), and mild behavioral impairment (MBI).Kynurenine is a metabolite of tryptophan that regulates microbiome signalling, immune cell response, and neuronal excitation. A disruption in the kynurenine pathway may be associated with the neuropsychiatric symptoms and cognitive prognosis in mild dementia.In this stage signs and symptoms may be subtle. Often, the early signs become apparent when looking back. 70% of those diagnosed with MCI later progress to dementia. In MCI, changes in the persons brain have been happening for a long time, but symptoms are just beginning to appear. These problems, however, are not severe enough to affect daily function. If and when they do, the diagnosis becomes dementia. They may have some memory trouble and trouble finding words, but they solve everyday problems and competently handle their life affairs.Mild cognitive impairment has been relisted in both DSM-5, and ICD-11, as mild neurocognitive disorders – milder forms of the major neurocognitive disorder (dementia) subtypes. Early In the early stage of dementia, symptoms become noticeable to other people. In addition, the symptoms begin to interfere with daily activities, and will register a score on a Mini–Mental State Examination (MMSE). MMSE scores are set at 24 to 30 for a normal cognitive rating and lower scores reflect severity of symptoms. The symptoms are dependent on the type of dementia. More complicated chores and tasks around the house or at work become more difficult. The person can usually still take care of themselves but may forget things like taking pills or doing laundry and may need prompting or reminders.The symptoms of early dementia usually include memory difficulty, but can also include some word-finding problems, and problems with executive functions of planning and organization. Managing finances may prove difficult. Other signs might be getting lost in new places, repeating things, and personality changes.In some types of dementia, such as dementia with Lewy bodies and frontotemporal dementia, personality changes and difficulty with organization and planning may be the first signs. Middle As dementia progresses, initial symptoms generally worsen. The rate of decline is different for each person. MMSE scores between 6–17 signal moderate dementia. For example, people with moderate Alzheimers dementia lose almost all new information. People with dementia may be severely impaired in solving problems, and their social judgment is usually also impaired. They cannot usually function outside their own home, and generally should not be left alone. They may be able to do simple chores around the house but not much else, and begin to require assistance for personal care and hygiene beyond simple reminders. A lack of insight into having the condition will become evident. Late People with late-stage dementia typically turn increasingly inward and need assistance with most or all of their personal care. Persons with dementia in the late stages usually need 24-hour supervision to ensure their personal safety, and meeting of basic needs. If left unsupervised, they may wander or fall; may not recognize common dangers such as a hot stove; or may not realize that they need to use the bathroom and become incontinent. They may not want to get out of bed, or may need assistance doing so. Commonly, the person no longer recognizes familiar faces. They may have significant changes in sleeping habits or have trouble sleeping at all.Changes in eating frequently occur. Cognitive awareness is needed for eating and swallowing and progressive cognitive decline results in eating and swallowing difficulties. This can cause food to be refused, or choked on, and help with feeding will often be required. For ease of feeding, food may be liquidized into a thick purée. They may also struggle to walk, particularly among those with Alzheimers disease. Subtypes Many of the subtypes of dementia are neurodegenerative, and protein toxicity is a cardinal feature of these. Alzheimers disease Alzheimers disease accounts for 60–70% of cases of dementia worldwide. The most common symptoms of Alzheimers disease are short-term memory loss and word-finding difficulties. Trouble with visuospatial functioning (getting lost often), reasoning, judgment and insight fail. Insight refers to whether or not the person realizes they have memory problems. The part of the brain most affected by Alzheimers is the hippocampus. Other parts that show atrophy (shrinking) include the temporal and parietal lobes. Although this pattern of brain shrinkage suggests Alzheimers, it is variable and a brain scan is insufficient for a diagnosis. The relationship between general anesthesia and Alzheimers in elderly people is unclear.Little is known about the events that occur during and that actually cause Alzheimers disease. This is due to the fact that brain tissue from patients with the disease can only be studied after the persons death. However, it is known that one of the first aspects of the disease is a dysfunction in the gene that produces amyloid. Extracellular senile plaques (SPs), consisting of beta-amyloid (Aβ) peptides, and intracellular neurofibrillary tangles (NFTs) that are formed by hyperphosphorylated tau proteins, are two well-established pathological hallmarks of AD. Amyloid causes inflammation around the senile plaques of the brain, and too much build up of this inflammation leads to changes in the brain that cannot be controlled, leading to the symptoms of Alzheimers. Vascular Vascular dementia accounts for at least 20% of dementia cases, making it the second most common type. It is caused by disease or injury affecting the blood supply to the brain, typically involving a series of mini-strokes. The symptoms of this dementia depend on where in the brain the strokes occurred and whether the blood vessels affected were large or small. Multiple injuries can cause progressive dementia over time, while a single injury located in an area critical for cognition such as the hippocampus, or thalamus, can lead to sudden cognitive decline. Elements of vascular dementia may be present in all other forms of dementia.Brain scans may show evidence of multiple strokes of different sizes in various locations. People with vascular dementia tend to have risk factors for disease of the blood vessels, such as tobacco use, high blood pressure, atrial fibrillation, high cholesterol, diabetes, or other signs of vascular disease such as a previous heart attack or angina. Lewy bodies The prodromal symptoms of dementia with Lewy bodies (DLB) include mild cognitive impairment, and delirium onset. The symptoms of DLB are more frequent, more severe, and earlier presenting than in the other dementia subtypes. Dementia with Lewy bodies has the primary symptoms of fluctuating cognition, alertness or attention; REM sleep behavior disorder (RBD); one or more of the main features of parkinsonism, not due to medication or stroke; and repeated visual hallucinations. The visual hallucinations in DLB are generally vivid hallucinations of people or animals and they often occur when someone is about to fall asleep or wake up. Other prominent symptoms include problems with planning (executive function) and difficulty with visual-spatial function, and disruption in autonomic bodily functions. Abnormal sleep behaviors may begin before cognitive decline is observed and are a core feature of DLB. RBD is diagnosed either by sleep study recording or, when sleep studies cannot be performed, by medical history and validated questionnaires. Parkinsons disease Parkinsons disease is a Lewy body disease that often progresses to Parkinsons disease dementia following a period of dementia-free Parkinsons disease. Frontotemporal Frontotemporal dementias (FTDs) are characterized by drastic personality changes and language difficulties. In all FTDs, the person has a relatively early social withdrawal and early lack of insight. Memory problems are not a main feature. There are six main types of FTD. The first has major symptoms in personality and behavior. This is called behavioral variant FTD (bv-FTD) and is the most common. The hallmark feature of bv-FTD is impulsive behavior, and this can be detected in pre-dementia states. In bv-FTD, the person shows a change in personal hygiene, becomes rigid in their thinking, and rarely acknowledges problems; they are socially withdrawn, and often have a drastic increase in appetite. They may become socially inappropriate. For example, they may make inappropriate sexual comments, or may begin using pornography openly. One of the most common signs is apathy, or not caring about anything. Apathy, however, is a common symptom in many dementias.Two types of FTD feature aphasia (language problems) as the main symptom. One type is called semantic variant primary progressive aphasia (SV-PPA). The main feature of this is the loss of the meaning of words. It may begin with difficulty naming things. The person eventually may lose the meaning of objects as well. For example, a drawing of a bird, dog, and an airplane in someone with FTD may all appear almost the same. In a classic test for this, a patient is shown a picture of a pyramid and below it a picture of both a palm tree and a pine tree. The person is asked to say which one goes best with the pyramid. In SV-PPA the person cannot answer that question. The other type is called non-fluent agrammatic variant primary progressive aphasia (NFA-PPA). This is mainly a problem with producing speech. They have trouble finding the right words, but mostly they have a difficulty coordinating the muscles they need to speak. Eventually, someone with NFA-PPA only uses one-syllable words or may become totally mute. A frontotemporal dementia associated with amyotrophic lateral sclerosis (ALS) known as (FTD-ALS) includes the symptoms of FTD (behavior, language and movement problems) co-occurring with amyotrophic lateral sclerosis (loss of motor neurons). Two FTD-related disorders are progressive supranuclear palsy (also classed as a Parkinson-plus syndrome), and corticobasal degeneration. These disorders are tau-associated. Huntingtons disease Huntingtons disease is a neurodegenerative disease caused by mutations in a single gene HTT, that encodes for huntingtin protein. Symptoms include cognitive impairment and this usually declines further into dementia.The first main symptoms of Huntingtons disease often include: difficulty concentrating memory lapses depression - this can include low mood, lack of interest in things, or just abnormal feelings of hopelessness stumbling and clumsiness that is out of the ordinary mood swings, such as irritability or aggressive behavior to insignificant things HIV HIV-associated dementia results as a late stage from HIV infection, and mostly affects younger people. The essential features of HIV-associated dementia are disabling cognitive impairment accompanied by motor dysfunction, speech problems and behavioral change. Cognitive impairment is characterised by mental slowness, trouble with memory and poor concentration. Motor symptoms include a loss of fine motor control leading to clumsiness, poor balance and tremors. Behavioral changes may include apathy, lethargy and diminished emotional responses and spontaneity. Histopathologically, it is identified by the infiltration of monocytes and macrophages into the central nervous system (CNS), gliosis, pallor of myelin sheaths, abnormalities of dendritic processes and neuronal loss. Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease is a rapidly progressive prion disease that typically causes dementia that worsens over weeks to months. Prions are disease-causing pathogens created from abnormal proteins. Alcoholism Alcohol-related dementia, also called alcohol-related brain damage, occurs as a result of excessive use of alcohol particularly as a substance abuse disorder. Different factors can be involved in this development including thiamine deficiency and age vulnerability. A degree of brain damage is seen in more than 70% of those with alcohol use disorder. Brain regions affected are similar to those that are affected by aging, and also by Alzheimers disease. Regions showing loss of volume include the frontal, temporal, and parietal lobes, as well as the cerebellum, thalamus, and hippocampus. This loss can be more notable, with greater cognitive impairments seen in those aged 65 years and older. Mixed dementia More than one type of dementia, known as mixed dementia, may exist together in about 10% of dementia cases. The most common type of mixed dementia is Alzheimers disease and vascular dementia. This particular type of mixed dementias main onsets are a mixture of old age, high blood pressure, and damage to blood vessels in the brain.Diagnosis of mixed dementia can be difficult, as often only one type will predominate. This makes the treatment of people with mixed dementia uncommon, with many people missing out on potentially helpful treatments. Mixed dementia can mean that symptoms onset earlier, and worsen more quickly since more parts of the brain will be affected.Genetics Although it is not very common to inherit dementia from a parent or grandparent, there are genetic linked causes of dementia. These are only a small overall portion of the overall cases of dementia, but it is possible. Other Chronic inflammatory conditions that may affect the brain and cognition include Behçets disease, multiple sclerosis, sarcoidosis, Sjögrens syndrome, lupus, celiac disease, and non-celiac gluten sensitivity. These types of dementias can rapidly progress, but usually have a good response to early treatment. This consists of immunomodulators or steroid administration, or in certain cases, the elimination of the causative agent. A 2019 review found no association between celiac disease and dementia overall but a potential association with vascular dementia. A 2018 review found a link between celiac disease or non-celiac gluten sensitivity and cognitive impairment and that celiac disease may be associated with Alzheimers disease, vascular dementia, and frontotemporal dementia. A strict gluten-free diet started early may protect against dementia associated with gluten-related disorders.Cases of easily reversible dementia include hypothyroidism, vitamin B12 deficiency, Lyme disease, and neurosyphilis. For Lyme disease and neurosyphilis, testing should be done if risk factors are present. Because risk factors are often difficult to determine, testing for neurosyphilis and Lyme disease, as well as other mentioned factors, may be undertaken as a matter of course where dementia is suspected.: 31–32 Many other medical and neurological conditions include dementia only late in the illness. For example, a proportion of patients with Parkinsons disease develop dementia, though widely varying figures are quoted for this proportion. When dementia occurs in Parkinsons disease, the underlying cause may be dementia with Lewy bodies or Alzheimers disease, or both. Cognitive impairment also occurs in the Parkinson-plus syndromes of progressive supranuclear palsy and corticobasal degeneration (and the same underlying pathology may cause the clinical syndromes of frontotemporal lobar degeneration). Although the acute porphyrias may cause episodes of confusion and psychiatric disturbance, dementia is a rare feature of these rare diseases. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a type of dementia that primarily affects people in their 80s or 90s and in which TDP-43 protein deposits in the limbic portion of the brain.Hereditary disorders that can also cause dementia include: some metabolic disorders, lysosomal storage disorders, leukodystrophies, and spinocerebellar ataxias. Diagnosis Symptoms are similar across dementia types and it is difficult to diagnose by symptoms alone. Diagnosis may be aided by brain scanning techniques. In many cases, the diagnosis requires a brain biopsy to become final, but this is rarely recommended (though it can be performed at autopsy). In those who are getting older, general screening for cognitive impairment using cognitive testing or early diagnosis of dementia has not been shown to improve outcomes. However, screening exams are useful in 65+ persons with memory complaints.Normally, symptoms must be present for at least six months to support a diagnosis. Cognitive dysfunction of shorter duration is called delirium. Delirium can be easily confused with dementia due to similar symptoms. Delirium is characterized by a sudden onset, fluctuating course, a short duration (often lasting from hours to weeks), and is primarily related to a somatic (or medical) disturbance. In comparison, dementia has typically a long, slow onset (except in the cases of a stroke or trauma), slow decline of mental functioning, as well as a longer trajectory (from months to years).Some mental illnesses, including depression and psychosis, may produce symptoms that must be differentiated from both delirium and dementia. These are differently diagnosed as pseudodementias, and any dementia evaluation needs to include a depression screening such as the Neuropsychiatric Inventory or the Geriatric Depression Scale. Physicians used to think that people with memory complaints had depression and not dementia (because they thought that those with dementia are generally unaware of their memory problems). However, researchers have realized that many older people with memory complaints in fact have mild cognitive impairment the earliest stage of dementia. Depression should always remain high on the list of possibilities, however, for an elderly person with memory trouble. Changes in thinking, hearing and vision are associated with normal ageing and can cause problems when diagnosing dementia due to the similarities. Given the challenging nature of predicting the onset of dementia and making a dementia diagnosis clinical decision making aids underpinned by machine learning and artificial intelligence have the potential to enhance clinical practice. Cognitive testing Various brief cognitive tests (5–15 minutes) have reasonable reliability to screen for dementia, but may be affected by factors such as age, education and ethnicity. While many tests have been studied, presently the mini mental state examination (MMSE) is the best studied and most commonly used. The MMSE is a useful tool for helping to diagnose dementia if the results are interpreted along with an assessment of a persons personality, their ability to perform activities of daily living, and their behaviour. Other cognitive tests include the abbreviated mental test score (AMTS), the, Modified Mini-Mental State Examination (3MS), the Cognitive Abilities Screening Instrument (CASI), the Trail-making test, and the clock drawing test. The MoCA (Montreal Cognitive Assessment) is a reliable screening test and is available online for free in 35 different languages. The MoCA has also been shown somewhat better at detecting mild cognitive impairment than the MMSE. The AD-8 – a screening questionnaire used to assess changes in function related to cognitive decline – is potentially useful, but is not diagnostic, is variable, and has risk of bias. An integrated cognitive assessment (CognICA) is a five-minute test that is highly sensitive to the early stages of dementia, and uses an application deliverable to an iPad. Previously in use in the UK, in 2021 CognICA was given FDA approval for its commercial use as a medical device.Another approach to screening for dementia is to ask an informant (relative or other supporter) to fill out a questionnaire about the persons everyday cognitive functioning. Informant questionnaires provide complementary information to brief cognitive tests. Probably the best known questionnaire of this sort is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Evidence is insufficient to determine how accurate the IQCODE is for diagnosing or predicting dementia. The Alzheimers Disease Caregiver Questionnaire is another tool. It is about 90% accurate for Alzheimers when by a caregiver. The General Practitioner Assessment Of Cognition combines both a patient assessment and an informant interview. It was specifically designed for use in the primary care setting. Clinical neuropsychologists provide diagnostic consultation following administration of a full battery of cognitive testing, often lasting several hours, to determine functional patterns of decline associated with varying types of dementia. Tests of memory, executive function, processing speed, attention and language skills are relevant, as well as tests of emotional and psychological adjustment. These tests assist with ruling out other etiologies and determining relative cognitive decline over time or from estimates of prior cognitive abilities. Laboratory tests Routine blood tests are usually performed to rule out treatable causes. These include tests for vitamin B12, folic acid, thyroid-stimulating hormone (TSH), C-reactive protein, full blood count, electrolytes, calcium, renal function, and liver enzymes. Abnormalities may suggest vitamin deficiency, infection, or other problems that commonly cause confusion or disorientation in the elderly. Imaging A CT scan or MRI scan is commonly performed to possibly find either normal pressure hydrocephalus, a potentially reversible cause of dementia, or connected tumor. The scans can also yield information relevant to other types of dementia, such as infarction (stroke) that would point at a vascular type of dementia. These tests do not pick up diffuse metabolic changes associated with dementia in a person who shows no gross neurological problems (such as paralysis or weakness) on a neurological exam.The functional neuroimaging modalities of SPECT and PET are more useful in assessing long-standing cognitive dysfunction, since they have shown similar ability to diagnose dementia as a clinical exam and cognitive testing. The ability of SPECT to differentiate vascular dementia from Alzheimers disease, appears superior to differentiation by clinical exam.The value of PiB-PET imaging using Pittsburgh compound B (PiB) as a radiotracer has been established in predictive diagnosis, particularly Alzheimers disease. Prevention Risk factors An influential review increased the number of associated risk factors for dementia from nine to twelve in 2020. The three newly added risks are over-indulgence in alcohol, traumatic brain injury, and air pollution. The other nine risk factors are: lower levels of education, high blood pressure, hearing loss, smoking, obesity, depression, inactivity, diabetes, and low social contact. Many of these identified risk factors including, the lower level of education, smoking, physical inactivity and diabetes, are modifiable. Several of the group are known vascular risk factors that may be able to be reduced or eliminated. Managing these risk factors can reduce the risk of dementia in individuals in their late midlife or older age. A reduction in a number of these risk factors can give a positive outcome. The decreased risk achieved by adopting a healthy lifestyle is seen even in those with a high genetic risk.In addition to the above risk factors, meta-analyses indicate that there is robust evidence that other psychological traits, including personality (high neuroticism, and low conscientiousness), low purpose in life, and high loneliness, are risk factors for Alzheimers disease and related dementias. For example, based on the English Longitudinal Study of Ageing (ELSA), research found that loneliness in older people increased the risk of dementia by one-third. Not having a partner (being single, divorced, or widowed) doubled the risk of dementia. However, having two or three closer relationships reduced the risk by three-fifths.The two
Dementia	most modifiable risk factors for dementia are physical inactivity and lack of cognitive stimulation. Physical activity, in particular aerobic exercise, is associated with a reduction in age-related brain tissue loss, and neurotoxic factors thereby preserving brain volume and neuronal integrity. Cognitive activity strengthens neural plasticity and together they help to support cognitive reserve. The neglect of these risk factors diminishes this reserve.Studies suggest that sensory impairments of vision and hearing are modifiable risk factors for dementia. These impairments may precede the cognitive symptoms of Alzheimers disease for example, by many years. Hearing loss may lead to social isolation which negatively affects cognition. Social isolation is also identified as a modifiable risk factor. Age-related hearing loss in midlife is linked to cognitive impairment in late life, and is seen as a risk factor for the development of Alzheimers disease and dementia. Such hearing loss may be caused by a central auditory processing disorder that makes the understanding of speech against background noise difficult. Age-related hearing loss is characterised by slowed central processing of auditory information. Worldwide, mid-life hearing loss may account for around 9% of dementia cases.Evidence suggests that frailty may increase the risk of cognitive decline, and dementia, and that the inverse also holds of cognitive impairment increasing the risk of frailty. Prevention of frailty may help to prevent cognitive decline.A 2018 review however concluded that no medications have good evidence of a preventive effect, including blood pressure medications. A 2020 review found a decrease in the risk of dementia or cognitive problems from 7.5% to 7.0% with blood pressure lowering medications.Economic disadvantage has been shown to have a strong link to higher dementia prevalence, which cannot yet be fully explained by other risk factors. Dental health Limited evidence links poor oral health to cognitive decline. However, failure to perform tooth brushing and gingival inflammation can be used as dementia risk predictors. Oral bacteria The link between Alzheimers and gum disease is oral bacteria. In the oral cavity, bacterial species include P. gingivalis, F. nucleatum, P. intermedia, and T. forsythia. Six oral treponema spirochetes have been examined in the brains of Alzheimers patients. Spirochetes are neurotropic in nature, meaning they act to destroy nerve tissue and create inflammation. Inflammatory pathogens are an indicator of Alzheimers disease and bacteria related to gum disease have been found in the brains of patients with Alzheimers disease. The bacteria invade nerve tissue in the brain, increasing the permeability of the blood–brain barrier and promoting the onset of Alzheimers. Individuals with a plethora of tooth plaque risk cognitive decline. Poor oral hygiene can have an adverse effect on speech and nutrition, causing general and cognitive health decline. Oral viruses Herpes simplex virus (HSV) has been found in more than 70% of those aged over 50. HSV persists in the peripheral nervous system and can be triggered by stress, illness or fatigue. High proportions of viral-associated proteins in amyloid plaques or neurofibrillary tangles (NFTs) confirm the involvement of HSV-1 in Alzheimers disease pathology. NFTs are known as the primary marker of Alzheimers disease. HSV-1 produces the main components of NFTs. Diet Diet is seen to be a modifiable risk factor for the development of dementia. Thiamine deficiency is identified to increase the risk of Alzheimers disease in adults. The role of thiamine in brain physiology is unique and essential for the normal cognitive function of older people. Many dietary choices of the elderly population, including the higher intake of gluten-free products, compromise the intake of thiamine as these products are not fortified with thiamine.The Mediterranean and DASH diets are both associated with less cognitive decline. A different approach has been to incorporate elements of both of these diets into one known as the MIND diet. These diets are generally low in saturated fats while providing a good source of carbohydrates, mainly those that help stabilize blood sugar and insulin levels. Raised blood sugar levels over a long time, can damage nerves and cause memory problems if they are not managed. Nutritional factors associated with the proposed diets for reducing dementia risk include unsaturated fatty acids, vitamin E, vitamin C, flavonoids, vitamin B, and vitamin D.The MIND diet may be more protective but further studies are needed. The Mediterranean diet seems to be more protective against Alzheimers than DASH but there are no consistent findings against dementia in general. The role of olive oil needs further study as it may be one of the most important components in reducing the risk of cognitive decline and dementia.In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve the symptoms given a mild cognitive impairment. Once dementia is advanced no evidence suggests that a gluten-free diet is useful.Omega-3 fatty acid supplements do not appear to benefit or harm people with mild to moderate symptoms. However, there is good evidence that omega-3 incorporation into the diet is of benefit in treating depression, a common symptom, and potentially modifiable risk factor for dementia. Management There are limited options for treating dementia, with most approaches focused on managing or reducing individual symptoms. There are no treatment options available to delay the onset of dementia. Acetylcholinesterase inhibitors are often used early in the disorder course; however, benefit is generally small. More than half of people with dementia may experience psychological or behavioral symptoms including agitation, sleep problems, aggression, and/or psychosis. Treatment for these symptoms is aimed at reducing the persons distress and keeping the person safe. Treatments other than medication appear to be better for agitation and aggression. Cognitive and behavioral interventions may be appropriate. Some evidence suggests that education and support for the person with dementia, as well as caregivers and family members, improves outcomes. Palliative care interventions may improve lead to improvements in comfort in dying, but the evidence is low. Exercise programs are beneficial with respect to activities of daily living, and potentially improve dementia.The effect of therapies can be evaluated for example by assessing agitation using the Cohen-Mansfield Agitation Inventory (CMAI); by assessing mood and engagement with the Menorah Park Engagement Scale (MPES); and the Observed Emotion Rating Scale (OERS) or by assessing indicators for depression using the Cornell Scale for Depression in Dementia (CSDD) or a simplified version thereof.Often overlooked in treating and managing dementia is the role of the caregiver and what is known about how they can support multiple interventions. Findings from a 2021 systematic review of the literature found caregivers of people with dementia in nursing homes do not have sufficient tools or clinical guidance for behavioral and psychological symptoms of dementia (BPSD) along with medication use. Simple measures like talking to people about their interest can improve the quality of life for care home residents living with dementia. A programme showed that such simple measures reduced residents agitation and depression. They also needed fewer GP visits and hospital admissions, which also meant that the programme was cost-saving. Psychological and psychosocial therapies Psychological therapies for dementia include some limited evidence for reminiscence therapy (namely, some positive effects in the areas of quality of life, cognition, communication and mood – the first three particularly in care home settings), some benefit for cognitive reframing for caretakers, unclear evidence for validation therapy and tentative evidence for mental exercises, such as cognitive stimulation programs for people with mild to moderate dementia. Offering personally tailored activities may help reduce challenging behavior and may improve quality of life. It is not clear if personally tailored activities have an impact on affect or improve for the quality of life for the caregiver.Adult daycare centers as well as special care units in nursing homes often provide specialized care for dementia patients. Daycare centers offer supervision, recreation, meals, and limited health care to participants, as well as providing respite for caregivers. In addition, home care can provide one-to-one support and care in the home allowing for more individualized attention that is needed as the disorder progresses. Psychiatric nurses can make a distinctive contribution to peoples mental health.Since dementia impairs normal communication due to changes in receptive and expressive language, as well as the ability to plan and problem solve, agitated behavior is often a form of communication for the person with dementia. Actively searching for a potential cause, such as pain, physical illness, or overstimulation can be helpful in reducing agitation. Additionally, using an "ABC analysis of behavior" can be a useful tool for understanding behavior in people with dementia. It involves looking at the antecedents (A), behavior (B), and consequences (C) associated with an event to help define the problem and prevent further incidents that may arise if the persons needs are misunderstood. The strongest evidence for non-pharmacological therapies for the management of changed behaviors in dementia is for using such approaches. Low quality evidence suggests that regular (at least five sessions of) music therapy may help institutionalized residents. It may reduce depressive symptoms and improve overall behaviors. It may also supply a beneficial effect on emotional well-being and quality of life, as well as reduce anxiety. In 2003, The Alzheimers Society established Singing for the Brain (SftB) a project based on pilot studies which suggested that the activity encouraged participation and facilitated the learning of new songs. The sessions combine aspects of reminiscence therapy and music. Musical and interpersonal connectedness can underscore the value of the person and improve quality of life.Some London hospitals found that using color, designs, pictures and lights helped people with dementia adjust to being at the hospital. These adjustments to the layout of the dementia wings at these hospitals helped patients by preventing confusion.Life story work as part of reminiscence therapy, and video biographies have been found to address the needs of clients and their caregivers in various ways, offering the client the opportunity to leave a legacy and enhance their personhood and also benefitting youth who participate in such work. Such interventions can be more beneficial when undertaken at a relatively early stage of dementia. They may also be problematic in those who have difficulties in processing past experiencesAnimal-assisted therapy has been found to be helpful. Drawbacks may be that pets are not always welcomed in a communal space in the care setting. An animal may pose a risk to residents, or may be perceived to be dangerous. Certain animals may also be regarded as "unclean" or "dangerous" by some cultural groups.Occupational therapy also addresses psychological and psychosocial needs of patients with dementia through improving daily occupational performance and caregivers competence. When compensatory intervention strategies are added to their daily routine, the level of performance is enhanced and reduces the burden commonly placed on their caregivers. Occupational therapists can also work with other disciplines to create a client centered intervention. To manage cognitive disability, and coping with behavioral and psychological symptoms of dementia, combined occupational and behavioral therapies can support patients with dementia even further. Cognitive training There is no strong evidence to suggest that cognitive training is beneficial for people with Parkinsons disease, dementia, or mild cognitive impairment. Personally tailored activities Offering personally tailored activity sessions to people with dementia in long-term care homes may help manage challenging behavior. Medications No medications have been shown to prevent or cure dementia. Medications may be used to treat the behavioral and cognitive symptoms, but have no effect on the underlying disease process.Acetylcholinesterase inhibitors, such as donepezil, may be useful for Alzheimers disease, Parkinsons disease dementia, DLB, or vascular dementia. The quality of the evidence is poor and the benefit is small. No difference has been shown between the agents in this family. In a minority of people side effects include a slow heart rate and fainting. Rivastigmine is recommended for treating symptoms in Parkinsons disease dementia.Medications that have anticholinergic effects increase all-cause mortality in people with dementia, although the effect of these medications on cognitive function remains uncertain, according to a systematic review published in 2021.Before prescribing antipsychotic medication in the elderly, an assessment for an underlying cause of the behavior is needed. Severe and life-threatening reactions occur in almost half of people with DLB, and can be fatal after a single dose. People with Lewy body dementias who take neuroleptics are at risk for neuroleptic malignant syndrome, a life-threatening illness. Extreme caution is required in the use of antipsychotic medication in people with DLB because of their sensitivity to these agents. Antipsychotic drugs are used to treat dementia only if non-drug therapies have not worked, and the persons actions threaten themselves or others. Aggressive behavior changes are sometimes the result of other solvable problems, that could make treatment with antipsychotics unnecessary. Because people with dementia can be aggressive, resistant to their treatment, and otherwise disruptive, sometimes antipsychotic drugs are considered as a therapy in response. These drugs have risky adverse effects, including increasing the persons chance of stroke and death. Given these adverse events and small benefit antipsychotics are avoided whenever possible. Generally, stopping antipsychotics for people with dementia does not cause problems, even in those who have been on them a long time.N-methyl-D-aspartate (NMDA) receptor blockers such as memantine may be of benefit but the evidence is less conclusive than for AChEIs. Due to their differing mechanisms of action memantine and acetylcholinesterase inhibitors can be used in combination however the benefit is slight.An extract of Ginkgo biloba known as EGb 761 has been widely used for treating mild to moderate dementia and other neuropsychiatric disorders. Its use is approved throughout Europe. The World Federation of Biological Psychiatry guidelines lists EGb 761 with the same weight of evidence (level B) given to acetylcholinesterase inhibitors, and mementine. EGb 761 is the only one that showed improvement of symptoms in both AD and vascular dementia. EGb 761 is seen as being able to play an important role either on its own or as an add-on particularly when other therapies prove ineffective. EGb 761 is seen to be neuroprotective; it is a free radical scavenger, improves mitochondrial function, and modulates serotonin and dopamine levels. Many studies of its use in mild to moderate dementia have shown it to significantly improve cognitive function, activities of daily living, neuropsychiatric symptoms, and quality of life. However, its use has not been shown to prevent the progression of dementia.While depression is frequently associated with dementia, the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) do not appear to affect outcomes. However, the SSRIs sertraline and citalopram have been demonstrated to reduce symptoms of agitation, compared to placebo.The use of medications to alleviate sleep disturbances that people with dementia often experience has not been well researched, even for medications that are commonly prescribed. In 2012 the American Geriatrics Society recommended that benzodiazepines such as diazepam, and non-benzodiazepine hypnotics, be avoided for people with dementia due to the risks of increased cognitive impairment and falls. Benzodiazepines are also known to promote delirium. Additionally, little evidence supports the effectiveness of benzodiazepines in this population. No clear evidence shows that melatonin or ramelteon improves sleep for people with dementia due to Alzheimers, but it is used to treat REM sleep behavior disorder in dementia with Lewy bodies. Limited evidence suggests that a low dose of trazodone may improve sleep, however more research is needed.No solid evidence indicates that folate or vitamin B12 improves outcomes in those with cognitive problems. Statins have no benefit in dementia. Medications for other health conditions may need to be managed differently for a person who has a dementia diagnosis. It is unclear whether blood pressure medication and dementia are linked. People may experience an increase in cardiovascular-related events if these medications are withdrawn.The Medication Appropriateness Tool for Comorbid Health Conditions in Dementia (MATCH-D) criteria can help identify ways that a diagnosis of dementia changes medication management for other health conditions. These criteria were developed because people with dementia live with an average of five other chronic diseases, which are often managed with medications. The systematic review that informed the criteria were published subsequently in 2018 and updated in 2022. Pain As people age, they experience more health problems, and most health problems associated with aging carry a substantial burden of pain; therefore, between 25% and 50% of older adults experience persistent pain. Seniors with dementia experience the same prevalence of conditions likely to cause pain as seniors without dementia. Pain is often overlooked in older adults and, when screened for, is often poorly assessed, especially among those with dementia, since they become incapable of informing others of their pain. Beyond the issue of humane care, unrelieved pain has functional implications. Persistent pain can lead to decreased ambulation, depressed mood, sleep disturbances, impaired appetite, and exacerbation of cognitive impairment and pain-related interference with activity is a factor contributing to falls in the elderly.Although persistent pain in people with dementia is difficult to communicate, diagnose, and treat, failure to address persistent pain has profound functional, psychosocial and quality of life implications for this vulnerable population. Health professionals often lack the skills and usually lack the time needed to recognize, accurately assess and adequately monitor pain in people with dementia. Family members and friends can make a valuable contribution to the care of a person with dementia by learning to recognize and assess their pain. Educational resources and observational assessment tools are available. Eating difficulties Persons with dementia may have difficulty eating. Whenever it is available as an option, the recommended response to eating problems is having a caretaker assist them. A secondary option for people who cannot swallow effectively is to consider gastrostomy feeding tube placement as a way to give nutrition. However, in bringing comfort and maintaining functional status while lowering risk of aspiration pneumonia and death, assistance with oral feeding is at least as good as tube feeding. Tube-feeding is associated with agitation, increased use of physical and chemical restraints and worsening pressure ulcers. Tube feedings may cause fluid overload, diarrhea, abdominal pain, local complications, less human interaction and may increase the risk of aspiration.Benefits in those with advanced dementia has not been shown. The risks of using tube feeding include agitation, rejection by the person (pulling out the tube, or otherwise physical or chemical immobilization to prevent them from doing this), or developing pressure ulcers. The procedure is directly related to a 1% fatality rate with a 3% major complication rate. The percentage of people at end of life with dementia using feeding tubes in the US has dropped from 12% in 2000 to 6% as of 2014.The immediate and long-term effects of modifying the thickness of fluids for swallowing difficulties in people with dementia are not well known. While thickening fluids may have an immediate positive effect on swallowing and improving oral intake, the long-term impact on the health of the person with dementia should also be considered. Exercise Exercise programs may improve the ability of people with dementia to perform daily activities, but the best type of exercise is still unclear. Getting more exercise can slow the development of cognitive problems such as dementia, proving to reduce the risk of Alzheimers disease by about 50%. A balance of strength exercise, to help muscles pump blood to the brain, and balance exercises are recommended for aging people. A suggested amount of about 2+1⁄2 hours per week can reduce risks of cognitive decay as well as other health risks like falling. Assistive technology There is a lack of high-quality evidence to determine whether assistive technology effectively supports people with dementia to manage memory issues. Some of the specific things that are used today that helps with dementia today are: clocks, communication aids, electrical appliances the use monitoring, GPS location/ tracking devices, home care robots, in-home cameras, and medication management are just to name a few. Alternative medicine Aromatherapy and massage have unclear evidence. It is not clear if cannabinoids are harmful or effective for people with dementia. Palliative care Given the progressive and terminal nature of dementia, palliative care can be helpful to patients and their caregivers by helping people with the disorder and their caregivers understand what to expect, deal with loss of physical and mental abilities, support the persons wishes and goals including surrogate decision making, and discuss wishes for or against CPR and life support. Because the decline can be rapid, and because most people prefer to allow the person with dementia to make their own decisions, palliative care involvement before the late stages of dementia is recommended. Further research is required to determine the appropriate palliative care interventions and how well they help people with advanced dementia.Person-centered care helps maintain the dignity of people with dementia. Remotely delivered information for caregivers Remotely delivered interventions including support, training and information may reduce the burden for the informal caregiver and improve their depressive symptoms. There is no certain evidence that they improve health-related quality of life.In several localities in Japan, digital surveillance may be made available to family members, if a dementia patient is prone to wandering and going missing. Epidemiology The most common type of dementia is Alzheimers disease. Other common types include vascular dementia, dementia with Lewy bodies, frontotemporal dementia, and mixed dementia (commonly Alzheimers disease and vascular dementia). Less common causes include normal pressure hydrocephalus, Parkinsons disease dementia, syphilis, HIV, and Creutzfeldt–Jakob disease. The number of cases of dementia worldwide in 2021 was estimated at 55 million, with close to 10 million new cases each year. By 2050, the number of people living with dementia is estimated to be over 150 million globally. An estimated 58% of people with dementia are living in low and middle income countries. The prevalence of dementia differs in different world regions, ranging from 4.7% in Central Europe to 8.7% in North Africa/Middle East; the prevalence in other regions is estimated to be between 5.6 and 7.6%. The number of people living with dementia is estimated to double every 20 years. In 2016 dementia resulted in about 2.4 million deaths, up from 0.8 million in 1990.The annual incidence of dementia diagnosis is nearly 10 million worldwide. Almost half of new dementia cases occur in Asia, followed by Europe (25%), the Americas (18%) and Africa (8%). The incidence of dementia increases exponentially with age, doubling with every 6.3 year increase in age. Dementia affects 5% of the population older than 65 and 20–40% of those older than 85. Rates are slightly higher in women than men at ages 65 and greater. The disease trajectory is varied and the median time from diagnosis to death depends strongly on age at diagnosis, from 6.7 years for people diagnosed aged 60–69 to 1.9 years for people diagnosed at 90 or older.Dementia impacts not only individuals with dementia, but also their carers and the wider society. Among people aged 60 years and over, dementia is ranked the 9th most burdensome condition according to the 2010 Global Burden of Disease (GBD) estimates. The global costs of dementia was around US$818 billion in 2015, a 35.4% increase from US$604 billion in 2010. Affected ages About 3% of people between the ages of 65–74 have dementia, 19% between 75 and 84, and nearly half of those over 85 years of age. As more people are living longer, dementia is becoming more common. For people of a specific age, however, it may be becoming less frequent in the developed world, due to a decrease in modifiable risk factors made possible by greater financial and educational resources. It is one of the most common causes of disability among the elderly but can develop before the age of 65 when it is known as early-onset dementia or presenile dementia. Less than 1% of those with Alzheimers have gene mutations that cause a much earlier development of the disease, around the age of 45, known as early-onset Alzheimers disease. More than 95% of people with Alzheimers disease have the sporadic form (late onset, 80–90 years of age). Worldwide the cost of dementia in 2015 was put at US$818 billion. People with dementia are often physically or chemically restrained to a greater degree than necessary, raising issues of human rights. Social stigma is commonly perceived by those with the condition, and also by their caregivers. History Until the end of the 19th century, dementia was a much broader clinical concept. It included mental illness and any type of psychosocial incapacity, including reversible conditions. Dementia at this time simply referred to anyone who had lost the ability to reason, and was applied equally to psychosis, "organic" diseases like syphilis that destroy the brain, and to the dementia associated with old age, which was attributed to "hardening of the arteries". Dementia has been referred to in medical texts since antiquity. One of the earliest known allusions to dementia is attributed to the 7th-century BC Greek philosopher Pythagoras, who divided the human lifespan into six distinct phases: 0–6 (infancy), 7–21 (adolescence), 22–49 (young adulthood), 50–62 (middle age), 63–79 (old age), and 80–death (advanced age). The last two he described as the "senium", a period of mental and physical decay, and that the final phase was when "the scene of mortal existence closes after a great length of time that very fortunately, few of the human species arrive at, where the mind is reduced to the imbecility of the first epoch of infancy". In 550 BC, the Athenian statesman and poet Solon argued that the terms of a mans will might be invalidated if he exhibited loss of judgement due to advanced age. Chinese medical texts made allusions to the condition as well, and the characters for "dementia" translate literally to "foolish old person".Athenian philosophers Aristotle and Plato discussed the mental decline that can come with old age and predicted that this affects everyone who becomes old and nothing can be done to stop this decline from taking place. Plato specifically talked about how the elderly should not be in positions that require responsibility because, "There is not much acumen of the mind that once carried them in their youth, those characteristics one would call judgement, imagination, power of reasoning, and memory. They see them gradually blunted by deterioration and can hardly fulfill their function."For comparison, the Roman statesman Cicero held a view much more in line with modern-day medical wisdom that loss of mental function was not inevitable in the elderly and "affected only those old men who were weak-willed". He spoke of how those who remained mentally active and eager to learn new things could stave off dementia. However, Ciceros views on aging, although progressive, were largely ignored in a world that would be dominated for centuries by Aristotles medical writings. Physicians during the Roman Empire, such as Galen and Celsus, simply repeated the beliefs of Aristotle while adding few new contributions to medical knowledge. Byzantine physicians sometimes wrote of dementia. It is recorded that at least seven emperors whose lifespans exceeded 70 years displayed signs of cognitive decline. In Constantinople, special hospitals housed those diagnosed with dementia or insanity, but these did not apply to the emperors, who were above the law and whose health conditions could not be publicly acknowledged. Otherwise, little is recorded about dementia in Western medical texts for nearly 1700 years. One of the few references was the 13th-century friar Roger Bacon, who viewed old age as divine punishment for original sin. Although he repeated existing Aristotelian beliefs that dementia was inevitable, he did make the progressive assertion that the brain was the center of memory and thought rather than the heart. Poets, playwrights, and other writers made frequent allusions to the loss of mental function in old age. William Shakespeare notably mentions it in plays such as Hamlet and King Lear. During the 19th century, doctors generally came to believe that elderly dementia was the result of cerebral atherosclerosis, although opinions fluctuated between the idea that it was due to blockage of the major arteries supplying the brain or small strokes within the vessels of the cerebral cortex. In 1907, Bavarian psychiatrist Alois Alzheimer was the first to identify and describe the characteristics of progressive dementia in the brain of 51-year-old Auguste Deter. Deter had begun to behave uncharacteristically, including accusing her husband of adultery, neglecting household chores, exhibiting difficulties writing and engaging in conversations, heightened insomnia, and loss of directional sense. At one point, Deter was reported to have "dragged a
Dementia	bed sheet outside, wandered around wildly, and cried for hours at midnight." Alzheimer began treating Deter when she entered a Frankfurt mental hospital on November 25, 1901. During her ongoing treatment, Deter and her husband struggled to afford the cost of the medical care, and Alzheimer agreed to continue her treatment in exchange for Deters medical records and donation of her brain upon death. Deter died on April 8, 1906, after succumbing to sepsis and pneumonia. Alzheimer conducted the brain biopsy using the Bielschowsky stain method, which was a new development at the time, and he observed senile plaques, neurofibrillary tangles, and atherosclerotic alteration. At the time, the consensus among medical doctors had been that senile plaques were generally found in older patients, and the occurrence of neurofibrillary tangles was an entirely new observation at the time. Alzheimer presented his findings at the 37th psychiatry conference of southwestern Germany in Tübingen on April 11, 1906; however, the information was poorly received by his peers. By 1910, Alois Alzheimers teacher, Emil Kraepelin, published a book in which he coined the term "Alzheimers disease" in an attempt to acknowledge the importance of Alzheimers discovery.By the 1960s, the link between neurodegenerative diseases and age-related cognitive decline had become more established. By the 1970s, the medical community maintained that vascular dementia was rarer than previously thought and Alzheimers disease caused the vast majority of old age mental impairments. More recently however, it is believed that dementia is often a mixture of conditions. In 1976, neurologist Robert Katzmann suggested a link between senile dementia and Alzheimers disease. Katzmann suggested that much of the senile dementia occurring (by definition) after the age of 65, was pathologically identical with Alzheimers disease occurring in people under age 65 and therefore should not be treated differently. Katzmann thus suggested that Alzheimers disease, if taken to occur over age 65, is actually common, not rare, and was the fourth- or 5th-leading cause of death, even though rarely reported on death certificates in 1976. A helpful finding was that although the incidence of Alzheimers disease increased with age (from 5–10% of 75-year-olds to as many as 40–50% of 90-year-olds), no threshold was found by which age all persons developed it. This is shown by documented supercentenarians (people living to 110 or more) who experienced no substantial cognitive impairment. Some evidence suggests that dementia is most likely to develop between ages 80 and 84 and individuals who pass that point without being affected have a lower chance of developing it. Women account for a larger percentage of dementia cases than men, although this can be attributed to their longer overall lifespan and greater odds of attaining an age where the condition is likely to occur.Much like other diseases associated with aging, dementia was comparatively rare before the 20th century, because few people lived past 80. Conversely, syphilitic dementia was widespread in the developed world until it was largely eradicated by the use of penicillin after World War II. With significant increases in life expectancy thereafter, the number of people over 65 started rapidly climbing. While elderly persons constituted an average of 3–5% of the population prior to 1945, by 2010 many countries reached 10–14% and in Germany and Japan, this figure exceeded 20%. Public awareness of Alzheimers Disease greatly increased in 1994 when former US president Ronald Reagan announced that he had been diagnosed with the condition. In the 21st century, other types of dementia were differentiated from Alzheimers disease and vascular dementias (the most common types). This differentiation is on the basis of pathological examination of brain tissues, by symptomatology, and by different patterns of brain metabolic activity in nuclear medical imaging tests such as SPECT and PETscans of the brain. The various forms have differing prognoses and differing epidemiologic risk factors. The main cause for many diseases, including Alzheimers disease, remains unclear. Terminology Dementia in the elderly was once called senile dementia or senility, and viewed as a normal and somewhat inevitable aspect of aging.By 1913–20 the term dementia praecox was introduced to suggest the development of senile-type dementia at a younger age. Eventually the two terms fused, so that until 1952 physicians used the terms dementia praecox (precocious dementia) and schizophrenia interchangeably. Since then, science has determined that dementia and schizophrenia are two different disorders, though they share some similarities. The term precocious dementia for a mental illness suggested that a type of mental illness like schizophrenia (including paranoia and decreased cognitive capacity) could be expected to arrive normally in all persons with greater age (see paraphrenia). After about 1920, the beginning use of dementia for what is now understood as schizophrenia and senile dementia helped limit the words meaning to "permanent, irreversible mental deterioration". This began the change to the later use of the term. In recent studies, researchers have seen a connection between those diagnosed with schizophrenia and patients who are diagnosed with dementia, finding a positive correlation between the two diseases.The view that dementia must always be the result of a particular disease process led for a time to the proposed diagnosis of "senile dementia of the Alzheimers type" (SDAT) in persons over the age of 65, with "Alzheimers disease" diagnosed in persons younger than 65 who had the same pathology. Eventually, however, it was agreed that the age limit was artificial, and that Alzheimers disease was the appropriate term for persons with that particular brain pathology, regardless of age. After 1952, mental illnesses including schizophrenia were removed from the category of organic brain syndromes, and thus (by definition) removed from possible causes of "dementing illnesses" (dementias). At the same, however, the traditional cause of senile dementia – "hardening of the arteries" – now returned as a set of dementias of vascular cause (small strokes). These were now termed multi-infarct dementias or vascular dementias. Society and culture The societal cost of dementia is high, especially for caregivers. According to a UK-based study, almost two out of three carers of people with dementia feel lonely. Most of the carers in the study were family members or friends.As of 2015, the annual cost per Alzheimers patient in the United States was around $19,144.36. The total costs for the nation is estimated to be about $167.74 billion. By 2030, it is predicted the annual socioeconomic cost will total to about $507 billion, and by 2050 that number is expected to reach $1.89 trillion. This steady increase will be seen not just within the United States but globally. Global estimates for the costs of dementia were $957.56 billion in 2015, but by 2050 the estimated global cost is 9.12 trillion. Many countries consider the care of people living with dementia a national priority and invest in resources and education to better inform health and social service workers, unpaid caregivers, relatives and members of the wider community. Several countries have authored national plans or strategies. These plans recognize that people can live reasonably with dementia for years, as long as the right support and timely access to a diagnosis are available. Former British Prime Minister David Cameron described dementia as a "national crisis", affecting 800,000 people in the United Kingdom. In fact, dementia has become the leading cause of death for women in England.There, as with all mental disorders, people with dementia could potentially be a danger to themselves or others, they can be detained under the Mental Health Act 1983 for assessment, care and treatment. This is a last resort, and is usually avoided by people with family or friends who can ensure care. Some hospitals in Britain work to provide enriched and friendlier care. To make the hospital wards calmer and less overwhelming to residents, staff replaced the usual nurses station with a collection of smaller desks, similar to a reception area. The incorporation of bright lighting helps increase positive mood and allow residents to see more easily.Driving with dementia can lead to injury or death. Doctors should advise appropriate testing on when to quit driving. The United Kingdom DVLA (Driver & Vehicle Licensing Agency) states that people with dementia who specifically have poor short-term memory, disorientation, or lack of insight or judgment are not allowed to drive, and in these instances the DVLA must be informed so that the driving license can be revoked. They acknowledge that in low-severity cases and those with an early diagnosis, drivers may be permitted to continue driving. Many support networks are available to people with dementia and their families and caregivers. Charitable organizations aim to raise awareness and campaign for the rights of people living with dementia. Support and guidance are available on assessing testamentary capacity in people with dementia.In 2015, Atlantic Philanthropies announced a $177 million gift aimed at understanding and reducing dementia. The recipient was Global Brain Health Institute, a program co-led by the University of California, San Francisco and Trinity College Dublin. This donation is the largest non-capital grant Atlantic has ever made, and the biggest philanthropic donation in Irish history.In October 2020, the Caretakers last music release, Everywhere at the End of Time, was popularized by TikTok users for its depiction of the stages of dementia. Caregivers were in favor of this phenomenon; Leyland Kirby, the creator of the record, echoed this sentiment, explaining it could cause empathy among a younger public.On 2 November 2020, Scottish billionaire Sir Tom Hunter donated £1 million to dementia charities, after watching a former music teacher with dementia, Paul Harvey, playing one of his own compositions on the piano in a viral video. The donation was announced to be split between the Alzheimers Society and Music for Dementia. Notes References External links Dementia at Curlie
Esophageal web	Esophageal webs are thin membranes occurring anywhere along the esophagus. Presentation Its main symptoms are pain and difficulty in swallowing (dysphagia).Esophageal webs are thin 2–3 mm (0.08–0.12 in) membranes of normal esophageal tissue consisting of mucosa and submucosa that can partially protrude/obstruct the esophagus. They can be congenital or acquired. Congenital webs commonly appear in the middle and inferior third of the esophagus, and they are more likely to be circumferential with a central or eccentric orifice. Acquired webs are much more common than congenital webs and typically appear in the cervical area (postcricoid).Clinical symptoms of this condition are selective (solid more than liquids) dysphagia, thoracic pain, nasopharyngeal reflux, aspiration, perforation and food impaction (the last two are very rare). Causes They are mainly observed in the Plummer–Vinson syndrome, which is associated with chronic iron deficiency anemia. One in 10 patients with Plummer-Vinson syndrome will eventually develop squamous cell carcinoma of the esophagus, but it is unclear if esophageal webs in and of themselves are a risk factor. Esophageal webs are associated with bullous diseases (such as epidermolysis bullosa, pemphigus, and bullous pemphigoid), with graft versus host disease involving the esophagus, and with celiac disease.Esophageal webs are more common in white individuals and in women (with a ratio of 2:1). The literature describes relations between these webs and Plummer-Vinson Syndrome, bullous dermatologic disorders, inlet patch, graft-versus-host disease and celiac disease. The postulated mechanisms are sideropenic anemia (mechanism unknown) or some interference of the immune system. Esophageal webs can be ruptured during upper endoscopy. Diagnosis The diagnostic test of choice is a barium swallow. Treatment Esophageal webs and rings can be treated with endoscopic dilation. References == External links ==
Fovilles syndrome	Fovilles syndrome is caused by the blockage of the perforating branches of the basilar artery in the region of the brainstem known as the pons. It is most frequently caused by vascular disease or tumors involving the dorsal pons. Structures affected by the infarct are the dorsal pons(pontine tegmentum) which comprises paramedian pontine reticular formation (PPRF), nuclei of cranial nerves VI and VII, corticospinal tract, medial lemniscus, and the medial longitudinal fasciculus. There is involvement of the fifth to eighth cranial nerves, central sympathetic fibres (Horner syndrome) and horizontal gaze palsy. Presentation This produces ipsilateral horizontal gaze palsy and facial nerve palsy and contralateral hemiparesis, hemisensory loss, and internuclear ophthalmoplegia. Diagnosis Treatment History Fovilles syndrome was initially described by Achille-Louis Foville, a French physician, in 1859. References == External links ==
Benedikt syndrome	Benedikt syndrome, also called Benedikts syndrome or paramedian midbrain syndrome, is a rare type of posterior circulation stroke of the brain, with a range of neurological symptoms affecting the midbrain, cerebellum and other related structures. Signs and symptoms It is characterized by the presence of an oculomotor nerve (CN III) palsy and cerebellar ataxia including tremor and involuntary choreoathetotic movements. Neuroanatomical structures affected include the oculomotor nucleus, red nucleus, corticospinal tracts and superior cerebellar peduncle decussation. It has a similar cause, morphology, signs and symptoms to Webers syndrome; the main difference between the two being that Webers is more associated with hemiplegia (i.e. paralysis), and Benedikts with hemiataxia (i.e. disturbed coordination of movements). It is also similar to Claudes syndrome, but is distinguishable in that Benedikts has more predominant tremor and choreoathetotic movements while Claudes is more marked by the ataxia. Causes Benedikt syndrome is caused by a lesion (infarction, hemorrhage, tumor, or tuberculosis) in the tegmentum of the midbrain and cerebellum. Specifically, the median zone is impaired. It can result from occlusion of the posterior cerebral artery or paramedian penetrating branches of the basilar artery. Diagnosis Oculomotor nerve palsy: eyeball gazing downward and outward position, diplopia, miosis, mydriasis, and loss of accommodation reflex. Contralateral loss of proprioception and vibration sensations. Cerebellar ataxia: involuntary movements. Treatment Deep brain stimulation may provide relief from some symptoms of Benedikt syndrome, particularly the tremors associated with the disorder. See also Claudes syndrome Wallenberg syndrome References == External links ==
Pityriasis alba	Pityriasis alba is a skin condition, a type of dermatitis, commonly seen in children and young adults as dry, fine-scaled, pale patches on the face. It is self-limiting and usually only requires use of moisturizer creams.The condition is so named for the fine scaly appearance initially present (pityriasis), and alba (Latin for white) refers to the pallor of the patches that develop. The patches are not totally depigmented. Signs and symptoms The dry scaling appearance is most noticeable during the winter as a result of dry air inside peoples homes. During the summer, tanning of the surrounding normal skin makes the pale patches of pityriasis alba more prominent.Individual lesions develop through 3 stages and sometimes are itchy: Raised and red – although the redness is often mild and not noticed by parents Raised and pale Smooth flat pale patchesLesions are round or oval raised or flat, of 0.5–2 cm in size although may be larger if they occur on the body (up to 4 cm), and usually number from 4 or 5 to over 20. The patches are dry with very fine scales. They most commonly occur on the face (cheeks), but in 20% appear also on the upper arms, neck, or shoulders.The diagnostic differential should consider tinea and vitiligo amongst other causative factors. Cause Any dermatitis may heal leaving pale skin, as may excessive use of corticosteroid creams used to treat episodes of eczema. The hypopigmentation is due to both reduced activity of melanocytes with fewer and smaller melanosomes.The cause of pityriasis alba is not known. Dry skin and atopic dermatitis may co-exist. The patches may become more apparent after sun exposure, when the normal surrounding skin is tanned. The role of ultraviolet radiation, bathing or not bathing, low serum copper and Malassezia yeasts is not clear. Diagnosis Diagnosis is mainly done by clinical examination. Shining a Woods light over the skin may reveal further lesions not obviously visible otherwise. Differential diagnosis Pityriasis versicolor and leprosy. Treatment No treatment is required and the patches in time will settle. The redness, scale and itch if present may be managed with simple emollients and sometimes hydrocortisone, a weak steroid, is also used.As the patches of pityriasis alba do not darken normally in sunlight, effective sun protection helps minimise the discrepancy in colouration against the surrounding normal skin. Cosmetic camouflage may be required. Tacrolimus has been reported as speeding resolution.In exceptionally severe cases PUVA therapy may be considered. Prognosis The patches of pityriasis alba may last from 1 month to about one year, but commonly on the face last a year. However it is possible that the white patches may last for more than 1 year on the face. Epidemiology It occurs in mainly children and adolescents of all races, particularly people with dark skin. The worldwide prevalence is 5% in children, with boys and girls affected equally. adults can also have this disease.Up to a third of US school children may at some stage have this condition. Single-point prevalence studies from India have shown variable rates from 8.4% to 31%. Other studies have shown prevalence rates in Brazil of 9.9%, Egypt 13.49%, Romania 5.1%, Turkey 12% where higher rates were seen in those with poor socioeconomic conditions, and just 1% in school children in Hong Kong. In 1963, one school health clinic reported features of pityriasis alba in two fifths of their children. History It was first described in 1923. Having been known under a variety of names, the term Pityriasis alba, coined in 1956, has stayed. See also Leprosy List of cutaneous conditions Vitiligo which, by comparison, causes total loss of skin colour or on the face and tends to occur around the mouth and eyes. References == External links ==
Angina	Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.Angina is typically the result of obstruction or spasm of the arteries that supply blood to the heart muscle. The main mechanism of coronary artery obstruction is atherosclerosis as part of coronary artery disease. Other causes of angina include abnormal heart rhythms, heart failure and, less commonly, anemia. The term derives from the Latin angere ("to strangle") and pectus ("chest"), and can therefore be translated as "a strangling feeling in the chest". The severity of angina pain does not always match the degree of oxygen deprivation to the heart or the risk of a myocardial infarction (heart attack). Some people may experience severe pain even though there is little or no risk of a heart attack. Others may have a heart attack and experience little or no pain. In some cases, angina can be quite severe. Worsening angina attacks, sudden-onset angina at rest, and angina lasting more than 15 minutes are symptoms of unstable angina (usually grouped with similar conditions as the acute coronary syndrome). As these may precede a heart attack, they require urgent medical attention and are, in general, treated similarly to myocardial infarction.In the early 20th century, severe angina was seen as a sign of impending death. However, modern medical therapies have improved the outlook substantially. Middle-age patients who experience moderate to severe angina (grading by classes II, III, and IV) have a five-year survival rate of approximately 92%. Classification Stable angina Also known as effort angina, this refers to the classic type of angina related to myocardial ischemia. A typical presentation of stable angina is that of chest discomfort and associated symptoms precipitated by some activity (running, walking, etc.) with minimal or non-existent symptoms at rest or after administration of sublingual nitroglycerin. Symptoms typically abate several minutes after activity and recur when activity resumes. In this way, stable angina may be thought of as being similar to intermittent claudication symptoms. Other recognized precipitants of stable angina include cold weather, heavy meals, and emotional stress. Unstable angina Unstable angina (UA) (also "crescendo angina"; this is a form of acute coronary syndrome) is defined as angina pectoris that changes or worsens.It has at least one of these three features: it occurs at rest (or with minimal exertion), usually lasting more than 10 minutes it is severe and of new-onset (i.e., within the prior 4–6 weeks) it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or frequent than before).UA may occur unpredictably at rest, which may be a serious indicator of an impending heart attack. What differentiates stable angina from unstable angina (other than symptoms) is the pathophysiology of the atherosclerosis. The pathophysiology of unstable angina is the reduction of coronary flow due to transient platelet aggregation on apparently normal endothelium, coronary artery spasms, or coronary thrombosis. The process starts with atherosclerosis, progresses through inflammation to yield an active unstable plaque, which undergoes thrombosis and results in acute myocardial ischemia, which, if not reversed, results in cell necrosis (infarction). Studies show that 64% of all unstable anginas occur between 22:00 and 08:00 when patients are at rest.In stable angina, the developing atheroma is protected with a fibrous cap. This cap may rupture in unstable angina, allowing blood clots to precipitate and further decrease the area of the coronary vessels lumen. This explains why, in many cases, unstable angina develops independently of activity. Microvascular angina Microvascular angina, also known as cardiac syndrome X, is characterized by angina-like chest pain, in the context of normal epicardial coronary arteries (the largest vessels on the surface of the heart, prior to significant branching) on angiography. The original definition of cardiac syndrome X also mandated that ischemic changes on exercise (despite normal coronary arteries) were displayed, as shown on cardiac stress tests. The primary cause of microvascular angina is unknown, but factors apparently involved are endothelial dysfunction and reduced flow (perhaps due to spasm) in the tiny "resistance" blood vessels of the heart. Since microvascular angina is not characterized by major arterial blockages, it is harder to recognize and diagnose. Microvascular angina was previously considered a rather benign condition, but more recent data has changed this attitude. Studies, including the Womens Ischemia Syndrome Evaluation (WISE), suggest that microvascular angina is part of the pathophysiology of ischemic heart disease, perhaps explaining the higher rates of angina in women than in men, as well as their predilection towards ischemia and acute coronary syndromes in the absence of obstructive coronary artery disease. Signs and symptoms Angina pectoris can be quite painful, but many patients with angina complain of chest discomfort rather than actual pain: the discomfort is usually described as a pressure, heaviness, tightness, squeezing, burning, or choking sensation. Apart from chest discomfort, anginal pains may also be experienced in the epigastrium (upper central abdomen), back, neck area, jaw, or shoulders. This is explained by the concept of referred pain and is because the spinal level that receives visceral sensation from the heart simultaneously receives cutaneous sensation from parts of the skin specified by that spinal nerves dermatome, without an ability to discriminate the two. Typical locations for referred pain are arms (often inner left arm), shoulders, and neck into the jaw. Angina is typically precipitated by exertion or emotional stress. It is exacerbated by having a full stomach and by cold temperatures. Pain may be accompanied by breathlessness, sweating, and nausea in some cases. In this case, the pulse rate and the blood pressure increases. Chest pain lasting only a few seconds is normally not angina (such as precordial catch syndrome). Myocardial ischemia comes about when the myocardium (the heart muscle) receives insufficient blood and oxygen to function normally either because of increased oxygen demand by the myocardium or because of decreased supply to the myocardium. This inadequate perfusion of blood and the resulting reduced delivery of oxygen and nutrients are directly correlated to blocked or narrowed blood vessels. Some experience "autonomic symptoms" (related to increased activity of the autonomic nervous system) such as nausea, vomiting, and pallor. Major risk factors for angina include cigarette smoking, diabetes, high cholesterol, high blood pressure, sedentary lifestyle, and family history of premature heart disease. A variant form of angina—Prinzmetals angina—occurs in patients with normal coronary arteries or insignificant atherosclerosis. It is believed caused by spasms of the artery. It occurs more in younger women.Coital angina, also known as angina damour, is angina subsequent to sexual intercourse. It is generally rare, except in patients with severe coronary artery disease. Cause Major risk factors Routine counseling of adults by physicians to advise them to improve their diet and increase their physical activity has, in general, been found to induce only small changes in actual behavior. Therefore, as of 2012, The U.S. Preventive Services Task Force does not recommend routine lifestyle counseling of all patients without known cardiovascular disease, hypertension, hyperlipidemia, or diabetes, and instead recommends selectively counseling only those patients who seem most ready to make lifestyle changes and using available time with other patients to explore other types of intervention that would be more likely to have a preventative impact. Conditions that exacerbate or provoke angina One study found that smokers with coronary artery disease had a significantly increased level of sympathetic nerve activity when compared to those without. This is in addition to increases in blood pressure, heart rate, and peripheral vascular resistance associated with nicotine, which may lead to recurrent angina attacks. In addition, the Centers for Disease Control and Prevention (CDC) reports that the risk of CHD (Coronary heart disease), stroke, and PVD (Peripheral vascular disease) is reduced within 1–2 years of smoking cessation. In another study, it was found that, after one year, the prevalence of angina in smoking men under 60 after an initial attack was 40% less in those having quit smoking compared to those that continued. Studies have found that there are short-term and long-term benefits to smoking cessation. Other medical problems Esophageal disorders Gastroesophageal reflux disease (GERD) Hyperthyroidism Hypoxemia Profound anemia Uncontrolled hypertension Other cardiac problems Bradyarrhythmia Hypertrophic cardiomyopathy Tachyarrhythmia Valvular heart diseaseMyocardial ischemia can result from: a reduction of blood flow to the heart that can be caused by stenosis, spasm, or acute occlusion (by an embolus) of the hearts arteries. resistance of the blood vessels. This can be caused by narrowing of the blood vessels; a decrease in radius. Blood flow is proportional to the radius of the artery to the fourth power. reduced oxygen-carrying capacity of the blood, due to several factors such as a decrease in oxygen tension and hemoglobin concentration. This decreases the ability of hemoglobin to carry oxygen to myocardial tissue.Atherosclerosis is the most common cause of stenosis (narrowing of the blood vessels) of the hearts arteries and, hence, angina pectoris. Some people with chest pain have normal or minimal narrowing of heart arteries; in these patients, vasospasm is a more likely cause for the pain, sometimes in the context of Prinzmetals angina and syndrome X. Myocardial ischemia also can be the result of factors affecting blood composition, such as the reduced oxygen-carrying capacity of blood, as seen with severe anemia (low number of red blood cells), or long-term smoking. Pathophysiology Angina results when there is an imbalance between the hearts oxygen demand and supply. This imbalance can result from an increase in demand (e.g., during exercise) without a proportional increase in supply (e.g., due to obstruction or atherosclerosis of the coronary arteries). However, the pathophysiology of angina in females varies significantly as compared to males. Non-obstructive coronary disease is more common in females. Diagnosis Angina should be suspected in people presenting tight, dull, or heavy chest discomfort that is: Retrosternal or left-sided, radiating to the left arm, neck, jaw, or back. Associated with exertion or emotional stress and relieved within several minutes by rest. Precipitated by cold weather or a meal.Some people present with atypical symptoms, including breathlessness, nausea, or epigastric discomfort, or burning. These atypical symptoms are particularly likely in older people, women, and those with diabetes.Anginal pain is not usually sharp or stabbing or influenced by respiration. Antacids and simple analgesics do not usually relieve the pain. If chest discomfort (of whatever site) is precipitated by exertion, relieved by rest, and relieved by glyceryl trinitrate, the likelihood of angina is increased.In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is typically normal unless there have been other cardiac problems in the past. During periods of pain, depression, or elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test ("treadmill test") may be performed, during which the patient exercises to his/her maximum ability before fatigue, breathlessness, or pain intervenes; if characteristic ECG changes are documented (typically more than 1 mm of flat or downsloping ST depression), the test is considered diagnostic for angina. Even constant monitoring of the blood pressure and the pulse rate can lead to some conclusions regarding angina. The exercise test is also useful in looking for other markers of myocardial ischemia: blood pressure response (or lack thereof, in particular, a drop in systolic blood pressure), dysrhythmia, and chronotropic response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi scintigram (in patients unable to exercise enough for the treadmill tests, e.g., due to asthma or arthritis or in whom the ECG is too abnormal at rest) or stress echocardiography. In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to identify the nature of the coronary lesion, and whether this would be a candidate for angioplasty, coronary artery bypass graft (CABG), treatment only with medication, or other treatments. In hospitalized patients with unstable angina (or the newer term of "high-risk acute coronary syndromes"), those with resting ischaemic ECG changes or those with raised cardiac enzymes such as troponin may undergo coronary angiography directly. Treatment Angina pectoris occurs as a result of coronary blood flow insufficiency in the face of increased oxygen demand. The principal goal in the prevention and relief of angina is to limit the oxygen requirement of the heart so it can meet the inadequate oxygen supply derived through the blood supplied from the stenosed or constricted arteries. The main goals of treatment in angina pectoris are relief of symptoms, slowing progression of the disease, and reduction of future events, especially heart attacks and death. Beta blockers (e.g., carvedilol, metoprolol, propranolol) have a large body of evidence in morbidity and mortality benefits (fewer symptoms, less disability, and longer life) and short-acting nitroglycerin medications have been used since 1879 for symptomatic relief of angina. There are differing course of treatments for the patient depending on the type of angina the patient has. However, this second can provide a brief overview of the types of medications provided for angina and the purpose by which they are prescribed. Beta blockers, specifically B1 adrenergic blockers without intrinsic sympathomimetic activity are the most preferred for the angina treatment out of B1 selective and non-selective as well as B1 ISA agents. B1 blockers are cardioselective blocking agents such as Nevibolol, Atenolol, Metoprolol and Bisoprolol, which result in blocking cAMP in the heart muscle cells. The cAMP which plays a vital role in phosphorylating the ryanodine receptor and LTCC will usually increase Ca+2 levels in the heart muscle cells, which will then result in contraction is blocked. Therefore, B1 blockade decreases the HR and contraction of the heart muscle, making it need less oxygen demand. An important thing to note is that the B1 cardioselective blockers are cardioselective and not cardio specific. This means that if the beta-adrenergic antagonist is prescribed in higher doses, it can lose the selectivity aspect and begin causing hypertension from B2 adrenergic stimulation of smooth muscle cells. This is why in therapy for patients with angina, the vasodilatory organonitrates complement the use of B-blockers when prescribed the use of angina. The preference for Beta-1 cardioselective blockers is for B1 cardioselective blockers without instrinsic sympathetic activity. Beta blockers with intrinsic sympathetic activity will still do the beta blockade of the heart muscle cells and have a decreased ionotrophic and chronotropic effect, but this effect will be to a lesser extent than if the beta blocker did not have the instrinsic sympathetic activity. A common beta-blocker with ISA prescribed for the treatment of angina is Acebutolol. Non-selective beta-adrenergic antagonists will yield the same action on B1 receptors, however will also act on B2 receptors. These medications, such as Propranolol and Nadolol, act on B1 receptors on smooth muscle cells as well. B1 blockade occurs in the smooth muscle cells. Specifically cAMP is responsible for inhibiting Myosin Light Kinase, the enzyme responsible for acting on Actin-Myosin. The inhibition of B1 will result in decreased levels of cAMP which will lead to increased levels of Myosin Light Chain Kinase in the smooth muscle cells, the enzyme responsible for acting on Actin-Myosin and leading to contraction of the smooth muscle cell. This increased contraction of the smooth muscle cell from B1 blockade is not desirable since it explains the hypertension that may arise with patients taking that medication. Calcium channel blockers act to decrease the hearts workload, and thus its requirement for oxygen by blocking the calcium channels of the heart muscle cell. With decreased intracellular calcium, the calcium-troponin complex does not form in the heart muscle cell and it does not contract, therefore reducing the need for oxygen. The other class of medication that can be used to treat angina are the organic nitrates. Organic nitrates are used extensively to treat angina. They improve coronary blood flow of the coronary arteries (arteries which supply blood to the heart muscle) by reversing and preventing vasospasm, which increases the blood flow to the heart, improving perfusion and oxygen delivery to the heart associated with the pain of angina. These drugs also reduce systemic vascular resistance, of both veins and arteries but the veins to a greater extent. The decrease in the resistance of the arteries and veins decreases the myocardial oxygen demand, which also reduces myocardial oxygen demand. Nitroglycerin is a potent vasodilator that decreases myocardial oxygen demand by decreasing the hearts workload. Nitroglycerin should not be given if certain inhibitors such as sildenafil, tadalafil, or vardenafil have been taken within the previous 12 hours as the combination of the two could cause a serious drop in blood pressure. Treatments for angina are balloon angioplasty, in which the balloon is inserted at the end of a catheter and inflated to widen the arterial lumen. Stents to maintain the arterial widening are often used at the same time. Coronary bypass surgery involves bypassing constricted arteries with venous grafts. This is much more invasive than angioplasty. Calcium channel blockers (such as nifedipine (Adalat) and amlodipine), isosorbide mononitrate and nicorandil are vasodilators commonly used in chronic stable angina. A new therapeutic class, called If inhibitor, has recently been made available: Ivabradine provides heart rate reduction without affecting contractility leading to major anti-ischemic and antianginal efficacy. ACE inhibitors are also vasodilators with both symptomatic and prognostic benefit. Statins are the most frequently used lipid/cholesterol modifiers, which probably also stabilize existing atheromatous plaque. Low-dose aspirin decreases the risk of heart attack in patients with chronic stable angina, and was part of standard treatment. However, in patients without established cardiovascular disease, the increase in hemorrhagic stroke and gastrointestinal bleeding offsets any benefits and it is no longer advised unless the risk of myocardial infarction is very high.Exercise is also a very good long-term treatment for the angina (but only particular regimens – gentle and sustained exercise rather than intense short bursts), probably working by complex mechanisms such as improving blood pressure and promoting coronary artery collateralisation. Though sometimes used by patients, evidence does not support the use of traditional Chinese herbal products (THCP) for angina.Identifying and treating risk factors for further coronary heart disease is a priority in patients with angina. This means testing for elevated cholesterol and other fats in the blood, diabetes and hypertension (high blood pressure), and encouraging smoking cessation and weight optimization. The calcium channel blocker nifedipine prolongs cardiovascular event- and procedure-free survival in patients with coronary artery disease. New overt heart failures were reduced by 29% compared to placebo; however, the mortality rate difference between the two groups was statistically insignificant. Microvascular angina in women Women with myocardial ischemia often have either no or atypical symptoms, such as palpitations, anxiety, weakness, and fatigue. Additionally, many women with angina are found to have cardiac ischemia, yet no evidence of obstructive coronary artery disease on cardiac catheterization. Evidence is accumulating that nearly half of women with myocardial ischemia have coronary microvascular disease, a condition often called microvascular angina (MVA). Small intramyocardial arterioles constrict in MVA causing ischemic pain that is less predictable than with typical epicardial coronary artery disease (CAD). The pathophysiology is complex and still being elucidated, but there is strong evidence that endothelial dysfunction, decreased endogenous vasodilators, inflammation, changes in adipokines, and platelet activation are contributing factors. The diagnosis of MVA may require catheterization during which there is an assessment of the microcirculatory response to adenosine or acetylcholine and measurement of coronary and fractional flow reserve. New techniques include positron emission tomography (PET) scanning, cardiac magnetic resonance imaging (MRI), and transthoracic Doppler echocardiography. Managing MVA can be challenging, for example, women with this condition have less coronary microvascular dilation in response to nitrates than do those without MVA. Women with MVA often have traditional risk factors for CAD such as obesity, dyslipidemia, diabetes, and hypertension. Aggressive interventions to reduce modifiable risk factors are an important component of management, especially smoking cessation, exercise, and diabetes management. The combination of non-nitrate vasodilators, such as calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors along with HMG-CoA reductase inhibitors (statins), also is effective in many women, and new drugs, such as Ranolazine and Ivabradine, have shown promise in the treatment of MVA. Other approaches include spinal cord stimulators, adenosine receptor blockade, and psychiatric intervention. Suspected angina Hospital admission for people with the following symptoms is recommended, as they may have unstable angina: pain at rest (which may occur at night), pain on minimal exertion, angina that seems to progress rapidly despite increasing medical treatment. All people with suspected angina should be urgently referred to a chest pain evaluation service, for confirmation of the diagnosis and assessment of the severity of coronary heart disease. Epidemiology As of 2010, angina due to ischemic heart disease affects approximately 112 million people (1.6% of the population) being slightly more common in men than women (1.7% to 1.5%).In the United States, 10.2 million are estimated to experience angina with approximately 500,000 new cases occurring each year. Angina is more often the presenting symptom of coronary artery disease in women than in men. The prevalence of angina rises with increasing age, with a mean age of onset of 62.3 years. After five years post-onset, 4.8% of individuals with angina subsequently died from coronary heart disease. Men with angina were found to have an increased risk of subsequent acute myocardial infarction and coronary heart disease related death than women. Similar figures apply in the remainder of the Western world. All forms of coronary heart disease are much less-common in the Third World, as its risk factors are much more common in Western and Westernized countries; it could, therefore, be termed a disease of affluence. History The condition was named "hritshoola" in ancient India and was described by Sushruta (6th century BC).The first clinical description of angina pectoris was by a British physician Dr. William Heberden in 1768. References External links Treatment of stable angina recommendations for patients in laymans terms British Heart Foundation - Angina Angina Pectoris Animation Video 3D Guidelines on the management of stable angina pectoris - European Society of Cardiology Heart Attack and Angina Statistics by American Heart Association: Final 2006 statistics for the United States
Madelungs deformity	Madelungs deformity is usually characterized by malformed wrists and wrist bones and is often associated with Léri-Weill dyschondrosteosis. It can be bilateral (in both wrists) or just in the one wrist. It has only been recognized within the past hundred years. Named after Otto Wilhelm Madelung (1846–1926), a German surgeon, who described it in detail, it was noted by others. Guillaume Dupuytren mentioned it in 1834, Auguste Nélaton in 1847, and Joseph-François Malgaigne in 1855. Signs and symptoms It is a congenital subluxation or dislocation of the ulnas distal end, due to malformation of the bones. Sometimes, minor abnormalities of other bone structures, often caused by disease or injury, such as a fracture of the distal end of the radius with upward displacement of the distal fragment. The deformity varies in degree from a slight protrusion of the lower end of the ulna, to complete dislocation of the inferior radio-ulnar joint with marked ulnar deviation of the hand. Severe deformities are associated with congenital absence or hypoplasia of the radius.The male:female rate of this disorder is 1:4. The incidence is unknown, and there is no described racial predominance. Even though Madelungs Deformity is considered a congenital disorder, symptoms sometimes arent seen until adulthood. In most cases, symptoms find their onset during midchildhood. At this age, the relatively slower growth of the ulnar and palmar part of the radius, leads to an increasingly progressive deformity. Pain and deformity are the main symptoms patients present with. Typical clinical presentation consists of a short forearm, anterior-ulnar bow of the radius and a forward subluxation of the hand on the forearm. As mentioned before, the severity of the disorder varies greatly, which also leads to a spectrum of presentation. Genetics Leri-Weill dyschondrosteosis is a pseudoautosomal dominant disorder which occurs more frequently in females and is due to a mutation, deletion or duplication of the SHOX gene. The SHOX gene plays a particularly important role in the growth and maturation of bones in the arms and legs. The SHOX gene is located within band Xp22.3 of the pseudoautosomal region of the X chromosome, which escapes X-inactivation. Homozygous SHOX gene mutations result in Langer mesomelic dysplasia. Pathogenesis Madelung deformity of the wrist is caused by a growth disturbance in the inferior volar part of the epiphysial growth plate in the distal radius, resulting in a volar placed slope of the lunate facet and scaphoid facet. This produces volar translation of the hand and wrist. The ulna continues growing straight, resulting in a dorsally prominent distal ulna. It occurs predominantly in adolescent females, who present with pain, decreased range of motion, and deformity. It often has a genetic cause and is associated with mesomelic dwarfism and a mutation on the X chromosome. Attempts can be made to treat the deformity surgically by addressing the deforming bone and fibrous bands called "Vickers ligament". This is an abnormal ligament formed between the Lunate bone of the wrist and the radius and is found in 91% of cases of Madelungs deformity. Diagnosis Diagnosis is normally confirmed by X-rays. Treatment Non-surgical First options for treatment are conservative, using hot or cold packs, rest and NSAIDs at first. If no improvement is made, a splint or brace can be used to keep the deviated arm straight. When none of the conservative treatments work surgical intervention is designated. Surgical Pediatrics Physiolysis Purpose of the treatment is the removal of the epiphysis that causes the abnormal growth of the wrist. This is done by making a small incision at the volar-radial side. This approach passes the Flexor pollicis longus and Palmaris longus and leaves the Median nerve and Radial artery protected. Then the Pronator quadratus muscle is found and detached from the radius. Here a cut into the bone will find the abnormal epiphysis. When the epiphysis is clearly defined more bone is removed so the radius is in its normal position and prevents a new bone bar from forming. This is the end of the physiolisis. This is always combined with a Vickers Ligament release.Dome osteotomy Purpose of this treatment option is to straighten the abnormal radius. To do this, an 8 cm incision is made from the wrist crease at the palmair radial side. The approach is made passing the Flexor carpi radialis with detachment of the Pronator quadratus muscle from the radius. Now the Vickers ligament release is done. After this the periosteum is elevated and a crescent-shaped osteotomy, concave at the end, is marked on the bone. Now the radius is cut dome shaped and straightened. The distal end of the radius stays attached to the ulna. The dome shape of the osteotomy allows adequate bony contact for stability and a subperiosteal void for rapid healing.Vickers Ligament Release This ligament causes the wrist to deform even more. The purpose of this release is to release the tension and leave the wrist straight in further growth. In both physiolysis and dome osteotomy there should be a clear view of the abnormal. Adults Ulna reduction Adults with Madelung’s deformity may suffer from ulnar-sided wrist pain. Madelungs Deformity is usually treated by treating the distal radial deformity. However, if patients have a positive ulnar variance and focal wrist pathology, it’s possible to treat with an isolated ulnar-shortening osteotomy. In these patients the radial deformity is not treated.The ulna is approached from the subcutaneous border. A plate is attached to the distal end of the ulna, to plan the osteotomy. An oblique segment is removed from the ulna, after which the distal radial-ulnar joint is freed, making sure structures stay attached to the styloid process. After this, the freed distal end is reattached to the proximal ulna with the formerly mentioned plate.Total DRUJ replacement An alternative treatment for patients with ulnar-sided wristpain is a total replacement of the distal radial-ulnar joint. There are many surgical treatments of the condition, but most of these only improve the alignment and function of the radiocarpal joint. A persistent problem in these treatments has been the stiff DRUJ. However, a prosthesis helps in managing the pain, and might also improve the range of motion of the wrist.The procedure consists of making a hockey-stick shaped incision along the ulnar border. This incision is made between the fifth and sixth dorsal compartment. Being careful not to harm any essential structures, like the posterior interosseous nerve, the incision is continued between the extensor carpi ulnaris and the extensor digiti quinti, until the ulna is found. The ulnar head is then removed. A guide wire is then inserted in the medullary canal of the ulna, allowing centralization for a cannulated drill bit. A poly-ethylene ball, which will serve as the prosthesis, is then placed over the distal peg. After confirming full range of motion, the skin will be closed.Dome Osteotomy In case of Madelungs Deformity in conjunction with radial pain, a dome osteotomy may be conducted. For more information about this procedure, please refer to the treatment of Madelungs Deformity in children. Eponym It is named for Otto Wilhelm Madelung. References == External links ==
Left atrial enlargement	Left atrial enlargement (LAE) or left atrial dilation refers to enlargement of the left atrium (LA) of the heart, and is a form of cardiomegaly. Signs and symptoms Left atrial enlargement can be mild, moderate or severe depending on the extent of the underlying condition. Although other factors may contribute, left atrium size has been found to be a predictor of mortality due to both cardiovascular issues as well as all-cause mortality. Research suggests that left atrium size as measured by an echo-cardiograph may be linked to cardiovascular disease. However, studies that have found LAE to be a predictor for mortality recognize the need for more standardized left atrium measurements than those found in an echo-cardiogram. Causes In the general population, obesity appears to be the most important risk factor for LAE. LAE has been found to be correlated to body size, independent of obesity, meaning that LAE is more common in people with a naturally large body size. Also, a study found that LAE can occur as a consequence of atrial fibrillation (AF), although another study found that AF by itself does not cause LAE. The latter study also showed that the persistent type of AF was associated with LAE, but the number of years that a subject had AF was not.Obstructive sleep apnea (OSA) may be a cause of LAE in some cases. When an OSA event occurs, an attempt is made to breathe with an obstructed airway and the pressure inside the chest is suddenly lowered. The negative intrathoracic pressure may cause the left atrium to expand and stretch its walls during each OSA event. Over time, the repetitive stretching of the left atrium may result in a persistent left atrial enlargement. Diagnosis LAE is suggested by an electrocardiogram (ECG) that has a pronounced notch in the P wave. However, if atrial fibrillation is present, a P wave would not be present. In any case, LAE can be diagnosed and measured using an echocardiogram (ECHO) by measuring the left atrial volume (LAVI). Characterizing the size of the left atrium according to its volume is preferred over a single linear dimension since enlargement can be different for different directions. For example, because of the smaller distance in the thoracic cavity between the sternum and spine, compared to the other directions, less room exists for enlargement of the left atrium along the anteroposterior axis. By approximating the shape of the left atrium as an ellipsoid, its volume can be calculated from measurements of its dimensions along three perpendicular directions.Indexing the left atrial volume to body surface area (volume/BSA) is recommended by the American Society of Echocardiography and the European Association of Echocardiography. The values for volume/BSA in the following table are the best validated, and are the same for both men and women. == References ==
Coma	A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhibit a complete absence of wakefulness and are unable to consciously feel, speak or move. Comas can be derived by natural causes, or can be medically induced.Clinically, a coma can be defined as the inability consistently to follow a one-step command. It can also be defined as a score of ≤ 8 on the Glasgow Coma Scale (GCS) lasting ≥ 6 hours. For a patient to maintain consciousness, the components of wakefulness and awareness must be maintained. Wakefulness describes the quantitative degree of consciousness, whereas awareness relates to the qualitative aspects of the functions mediated by the cortex, including cognitive abilities such as attention, sensory perception, explicit memory, language, the execution of tasks, temporal and spatial orientation and reality judgment. From a neurological perspective, consciousness is maintained by the activation of the cerebral cortex—the gray matter that forms the outer layer of the brain—and by the reticular activating system (RAS), a structure located within the brainstem. Etymology The term coma, from the Greek κῶμα koma, meaning deep sleep, had already been used in the Hippocratic corpus (Epidemica) and later by Galen (second century AD). Subsequently, it was hardly used in the known literature up to the middle of the 17th century. The term is found again in Thomas Willis (1621–1675) influential De anima brutorum (1672), where lethargy (pathological sleep), coma (heavy sleeping), carus (deprivation of the senses) and apoplexy (into which carus could turn and which he localized in the white matter) are mentioned. The term carus is also derived from Greek, where it can be found in the roots of several words meaning soporific or sleepy. It can still be found in the root of the term carotid. Thomas Sydenham (1624–89) mentioned the term coma in several cases of fever (Sydenham, 1685). Signs and symptoms General symptoms of a person in a comatose state are: Inability to voluntarily open the eyes A non-existent sleep-wake cycle Lack of response to physical (painful) or verbal stimuli Depressed brainstem reflexes, such as pupils not responding to light Irregular breathing Scores between 3 and 8 on the Glasgow Coma Scale Causes Many types of problems can cause a coma. Forty percent of comatose states result from drug poisoning. Certain drug use under certain conditions can damage or weaken the synaptic functioning in the ascending reticular activating system (ARAS) and keep the system from properly functioning to arouse the brain. Secondary effects of drugs, which include abnormal heart rate and blood pressure, as well as abnormal breathing and sweating, may also indirectly harm the functioning of the ARAS and lead to a coma. Given that drug poisoning is the cause for a large portion of patients in a coma, hospitals first test all comatose patients by observing pupil size and eye movement, through the vestibular-ocular reflex. (See Diagnosis below.)The second most common cause of coma, which makes up about 25% of cases, is lack of oxygen, generally resulting from cardiac arrest. The Central Nervous System (CNS) requires a great deal of oxygen for its neurons. Oxygen deprivation in the brain, also known as hypoxia, causes sodium and calcium from outside of the neurons to decrease and intracellular calcium to increase, which harms neuron communication. Lack of oxygen in the brain also causes ATP exhaustion and cellular breakdown from cytoskeleton damage and nitric oxide production.Twenty percent of comatose states result from the side effects of a stroke. During a stroke, blood flow to part of the brain is restricted or blocked. An ischemic stroke, brain hemorrhage, or tumor may cause restriction of blood flow. Lack of blood to cells in the brain prevents oxygen from getting to the neurons, and consequently causes cells to become disrupted and die. As brain cells die, brain tissue continues to deteriorate, which may affect the functioning of the ARAS.The remaining 15% of comatose cases result from trauma, excessive blood loss, malnutrition, hypothermia, hyperthermia, hyperammonemia, abnormal glucose levels, and many other biological disorders. Furthermore, studies show that 1 out of 8 patients with traumatic brain injury experience a comatose state. Pathophysiology Injury to either or both of the cerebral cortex or the reticular activating system (RAS) is sufficient to cause a person to enter coma.The cerebral cortex is the outer layer of neural tissue of the cerebrum of the brain. The cerebral cortex is composed of gray matter which consists of the nuclei of neurons, whereas the inner portion of the cerebrum is composed of white matter and is composed of the axons of neuron. White matter is responsible for perception, relay of the sensory input via the thalamic pathway, and many other neurological functions, including complex thinking. The RAS, on the other hand, is a more primitive structure in the brainstem which includes the reticular formation (RF). The RAS has two tracts, the ascending and descending tract. The ascending tract, or ascending reticular activating system (ARAS), is made up of a system of acetylcholine-producing neurons, and works to arouse and wake up the brain. Arousal of the brain begins from the RF, through the thalamus, and then finally to the cerebral cortex. Any impairment in ARAS functioning, a neuronal dysfunction, along the arousal pathway stated directly above, prevents the body from being aware of its surroundings. Without the arousal and consciousness centers, the body cannot awaken, remaining in a comatose state.The severity and mode of onset of coma depends on the underlying cause. There are two main subdivisions of a coma: structural and diffuse neuronal. A structural cause, for example, is brought upon by a mechanical force that brings about cellular damage, such as physical pressure or a blockage in neural transmission. While a diffuse cause is limited to aberrations of cellular function, that fall under a metabolic or toxic subgroup. Toxin-induced comas are caused by extrinsic substances, whereas metabolic-induced comas are caused by intrinsic processes, such as body thermoregulation or ionic imbalances(e.g. sodium). For instance, severe hypoglycemia (low blood sugar) or hypercapnia (increased carbon dioxide levels in the blood) are examples of a metabolic diffuse neuronal dysfunction. Hypoglycemia or hypercapnia initially cause mild agitation and confusion, but progress to obtundation, stupor, and finally, complete unconsciousness. In contrast, coma resulting from a severe traumatic brain injury or subarachnoid hemorrhage can be instantaneous. The mode of onset may therefore be indicative of the underlying cause.Structural and diffuse causes of coma are not isolated from one another, as one can lead to the other in some situations. For instance, coma induced by a diffuse metabolic process, such as hypoglycemia, can result in a structural coma if it is not resolved. Another example is if cerebral edema, a diffuse dysfunction, leads to ischemia of the brainstem, a structural issue, due to the blockage of the circulation in the brain. Diagnosis Although diagnosis of coma is simple, investigating the underlying cause of onset can be rather challenging. As such, after gaining stabilization of the patients airways, breathing and circulation (the basic ABCs) various diagnostic tests, such as physical examinations and imaging tools (CT scan, MRI, etc.) are employed to access the underlying cause of the coma.When an unconscious person enters a hospital, the hospital utilizes a series of diagnostic steps to identify the cause of unconsciousness. According to Young, the following steps should be taken when dealing with a patient possibly in a coma: Perform a general examination and medical history check Make sure the patient is in an actual comatose state and is not in a locked-in state or experiencing psychogenic unresponsiveness. Patients with locked-in syndrome present with voluntary movement of their eyes, whereas patients with psychogenic comas demonstrate active resistance to passive opening of the eyelids, with the eyelids closing abruptly and completely when the lifted upper eyelid is released (rather than slowly, asymmetrically and incompletely as seen in comas due to organic causes). Find the site of the brain that may be causing coma (e.g., brainstem, back of brain...) and assess the severity of the coma with the Glasgow Coma Scale Take blood work to see if drugs were involved or if it was a result of hypoventilation/hyperventilation Check for levels of serum glucose, calcium, sodium, potassium, magnesium, phosphate, urea, and creatinine Perform brain scans to observe any abnormal brain functioning using either CT or MRI scans Continue to monitor brain waves and identify seizures of patient using EEGs Initial evaluation In the initial assessment of coma, it is common to gauge the level of consciousness on the AVPU (alert, vocal stimuli, painful stimuli, unresponsive) scale by spontaneously exhibiting actions and, assessing the patients response to vocal and painful stimuli. More elaborate scales, such as the Glasgow Coma Scale, quantify an individuals reactions such as eye opening, movement and verbal response in order to indicate their extent of brain injury. The patients score can vary from a score of 3 (indicating severe brain injury and death) to 15 (indicating mild or no brain injury).In those with deep unconsciousness, there is a risk of asphyxiation as the control over the muscles in the face and throat is diminished. As a result, those presenting to a hospital with coma are typically assessed for this risk ("airway management"). If the risk of asphyxiation is deemed high, doctors may use various devices (such as an oropharyngeal airway, nasopharyngeal airway or endotracheal tube) to safeguard the airway. Imaging and testing Imaging basically encompasses computed tomography (CAT or CT) scan of the brain, or MRI for example, and is performed to identify specific causes of the coma, such as hemorrhage in the brain or herniation of the brain structures. Special tests such as an EEG can also show a lot about the activity level of the cortex such as semantic processing, presence of seizures, and are important available tools not only for the assessment of the cortical activity but also for predicting the likelihood of the patients awakening. The autonomous responses such as the skin conductance response may also provide further insight on the patients emotional processing.In the treatment of traumatic brain injury (TBI), there are 4 examination methods that have proved useful: skull x-ray, angiography, computed tomography (CT), and magnetic resonance imaging (MRI). The skull x-ray can detect linear fractures, impression fractures (expression fractures) and burst fractures. Angiography is used on rare occasions for TBIs i.e. when there is suspicion of an aneurysm, carotid sinus fistula, traumatic vascular occlusion, and vascular dissection. A CT can detect changes in density between the brain tissue and hemorrhages like subdural and intracerebral hemorrhages. MRIs are not the first choice in emergencies because of the long scanning times and because fractures cannot be detected as well as CT. MRIs are used for the imaging of soft tissues and lesions in the posterior fossa which cannot be found with the use of CT. Body movements Assessment of the brainstem and cortical function through special reflex tests such as the oculocephalic reflex test (dolls eyes test), oculovestibular reflex test (cold caloric test), corneal reflex, and the gag reflex. Reflexes are a good indicator of what cranial nerves are still intact and functioning and is an important part of the physical exam. Due to the unconscious status of the patient, only a limited number of the nerves can be assessed. These include the cranial nerves number 2 (CN II), number 3 (CN III), number 5 (CN V), number 7 (CN VII), and cranial nerves 9 and 10 (CN IX, CN X). Assessment of posture and physique is the next step. It involves general observation about the patients positioning. There are often two stereotypical postures seen in comatose patients. Decorticate posturing is a stereotypical posturing in which the patient has arms flexed at the elbow, and arms adducted toward the body, with both legs extended. Decerebrate posturing is a stereotypical posturing in which the legs are similarly extended (stretched), but the arms are also stretched (extended at the elbow). The posturing is critical since it indicates where the damage is in the central nervous system. A decorticate posturing indicates a lesion (a point of damage) at or above the red nucleus, whereas a decerebrate posturing indicates a lesion at or below the red nucleus. In other words, a decorticate lesion is closer to the cortex, as opposed to a decerebrate posturing which indicates that the lesion is closer to the brainstem. Pupil size Pupil assessment is often a critical portion of a comatose examination, as it can give information as to the cause of the coma; the following table is a technical, medical guideline for common pupil findings and their possible interpretations: Severity A coma can be classified as (1) supratentorial (above Tentorium cerebelli), (2) infratentorial (below Tentorium cerebelli), (3) metabolic or (4) diffused. This classification is merely dependent on the position of the original damage that caused the coma, and does not correlate with severity or the prognosis. The severity of coma impairment however is categorized into several levels. Patients may or may not progress through these levels. In the first level, the brain responsiveness lessens, normal reflexes are lost, the patient no longer responds to pain and cannot hear. The Rancho Los Amigos Scale is a complex scale that has eight separate levels, and is often used in the first few weeks or months of coma while the patient is under closer observation, and when shifts between levels are more frequent. Treatment Treatment for people in a coma will depend on the severity and cause of the comatose state. Upon admittance to an emergency department, coma patients will usually be placed in an Intensive Care Unit (ICU) immediately, where maintenance of the patients respiration and circulation become a first priority. Stability of their respiration and circulation is sustained through the use of intubation, ventilation, administration of intravenous fluids or blood and other supportive care as needed. Continued care Once a patient is stable and no longer in immediate danger, there may be a shift of priority from stabilizing the patient to maintaining the state of their physical wellbeing. Moving patients every 2–3 hours by turning them side to side is crucial to avoiding bed sores as a result of being confined to a bed. Moving patients through the use of physical therapy also aids in preventing atelectasis, contractures or other orthopedic deformities which would interfere with a coma patients recovery.Pneumonia is also common in coma patients due to their inability to swallow which can then lead to aspiration. A coma patients lack of a gag reflex and use of a feeding tube can result in food, drink or other solid organic matter being lodged within their lower respiratory tract (from the trachea to the lungs). This trapping of matter in their lower respiratory tract can ultimately lead to infection, resulting in aspiration pneumonia.Coma patients may also deal with restlessness or seizures. As such, soft cloth restraints may be used to prevent them from pulling on tubes or dressings and side rails on the bed should be kept up to prevent patients from falling. Caregivers Coma has a wide variety of emotional reactions from the family members of the affected patients, as well as the primary care givers taking care of the patients. Research has shown that the severity of injury causing coma was found to have no significant impact compared to how much time has passed since the injury occurred. Common reactions, such as desperation, anger, frustration, and denial are possible. The focus of the patient care should be on creating an amicable relationship with the family members or dependents of a comatose patient as well as creating a rapport with the medical staff. Although there is heavy importance of a primary care taker, secondary care takers can play a supporting role to temporarily relieve the primary care takers burden of tasks. Prognosis Comas can last from several days to, in particularly extreme cases, years. Some patients eventually gradually come out of the coma, some progress to a vegetative state, and others die. Some patients who have entered a vegetative state go on to regain a degree of awareness; and in some cases may remain in vegetative state for years or even decades (the longest recorded period is 42 years).Predicted chances of recovery will differ depending on which techniques were used to measure the patients severity of neurological damage. Predictions of recovery are based on statistical rates, expressed as the level of chance the person has of recovering. Time is the best general predictor of a chance of recovery. For example, after four months of coma caused by brain damage, the chance of partial recovery is less than 15%, and the chance of full recovery is very low.The outcome for coma and vegetative state depends on the cause, location, severity and extent of neurological damage. A deeper coma alone does not necessarily mean a slimmer chance of recovery; similarly, a milder coma does not indicate a higher chance of recovery. The most common cause of death for a person in a vegetative state is secondary infection such as pneumonia, which can occur in patients who lie still for extended periods. Recovery People may emerge from a coma with a combination of physical, intellectual, and psychological difficulties that need special attention. It is common for coma patients to awaken in a profound state of confusion and experience dysarthria, the inability to articulate any speech. Recovery is usually gradual. In the first days, the patient may only awaken for a few minutes, with increased duration of wakefulness as their recovery progresses, and they may eventually recover full awareness. That said, some patients may never progress beyond very basic responses.There are reports of people coming out of a coma after long periods of time. After 19 years in a minimally conscious state, Terry Wallis spontaneously began speaking and regained awareness of his surroundings.A man with brain-damage and trapped in a coma-like state for six years, was brought back to consciousness in 2003 by doctors who planted electrodes deep inside his brain. The method, called deep brain stimulation (DBS), successfully roused communication, complex movement and eating ability in the 38-year-old American man with a traumatic brain injury. His injuries left him in a minimally conscious state, a condition akin to a coma but characterized by occasional, but brief, evidence of environmental and self-awareness that coma patients lack. Society and culture Research by Dr. Eelco Wijdicks on the depiction of comas in movies was published in Neurology in May 2006. Dr. Wijdicks studied 30 films (made between 1970 and 2004) that portrayed actors in prolonged comas, and he concluded that only two films accurately depicted the state of a coma patient and the agony of waiting for a patient to awaken: Reversal of Fortune (1990) and The Dreamlife of Angels (1998). The remaining 28 were criticized for portraying miraculous awakenings with no lasting side effects, unrealistic depictions of treatments and equipment required, and comatose patients remaining muscular and tanned. Bioethics A person in a coma is said to be in an unconscious state. Perspectives on personhood, identity and consciousness come into play when discussing the metaphysical and bioethical views on comas. It has been argued that unawareness should be just as ethically relevant and important as a state of awareness and that there should be metaphysical support of unawareness as a state.In the ethical discussions about disorders of consciousness (DOCs), two abilities are usually considered as central: experiencing well-being and having interest. Well-being can broadly be understood as the positive effect related to what makes life good (according to specific standards) for the individual in question. The only condition for well-being broadly considered is the ability to experience its ‘positiveness’. That said, because experiencing positiveness is a basic emotional process with phylogenetic roots, it is likely to occur at a completely unaware level and therefore, introduces the idea of an unconscious well-being. As such, the ability of having interests, is crucial for describing two abilities which those with comas are deficient in. Having an interest in a certain domain can be understood as having a stake in something that can affect what makes our life good in that domain. An interest is what directly and immediately improves life from a certain point of view or within a particular domain, or greatly increases the likelihood of life improvement enabling the subject to realize some good. That said, sensitivity to reward signals is a fundamental element in the learning process, both consciously and unconsciously. Moreover, the unconscious brain is able to interact with its surroundings in a meaningful way and to produce meaningful information processing of stimuli coming from the external environment, including other people.According to Hawkins, "1. A life is good if the subject is able to value, or more basically if the subject is able to care. Importantly, Hawkins stresses that caring has no need for cognitive commitment, i.e. for high-level cognitive activities: it requires being able to distinguish something, track it for a while, recognize it over time, and have certain emotional dispositions vis-à-vis something. 2. A life is good if the subject has the capacity for relationship with others, i.e. for meaningfully interacting with other people." This suggests that unawareness may (at least partly) fulfill both conditions identified by Hawkins for life to be good for a subject, thus making the unconscious ethically relevant. See also Brain death, lack of activity in both cortex, and lack of brainstem function Coma scale, a system to assess the severity of coma Locked-in syndrome, paralysis of most muscles, except ocular muscles of the eyes, while patient is conscious Persistent vegetative state (vegetative coma), deep coma without detectable awareness. Damage to the cortex, with an intact brainstem. Process Oriented Coma Work, for an approach to working with residual consciousness in comatose patients. Suspended animation, the inducement of a temporary cessation or decay of main body functions. References == External links ==
Carcinoid	A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) are associated with carcinoid syndrome. Carcinoid tumors are the most common malignant tumor of the appendix, but they are most commonly associated with the small intestine, and they can also be found in the rectum and stomach. They are known to grow in the liver, but this finding is usually a manifestation of metastatic disease from a primary carcinoid occurring elsewhere in the body. They have a very slow growth rate compared to most malignant tumors. The median age at diagnosis for all patients with neuroendocrine tumors is 63 years. Signs and symptoms While most carcinoids are asymptomatic through the natural life and are discovered only upon surgery for unrelated reasons (so-called coincidental carcinoids), all carcinoids are considered to have malignant potential. About 10% of carcinoids secrete excessive levels of a range of hormones, most notably serotonin (5-HT), causing: Flushing (serotonin itself does not cause flushing). Potential causes of flushing in carcinoid syndrome include bradykinins, prostaglandins, tachykinins, substance P, and/or histamine, diarrhea, and heart problems. Because of serotonins growth-promoting effect on cardiac myocytes, a serotonin-secreting carcinoid tumour may cause a tricuspid valve disease syndrome, due to the proliferation of myocytes onto the valve. Diarrhea Wheezing Abdominal cramping Peripheral edemaThe outflow of serotonin can cause a depletion of tryptophan leading to niacin deficiency. Niacin deficiency, also known as pellagra, is associated with dermatitis, dementia, and diarrhea. This constellation of symptoms is called carcinoid syndrome or (if acute) carcinoid crisis. Occasionally, haemorrhage or the effects of tumor bulk are the presenting symptoms. The most common originating site of carcinoid is the small bowel, particularly the ileum; carcinoid tumors are the most common malignancy of the appendix. Carcinoid tumors may rarely arise from the ovary or thymus.They are most commonly found in the midgut at the level of the ileum or in the appendix. The next most commonly affected area is the respiratory tract, with 28% of all cases—per PAN-SEER data (1973–1999). The rectum is also a common site. Gastrointestinal Carcinoid tumors are apudomas that arise from the enterochromaffin cells throughout the gut. Over two-thirds of carcinoid tumors are found in the gastrointestinal tract. Lung Carcinoid tumors are also found in the lungs. Other sites and metastases Metastasis of carcinoid can lead to carcinoid syndrome. This is due to the over-production of many substances, including serotonin, which are released into the systemic circulation, and which can lead to symptoms of cutaneous flushing, diarrhea, bronchoconstriction, and right-sided cardiac valve disease. It is estimated that less than 6% of carcinoid patients will develop carcinoid syndrome, and of these, 50% will have cardiac involvement. Goblet cell carcinoid This is considered to be a hybrid between an exocrine and endocrine tumor derived from crypt cells of the appendix. Histologically, it forms clusters of goblet cells containing mucin with a minor admixture of Paneth cells and endocrine cells. The growth pattern is distinctive: typically producing a concentric band of tumor nests interspersed among the muscle and stroma of the appendiceal wall extending up the shaft of the appendix. This makes the lesion difficult to suspect grossly and difficult to measure. Small tumor nests may be camouflaged amongst the muscle or in periappendiceal fat; cytokeratin preparations best demonstrate the tumor cells; mucin stains are also helpful in identifying them. They behave in a more aggressive manner than do classical appendiceal carcinoids. Spread is usually to regional lymph nodes, peritoneum, and particularly the ovary. They do not produce sufficient hormonal substances to cause carcinoid or other endocrine syndromes. In fact, they more closely resemble exocrine than endocrine tumors. The term crypt cell carcinoma has been used for them, and though perhaps more accurate than considering them carcinoids, has not been a successful competitor. Cause Carcinoid syndrome involves multiple tumors in one out of five males. The incidence of gastric carcinoids is increased in achlorhydria, Hashimotos thyroiditis, and pernicious anemia. Treatment Surgery, if feasible, is the only curative therapy. If the tumor has metastasized (most commonly, to the liver) and is considered incurable, there are some promising treatment modalities, such as radiolabeled octreotide (e.g. Lutetium (177Lu) DOTA-octreotate) or the radiopharmaceutical 131I-mIBG (meta iodo benzyl guanidine) for arresting the growth of the tumors and prolonging survival in patients with liver metastases, though these are currently experimental. Chemotherapy is of little benefit and is generally not indicated. Octreotide or lanreotide (somatostatin analogues) may decrease the secretory activity of the carcinoid, and may also have an anti-proliferative effect. Interferon treatment is also effective, and usually combined with somatostatin analogues. As the metastatic potential of a coincidental carcinoid is probably low, the current recommendation is for follow up in 3 months with CT or MRI, labs for tumor markers such as serotonin, and a history and physical, with annual physicals thereafter. History They were first characterized in 1907 by Siegfried Oberndorfer, a German pathologist at the University of Munich, who coined the term karzinoide, or "carcinoma-like", to describe the unique feature of behaving like a benign tumor despite having a malignant appearance microscopically. The recognition of their endocrine-related properties was later described by Gosset and Masson in 1914, and these tumors are now known to arise from the enterochromaffin (EC) and enterochromaffin-like (ECL) cells of the gut. Some sources credit Otto Lubarsch with the discovery. In 2000, the World Health Organization redefined "carcinoid", but this new definition has not been accepted by all practitioners. This has led to some complexity in distinguishing between carcinoid and other neuroendocrine tumors in the literature. According to the American Cancer Society, the 2000 WHO definition states: The WHO now divides these growths into neuroendocrine tumors and neuroendocrine cancers. Neuroendocrine tumors are growths that look benign but that might possibly be able to spread to other parts of the body. Neuroendocrine cancers are abnormal growths of neuroendocrine cells which can spread to other parts of the body. See also Carcinoid syndrome Don Meyer, head coach emeritus of the Northern State University mens basketball team. Meyer was found to have carcinoid cancer following an automobile accident in September 2009. Derrick Bell, professor and legal scholar, died of carcinoid cancer on October 5, 2011. References == External links ==
Combined hyperlipidemia	Combined hyperlipidemia (or -aemia) is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL.: 534 On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most commonly inherited lipid disorder, occurring in around one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 have this disorder. The elevated triglyceride levels (>5 mmol/L) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoproteins prone to cause atherosclerosis. Cause Hereditary factors are the most common cause. A diet high in saturated fat and cholesterol increases blood cholesterol and triglyceride levels. Other disorders, such as diabetes mellitus, kidney disease, and hypothyroidism, may promote hypertriglyceridemia. Certain drugs, such as estrogen, corticosteroids, retinoids, protease inhibitors, thiazide diuretics, and beta-blockers, may cause hypertriglyceridemia. Obesity increases the risk of hyperlipidemia. Chronic, excessive alcohol use increases the risk of hypertriglyceridemia. Smoking and not exercising may lead to hyperlipidemia. Steroid uses, alcoholism, hypothyroidism, oral contraceptives, chronic kidney failure, hypopituitarism, and nephritic syndrome are other contributors to hyperlipidemia. Diagnosis Types The two forms of this lipid disorder are: Familial combined hyperlipidemia (FCH) is the familial occurrence of this disorder, probably caused by decreased LDL receptor and increased ApoB. Acquired combined hyperlipidemia is extremely common in patients who have other diseases from the metabolic syndrome ("syndrome X", incorporating diabetes mellitus type II, hypertension, central obesity and CH). Excessive free fatty acid production by various tissues leads to increased VLDL synthesis by the liver. Initially, most VLDL is converted into LDL until this mechanism is saturated, after which VLDL levels elevate. Treatment Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production. Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin), can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression. See also Hyperlipidemia References == External links ==
Anal fistula	Anal fistula is a chronic abnormal communication between the epithelialised surface of the anal canal and usually the perianal skin. An anal fistula can be described as a narrow tunnel with its internal opening in the anal canal and its external opening in the skin near the anus. Anal fistulae commonly occur in people with a history of anal abscesses. They can form when anal abscesses do not heal properly.Anal fistulae originate from the anal glands, which are located between the internal and external anal sphincter and drain into the anal canal. If the outlet of these glands becomes blocked, an abscess can form which can eventually extend to the skin surface. The tract formed by this process is a fistula.Abscesses can recur if the fistula seals over, allowing the accumulation of pus. It can then extend to the surface again – repeating the process.Anal fistulae per se do not generally harm, but can be very painful, and can be irritating because of the drainage of pus (it is also possible for formed stools to be passed through the fistula). Additionally, recurrent abscesses may lead to significant short term morbidity from pain and, importantly, create a starting point for systemic infection.Treatment, in the form of surgery, is considered essential to allow drainage and prevent infection. Repair of the fistula itself is considered an elective procedure which many patients opt for due to the discomfort and inconvenience associated with an actively draining fistula. Signs and symptoms Anal fistulae can present with the following symptoms: skin maceration pus, serous fluid and/or (rarely) feces discharge — can be bloody or purulent pruritus ani — itching depending on presence and severity of infection:pain swelling tenderness fever unpleasant odorThick discharge, which keeps the area wet Diagnosis Diagnosis is by examination, either in an outpatient setting or under anaesthesia (referred to as EUA or Examination Under Anaesthesia). The fistula may be explored by using a fistula probe (a narrow instrument). In this way, it may be possible to find both openings. The examination can be an anoscopy. Diagnosis may be aided by performing a fistulogram, proctoscopy and/or sigmoidoscopy. Possible findings: The opening of the fistula onto the skin may be observed The area may be painful on examination There may be redness An area of induration may be felt; thickening due to chronic infection A discharge may be seen Classification Parks classification: This was done by Parks et al. from the UK in 1976, before MRI or endoanal ultrasound was available. It classified the fistula in four grades: St James University Hospital Classification: This was done by Morris et al. in the year 2000. This classification was improvement over Parks classification as it was based on MRI studies. It classified the fistula in five grades. Garg classification: This was done by Pankaj Garg in 2017. This classification is improvement over both Parks and St James University Hospital Classification. This was based on MRI studies and operative findings in 440 patients. It classified the fistula in five grades. The grades of this classification correlate quite well with the severity of the disease. Grade I & II are simpler fistulas and can be managed by Fistulotomy whereas Grade III-V are complex fistulas in which fistulotomy should be not be done. They should be managed by Fistula experts. Unlike Parks and St James University Hospital Classification, this correlation is quite accurate with Gargs classification. Therefore this new classification is useful to both surgeons and radiologists. Types Depending on their relationship with the internal and external sphincter muscles, fistulae are classified into five types: Extrasphincteric fistulae begin at the rectum or sigmoid colon and proceed downward, through the levator ani muscle and open into the skin surrounding the anus. Note that this type does not arise from the dentate line (where the anal glands are located). Causes of this type could be from a rectal, pelvic or supralevator origin, usually secondary to Crohns disease or an inflammatory process such as appendiceal or diverticular abscesses. Suprasphincteric fistulae begin between the internal and external sphincter muscles, extend above and cross the puborectalis muscle, proceed downward between the puborectalis and levator ani muscles, and open an inch or more away from the anus. Transphincteric fistulae begin between the internal and external sphincter muscles or behind the anus, cross the external sphincter muscle and open an inch or more away from the anus. These may take a U shape and form multiple external openings. This is sometimes termed a horseshoe fistula. Intersphincteric fistulae begin between the internal and external sphincter muscles, pass through the internal sphincter muscle, and open very close to the anus. Submucosal fistulae pass superficially beneath the submucosa and do not cross either sphincter muscle. Differential diagnosis Other conditions in which infected perianal "holes" or openings may include pilonidal cyst. Treatment There are several stages to treating an anal fistula: Definitive treatment of A fistula aims to stop it recurring. Treatment depends on where the fistula lies, and which parts of the internal and external anal sphincters it crosses. Lay-open of fistula-in-ano – this option involves an operation to cut the fistula open. Once the fistula has been laid open it will be packed on a daily basis for a short period of time to ensure that the wound heals from the inside out. This option leaves behind a scar, and depending on the position of the fistula in relation to the sphincter muscle, can cause problems with incontinence. This option is not suitable for fistulae that cross the entire internal and external anal sphincter. Cutting seton – if the fistula is in a high position and it passes through a significant portion of the sphincter muscle, a cutting seton (from the Latin seta, "bristle") may be used. This involves inserting a thin tube through the fistula tract and tying the ends together outside of the body. The seton is tightened over time, gradually cutting through the sphincter muscle and healing as it goes. This option minimizes scarring but can cause incontinence in a small number of cases, mainly of flatus. Once the fistula tract is in a low enough position it may be laid open to speed up the process, or the seton can remain in place until the fistula is completely cured. This was the traditional modality used by physicians in Ancient Egypt and formally codified by Hippocrates, who used horsehair and linen. Seton stitch – a length of suture material looped through the fistula which keeps it open and allows pus to drain out. In this situation, the seton is referred to as a draining seton. The stitch is placed close to the ano-rectal ring – which encourages healing and makes further surgery easy. Fistulotomy – till anorectal ring Colostomy – to allow healing Fibrin glue injection is a method explored in recent years, with variable success. It involves injecting the fistula with a biodegradable glue which should, in theory, close the fistula from the inside out, and let it heal naturally. This method is perhaps best tried before all others since, if successful, it avoids the risk of incontinence, and creates minimal stress for the patient. Fistula plug involves plugging the fistula with a device made from small intestinal submucosa. The fistula plug is positioned from the inside of the anus with suture. According to some sources, the success rate with this method is as high as 80%. As opposed to the staged operations, which may require multiple hospitalizations, the fistula plug procedure requires hospitalization for only about 24 hours. Currently, there are two different anal fistula plugs cleared by the FDA for treating ano-rectal fistulae in the United States. This treatment option does not carry any risk of bowel incontinence. In the systematic review published by Dr Pankaj Garg, the success rate of the fistula plug is 65–75%. Endorectal advancement flap is a procedure in which the internal opening of the fistula is identified and a flap of mucosal tissue is cut around the opening. The flap is lifted to expose the fistula, which is then cleaned and the internal opening is sewn shut. After cutting the end of the flap on which the internal opening was, the flap is pulled down over the sewn internal opening and sutured in place. The external opening is cleaned and sutured. Success rates are variable and high recurrence rates are directly related to previous attempts to correct the fistula. LIFT Technique is a novel modified approach through the intersphincteric plane for the treatment of fistula-in-ano, known as LIFT (ligation of intersphincteric fistula tract) procedure. LIFT procedure is based on secure closure of the internal opening and removal of infected cryptoglandular tissue through the intersphincteric approach. Essential steps of the procedure include, incision at the intersphincteric groove, identification of the intersphincteric tract, ligation of intersphincteric tract close to the internal opening and removal of intersphincteric tract, scraping out all granulation tissue in the rest of the fistulous tract, and suturing of the defect at the external sphincter muscle. The procedure was developed by Thai colorectal surgeon, Arun Rojanasakul, The first reports of preliminary healing result from the procedure were 94% in 2007. Additional ligation of the intersphincteric fistula tract did not improve the outcome after endorectal advancement flap. Fistula clip closure (OTSC Proctology) is a recent surgical development, which involves the closure of the internal fistula opening with a superelastic clip made of nitinol (OTSC). During surgery, the fistula tract is debrided with a special fistula brush and the clip is transanally applied with the aid of a preloaded clip applicator. The surgical principle of this technique relies on the dynamic compression and permanent closure of the internal fistula opening by the superelastic clip. Consequently, the fistula tract dries out and heals instead of being kept open by continuous feeding with stool and fecal organisms. This minimally-invasive sphincter-preserving technique has been developed and clinically implemented by the German surgeon Ruediger Prosst. First clinical data of the clip closure technique demonstrate a success rate of 90% for previously untreated fistulae and a success rate of 70% for recurrent fistulae. VAAFT is a surgical kit for treating anal fistulae. The system comprises: A video telescope (fistuloscope) to allow surgeons to see inside the fistula tract. A unipolar electrode for diathermy of the internal tract. This is connected to a high frequency generator. A fistula brush and forceps for cleaning the tract and clearing any granulation tissue.The VAAFT procedure is done in 2 phases, diagnostic and operative. Before the procedure, the patient is given a spinal or general anaesthetic and is placed in the lithotomy position (legs in stirrups with the perineum at the edge of the table). In the diagnostic phase, the fistuloscope is inserted into the fistula to locate the internal opening in the anus and to identify any secondary tracts or abscess cavities. The anal canal is held open using a speculum and irrigation solution is used to give a clear view of the fistula tract. Light from the fistuloscope can be seen from inside the anal canal at the location of the internal opening of the fistula, which helps to locate the internal opening. In the operative phase of the procedure, the fistula tract is cleaned and the internal opening of the fistula is sealed. To do this, the surgeon uses the unipolar electrode, under video guidance, to cauterise material in the fistula tract. Necrotic material is removed at the same time using the fistula brush and forceps, as well as by continuous irrigation. The surgeon then closes the internal opening from inside the anal canal using stitches and staples. Infection Some people will have an active infection when they present with a fistula, and this requires clearing up before definitive treatment can be decided. Antibiotics can be used as with other infections, but the best way of healing infection is to prevent the buildup of pus in the fistula, which leads to abscess formation. This can be done with a seton. Epidemiology A literature review published in 2018 showed an incidence as high as 21 people per 100,000. "Anal fistulas are 2–6 times more prevalent in males than females, with the condition occurring most frequently in patients in their 30s and 40s." References == External links ==
Phakomatosis pigmentokeratotica	Phakomatosis pigmentokeratotica is a rare neurocutanous condition characterized by the combination of an organoid sebaceous nevus and speckled lentiginous nevus.: 634–5 : 776 It is an unusual variant of epidermal naevus syndrome. It was first described by Happle et al. It is often associated with neurological or skeletal anomalies such as hemiatrophy, dysaesthesia and hyperhidrosis in a segmental pattern, mild mental retardation, seizures, deafness, ptosis and strabismus. See also Skin lesion List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer References == External links ==
Ameboma	An ameboma, also known as an amebic granuloma, is a rare complication of Entamoeba histolytica infection, where in response to the infecting amoeba there is formation of annular colonic granulation, which results in a large local lesion of the bowel. Presentation The ameboma may manifest as a right lower quadrant abdominal mass, which may be mistaken for carcinoma, tuberculosis, Crohns disease, actinomycosis, or lymphoma. Diagnosis Biopsy is necessary for definitive diagnosis. == References ==
Psychogenic alopecia	Psychogenic alopecia, also called over-grooming or psychological baldness, is a compulsive behavior that affects domestic cats. Generally, psychogenic alopecia does not lead to serious health consequences or a decreased lifespan. Causes Grooming is a natural behavior for cats. Cats spend 5–25% of their waking hours grooming. Grooming becomes excessive when it takes precedence over other activities or no longer seems functional. Excessive grooming, which can lead to hair loss, skin wounds, and ulceration, can result from chronic stress or develop in cats who already exhibit nervous temperaments. Even when the source of stress is resolved or removed, excessive grooming may continue. There may be some genetic basis for the behavior, and it predominantly affects purebred cats of oriental breeds, but can develop in any feline. Female cats appear more susceptible. Environmental factors suspected of causing over-grooming include flea allergy, boredom, food allergy, dust or pollen causing an allergic reaction, constipation and urinary tract infection caused by avoidance of a dirty litter tray, dermatitis, and anxiety caused by inconsistent meal times. Deprivation of sunlight could be the part of the problem for indoors only cats. Symptoms Areas affected are those the cat can access most easily, including the abdomen, legs, flank, and chest. Baldness, usually beginning with the abdomen. Obvious over-grooming (although some cats may only engage in the behavior in the absence of owners). Redness, rashes, pus, scabs on the bald area or areas traumatized by over-grooming. A highly irritable cat may even cut its face with the claw of its hind foot if over-zealously scratching the back of its head. Treatment The cat should be taken to a veterinarian. The most suspected cause of skin problems in cats will be fleas. Other causes of over-grooming are not as easily ascertained. As household antiseptics are known to be toxic to cats, veterinary antiseptics for cats can be used to treat open sores, if they do occur. Sores can also be treated with cream, oral or injected anti-inflammatories, however if the problem continues to recur it may be more cost effective to subject the cat to laboratory testing early on. It may be difficult to keep a clean dressing on a cats belly, and an anti-lick collar is adequate to let the wound heal. If an anti-lick collar is used, a soft anti-lick collar is less cumbersome, although they are less durable. If the cat wears a plastic anti-lick collar, it may use the edge of the collar to grind against existing wounds, making them worse. A soft anti-lick collar will become less effective as it is kicked out of the shape by the cats hind leg, and will need prompt replacement. The cat can sanitize the wound if the collar is removed for daily short periods of time, also giving the cat an opportunity for an overall grooming. Scratches and wounds can heal completely using this method. When the cat stops wearing the collar, thinned hair, redness of skin or cracked nipples on the cat are early indicators that the cat has started to over-groom again. Antidepressants for cats may be suggested by a vet. See also Cat flea Cat health Cat skin disorders Feather-plucking Trichotillomania: a compulsive hair-pulling behavior in humans that can cause hair loss == References ==
Lipedema	Lipedema is a condition that is almost exclusively found in women and results in enlargement of both legs due to deposits of fat under the skin. Women of any weight may develop lipedema and the fat associated with lipedema is resistant to traditional weight-loss methods. There is no cure and typically it gets worse over time, pain may be present, and patients bruise easily. Over time mobility may be reduced, and due to reduced quality of life, patients often experience depression. In severe cases the trunk and upper body may be involved. Lipedema is commonly misdiagnosed and is now becoming known as lipoalgia due to there being no oedema.The cause is unknown but is believed to involve genetics and hormonal factors. It often runs in families; having a family member with the condition is a risk factor for developing it. Other conditions that may present similarly include lipohypertrophy, chronic venous insufficiency, and lymphedema. It is estimated to affect up to 11% of women. Onset is typically during puberty, pregnancy, or menopause.The fat associated with lipedema is shown to be resistant to weight loss methods; however, unlike other fat, lipedema is not associated with increased risks of diabetes or cardiovascular disease. Physiotherapy may help to preserve mobility for a little longer than would otherwise be the case. Exercise, only as much as the patient is able to do without causing damage to the joints, may help with overall fitness but will not prevent progression of the disease. Compression stockings can help with pain and make walking easier. Regularly moisturising with emollients protects the skin and prevents it from drying out. Liposuction to remove the fat can help if the symptoms are particularly severe. While surgery can remove fat tissue it can also damage lymphatic vessels. Treatment does not typically result in complete resolution. Presentation Associated conditions Depression and anxiety are very common for a variety of reasons, particularly the fact that diagnosis usually takes a long time and patients have received much advice on diet and exercise in the meantime, neither of which are effective treatment for the lipedema although they may help associated conditions. Joint pain, arthritis, dry skin, fungal infections, cellulitis and slow wound healing are also associated with lipedema. Diagnosis Differential diagnosis Lipedema stages Lipedema is classified by stage: Stage 1: Normal skin surface with enlarged hypodermis (lipedema fat). Stage 2: Uneven skin with indentations in fat and larger hypodermal masses (lipomas). Stage 3: Bulky extrusions of skin and fat cause large deformations especially on the thighs and around the knees. These large extrusions of tissue drastically inhibit mobility. Similar conditions Lipedema is often underdiagnosed due to the difficulty in differentiating it from lymphedema, obesity, or other edemas. Lipo-lymphedema Lipo-lymphedema, a secondary lymphedema, is associated with both lipedema and obesity (which occur together in the majority of cases), most often lipedema stages 2 and 3. Dercums disease Lipedema / Dercums disease differentiation – these conditions may co-exist. Dercums disease is a syndrome of painful growths in subcutaneous fat. Unlike lipedema, which occurs primarily in the trunk and legs, the fatty growths can occur anywhere on the body. Treatment A number of treatments may be useful including physiotherapy and light exercise which does not put undue stress on the lymphatic system. The two most common conservative treatments are manual lymphatic drainage (MLD) where a therapist gently opens lymphatic channels and moves the lymphatic fluid using hands-on techniques, and compression garments that keep the fluid at bay and assist the sluggish lymphatic flow.The use of surgical techniques is not universal but research has shown positive results in both short-term and long-term studies regarding lymph-sparing liposuction and lipectomy.The studies of highest quality involve tumescent local anesthesia (TLA), often referred to as simply tumescent liposuction. This can be accomplished via both Suction-Assisted Liposuction (SAL) and Power-Assisted (vibrating) liposuction. The treatment of lipedema with tumescent liposuction may require multiple procedures. While many health insurance carriers in the United States do not reimburse for liposuction for lipedema, in 2020 several carriers regard the procedure as reconstructive and medically necessary and do reimburse. Water Assisted Liposuction (WAL) is technically not considered to be tumescent but achieves the same goal as the anesthetic solution is injected as part of the procedure rather than before-hand. Developed by Doctor Ziah Taufig from Germany, it is usually performed under general anesthesia and is also considered to be lymph-sparing and protective of other tissues such blood vessels. Prognosis There is no cure. Complications include a malformed appearance, reduced functionality (mobility and gait), poor Quality of Life (QOL), depression, anxiety, and pain. Epidemiology According to an epidemiologic study by Földi E and Földi M, lipedema affects 11% of the female population, although rates from 6-39% have also been reported. History Lipedema was first identified in the United States, at the Mayo Clinic in 1940. Most attribute the original identification of lipedema to EA Hines and LE Wold (1951). In spite of that lipedema is barely known in the United States to physicians or to the patients who have the disease. Lipedema often is confused with obesity or lymphedema, and a significant number of patients currently diagnosed as obese are believed to have lipedema, either instead of or in addition to obesity. See also Lymphedema Steatopygia Adiposis dolorosa Lipodystrophy References == External links ==
Post-traumatic epilepsy	Post-traumatic epilepsy (PTE) is a form of acquired epilepsy that results from brain damage caused by physical trauma to the brain (traumatic brain injury, abbreviated TBI). A person with PTE experiences repeated post-traumatic seizures (PTS, seizures that result from TBI) more than a week after the initial injury. PTE is estimated to constitute 5% of all cases of epilepsy and over 20% of cases of acquired epilepsy (in which seizures are caused by an identifiable organic brain condition).It is not known who will develop epilepsy after TBI and who will not. However, the likelihood that a person will develop PTE is influenced by the severity and type of injury; for example penetrating injuries and those that involve bleeding within the brain confer a higher risk. The onset of PTE can occur within a short time of the physical trauma that causes it, or months or years after. People with head trauma may remain at a higher risk for post-traumatic seizures than the general population even decades after the injury. PTE may be caused by several biochemical processes that occur in the brain after trauma, including overexcitation of brain cells and damage to brain tissues by free radicals.Diagnostic measures include electroencephalography (EEG) and brain imaging techniques such as magnetic resonance imaging, but these are not totally reliable. Antiepileptic drugs do not prevent the development of PTE after head injury, but may be used to treat the condition if it does occur. When medication does not work to control the seizures, surgery may be needed. Modern surgical techniques for PTE have their roots in the 19th century, but trepanation (cutting the skull to make a hole) may have been used for the condition in ancient cultures. Classification Seizures may occur after traumatic brain injury; these are known as post-traumatic seizures (PTS). However, not everyone who has post-traumatic seizures will continue to have post-traumatic epilepsy, because the latter is a chronic condition. However, the terms PTS and PTE are used interchangeably in medical literature. Seizures due to post-traumatic epilepsy are differentiated from non-epileptic post-traumatic seizures based on their cause and timing after the trauma. A person with PTE has late seizures, those occurring more than a week after the initial trauma. Late seizures are considered to be unprovoked, while early seizures (those occurring within a week of trauma) are thought to result from direct effects of the injury. A provoked seizure is one that results from an exceptional, nonrecurring cause such as the immediate effects of trauma rather than a defect in the brain; it is not an indication of epilepsy. Thus for a diagnosis of PTE, seizures must be unprovoked. Disagreement exists about whether to define PTE as the occurrence of one or more late, unprovoked seizures, or whether the condition should only be diagnosed in people with two or more. Medical sources usually consider PTE to be present if even one unprovoked seizure occurs, but more recently it has become accepted to restrict the definition of all types of epilepsy to include only conditions in which more than one occur. Requiring more than one seizure for a diagnosis of PTE is more in line with the modern definition of epilepsy, but it eliminates people for whom seizures are controlled by medication after the first seizure.As with other forms of epilepsy, seizure types in PTE may be partial (affecting only part of one hemisphere of the brain) or generalized (affecting both hemispheres and associated with loss of consciousness). In about a third of cases, people with PTE have partial seizures; these may be simple or complex. In simple partial seizures, level of consciousness is not altered, while in complex partial seizures consciousness is impaired. When generalized seizures occur, they may start out as partial seizures and then spread to become generalized. Causes It is not clear why some patients develop PTE while others with very similar injuries do not. However, possible risk factors have been identified, including severity and type of injury, presence of early seizures, and genetic factors. Genetics Genetics may play a role in the risk that a person will develop PTE; people with the ApoE-ε4 allele may be at higher risk for PTE. The haptoglobin Hp2-2 allele may be another genetic risk factor, possibly because it binds hemoglobin poorly and thus allows more iron to escape and damage tissues. However, most studies have found that having family members with epilepsy does not significantly increase the risk of PTS, suggesting that genetics are not a strong risk factor. Severity of trauma The more severe the brain trauma is, the more likely a person is to have late PTE. Evidence suggests that mild head injuries do not confer an increased risk of developing PTE, while more severe types do. In simple mild TBI, the risk for PTE is about 1.5 times that of the uninjured population. By some estimates, as many as half of individuals with severe brain trauma experience PTE; other estimates place the risk at 5% for all TBI patients and 15–20% for severe TBI. One study found that the 30-year risk of developing PTE was 2.1% for mild TBI, 4.2% for moderate, and 16.7% for severe injuries, as shown in the chart at right. Nature of trauma The nature of the head trauma also influences the risk of PTE. People who have depressed skull fractures, penetrating head trauma, early PTS, and intracerebral and subdural haematomas due to the TBI are especially likely to have PTE, which occurs in more than 30% of people with any one of these findings. About 50% of patients with penetrating head trauma develop PTE, and missile injuries and loss of brain volume are associated with an especially high likelihood of developing the condition. Injuries that occur in military settings carry higher-than-usual risk for PTE, probably because they more commonly involve penetrating brain injury and brain damage over a more widespread area. Intracranial hematomas, in which blood accumulates inside the skull, are one of the most important risk factors for PTE. Subdural hematoma confers a higher risk of PTE than does epidural hematoma, possibly because it causes more damage to brain tissue. Repeated intracranial surgery confers a high risk for late PTE, possibly because people who need more surgery are more likely to have factors associated with worse brain trauma such as large hematomas or cerebral swelling. In addition, the chances of developing PTE differ by the location of the brain lesion: brain contusion that occurs on in one or the other of the frontal lobes has been found to carry a 20% PTE risk, while a contusion in one of the parietal lobes carries a 19% risk and one in a temporal lobe carries a 16% chance. When contusions occur in both hemispheres, the risk is 26% for the frontal lobes, 66% for the parietal, and 31% for the temporal. Post-traumatic seizures The risk that a person will develop PTE is heightened but not 100% if PTS occur. Because many of the risk factors for both PTE and early PTS are the same, it is unknown whether the occurrence of PTS is a risk factor in and of itself. However, even independent of other common risk factors, early PTS have been found to increase the risk of PTE to over 25% in most studies. A person who has one late seizure is at even greater risk for having another than one who has early PTS; epilepsy occurs in 80% of people who have a late seizure. Status epilepticus, a continuous seizure or multiple seizures in rapid succession, is especially strongly correlated with the development of PTE; status seizures occur in 6% of all TBIs but are associated with PTE 42% of the time, and quickly halting a status seizure reduces chances of PTE development. Pathophysiology For unknown reasons, trauma can cause changes in the brain that lead to epilepsy. There are a number of proposed mechanisms by which TBI causes PTE, more than one of which may be present in a given person. In the period between a brain injury and onset of epilepsy, brain cells may form new synapses and axons, undergo apoptosis or necrosis, and experience altered gene expression. In addition, damage to particularly vulnerable areas of the cortex such as the hippocampus may give rise to PTE.Blood that gathers in the brain after an injury may damage brain tissue and thereby cause epilepsy. Products that result from the breakdown of hemoglobin from blood may be toxic to brain tissue. The "iron hypothesis" holds that PTE is due to damage by oxygen free radicals, the formation of which is catalyzed by iron from blood. Animal experiments using rats have shown that epileptic seizures can be produced by injecting iron into the brain. Iron catalyzes the formation of hydroxyl radicals by the Haber-Weiss reaction; such free radicals damage brain cells by peroxidizing lipids in their membranes. The iron from blood also reduces the activity of an enzyme called nitric oxide synthase, another factor thought to contribute to PTE.After TBI, abnormalities exist in the release of neurotransmitters, chemicals used by brain cells to communicate with each other; these abnormalities may play a role in the development of PTE. TBI may lead to the excessive release of glutamate and other excitatory neurotransmitters (those that stimulate brain cells and increase the likelihood that they will fire). This excessive glutamate release can lead to excitotoxicity, damage to brain cells through overactivation of the biochemical receptors that bind and respond to excitatory neurotransmitters. Overactivation of glutamate receptors damages neurons; for example it leads to the formation of free radicals. Excitotoxicity is a possible factor in the development of PTE; it may lead to the formation of a chronic epileptogenic focus. An epileptic focus is the part of the brain from which epileptic discharges originate.In addition to chemical changes in cells, structural changes that lead to epilepsy may occur in the brain. Seizures that occur shortly after TBI can reorganize neural networks and cause seizures to occur repeatedly and spontaneously later on. The kindling hypothesis suggests that new neural connections are formed in the brain and cause an increase in excitability. The word kindling is a metaphor: the way the brains response to stimuli increases over repeated exposures is similar to the way small burning twigs can produce a large fire. This reorganization of neural networks may make them more excitable. Neurons that are in a hyperexcitable state due to trauma may create an epileptic focus in the brain that leads to seizures. In addition, an increase in neurons excitability may accompany loss of inhibitory neurons that normally serve to reduce the likelihood that other neurons will fire; these changes may also produce PTE. Diagnosis To be diagnosed with PTE, a person must have a history of head trauma and no history of seizures prior to the injury. Witnessing a seizure is the most effective way to diagnose PTE. Electroencephalography (EEG) is a tool used to diagnose a seizure disorder, but a large portion of people with PTE may not have the abnormal "epileptiform" EEG findings indicative of epilepsy. In one study, about a fifth of people who had normal EEGs three months after an injury later developed PTE. However, while EEG is not useful for predicting who will develop PTE, it can be useful to localize the epileptic focus, to determine severity, and to predict whether a person will have more seizures if they stop taking antiepileptic medications.Magnetic resonance imaging (MRI) is performed in people with PTE, and CT scanning can be used to detect brain lesions if MRI is unavailable. However, it is frequently not possible to detect the epileptic focus using neuroimaging.For a diagnosis of PTE, seizures must not be attributable to another obvious cause. Seizures that occur after head injury are not necessarily due to epilepsy or even to the head trauma. Like anyone else, TBI survivors may have seizures due to factors including imbalances of fluid or electrolytes, epilepsy from other causes, hypoxia (insufficient oxygen), and ischemia (insufficient blood flow to the brain). Withdrawal from alcohol is another potential cause of seizures. Thus these factors must be ruled out as causes of seizures in people with head injury before a diagnosis of PTE can be made. Prevention Prevention of PTE involves preventing brain trauma in general; protective measures include bicycle helmets and child safety seats. No specific treatment exists to prevent the development of epilepsy after TBI occurs. In the past, antiepileptic drugs were used with the intent of preventing the development of PTE. However, while antiepileptic drugs can prevent early PTS, clinical studies have failed to show that prophylactic use of antiepileptic drugs prevents the development of PTE. Why antiepileptic drugs in clinical trials have failed to stop PTE from developing is not clear, but several explanations have been offered. The drugs may simply not be capable of preventing epilepsy, or the drug trials may have been set up in a way that did not allow a benefit of the drugs to be found (e.g. drugs may have been given too late or in inadequate doses). Animal studies have similarly failed to show much protective effect of the most commonly used seizure medications in PTE trials, such as phenytoin and carbamazepine. Antiepileptic drugs are recommended to prevent late seizures only for people in whom PTE has already been diagnosed, not as a preventative measure. On the basis of the aforementioned studies, no treatment is widely accepted to prevent the development of epilepsy. However, it has been proposed that a narrow window of about one hour after TBI may exist during which administration of antiepileptics could prevent epileptogenesis (the development of epilepsy).Corticosteroids have also been investigated for the prevention of PTE, but clinical trials revealed that the drugs did not reduce late PTS and were actually linked to an increase in the number of early PTS. Treatment Antiepileptic drugs may be given to prevent further seizures; these drugs eliminate seizures for about 35% of people with PTE. However, antiepileptics only prevent seizures while they are being taken; they do not reduce the occurrence once the patient stops taking the drugs. Medication may be stopped after seizures have been controlled for two years. PTE is commonly difficult to treat with drug therapy, and antiepileptic drugs may be associated with side effects. The antiepileptics carbamazepine and valproate are the most common drugs used to treat PTE; phenytoin may also be used but may increase risk of cognitive side effects such as impaired thinking. Other drugs commonly used to treat PTE include clonazepam, phenobarbitol, primidone, gabapentin, and ethosuximide. Among antiepileptic drugs tested for seizure prevention after TBI (phenytoin, sodium valproate, carbamazepine, phenobarbital), no evidence from randomized controlled trials has shown superiority of one over another.People whose PTE does not respond to medication may undergo surgery to remove the epileptogenic focus, the part of the brain that is causing the seizures. However surgery for PTE may be more difficult than it is for epilepsy due to other causes, and is less likely to be helpful in PTE than in other forms of epilepsy. It can be particularly difficult in PTE to localize the epileptic focus, in part because TBI may affect diffuse areas of the brain. Difficulty locating the seizure focus is seen as a deterrent to surgery. However, for people with sclerosis in the mesial temporal lobe (in the inner aspect of the temporal lobe), who comprise about one third of people with intractable PTE, surgery is likely to have good outcome. When there are multiple epileptic foci or the focus cannot be localized, and drug therapy is not effective, vagus nerve stimulation is another option for treating PTE.People with PTE have follow-up visits, in which health care providers monitor neurological and neuropsychological function and assess the efficacy and side effects of medications. As with other types of epilepsy, individuals with PTE are advised to exercise caution when performing activities for which seizures could be particularly risky, such as rock climbing. Prognosis The prognosis for epilepsy due to trauma is worse than that for epilepsy of undetermined cause. People with PTE are thought to have shorter life expectancies than people with brain injury who do not have seizures. Compared to people with similar structural brain injuries but without PTE, people with PTE take longer to recover from the injury, have more cognitive and motor problems, and perform worse at everyday tasks. This finding may suggest that PTE is an indicator of a more severe brain injury, rather than a complication that itself worsens outcome. PTE has also been found to be associated with worse social and functional outcomes but not to worsen patients rehabilitation or ability to return to work. However, people with PTE may have trouble finding employment if they admit to having seizures, especially if their work involves operating heavy machinery.The period of time between an injury and development of epilepsy varies, and it is not uncommon for an injury to be followed by a latent period with no recurrent seizures. The longer a person goes without developing seizures, the lower the chances are that epilepsy will develop. At least 80–90% of people with PTE have their first seizure within two years of the TBI. People with no seizures within three years of the injury have only a 5% chance of developing epilepsy. However, one study found that head trauma survivors are at an increased risk for PTE as many as 10 years after moderate TBI and over 20 years after severe TBI. Since head trauma is fairly common and epilepsy can occur late after the injury, it can be difficult to determine whether a case of epilepsy resulted from head trauma in the past or whether the trauma was incidental.The question of how long a person with PTE remains at higher risk for seizures than the general population is controversial. About half of PTE cases go into remission, but cases that occur later may have a smaller chance of doing so. Epidemiology Studies have found that the incidence of PTE ranges between 1.9 and more than 30% of those with TBI, varying by severity of injury and by the amount of time after TBI for which the studies followed subjects.Brain trauma is one of the strongest predisposing factors for epilepsy development, and is an especially important factor in young adults. Young adults, who are at the highest risk for head injury, also have the highest rate of PTE, which is the largest cause of new-onset epilepsy cases in young people. Children have a lower risk for developing epilepsy; 10% of children with severe TBI and 16–20% of similarly injured adults develop PTE. Being older than 65 is also a predictive factor in the development of epilepsy after brain trauma. One study found PTE to be more common in male TBI survivors than in females. History Records of PTE exist from as early as 3000 BC. Trepanation, in which a hole is cut in the skull, may have been used to treat PTE in ancient cultures. In the early 19th century, the surgeons Baron Larrey and WC Wells each reported having performed the operation for PTE. The French-educated American surgeon Benjamin Winslow Dudley (1785–1870) performed six trepanations for PTE between the years of 1819 and 1832 in Kentucky and had good results despite the unavailability of antisepsis. The surgery involved opening the skull at the site of injury, debriding injured tissue, and sometimes draining blood or fluid from under the dura mater. Dudleys work was the largest series of its kind that had been done up to that point, and it encouraged other surgeons to use trepanation for post-traumatic seizures. His reports on the operations came before it was accepted that surgery to relieve excess pressure within the skull was effective in treating epilepsy, but it helped set the stage for trepanation for PTE to become common practice. The procedure became more accepted in the late 19th century once antisepsis was available and cerebral localization was a familiar concept. However, in 1890, the prominent German physician Ernest von Bergmann criticized the procedure; he questioned its efficacy (except in particular circumstances) and suggested that operations had been declared successful too soon after the procedures to know whether they would confer a long-term benefit. The late 19th century saw the advent of intracranial surgery, operating on brain lesions believed to be causing seizures, a step beyond cranial surgery which involved just the skull and meninges. By 1893, at least 42 intracranial operations had been performed for PTE in the US, with limited success.Surgery was the standard treatment for PTE until the years following World War II, when the condition received more attention as soldiers who had survived head trauma developed it. The increased need for drugs to treat PTE led to trials with antiepileptics; these early trials suggested that the drugs could prevent epileptogenesis (the development of epilepsy). It was still thought that antiepileptic drugs could prevent epileptogeneis in the 1970s; in 1973, 60% of physicians surveyed used them to prevent PTE. However, the clinical trials which had supported a protective effect of antiepileptics were uncontrolled; in later, controlled trials the drugs failed to demonstrate an antiepileptogenic effect. Studies did show that antiepileptics prevented seizures occurring within a week after injury, and in 1995 the task force of the Brain Trauma Foundation published a recommendation suggesting their use to protect against seizures early after trauma. However, recommendations were published against the prophylactic use of antiepileptic drugs more than a week after injury by the Brain Injury Special Interest group of the American Academy of Physical Medicine and Rehabilitation in 1998 and by the American Association of Neurological Surgeons in 2000. Research How epilepsy develops after an injury to the brain is not fully understood, and gaining such understanding may help researchers find ways to prevent it, or make it less severe or easier to treat. Researchers hope to identify biomarkers, biological indications that epileptogenesis is occurring, as a means to find drugs that can target pathways by which epilepsy develops. For example, drugs could be developed to interfere with secondary brain injury (injury that does not occur at the moment of trauma but results from processes initiated by it), by blocking pathways such as free radical damage to brain tissue. An increase in understanding of age differences in epilepsy development after trauma may also help researchers find biomarkers of epileptogenesis. There is also interest in finding more antiepileptic drugs, with the potential to interfere with epileptogenesis. Some new antiepileptic drugs such as topiramate, gabapentin, and lamotrigine have already been developed and have shown promise in treatment of PTE. No animal model has all the characteristics of epileptogenesis in humans, so research efforts aim to identify one. Such a model may help researchers find new treatments and identify the processes involved in epileptogenesis. However, the most common mechanical models of traumatic brain injury such as fluid percussion injury, controlled cortical impact, and weight-drop injury models exhibit epileptogenesis at chronic time points with documented remote electroencephalographic and behavioral seizures, and increased seizure susceptibility. It has been reported that PTE can also occur in zebrafish, resulting in similar pathophysiological responses to human TBI. See also Complications of traumatic brain injury References == External links ==
Schmorls nodes	Schmorls nodes are protrusions of the nucleus pulposus of the intervertebral disc through the vertebral body endplate and into the adjacent vertebra. Signs and symptoms These are protrusions of disc material into the surface of the vertebral body, which may contact the marrow of the vertebra and lead to inflammation. The protrusions are also associated with necrosis of the vertebral bone and the question of whether these protrusions and inflammation cause the necrosis, or whether the cartilage migrates into areas that have become necrotic due to other conditions, is under investigation.They may or may not be symptomatic, and their link to back pain is controversial. Williams and colleagues note that this relationship may be due to lumbar disc disease, as the two commonly occur simultaneously. Causes Schmorls nodes are fairly common, especially with minor degeneration of the aging spine, but they are also seen in younger spines. Schmorls nodes often cause no symptoms, but may simply reflect that "wear and tear" of the spine has occurred over time; they may also reflect that bone strength was at one time somewhat compromised, perhaps due to a vitamin D deficiency although this has yet to be confirmed with studies, or if heavy lifting is done at a young age before the vertebral bodies are completely ossified such as in young farm workers. There is also a strong heritability of Schmorls Nodes (>70%). While often non-complicating, Schmorls nodes also tend to occur more often in cases of spinal deformity, specifically Scheuermanns disease. These defects are caused when the vertebra loses its normal function and is not moving/hypomobile/subluxated. During this time the forces normally distributed by the nucleus pulposus (the incompressible gelatinous center of the intervertebral disc) are concentrated in a certain area causing endplates to deform in a concave manner. Diagnosis Schmorls nodes can be detected with X-rays, although they can be imaged better by CT or MRI. They are considered to be vertical disc herniations through the cartilaginous vertebral body endplates. Schmorls nodes can sometimes be seen radiographically, however they are more often seen on MRI, even when not visible on plain X-rays. They may or may not be symptomatic, and their etiological significance for back pain is controversial. In a study in Spine by Hamanishi, et al., Schmorls nodes were observed on MRI in 19% of 400 patients with back pain, and in only 9% of an asymptomatic control group. The authors concluded that Schmorls nodes are areas of "vertical disc herniation" through areas of weakness in the endplate. Management Painful Schmorls node can be diagnosed by discography, which demonstrates an intravertebral disc herniation with concomitant back pain. Surgical treatment should be considered in a patient with persistent disabling back pain. When surgical treatment is indicated, eradication of the intervertebral disc including Schmorls node and segmental fusion are preferable. Eponym Schmorls nodes are named after German pathologist Christian Georg Schmorl (1861–1932). References Further reading Plomp, Kimberly A; Viðarsdóttir, Una Strand; Weston, Darlene A; Dobney, Keith; Collard, Mark (2015). "The ancestral shape hypothesis: An evolutionary explanation for the occurrence of intervertebral disc herniation in humans". BMC Evolutionary Biology. 15: 68. doi:10.1186/s12862-015-0336-y. PMC 4410577. PMID 25927934. McFadden, K D; Taylor, J R (1989). "End-Plate Lesions of the Lumbar Spine". Spine. 14 (8): 867–9. doi:10.1097/00007632-198908000-00017. PMID 2781398. S2CID 38418323. Peng, B.; Wu, W.; Hou, S.; Shang, W.; Wang, X.; Yang, Y. (August 2003). "The pathogenesis of Schmorls nodes". The Journal of Bone and Joint Surgery. British Volume. 85-B (6): 879–882. doi:10.1302/0301-620X.85B6.13555. PMID 12931811. Takahashi, K.; Miyazaki, T.; Ohnari, H.; Takino, T.; Tomita, K. (1995). "Schmorls nodes and low-back pain". European Spine Journal. 4 (1): 56–9. doi:10.1007/bf00298420. PMID 7749909. S2CID 26284846. Sherrell, Zia (19 May 2022). "Schmorl nodes: Symptoms, causes, and treatment". Medical News Today. Kim, Hyeun Sung; Raorane, Harshavardhan Dilip; Sharma, Sagar Bhupendra; Wu, Pang Hung; Jang, Il-Tae (December 2020). "Infected Schmorls node: a case report". BMC Musculoskeletal Disorders. 21 (1): 280. doi:10.1186/s12891-020-03276-4. PMC 7196219. PMID 32359347. == External links ==
Teratoma	A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx. Symptoms Symptoms may be minimal if the tumor is small. A testicular teratoma may present as a painless lump. Complications may include ovarian torsion, testicular torsion, or hydrops fetalis.They are a type of germ cell tumor (a tumor that begins in the cells that give rise to sperm or eggs). They are divided into two types: mature and immature. Mature teratomas include dermoid cysts and are generally benign. Immature teratomas may be cancerous. Most ovarian teratomas are mature. In adults, testicular teratomas are generally cancerous. Definitive diagnosis is based on a tissue biopsy.Treatment of coccyx, testicular, and ovarian teratomas is generally by surgery. Testicular and immature ovarian teratomas are also frequently treated with chemotherapy.Teratomas occur in the coccyx in about one in 30,000 newborns, making them one of the most common tumors in this age group. Females are affected more often than males. Ovarian teratomas represent about a quarter of ovarian tumors and are typically noticed during middle age. Testicular teratomas represent almost half of testicular cancers. They can occur in both children and adults. The term comes from the Greek word for "monster" plus the "-oma" suffix used for tumors. Types Mature teratoma A mature teratoma is a grade 0 teratoma. They are highly variable in form and histology, and may be solid, cystic, or a combination of the two. A mature teratoma often contains several different types of tissue such as skin, muscle, and bone. Skin may surround a cyst and grow abundant hair (see dermoid cyst). Mature teratomas generally are benign, with 0.17-2% of mature cystic teratomas becoming malignant. Immature teratoma Immature teratoma is the malignant counterpart of the mature teratoma and contains immature tissues which typically show primitive or embryonal neuroectodermal histopathology. Immature teratoma has one of the lowest rates of somatic mutation of any tumor type and results from one of five mechanisms of meiotic failure. Gliomatosis peritoneii Gliomatosis peritoneii, which presents as a deposition of mature glial cells in the peritoneum, is almost exclusively seen in conjunction with cases of ovarian teratoma. Through genetic studies of exome sequence, it was found that gliomatosis is genetically identical to the parent ovarian tumor and developed from cells that disseminate from the ovarian teratoma. Dermoid cyst A dermoid cyst is a mature cystic teratoma containing hair (sometimes very abundant) and other structures characteristic of normal skin and other tissues derived from the ectoderm. The term is most often applied to teratoma on the skull sutures and in the ovaries of females. Fetus in fetu and fetiform teratoma Fetus in fetu and fetiform teratoma are rare forms of mature teratomas that include one or more components resembling a malformed fetus. Both forms may contain or appear to contain complete organ systems, even major body parts such as a torso or limbs. Fetus in fetu differs from fetiform teratoma in having an apparent spine and bilateral symmetry.Most authorities agree that fetiform teratomas are highly developed mature teratomas; the natural history of fetus in fetu is controversial. There also may be a cultural difference, with fetiform teratoma being reported more often in ovarian teratomas (by gynecologists) and fetus in fetu being reported more often in retroperitoneal teratomas (by general surgeons). Fetus in fetu has often been interpreted as a fetus growing within its twin. As such, this interpretation assumes a special complication of twinning, one of several grouped under the term parasitic twin. In this regard, in many cases the fetus in fetu is reported to occupy a fluid-filled cyst within a mature teratoma. Cysts within mature teratoma may have partially developed organ systems; reports include cases of partial cranial bones, long bones and a rudimentary beating heart.Regardless of whether fetus in fetu and fetiform teratoma are one entity or two, they are distinct from and not to be confused with ectopic pregnancy. Struma ovarii A struma ovarii (also known as goitre of the ovary or ovarian goiter) is a rare form of mature teratoma that contains mostly thyroid tissue. Epignathus Epignathus is a rare teratoma originating in the oropharyngeal area that occurs in utero. It presents with a mass protruding from the mouth at birth. Untreated, breathing is impossible. An EXIT procedure is the recommended initial treatment. Signs and symptoms Teratomas may be found in babies, children, and adults. Teratomas of embryonal origin are most often found in babies at birth, in young children, and, since the advent of ultrasound imaging, in fetuses. The most diagnosed fetal teratomas are sacrococcygeal teratoma (Altman types I, II, and III) and cervical (neck) teratoma. Because these teratomas project from the fetal body into the surrounding amniotic fluid, they can be seen during routine prenatal ultrasound exams. Teratomas within the fetal body are less easily seen with ultrasound; for these, MRI of the pregnant uterus is more informative. Complications Teratomas are not dangerous for the fetus unless either a mass effect occurs or a large amount of blood flows through the tumor (known as vascular steal). The mass effect frequently consists of obstruction of normal passage of fluids from surrounding organs. The vascular steal can place a strain on the growing heart of the fetus, even resulting in heart failure, thus must be monitored by fetal echocardiography. Teratomas can cause an autoimmune illness called N-methyl-D-aspartate (NMDA) receptor encephalitis. In this condition, the teratomas may contain B cells with NMDA-receptor specificities.After surgery, a risk exists of regrowth in place, or in nearby organs. Pathophysiology Teratomas belong to a class of tumors known as nonseminomatous germ cell tumor. All tumors of this class are the result of abnormal development of pluripotent cells: germ cells and embryonal cells. Teratomas of embryonic origin are congenital; teratomas of germ cell origin may or may not be congenital. The kind of pluripotent cell appears to be unimportant, apart from constraining the location of the teratoma in the body. Teratomas derived from germ cells occur in the testicle and ovaries. Teratomas derived from embryonic cells usually occur on the subjects midline: in the brain, elsewhere in the skull, in the nose, in the tongue, under the tongue, and in the neck (cervical teratoma), mediastinum, retroperitoneum, and attached to the coccyx. Teratomas may also occur elsewhere: very rarely in solid organs (most notably the heart and liver) and hollow organs (such as the stomach and bladder), and more commonly on the skull sutures. Teratoma rarely include more complicated body parts such as teeth, brain matter, eyes, or torso. Hypotheses of origin Concerning the origin of teratomas, numerous hypotheses exist. These hypotheses are not to be confused with the unrelated hypothesis that fetus in fetu (see below) is not a teratoma at all, but rather a parasitic twin. Diagnosis Teratomas are thought to originate in utero, so can be considered congenital tumors. Many teratomas are not diagnosed until much later in childhood or in adulthood. Large tumors are more likely to be diagnosed early on. Sacrococcygeal and cervical teratomas are often detected by prenatal ultrasound. Additional diagnostic methods may include prenatal magnetic resonance imaging. In rare circumstances, the tumor is so large that the fetus may be damaged or die. In the case of large sacrococcygeal teratomas, a significant portion of the fetus blood flow is redirected toward the teratoma (a phenomenon called steal syndrome), causing heart failure, or hydrops, of the fetus. In certain cases, fetal surgery may be indicated. Beyond the newborn period, symptoms of a teratoma depend on its location and organ of origin. Ovarian teratomas often present with abdominal or pelvic pain, caused by torsion of the ovary or irritation of its ligaments. A recently discovered condition where ovarian teratomas cause encephalitis associated with antibodies against the N-methyl-D-aspartate receptor antibody (NMDAR) - often referred to as "anti-NMDA receptor encephalitis", was identified as a serious complication. Patients develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. Testicular teratomas present as a palpable mass in the testis; mediastinal teratomas often cause compression of the lungs or the airways and may present with chest pain and/or respiratory symptoms. Some teratomas contain yolk sac elements, which secrete alpha-fetoprotein. Its detection may help to confirm the diagnosis and is often used as a marker for recurrence or treatment efficacy, but is rarely the method of initial diagnosis. (Maternal serum alpha-fetoprotein is a useful screening test for other fetal conditions, including Down syndrome, spina bifida, and abdominal wall defects such as gastroschisis.) Classification Regardless of location in the body, a teratoma is classified according to a cancer staging system. This indicates whether chemotherapy or radiation therapy may be needed in addition to surgery. Teratomas commonly are classified using the Gonzalez-Crussi grading system: 0 or mature (benign); 1 or immature, probably benign; 2 or immature, possibly malignant (cancerous); and 3 or frankly malignant. If frankly malignant, the tumor is a cancer for which additional cancer staging applies.Teratomas are also classified by their content; a solid teratoma contains only tissues (perhaps including more complex structures); a cystic teratoma contains only pockets of fluid or semifluid such as cerebrospinal fluid, sebum, or fat; a mixed teratoma contains both solid and cystic parts. Cystic teratomas usually are grade 0 and, conversely, grade 0 teratomas usually are cystic. Grades 0, 1, and 2 pure teratomas have the potential to become malignant (grade 3), and malignant pure teratomas have the potential to metastasize. These rare forms of teratoma with malignant transformation may contain elements of somatic (not germ cell) malignancy such as leukemia, carcinoma, or sarcoma. A teratoma may contain elements of other germ cell tumors, in which case it is not a pure teratoma, but rather is a mixed germ cell tumor and is malignant. In infants and young children, these elements usually are endodermal sinus tumor, followed by choriocarcinoma. Finally, a teratoma can be pure and not malignant yet highly aggressive; this is exemplified by growing teratoma syndrome, in which chemotherapy eliminates the malignant elements of a mixed tumor, leaving pure teratoma, which paradoxically begins to grow very rapidly. Malignant transformation A "benign" grade 0 (mature) teratoma nonetheless has a risk of malignancy. Recurrence with malignant endodermal sinus tumor has been reported in cases of formerly benign mature teratoma, even in fetiform teratoma and fetus in fetu. Squamous cell carcinoma has been found in a mature cystic teratoma at the time of initial surgery. A grade 1 immature teratoma that appears to be benign (e.g., because AFP is not elevated) has a much higher risk of malignancy, and requires adequate follow-up. This grade of teratoma also may be difficult to diagnose correctly. It can be confused with other small round cell neoplasms such as neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor, and non-Hodgkin lymphoma.A teratoma with malignant transformation is a very rare form of teratoma that may contain elements of somatic malignant tumors such as leukemia, carcinoma, or sarcoma. Of 641 children with pure teratoma, nine developed TMT: five carcinoma, two glioma, and two embryonal carcinoma (here, these last are classified among germ cell tumors). Extraspinal ependymoma Extraspinal ependymoma, usually considered to be a glioma (a type of nongerm cell tumor), may be an unusual form of mature teratoma. Treatment Surgery The treatment of choice is complete surgical removal (i.e., complete resection). Teratomas are normally well-encapsulated and noninvasive of surrounding tissues, hence they are relatively easy to resect from surrounding tissues. Exceptions include teratomas in the brain, and very large, complex teratomas that have pushed into and become interlaced with adjacent muscles and other structures. Prevention of recurrence does not require en bloc resection of surrounding tissues. Chemotherapy For malignant teratomas, usually, surgery is followed by chemotherapy. Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy. Follow-up Although often described as benign, a teratoma does have malignant potential. A UK study of 351 infants and children diagnosed with "benign" teratoma reported 227 with MT, 124 with IT. Five years after surgery, event-free survival was 92.2% and 85.9%, respectively, and overall survival was 99% and 95.1%. A similar study in Italy reported on 183 infants and children diagnosed with teratoma. At 10 years after surgery, event-free and overall survival were 90.4% and 98%, respectively.Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals with systemic effects. Some teratomas secrete the "pregnancy hormone" human chorionic gonadotropin (βhCG), which can be used in clinical practice to monitor the successful treatment or relapse in patients with a known HCG-secreting teratoma. This hormone is not recommended as a diagnostic marker, because most teratomas do not secrete it. Some teratomas secrete thyroxine, in some cases to such a degree that it can lead to clinical hyperthyroidism in the patient. Of special concern is the secretion of alpha-fetoprotein (AFP); under some circumstances, AFP can be used as a diagnostic marker specific for the presence of yolk sac cells within the teratoma. These cells can develop into a frankly malignant tumor known as yolk sac tumor or endodermal sinus tumor. Adequate follow-up requires close observation, involving repeated physical examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or βhCG. Epidemiology Embryonal teratomas most commonly occur in the sacrococcygeal region; sacrococcygeal teratoma is the single most common tumor found in newborn humans. Of teratomas on the skull sutures, about 50% are found in or adjacent to the orbit. Limbal dermoid is a choristoma, not a teratoma. Teratoma qualifies as a rare disease, but is not extremely rare. Sacrococcygeal teratoma alone is diagnosed at birth in one out of 40,000 humans. Given the current human population and birth rate, this equals five per day or 1800 per year. Add to that number sacrococcygeal teratomas diagnosed later in life, and teratomas in other locales, and the incidence approaches 10,000 new diagnoses of teratoma per year. Other animals Ovarian teratomas have been reported in mares,mountain lions, and canines. Teratomas also occur, rarely, in other species. Use in stem cell research Pluripotent stem cells including human induced pluripotent stem cells have a unique property of being able to generate teratomas when injected in rodents in the research laboratory. For this reason, the so-called "teratoma assay" is one of the gold-standard validation assays for pluripotent stem cells. Because differentiated human pluripotent stem cells are being developed as the basis for numerous regenerative medicine therapies, there is concern that residual undifferentiated stem cells could lead to teratoma formation in injected patients, and researchers are working to develop methods to address this concern.New research has looked at utilizing the human teratoma in chimeric animal studies as a promising platform for modeling multi-lineage human development, pan-tissue functional genetic screening, and tissue engineering. References This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute. External links humpath pathology images #2657 (Teratomas), #4541 (Mature teratoma), #5350 (Immature teratoma) cystic teratoma at eMedicine (also search EMedicine for all articles containing the word teratoma)
Late onset congenital adrenal hyperplasia	Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia (NCCAH or NCAH), is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.The causes of LOCAH are the same as of classic CAH, and in the majority of the cases are the mutations in the CYP21A2 gene resulting in corresponding activity changes in the associated P450c21 (21-hydroxylase) enzyme which ultimately leads to excessive androgen production. Other causes, albeit less frequent, are mutations in genes affecting other enzymes involved in steroid metabolism, like 11β-hydroxylase or 3β-hydroxysteroid dehydrogenase. It has a prevalence between 0.1% and 2% depending on population, and is one of the most common autosomal recessive genetic diseases in humans. The pathophysiology is complex and not all individuals are symptomatic. Presentation Patients with LOCAH usually present with signs of hyperandrogenism, rather than of glucocorticoid deficiency, a condition characterized by inadequate cortisol production. Cortisol synthesis impairment is mild but clinically silent. LOCAH patients usually have the same baseline but lower peak cortisol levels comparing to healthy controls. Flatter diurnal cortisol slopes contribute to stress-related dysregulation of central and peripheral circadian mechanisms with negative health outcomes.Due to hyperandrogenism, females may present with symptoms like hirsutism, oligomenorrhea, acne, infertility, and male-pattern baldness.Males are generally asymptomatic, but may present with acne, early balding, chronic prostatitis, chronic pelvic pain syndrome, and very rarely, testicular adrenal rest tumors.While symptoms are usually diagnosed after puberty, children may present with premature adrenarche.The degree of hormonal disorder in patients with LOCAH is relatively mild. However, alterations in the hypothalamic–pituitary–adrenal axis are present even in this mild form of the disease and might contribute to psychiatric vulnerability. Molecular genetics LOCAH is most commonly attributed to mutations in the CYP21A2 gene, which encodes the 21-hydroxylase enzyme. Cases of LOCAH due to deficiencies in other enzymes that are known causes of CAH (3β-hydroxysteroid dehydrogenase, steroid 11β-hydroxylase, etc.) are rare and have no established prevalence estimates.Several severe mutations have been associated with LOCAH: the deletion of the CYP21A2 gene, small gene conversions, the p. I172N (rs6475, c.518T>A, CYP21A211) mutation, the c.293-13A/C>G (rs6467, CYP21A29) mutation, and the p.Gln318Stop (p.Q318X, rs7755898, c.952C>T, CYP21A217) mutation. Besides that, LOCAH due to 21-hydroxylase deficiency can be caused by duplications of CYP21A1P pseudogene and C4B gene. Due to the high degree of homology between the CYP21A2 gene and the CYP21A1P pseudogene, and the complexity of the locus, research on the sequencing level can be difficult. A 2021 study showed that mild genotypes associated with LOCAH have a low concordance rate with those phenotypes, probably due to the complex characteristics of 21-hydroxylase genotyping and the limitation of using massive parallel sequencing alone without combining with other comprehensive methods.The following three mutations to the CYP21A2 gene have been found to result in a moderate reduction in enzyme activity associated with that allele (20–60% residual activity), and are associated with LOCAH: p.V281L (rs6471, c.844G>C, CYP21A215); p.P453S (rs6445, c.1360C>T, CYP21A219); p.P30L (rs9378251, c.92C>T, CYP21A28).A point mutation in exon 7 of CYP21A2, (p.V281L), is commonly found in LOCAH-associated alleles. Carriers for this mutation retain 20%–50% of 21-hydroxylase activity, but are at higher risk of symptoms of androgen excess than carriers of the severe mutations and had higher adrenocorticotropic hormone (ACTH) stimulated 17α-hydroxyprogesterone, suggesting heterozygous mutations on CYP21A2 play an important role in disease.The particularly mild clinical symptoms of LOCAH such as hyperandrogenism, hirsutism and acne or infertility overlap with other diseases such as polycystic ovary syndrome. Biochemical parameters like 17α-hydroxyprogesterone may not be elevated in very mild cases of LOCAH, and may vary between labs that makes interpretation difficult. It may not be possible to perform ACTH stimulation tests in all institutions, depending on the availability of the injectable adrenocorticotropic hormone medication. This is why a comprehensive CYP21A2 genotyping (rather than variant-specific assays alone) is a good way to exclude/confirm 21-hydroxylase deficiency and heterozygosity (carrier) status. Genetic testing can be used to exclude false positive diagnosis based on biochemical parameters alone, even with ACTH stimulation, since elevated 17-OHP levels may be also caused by ovarian or adrenal tumors, rather than by the variants in the CYP21A2 gene. Diagnosis Originally characterized in 1957 by French biochemist Jacques Decourt, LOCAH differs from classic CAH in that it does not cause atypical neonatal genital morphology, is not life-threatening and presents after birth. Unlike classic CAH, LOCAH generally cannot be reliably detected with neonatal screening. Many individuals (both male and female) present no symptoms during childhood and adolescence and only become aware of the possibility of LOCAH due to the diagnosis of another family member. It is thought that 90% of women with LOCAH never receive a diagnosis. In young females, premature pubarche is generally the first symptom to present. The earliest known diagnosis was in a 6 month old female who developed pubic hair. Additional symptoms include acne, menstrual irregularities and hirsutism in females as well as alopecia in males. LOCAH is often misdiagnosed as polycystic ovarian disease (PCOS).LOCAH is often diagnosed in the context of infertility assessment in women. During the follicular phase of the menstrual cycle, progesterone accumulates along with 17α-hydroxyprogesterone which can thin the endometrium and change cervical mucus in a manner similar to the effect of progestogen contraceptives, interferes with the normal menstrual cycle, which can lead to oligomenorrhea or amenorrhea and impairs sperm penetration. Abnormal endometrial development leads to decreased uterine receptivity, which also contributes to infertility. Once attempting to conceive, most women with LOCAH will become pregnant within a year with or without treatment, but women with LOCAH have an increased risk of miscarriage.The diagnostic procedure varies according to the specific enzyme deficiency causing LOCAH and the precise serum androgen levels required for diagnosis are the subject to variance from different measurement methods, refinement in specific cases and are under active research. Some protocols are based on measuring 17α-hydroxyprogesterone levels, with or without ACTH stimulation test. 21-Hydroxylase deficiency Screening The condition of 21-hydroxylase deficiency is screened by measuring serum levels of 17α-hydroxyprogesterone (17-OHP) in the morning and between day 3 and 5 of the menstrual cycle (for females) to reduce the possibility of false positive results. 17-OHP is used as a marker of the 21-hydroxylase enzyme activity since the 1980s. The cutoff basal 17-OHP value is matter of debate. Most commonly, the value of 2.0 ng/mL is used, but a value of 1.7 ng/mL provides better selectivity. Most research on the biochemical diagnosis of LOCAH relied on direct immunoassays, such as radioimmunoassays or time-resolved fluorescence assay to measure 17-OHP, therefore, cross-reactivity and reliability problems of these methods might have caused differences in the 17-OHP cutoff values recommended, so the use of liquid chromatography–mass spectrometry aims to improve the accuracy of 17-OHP measurement and increase diagnostic quality of LOCAH. Randomly timed measurements of 17-OHP have not been shown to be useful for screening since they are often normal and are known to be very high in the luteal phase of the female menstrual cycle. After basal levels have been measured, confirmation is done by administering ACTH, and comparing 17-OHP pre and post test. 17-OHP levels over 10 ng/mL at the 60th minute post stimulation is considered diagnostic for LOCAH. Androgen backdoor pathway In 21-hydroxylase deficiency, especially in mild cases (LOCAH), the androgen "backdoor" pathway may be the reason of androgen excess. This backdoor pathway is not always considered in the clinical evaluation of patients with hyperandrogenism conditions such as LOCAH and may be a source of diagnostic pitfalls and confusion. One case study demonstrated the importance of considering serum 5α-dihydrotestosterone (DHT) levels and the androgen backdoor pathway in a LOCAH diagnosis that would have not been apparent from testosterone levels alone. 11β-Hydroxylase deficiency The activity of 11β-hydroxylase can be determined by observing the basal 11-deoxycortisol level. A level over 10 ng/mL, indicates followup with ACTH stimulation test. The 60th minute post-stimulation 11-deoxycortisol levels higher than 18 ng/mL are diagnostic of LOCAH. 3β-Hydroxysteroid dehydrogenase deficiency The activity of 3β-hydroxysteroid dehydrogenase can be determined by observing the basal 17α-hydroxypregnenolone level. A level above 30 ng/mL and 17α-hydroxypregnenolone/cortisol ratio above 10 SD are diagnostic of LOCAH. Management Management and treatment of LOCAH is case specific and the application of glucocorticoid treatment is not standard as it is in classic CAH. LOCAH is not a life-threatening medical condition and the risks of treatment given prenatally or to asymptomatic children outweigh potential benefits. In appropriate cases, glucocorticoids (usually hydrocortisone in children) are administered to suppress secretion of corticotropin releasing hormone (CRH) produced by hypothalamus and of adrenocorticotropic hormone (ACTH) produced by pituitary gland. This suppression will reduce concentration in blood of sex steroids produced by adrenal glands. Some of the main considerations in treatment include the watchful waiting of symptom severity as well as adverse responses to glucocorticoids administered as drugs, seen in patient bone mineral density, height and weight. For women, an oral contraceptive pill and androgen blockers such as spironolactone or cyproterone acetate are alternatives to glucocorticoids for managing symptoms of androgen excess. Women with LOCAH being treated with hydrocortisone have a lower miscarriage risk. Prevalence According to haplotype association studies, the prevalence of LOCAH in the general white population is estimated to be 1:500 to 1:1000, but in people with a high rate of marriage between relatives, the prevalence rate is as high as 1:50 to 1:100. A 2017 CYP21A2 genotype analysis predicted that the total frequency of LOCAH in the white population of the United States is about 1:200 (95% confidence level, from 1:100 to 1:280).According to a 2017 meta-analysis, the prevalence of LOCAH among women with signs and symptoms of androgen excess is 4.2% globally, and between 1% and 10% depending on the ethnicity of the population being studied.LOCAH-affected individuals account for 88% of Anne Fausto-Sterlings 1.7% prevalence estimate of intersex conditions, which is cited by a number of prominent intersex advocacy organizations. From the clinical perspective, LOCAH is not an intersex condition and including LOCAH in intersex prevalence estimates has been cited as an example of dubious statistical practice. See also Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency Lipoid congenital adrenal hyperplasia References == External links ==
Subdural hematoma	A subdural hematoma (SDH) is a type of bleeding in which a collection of blood—usually but not always associated with a traumatic brain injury—gathers between the inner layer of the dura mater and the arachnoid mater of the meninges surrounding the brain. It usually results from tears in bridging veins that cross the subdural space. Subdural hematomas may cause an increase in the pressure inside the skull, which in turn can cause compression of and damage to delicate brain tissue. Acute subdural hematomas are often life-threatening. Chronic subdural hematomas have a better prognosis if properly managed. In contrast, epidural hematomas are usually caused by tears in arteries, resulting in a build-up of blood between the dura mater and the skull. The third type of brain hemorrhage, known as a subarachnoid hemorrhage, causes bleeding into the subarachnoid space between the arachnoid mater and the pia mater. Signs and symptoms The symptoms of a subdural hematoma have a slower onset than those of epidural hematomas because the lower-pressure veins involved bleed more slowly than arteries. Signs and symptoms of acute hematomas may appear in minutes, if not immediately, but can also be delayed as much as two weeks. Symptoms of chronic subdural hematomas are usually delayed more than three weeks after Injury.If the bleeds are large enough to put pressure on the brain, signs of increased intracranial pressure or brain damage will be present. Other symptoms of subdural hematoma can include any combination of the following: Causes Subdural hematomas are most often caused by head injury, in which rapidly changing velocities within the skull may stretch and tear small bridging veins. Much more common than epidural hemorrhages, subdural hemorrhages generally result from shearing injuries due to various rotational or linear forces. There are claims that they can occur in cases of shaken baby syndrome, although there is no scientific evidence for this.They are also commonly seen in the elderly and in people with an alcohol use disorder who have evidence of cerebral atrophy. Cerebral atrophy increases the length the bridging veins have to traverse between the two meningeal layers, thus increasing the likelihood of shearing forces causing a tear. It is also more common in patients on anticoagulants or antiplatelet medications, such as warfarin and aspirin, respectively. People on these medications can have a subdural hematoma after a relatively minor traumatic event. Another cause can be a reduction in cerebrospinal fluid pressure, which can reduce pressure in the subarachnoid space, pulling the arachnoid away from the dura mater and leading to a rupture of the blood vessels. Risk factors Factors increasing the risk of a subdural hematoma include very young or very old age. As the brain shrinks with age, the subdural space enlarges and the veins that traverse the space must cover a wider distance, making them more vulnerable to tears. The elderly also have more brittle veins, making chronic subdural bleeds more common. Infants, too, have larger subdural spaces and are more predisposed to subdural bleeds than are young adults. It is often claimed that subdural hematoma is a common finding in shaken baby syndrome, although there is no science to support this. In juveniles, an arachnoid cyst is a risk factor for subdural hematoma.Other risk factors include taking blood thinners (anticoagulants), long-term excessive alcohol consumption, dementia, and cerebrospinal fluid leaks. Pathophysiology Acute Acute subdural hematoma is usually caused by external trauma that creates tension in the wall of a bridging vein as it passes between the arachnoid and dural layers of the brains lining—i.e., the subdural space. The circumferential arrangement of collagen surrounding the vein makes it susceptible to such tearing.Intracerebral hemorrhage and ruptured cortical vessels (blood vessels on the surface of the brain) can also cause subdural hematoma. In these cases, blood usually accumulates between the two layers of the dura mater. This can cause ischemic brain damage by two mechanisms: one, pressure on the cortical blood vessels, and two, vasoconstriction due to the substances released from the hematoma, which causes further ischemia by restricting blood flow to the brain. When the brain is denied adequate blood flow, a biochemical cascade known as the ischemic cascade is unleashed, and may ultimately lead to brain cell death.Subdural hematomas grow continually larger as a result of the pressure they place on the brain: As intracranial pressure rises, blood is squeezed into the dural venous sinuses, raising the dural venous pressure and resulting in more bleeding from the ruptured bridging veins. They stop growing only when the pressure of the hematoma equalizes with the intracranial pressure, as the space for expansion shrinks. Chronic In chronic subdural hematomas, blood accumulates in the dural space as a result of damage to the dural border cells. The resulting inflammation leads to new membrane formation through fibrosis and produces fragile and leaky blood vessels through angiogenesis, permitting the leakage of red blood cells, white blood cells, and plasma into the hematoma cavity. Traumatic tearing of the arachnoid mater also causes leakage of cerebrospinal fluid into the hematoma cavity, increasing the size of the hematoma over time. Excessive fibrinolysis also causes continuous bleeding.Pro-inflammatory mediators active in the hematoma expansion process include Interleukin 1α (IL1A), Interleukin 6, and Interleukin 8, while the anti-inflammatory mediator is Interleukin 10. Mediators that promote angiogenesis are angiopoietin and vascular endothelial growth factor (VEGF). Prostaglandin E2 promotes the expression of VEGF. Matrix metalloproteinases remove surrounding collagen, providing space for new blood vessels to grow.Craniotomy for unruptured intracranial aneurysm is another risk factor for the development of chronic subdural hematoma. The incision in the arachnoid membrane during the operation causes cerebrospinal fluid to leak into the subdural space, leading to inflammation. This complication usually resolves on its own. Diagnosis It is important that a person receive medical assessment, including a complete neurological examination, after any head trauma. A CT scan or MRI scan will usually detect significant subdural hematomas.Subdural hematomas occur most often around the tops and sides of the frontal and parietal lobes. They also occur in the posterior cranial fossa, and near the falx cerebri and tentorium cerebelli. Unlike epidural hematomas, which cannot expand past the sutures of the skull, subdural hematomas can expand along the inside of the skull, creating a concave shape that follows the curve of the brain, stopping only at dural reflections like the tentorium cerebelli and falx cerebri.On a CT scan, subdural hematomas are classically crescent-shaped, with a concave surface away from the skull. However, they can have a convex appearance, especially in the early stages of bleeding. This may cause difficulty in distinguishing between subdural and epidural hemorrhages. A more reliable indicator of subdural hemorrhage is its involvement of a larger portion of the cerebral hemisphere. Subdural blood can also be seen as a layering density along the tentorium cerebelli. This can be a chronic, stable process, since the feeding system is low-pressure. In such cases, subtle signs of bleeding—such as effacement of sulci or medial displacement of the junction between gray matter and white matter—may be apparent. Fresh subdural bleeding is hyperdense, but becomes more hypodense over time due to dissolution of cellular elements. After 3–14 days, the bleeding becomes isodense with brain tissue and may therefore be missed. Subsequently, it will become more hypodense than brain tissue. Classification Subdural hematomas are classified as acute, subacute, or chronic, depending on the speed of their onset.Acute bleeds often develop after high-speed acceleration or deceleration injuries. They are most severe if associated with cerebral contusions. Though much faster than chronic subdural bleeds, acute subdural bleeding is usually venous and therefore slower than the arterial bleeding of an epidural hemorrhage. Acute subdural hematomas due to trauma are the most lethal of all head injuries and have a high mortality rate if they are not rapidly treated with surgical decompression. The mortality rate is higher than that of epidural hematomas and diffuse brain injuries because the force required to cause subdural hematomas tends to cause other severe injuries as well.Chronic subdural bleeds develop over a period of days to weeks, often after minor head trauma, though a cause is not identifiable in 50% of patients. They may not be discovered until they present clinically months or years after a head injury. The bleeding from a chronic hematoma is slow and usually stops by itself. Because these hematomas progress slowly, they can more often be stopped before they cause significant damage, especially if they are less than a centimeter wide. In one study, only 22% of patients with chronic subdural bleeds had outcomes worse than "good" or "complete recovery". Chronic subdural hematomas are common in the elderly. Differential diagnosis Treatment Treatment of a subdural hematoma depends on its size and rate of growth. Some small subdural hematomas can be managed by careful monitoring as the blood clot is eventually resorbed naturally. Others can be treated by inserting a small catheter through a hole drilled through the skull and sucking out the hematoma.Large or symptomatic hematomas require a craniotomy. A surgeon opens the skull and then the dura mater; removes the clot with suction or irrigation; and identifies and controls sites of bleeding. The injured vessels must be repaired. Postoperative complications can include increased intracranial pressure, brain edema, new or recurrent bleeding, infection, and seizures. In patients with a chronic subdural hematoma but no history of seizures, it is unclear whether anticonvulsants are harmful or beneficial.Those with chronic subudural haematoma (CSDH) with few or no symptoms or have high risk of complication during surgery may be treated conservatively with medications such as atorvastatin, dexamethasone, and mannitol, although supporting conservative treatment is still weak. HMG-CoA reductase inhibitor such as Atorvastatin can reduce the haematoma volume and improving neurological function in eight weeks. HMG-CoA reductase inhibitor may also reduce risk of recurrences in CSDH. Dexamethasone, when used together with surgical drainage, may reduce the recurrence rate of subdural haematoma. Even with surgical evacuation of chronic subdural haematoma, the recurrence rate is high, ranging from 7 to 20%. Prognosis Acute subdural hematomas have one of the highest mortality rates of all head injuries, with 50 to 90 percent of cases resulting in death. About 20 to 30 percent of patients recover brain function. Additionally, chronic subdural hematomas (CSDHs) have a relatively high mortality rate (up to 16.7% in patients over the age of 65); however, they have an even higher rate of recurrence (as mentioned in the previous section). For the aforementioned reasons, researchers have developed predictive grading scales to identify patients at high risk of CSDH recurrence, one of which is the Puerto Rico Recurrence Scale developed by Mignucci-Jiménez et al. See also Concussion Diffuse axonal injury Extra-axial hemorrhage Intra-axial hemorrhage References External links Subdural Hematoma at eMedicine Imaging and Mechanism of Subdural Hematoma - MedPix
Subgaleal hemorrhage	Subgaleal hemorrhage, also known as subgaleal hematoma, is bleeding in the potential space between the skull periosteum and the scalp galea aponeurosis. Symptoms The diagnosis is generally clinical, with a fluctuant boggy mass developing over the scalp (especially over the occiput) with superficial skin bruising. The swelling develops gradually 12–72 hours after delivery, although it may be noted immediately after delivery in severe cases. Subgaleal hematoma growth is insidious, as it spreads across the whole calvaria and may not be recognized for hours to days. If enough blood accumulates, a visible fluid wave may be seen. Patients may develop periorbital ecchymosis ("raccoon eyes").Patients with subgaleal hematoma may present with hemorrhagic shock given the volume of blood that can be lost into the potential space between the skull periosteum and the scalp galea aponeurosis, which has been found to be as high as 20-40% of the neonatal blood volume in some studies. The swelling may obscure the fontanel and cross cranial suture lines, distinguishing it from cephalohematoma, in which the bleed is confined by its subperiosteal location.Patients with subgaleal hemorrhage may also have significant hyperbilirubinemia due to resorption of hemolyzed blood. Laboratory studies may demonstrate reduced hemoglobin and hematocrit due to blood loss into the subgaleal space, and coagulation studies may reflect an underlying coagulopathy. Mortality has been reported to occur in 12-14% of cases, generally as a consequence of massive blood loss presenting with shock, often in the setting of uncorrected coagulopathy. However, with early identification and prompt treatment, the prognosis is good, and there are usually no long-term consequences. Causes The majority of neonatal cases (90%) result from applying a vacuum to the head at delivery (ventouse-assisted delivery). The vacuum assist ruptures the emissary veins (i.e., connections between dural sinus and scalp veins) leading to accumulation of blood under the aponeurosis of the scalp muscle and superficial to the periosteum.Additionally, subgaleal hematoma has a high frequency of occurrence of associated head trauma (40%), such as intracranial hemorrhage or skull fracture. The occurrence of these features does not correlate significantly with the severity of subgaleal hemorrhage. Diagnosis Early recognition of this injury is crucial for survival. Infants who have experienced a difficult operative delivery or are suspected to have a SGH require ongoing monitoring including frequent vital signs (minimally every hour), and serial measurements of hematocrits and their occipital frontal circumference, which increases 1 cm with each 40 mL of blood deposited into the subgaleal space. Head imaging, using either CT or MRI, can be useful for differentiating subgaleal hemorrhage from other sources of cranial bleeding. Head ultrasound is useful for the diagnosis of SGH in the hands of an operator experienced in imaging the neonatal head and scalp, and is preferable to CT due to lack of ionizing radiation. Coagulation studies are required to detect coagulopathy that may be associated with the bleeding. Management Management consists of vigilant observation over days to detect progression and, if required, manage complications (e.g. hemorrhagic shock, unconjugated hyperbilirubinemia and jaundice from hemolyzed red blood cells). The subgaleal space is capable of holding up to 40% of a newborn babys blood and can therefore result in acute shock and death. Fluid bolus may be required if blood loss is significant and the patient becomes tachycardic. Transfusion and phototherapy may be necessary. Investigation for coagulopathy may be indicated. See also Caput succedaneum Cephal Cephalohematoma Hematoma References == External links ==
Stewart–Treves syndrome	Stewart–Treves syndrome refers to a lymphangiosarcoma, a rare disorder marked by the presence of an angiosarcoma (a malignant tumor of blood or lymph vessels) in a person with chronic (long-term) lymphedema. Although it most commonly refers to malignancies associated with chronic lymphedema resulting from mastectomy and/or radiotherapy for breast cancer, it may also describe lymphangiosarcomas that result from congenital and other causes of chronic secondary lymphedema. Lymphangiosarcoma arising from cancer-related lymphedema has become much less common with better surgical techniques, radiation therapy, and conservative treatment. The prognosis, even with wide surgical excision and subsequent radiotherapy, is poor. Cause Common risk factors that may lead to the development of lymphangiosarcoma include lymphatic blockage, radiotherapy, mastectomy, cardiovascular diseases, and hypertension. The sarcoma first appears as a bruise mark, a purplish discoloration or a tender skin nodule in the extremity, typically on the anterior surface. Lymphangiosarcoma is caused by chronic lymphedema. Causes of lymphedema include: Primary lymphedema Congenital Precox (adolescence) Tarda (adulthood) Secondary lymphedema Malignancy Recurrent cellulitis Connective tissue disease Infection (filariasis) Contact dermatitis Lymphatic damage (surgery, radiation therapy, burns, etc.). Treatment The treatment of choice is a large resection or amputation of the affected limb. Radiation therapy can precede or follow surgical treatment. Tumors that have advanced locally or have metastasized can be treated with mono or polychemotherapy, systemically or locally. However, chemotherapy and radiation therapy have not been shown to improve survivorship significantly. In cases of upper limbs, forequarter amputation (disarticulation of upperlimb along with clavicle and scapula) is preferred. Prognosis Early detection is key. Prognosis is generally poor, and the 5 year survival rate of patients with lymphangiosarcoma is less than 5%. Incidence In the 1960s, the incidence five years after a radical mastectomy varied from 0.07% to 0.45%. Today, it occurs in 0.03% of patients surviving 10 or more years after radical mastectomy. History It was discovered by Fred W. Stewart and Norman Treves in 1948. See also Angiosarcoma List of cutaneous conditions Lymphangiosarcoma Lymphedema Postcardiotomy syndrome References == External links ==
Frontal lobe epilepsy	Frontal lobe epilepsy (FLE) is a neurological disorder which is a subtype of the larger group of epilepsy and then focal epilepsy is characterized by brief, recurring seizures that arise in the frontal lobes of the brain, often while the patient is sleeping. It is the second most common type of focal epilepsy after temporal lobe epilepsy (TLE), and is related to the temporal form by the fact that both forms are characterized by the occurrence of partial (focal) seizures. Partial seizures occurring in the frontal lobes can occur in one of two different forms: either “focal aware”, the old term was simple partial seizures (that do not affect awareness or memory) “focal unaware” the old term was complex partial seizures (that affect awareness or memory either before, during or after a seizure). The symptoms and clinical manifestations of frontal lobe epilepsy can differ depending on which specific area of the frontal lobe is affected.The onset of a seizure may be hard to detect since the frontal lobes contain and regulate many structures and functions about which relatively little is known. Due to the lack of knowledge surrounding the functions associated with the frontal lobes, seizures occurring in these regions of the brain may produce unusual symptoms which can often be misdiagnosed as a psychiatric disorder, non-epileptic seizure or a sleep disorder.During the onset of a seizure, the patient may exhibit abnormal body posturing, sensorimotor tics, or other abnormalities in motor skills. In some cases, uncontrollable laughing or crying may occur during a seizure. Affected persons may or may not be aware that they are behaving in an abnormal manner, depending on the patient and type of seizure. A brief period of confusion known as a postictal state may sometimes follow a seizure occurring in the frontal lobes. However, these postictal states are often undetectable and generally do not last as long as the periods of confusion following seizures that occur in the temporal lobes.There are many different causes of frontal lobe epilepsy ranging from genetics to head trauma that result in lesions in the frontal lobes. Although frontal lobe epilepsy is often misdiagnosed, tests such as prolonged EEG monitoring, video EEG and/or an MRI scan of the frontal lobes can be administered in order to reveal the presence of a tumor or vascular malformation. Unlike most epileptic EEGs, the abnormalities in FLE EEGs precede the physical onset of the seizure and aid in localization of the seizures origin. Medications such as anti-epileptic drugs can typically control the onset of seizures, however, if medications are ineffective the patient may undergo surgery to have focal areas of the frontal lobe removed. Signs and symptoms Signs and symptoms of frontal lobe seizures may include Head and eye movements to one side Complete or partial unresponsiveness or difficulty speaking Explosive screams, including profanities, or laughter Abnormal body posturing, especially fencing position Repetitive movements, such as rocking, bicycle pedaling or pelvic thrustingEpileptic symptoms are frequently the product of the spread of overactivation occurring within one central foci that travels to lateral brain regions thereby causing an array of symptoms. Due to the massive amount of diversity in both the cognitive and motor functions that occur within the frontal lobes, there is an immense variety in the types of symptoms that can arise from epileptic seizures based on the side and topography of the focal origin. In general these symptoms can range anywhere from asymmetric and abnormal body positioning to repetitive vocal outbursts and repetitive jerking movements. The symptoms typically come in short bursts that last less than a minute and often occur while a patient is sleeping. In most cases, a patient will experience a physical or emotional Aura of tingling, numbness or tension prior to a seizure occurring. Fear is associated with temporal and frontal lobe epilepsies, but in FLE the fear is predominantly expressed on the persons face whereas in TLE the fear is subjective and internal, not perceptible to the observer.Tonic posture and clonic movements are common symptoms among most of the areas of the frontal lobe, therefore the type of seizures associated with frontal lobe epilepsy are commonly called tonic-clonic seizures. Dystonic motor movements are common to both TLE and FLE, but are usually the first symptom in FLE episodes where they are quite brief and do not affect consciousness. The seizures are complex partial, simple partial, secondarily generalized or a combination of the three. These partial seizures are often misdiagnosed as psychogenic seizures. Symptomatology A wide range of more specific symptoms arise when different parts of the frontal cortex are affected. Supplementary motor area (SMA) The onset and relief of the seizure are quite abrupt. The tonic posturing in this area is unilateral or asymmetric between the left and right hemispheres. A somatosensory aura frequently precedes many large motor and vocal symptoms and most often the affected person is responsive. Motor symptoms: Facial grimacing and complex automatisms like kicking and pelvic thrusting Vocal symptoms: Laughing, yelling, or speech arrest. Primary motor cortex The primary motor cortex has jacksonian seizures that spread to adjacent areas of the lobe which often trigger a second round of seizures originating in another cortical area. The seizures are much simpler than those that originate in the SMA and are usually clonic or myoclonic movements with speech arrest. Some dystonic or contralateral adversive posturing may also be present. Medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions Motor symptoms of seizures in this area are accompanied by emotional feelings and viscerosensory symptoms. Motor and vocal agitation are similar to that of the SMA with short repetitive thrashing, pedaling, thrusting, laughing, screaming and/or crying. This is some of what can cause the misdiagnosis of a psychological disorder. Dorsolateral cortex This area does not seem to have many motor symptoms beyond tonic posturing or clonic movements. Contralateral or less commonly ipsilateral head turn and eye deviation are commonly associated with this area as well. Operculum Many of the symptoms associated with this area involve the head and digestive tract: swallowing, salivation, mastication and possibly gustatory hallucinations. Preceding the seizure the person is fearful and often has an epigastric aura. There is not much physical movement except clonic facial movements. Speech is often arrested. Diagnosis The diagnosis of FLE is difficult due to the overlapping and similar symptoms to psychiatric disorders. The diagnosis of FLE has been done by clinicians, and their reviews of the medical history, and physical and neurological examinations. The following neurological tests can be helpful for diagnosing FLE Electroencephalography (EEG) MRI Video EEG Electroencephalography (EEG) EEG helps in finding out the exact area of the brain where seizures occur. In the case of FLE, the EEG is almost normal. MEG and electroencephalography (EEG) in the temporal domain provides a better and wider view of information exchange across networks in patients with impaired and unimpaired FLE. Neuroimaging for diagnosis Advancements in technology, has given rise to newer, more efficient methods of diagnosis, most prominent being in the domain of neuroimaging. The high spatial resolution from fMRI has implications on certain brain regions contributing to memory. The usage of task fMRI for examination of memory or other higher cognitive networks may also be used to predict ictal onset zone(s) in patients with FLE, giving the advantage of refinement of patient-specific analyses. The use of multi-modal approaches in association with neuroimaging techniques like fMRI and MEG or EEG will be informative in characterizing atypical functional brain networks in FLE. But, difficulty remains in the evaluation of potential compensatory mechanisms between patients with FLE with normal and impaired memory, without properly characterizing transfer of information during memory tasks. Genetic Counselling Diagnosis of ADNFLE, however, is not only based on neuroimaging, and ictal and interictal EEGs, but also on family history and genetic counseling. Certain molecular and genomics testing that can include multi-gene panel of CHRNA4, CHRNB2, CHRNA2, KCNT1, DEPDC5, CRH, serial single gene testing of pathogenic variants, and can also be comprehensive genomic testing. There has to be continuous neuroimaging and EEGs, for reevaluation at regular intervals, to keep a check on disease progression. Video EEG As the FLE occurred during sleep video EEG is one of the useful tools for diagnosis of FLE. The monitoring can be done in the sleep lab in the hospital overnight. Both brain activity, as well as behavioral movement, can be captured by using video EEG. PET Scan Positron emission tomography (PET) helps to locate epileptogenic loci. If the MRI were normal the PET scan could locate some abnormalities. Common misdiagnoses Episodes that include complex hyperactivity of the proximal portions of the limbs that lead to increased overall motor activity are called hypermotor seizures. When associated with bizarre movements and vocalizations these seizures are often misdiagnosed as psychogenic or functional sezures or other episodic movement disorders such as psychogenic movement disorders, familial paroxysmal dystonic choreoathetosis, paroxysmal kinesogenic choreoathetosis, or episodic ataxia type 1. Hypermotor seizure in children are often confused with pavor nocturnus (night terrors). Paroxysmal nocturnal dystonia or hypnogenic paroxysmal dystonia are other names given to describe FLE symptoms but are simply just FLE.Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the best understood form of frontal lobe epilepsy but is often misdiagnosed as sleep apnea. Both disorders are characterized by awakening during the night which leads to daytime sleepiness. Some symptoms of sleep apnea overlap with those of ADNFLE, such as sudden awakening accompanied by a feeling of choking and on occasion motor activity which makes diagnosis difficult based on symptoms alone. Video surveillance as well as EEG is occasionally needed to differentiate between the two disorders. It has been reported that sleep apnea might be associated with epilepsy which would account for some of the misdiagnoses. Causes The origins of frontal lobe seizures can be different deviations. One of the major reasons for FLE is abnormal cognitive development or sometimes congenital abnormal brain development. Other reasons are: Tumors Head Trauma GeneticApart from the above-mentioned reason, there are a few unknown factors that can trigger the seizures: Sleep deprivation Waking up Stress Hormonal changes, such as during menstruation Alcohol Certain medications Illegal substances Tumors Tumors account for about one-third of all frontal lobe epilepsy cases. Low-grade tumors such as gangliogliomas, low-grade gliomas, and epidermoid tumors are most common, but many high-grade tumors were most likely once involved with seizures. Other lesions on the frontal lobe such as hamartomas and nodular heterotopias can cause frontal lobe symptoms as well. Birth defects such as vascular malformation are known to cause seizures, especially arteriovenous malformations, and cavernous angiomas. Head Trauma Head trauma frequently causes damage to the frontal lobe and can cause seizures directly or indirectly through gliosis. Seizures originating directly from head trauma usually occur within a few months, but occasionally they can take years to manifest. On occasion, encephalitis can cause frontal lobe seizures but it is most often associated with an affected temporal lobe. Genetic Cause The main genetic cause of frontal lobe epilepsy is an autosomal dominant disease called Autosomal Dominant Nocturnal Frontal Lobe Epilepsy, which involves mutations in 2 nicotinic acetylcholine receptor genes. A genetic mutation on chromosome 22 has also been associated with another genetic form of the disorder. Mechanism Due to the difference in brain processing and function as well as various surface anatomy landmarks, the frontal lobes have traditionally been divided into two major areas known as the precentral cortex and prefrontal cortex. Precentral cortex The precentral cortex is an area of the frontal cortex that is located directly anterior to the central sulcus and includes both the primary motor cortex and the supplementary motor area. Inputs that project to both of these areas arise from a variety of locations in the brain that integrate sensory stimuli including the primary motor cortex, the thalamus and corticospinal projections. These two areas along with several other main functional areas control both the preparation of motor movement as well as the execution of movements. These main functional areas are crucial to the development of the motor related symptoms associated with frontal lobe epilepsy focally when seizures are located within these defined areas. The major functional areas include: Primary motor cortex Contains large neurons that project axons down to the spinal cord where they synapse onto alpha motor neurons. These neurons are involved in the planning of motor movements and the refining of motor movements based on sensory inputs that are received from the cerebellum. Supplementary motor area Area anterior to the primary motor cortex that is involved in planning complex motor movements and coordinating movements along both hands. The main inputs for this area are received from the thalamus. Frontal eye field The frontal eye field is a posterior part of the middle frontal gyrus and is involved in the control of saccadic, contralateral and conjugate eye movement. This area receives its main inputs from both the occipital cortex and dorsal thalamus. Brocas area Controls the motor movements of both the tongue and larynx that enables speech formation. This area receives direct inputs from the primary motor area as well as Wernickes area located in the temporal lobe. Prefrontal cortex The prefrontal cortex, the most anterior region of the brain, comprises several key areas that are particularly important for higher mental functions that control various aspects of human personality including anticipation and planning, initiative/judgement, memory and the control of decision making. Damage or lesions to this region of the brain can result in major changes in personality. A classic example is Phineas Gage, who exhibited a change in behavior after one or both frontal lobes were destroyed by a large iron bar accidentally driven through his head (though Gage, despite conventional presentations of his case, did not exhibit the aggression, antisocial behavior, or loss of impulse control sometimes reported in patients with similar injuries). There are two main regions of the prefrontal cortex that each control various aspects of behavior and personality: Dorsolateral prefrontal cortex This area is associated with the impairment of the cognitive abilities that control and regulate behavior and long-term memory formation (especially relating to procedural sequence memory) when either brain damage or a lesion is present. Orbitofrontal cortex The orbitofrontal cortex has similar functions as the dorsolateral prefrontal cortex but is thought to be mainly responsible for the ability to make choices and determine right from wrong. Social effects and quality of life Epilepsy has a substantial impact on the quality of life of the individuals that are affected by it, yet there is lack of proper examination of social cognitive functions. Physicians and researchers are coming to understand that the impact on the quality of life of the patient is as important as the effects of the seizures. Quality of life questionnaires and other assessment tools have been created to help quantify quality of life for individual patients. They consider such factors as physical health (including numbers and severity of seizures, medication side effects etc.), mental health, social relationships, lifestyle, role activities and life fulfillment. A Center for Disease Control study reported that people with seizures were more likely to have lower education levels, higher unemployment, higher levels of pain, hypersomnia/insomnia, increased psychological distress and social isolation/connection issues. Some of the issues which impact quality of life for people with epilepsy are: ability to drive and travel, the ability to date, marry and have children, the ability to have a job and independence, the ability to have an education and learn, and the ability to have good health and mental functioning. Future research is needed to find ways of not only controlling frontal lobe seizures, but of also addressing the specific quality-of-life issues that plague those with frontal lobe epilepsy, especially as studies show a higher emotional recognition anomaly in cases of FLE, compared to TLE. Driving and transportation restrictionsDriving and travel restrictions are one of the greatest limitations that epileptic patients experience. Laws restricting driving privileges vary greatly in the United States as well as across the world. In the United States, 28 states require a patient to be seizure free for fixed periods of time ranging from 3–12 months. However, research done by Johns Hopkins University showed that there was no difference in seizure-related fatal crash rates in states with 3-month restrictions versus states with 6-12 month seizure-free restrictions. In 23 states, the restrictions and seizure free periods vary depending on the type of epilepsy and the individual case and in 13 states physicians were responsible for determining whether their patients should be allowed to drive. In 6 of those 13 states physicians could be held legally liable for their decisions regarding their epileptic patients driving capabilities. In many states, patients can also be legally liable for accidents, injury, damage and death caused by seizure related accidents. One of the major arguments in favor of restricting the licensing of epileptic drivers is the concern for public safety. However, the Johns Hopkins study showed that in a particular 2 year timeframe only 0.2% of fatal crashes occurred as a result of seizures. Alcohol related crash fatalities caused 156 times more driver deaths than seizure related crashes and young drivers between the ages of 16 and 24 were 123 times more likely to die in a fatal crash caused by their inexperience than an epileptic driver was to die in a crash that resulted from a seizure. Frontal lobe epileptic seizures unlike other epileptic seizures create symptoms that are as dangerous as loss of consciousness and much more difficult to discern from other problems such as substance use disorders, psychiatric disorders and disobedience. Jerking movements/lack of motor control, pedaling, pelvic thrusting, lapses in cognitive functioning and other hallmark symptoms of frontal lobe epileptic seizures all create dangerous behavior behind the wheel. Studies have not been done to date to determine the differential risk posed by drivers with frontal lobe epilepsy relative to the general epileptic population.Hormones and pregnancy issuesHormonal changes and pregnancy can shift seizure activity and the use of antiepileptic drugs can alter the efficacy of hormones as well as cause congenital malformations in fetuses. Seizure control in pregnant women is very important to the welfare of both the developing fetus and the mother. Hormonal shifts at puberty, with birth control and at menopause can also cause changes in the frequency and severity of seizures and must be closely monitored. Increased seizure activity is reported by 50% of women during the course of the pregnancy due to changing levels of hormones, fluids, salts and absorption and elimination of medications.EmploymentA report by the Epilepsy Foundation noted that the unemployment rate amongst people with epilepsy is 25% and in patients whose seizures are poorly controlled the rate jumps to 50%. Even though people with epilepsy are protected under The Americans with Disabilities Act, employment discrimination and high rates of unemployment due to employer attitudes still exist. A study in the UK showed that 16% of employers surveyed felt there were no jobs in their company suitable for people with epilepsy and that 21% felt that employing an epileptic would be a "major issue". Fifty percent of the employers said they had a high concern regarding employing people with epilepsy with most citing safety concerns/workplace accidents as their major issue. Patients with frontal lobe epilepsy may be particularly prone to being discriminated against in employment and subject to higher rates of termination due to the unusual motor symptoms, speech, vocal outbursts and cognitive/judgment symptoms displayed during frontal lobe seizures. Frontal lobe seizures also tend to come on suddenly and progress rapidly making it difficult for an employer to control the exposure of the seizure to others.Education, learning and cognitive functionPatients with frontal lobe epilepsy will likely also experience issues with learning and education. Many factors contribute to these issues including the impact of anticonvulsant medications. Anticonvulsant medications cause patients to feel "foggy" and sluggish. Drugs such as Topiramate cause problems such as mental blunting, word retrieval difficulties and irritability. Phenobarbital, Primidone and Vigabatrin can cause depression and suicidal tendencies. Stress and lack of sleep during exam periods can trigger seizures and many school sports teams restrict or ban people with epilepsy from sports for safety and liability reasons. People with frontal lobe epilepsy also exhibit dysfunctional cognitive skills and memory issues which can make learning challenging. Research has shown that frontal lobe epilepsy has a greater negative impact than other forms of epilepsy on cognitive functioning. People with frontal lobe epilepsy show decreased cognitive capabilities in the following areas: humor appreciation, recognition of emotional expressions, response selection/initiation and inhibition, hyperactivity, conscientiousness, obsession, addictive behavior, motor coordination and planning, attention span, performance speed, continuous performance without intrusion and interference errors, copying and recall, concept formation, anticipatory behavior, memory span, working memory, executive planning, visuo-spatial organization, mental flexibility, conceptual shift, problem solving, programming of complex motor sequences, impulse control, judgment and forecasting of consequences.Physical health and risk of other conditionsPatients with epilepsy face a greater risk of accidents, injury and other medical conditions than the general population. A European study showed that people with epilepsy were at greater risk for accidental injuries related to seizures such as concussions, abrasions and wounds and reported more hospitalizations and medical action than the general population. Other studies have shown that people with epilepsy are at a greater risk of seizure related drowning, suffocation, broken bones and burns and more likely to die in a fatal automobile crash. Epilepsy Ontario reports that people with epilepsy are also more likely to have other conditions than the general population such as: 30% of autistic children have epilepsy, 33% of cerebral palsy patients have epilepsy, 15-20% of fragile X syndrome patients have epilepsy, 50% of children with learning disabilities will have some form of epilepsy, 3-10% of patients with Lennox-Gastaut syndrome will have epilepsy, 80% of children with Rett syndrome will have epilepsy and 80% of patients with Tuberous Sclerosis will have epilepsy. The frontal lobe has a significant function in attention regulation. Therefore, patients with frontal lobe epilepsy are often found to be co-morbid for another disease called attention-deficit hyperactivity disorder (ADHD), which has a higher prevalence in children. This adds to the various cognitive and behavioral challenges, that they already face.Mental and emotional healthEpileptic patients are more prone to develop psychological and social dysfunction than individuals that do not have epilepsy. They report higher levels of anxiety and stress due to social isolation, discrimination, the unpredictability of their seizures and peoples reactions to them as well as fear of injury, death and brain damage from their seizures. Anticonvulsants can also result in lower functioning, depression, sluggishness and suicidal thoughts. Approximately 20% of people with epilepsy are depressed and the rate of suicide amongst people with epilepsy is 5 times the rate in the general population. People with frontal lobe epilepsy experience more significant social effects because the manifested symptoms are more unusual. Symptoms such as screaming, bicycling limbs, pelvic thrusting, inhibition control and other outbursts can be particularly embarrassing and isolating for the patient. The ultimate result from all these, is a significant impact on overall personality development. Treatments There are several different ways to treat frontal lobe epileptic seizures, however, the most common form of treatment is through the use of anticonvulsant medications that help to prevent seizures from occurring. In some cases, however, when medications are ineffective, a neurologist may choose to operate on the patient in order to remove the focal area of the brain in which the seizures are occurring. Other treatments that can be administered to aid in reducing the occurrence of seizures include the implementation of a specific, regimented diet and/or the implantation of a vagus nerve stimulator, or deep brain stimulation (DBS). Medications Anticonvulsants like oxcarbazepine or other drugs are the most successful medication in reducing and preventing frontal lobe seizures. Oxcarbazepine helps in the reduction of seizure frequencies. There are a wide range of anticonvulsants that have both different modes of action and different abilities in preventing certain types of seizures. Some of the anticonvulsants that are prescribed to patients today include: Oxcarbazepine (Trileptal), Carbamazepine (Tegretol), Phenytoin (Dilantin Kapseals), Gabapentin (Neurontin), Levetiracetam (Keppra), Lamotrigine (Lamictal), Topiramate (Topamax), Tiagabine (Gabitril), Zonisamide (Zonegran) and Pregabalin (Lyrica). KCNT1 pathogenic variant associated ADNFLE can be managed by treatment with quinidine, and ADNFLE associated with CHRNA4 shows better responsiveness to zonisamide. Note on medications Lorazepam, diazepam and clonazepam are front line treatments for severe convulsions, belonging to the benzodiazepine class of medications. Alternative medicine Herbal medicines Acupuncture Psychotherapy Mind–body interventions Surgical treatment Surgery may involve the following: Isolating the focal point. Responding to a seizure. Removing the focal point.When both the amount and severity of seizures becomes uncontrollable and seizures remain resistant to the various anticonvulsants, a patient most likely will be considered for epilepsy surgery. But, while performing it, there is the need for identifying or pinpointing the exact location of the seizure in the brain. This, in recent times have been aided by some of the modern techniques such as, SISCOM i.e., subtraction ictal SPECT co registered to MRI, SPECT i.e. single-photon emission computerized tomography, brain mapping performed before the surgery and functional MRI (fMRI), especially for the language area mapping.Surgeries include, a frontal lobectomy. This procedure involves the removal of focal regions of the frontal lobes that have been identified as being problematic for the patient. It has been found that around 30% to 50% of patients that undergo a frontal lobectomy will forever be free from seizures that cause a loss of consciousness or cause abnormal movements. However, frontal lobectomy and MCD contribute to lower seizure controls. But, in children with conditions like Sturge–Weber syndrome (SWS) or tumors, there is report of greater seizure control rates. If on the other hand, the seizures occur in an area that is too vital to remove (such as areas that control motor, sensory or language functions), then the surgeon will perform a procedure known as a multiple subpial transection. This procedure involves making a series of cuts that surround the focal region where the seizures have originated. By making cuts surrounding the focal region, the surgeon is able to isolate that specific section of the brain and prevent electrical impulses from being able to travel horizontally to other areas of the brain. Neuromodulation Vagus nerve stimulation (VNS):The last surgical procedure that can be done to help prevent the reoccurrence of seizures in the frontal lobes is to implant a stimulator on the vagus nerve. This device is a self-activating device that is inserted directly under the skin and can be controlled directly by the patient. When a patient is feeling the onset of an aura, he/she can activate the stimulator which in turn will provide stimulation to the left vagus nerve (the left vagus nerve is used because the right nerve plays a role in cardiac function). Although little is understood about the exact mechanism for vagal nerve stimulation, it has been proven to be a successful treatment that can often terminate seizures before they begin. It has the potential of being helpful in patients with resistance to AEDs.This procedure named Deep brain stimulation (DBS) another novel procedure that can be used utilizes a mechanism similar to that of a cardiac pacemaker The electrode is implanted into the patients brain, while a neuro-stimulator machine is placed beneath the skin of the chest. The stimulator sends an indication to the electrode in the brain to prevent any signal that potentially triggers or can trigger a seizure.Surgeries have been used as a treatment for FLE, however, meta-analyses have shown that proper etiological studies are important to give best post
Frontal lobe epilepsy	operative results, with children <3 years of age showing pathology and location of the surgery as important factors. It also showed the malformation of cortical development (MCD) induced FLE traced down to worst postoperative conditions, hence, poor accuracy and efficacy. Diet The use of a regimented diet is an approach that has been found to help control seizures in children with severe, medically intractable frontal lobe epilepsy. Although the use of dieting to prevent seizures from occurring is a lost treatment that has been replaced by the use of new types of anticonvulsants, it is still recommended to patients to this day. A ketogenic diet is a high-fat, low-carbohydrate based diet that patients are typically asked to follow in conjunction with their anticonvulsant medications. This diet was designed in order to mimic many of the effects that starvation has on the metabolic functioning of the body. By limiting the amount of carbohydrates and increasing the amount of exogenous fats available to the metabolism, the body will create an excess of water-soluble compounds known as ketone bodies. Although the mechanism of action is still unknown, it is believed that these excessive amounts of ketone bodies become the brains main source of energy and in turn are able to suppress the frequency of seizure occurrence. Epidemiology Epilepsy is a relatively common disorder, affecting between 0.5-1% of the population, and frontal lobe epilepsy accounts for about 1-2% of all epilepsies. The most common subdivision of epilepsy is symptomatic partial epilepsy, which causes simple partial seizures, and can be further divided into temporal and frontal lobe epilepsy. Although the exact number of cases of frontal lobe epilepsy is not currently known, it is known that FLE is the less common type of partial epilepsy, accounting for 20-30% of operative procedures involving intractable epilepsy. Patients with medically refractive epilepsy, over a fraction of one-fourth have been diagnosed with FLE, only one-third of which have been found to get relief from seizures by surgical interventions. The disorder also has no gender or age bias, affecting males and females of all ages. In a recent study, the mean subject age with frontal lobe epilepsy was 28.5 years old, and the average age of epilepsy onset for left frontal epilepsy was 9.3 years old whereas for right frontal epilepsy it was 11.1 years old. Research Over the past decade or so, researchers have been attempting to discover less invasive, safer and more efficient technologies that enable surgeons to remove epileptogenic focal zones without causing any damage to neighboring cortical areas. One such technology that has emerged and has great promise, is the use of gamma knife radiosurgery to either excise a brain tumor or repair a vascular malformation.In Gamma Knife radiosurgery, intersecting gamma radiation beams are applied directly to the tumor site or vascular malformation site that had been established using neuroimaging. Although each beam itself is not strong enough to damage brain tissue, when the beams intersect they are strong enough to destroy the specific brain tissue that is to be excised. This process is extremely efficient and entirely non-invasive and is therefore much safer than actual neurosurgery itself. Recently researchers and surgeons alike have begun to use Gamma Knife radiosurgery to treat cases of epilepsy by removing tumors responsible for causing the seizures. The early success rates in being able to alleviate seizures seem to be similar to those of temporal resective surgery however Gamma Knife radiosurgery has less associated risk factors. Current research on this topic is aimed at improving the technique in order to increase success rates as well as developing non-invasive forms of physiologic monitoring in order to determine the epileptogenic focus conclusively.Another way of understanding or studying FLE, highly under study is the network approach. When conventional imaging does not show the structural lesions, HFO analysis shows the pathophysiology, locally at the neural circuit level. Genetic analysis along with neuroimaging like fMRI, EEG, MEG, and in-depth semiological analysis, aids in the network approach study of FLE, both at micro and macro levels, giving it a comprehensive view. References External links Frontal lobe epilepsy on Epilepsy.com Epilepsy Foundation
Duane syndrome	Duane syndrome is a congenital rare type of strabismus most commonly characterized by the inability of the eye to move outward. The syndrome was first described by ophthalmologists Jakob Stilling (1887) and Siegmund Türk (1896), and subsequently named after Alexander Duane, who discussed the disorder in more detail in 1905.Other names for this condition include: Duanes retraction syndrome, eye retraction syndrome, retraction syndrome, congenital retraction syndrome and Stilling-Türk-Duane syndrome. Presentation The characteristic features of the syndrome are: Limitation of abduction (outward movement) of the affected eye. Less marked limitation of adduction (inward movement) of the same eye. Retraction of the eyeball into the socket on adduction, with associated narrowing of the palpebral fissure (eye closing). Widening of the palpebral fissure on attempted abduction. (N. B. Mein and Trimble point out that this is "probably of no significance" as the phenomenon also occurs in other conditions in which abduction is limited.) Poor convergence. A head turn to the side of the affected eye to compensate for the movement limitations of the eye(s) and to maintain binocular vision.While usually isolated to the eye abnormalities, Duane syndrome can be associated with other problems including cervical spine abnormalities Klippel–Feil syndrome, Goldenhar syndrome, heterochromia, and congenital deafness. Causes Duane syndrome is most probably a miswiring of the eye muscles, causing some eye muscles to contract when they shouldnt and other eye muscles not to contract when they should. Alexandrakis and Saunders found that in most cases the abducens nucleus and nerve are absent or hypoplastic, and the lateral rectus muscle is innervated by a branch of the oculomotor nerve. This view is supported by the earlier work of Hotchkiss et al. who reported on the autopsy findings of two patients with Duanes syndrome. In both cases the sixth cranial nerve nucleus and nerve was absent, and the lateral rectus muscle was innervated by the inferior division of the third or oculomotor nerve. This misdirection of nerve fibres results in opposing muscles being innervated by the same nerve. Thus, on attempted abduction, stimulation of the lateral rectus via the oculomotor nerve will be accompanied by stimulation of the opposing medial rectus via the same nerve; a muscle which works to adduct the eye. Thus, co-contraction of the muscles takes place, limiting the amount of movement achievable and also resulting in retraction of the eye into the socket. They also noticed mechanical factors and considered them secondary to loss of innervation: During corrective surgery fibrous attachments have been found connecting the horizontal recti and the orbital walls and fibrosis of the lateral rectus has been confirmed by biopsy. This fibrosis can result in the lateral rectus being tight and acting as a tether or leash. Co-contraction of the medial and lateral recti allows the globe to slip up or down under the tight lateral rectus producing the up and down shoots characteristic of the condition. Genetics There are two known genetic associations with Duane Syndrome. In some families the condition is associated with variants in the Chimerin 1 gene and in others it is associated with variants in the Transcription factor MafB gene. Diagnosis Classification Duanes syndrome has three variants: Type I: Limited abduction with or without esotropia Type II: Limited adduction with or without exotropia Type III: Limitation of both abduction and adduction and any form of horizontal strabismusBrown(1950) has classified Duanes syndrome according to the characteristics of the limitation of movement- Type A: with limited abduction and less-marked limitation of adduction Type B: showing limited abduction but normal adduction Type C: the limitation of adduction exceeds the limitation of abduction. There is an exotropic deviation and a head turn to compensate the loss of adductionThe first type is more common and accounts for 85% of the cases. Differential diagnosis In the clinical setting, the principal difficulties in differential diagnosis arise as a consequence of the very early age at which patients with this condition first present. The clinician must be persistent in examining abduction and adduction, and in looking for any associated palpebral fissure changes or head postures, when attempting to determine whether what often presents as a common childhood squint (note-"squint" is a British term for two eyes not looking in the same direction) is in fact Duane syndrome. Fissure changes, and the other associated characteristics of Duanes such as up or down shoots and globe retraction, are also vital when deciding whether any abduction limitation is the result of Duanes and not a consequence of VI or abducens cranial nerve palsy. Acquired Duanes syndrome is a rare event occurring after peripheral nerve palsy. Treatment The majority of patients remain symptom free and able to maintain binocularity with only a slight face turn. Amblyopia is uncommon and, where present, rarely dense. This can be treated with occlusion, and any refractive error can also be corrected. Duane syndrome cannot be cured, as the "missing" cranial nerve cannot be replaced, and traditionally there has been no expectation that surgery will result in any increase in the range of eye movement. Surgical intervention, therefore, has only been recommended where the patient is unable to maintain binocularity, where they are experiencing symptoms, or where they are forced to adopt a cosmetically unsightly or uncomfortable head posture in order to maintain binocularity. The aims of surgery are to place the eye in a more central position and, thus, place the field of binocularity more centrally also, and to overcome or reduce the need for the adoption of an abnormal head posture. Occasionally, surgery is not needed during childhood, but becomes appropriate later in life, as head position changes (presumably due to progressive muscle contracture).Surgical approaches include: Medial rectus recession in the involved eye or both eyes. By weakening the medial rectus muscles this procedure improves the crossed-eye appearance but does not improve outward eye movements (abductions). Morad et al. showed improved abduction after modest unilateral medial rectus recession and lateral rectus resection in a subgroup of patients with mild eye retraction and good adduction before surgery. Lateral transposition of the vertical muscles described by Rosenbaum has been shown to improve range of movement of the eye. The surgical procedure produces 40-65 degrees of binocular field. Orbital wall fixation of the lateral rectus muscle (muscle is disinserted and reattached to lateral orbital wall) is recommended an effective method to inactivate a lateral rectus muscle in cases of marked anomalous innervation and severe cocontraction. Epidemiology Most patients are diagnosed by the age of 10 years and Duanes is more common in girls (60 percent of the cases) than boys (40 percent of the cases). A French study reports that this syndrome accounts for 1.9% of the population of strabismic patients, 53.5% of patients are female, is unilateral in 78% of cases, and the left eye (71.9%) is affected more frequently than the right. Around 10–20% of cases are familial; these are more likely to be bilateral than non-familial Duane syndrome. Duane syndrome has no particular race predilection. See also Pediatric ophthalmology References Further reading Andrews, Caroline V.; Hunter, David G.; Engle, Elizabeth C. (1993). "Duane Syndrome". GeneReviews. University of Washington, Seattle. PMID 20301369. Retrieved 28 April 2019. External links Duanes Syndrome at eMedicine
Logopenic progressive aphasia	Logopenic progressive aphasia (LPA) is a variant of primary progressive aphasia. It is defined clinically by impairments in naming and sentence repetition. It is similar to conduction aphasia and is associated with atrophy to the left posterior temporal cortex and inferior parietal lobule. It is suspected that an atypical form of Alzheimers disease is the most common cause of logopenic progressive aphasia.Although patients with the logopenic variant of PPA are still able to produce speech, their speech rate may be significantly slowed due to word retrieval difficulty. Over time, they may experience the inability to retain lengthy information, causing problems with understanding complex verbal information. Some additional behavioral features include irritability, anxiety and agitation.Compared to other subtypes of primary progressive aphasia, the logopenic variant has been found to be associated with cognitive and behavioral characteristics. Studies have shown that patients with the logopenic variant perform significantly worse on tests of calculation than other primary progressive aphasia patients. Several logopenic variant patients, especially those with Alzheimers disease pathology, have also been found to perform poorly on memory tasks.Logopenic progressive aphasia is caused by damage to segregated brain regions, specifically the inferior parietal lobe and superior temporal regions. Difficulties in naming are produced from the thinning of the inferior parietal lobe. Damage to the dorsal pathways creates language deficiency in patients that is characteristic of logopenic progressive aphasia. See also Aphasia Dementia Early-onset Alzheimers disease References Further reading Harciarek M, Kertesz A (September 2011). "Primary progressive aphasias and their contribution to the contemporary knowledge about the brain-language relationship". Neuropsychol Rev. 21 (3): 271–87. doi:10.1007/s11065-011-9175-9. PMC 3158975. PMID 21809067. Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. (March 2004). "Cognition and anatomy in three variants of primary progressive aphasia". Ann. Neurol. 55 (3): 335–46. doi:10.1002/ana.10825. PMC 2362399. PMID 14991811. Rohrer JD, Knight WD, Warren JE, Fox NC, Rossor MN, Warren JD (January 2008). "Word-finding difficulty: a clinical analysis of the progressive aphasias". Brain. 131 (Pt 1): 8–38. doi:10.1093/brain/awm251. PMC 2373641. PMID 17947337.
Vesicovaginal fistula	Vesicovaginal fistula (VVF) is a subtype of female urogenital fistula (UGF). Presentation Vesicovaginal fistula, or VVF, is an abnormal fistulous tract extending between the bladder (vesica) and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault.In addition to the medical sequela from these fistulas, they often have a profound effect on the patients emotional well-being. Causes It may be the result of a congenital birth condition such as VACTERL association. It is often caused by childbirth (in which case it is known as an obstetric fistula), when a prolonged labor presses the unborn child tightly against the pelvis, cutting off blood flow to the vesicovaginal wall. The affected tissue may necrotize (die), leaving a hole.Vaginal fistulas can also result from particularly violent cases of rape, especially those involving multiple rapists and/or foreign objects. Some health centers in countries such as the Democratic Republic of Congo have begun to specialize in the surgical repair of vaginal fistulas. It can also be associated with hysterectomy, cancer operations, radiation therapy and cone biopsy. Treatment Vesicovaginal fistulae are typically repaired either transvaginally or laparoscopically, although patients who have had multiple transvaginal procedures sometimes attempt a final repair through a large abdominal incision, or laparotomy.The laparoscopic (minimally invasive) approach to VVF repair has become more prevalent due to its greater visualization, higher success rate, and lower rate of complications. Possible complications of surgical treatment Recurrent formation of the fistula Injury to ureter, bowel, or intestines Vaginal shortening History Before the 19th century, women who suffered from VVF were judged harshly and rejected by society. Throughout the 19th century, treatment for VVF was limited because the practice of gynecology was perceived as taboo. Doctors were almost entirely male at this time and looking at a nude female, even for medical purposes, was seen as divergent from 19th-century values.One of the most famous gynecological surgeons of this time was Dr. J. Marion Sims, who developed a successful technique for treating VVF in the mid-1800s, for which he is hailed as a pioneer of gynecology.Black enslaved women in the American South were particularly prone to VVF because they were denied proper nutrients and medical care. Sims performed on these women without anesthesia, which had not been introduced until after he started his experiments, and which in its infancy Dr. Sims hesitated to use. (Ether anesthesia was publicly demonstrated in Boston in 1846, a year after Sims began his experimentation.) Sims did not have a white female patient until he made ether available to them, although he publicly noted that he never resorted to using anesthetics because he believed that the pain did not justify the risks. A detailed case study of Dr. Sims even discusses the case of a white woman who underwent three operations, all without anesthesia. It was considered acceptable to operate on them without anesthetic because, Sims claimed, African-American women have a naturally higher pain tolerance.The healing process of the VVF procedure is still arduous. To have a successful recovery from the surgery, it must be successful on the first attempt. Dr. J. Marion Sims operations on African-American enslaved women showcase the dangerous nature of the procedure. There still have not been clear instructions on how to properly recover from the procedure other than taking prescribed antibiotics. See also Colposcopy Double dye test Rectovaginal fistula Urinary incontinence References == External links ==
Hemochromatosis type 4	Hemochromatosis type 4 is a hereditary iron overload disorder that affects ferroportin, an iron transport protein needed to export iron from cells into circulation. Although the disease is rare, it is found throughout the world and affects people from various ethnic groups. While the majority of individuals with type 4 hemochromatosis have a relatively mild form of the disease, some affected individuals have a more severe form. As the disease progresses, iron may accumulate in the tissues of affected individuals over time, potentially resulting in organ damage. Signs and symptoms Symptoms vary greatly between individuals with type 4 hemochromatosis. This difference in symptoms is likely due to the different types of SLC40A1 mutations patients may have. In general, signs and symptoms of type 4 hemochromatosis are caused by excess iron in cells, which leads to tissue damage. The damage is largely due to iron-catalyzed oxidative reactions. Iron can exchange electrons with a variety of substrates, which can lead to generation of reactive oxygen species. This can lead to oxidative stress, lipid peroxidation, and DNA damage, which may result in cell death. Two main forms of hemochromatosis type 4 exist (A and B), and the symptoms of these forms are distinct from one another.Type 4A hemochromatosis typically has milder symptoms than other types of hemochromatosis. Individuals with type 4A hemochromatosis tend to have hyperferritinemia (elevated ferritin in the blood plasma) and low saturated transferrin levels. These individuals are likely to have liver and spleen iron overload, primarily in Kupffer cells and other macrophages. Because iron export is impaired, iron is unavailable for transport by circulating transferrin. This iron unavailability potentially leads to mild anemia in type 4A hemochromatosis patients because iron is necessary for hemoglobin synthesis, and red blood cells have a relatively high turnover rate. Over time, iron stores increase, and individuals with type 4A hemochromatosis may develop hepatic fibrosis.The symptoms of type 4B hemochromatosis tend to be more severe. They resemble the symptoms of hemochromatosis types 1, 2, and 3. Plasma iron concentration is elevated, and symptoms include joint pain, diabetes, and arrhythmia. Liver iron deposition tends to be greater in type 4B than in type 4A. Liver damage occurs more frequently in this form of hemochromatosis than in type 4A, and some individuals develop cirrhosis of the liver. Genetics Type 4 hemochromatosis is caused by mutations of the SLC40A1 gene, located on the long arm of chromosome 2, specifically at 2q32.2. The SLC40A1 gene encodes ferroportin, a protein responsible for exporting iron from cells in the intestine, liver, spleen, and kidney, as well as from reticuloendothelial macrophages and the placenta. More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. All reported SLC40A1 mutations are deletions or missense mutations, which lead to amino acid substitution.Mutations to SLC40A1 that change the amino acid sequence can result in loss of function or gain of function for the resulting ferroportin protein. The loss of function mutation results in a phenotype that is different from that of a gain of function mutation, and these phenotypes are associated with two different forms of type 4 hemochromatosis. Loss-of-function mutations are more frequent and are associated with type 4A hemochromatosis. These mutations lead to a defect in the localization of ferroportin. Gain-of-function mutations are associated with type 4B and lead to production of ferroportin that resists negative regulation by hepcidin.Unlike other forms of hemochromatosis, which have a recessive pattern of inheritance, type 4 is an autosomal dominant disorder. The dominant inheritance pattern occurs in hemochromatosis type 4 because ferroportin is multimeric. Consequently, mutant ferroportin can associate with wild-type ferroportin in multimers and interfere with the function of normal ferroportin proteins. Pathophysiology In normal iron regulation, iron is absorbed in the intestine, and ferroportin transports iron from the cells of the intestinal lining into the bloodstream. Iron in the bloodstream is then bound by transferrin, which carries the iron to target cells. Iron is stored in cells and blood serum in a protein called ferritin. Reticuloendothelial macrophages, which can phagocytose red blood cells, are important in the iron recycling process. Ferroportin is upregulated in the reticuloendothelial macrophages after phagocytosis occurs so that iron from the degraded red blood cells can be released into the bloodstream and transported to other types of cells as needed. Hepcidin, a protein synthesized in the liver in response to iron or inflammation, is a regulator of ferroportin expression. When hepcidin binds ferroportin, ferroportin is phosphorylated, endocytosed, tagged with ubiquitin, and degraded. More than 39 mutations to the SLC40A1 gene have been identified in patients with type 4 hemochromatosis. The misregulation of ferroportin in type 4 hemochromatosis can involve a failure of ferroportin to be properly expressed at the cell membrane, or it can involve a failure of ferroportin to respond to negative regulation by hepcidin.Hemochromatosis type 4A is characterized by impaired iron export in cells. Reticuloendothelial macrophages are most affected. Iron accumulates preferentially in Kupffer cells, which are located in the liver, and serum ferritin increases; less iron is available for circulating transferrin, a protein that binds iron and transports it through the bloodstream to cell receptors. This means that, while iron is trapped in certain types of tissues, it cannot be transported to tissues where it is needed. The accumulation of iron in tissues due to impaired iron export can lead to increasing transferrin iron saturation and liver parenchymal iron overload in advanced stages of the disease. More ferritin is produced to suppress oxidative cell damage, although the amount of ferritin that cells can accumulate is limited.Hemochromatosis type 4B is characterized by abnormal iron release from macrophages and enterocytes because the mutant ferroportin is resistant to the hepcidin protein, which serves a regulatory function in wild-type ferroportin. Intestinal iron absorption and release of iron from macrophages is increased. Thus, this form of the disease leads to elevated transferrin saturation levels. Systemic iron overload results, and liver iron deposition is primarily in the hepatocytes. Diagnosis Diagnosis is based upon identification of symptoms, medical history, family history, and laboratory tests. Blood tests may show high levels of ferritin and low, normal, or high levels of transferrin saturation, depending on the form of hemochromatosis. The diagnosis must be confirmed by genetic testing for SLC40A1 mutations. Treatment Treatment is based on the symptoms and severity of the disease. Iron chelators may be used to bind excess iron in tissues and allow for excretion of the excess metal. Individuals with hemochromatosis type 4B may be treated with therapeutic phlebotomy. However, individuals with hemochromatosis type 4A may not require treatment. Additionally, therapeutic phlebotomy may not be tolerated in individuals with type 4A because anemia may develop despite the elevated serum ferritin levels typically found in these individuals. Epidemiology Ferroportin disease is rare. References == External links ==
Labyrinthine fistula	A labyrinthine fistula is an abnormal opening in the inner ear. This can result in leakage of the perilymph into the middle ear. This includes specifically a perilymph fistula (PLF), an abnormal connection between the fluid of the inner ear and the air-filled middle ear. This is caused by a rupture of the round window or oval window ligaments separating the inner and middle ear.Another type of labyrinthine fistula is the superior semicircular canal dehiscence, which allows the inner ear to be influenced by the intracranial pressure directly. Signs and symptoms PLF usually induces one or all the following pathological states: aural fullness, fluctuating or non-fluctuating hearing loss, tinnitus and dizziness, which may sometimes include vertigo and balance disorders. Cause Labyrinthine fistula can be both congenital or develop over time with the thinning of the otic capsule by the persistent pulsations of the intracranial pressures against the bones of the skull. Finally, disease conditions—for example cholesteatoma—can result in a labyrinthine fistula. Traumatic events, with excessive pressure changes to the inner ear such as in scuba diving, head trauma, or an extremely loud noise can lead to rupture and leakage. The most common causes of PLF are: head or ear traumas, rapid increases of intracranial pressure, congenital abnormalities (in children), complication of stapedectomy, barotraumas (e.g. slap/suction, scuba diving, skydiving, strong and repetitive nose-blowing or sneezing, heavy lifting). Diagnosis When diagnosing, PLF should be differentiated from Ménières disease. Tympanostomy has been reported to be a way to diagnose and cure PLF. Treatment Patients are advised to treat with bed rest and avoiding activities that increase intracranial pressure (i.e. weightlifting, Valsalva maneuver, scuba diving, flying in airplanes) with the hopes of the membrane healing on its own. Appropriate Physical therapy / vestibular rehabilitation techniques can be helpful in managing symptoms of movement sensitivity. References External links http://www.dizziness-and-balance.com/disorders/unilat/fistula.html
Osteoporotic bone marrow defect	Osteoporotic bone marrow defect is a condition which may be found in the body of the mandible. It is usually painless and found during routine radiographs. It appears as a poorly defined radiolucency (dark area) where there was a previous history of an extraction of a tooth. It may resemble a metastatic disease. It is a localized increase of hematopoietic bone marrow that creates a radiolucent radiographic defect. They occur more commonly in women in the midyears and show a predilection for the molar region of the mandible. They are especially common in extraction sites. Scattered trabeculae may extend short distances into the defect or, in some instances, through it, giving the defect a fairly characteristic appearance. Naturally there are no clinical symptoms. Cause The cause remains unknown. Diagnosis Differential diagnosis This defect may easily be mistaken for a cyst or tumor. Biopsy is required to rule these out. Treatment No treatment is required. References Kahn, Michael A. Basic Oral and Maxillofacial Pathology. Volume 1. 2001.
Yao syndrome	Yao syndrome (YAOS) (formerly called NOD2-associated autoinflammatory disease) is an autoinflammatory syndrome involving episodes of fever and abnormal inflammation affecting many parts of the body, particularly the skin, joints, and gastrointestinal system. Signs and symptoms Arthralgia (Arthritis) Fever Diarrhea Abdominal Pain Keratoconjunctivitis Sicca (Dry eyes) Pleurisy Idiopathic Pericarditis Xerostomia (Dry mouth) Erythematous Plaques Dermatitis Diagnostic criteria Yao syndrome is diagnosed if 2 major criteria, at least one minor criterion, the molecular criterion, and exclusion criteria are fulfilled. Treatment A study to determine the effectiveness of Novartis pharmaceutical drug Canakinumab was conducted. In this study, canakinumab was effective in patients with YAOS, and thus clinical trial of canakinumab may be warranted as a therapeutic option for this disease. Inheritance Yao Syndrome inheritance is classified as Multifactorial Inheritance. References External links MedGen-Yao Syndrome Genetics Home Reference-Yao Syndrome
Pre-excitation syndrome	Pre-excitation syndrome is a heart condition in which part of the cardiac ventricles are activated too early. Pre-excitation is caused by an abnormal electrical connection or accessory pathway between or within the cardiac chambers. Pre-excitation may not cause any symptoms but may lead to palpitations caused by abnormal heart rhythms. It is usually diagnosed using an electrocardiogram, but may only be found during an electrophysiological study. The condition may not require any treatment at all, but symptoms can be controlled using medication or catheter ablation. Types Several types of pre-excitation syndrome have been described. Pathophysiology Normally, the atria and the ventricles are electrically isolated, and electrical contact between them exists only at the "atrioventricular node". In all pre-excitation syndromes, at least one more conductive pathway is present. Physiologically, the normal electrical depolarization wave is delayed at the atrioventricular node to allow the atria to contract before the ventricles. However, there is no such delay in the abnormal pathway, so the electrical stimulus passes to the ventricle by this tract faster than via normal atrioventricular/bundle of His system, and the ventricles are depolarized (excited) before (pre-) normal conduction system. References == External links ==
Hippus	Pupillary hippus, also known as pupillary athetosis, is spasmodic, rhythmic, but regular dilating and contracting pupillary movements between the sphincter and dilator muscles. Pupillary hippus comes from the Greek hippos meaning horse, perhaps due to the rhythm of the contractions representing a galloping horse.It is particularly noticeable when pupil function is tested with a light, but is independent of eye movements or changes in illumination. It is usually normal, however pathological hippus can occur.Pathologic hippus, the phenomenon of increased oscillation or their amplitude, is associated with aconite poisoning, altered mental status, trauma, cirrhosis, and renal disease; suggesting a common pathway of frontal lobe dysfunction. A retrospective study of 117 hospitalized patients with hippus noted an increased 30-day mortality when compared to controls and adjusted for other factors. See also Athetosis Anisocoria - condition characterized by an unequal size of the eyes pupils. == References ==
Balantidiasis	Balantidiasis is a protozoan infection caused by infection with Balantidium coli. Symptoms and signs Usually asymptomatic in immunocompetent individuals, but the symptoms of balantidiasis include: Intermittent diarrhea Constipation Vomiting Abdominal pain Anorexia Weight loss Headache Colitis Marked fluid lossThe most common ones are intermittent diarrhea and constipation or inflammation of the colon combined with abdominal cramps and bloody stools. Transmission Balantidium is the only ciliated protozoan known to infect humans. Balantidiasis is a zoonotic disease and is acquired by humans via the feco-oral route from the normal host, the pig, where it is asymptomatic. “Contaminated water is the most common mechanism of transmission. Equally dangerous, however, is the ingestion of contaminated food.” Morphology Balantidium coli exists in either of two developmental stages: trophozoites and cysts. In the trophozoite form, they can be oblong or spherical, and are typically 30 to 150 µm in length and 25 to 120 µm in width. It is its size at this stage that allows Balantidium coli to be characterized as the largest protozoan parasite of humans. Trophozoites possess both a macronucleus and a micronucleus, and both are usually visible. The macronucleus is large and sausage-shaped while the micronucleus is less prominent. At this stage, the organism is not infective but it can replicate by transverse binary fission.In its cyst stage, the parasite takes on a smaller, more spherical shape, with a diameter of around 40 to 60 µm. Unlike the trophozoite, whose surface is covered only with cilia, the cyst form has a tough wall made of one or more layers. The cyst form also differs from the trophozoite form because it is non-motile and does not undergo reproduction. Instead, the cyst is the form that the parasite takes when it causes infection. Diagnosis The diagnosis of balantidiasis can be an intricate process, partly because the related symptoms may or may not be present. However, the diagnosis of balantidiasis can be considered when a patient has diarrhea combined with a probable history of current exposure to pigs (since pigs are the primary reservoir), contact with infected persons, or anal intercourse. In addition, the diagnosis of balantidiasis can be made by microscopic examination of stools in search of trophozoites or cysts, or colonoscopy or sigmoidoscopy to obtain a biopsy from the large intestines which may provide evidence for the presence of trophozoites. Prevention Preventative measures require effective personal and community hygiene. Some specific safeguards include the following: Purification of drinking water. Proper handling of food. Careful disposal of human feces. Monitoring the contacts of balantidiasis patients. Treatment Balantidiasis can be treated with tetracycline, metronidazole or iodoquinol. History The first study to generate balantidiasis in humans was undertaken by Cassagrandi and Barnagallo in 1896. However, this experiment was not successful in creating an infection and it was unclear whether Balantidium coli was the actual parasite used. The first case of balantidiasis in the Philippines, where it is the most common, was reported in 1904. Currently, Balantidium coli is distributed worldwide but less than 1% of the human population is infected. Pigs are a major reservoir of the parasite, and infection of humans occurs more frequently in areas where pigs comingle with people. This includes places like the Philippines, as previously mentioned, but also includes countries such as Bolivia and Papua New Guinea. But pigs are not the only animal where the parasite is found. For example, Balantidium coli also has a high rate of incidence in rats. In a Japanese study that analyzed the fecal samples in 56 mammalian species, Balantidium coli was found to be present not just in all the wild boars tested (with wild boars and pigs being considered the same species), it was also found in five species of non human primate: Chimpanzee (Pan troglodytes), White-handed gibbon (Hylobates lar), Squirrelmonkey (Saimiri sciurea), Sacred baboon (Comopithecus hamadryas), and Japanese macaque (Macaca fuscata). In other studies, Balantidium coli was also found in species from the orders Rodentia and Carnivora. References == External links ==
Pityriasis lichenoides et varioliformis acuta	Pityriasis lichenoides et varioliformis acuta is a disease of the immune system. It is the more severe version of pityriasis lichenoides chronica. The disease is characterized by rashes and small lesions on the skin. The disease is more common in males and usually occurs in young adulthood, although it has been seen in every age group and every race. It is possible for the disease to go into remission for short periods of time or forever. Causes There is no known cause of this disease; There is some evidence associating it with Parvovirus B19. Diagnosis It is commonly misdiagnosed as chickenpox or rosacea, or misidentified as a form of Staph infection. The most accurate way to diagnose it is by biopsy. This disease has not been known to be life-threatening. Treatment It is not contagious and currently there is no cure for the disease, although the lesions can be treated with phototherapy as well as antibiotics, including erythromycin, azithromycin and tetracycline. Treatment often involves multiple therapies that address the immune system and bacterial, viral, or dermatological causes. Eponym Pityriasis lichenoides et varioliformis acuta is also known as Mucha–Habermann disease. It is named for Rudolf Habermann (1884–1941), a German dermatologist, and Viktor Mucha, an Austrian dermatologist. See also Cutaneous T-cell lymphoma Pityriasis lichenoides Parapsoriasis List of cutaneous conditions References External links DermNet scaly/pityriasis-lichenoides
Hypertensive disease of pregnancy	Hypertensive disease of pregnancy, also known as maternal hypertensive disorder, is a group of high blood pressure disorders that include preeclampsia, preeclampsia superimposed on chronic hypertension, gestational hypertension, and chronic hypertension.Maternal hypertensive disorders occurred in about 20.7 million women in 2013. About 10% of pregnancies globally are complicated by hypertensive diseases. In the United States, hypertensive disease of pregnancy affects about 8% to 13% of pregnancies. Rates have increased in the developing world. They resulted in 29,000 deaths in 2013 down from 37,000 deaths in 1990. They are one of the three major causes of death in pregnancy (16%) along with post partum bleeding (13%) and puerperal infections (2%). Signs and symptoms Although many pregnant women with high blood pressure have healthy babies without serious problems, high blood pressure can be dangerous for both the mother and baby. Women with pre-existing, or chronic, high blood pressure are more likely to have certain complications during pregnancy than those with normal blood pressure. However, some women develop high blood pressure while they are pregnant (often called gestational hypertension).Chronic poorly-controlled high blood pressure before and during pregnancy puts a pregnant woman and her baby at risk for problems. It is associated with an increased risk for maternal complications such as preeclampsia, placental abruption (when the placenta separates from the wall of the uterus), and gestational diabetes. These women also face a higher risk for poor birth outcomes such as preterm delivery, having an infant small for his/her gestational age, and infant death. Risk factors Some women have a greater risk of developing hypertension during pregnancy. These are: Women with chronic hypertension (high blood pressure before becoming pregnant). Women who developed high blood pressure or preeclampsia during a previous pregnancy, especially if these conditions occurred early in the pregnancy. Women who are obese prior to pregnancy. Pregnant women under the age of 20 or over the age of 40. Women who are pregnant with more than one baby. Women with diabetes, kidney disease, rheumatoid arthritis, lupus, or scleroderma. Diagnosis There is no single test to predict or diagnose preeclampsia. Key signs are increased blood pressure and protein in the urine (proteinuria). Other symptoms that seem to occur with preeclampsia include persistent headaches, blurred vision or sensitivity to light, and abdominal pain.All of these sensations can be caused by other disorders; they can also occur in healthy pregnancies. Regular visits are scheduled to track blood pressure and level of protein in urine, to order and analyze blood tests that detect signs of preeclampsia, and to monitor fetal development more closely. Classification A classification of hypertensive disorders of pregnancy uses 4 categories as recommended by the U.S. National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: Chronic hypertension; Preeclampsia-eclampsia; Preeclampsia superimposed on chronic hypertension; Gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy).This terminology is preferred over the older but widely used term pregnancy-induced hypertension (PIH) because it is more precise. The newer terminology reflects simply relation of pregnancy with either the onset or first detection of hypertension; the question of causation, while pathogenetically interesting, is not the important point for most health care purposes. This classification treats HELLP syndrome as a type of preeclampsia rather than a parallel entity. Chronic hypertension Chronic hypertension is a type of high blood pressure in a pregnant woman that is pre-existing before conception, diagnosed early in pregnancy, or persists significantly after the end of pregnancy. It affects about 5% of all pregnancies and can be a primary disorder of essential hypertension or secondary to another condition; it is not caused by pregnancy itself.The diagnostic criteria for chronic hypertension are typically considered to be at least two separate blood pressure readings taken at least four hours apart with systolic blood pressure ≥ 140mmHg, diastolic blood pressure ≥90 mmHg, or both, identified before pregnancy, before 20 weeks gestation, or persisting at least 12 weeks after giving birth. However, there is some controversy over the utility of adopting lower thresholds for diagnosis of chronic hypertension, which is more consistent with recent recommendations from the American College of Cardiology and the American Heart Association for the diagnosis of hypertension in adults. Chronic hypertension in pregnancy is now considered mild if blood pressures do not exceed 159 mmHg systolic and 109 mmHg diastolic and severe if pressures are ≥ 160 mmHg systolic or 110 mmHg diastolic, although controversy also exists as to the most appropriate cutoffs for this definition.Because chronic hypertension can progress to more severe forms of disease, it is important to accurately diagnose the condition early, ideally prior to pregnancy, and initiate management to control parental blood pressure. This is often difficult, as many reproductive individuals may not regularly visit the doctor and, when pregnant, may initially present for prenatal care in the second trimester. Pre-eclampsia and eclampsia Preeclampsia is a medical condition which usually develops after 20 weeks of gestation and traditionally involves both newly increased blood pressure (blood pressure > 140/90 mmHg) and proteinuria. Preeclampsia is a leading cause of fetal complications, which include low birth weight, preterm birth, and stillbirth. Women with preeclampsia are encouraged to deliver the child after 37 weeks of gestation to minimize the risks of the severe complications.Preeclampsia can also be diagnosed if a woman has both increased blood pressure and 1 or more signs of significant organ damage. Signs of significant organ damage include: Severely elevated blood pressure (blood pressure > 160/110) Thrombocytopenia Increased or rapidly elevating levels of creatinine in the blood Increased liver enzymes Pulmonary edema New or persistent headaches that do not respond to pain medication Blurred or altered visionIf a woman with preeclampsia has any of these signs of significant organ damage, then her condition is classified as preeclampsia with severe features. This diagnosis can be made even if the patient does not have proteinuria. Women with preeclampsia with severe features are encouraged to deliver the child after 34 weeks of gestation to minimize the risks of the severe complications.Preeclampsia can also present with seizures in the pregnant mother. In this case, the patient would be diagnosed with eclampsia.There is no proven way to prevent preeclampsia/eclampsia. Most women who develop signs of preeclampsia, however, are closely monitored to lessen or avoid related problems. The only way to "cure" preeclampsia/eclampsia is to deliver or abort the baby. Eclampsia Eclampsia is one particularly concerning form of preeclampsia in which a pregnant woman who previously presented with signs of newly increased blood pressure begins to experience new generalized seizures or coma. Up to 70% of patients with eclampsia experience complications associated with pregnancy. These complications can include HELLP syndrome, acute kidney injury, and disseminated intravascular coagulation among others. HELLP Syndrome HELLP Syndrome is a type of preeclampsia with severe features that involves increased hemolysis, increased liver enzymes, and low platelet levels. While most women with HELLP syndrome have high blood pressure and proteinuria, up to 20% of HELLP syndrome cases do not present with these classical signs of preeclampsia. However, like pre-eclampsia, HELLP syndrome can also lead to low birth weight and premature birth of the fetus/neonate. HELLP syndrome has a fetal/neonatal mortality rate of 7-20%. Preeclampsia superimposed on chronic hypertension Preeclampsia superimposed on chronic hypertension occurs when a pregnant woman with chronic hypertension develops signs of pre-eclampsia, typically defined as new onset of proteinuria ≥30 mg/dL (1+ in the dipstick) in at least 2 random urine specimens that were collected ≥4 h apart (but within a 7-day interval) or 0.3 g in a 24-h period. Like ordinary pre-eclampsia, superimposed pre-eclampsia can also occur with severe features, which are defined as: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg despite escalation of antihypertensive therapy; thrombocytopenia (platelet count <100,000/microL); impaired liver function; new-onset or worsening renal insufficiency; pulmonary edema; or persistent cerebral or visual disturbances. As a result, superimposed pre-eclampsia can be diagnosed without proteinuria when a sudden increase in previously well-controlled blood pressure is accompanied by severe features of pre-eclampsia. Gestational hypertension Gestational hypertension is a provisional diagnosis that involves newly increased blood pressure in a pregnant woman that usually develops after 20 weeks of gestation, but does not currently show any signs of proteinuria or other features associated with preeclampsia. Up to 50% of gestational hypertension patients go on to develop some form of preeclampsia.Gestational hypertension will normally resolve by 12 weeks postpartum. In this case, the diagnosis of gestational hypertension will be updated to be transient hypertension of pregnancy. If the increased blood pressure does not resolve by 12 weeks postpartum, then the diagnosis of gestational hypertension will be updated to be chronic hypertension. Prevention Blood pressure control can be accomplished before pregnancy. Medications can control blood pressure. Certain medications may not be ideal for blood pressure control during pregnancy such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor antagonists. Controlling weight gain during pregnancy can help reduce the risk of hypertension during pregnancy.There is limited evidence to suggest that calcium supplementation may reduce the risk of pre-eclampsia or stillbirth but it is unclear if it has other benefits. Management The only way to definitively treat a hypertensive disease of pregnancy (i.e. preeclampsia/eclampsia, gestational hypertension, etc. ) is to deliver the fetus. This prevents further development of complications related to the disorder in both the mother and the fetus. Therefore, the first line approach to management of these conditions is to consider induction of preterm labor. The exact timing of when to induce labor is dependent on the severity of symptoms related to the hypertensive disease, as well as the medical condition of both the mother and the fetus. Generally, in mothers with preeclampsia, labor is induced once the gestational age is >37 weeks. In patients with preeclampsia with severe features or eclampsia, labor is induced once the gestational age is >34 weeks. In patients with gestational hypertension and no other signs of severe disease, labor is generally induced at term.In cases where the fetus has not yet reached a safe gestational age to be delivered, management is focused on managing symptoms to give the fetus more time to mature. In women with gestational hypertension, some studies have found that usage of baby aspirin can prevent the progression of the condition to preeclampsia/eclampsia and reduce the risk of complications associated with hypertensive disorders of pregnancy.Pregnant women with chronic hypertension diagnosed before or early in pregnancy should be evaluated to identify the underlying cause of hypertension as well as possible existing end-organ damage caused by hypertension, such as cardiac and kidney injury. Although most cases of chronic hypertension are primary, and thus classified as essential hypertension, secondary causes such as renal, vascular, and endocrine disorders must also be considered, especially in patients with chronic hypertension presenting abnormally, for instance at a young age or refractory to first-line treatment. If end-organ damage or an underlying cause of hypertension is identified, these conditions must also be treated. Women with chronic hypertension in pregnancy must be closely monitored because they are five times as likely as those with normal blood pressure to develop pre-eclampsia, which is a much more severe condition with serious risks for the mother and fetus.For all hypertensive disorders of pregnancy, a major component of care is management of the associated hypertension. This involves use of antihypertensive medication as well as restricting activity to lower blood pressure to reduce the risk of stroke. In women with preeclampsia or eclampsia, magnesium sulfate is often prescribed to prevent the occurrence of seizures in the gestational parent. Treatment should be continued from the time of diagnosis to several weeks postpartum given the increased risk of medical complications immediately following delivery of the fetus. Prognosis The effects of high blood pressure during pregnancy vary depending on the disorder and other factors. Preeclampsia does not in general increase a womans risk for developing chronic hypertension or other heart-related problems. Women with normal blood pressure who develop preeclampsia after the 20th week of their first pregnancy, short-term complications, including increased blood pressure, usually go away within about six weeks after delivery.Some women, however, may be more likely to develop high blood pressure or other heart disease later in life. More research is needed to determine the long-term health effects of hypertensive disorders in pregnancy and to develop better methods for identifying, diagnosing, and treating women at risk for these conditions.Even though high blood pressure and related disorders during pregnancy can be serious, most women with high blood pressure and those who develop preeclampsia have successful pregnancies. Obtaining early and regular prenatal care for pregnant women is important to identify and treat blood pressure disorders. Epidemiology High blood pressure problems occur in six percent to eight percent of all pregnancies in the U.S., about 70 percent of which are first-time pregnancies. In 1998, more than 146,320 cases of preeclampsia alone were diagnosed.Although the proportion of pregnancies with gestational hypertension and eclampsia has remained about the same in the U.S. over the past decade, the rate of preeclampsia has increased by nearly one-third. This increase is due in part to a rise in the numbers of older mothers and of multiple births, where preeclampsia occurs more frequently. For example, in 1998 birth rates among women ages 30 to 44 and the number of births to women ages 45 and older were at the highest levels in three decades, according to the National Center for Health Statistics. Furthermore, between 1980 and 1998, rates of twin births increased about 50 percent overall and 1,000 percent among women ages 45 to 49; rates of triplet and other higher-order multiple births jumped more than 400 percent overall, and 1,000 percent among women in their 40s. == References ==
Gastroschisis	Gastroschisis is a birth defect in which the babys intestines extend outside of the abdomen through a hole next to the belly button. The size of the hole is variable, and other organs including the stomach and liver may also occur outside the babys body. Complications may include feeding problems, prematurity, intestinal atresia, and intrauterine growth restriction.The cause is typically unknown. Rates are higher in babies born to mothers who smoke, drink alcohol, or are younger than 20 years old. Ultrasounds during pregnancy may make the diagnosis. Otherwise diagnosis occurs at birth. It differs from omphalocele in that there is no covering membrane over the intestines.Treatment involves surgery. This typically occurs shortly after birth. In those with large defects the exposed organs may be covered with a special material and slowly moved back into the abdomen. The condition affects about 4 per 10,000 newborns. Rates of the condition appear to be increasing. Signs and symptoms There are no signs during pregnancy. About sixty percent of infants with gastroschisis are born prematurely. At birth, the baby will have a relatively small (<4 cm) hole in the abdominal wall, usually just to the right of the belly button. Some of the intestines are usually outside the body, passing through this opening. In rare circumstances, the liver and stomach may also come through the abdominal wall. After birth these organs are directly exposed to air. Causes The cause of gastroschisis is not known. There may be genetic causes in some cases, and there may be environmental factors to which the mother is exposed during pregnancy.Risk factors include the mother being young, and use of alcohol or tobacco. Pathophysiology During the fourth week of human embryonic development, the lateral body wall folds of the embryo meet at the midline and fuse together to form the anterior body wall. However, in gastroschisis and other anterior body wall defects, this fails to occur by either one or both of the lateral body wall folds not moving properly to meet with the other and fusing together. This incomplete fusion results in a defect that allows abdominal organs to protrude through the abdominal wall, and the intestines typically herniate through the rectus abdominis muscle, lying to the right of the umbilicus. The forces responsible for the movement of the lateral body wall folds are poorly understood, and a better understanding of these forces would help to explain why gastroschisis occurs mostly to the right of the umbilicus, while other ventral body wall defects occur in the midline.At least six hypotheses have been proposed for the pathophysiology: Failure of mesoderm to form in the body wall Rupture of the amnion around the umbilical ring with subsequent herniation of bowel Abnormal involution of the right umbilical vein leading to weakening of the body wall and gut herniation Disruption of the right vitelline (yolk sac) artery with subsequent body wall damage and gut herniation Abnormal folding of the body wall results in a ventral body wall defect through which the gut herniates Failure to incorporate the yolk sac and related vitelline structures into the umbilical stalkThe first hypothesis does not explain why the mesoderm defect would occur in such a specific small area. The second hypothesis does not explain the low percentage of associated abnormality compared with omphalocele. The third hypothesis was criticized due to no vascular supplement of anterior abdominal wall by umbilical vein. The fourth hypothesis was commonly accepted, but it was later shown that the right vitelline artery (right omphalomesenteric artery) did not supply the anterior abdominal wall in this area. More evidence is needed to support the fifth hypothesis. Diagnosis In the developed world, around 90% of cases are identified during normal ultrasound screens, usually in the second trimester.Distinguished from other ventral body wall defects such as omphalocele, there is no overlying sac or peritoneum, and the defect is usually much smaller in gastroschisis. Treatment Gastroschisis requires surgical treatment to return the exposed intestines to the abdominal cavity and close the hole in the abdomen. Sometimes this is done immediately but more often the exposed organs are covered with sterile drapings, and only later is the surgery done. Affected newborns frequently require more than one surgery, as only about 10% of cases can be closed in a single surgery.: 1141–1142 Given the urgent need for surgery after birth, it is recommended that delivery occur at a facility equipped for caring for these high-risk neonates, as transfers to other facilities may increase risk of adverse outcomes. There is no evidence that cesarean deliveries lead to better outcomes for babies with gastroschisis, so cesarean delivery is only considered if there are other indications.The main cause for lengthy recovery periods is the time taken for the infants bowel function to return to normal. After surgery infants are fed through IV fluids and gradually introduced to normal feeding. Prognosis If left untreated, gastroschisis is fatal to the infant; however, in adequate settings the survival rate for treated infants is 90%.Most risks of gastroschisis are related to decreased bowel function. Sometimes blood flow to the exposed organs is impaired or there is less than the normal amount of intestine. This may put infants at risk for other dangerous conditions such as necrotizing enterocolitis. Also, because their intestines are exposed, infants with gastroschisis are at increased risk for infection, and must be closely monitored.After surgery a child with gastroschisis will have some degree of intestinal malrotation. About 1% of children will experience a midgut volvulus after surgery. Epidemiology As of 2015 the worldwide incidence was about 2 to 5 per 10 000 live births, and this number seemed to be increasing.As of 2017 the CDC estimates that about 1,871 babies are born each year in the United States with gastroschisis. See also Smoking and pregnancy References == External links ==
Hyperemesis gravidarum	Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration. Feeling faint may also occur. It is considered more severe than morning sickness. Symptoms often get better after the 20th week of pregnancy but may last the entire pregnancy duration.The exact causes of hyperemesis gravidarum are unknown. Risk factors include the first pregnancy, multiple pregnancy, obesity, prior or family history of HG, trophoblastic disorder, and a history of eating disorders. Diagnosis is usually made based on the observed signs and symptoms. HG has been technically defined as more than three episodes of vomiting per day such that weight loss of 5% or three kilograms has occurred and ketones are present in the urine. Other potential causes of the symptoms should be excluded, including urinary tract infection and an overactive thyroid.Treatment includes drinking fluids and a bland diet. Recommendations may include electrolyte-replacement drinks, thiamine, and a higher protein diet. Some people require intravenous fluids. With respect to medications, pyridoxine or metoclopramide are preferred. Prochlorperazine, dimenhydrinate, ondansetron (sold under the brand-name Zofran) or corticosteroids may be used if these are not effective. Hospitalization may be required due to the severe symptoms associated. Psychotherapy may improve outcomes. Evidence for acupressure is poor.While vomiting in pregnancy has been described as early as 2,000 BC, the first clear medical description of HG was in 1852 by Paul Antoine Dubois. HG is estimated to affect 0.3–2.0% of pregnant women, although some sources say the figure can be as high as 3%. While previously known as a common cause of death in pregnancy, with proper treatment this is now very rare. Those affected have a lower risk of miscarriage but a higher risk of premature birth. Some pregnant women choose to have an abortion due to HG symptoms. Signs and symptoms When vomiting is severe, it may result in the following: Loss of 5% or more of pre-pregnancy body weight Dehydration, causing ketosis, and constipation Nutritional disorders, such as vitamin B1 (thiamine) deficiency, vitamin B6 (pyridoxine) deficiency or vitamin B12 (cobalamin) deficiency Metabolic imbalances such as metabolic ketoacidosis or thyrotoxicosis Physical and emotional stress Difficulty with activities of daily livingSymptoms can be aggravated by hunger, fatigue, prenatal vitamins (especially those containing iron), and diet. Many women with HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. Excessive salivation, also known as sialorrhea gravidarum, is another symptom experienced by some women. Hyperemesis gravidarum tends to occur in the first trimester of pregnancy and lasts significantly longer than morning sickness. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some people with HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth.A small percentage rarely vomit, but the nausea still causes most (if not all) of the same issues that hyperemesis with vomiting does. Causes There are numerous theories regarding the cause of HG, but the cause remains controversial. It is thought that HG is due to a combination of factors which may vary between women and include genetics. Women with family members who had HG are more likely to develop the disease.One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (β-hCG). This theory would also explain why hyperemesis gravidarum is most frequently encountered in the first trimester (often around 8–12 weeks of gestation), as β-hCG levels are highest at that time and decline afterward. Another postulated cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to nausea/vomiting).More recently, another cause of HG was discovered: "Evidence suggests abnormal levels of the hormone GDF15 are associated with HG. The validation of a second risk variant, rs1054221, provides further support for GDF15s role in the etiology of HG. Additionally, maternal genes appear to play a more significant role than paternal DNA in contributing to the severity of NVP." Pathophysiology Although the pathophysiology of HG is poorly understood, the most commonly accepted theory suggests that levels of β-hCG are associated with it. Leptin, a hormone that inhibits hunger, may also play a role.Possible pathophysiological processes involved are summarized in the following table: Diagnosis Hyperemesis gravidarum is considered a diagnosis of exclusion. HG can be associated with serious problems in the mother or baby, such as Wernickes encephalopathy, coagulopathy and peripheral neuropathy.Women experiencing hyperemesis gravidarum often are dehydrated and lose weight despite efforts to eat. The onset of the nausea and vomiting in hyperemesis gravidarum is typically before the 20th week of pregnancy. Differential diagnosis Diagnoses to be ruled out include the following: Investigations Common investigations include blood urea nitrogen (BUN) and electrolytes, liver function tests, urinalysis, and thyroid function tests. Hematological investigations include hematocrit levels, which are usually raised in HG. An ultrasound scan may be needed to know gestational status and to exclude molar or partial molar pregnancy. Management Dry bland food and oral rehydration are first-line treatments. Due to the potential for severe dehydration and other complications, HG is treated as an emergency. If conservative dietary measures fail, more extensive treatment such as the use of antiemetic medications and intravenous rehydration may be required. If oral nutrition is insufficient, intravenous nutritional support may be needed. For women who require hospital admission, thromboembolic stockings or low-molecular-weight heparin may be used as measures to prevent the formation of a blood clot. Intravenous fluids Intravenous (IV) hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. Likewise, supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernickes encephalopathy. A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, electrolyte levels should be monitored and supplemented; of particular concern are sodium and potassium. After IV rehydration is completed, patients typically begin to tolerate frequent small liquid or bland meals. After rehydration, treatment focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making continuing care necessary. Home care is available in the form of a peripherally inserted central catheter (PICC) line for hydration and nutrition. Home treatment is often less expensive and reduces the risk for a hospital-acquired infection compared with long-term or repeated hospitalizations. Medications A number of antiemetics are effective and safe in pregnancy including: pyridoxine/doxylamine, antihistamines (such as diphenhydramine), and phenothiazines (such as promethazine). With respect to effectiveness, it is unknown if one is superior to another for relieving nausea or vomiting. Limited evidence from published clinical trials suggests the use of medications to treat hyperemesis gravidarum.While pyridoxine/doxylamine, a combination of vitamin B6 and doxylamine, is effective in nausea and vomiting of pregnancy, some have questioned its effectiveness in HG.Ondansetron may be beneficial, however, there are some concerns regarding an association with cleft palate, and there is little high-quality data. Metoclopramide is also used and relatively well tolerated. Evidence for the use of corticosteroids is weak; there is some evidence that corticosteroid use in pregnant women may slightly increase the risk of cleft lip and cleft palate in the infant and may suppress fetal adrenal activity. However, hydrocortisone and prednisolone are inactivated in the placenta and may be used in the treatment of hyperemesis gravidarum after 12 weeks.Medicinal cannabis has been used to treat pregnancy-associated hyperemesis. Nutritional support Women not responding to IV rehydration and medication may require nutritional support. Patients might receive parenteral nutrition (intravenous feeding via a PICC line) or enteral nutrition (via a nasogastric tube or a nasojejunal tube). There is only limited evidence from trials to support the use of vitamin B6 to improve outcome. An oversupply of nutrition (hyperalimentation) may be necessary in certain cases to help maintain volume requirements and allow weight gain. A physician might also prescribe Vitamin B1 (to prevent Wernickes encephalopathy) and folic acid. Alternative medicine Acupuncture (both with P6 and traditional method) has been found to be ineffective. The use of ginger products may be helpful, but evidence of effectiveness is limited and inconsistent, though three recent studies support ginger over placebo. Complications Pregnant woman If HG is inadequately treated, anemia, hyponatremia, Wernickes encephalopathy, kidney failure, central pontine myelinolysis, coagulopathy, atrophy, Mallory-Weiss tears, hypoglycemia, jaundice, malnutrition, pneumomediastinum, rhabdomyolysis, deconditioning, deep vein thrombosis, pulmonary embolism, splenic avulsion, or vasospasms of cerebral arteries are possible consequences. Depression and post-traumatic stress disorder are common secondary complications of HG and emotional support can be beneficial. Infant The effects of HG on the fetus are mainly due to electrolyte imbalances caused by HG in the mother. Infants of women with severe hyperemesis who gain less than 7 kilograms (15 lb) during pregnancy tend to be of lower birth weight, small for gestational age, and born before 37 weeks gestation. In contrast, infants of women with hyperemesis who have a pregnancy weight gain of more than 7 kilograms appear similar to infants from uncomplicated pregnancies. There is no significant difference in the neonatal death rate in infants born to mothers with HG compared to infants born to mothers who do not have HG. Children born to mothers with undertreated HG have a fourfold increase in neurobehavioral diagnoses. Epidemiology Vomiting is a common condition affecting about 50% of pregnant women, with another 25% having nausea. However, the incidence of HG is only 0.3–1.5%. After preterm labor, hyperemesis gravidarum is the second most common reason for hospital admission during the first half of pregnancy. Factors such as infection with Helicobacter pylori, a rise in thyroid hormone production, low age, low body mass index prior to pregnancy, multiple pregnancies, molar pregnancies, and a history of hyperemesis gravidarum have been associated with the development of HG. History Thalidomide was prescribed for treatment of HG in Europe until it was recognized that thalidomide is teratogenic and is a cause of phocomelia in neonates. Etymology Hyperemesis gravidarum is from the Greek hyper-, meaning excessive, and emesis, meaning vomiting, and the Latin gravidarum, the feminine genitive plural form of an adjective, here used as a noun, meaning "pregnant [woman]". Therefore, hyperemesis gravidarum means "excessive vomiting of pregnant women". Notable cases Author Charlotte Brontë is often thought to have had hyperemesis gravidarum. She died in 1855 while four months pregnant, having been affected by intractable nausea and vomiting throughout her pregnancy, and was unable to tolerate food or even water.Catherine, Princess of Wales was hospitalised due to hyperemesis gravidarum during her first pregnancy, and was treated for a similar condition during the subsequent two.Comedienne Amy Schumer cancelled the remainder of a tour due to hyperemesis gravidarum. References == External links ==
Superficial pustular folliculitis	Superficial pustular folliculitis is a superficial folliculitis with thin-walled pustules at the follicular openings.: 252 See also Streptococcal intertrigo List of cutaneous conditions References External links Special types of folliculitis which should be differentiated from acne, US National Library of Medicine, Published 2017 Sep 27
Attenuated patella alta	Attenuated patella alta is an extremely rare condition affecting mobility and leg strength. It is characterized by an unusually small knee cap (patella) that develops out of and above the joint. Typically, as the knee cap sits in the joint, it is stimulated to growth by abrasion from the opposing bones. When not situated properly in the joint, the knee cap does not experience such stimulation and remains small and undeveloped. Note that the cartilage under and around the kneecap is eight times smoother than ice, so "abrasion" may not be the best term.A similar condition, patella alta, can occur as the result of a sports injury, though the large majority of the time it is a congenital/developmental condition that is unrelated to trauma. A kneecap in an "alta" position sits above the "trochlear groove" and therefore is less stable. The "patellar tendon" that connects the kneecap to the tibia (shinbone) is elongated (longer than normal). This cannot happen by way of trauma, unless there has been a rupture of the tendon and a less-than-optimal surgical repair. There have been only three documented case of the disorder noted from birth. In 1988, three-year-old Eric Rogstad of Minneapolis, Minnesota was discovered to have the condition in both knees after several attempts by his parents and family physician to discover the cause of his difficulties with walking and running. After surgery and physical therapy, Eric gained the ability to walk and run without significant difficulty. Surprisingly, in 2016, two cases were discovered. 42 year old Anne Stone of Birmingham, England, and 27 year old Michael Brennan of Phoenix, Arizona, were independently diagnosed with bilateral attenuated patella alta. Insall Ratio: This ratio is calculated with the knee flexed to 30 degrees. It is the ratio of the length of the patella to the length of the patellar tendon. Typically, this ratio is 1:1 but 20% variation represents patella alta or patella infera. Actually, the Insall-Salvati ratio can be measured at any degree of flexion, which is one reason for its popularity. See also Patella == References ==
Leukemoid reaction	The term leukemoid reaction describes an increased white blood cell count (> 50,000 cells/μL), which is a physiological response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood. It may be lymphoid or myeloid. Causes As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include: Severe hemorrhage (retroperitoneal hemorrhage) Drugs Use of sulfa drugs Use of dapsone Use of glucocorticoids Use of G-CSF or related growth factors All-trans retinoic acid (ATRA) Ethylene glycol intoxication Infections Clostridium difficile Tuberculosis Pertussis Infectious mononucleosis (lymphocyte predominant) Visceral larva migrans (eosinophil predominant) Asplenia Diabetic ketoacidosis Organ necrosis Hepatic necrosis Ischemic colitis As a feature of trisomy 21 in infancy (incidence of ~10%) As a paraneoplastic phenomenon (rare) Diagnosis Conventionally, a leukocytosis exceeding 50,000 WBC/mm3 with a significant increase in early neutrophil precursors is referred to as a leukemoid reaction. The peripheral blood smear may show myelocytes, metamyelocytes, promyelocytes, and rarely myeloblasts; however, there is a mixture of early mature neutrophil precursors, in contrast to the immature forms typically seen in acute leukemia. Serum leukocyte alkaline phosphatase is normal or elevated in leukemoid reaction, but is depressed in chronic myelogenous leukemia. The bone marrow in a leukemoid reaction, if examined, may be hypercellular but is otherwise typically unremarkable.Leukemoid reactions are generally benign and are not dangerous in and of themselves, although they are often a response to a significant disease state (see Causes above). However, leukemoid reactions can resemble more serious conditions such as chronic myelogenous leukemia (CML), which can present with identical findings on the peripheral blood smear. Historically, various clues including the leukocyte alkaline phosphatase score and the presence of basophilia were used to distinguish CML from a leukemoid reaction. However, at present the test of choice in adults to distinguish CML is an assay for the presence of the Philadelphia chromosome, either via cytogenetics and FISH, or via PCR for the BCR/ABL fusion gene. The LAP (leukocyte alkaline phosphatase) score is high in reactive states but is low in CML. In cases where the diagnosis is uncertain, a qualified hematologist or oncologist should be consulted. Treatment Treatment of underlying condition. If drug induced, discontinue drug. If the reaction is found to be from anything besides drug use, certain anti neoplastic drugs may be indicated. See also Leukemid Leukocytosis Neutrophilia References == External links ==
Giant solitary trichoepithelioma	A giant solitary trichoepithelioma is a cutaneous condition characterized by a skin lesion that may be up to several centimeters in diameter.: 672 See also Trichoepithelioma Skin lesion References == External links ==
Autosomal dominant multiple pterygium syndrome	Multiple pterygium syndrome is a cutaneous condition inherited in an autosomal dominant fashion. Society Musician Patrick Henry Hughes has a type of this condition. See also Popliteal pterygium syndrome List of cutaneous conditions Datagenno - Escobar Syndrome References == External links ==
Corpus luteum cyst	A corpus luteum cyst is a type of ovarian cyst which may rupture about the time of menstruation, and take up to three months to disappear entirely. A corpus luteum cyst rarely occurs in women over the age of 50, because eggs are no longer being released after menopause. Corpus luteum cysts may contain blood and other fluids. The physical shape of a corpus luteum cyst may appear as an enlargement of the ovary itself, rather than a distinct mass -like growth on the surface of the ovary. Signs and symptoms Corpus luteum cysts are a normal part of the menstrual cycle. They can, however, grow to almost 10 cm (4 inches) in diameter and have the potential to bleed into themselves or twist the ovary, causing pelvic or abdominal pain. It is possible the cyst may rupture, causing internal bleeding and pain. This pain typically disappears within a few days of the rupture. If the corpus luteum becomes large it may cause ovarian torsion, where the ovary twists and blood flow is cut off. Ovarian torsion is rare and is accompanied by severe pain. Pathophysiology This type of functional cyst occurs after an egg has been released from a follicle. The follicle then becomes a secretory gland that is known as the corpus luteum. The ruptured follicle begins producing large quantities of estrogen and progesterone in preparation for conception. If a pregnancy doesnt occur, the corpus luteum usually breaks down and disappears. It may, however, fill with fluid or blood, causing the corpus luteum to expand into a cyst, and stay in the ovary. Usually, this cyst is on only one side, and does not produce any symptoms.In women of reproductive age cysts with a diameter of less than 5 cm are common, clinically inconsequential, and almost always a physiological condition rather than a cancer or other disease condition. In postmenopausal women the threshold for concern is 1 cm. Although ovarian cancer may be cystic, it does not arise from benign corpus luteum cysts. Medical specialty professional organizations recommend no follow-up imaging for cysts which are considered clinically inconsequential.A ruptured corpus luteum can cause hemoperitoneum with abdominal pain, and is a common condition in women of reproductive age. It may be confused with ectopic pregnancy. Interaction with medication The fertility drug clomiphene citrate (Clomid, Serophene), used to induce ovulation, increases the risk of a corpus luteum cyst developing after ovulation. These cysts do not prevent or threaten a resulting pregnancy. Women on birth control pills usually do not form these cysts; in fact, preventing these cysts is one way birth control pills work. In contrast, the progesterone-only pill can cause increased frequency of these cysts. References == External links ==
Voyeurism	Voyeurism is the sexual interest in or practice of watching other people engaged in intimate behaviors, such as undressing, sexual activity, or other actions usually considered to be of a private nature.The term comes from the French voir which means "to see". A male voyeur is commonly labelled as "Peeping Tom" or a "Jags", a term which originates from the Lady Godiva legend. However, that term is usually applied to a male who observes somebody secretly and, generally, not in a public space. The American Psychiatric Association has classified certain voyeuristic fantasies, urges and behaviour patterns as a paraphilia in the Diagnostic and Statistical Manual (DSM-IV) if the person has acted on these urges, or the sexual urges or fantasies cause marked distress or interpersonal difficulty. It is described as a disorder of sexual preference in the ICD-10. The DSM-IV defines voyeurism as the act of looking at "unsuspecting individuals, usually strangers, who are naked, in the process of disrobing, or engaging in sexual activity". The diagnosis would not be given to people who experience typical sexual arousal simply by seeing nudity or sexual activity. In order to be diagnosed with voyeuristic disorder the symptoms must persist for over six months and the person in question must be over the age of 18. Historical perspectives There is relatively little academic research regarding voyeurism. When a review was published in 1976 there were only 15 available resources. Voyeurs were well-paying hole-lookers in especially Parisian brothels, a commercial innovation described as far back as 1857 but not gaining much notoriety until the 1880s, and not attracting formal medical-forensic recognition until the early 1890s. Society has accepted the use of the term voyeur as a description of anyone who views the intimate lives of others, even outside of a sexual context. This term is specifically used regarding reality television and other media which allow people to view the personal lives of others. This is a reversal from the historical perspective, moving from a term which describes a specific population in detail, to one which describes the general population vaguely. One of the few historical theories on the causes of voyeurism comes from psychoanalytic theory. Psychoanalytic theory proposes that voyeurism results from a failure to accept castration anxiety and as a result of failure to identify with the father. Prevalence Voyeurism has high prevalence rates in most studied populations. Voyeurism was initially believed to only be present in a small portion of the population. This perception changed when Alfred Kinsey discovered that 30% of men prefer coitus with the lights on. This behaviour is not considered voyeurism by todays diagnostic standards, but there was little differentiation between normal and pathological behaviour at the time. Subsequent research showed that 65% of men had engaged in peeping, which suggests that this behaviour is widely spread throughout the population. Congruent with this, research found voyeurism to be the most common sexual law-breaking behaviour in both clinical and general populations. An earlier study, based on 60 college men from a rural area, indicates that 54% had voyeuristic fantasies, and that 42% had tried voyeurism, concluding that young men are more easily aroused by the idea.In a national study of Sweden it was found that 7.7% of the population (16% of men and 4% of women) had engaged in voyeurism at some point. It is also believed that voyeurism occurs up to 150 times more frequently than police reports indicate. This same study also indicates that there are high levels of co-occurrence between voyeurism and exhibitionism, finding that 63% of voyeurs also report exhibitionist behaviour. Characteristics People engage in voyeuristic behaviours for diverse reasons, but statistics can indicate which groups are likelier to engage in the act. Early research indicated that voyeurs were more mentally healthy than other groups with paraphilias. Compared to the other groups studied, it was found that voyeurs were unlikely to be alcoholics or drug users. More recent research shows that, compared to the general population, voyeurs were moderately more likely to have psychological problems, use alcohol and drugs, and have higher sexual interest generally. This study also shows that voyeurs have a greater number of sexual partners per year, and are more likely to have had a same-sex partner than most of the populations. Both older and newer research found that voyeurs typically have a later age of first sexual intercourse. However, other research found no difference in sexual history between voyeurs and non-voyeurs. Voyeurs who are not also exhibitionists tend to be from a higher socioeconomic status than those who do show exhibitionist behaviour. Gender differences Research shows that, like almost all paraphilias, voyeurism is more common in men than in women. However, research has found that men and women both report roughly the same likelihood that they would hypothetically engage in voyeurism. There appears to be a greater gender difference when actually presented with the opportunity to perform voyeurism. There is very little research done on voyeurism in women, so very little is known on the subject. One of the few studies deals with a case study of a woman who also had schizoid personality disorder, which limits the degree to which it can generalize to normal populations.A 2021 study found that 36.4% of men and 63.8% of women were strongly repulsed by the idea of voyeurism. Men were more likely to be mildly or moderately aroused than women, but there was little gender difference among those who reported strong arousal. Men reported slightly higher willingness to commit voyeurism but, when risk is introduced, willingness diminishes in both sexes proportionally to the risk involved. Individual differences in sociosexuality and sexual compulsivity were found to contribute to the sex differences in voyeurism. Current perspectives Lovemap theory suggests that voyeurism exists because looking at naked others shifts from an ancillary sexual behaviour, to a primary sexual act. This results in a displacement of sexual desire making the act of watching someone the primary means of sexual satisfaction. Voyeurism has also been linked with obsessive–compulsive disorder (OCD). When treated by the same approach as OCD, voyeuristic behaviours significantly decrease. Treatment Professional treatment Historically voyeurism has been treated in a variety of ways. Psychoanalytic, group psychotherapy and shock aversion approaches have all been attempted with limited success. There is some evidence which shows that pornography can be used as a form of treatment for voyeurism. This is based on the idea that countries with pornography censorship have high amounts of voyeurism. Additionally shifting voyeurs from voyeuristic behaviour, to looking at graphic pornography, to looking at the nudes in Playboy has been successfully used as a treatment. These studies show that pornography can be used as a means of satisfying voyeuristic desires without breaking the law. Voyeurism has also been successfully treated with a mix of anti-psychotics and antidepressants. However the patient in this case study had a multitude of other mental health problems. Intense pharmaceutical treatment may not be required for most voyeurs.There has also been success in treating voyeurism through using treatment methods for obsessive compulsive disorder. There have been multiple instances of successful treatment of voyeurism through putting patients on fluoxetine and treating their voyeuristic behaviour as a compulsion. Techniques The increased miniaturisation of hidden cameras and recording devices since the 1950s has enabled those so minded to surreptitiously photograph or record others without their knowledge and consent. The vast majority of mobile phones, for example, are readily available to be used for their camera and recording ability. Criminology Non-consensual voyeurism is considered to be a form of sexual abuse. When the interest in a particular subject is obsessive, the behaviour may be described as stalking. The United States FBI assert that some individuals who engage in "nuisance" offences (such as voyeurism) may also have a propensity for violence based on behaviours of serious sex offenders. An FBI researcher has suggested that voyeurs are likely to demonstrate some characteristics that are common, but not universal, among serious sexual offenders who invest considerable time and effort in the capturing of a victim (or image of a victim); careful, methodical planning devoted to the selection and preparation of equipment; and often meticulous attention to detail.Little to no research has been done into the demographics of voyeurs. Legal status Voyeurism is not a crime at common law. In common law countries it is only a crime if made so by legislation. In Canada, for example, voyeurism was not a crime when the case Frey v. Fedoruk et al. arose in 1947. In that case, in 1950, the Supreme Court of Canada held that courts could not criminalise voyeurism by classifying it as a breach of the peace and that Parliament would have to specifically outlaw it. On November 1, 2005, this was done when section 162 was added to the Canadian Criminal Code, declaring voyeurism to be a sexual offence when it violates a reasonable expectation of privacy. In the case of R v Jarvis, the Supreme Court of Canada held that for the purposes of that law, the expectation of privacy is not all-or-nothing; rather there are degrees of privacy, and although secondary-school pupils in the school building cannot reasonably expect as much privacy as in the bedroom, nonetheless they can expect enough privacy so that photographing them without their consent for the purpose of sexual gratification is forbidden.In some countries voyeurism is considered to be a sex crime. In the United Kingdom, for example, non-consensual voyeurism became a criminal offence on May 1, 2004. In the English case of R v Turner (2006), the manager of a sports centre filmed four women taking showers. There was no indication that the footage had been shown to anyone else or distributed in any way. The defendant pleaded guilty. The Court of Appeal confirmed a sentence of nine months imprisonment to reflect the seriousness of the abuse of trust and the traumatic effect on the victims. In another English case in 2009, R v Wilkins (2010), a man who filmed his intercourse with five of his lovers for his own private viewing was sentenced to eight months in prison and ordered to sign onto the Sex Offender Register for ten years. In 2013, 40-year-old Mark Lancaster was found guilty of voyeurism and jailed for 16 months, after he tricked an 18-year-old student into traveling to a rented flat in Milton Keynes, where he filmed her with four secret cameras dressing up as a schoolgirl and posing for photographs before he had sex with her.In a more recent English case in 2020, the Court of Appeal upheld the conviction of Tony Richards after Richards sought "to have two voyeurism charges under section 67 of the Sexual Offences Act dismissed on the grounds that he had committed no crime". Richards "secretly videoed himself having sex with two women who had consented to sex in return for money but had not agreed to being captured on camera". In an unusual step, the court allowed Emily Hunt, a person not involved in the case, to intervene on behalf of the Crown Prosecution Service (CPS). Hunt had an ongoing judicial review against the CPS since the CPS had argued that Hunts alleged attacker had not violated the law when he "took a video lasting over one minute of her naked and unconscious" in a hotel room on the basis that there should be no expectation of privacy in the bedroom. However, in terms of what is considered a private act for the purposes of voyeurism, the CPS was arguing the opposite in the Richards appeal. The Court of Appeal clarified that consenting to sex in a private place does not amount to consent to be filmed without that persons knowledge. Anyone who films or photographs another person naked, without their permission, is breaking the law under sections 67 and 68 of the Sexual Offences Act.In the United States, video voyeurism is an offense in twelve states and may require the convicted person to register as a sex offender. The original case that led to the criminalisation of voyeurism has been made into a television movie called Video Voyeur and documents the criminalisation of secret photography. Criminal voyeurism statutes are related to invasion of privacy laws but are specific to unlawful surreptitious surveillance without consent and unlawful recordings including the broadcast, dissemination, publication, or selling of recordings involving places and times when a person has a reasonable expectation of privacy and a reasonable supposition they are not being photographed or filmed by "any mechanical, digital or electronic viewing device, camera or any other instrument capable of recording, storing or transmitting visual images that can be utilised to observe a person."Saudi Arabia banned the sale of camera phones nationwide in April 2004, but reversed the ban in December 2004. Some countries, such as South Korea and Japan, require all camera phones sold in their country to make a clearly audible sound whenever a picture is being taken. In 2013, the Indian Parliament made amendments to the Indian Penal Code, introducing voyeurism as a criminal offence. A man committing the offence of voyeurism would be liable for imprisonment not less than one year and which may extend up to three years for the first offence, and shall also be liable to fine and for any subsequent conviction would be liable for imprisonment for not less than three years and which may extend up to seven years and with fine. Voyeurism is generally deemed illegal in Singapore. It sentences technologically-enabled voyeurs to a maximum punishment of one years jail and a fine under the context of insulting a womans modesty. Recent cases in 2016 include the sentencing of church facility manager Kenneth Yeo Jia Chuan who filmed women in toilets by planting pinhole cameras in a handicapped toilet at the Church of Singapore at Bukit Timah, and in the unisex toilet of the churchs office at Bukit Timah Shopping Centre.Secret photography by law enforcement authorities is called surveillance and is not considered to be voyeurism, though it may be unlawful or regulated in some countries. Popular culture Films Voyeurism is a main theme in films such as The Secret Cinema (1968), Peepers (2010), and Sliver (1993), based on a book of the same name by Ira Levin. Voyeurism is a common plot device in both: Serious films, e.g., Rear Window (1954), Klute (1971), Blue Velvet (1986), Disturbia (2007), and X (2022) and Humorous films, e.g., Animal House (1978), Gregorys Girl (1981), Porkys (1981), American Pie (1999), and Semi-Pro (2008) Voyeuristic photography has been a central element of the mis-en-scene of films such as: Michael Powells Peeping Tom (1960), and Michelangelo Antonionis Blowup (1966) Pedro Almodovars Kika (1993) deals with both sexual and media voyeurism. In Malèna, a teenage boy constantly spies on the title character. The television movie Video Voyeur: The Susan Wilson Story (2002) is based on a true story about a woman who was secretly videotaped and subsequently helped to get laws against voyeurism passed in parts of the United States. Voyeurism is a key plot device in the Japanese movie Love Exposure (Ai no Mukidashi). The main character Yu Honda takes upskirt photos to find his Maria to become a man and get his first taste of sexual stimulation. Literature In the light novel series Baka to Test to Shōkanjū, Kōta Tsuchiya is subject to voyeurism, explaining why he is referred to as "Voyeur". Manga The manga Colourful, Nozo×Kimi and Nozoki Ana included elements of voyeurism in their plot. Music "Voyeur", the second track on blink-182s album Dude Ranch, written by Tom DeLonge, features explicit references to the practice of voyeurism. "Sirens", also written by DeLonge, from Angels & Airwaves album I-Empire is also about voyeurism, albeit in a more subtle way. Photography Merry Alpern with his works, Dirty Windows, 1993–1994. Kohei Yoshiyuki with his works called The Park. See also Courtship disorder Exhibitionism Frey v. Fedoruk et al. Gaze Male gaze Invasion of privacy Peep show Sex show Scopophilia Scopophobia, the fear of being stared at Sexual attraction Upskirt References External links UK law on voyeurism Proposed US Video Voyeurism Prevention Act of 2003 Archived 2008-11-29 at the Wayback Machine Video Voyeurism Laws Expert: Technology fosters voyeurism
Elbow fracture	Elbow fractures are any broken bone around the elbow joint.They include among others: Olecranon fractures Supracondylar humerus fractures Radial head fracturesThe terrible triad of the elbow (not to be confused with the terrible triad of the knee) is a combination of: A fracture of the head of radius A fracture of the coronoid process of the ulna Humeroulnar dislocation (generally posterior or posterolateral)The terrible triad of the elbow is confers joint instability and a major risk of developing osteoarthritis. == References ==
Meningioma	Meningioma, also known as meningeal tumor, is typically a slow-growing tumor that forms from the meninges, the membranous layers surrounding the brain and spinal cord. Symptoms depend on the location and occur as a result of the tumor pressing on nearby tissue. Many cases never produce symptoms. Occasionally seizures, dementia, trouble talking, vision problems, one sided weakness, or loss of bladder control may occur.Risk factors include exposure to ionizing radiation such as during radiation therapy, a family history of the condition, and neurofibromatosis type 2. As of 2014 they do not appear to be related to cell phone use. They appear to be able to form from a number of different types of cells including arachnoid cells. Diagnosis is typically by medical imaging.If there are no symptoms, periodic observation may be all that is required. Most cases that result in symptoms can be cured by surgery. Following complete removal fewer than 20% recur. If surgery is not possible or all the tumor cannot be removed radiosurgery may be helpful. Chemotherapy has not been found to be useful. A small percentage grow rapidly and are associated with worse outcomes.About one per thousand people in the United States are currently affected. Onset is usually in adults. In this group they represent about 30% of brain tumors. Women are affected about twice as often as men. Meningiomata were reported as early as 1614 by Felix Plater. Signs and symptoms Small tumors (e.g., < 2.0 cm) usually are incidental findings at autopsy without having caused symptoms. Larger tumors may cause symptoms, depending on the size and location. Focal seizures may be caused by meningiomata that overlie the cerebrum. Progressive spastic weakness in legs and incontinence may be caused by tumors that overlie the parasagittal frontoparietal region. Tumors of the Sylvian aqueduct may cause myriad motor, sensory, aphasic, and seizure symptoms, depending on the location. Increased intracranial pressure eventually occurs, but is less frequent than in gliomas. Diplopia (Double vision) or uneven pupil size may be symptoms if related pressure causes a third and/or sixth nerve palsy. Causes The causes of meningiomata are not well understood. Most cases are sporadic, appearing randomly, while some are familial. Persons who have undergone radiation, especially to the scalp, are more at risk for developing meningiomata, as are those who have had a brain injury. Atomic bomb survivors from Hiroshima had a higher than typical frequency of developing meningiomata, with the incidence increasing the closer that they were to the site of the explosion. Dental X-rays are correlated with an increased risk of meningioma, in particular for people who had frequent dental X-rays in the past, when the X-ray dose of a dental X-ray was higher than in the present.Having excess body fat increases the risk.A 2012 review found that mobile telephone use was unrelated to meningioma.People with neurofibromatosis type 2 (NF-2) have a 50% chance of developing one or more meningiomata.Ninety-two percent of meningiomata are benign. Eight percent are either atypical or malignant. Genetics The most frequent genetic mutations (~50%) involved in meningiomata are inactivation mutations in the neurofibromatosis 2 gene (merlin) on chromosome 22q.TRAF7 mutations are present in about one-fourth of meningiomata. Mutations in the TRAF7, KLF4, AKT1, and SMO genes are commonly expressed in benign skull-base meningiomata. Mutations in NF2 are commonly expressed in meningiomata located in the cerebral and cerebellar hemispheres. Pathophysiology Meningiomata arise from arachnoidal cap cells, most of which are near the vicinity of the venous sinuses, and this is the site of greatest prevalence for meningioma formation. Some subtypes may arise from the pial cap cells that migrate during the development together with blood vessels into the brain parenchyma. They most frequently are attached to the dura over the superior parasagittal surface of frontal and parietal lobes, along the sphenoid ridge, in the olfactory grooves, the sylvian region, superior cerebellum along the falx cerebri, cerebellopontine angle, and the spinal cord. The tumor is usually gray, well-circumscribed, and takes on the form of the space it occupies. They usually are dome-shaped, with the base lying on the dura. Locations Parasagittal/falcine (25%) Convexity (surface of the brain) (19%) Sphenoid ridge (17%) Suprasellar (9%) Posterior fossa (8%) Olfactory groove (8%) Middle fossa/Meckels cave (4%) Tentorial (3%) Peri-torcular (3%) Intraparenchymal (rare)Other uncommon locations are the lateral ventricle, foramen magnum, and the orbit/optic nerve sheath. Meningiomata also may occur as a spinal tumor, more often in women than in men. This occurs more often in Western countries than Asian.Histologically, meningioma cells are relatively uniform, with a tendency to encircle one another, forming whorls and psammoma bodies (laminated calcific concretions). As such, they also have a tendency to calcify and are highly vascularized.Meningiomata often are considered benign tumors that can be removed by surgery, but most recurrent meningiomata correspond to histologic benign tumors. The metabolic phenotype of these benign recurrent meningiomata indicated an aggressive metabolism resembling that observed for atypical meningioma. Diagnosis Meningiomata are visualized readily with contrast CT, MRI with gadolinium, and arteriography, all attributed to the fact that meningiomata are extra-axial and vascularized. CSF protein levels are usually found to be elevated when lumbar puncture is used to obtain spinal fluid. On T1-weighted contrast-enhanced MRI, they may show a typical dural tail sign absent in some rare forms of meningiomas.Although the majority of meningiomata are benign, they may have malignant presentations. Classification of meningiomata are based upon the WHO classification system. Benign (Grade I) – (90%) – meningothelial, fibrous, transitional, psammomatous, angioblastic Atypical (Grade II) – (7%) – chordoid, clear cell, atypical (includes brain invasion) Anaplastic/malignant (Grade III) – (2%) – papillary, rhabdoid, anaplastic (most aggressive)In a 2008 review of the latter two categories, atypical and anaplastic-meningioma cases, the mean overall survival for atypical meningiomata was found to be 11.9 years vs. 3.3 years for anaplastic meningiomata. Mean relapse-free survival for atypical meningiomata was 11.5 years vs. 2.7 years for anaplastic meningiomata.Malignant anaplastic meningioma is aggressive. Although anaplastic meningioma has higher chances of distant metastasis than the other two types, the overall incidence of meningioma metastasis is only 0.18%; which is considered rare. Even if, by general rule, neoplasms of the nervous system (brain tumors) cannot metastasize into the body because of the blood–brain barrier, anaplastic meningioma can. Although they are inside the cerebral cavity, they are located on the bloodside of the BBB, because meningiomata tend to be connected to blood vessels. Thus, cancerized cells can escape into the bloodstream, which is why meningiomata, when they metastasize, often turn up around the lungs.Anaplastic meningioma and hemangiopericytoma are difficult to distinguish, even by pathological means, as they look similar, especially, if the first occurrence is a meningeal tumor, and both tumors occur in the same types of tissue.Although usually benign a "petro-clival" menigioma is typically fatal without treatment due to its location. Until the 1970s no treatment was available for this type of meningioma; however, since that time a range of surgical and radiological treatments have evolved. Nevertheless, the treatment of this type of meningioma remains a challenge with relatively frequent poor outcomes. Prevention The risk of meningioma can be reduced by maintaining a normal body weight, and by avoiding unnecessary dental x-rays. Treatment Observation Observation with close imaging follow-up may be used in select cases if a meningioma is small and asymptomatic. In a retrospective study on 43 patients, 63% of patients were found to have no growth on follow-up, and the 37% found to have growth at an average of 4 mm / year. In this study, younger patients were found to have tumors that were more likely to have grown on repeat imaging; thus are poorer candidates for observation. In another study, clinical outcomes were compared for 213 patients undergoing surgery vs. 351 patients under watchful observation. Only 6% of the conservatively treated patients developed symptoms later, while among the surgically treated patients, 5.6% developed persistent morbid condition, and 9.4% developed surgery-related morbid condition.Observation is not recommended in tumors already causing symptoms. Furthermore, close follow-up with imaging is required with an observation strategy to rule out an enlarging tumor. Surgery Meningiomata usually can be surgically resected (removed) and result in a permanent cure if the tumor is superficial on the dural surface and easily accessible. Transarterial embolization has become a standard preoperative procedure in the preoperative management. If invasion of the adjacent bone occurs, total removal is nearly impossible. It is rare for benign meningiomata to become malignant.The probability of a tumor recurring or growing after surgery may be estimated by comparing the tumors WHO (World Health Organization) grade and by the extent of surgery by the Simpson Criteria. Radiation therapy Radiation therapy may include photon-beam or proton-beam treatment, or fractionated external beam radiation. Radiosurgery may be used in lieu of surgery in small tumors located away from critical structures. Fractionated external-beam radiation also can be used as primary treatment for tumors that are surgically unresectable or, for patients who are inoperable for medical reasons.Radiation therapy often is considered for WHO grade I meningiomata after subtotal (incomplete) tumor resections. The clinical decision to irradiate after a subtotal resection is somewhat controversial, as no class I randomized, controlled trials exist on the subject. Numerous retrospective studies, however, have suggested strongly that the addition of postoperative radiation to incomplete resections improves both progression-free survival (i.e. prevents tumor recurrence) and improves overall survival.In the case of a grade III meningioma, the current standard of care involves postoperative radiation treatment regardless of the degree of surgical resection. This is due to the proportionally higher rate of local recurrence for these higher-grade tumors. Grade II tumors may behave variably and there is no standard of whether to give radiotherapy following a gross total resection. Subtotally resected grade II tumors should be radiated. Chemotherapy Likely, current chemotherapies are not effective. Antiprogestin agents have been used, but with variable results. A 2007 study of whether hydroxyurea has the capacity to shrink unresectable or recurrent meningiomata is being further evaluated. Epidemiology Many individuals have meningiomata, but remain asymptomatic, so the meningiomata are discovered during an autopsy. One to two percent of all autopsies reveal meningiomata that were unknown to the individuals during their lifetime, since there were never any symptoms. In the 1970s, tumors causing symptoms were discovered in 2 out of 100,000 people, while tumors discovered without causing symptoms occurred in 5.7 out of 100,000, for a total incidence of 7.7/100,000. With the advent of modern sophisticated imaging systems such as CT scans, the discovery of asymptomatic meningiomata has tripled.Meningiomata are more likely to appear in women than men, though when they appear in men, they are more likely to be malignant. Meningiomata may appear at any age, but most commonly are noticed in men and women age 50 or older, with meningiomata becoming more likely with age. They have been observed in all cultures, Western and Eastern, in roughly the same statistical frequency as other possible brain tumors. History The neoplasms currently referred to as meningiomata were referred to with a wide range of names in older medical literature, depending on the source. Various descriptors included "fungoid tumors", "fungus of the dura mater", "epithelioma", "psammoma", "dural sarcoma", "dural endothelioma", "fibrosarcoma", "angioendothelioma", "arachnoidal fibroboastoma", "endotheliosis of the meninges", "meningeal fibroblastoma", "meningoblastoma", "mestothelioma of the meninges", "sarcoma of the dura", and others.The modern term of "meningioma" was used first by Harvey Cushing (1869–1939) in 1922, to describe a set of tumors that occur throughout the neuraxis (brain and spinal cord), but have various commonalities. Charles Oberling then separated these into subtypes based on cell structure and, over the years, several other researchers have defined dozens of different subtypes as well. In 1979, the World Health Organization (WHO) classified seven subtypes, upgraded in 2000 to a classification system with nine low-grade variants (grade I tumors) and three variants each of grade II and grade III meningiomata. The most common subtypes are Meningotheliomatous (63%), transitional or mixed-type (19%), fibrous (13%), and psammomatous (2%).The earliest evidence of a probable meningioma is from a skull approximately 365,000 years old, which was found in Germany. Other probable examples have been discovered in other continents around the world, including North and South America, and Africa.The earliest written record of what was probably a meningioma is from the 1600s, when Felix Plater (1536–1614) of the University of Basel performed an autopsy on Sir Caspar Bonecurtius. Surgery for removal of meningiomata was first attempted in the sixteenth century, but the first known successful surgery for removal of a meningioma of the convexity (parasagittal) was performed in 1770 by Anoine Luis. The first documented successful removal of a skull base meningioma was performed in 1835 by Zanobi Pecchioli, Professor of Surgery at the University of Siena. Other notable meningioma researchers have been William Macewen (1848–1924), and William W. Keen (1837–1932).Improvements in meningioma research and treatment over the last century have occurred in terms of the surgical techniques for removal of the tumor, and related improvements in anesthesia, antiseptic methods, techniques to control blood loss, better ability to determine which tumors are and are not operable, and to effectively differentiate between the different meningioma subtypes. Notable cases Leonard Wood (1860–1927), underwent successful surgery by Dr. Harvey Cushing for a meningioma circa 1910, a major advance in neurosurgery at the time. Crystal Lee Sutton (1940–2009), American union organizer and inspiration for the film Norma Rae, died of a malignant meningioma. Elizabeth Taylor (1932–2011), American actress, underwent surgery in February 1997 to remove a benign meningioma. Kathi Goertzen (1958–2012), television news anchor in Seattle who underwent a very public battle with recurring tumors. She died on August 13, 2012, of complications related to her treatment. Eileen Ford (1922–2014), American model agency executive and co-founder of Ford Models. Died on July 9, 2014, from complications of meningioma and osteoporosis. Mary Tyler Moore (1936–2017), American actress, underwent surgery in May 2011 to remove a benign meningioma. Jack Daulton (1956–), American trial lawyer and art collector, underwent three surgeries in 2011–2012 in connection with the removal of a golf-ball-size benign meningioma over his left motor cortex; he fully recovered without disability or recurrence. Simone Giertz (1990–), Swedish inventor and professional YouTuber, underwent surgery to remove a grade I meningioma in 2018 and radiation therapy after tumor regrowth in 2019. References External links MR/CT scans of meningioma from MedPix MR/CT scans of pneumosinus dilatans from MedPix Cancer.Net: Meningioma
Irukandji syndrome	Irukandji syndrome is a condition that results from envenomation by certain box jellyfish. In rare instances the sting may result in cardiac arrest and death. The most common jellyfish involved is the Carukia barnesi, a species of Irukandji jellyfish. Those stung may experience severe or even excruciating pain. The syndrome was given its name in 1952 by Hugo Flecker, after the Aboriginal Irukandji people who live in Palm Cove, north of Cairns, Queensland, Australia, where stings are common. Signs and symptoms Most stings occur during the summer wet season in October–May in North Queensland, with different seasonal patterns elsewhere. Because the jellyfish are very small, the venom is only injected through the tips of the nematocysts (the cnidocysts) rather than the entire lengths; as a result the sting may barely be noticed at first. It has been described as feeling like little more than a mosquito bite. The symptoms, however, gradually become apparent and then more and more intense in the subsequent 5 to 120 minutes (30 minutes on average). Irukandji syndrome includes an array of systemic symptoms, including severe headache, backache, muscle pains, chest and abdominal pain, nausea and vomiting, sweating, anxiety, hypertension, tachycardia, and pulmonary edema. Symptoms generally improve in four to 30 hours, but may take up to two weeks to resolve completely. Toxicity When properly treated, a single sting is almost never fatal; however, two people in Australia are believed to have died from Irukandji stings, which has greatly increased public awareness of Irukandji syndrome. It is unknown how many other deaths from Irukandji syndrome have been wrongly attributed to other causes. Pathophysiology The exact mechanism of action of the venom is unknown, but catecholamine excess may be an underlying mechanism in severe cases. Animal studies appear to confirm a relationship between envenoming and an increase in circulating noradrenaline and adrenaline. Treatment Similar to other box jellyfish stings, first aid consists of flushing the area with vinegar to neutralize the tentacle stinging apparatus. As no antivenom is available, treatment is largely supportive, with analgesia being the mainstay of management. Nitroglycerin, a common drug used for cardiac conditions, is utilised by medical personnel to minimise the risk of pulmonary edema and to reduce hypertension. Antihistamines may be of benefit for pain relief, but most cases require intravenous opioid analgesia. Fentanyl or morphine are usually chosen. Pethidine (meperidine, brand name Demerol in the US) should be avoided, as large doses are often required for pain relief and in this situation significant adverse effects from the pethidine metabolite norpethidine may occur.Magnesium sulfate (Epsom Salts) has been proposed as a treatment for Irukandji syndrome after being apparently successfully used in one case. Early evidence suggested a benefit; however, according to a later report, a series of three patients failed to show any improvement with magnesium; the author emphasized the experimental status of this treatment. Some preliminary laboratory experiments using the venom extracted from Malo maxima (the Broome Irukandji) on rat cardiovascular tissue in vitro has suggested that magnesium does in fact block many of the actions of this venom. Epidemiology Reports of Irukandji syndrome have come from Australia, the United States (Hawaii and Florida), the French Antilles, Bonaire, the Caribbean, Timor Leste and Papua New Guinea. Cubozoan species other than Carukia barnesi are presumed to be responsible for envenomations outside Australia. History In 1964 Jack Barnes confirmed the cause of the syndrome was a sting from a small box jellyfish: the Irukandji jellyfish, which can fire venom-filled stingers out of its body and into passing victims. To prove that the jellyfish was the cause of the syndrome, he captured one and deliberately stung himself, his 9-year-old son and a local lifeguard, then observed the resulting symptoms. Other cubozoans possibly can cause Irukandji syndrome; those positively identified include Carukia barnesi, Alatina mordens, Alatina alata, Malo maxima, Malo kingi, Carybdea xaymacana, Keesingia gigas, an as-yet unnamed "fire jelly", and another unnamed species. Culture and society A 2005 Discovery Channel program, Killer Jellyfish, portrayed the severity of the pain from an Irukandji jellyfish sting when two Australian researchers (Jamie Seymour and Teresa Carrette) were stung. Another program aired on the Discovery Channel, Stings, Fangs and Spines, featured a 20-minute spot on Irukandji syndrome. In the segment, a young Australian woman was stung and developed a severe case.A 2007 fictional Sea Patrol episode (S1, E4) involves two crew members of HMAS Hammersley being stung by an Irukandji jellyfish.On the television program Super Animal, a woman compared her experience with Irukandji syndrome to the pain of childbirth.Steve Backshall reports with accounts from victims of Irukandji stings on his ITV wildlife series Fierce in 2016. == References ==
TEMPI syndrome	TEMPI syndrome is an orphan disease where the patients share five characteristics from which the acronym is derived: telangiectasias, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting. Signs and symptoms The patients were all diagnosed at middle age. The symptoms were slowly and steadily progressive. Telangiectasias developed over the face, trunk and arms. Increased serum erythropoietin levels, eventually exceeding 5000 mU /ml, preceded the intrapulmonary shunting and the development of hypoxemia. Sampling of the perinephric fluid revealed a clear, serous fluid with low levels of protein, few leukocytes and no cholesterol or triglycerides. A monoclonal gammopathy was implicated in all patients tested. Spontaneous venous thromboses occurred in some patients, sometimes accompanied with spontaneous intracranial bleeding in the absence of blood vessels malformations. Cause The cause of the syndrome is unknown. The abnormal plasma-cell clone and/or the monoclonal gammopathy are suggested to be triggers of the disease. Diagnosis The diagnosis is based on the five characteristics described above. Treatment Complete and partial disappearance of the symptoms of the TEMPI syndrome was reported with the drugs bortezomib, daratumumab and autologous stem cell transplantation. History In 2010, the case of a man with unexplained erythrocytosis and perinephric fluid collection as main features was described in the Case Records of the Massachusetts General Hospital. As a consequence two strikingly similar cases were identified and a review of the literature revealed three more patients with similar characteristics and a novel multisystem disease, the TEMPI syndrome, was reported.As of January 2022, a total of 29 patients worldwide with the TEMPI syndrome have been identified. References External links Office of Rare Diseases Research (US) Orpha.net (EU) Hematopia TEMPI Page
Eosinophilic bronchitis	Eosinophilic bronchitis (EB) is a type of airway inflammation due to excessive mast cell recruitment and activation in the superficial airways as opposed to the smooth muscles of the airways as seen in asthma. It often results in a chronic cough. Lung function tests are usually normal. Inhaled corticosteroids are often an effective treatment. Signs and symptoms The most common symptom of eosinophilic bronchitis is a chronic dry cough lasting more than 6–8 weeks. Eosinophilic bronchitis is also defined by the increased number of eosinophils, a type of white blood cell, in the sputum compared to that of healthy people. As patients with asthma usually present with eosinophils in the sputum as well, some literature distinguish the two by classifying the condition as non-asthmatic eosinophilic bronchitis (NAEB) versus eosinophilic bronchitis in asthma. Non-asthmatic eosinophilic bronchitis is different from asthma in that it does not have airflow obstruction or airway hyperresponsiveness. Along with eosinophils, the number of mast cells, another type of white blood cell, is also significantly increased in the bronchial wash fluid of eosinophilic bronchitis patients compared to asthmatic patients and other healthy people. Asthmatic patients, however, have greater number of mast cells that go into the smooth muscle of the airway, distinguishing it from non-asthmatic eosinophilic bronchitis. The increased number of mast cells in the smooth muscle correlate with the increased hyperresponsiveness of the airway seen in asthma patients, and the difference in the mast cell infiltration of the smooth muscle may explain why eosinophilic bronchitis patients do not have airway hyperresponsiveness. Eosinophilic bronchitis has also been linked to other conditions such as COPD, atopic cough, and allergic rhinitis. Pathophysiology The number of eosinophils in the sputum samples of non-asthmatic eosinophilic bronchitis patients are similar to those of patients with asthma. In the sputum samples of those with NAEB, histamine and prostaglandin D2 is increased. This suggests that the superficial airways have significant mast cell activation and this may lead to the differing symptom presentation compared to asthma. Inflammation caused by eosinophils is associated with an increased cough reflex. In another study, however, some follow-up patients who were asymptomatic also had increased eosinophils in their sputum, indicating that the inflammation is not always associated with an increased cough reflex.The cause of the inflammation can be associated with environmental triggers or common allergens such as dust, chloramine, latex, or welding fumes. Diagnosis Diagnosis of eosinophilic bronchitis is not common as it requires the examination of the patients sputum for a definitive diagnosis, which can be difficult in those who present with a dry cough. In order to induce the sputum, the patient has to inhale increasing concentrations of hypertonic saline solution. If this is unavailable, a bronchoalveolar lavage can be done, and the bronchial wash fluid can be examined for eosinophils. The diagnosis is usually considered later by ruling out other life-threatening conditions or more common diagnoses such as asthma and GERD, and by seeing an improvement in symptoms with inhaled corticosteroid treatment. Chest X-rays and lung function tests are usually normal. CT scans may show some diffuse airway wall thickening. Management If the patient has a known allergen or trigger for the eosinophilic bronchitis, the recommended treatment is to avoid the triggers. If the cause of the eosinophilic bronchitis is unknown, the first line treatment is inhaled corticosteroids. Patients respond well to inhaled corticosteroids and their eosinophil counts in their sputum usually decrease after treatment.There has not been a study to determine the ideal dosage of inhaled corticosteroids for patients with eosinophilic bronchitis, and there is no consensus on whether the treatment should be discontinued once the patients symptoms resolve or to continue long-term. The use of oral corticosteroids for eosinophilic bronchitis is rare, but it may be considered when inhaled corticosteroids are ineffective in managing the symptoms. Epidemiology Approximately 10–30% of people who present with a chronic cough are suspected to be symptomatic due to eosinophilic bronchitis. == References ==
Urethral syndrome	Urethral syndrome is defined as symptoms suggestive of a lower urinary tract infection but in the absence of significant bacteriuria with a conventional pathogen. It is a diagnosis of exclusion in patients with dysuria and frequency without demonstrable infection. In women, vaginitis should also be ruled out. Causes Signs indicative of urethral syndrome include a history of chronic recurrent urinary tract infections (UTI) in the absence of both conventional bacterial growth and pyuria (more than 5 white blood cells per high power field). Episodes are often related to sexual intercourse. Some physicians believe that urethral syndrome may be due to a low grade infection of the Skenes glands on the sides and bottom of the urethra. The Skenes glands are embryologically related to the prostate gland in the male, thus urethral syndrome may share a comparable cause with chronic prostatitis.Possible non-infective causes include hormonal imbalance, trauma, allergies, anatomical features such as diverticula, and post-surgical scarring and adhesions. Treatment In a small minority of cases of the urethral syndrome, treatment with antibiotics is effective, which indicates that in some cases it may be caused by a bacterial infection which does not show up in either urinalysis or urine culture. For chronic urethral syndrome, a long term, low-dose antibiotic treatment is given on a continuous basis or after intercourse each time if intercourse appears to trigger symptoms.As low oestrogen may also be considered a source for urethral syndrome, hormone replacement therapy and oral contraceptive pill (birth-control pills) containing oestrogen are also used to treat the symptoms of this condition in women. See also Interstitial cystitis Prostatitis References External links patient.info
Keratolytic winter erythema	Keratolytic Winter erythema (also known as Oudtshoorn disease or Oudtshoorn skin) is a rare autosomal dominant skin disease of unknown cause which causes redness and peeling of the skin on the palms and soles. Onset, increased prominence and severity usually occurs during winter. It is a type of genodermatosis.The name "Oudtshoorn skin" derives from the town of Oudtshoorn in the Western Cape province of South Africa, where the disorder was first described. It is one of several genetic disorders known to be highly prevalent among the Afrikaner population. Presentation KWE is characterized by a number of anomalies affecting the skin. Erythema causes redness of the skin, which is generally associated with inflammation and irritation. Including erythema and hyperkeratosis (thickening of the stratum corneum), naturally occurring keratolytic peeling and scaling, with increased manifestation in winter, are prevailing features of the disorder.Erythema in KWE has been attributed to necrobiosis (cellular death) within the Malpighian layer (the innermost layer of the epidermis). Peeling and scaling are caused by spreading dissection of the stratum corneum, correlating to the underlying necrobiosis.The effects of KWE appear intermittently as patches on the skin of the palms and soles, with these patches appearing on the limbs, buttocks and torso in severe cases. Facial lesions of this type have also been reported with the disorder, though this is considered to be an extremely rare occurrence.Onset and cyclical recurrence of KWE have shown to be associated with the arrival of winter, or winter-like weather. Worsening of symptoms during this time may be considered as an indicator of recurrent onset in patients known to have the disorder, and age of initial onset can be from early childhood to young adulthood, with attenuation of symptoms sometimes happening after age 30. Patients first exhibiting the disorder at a younger age may also experience worsened symptoms. Currently, no specific correlating factor or reason for winter-related manifestation has been established, though the coldness and dryer air common to winter conditions may be suspect. Winter onset is, however, considered to be a distinguishing feature of KWE among other erythematic skin disorders.When peeling of skin occurs, the newly exposed layer of skin underneath is moist, raw and very sensitive. While this may result in minor discomfort and inconvenience, in severe cases of KWE where large areas of raw skin are present, it is often life-altering and debilitating. KWE is inherited in an autosomal dominant manner. This means that the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who also has the disorder.KWE can begin as a spontaneous mutation, first appearing in an individual with no previous family history of the disorder. This may be due to a genetic predisposition for the disorder, possibly connected to the Oudtshoorn ancestral line. Genetics KWE is inherited in an autosomal dominant manner. This means that the defective gene responsible for the disorder is located on an autosome (chromosome 8 is an autosome), and one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who also has the disorder. KWE can begin as a spontaneous mutation, first appearing in an individual with no previous family history of the disorder. This may be due to a genetic predisposition for the disorder, possibly connected to the Oudtshoorn ancestral line. Pathophysiology KWE is of unknown cause, as at the present time, no specific mutation of any gene has been established as the cause of the disorder. Research has shown, however, that the gene involved is located on human chromosome 8. The function of enzymes in general are fundamentally subject to temperature. A candidate gene is a gene that is suspected to cause a disease or disorder. In KWE, this gene is known to be located in the area between chromosome 8q22 and 8q23. Within this region, the occurrence of loss of heterozygosity (simultaneous loss of function in both alleles of a gene) has been associated with malignancy, including certain types of breast and lung cancer. During the investigation for a KWE candidate gene in this same region, twelve protein transcripts were evaluated between microsatellite markers D8S550 and D8S1759, which is a critical area shown to be the source of KWE pathogenesis. Among the twelve transcripts identified, one corresponded to the BLK gene, which encodes the enzyme B-lymphoid tyrosine kinase. Four other of these transcripts included a myotubularin (MTMR8), a potential human homologue of the mouse Amac1 enzyme, a transcript similar to the mouse L-threonine 3-dehydrogenase gene, and one similar to a human oncogene. The remaining seven transcripts did not resemble any currently known genes. In all, none of the twelve transcripts displayed any evidence of pathogenic involvement with KWE. As a transcriptional map of this critical area is being drawn, based on microsatellite identification, haplotype analysis and other measures; localization of the gene associated with KWE pathogenesis is an ongoing process. Diagnosis Treatment Epidemiology Oudtshoorn is a town in Western Cape (formerly Cape Province), South Africa, where KWE ("Oudtshoorn skin") was first described. The disorder is quite prevalent among Afrikaners of South Africa, a population which can be defined as caucasoid native-speakers of Afrikaans, with northwestern European lineage. Among this group, KWE occurs at a rate of approximately 1/7,200.This relatively high rate of occurrence has been attributed to the founder effect, in which a small, often consanguinous population is formed out of the larger ancestral population, resulting in a loss of genetic diversity. In the context of KWE, the founder effect was confirmed by haplotype analysis, which indicates that the chromosomal origin of a possible genetic mutation responsible for the disorder is particularly common among affected Afrikaners. This is also true in other South Africans of European descent with KWE, and the chromosome of interest in both these and Afrikaner patients strongly points to an unspecified ancestor or ancestral group that may have settled around the Oudtshoorn area.A second lineage known to exhibit KWE has been reported in Germany, although there it is less prevalent and appears to involve the chromosome from a different ancestral origin than that seen in Afrikaners. KWE has also been noted in other countries around the northwestern region of Europe, such as Denmark. See also Integumentary system Cape Town Africa List of cutaneous conditions References == External links ==
Antisocial personality disorder	Antisocial personality disorder (ASPD or infrequently APD) is a personality disorder characterized by a long-term pattern of disregard of, or violation of, the rights of others as well as a difficulty sustaining long-term relationships. Lack of empathy is often apparent, as well as a history of rule-breaking that can sometimes include law-breaking, a tendency towards substance abuse, and impulsive and aggressive behavior. Antisocial behaviors often have their onset before the age of 8, and in nearly 80% of ASPD cases, the subject will develop their first symptoms by age 11. The prevalence of ASPD peaks in people age 24 to 44 years old, and often decreases in people age 45 to 64 years. In the United States, the rate of antisocial personality disorder in the general population is estimated between 0.5 and 3.5 percent. In a study, a random sampling of 320 newly incarcerated offenders found ASPD was present in over 35 percent of those surveyed.Antisocial personality disorder is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), while the equivalent concept of dissocial personality disorder (DPD) is defined in the International Statistical Classification of Diseases and Related Health Problems (ICD); the primary theoretical distinction between the two is that antisocial personality disorder focuses on observable behaviours, while dissocial personality disorder focuses on affective deficits. Otherwise, both manuals provide similar criteria for diagnosing the disorder. Both have also stated that their diagnoses have been referred to, or include what is referred to, as psychopathy or sociopathy. However, some researchers have drawn distinctions between the concepts of antisocial personality disorder and psychopathy, with many researchers arguing that psychopathy is a disorder that overlaps with but is distinguishable from ASPD. Symptoms and behaviors Addiction ASPD is one of the personality disorders most likely to be associated with addiction. This is due to their tendency towards impulsive and reckless decision making, which puts them at risk of developing a substance abuse disorder, prepulse inhibition deficiency, misuse of oral administrations, drug overdoses, blood-borne diseases, shorter periods of abstinence, drug use at earlier ages, aggressive behavior, impulsivity, frequent illegal drug use, drug injections, and difficult interpersonal relationships. Substance abuse problems are far more common amongst people with ASPD who live in rural environments rather than urban ones. There are also gender differences between men and women in regard to substance abuse. Men who abuse substances are far more likely to have ASPD than women, who are more likely to have a mood disorder. The relationship between substance abuse and ASPD can be affected by other personality disorders. For example, one of the previously mentioned studies found that 27.6% of participants who had ASPD and alcohol abuse had more than one personality disorder. Heroin, methamphetamine, opiates, alcohol, nicotine, cannabis, polydrugs, cocaine, and crack cocaine are some prevalent drugs amongst people with ASPD. Alongside substance abuse, patients with ASPD are more likely to develop a gambling addiction. Impulsivity Antisocial personality disorder has been associated with higher levels of impulsivity, suicidality, and irresponsible behavior. Usually resulting in heightened levels of aggressive behavior, domestic violence, illegal drug use, pervasive anger, and violent crimes. This behavior usually has negative effects on their education, relationships, or job. Alongside this, risky sexual behavior such as having multiple sexual partners, seeing prostitutes, inconsistently using condoms, trading sex for drugs, and frequent anal sex is also common. Their impulsive behavior will usually jeopardize their own safety and the safety of others. Emotions The violent and impulsive behavior present in ASPD has been correlated with chronic boredom. Other studies have found that people with ASPD tend to describe emotions with ambivalence, and experience emotions such as happiness and fear less clearly than others. They may also experience negative emotions such as anger and frustration more frequently and clearly than other emotions. People with ASPD can have difficulty mentalizing, or understanding the mental state of others. They also may display a perfectly intact theory of mind, or the ability to attribute a mental state to oneself and others, but an impaired ability to understand how another individual may be affected by an aggressive action. These factors possibly contribute to their aggressive and criminal behavior as well as their empathy deficits. Despite this they may be adept at social cognition, or the ability to process and store information about other people, which can contribute to an increased ability to manipulate others. Criminality People with ASPD tend to experience more convictions, spend more time in jail, and are more likely to be charged with almost any crime. However, assault and other violent crimes are the most common charges. This disorder is also prominent among prisoner populations. Alongside other conduct problems, many people with ASPD had conduct disorder in youth, a disorder characterized by a pervasive pattern of violent, criminal, defiant, and anti-social behavior. Fire-setting and the destruction of others property is also a behavior commonly associated with ASPD and impulsivity. Fire starters with ASPD tend to have a history of robbery, harassment, threatening, blackmail, and difficulty fulfilling promises. Limited Empathy or Remorse People with ASPD may experience a limited capacity for empathy and can be more interested in benefiting themselves regardless of the expense it has on others. They may have no regard for morals, social norms, and the rights and feelings of others. People with Antisocial personality disorder may have difficulties in sustaining and maintaining relationships, and some have difficulty entering them. Interpersonal relationships often revolve around the exploitation and abuse of others. People with ASPD may display arrogance, think lowly and negatively of others, and have limited remorse for their harmful actions and have a callous attitude towards those they have harmed. Although behaviors vary in degree, individuals with this personality disorder will typically have limited compunction in exploiting others in harmful ways for their own gain or pleasure, and frequently manipulate and deceive other people. While some do so through a façade of superficial charm, others do so through intimidation and violence. It is possible that people with ASPD may have intact cognitive empathy, but with a deficient theory of mind. Studies have found that people with ASPD have difficulty understanding others emotions and mental states. It also may be possible that people with ASPD do not lack empathy but are less inclined to use it. Comorbidity ASPD commonly coexists with the following conditions: When combined with alcoholism, people may show frontal function deficits on neuropsychological tests greater than those associated with each condition. Alcohol use disorder is likely caused by lack of impulse and behavioral control exhibited by antisocial personality disorder patients. The rates of ASPD tends to register around 40–50% in male alcohol and opiate addicts. However, it is important to remember this is not a causal relationship, but rather a plausible consequence of cognitive deficits as a result of ASPD. Causes Personality disorders are seen to be caused by a combination and interaction of genetic and environmental influences. Genetically, it is the intrinsic temperamental tendencies as determined by their genetically influenced physiology, and environmentally, it is the social and cultural experiences of a person in childhood and adolescence encompassing their family dynamics, peer influences, and social values. People with an antisocial or alcoholic parent are considered to be at higher risk. Fire-setting, and cruelty to animals during childhood are also linked to the development of antisocial personality. The condition is more common in males than in females, and among incarcerated populations. Genetic Research into genetic associations in antisocial personality disorder suggests that ASPD has some or even a strong genetic basis. Prevalence of ASPD is higher in people related to someone with the disorder. Twin studies, which are designed to discern between genetic and environmental effects, have reported significant genetic influences on antisocial behavior and conduct disorder.In the specific genes that may be involved, one gene that has seen particular interest in its correlation with antisocial behavior is the gene that encodes for monoamine oxidase A (MAO-A), an enzyme that breaks down monoamine neurotransmitters such as serotonin and norepinephrine. Various studies examining the genes relationship to behavior have suggested that variants of the gene that results in less MAO-A being produced, such as the 2R and 3R alleles of the promoter region, have associations with aggressive behavior in men. The association is also influenced by negative experience in early life, with children possessing a low-activity variant (MAOA-L) who experience such maltreatment being more likely to develop antisocial behavior than those with the high-activity variant (MAOA-H). Even when environmental interactions (e.g. emotional abuse) are controlled for, a small association between MAOA-L and aggressive and antisocial behavior remains.The gene that encodes for the serotonin transporter (SCL6A4), a gene that is heavily researched for its associations with other mental disorders, is another gene of interest in antisocial behavior and personality traits. Genetic associations studies have suggested that the short "S" allele is associated with impulsive antisocial behavior and ASPD in the inmate population. However, research into psychopathy find that the long "L" allele is associated with the Factor 1 traits of psychopathy, which describes its core affective (e.g. lack of empathy, fearlessness) and interpersonal (e.g. grandiosity, manipulativeness) personality disturbances. This is suggestive of two different forms, one associated more with impulsive behavior and emotional dysregulation, and the other with predatory aggression and affective disturbance, of the disorder.Various other gene candidates for ASPD have been identified by a genome-wide association study published in 2016. Several of these gene candidates are shared with attention-deficit hyperactivity disorder, with which ASPD is comorbid. Furthermore, the study found that those who carry four mutations on chromosome 6 are 50 percent more likely to develop antisocial personality disorder than those who do not. Physiological Hormones and neurotransmitters Traumatic events can lead to a disruption of the standard development of the central nervous system, which can generate a release of hormones that can change normal patterns of development. Aggressiveness and impulsivity are among the possible symptoms of ASPD. Testosterone is a hormone that plays an important role in aggressiveness in the brain. For instance, criminals who have committed violent crimes tend to have higher levels of testosterone than the average person. The effect of testosterone is counteracted by cortisol which facilitates the cognitive control of impulsive tendencies.One of the neurotransmitters that has been discussed in individuals with ASPD is serotonin, also known as 5HT. A meta-analysis of 20 studies found significantly lower 5-HIAA levels (indicating lower serotonin levels), especially in those who are younger than 30 years of age.While it has been shown that lower levels of serotonin may be associated with ASPD, there has also been evidence that decreased serotonin function is highly correlated with impulsiveness and aggression across a number of different experimental paradigms. Impulsivity is not only linked with irregularities in 5HT metabolism, but may be the most essential psychopathological aspect linked with such dysfunction. Correspondingly, the DSM classifies "impulsivity or failure to plan ahead" and "irritability and aggressiveness" as two of seven sub-criteria in category A of the diagnostic criteria of ASPD.Some studies have found a relationship between monoamine oxidase A and antisocial behavior, including conduct disorder and symptoms of adult ASPD, in maltreated children. Neurological Antisocial behavior may be related to head trauma. Antisocial behavior is associated with decreased grey matter in the right lentiform nucleus, left insula, and frontopolar cortex. Increased volumes have been observed in the right fusiform gyrus, inferior parietal cortex, right cingulate gyrus, and post central cortex.Intellectual and cognitive ability is often found to be impaired or reduced in the ASPD population. Contrary to stereotypes in popular culture of the "psychopathic genius", antisocial personality disorder is associated with both reduced overall intelligence and specific reductions in individual aspects of cognitive ability. These deficits also occur in general-population samples of people with antisocial traits and in children with the precursors to antisocial personality disorder.People that exhibit antisocial behavior tend to demonstrate decreased activity in the prefrontal cortex. The association is more apparent in functional neuroimaging as opposed to structural neuroimaging. The prefrontal cortex is involved in many executive functions, including behavior inhibitions, planning ahead, determining consequences of action, and differentiating between right and wrong. However, some investigators have questioned whether the reduced volume in prefrontal regions is associated with antisocial personality disorder, or whether they result from co-morbid disorders, such as substance use disorder or childhood maltreatment. Moreover, it remains an open question whether the relationship is causal, i.e., whether the anatomical abnormality causes the psychological and behavioral abnormality, or vice versa.Cavum septi pellucidi (CSP) is a marker for limbic neural maldevelopment, and its presence has been loosely associated with certain mental disorders, such as schizophrenia and post-traumatic stress disorder. One study found that those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. Environmental Family environment Many studies suggest that the social and home environment has contributed to the development of antisocial behavior. The parents of these children have been shown to display antisocial behavior, which could be adopted by their children. A lack of parental stimulation and affection during early development leads to high levels of cortisol with the absence of balancing hormones such as oxytocin which disrupts and overloads the childs stress response systems, which is thought to lead to underdevelopment of the childs brain that deals with emotion, empathy and ability to connect to other humans on an emotional level. According to Dr. Bruce Perry in his book The Boy Who Was Raised as a Dog, "the [infants developing] brain needs patterned, repetitive stimuli to develop properly. Spastic, unpredictable relief from fear, loneliness, discomfort, and hunger keeps a babys stress system on high alert. An environment of intermittent care punctuated by total abandonment may be the worst of all worlds for a child." Cultural influences The sociocultural perspective of clinical psychology views disorders as influenced by cultural aspects; since cultural norms differ significantly, mental disorders such as ASPD are viewed differently. Robert D. Hare has suggested that the rise in ASPD that has been reported in the United States may be linked to changes in cultural mores, the latter serving to validate the behavioral tendencies of many individuals with ASPD.: 136 While the rise reported may be in part merely a byproduct of the widening use (and abuse) of diagnostic techniques, given Eric Bernes division between individuals with active and latent ASPD – the latter keeping themselves in check by attachment to an external source of control like the law, traditional standards, or religion – it has been suggested that the erosion of collective standards may indeed serve to release the individual with latent ASPD from their previously prosocial behavior.: 136–7 There is also a continuous debate as to the extent to which the legal system should be involved in the identification and admittance of patients with preliminary symptoms of ASPD. Controversial clinical psychiatrist Pierre-Édouard Carbonneau suggested that the problem with legal forced admittance is the rate of failure when diagnosing ASPD. He contends that the possibility of diagnosing and coercing a patient into prescribing medication to someone without ASPD, but is diagnosed with ASPD, could be potentially disastrous. But the possibility of not diagnosing ASPD and seeing a patient go untreated because of a lack of sufficient evidence of cultural or environmental influences is something a psychiatrist must ignore; and in his words, "play it safe". Conduct disorder While antisocial personality disorder is a mental disorder diagnosed in adulthood, it has its precedent in childhood. The DSM-5s criteria for ASPD require that the individual have conduct problems evident by the age of 15. Persistent antisocial behavior, as well as a lack of regard for others in childhood and adolescence, is known as conduct disorder and is the precursor of ASPD. About 25–40% of youths with conduct disorder will be diagnosed with ASPD in adulthood.Conduct disorder (CD) is a disorder diagnosed in childhood that parallels the characteristics found in ASPD and is characterized by a repetitive and persistent pattern of behavior in which the basic rights of others or major age-appropriate norms are violated. Children with the disorder often display impulsive and aggressive behavior, may be callous and deceitful, and may repeatedly engage in petty crime such as stealing or vandalism or get into fights with other children and adults. This behavior is typically persistent and may be difficult to deter with threat or punishment. Attention deficit hyperactivity disorder (ADHD) is common in this population, and children with the disorder may also engage in substance use. CD is differentiated from oppositional defiant disorder (ODD) in that children with ODD do not commit aggressive or antisocial acts against other people, animals, and property, though many children diagnosed with ODD are subsequently re-diagnosed with CD.Two developmental courses for CD have been identified based on the age at which the symptoms become present. The first is known as the "childhood-onset type" and occurs when conduct disorder symptoms are present before the age of 10 years. This course is often linked to a more persistent life course and more pervasive behaviors, and children in this group express greater levels of ADHD symptoms, neuropsychological deficits, more academic problems, increased family dysfunction, and higher likelihood of aggression and violence. The second is known as the "adolescent-onset type" and occurs when conduct disorder develops after the age of 10 years. Compared to the childhood-onset type, less impairment in various cognitive and emotional functions are present, and the adolescent-onset variety may remit by adulthood. In addition to this differentiation, the DSM-5 provides a specifier for a callous and unemotional interpersonal style, which reflects characteristics seen in psychopathy and are believed to be a childhood precursor to this disorder. Compared to the adolescent-onset subtype, the childhood-onset subtype, especially if callous and unemotional traits are present, tends to have a worse treatment outcome. Diagnosis DSM-5 Section II The main text of fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines antisocial personality disorder as being characterized by at least three of the following traits: Failure to conform to social norms and laws, indicated by repeatedly engaging in illegal activities. Deceitfulness, indicated by continuously lying, using aliases, or conning others for personal gain and pleasure. Exhibiting impulsivity or failing to plan ahead. Irritability and aggressiveness, indicated by repeatedly getting into fights or physically assaulting others. Reckless behaviors that disregard the safety of others. Irresponsibility, indicated by repeatedly failing to consistently work or honor financial obligations. Lack of remorse after hurting or mistreating another person.In order to be diagnosed with antisocial personality disorder under the DSM-5, one must be at least 18 years old, show evidence of onset of conduct disorder before age 15, and antisocial behavior cannot be explained by schizophrenia or bipolar disorder. Section III (Alternative Model of Personality Disorders) In response to criticisms of the extant (Section II/DSM-IV) criteria for personality disorders, including their discordance with current models in the scientific literature, high comorbidity rate, overuse of some categories and underuse of others, and overwhelming use of the personality disorder-not otherwise specified (PD-NOS) diagnosis, the DSM-5 Workgroup on personality disorders devised a dimensional model, wherein categoric personality diagnoses reflect extreme variations of normal personality traits. In response to criticisms of the extant Section II/DSM-IV criteria for ASPD, namely its failure to capture the interpersonal and affective features of psychopathy, new criteria were proposed.In addition to the new criteria, the individual must be at least 18 years old, the traits must cause dysfunction or distress, and should not be better explained by another mental disorder, the pathophysiological effects of a substance, or a persons cultural or social background. Also included as a "with psychopathic traits" specifier modelled after the Fearless Dominance scale of the Psychopathic Personality Inventory, defined by low Anxiousness and Withdrawal and high Attention-Seeking. Researchers have also proposed the inclusion of Grandiosity and Restricted Affectivity to better capture psychopathy. Psychopathy Psychopathy is commonly defined as a personality disorder characterized partly by antisocial behavior, a diminished capacity for empathy and remorse, and poor behavioral controls. Psychopathic traits are assessed using various measurement tools, including Canadian researcher Robert D. Hares Psychopathy Checklist, Revised (PCL-R). "Psychopathy" is not the official title of any diagnosis in the DSM or ICD; nor is it an official title used by other major psychiatric organizations. The DSM and ICD, however, state that their antisocial diagnoses are at times referred to (or include what is referred to) as psychopathy or sociopathy.American psychiatrist Hervey Cleckleys work on psychopathy formed the basis of the diagnostic criteria for ASPD, and the DSM states ASPD is often referred to as psychopathy. However, critics argue ASPD is not synonymous with psychopathy as the diagnostic criteria are not the same, since criteria relating to personality traits are emphasized relatively less in the former. These differences exist in part because it was believed such traits were difficult to measure reliably and it was "easier to agree on the behaviors that typify a disorder than on the reasons why they occur".Although the diagnosis of ASPD covers two to three times as many prisoners than the diagnosis of psychopathy, Robert Hare believes the PCL-R is better able to predict future criminality, violence, and recidivism than a diagnosis of ASPD. He suggests there are differences between PCL-R-diagnosed psychopaths and non-psychopaths on "processing and use of linguistic and emotional information", while such differences are potentially smaller between those diagnosed with ASPD and without. Additionally, Hare argued confusion regarding how to diagnose ASPD, confusion regarding the difference between ASPD and psychopathy, as well as the differing future prognoses regarding recidivism and treatability, may have serious consequences in settings such as court cases where psychopathy is often seen as aggravating the crime.Nonetheless, psychopathy has been proposed as a specifier under an alternative model for ASPD. In the DSM-5, under "Alternative DSM-5 Model for Personality Disorders", ASPD with psychopathic features is described as characterized by "a lack of anxiety or fear and by a bold interpersonal style that may mask maladaptive behaviors (e.g., fraudulence)". Low levels of withdrawal and high levels of attention-seeking combined with low anxiety are associated with "social potency" and "stress immunity" in psychopathy.: 765 Under the specifier, affective and interpersonal characteristics are comparatively emphasized over behavioral components. Research suggests that, even without the "with psychopathic traits" specifier, these Section III criteria accurately capture the affective-interpersonal features of psychopathy, though the specifier increases coverage of the Interpersonal and Lifestyle facets of the PCL-R. Millons Subtypes Theodore Millon suggested 5 subtypes of ASPD. However, these constructs are not recognized in the DSM and ICD. Elsewhere, Millon differentiates ten subtypes (partially overlapping with the above) – covetous, risk-taking, malevolent, tyrannical, malignant, disingenuous, explosive, and abrasive – but specifically stresses that "the number 10 is by no means special... Taxonomies may be put forward at levels that are more coarse or more fine-grained.": 223 Treatment ASPD is considered to be among the most difficult personality disorders to treat. Rendering an effective treatment for ASPD is further complicated due to the inability to look at comparative studies between psychopathy and ASPD due to differing diagnostic criteria, differences in defining and measuring outcomes and a focus on treating incarcerated patients rather than those in the community. Because of their very low or absent capacity for remorse, individuals with ASPD often lack sufficient motivation and fail to see the costs associated with antisocial acts. They may only simulate remorse rather than truly commit to change: they can be seductively charming and dishonest, and may manipulate staff and fellow patients during treatment. Studies have shown that outpatient therapy is not likely to be successful, but the extent to which persons with ASPD are entirely unresponsive to treatment may have been exaggerated.Most treatment done is for those in the criminal justice system to whom the treatment regimes are given as part of their imprisonment. Those with ASPD may stay in treatment only as required by an external source, such as parole conditions. Residential programs that provide a carefully controlled environment of structure and supervision along with peer confrontation have been recommended. There has been some research on the treatment of ASPD that indicated positive results for therapeutic interventions. Psychotherapy, also known as "talk" therapy, has been found to help treat patients with ASPD. Schema therapy is also being investigated as a treatment for ASPD. A review by Charles M. Borduin features the strong influence of multisystemic therapy (MST) that could potentially improve this issue. However, this treatment requires complete cooperation and participation of all family members. Some studies have found that the presence of ASPD does not significantly interfere with treatment for other disorders, such as substance use, although others have reported contradictory findings.Therapists working with individuals with ASPD may have considerable negative feelings toward patients with extensive histories of aggressive, exploitative, and abusive behaviors. Rather than attempt to develop a sense of conscience in these individuals, which is extremely difficult considering the nature of the disorder, therapeutic techniques are focused on rational and utilitarian arguments against repeating past mistakes. These approaches would focus on the tangible, material value of prosocial behavior and abstaining from antisocial behavior. However, the impulsive and aggressive nature of those with this disorder may limit the effectiveness of this form of therapy.The use of medications in treating antisocial personality disorder is still poorly explored, and no medications have been approved by the FDA to specifically treat ASPD. A 2020 Cochrane review of studies that explored the use of pharmaceuticals in ASPD patients, of which eight studies met the selection criteria for review, concluded that the current body of evidence was inconclusive for recommendations concerning the use of pharmaceuticals in treating the various issues of ASPD. Nonetheless, psychiatric medications such as antipsychotics, antidepressants, and mood stabilizers can be used to control symptoms such as aggression and impulsivity, as well as treat disorders that may co-occur with ASPD for which medications are indicated. Prognosis According to professor Emily Simonoff of the Institute of Psychiatry, Psychology and Neuroscience, there are many variables that are consistently connected to ASPD, such as: childhood hyperactivity and conduct disorder, criminality in adulthood, lower IQ scores and reading problems. The strongest relationship between these variables and ASPD are childhood hyperactivity and conduct disorder. Additionally, children who grow up with a predisposition of ASPD and interact with other delinquent children are likely to later be diagnosed with ASPD. Like many disorders, genetics play a role in this disorder but the environment holds an undeniable role in its development. Boys are almost twice as likely to meet all of the diagnostic criteria for ASPD than girls (40% versus 25%) and they will often start showing symptoms of the disorder much earlier in life. Children that do not show symptoms of the disease through age 15 will almost never develop ASPD later in life. If adults exhibit milder symptoms of ASPD, it is likely that they never met the criteria for the disorder in their childhood and were consequently never diagnosed. Overall, symptoms of ASPD tend to peak in late teens and early twenties, but can often reduce or improve through age 40.ASPD is ultimately a lifelong disorder that has chronic consequences, though some of these can be moderated over time. There may be a high variability of the long-term outlook of antisocial personality disorder. The treatment of this disorder can be successful, but it entails unique difficulties. It is unlikely to see rapid change especially when the condition is severe. In fact, past studies revealed that remission rates were small, with up to only 31% rates of improvement instead of remittance. As a result of the characteristics of ASPD (e.g., displaying charm in effort of personal gain, manipulation), patients seeking treatment (mandated or otherwise) may appear to be "cured" in order to get out of treatment. According to definitions found in the DSM-5, people with ASPD can be deceitful and intimidating in their relationships. When they are caught doing something wrong, they often appear to be unaffected and unemotional about the consequences. Over time, continual behavior that lacks empathy and concern may lead to someone with ASPD taking advantage of the kindness of others, including his or her
Antisocial personality disorder	therapist.Without proper treatment, individuals with ASPD could lead a life that brings about harm to themselves or others. This can be detrimental to their families and careers. Those with ASPD lack interpersonal skills (e.g., lack of remorse, lack of empathy, lack of emotional-processing skills). As a result of the inability to create and maintain healthy relationships due to the lack of interpersonal skills, individuals with ASPD may find themselves in predicaments such as divorce, unemployment, homelessness and even premature death by suicide. They also see higher rates of committed crime, reaching peaks in their late teens and often committing higher-severity crimes in their younger ages of diagnoses. Comorbidity of other mental illnesses such as depression or substance use disorder is prevalent among patients with ASPD. People with ASPD are also more likely to commit homicides and other crimes. Those who are imprisoned longer often see higher rates of improvement with symptoms of ASPD than others who have been imprisoned for a shorter amount of time.According to one study, aggressive tendencies show in about 72% of all male patients diagnosed with ASPD. About 29% of the men studied with ASPD also showed a prevalence of pre-meditated aggression. Based on the evidence in the study, the researchers concluded that aggression in patients with ASPD is mostly impulsive, though there are some long-term evidences of pre-meditated aggressions. It often occurs that those with higher psychopathic traits will exhibit the pre-meditated aggressions to those around them. Over the course of a patients life with ASPD, he or she can exhibit this aggressive behavior and harm those close to him or her. Additionally, many people (especially adults) who have been diagnosed with ASPD become burdens to their close relatives, peers, and caretakers. Harvard Medical School recommends that time and resources be spent treating victims who have been affected by someone with ASPD, because the patient with ASPD may not respond to the administered therapies. In fact, a patient with ASPD may only accept treatment when ordered by a court, which will make their course of treatment difficult and severe. Because of the challenges in treatment, the patients family and close friends must take an active role in decisions about therapies that are offered to the patient. Ultimately, there must be a group effort to aid the long-term effects of the disorder. Epidemiology As seen in two North American studies and two European studies, ASPD is more commonly seen in men than in women, with men three to five times more likely to be diagnosed with ASPD than women. The prevalence of ASPD is even higher in selected populations, like prisons, where there is a preponderance of violent offenders. It has been found that the prevalence of ASPD among prisoners is just under 50%. Similarly, the prevalence of ASPD is higher among patients in alcohol or other drug (AOD) use treatment programs than in the general population, suggesting a link between ASPD and AOD use and dependence. As part of the Epidemiological Catchment Area (ECA) study, men with ASPD were found to be three to five times more likely to excessively use alcohol and illicit substances than those men without ASPD. While ASPD occurs more often in men than women, there was found to be increased severity of this substance use in women with ASPD. In a study conducted with both men and women with ASPD, women were more likely to misuse substances compared to their male counterparts.Homelessness is also common amongst people with ASPD. A study on 31 youths of San Francisco and 56 youths in Chicago found that 84% and 48% of the homeless met the diagnostic criteria for ASPD respectively. Another study on the homeless found that 25% of participants had ASPD.Individuals with ASPD are at an elevated risk for suicide. Some studies suggest this increase in suicidality is in part due to the association between suicide and symptoms or trends within ASPD, such as criminality and substance use. Offspring of people with ASPD are also at risk. Some research suggests that negative or traumatic experiences in childhood, perhaps as a result of the choices a parent with ASPD might make, can be a predictor of delinquency later on in the childs life. Additionally, with variability between situations, children of a parent with ASPD may face consequences of delinquency if theyre raised in an environment in which crime and violence is common. Suicide is a leading cause of death among youth who display antisocial behavior, especially when mixed with delinquency. Incarceration, which could come as a consequence of actions from a person with ASPD, is a predictor for suicide ideation in youth. History The first version of the DSM in 1952 listed sociopathic personality disturbance. This category was for individuals who were considered "...ill primarily in terms of society and of conformity with the prevailing milieu, and not only in terms of personal discomfort and relations with other individuals." There were four subtypes, referred to as "reactions": antisocial, dyssocial, sexual, and addiction. The antisocial reaction was said to include people who were "always in trouble" and not learning from it, maintaining "no loyalties", frequently callous and lacking responsibility, with an ability to "rationalize" their behavior. The category was described as more specific and limited than the existing concepts of "constitutional psychopathic state" or "psychopathic personality" which had had a very broad meaning; the narrower definition was in line with criteria advanced by Hervey M. Cleckley from 1941, while the term sociopathic had been advanced by George Partridge in 1928 when studying the early environmental influence on psychopaths. Partridge discovered the correlation between antisocial psychopathic disorder and parental rejection experienced in early childhood.The DSM-II in 1968 rearranged the categories and "antisocial personality" was now listed as one of ten personality disorders but still described similarly, to be applied to individuals who are: "basically unsocialized", in repeated conflicts with society, incapable of significant loyalty, selfish, irresponsible, unable to feel guilt or learn from prior experiences, and who tend to blame others and rationalize. The manual preface contains "special instructions" including "Antisocial personality should always be specified as mild, moderate, or severe." The DSM-II warned that a history of legal or social offenses was not by itself enough to justify the diagnosis, and that a "group delinquent reaction" of childhood or adolescence or "social maladjustment without manifest psychiatric disorder" should be ruled out first. The dyssocial personality type was relegated in the DSM-II to "dyssocial behavior" for individuals who are predatory and follow more or less criminal pursuits, such as racketeers, dishonest gamblers, prostitutes, and dope peddlers. (DSM-I classified this condition as sociopathic personality disorder, dyssocial type). It would later resurface as the name of a diagnosis in the ICD manual produced by the WHO, later spelled dissocial personality disorder and considered approximately equivalent to the ASPD diagnosis.The DSM-III in 1980 included the full term antisocial personality disorder and, as with other disorders, there was now a full checklist of symptoms focused on observable behaviors to enhance consistency in diagnosis between different psychiatrists (inter-rater reliability). The ASPD symptom list was based on the Research Diagnostic Criteria developed from the so-called Feighner Criteria from 1972, and in turn largely credited to influential research by sociologist Lee Robins published in 1966 as "Deviant Children Grown Up". However, Robins has previously clarified that while the new criteria of prior childhood conduct problems came from her work, she and co-researcher psychiatrist Patricia ONeal got the diagnostic criteria they used from Lees husband the psychiatrist Eli Robins, one of the authors of the Feighner criteria who had been using them as part of diagnostic interviews.The DSM-IV maintained the trend for behavioral antisocial symptoms while noting "This pattern has also been referred to as psychopathy, sociopathy, or dyssocial personality disorder" and re-including in the Associated Features text summary some of the underlying personality traits from the older diagnoses. The DSM-5 has the same diagnosis of antisocial personality disorder. The Pocket Guide to the DSM-5 Diagnostic Exam suggests that a person with ASPD may present "with psychopathic features" if he or she exhibits "a lack of anxiety or fear and a bold, efficacious interpersonal style". See also References Further reading External links DSM-IV-TR Criteria for Antisocial personality disorder Psychopathy and Antisocial Personality Disorder: A Case of Diagnostic Confusion
Cutaneous focal mucinosis	Cutaneous focal mucinosis is a skin condition characterized by a solitary nodule or papule.: 189 See also List of cutaneous conditions == References ==
Argininosuccinic aciduria	Argininosuccinic aciduria is an inherited disorder that causes the accumulation of argininosuccinic acid (also known as "ASA") in the blood and urine. Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors. An infant with argininosuccinic aciduria may seem lethargic or be unwilling to eat, have poorly controlled breathing rate or body temperature, experience seizures or unusual body movements, or go into a coma. Complications from argininosuccinic aciduria may include developmental delay and mental retardation. Progressive liver damage, skin lesions, and brittle hair may also be seen. Immediate treatment and lifelong management (following a strict diet and using appropriate supplements) may prevent many of these complications. Occasionally, an individual may inherit a mild form of the disorder in which ammonia accumulates in the bloodstream only during periods of illness or other stress. Genetics Mutations in the ASL gene cause argininosuccinic aciduria. Argininosuccinic aciduria belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions in the cells of the liver. It processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys.In argininosuccinic aciduria, the enzyme argininosuccinate lyase, involved in the conversion of arginino succinate to arginine within the urea cycle, is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia. Ammonia is especially damaging to the nervous system, so argininosuccinic aciduria causes neurological problems as well as eventual damage to the liver.This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. Diagnosis Diagnosis is based mainly on clinical findings and laboratory test results. Plasma concentrations of ammonia (>150 μmol/L) and citrulline (200-300 μmol/L) are elevated. Elevated levels of argininosuccinic acid (5-110 μmol/L) in the plasma or urine are diagnostic. Molecular genetic testing confirms diagnosis. Newborn screening for ASA is available in the U.S. and parts of Australia, and is considered in several European countries Treatment During an acute hyperammonemic episode, oral proteins must be avoided and intravenous (I.V.) lipids, glucose and insulin (if needed) should be given to promote anabolism. I.V. nitrogen scavenging therapy (with sodium benzoate and/or sodium phenylacetate) should normalize ammonia levels, but if unsuccessful, hemodialysis is recommended. Long-term management involves dietary protein restriction as well as arginine supplementation. In those with frequent episodes of metabolic decompensation or with hyperammonemia even when following a protein-restricted diet, daily oral nitrogen scavenging therapy may be successful. Orthotopic liver transplantation offers long-term relief of hyperammonemia but does not seem to sufficiently correct neurological complications. Arterial hypertension can be treated by restoring nitric oxide deficiency Prognosis Due to the rarity of the disease, it is hard to estimate mortality rates or life expectancy. One 2003 study which followed 88 cases receiving two different kinds of treatment found that very few persons lived beyond age 20 and none beyond age 30. Incidence Argininosuccinic aciduria occurs in approximately 1 in 70,000 live births. Many patients can now be detected on the newborn screen if their blood citrulline is elevated. References Literature Kleijer WJ, Garritsen VH, Linnebank M, Mooyer P, Huijmans JG, Mustonen A, Simola KO, Arslan-Kirchner M, Battini R, Briones P, Cardo E, Mandel H, Tschiedel E, Wanders RJ, Koch HG (2002). "Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families". J Inherit Metab Dis. 25 (5): 399–410. doi:10.1023/A:1020108002877. PMID 12408190. S2CID 11129281. Lee B, Goss J (2001). "Long-term correction of urea cycle disorders". J Pediatr. 138 (1 Suppl): S62–71. doi:10.1067/mpd.2001.111838. PMID 11148551. Reid Sutton V, Pan Y, Davis EC, Craigen WJ (2003). "A mouse model of argininosuccinic aciduria: biochemical characterization". Mol Genet Metab. 78 (1): 11–6. doi:10.1016/S1096-7192(02)00206-8. PMID 12559843. Scaglia F, Brunetti-Pierri N, Kleppe S, Marini J, Carter S, Garlick P, Jahoor F, OBrien W, Lee B (2004). "Clinical consequences of urea cycle enzyme deficiencies and potential links to arginine and nitric oxide metabolism". J Nutr. 134 (10 Suppl): 2775S–2782S, discussion 2796S–2797S. doi:10.1093/jn/134.10.2775S. PMID 15465784. Full text Stadler S, Gempel K, Bieger I, Pontz BF, Gerbitz KD, Bauer MF, Hofmann S (2001). "Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry". J Inherit Metab Dis. 24 (3): 370–8. doi:10.1023/A:1010560704092. PMID 11486903. S2CID 11543156. Wilcken B, Smith A, Brown DA (1980). "Urine screening for aminoacidopathies: is it beneficial? Results of a long-term follow-up of cases detected bny screening one million babies". J Pediatr. 97 (3): 492–7. doi:10.1016/S0022-3476(80)80216-2. PMID 7411317. External links ucd-overview at NIH/UW GeneTests
Pulmonary atresia with ventricular septal defect	Pulmonary atresia with ventricular septal defect is a rare birth defect characterized by pulmonary valve atresia occurring alongside a defect on the right ventricular outflow tract.It is a type of congenital heart disease/defect, and one of the two recognized subtypes of pulmonary atresia, the other being pulmonary atresia with intact ventricular septum. Signs and symptoms The condition consists of atresia affecting the pulmonary valve and a hypoplastic right ventricular outflow tract. The ventricular septal defect doesnt impede the in and outflowing of blood in the ventricular septum, which helps it form during fetal life.The spectrum of symptoms exhibited by children with this condition depends on the severity of the condition, while some barely show symptoms, others might develop complications such as congestive heart failure.In symptomatic children, symptoms become apparent soon after birth, these usually consist of the following: Cyanosis Breathing difficulties Feeding difficulties Exhaustion while being fed Heart murmur Excessive daytime sleepiness Sticky skinOther features can occur alongside this birth defect, including other congenital anomalies such as polydactyly, microcephaly, congenital hearing loss (sensorineural type), renal agenesis, dextrocardia, etc.The condition has been called a severe form of Tetralogy of Fallot.If deformed blood vessels coming from the thoracic aorta appear alongside this condition, the phenotype is renamed to pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. Complications Children with this condition are at a higher risk of developing the following complications: Failure to thrive Recurrent chest infections Endocarditis Epilepsy Stroke Arrhythmia Heart failure Premature deathChildren whose PAVSD is caused by DiGeorge syndrome (also known as 22q11.2 deletion syndrome) are more likely to suffer from the post-surgical complications (especially respiratory ones) associated with surgeries that treat this defect.Women with PAVSD are at a slightly higher risk of being infertile and having miscarriages or children with a congenital heart defect.Airway hyperresponsiveness is a commonly seen co-morbidity among those afflicted with PAVSD. Pathogenesis Pulmonary atresia in PAVSD takes place during the first 8 weeks of fetal life, when the pulmonary valve that is supposed to form, fails to form, this doesnt allow blood to flow through the pulmonary artery from the right ventricle. The ventricular septal defect associated with PAVSD lets the right ventricule form.In some cases of PAVSD, major aortopulmonary collateral arteries develop; in a normal fetus, these arteries usually develop but then start deteriorating after pulmonary arteries grow, in fetuses with PAVSD, the pulmonary arteries dont develop, and this gives a chance to the major aortopulmonary collateral arteries to develop fully. Pathophysiology The mildest variant of pulmonary atresia with ventricular septal defect involves pulmonary atresia with normally developed main pulmonary artery and branch pulmonary arteries, the blood that flows to the lungs from the right side of the heart goes to the left side of the heart through the ventricular septum which then flows through the patent ductus arteriosus. The most severe variant involves the presence of severely hypoplastic main pulmonary arteries and branch pulmonary arteries, alongside agenesis of the patent ductus arteriosus. Blood flow to the lungs comes from various dysplastic (malformed) blood vessels from the thoracic aorta called major aortapulmonary collateral arteries, these blood vessels narrow down as time goes on. Causes Although this birth defect is congenital, the exact cause is unknown, and it may vary between children with the condition, the following factors have been known to influence the risk of a baby being born with the condition: Genetics The molecular genetics of this condition isnt known in most people with PA(VSD), however, there have been candidate genes found to be possibly implicated in the pathogenesis of this condition: DNAH10 DST FAT1 HMCN1 HNRNPC TEP1 TYK2 NDRG4 TBX5 NKX2.5 GATA4There have also been copy number variants described in the medical literature as associated with PA(VSD): Deletion in chromosome 16p11.2 Deletion in chromosome 5q35.3 Deletion in chromosome 5p13.1 Deletion in chromosome 22q11.2 Deletion in chromosome 15q11.2 Deletion in chromosome 8p23.2 Deletion in chromosome 17p13.2 Duplication in chromosome 5q14.1 Duplication in chromosome 10p13A 1998 study done in Britain revealed that children with a mother who had a congenital heart defect (including PAVSD) had a higher risk of being born with a congenital heart defect themselves than those whose father had a congenital heart defect. Syndromes Some cases of PA(VSD) have been associated with genetic syndromes such as VACTERL association, Alagille syndrome, CHARGE syndrome, trisomy 13, 18, and 21. Environmental While congenital heart defects cant be acquired, they can also be caused by environmental factors the mother exposed herself to before and/or during pregnancy, these include: Smoking Certain medications (e.g. thalidomide, retinoids, or vitamin A coegers) Alcohol consumption Vehicle exhaust components By-products of disinfectants Incinerators (proximity) Agricultural pesticides Solvents Landfill sites Heavy metalsMaternal exposure to carbon monoxide from smoke (e.g. from cigarettes) has been known for having the ability of quickly crossing the placenta into the fetus, which then attaches itself to fetal haemoglobin, leaving a shortage of nutrients and oxygen as a result. A relation between these events and congenital heart disease (including PAVSD) has been showed in 3 recent meta-analyses.Paternal smoking (that is, smoking by the father) has also been shown to be a contributing factor to congenital heart disease; while light smoking slightly increased the risk of the mans offspring having a (congenital) conotruncal heart defect, heavy smoking of more than 14 cigarettes a day doubled the risk for said man to have a child with congenital heart disease. Higher amounts than this were linked to a higher risk of having children with septal defects and/or obstruction of the left ventricular outflow tract.Other risk factors include maternal obesity, diabetes, rubella, indomethacin tocolysis, phenylketonuria, or elderly age. Multifactorial: involving genetic and environmental factors at the same time A link between certain genes and maternal smoking has been shown to increase the chance of having children with congenital heart disease (including PAVSD): mothers who have a CC genotype at position 677 of the MTHFR gene have an increased chance of having a CHD-ridden child. Other genes that increase the chance of a child with CHD in smoker mothers who carry genetic variations in them include ERCC1, ERCC5, PARP2, and OSGEP. Diagnosis There are various ways of diagnosing this congenital heart defect both prenatally and postnatally, these methods include: Ultrasound Pulse oximetry Chest X-ray Echocardiogram Electrocardiogram Cardiac catheterization Cardiac CT scan Genetic testing (particularly if other systemic birth anomalies are seen alongside the pulmonary atresia and ventricular septal defect). Management When the disorder is detected (usually before or soon after birth), prostaglandin will be temporarily used as soon as possible in order to keep the ductus arteriosus open for as long as possible until surgery can be done, this is done so that blood can keep flowing to the lungs, since the bodies of babies with pulmonary atresia usually use the ductus arteriosus for lung blood flow pre-natally until birth, after which it closes.Afterwards, this anomaly is usually managed with surgeries for improvement of blood flow and function of the heart, although what kind of treatment one gets depends on the structure of the cardiorespiratory system.The surgical methods that can be used to treat (for the long-term) this condition include: Catheter procedure for pulmonary artery branches Systemic-to-pulmonary artery shunt Neonatal complete repair One-stage complete repair Balloon septostomy Staged unifocalization Frequency Frequency estimates vary between populations, estimates range from 0.01% to 0.2% of live births with PAVSD. It is believed to make up for 1-2% of cases of congenital heart defects worldwide.Of all patients with PAVSD, around 25-32% of them have a microdeletion of the 22q11.2 chromosome. Prognosis Without treatment, it is a highly life-threatening condition, so prognosis is poor. If surgery isnt performed in severe cases, the child can (and will) die, since the phenotype of pulmonary atresia is not compatible with life due to the pulmonary valve atresia resulting in reduced blood oxygenation.Life expectancy for untreated children with PAVSD is 10 years. Survival rates for untreated people with this defect have been reported to be 50% at the tenth decade and 10% at the twentieth decade, and out of these untreated patients, those who do not have major aortopulmonary arteries have a higher chance of living to their 30s than those who do have them, as the latter have a 40% chance of surviving to the tenth decade and a 20% chance of doing so to the thirtieth decade.Prognosis after surgical intervention is generally good. History This combination of birth defects was first described in 1980 by DiChiara et al., their patients were a father and his son from the United States both of which had pulmonary atresia and a ventricular septal defect. Up until that point, there had been no familial cases of PA with a VSD. A multifactorial etiology (that is, a cause involving genetics and the environment) was suspected in these patients and they were offered medical counseling for the condition.As of 2011, the oldest patient with untreated PAVSD was a 59-year old woman from Japan. Her condition was discovered in childhood but she refused to get any surgery to treat it (including cardiac catheterization), she developed dyspnea during her teenage years. Radiological studies showed a ventricular septal defect alongside cardiac and arterial anomalies (heart silhouette enlargement, elevation of the cardiac apex, presence of a right aortic arch, enlargement affecting the main pulmonary arteries and their major branches, high pulmonary artery vascularity, and ventricular septal defect). See also Tricuspid atresia Mitral regurgitation == References ==
Extrapyramidal symptoms	Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brains cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia (continuous spasms and muscle contractions), akathisia (may manifest as motor restlessness), parkinsonism characteristic symptoms such as rigidity, bradykinesia (slowness of movement), tremor, and tardive dyskinesia (irregular, jerky movements). Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics (the CATIE trial (Clinical Antipsychotic Trials for Intervention Effectiveness), which included 1460 randomized subjects), 58 (27.2%) of those discontinuations were due to EPS. Causes Medications Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize dopamine D2 receptors. The most common typical antipsychotics associated with EPS are haloperidol and fluphenazine. Atypical antipsychotics have lower D2 receptor affinity or higher serotonin 5-HT2A receptor affinity which lead to lower rates of EPS.Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side effects. Short and long-term use of antidepressants such as selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI) have also resulted in EPS. Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been linked to the induction of EPS. Non-medication-related Other causes of extrapyramidal symptoms can include brain damage and meningitis. However, the term "extrapyramidal symptoms" generally refers to medication-induced causes in the field of psychiatry. Diagnosis Since it is difficult to measure extrapyramidal symptoms, rating scales are commonly used to assess the severity of movement disorders. The Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS), and Extrapyramidal Symptom Rating Scale (ESRS) are rating scales frequently used for such assessment and are not weighted for diagnostic purposes; these scales can help clinicians weigh the benefit/expected benefit of a medication against the degree of distress which the side effects are causing the patient, aiding in the decision to maintain, reduce, or discontinue the causative medication(s). Classification Acute dystonic reactions: painful, muscular spasms of neck, jaw, back, extremities, eyes, throat, and tongue; highest risk in young men.Oculogyric crisis is a kind of acute dystonic reaction that involves the prolonged involuntary upward deviation of the eyes. Akathisia: A feeling of internal motor restlessness that can present as tension, nervousness, or anxiety. Clinical manifestations include pacing and an inability to sit still. Pseudoparkinsonism: drug-induced parkinsonism (rigidity, bradykinesia, tremor, masked facies, shuffling gait, stooped posture, sialorrhoea, and seborrhoea; greater risk in the elderly). Although Parkinsons disease is primarily a disease of the nigrostriatal pathway and not the extrapyramidal system, loss of dopaminergic neurons in the substantia nigra leads to dysregulation of the extrapyramidal system. Since this system regulates posture and skeletal muscle tone, a result is the characteristic bradykinesia of Parkinsons. Tardive dyskinesia: involuntary muscle movements in the lower face and distal extremities; this can be a chronic condition associated with long-term use of antipsychotics. Treatment Medications are used to reverse the symptoms of extrapyramidal side effects caused by antipsychotics or other drugs, either by directly or indirectly inhibiting dopaminergic neurotransmission. The treatment varies by the type of the EPS, but may involve anticholinergic agents such as procyclidine, benztropine, diphenhydramine, and trihexyphenidyl, and (rarely) dopamine agonists like pramipexole.If the EPS are induced by an antipsychotic, EPS may be reduced by decreasing the dose of the antipsychotic or by switching from a typical antipsychotic to an (or to a different) atypical antipsychotic, such as aripiprazole, ziprasidone, quetiapine, olanzapine, risperidone, or clozapine. These medications possess an additional mode of action that is believed to mitigate their effect on the nigrostriatal pathway, which means they are associated with fewer extrapyramidal side-effects than "conventional" antipsychotics (chlorpromazine, haloperidol, etc.) Dystonia Anticholinergic medications are used to reverse acute dystonia. If the symptoms are particularly severe, the anticholinergic medication may be administered by injection into a muscle to rapidly reverse the dystonia. Akathisia Certain second-generation antipsychotics, such as lurasidone and the partial D2-agonist aripiprazole, are more likely to cause akathisia compared to other second-generation antipsychotics. If akathisia occurs, switching to an antipsychotic with a lower risk of akathisia may improve symptoms. Beta blockers (like propranolol) are frequently used to treat akathisia. Other medications that are sometimes used include clonidine, mirtazapine, or even benzodiazepines. Anticholinergic medications are not helpful for treating akathisia. Pseudoparkinsonism Medication interventions are generally reserved for cases in which withdrawing the medication that caused the pseudoparkinsonism is either ineffective or infeasible. Anticholinergic medications are sometimes used to treat pseudoparkinsonism, but they can be difficult to tolerate when given chronically. Amantadine is sometimes used as well. It is rare for dopamine agonists to be used for antipsychotic-induced EPS, as they may exacerbate psychosis. Tardive dyskinesia When other measures fail or are not feasible, medications are used to treat tardive dyskinesia. These include the vesicular monoamine transporter 2 inhibitors tetrabenazine and deutetrabenazine. History Extrapyramidal symptoms (also called extrapyramidal side effects) get their name because they are symptoms of disorders in the extrapyramidal system, which regulates posture and skeletal muscle tone. This is in contrast to symptoms originating from the pyramidal tracts. See also Neuroleptic malignant syndrome Rabbit syndrome References == External links ==
Exhibitionism	Exhibitionism is the act of exposing in a public or semi-public context ones intimate parts – for example, the breasts, genitals or buttocks. The practice may arise from a desire or compulsion to expose themselves in such a manner to groups of friends or acquaintances, or to strangers for their amusement or sexual satisfaction, or to shock the bystander. Exposing oneself only to an intimate partner is normally not regarded as exhibitionism. In law, the act of exhibitionism may be called indecent exposure, "exposing ones person", or other expressions. History Public exhibitionism by women has been recorded since classical times, often in the context of women shaming groups of men into committing, or inciting them to commit, some public action. The ancient Greek historian Herodotus gives an account of exhibitionistic behaviors from the fifth century BC in The Histories. Herodotus writes that: When people travel to Bubastis for the festival, this is what they do. Every baris carrying them there overflows with people, a huge crowd of them, men and women together. Some of the women have clappers, while some of the men have pipes which they play throughout the voyage. The rest of the men and women sing and clap their hands. When in the course of their journey they reach a community — not the city of their destination, but somewhere else — they steer the bareis close to the bank. Some of the women carry on doing what I have already described them as doing, but others shout out scornful remarks to the women in the town, or dance, or stand and pull up their clothes to expose themselves. Every riverside community receives this treatment. A case of what appears to be exhibitionism in a clinical sense was recorded in a report by the Commission against Blasphemy in Venice in 1550.In the UK the 4th draft of the revised Vagrancy Act of 1824 included an additional clause or openly and indecently exposing their persons which gave rise to difficulties because of its ill-defined scope. During the course of a subsequent debate on the topic in Parliament, the then Home Secretary, Mr Peel, observed that there was not a more flagrant offence than that of indecently exposing the person which had been carried to an immense extent in the parks...wanton exposure was a very different thing from accidental exposure.The development of new technologies such as smartphones and tablets has permitted some exhibitionists to reorient their methods such as with nude selfies. Psychological aspects The term exhibitionist was first used in 1877 by French physician and psychiatrist Charles Lasègue. Various earlier medical-forensic texts discuss genital self-exhibition, however.When exhibitionistic sexual interest is acted on with a non-consenting person or interferes with a persons quality of life or normal functioning, it can be diagnosed as exhibitionistic disorder in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). The DSM states that the highest possible prevalence for exhibitionistic disorder in men is 2% to 4%. It is thought to be much less common in women. In a Swedish survey, 2.1% of women and 4.1% of men admitted to becoming sexually aroused from the exposure of their genitals to a stranger.A research team asked a sample of 185 exhibitionists, "How would you have preferred a person to react if you were to expose your privates to him or her?" The most common response was "Would want to have sexual intercourse" (35.1%), followed by "No reaction necessary at all" (19.5%), "To show their privates also" (15.1%), "Admiration" (14.1%), and "Any reaction" (11.9%). Only very few exhibitionists chose "Anger and disgust" (3.8%) or "Fear" (0.5%). Types of exposure Various types of behavior are classified as exhibitionism, including: Anasyrma: the lifting of the skirt when not wearing underwear, to expose genitals. Candaulism: when a person exposes his or her partner in a sexually provocative manner. Flashing: the momentary display of bare female breasts by a woman, with an up-and-down lifting of the shirt or bra or, the exposure of a mans or womans genitalia in a similar manner Martymachlia: a paraphilia which involves sexual attraction to having others watch the execution of a sexual act. Mooning: the display of bare buttocks by pulling down of trousers and underwear. The act is most often done for the sake of humour, disparagement, or mockery. Reflectoporn: the act of stripping and taking a photograph using an object with a reflective surface as a mirror, then posting the image on the Internet in a public forum. Examples include "images of naked men and women reflected in kettles, TVs, toasters and even knives and forks". The instance generally credited with starting the trend involved a man selling a kettle on an Australian auction site featuring a photograph where his naked body is clearly visible; other instances followed, and the specific term "reflectoporn" was coined by Chris Stevens of Internet Magazine. Streaking: the act of running naked through a public place. The intent is not usually sexual but for shock value. Sexting: the act of sending, receiving, or forwarding sexually explicit messages, photographs, or videos. Telephone scatologia: the act of making obscene phone calls to random or known recipients. Some researchers have claimed that this is a variant of exhibitionism, even though it has no in-person physical component.The DSM-5 diagnosis for exhibitionistic disorder has three subtypes: exhibitionists interested in exposing themselves to non-consenting adults, to prepubescent children, or to both. See also References External links Nancollas, Chris (2012). Exhibitionism: The Biography: A Popular History of Performance and Display. London: Darton Longman & Todd. ISBN 9780232529159. OCLC 1062174649.
Trichostasis spinulosa	Trichostasis spinulosa is a common but rarely diagnosed disorder of the hair follicles that clinically gives the impression of blackheads, but the follicles are filled with funnel-shaped, horny plugs that are bundles of vellus hairs.: 768 Diagnosis Standard skin surface biopsy (SSSB) is a noninvasive method used for diagnosis. Treatment See also List of cutaneous conditions == References ==
Sibling rivalry	Sibling rivalry is a type of competition or animosity among siblings, whether blood-related or not. Siblings generally spend more time together during childhood than they do with parents. The sibling bond is often complicated and is influenced by factors such as parental treatment, birth order, personality, and people and experiences outside the family. Sibling rivalry is particularly intense when children are very close in age and of the same gender and/or where one or both children are intellectually gifted. Throughout the lifespan According to observational studies by Judith Dunn, children are sensitive from the age of one year to differences in parental treatment. From 18 months, siblings can understand family rules and know how to comfort and be kind to each other. By the age of 3, children have a sophisticated grasp of social rules, can evaluate themselves in relation to their siblings, and know how to adapt to circumstances within the family.Sibling rivalry often continues throughout childhood and can be very frustrating and stressful to parents. Adolescents fight for the same reasons younger children fight, but they are better equipped to physically, intellectually, and emotionally hurt and be intellectually and emotionally hurt by each other. Physical and emotional changes cause pressures in the teenage years, as do changing relationships with parents and friends. Fighting with siblings as a way to get parental attention may increase in adolescence. One study found that the age group 10 to 15 reported the highest level of competition between siblings.Sibling rivalry can continue into adulthood, and sibling relationships can change dramatically over the years. Events, such as a parent’s illness, may bring siblings closer together, whereas marriage may drive them apart, particularly if the in-law relationship is strained. Approximately one-third of adults describe their relationship with siblings as rivalrous or distant. However, rivalry often lessens over time. At least 80 percent of siblings over the age of 60 enjoy close ties. Causes According to Kyla Boyse from the University of Michigan, each child in a family competes to define who it is as an individual and wants to show that it is separate from its siblings. Children may feel they are getting unequal amounts of their parents’ attention, discipline, and responsiveness. Children fight most in families where there is neither any understanding that fighting is not an acceptable way to resolve conflicts nor any alternative way of handling such conflicts; in families in which physical fighting is forbidden but no method of non-physical conflict resolution (e.g., verbal argument) is permitted, the conversion and accumulation of everyday disputes into long-simmering hostilities can have an effect nearly as corrosive. Stress in the parents’ and children’s lives can create more conflict and increase sibling rivalry. Some research indicates that changes in the weather can increase the likelihood of children exhibiting deviant behavior. Other psychological approaches Alfred Adler saw siblings as "striving for significance" within the family and felt that birth order was an important aspect of personality development. In fact, psychologists and researchers today endorse the influence of birth order, as well as age and gender constellations, on sibling relationships. However, parents are seen as capable of having an important influence on whether they are competitive or not.David Levy introduced the term "sibling rivalry" in 1941, claiming that for an older sibling "the aggressive response to the new baby is so typical that it is safe to say it is a common feature of family life." Researchers today generally endorse this view, noting that parents can ameliorate this response by being vigilant to favoritism and by taking appropriate preventative steps. In fact, the ideal time to lay the groundwork for a lifetime of supportive relationships between siblings is during the months prior to the new babys arrival. Prevention Parents can reduce the opportunity for rivalry by refusing to compare or typecast their children, planning fun family activities together, and making sure each child has enough time and space of their own. They can also give each child individual attention, encourage teamwork, refuse to hold up one child (such as the oldest) as a role model for the others (such as the younger children), and avoid favoritism. Teaching the children positive ways to ask for attention from parents when they need it can also make it less likely that they will resort to aggressive attention-getting strategies. Eileen Kennedy-Moore notes that this remedy also requires that parents "catch children being good" by responding to childrens kind, helpful, and creative bids for attention. Additionally, by being proactive about teaching children emotional intelligence, problem solving skills, negotiation skills, and encouraging them to look for win-win solutions, parents can help children resolve conflicts that arise as a normal part of growing up together in the same household. A concerted effort by parents to reduce competitiveness while nurturing bonding can further help alleviate sibling rivalry. However, according to Sylvia Rimm, although sibling rivalry can be reduced, it is unlikely to be entirely eliminated. In moderate doses, rivalry may be a healthy indication that each child is assertive enough to express his or her differences with other siblings.Vernon Weihe suggests that four criteria should be used to determine if questioned and/or questionable behavior is rivalry or sibling abuse. First, given that children use different conflict-resolution tactics during various developmental stages, one must rule out the possibility that the questioned behavior is in fact age-appropriate for the child exhibiting it. Second, one must determine whether the behavior is an isolated incident or instead part of an enduring pattern: abuse is, by definition, a long-term pattern rather than occasional disagreements. Third, one must determine if there is an "aspect of victimization" to the behavior: rivalry tends to be incident-specific, reciprocal, and obvious to others, while abuse is characterized by secrecy and an imbalance of power. Fourth, one must determine the goal of the questioned and/or questionable behavior: while rivalry is motivated entirely or primarily by aspects of a childs self-interest in which the interests of others, including the childs rival, do not play a role, in scenarios featuring abuse, the perpetrators ultimate interests tend to include domination, humiliation, or at least embarrassment of the victim. Animals Sibling rivalry is common among various animal species, in the form of competition for food and parental attention. An extreme type of sibling rivalry occurs when young animals kill their siblings. For example, a black eagle mother lays two eggs, and the first-hatched chick pecks the younger one to death within the first few days. In the blue-footed booby, there is always the emergence of a brood hierarchy. The dominant chick will attack the subordinate one in times of food scarcity, often pecking it repeatedly or driving it from the nest. Among spotted hyenas, sibling competition begins as soon as the second cub is born, and 25% of cubs are killed by their siblings.Sibling relationships in animals are not always competitive. For example, among wolves, older siblings help to feed and guard the young. Famous instances In religion The Book of Genesis in the Bible contains several examples of sibling rivalry: the story of Cain and Abel tells of one brothers jealousy after God appears to favour his sibling, and the jealousy ultimately leads to murder. Esau was jealous of his brother Jacobs inheritance and blessing; sisters Leah and Rachel compete for the love of Jacob; Josephs brothers are so jealous that they effectively sell him into slavery. These stories are also present in the Quran. Another example is provided in the myth of Romulus and Remus, wherein twin brothers Romulus and Remus fight for control over Rome, and which ends with the death of Remus at the hands of his brother. In folk and fairy tales Sibling rivalry, bitter jealousy, and envy are notable in several fairy tales around the world. In some tales, the jealousy escalates to outright murder of the successful sibling. Some tale types, according to the Aarne-Thompson-Uther Index, heavily feature sibling and step-sibling rivalry as part of the plot: ATU 301, "The Three Stolen Princesses" or "Jean de lOurs": a hero, born with strong powers, descends to an underworld realm to rescue three princesses. He sends the three maidens to the upper realm with the help of his brothers (or companions), but they cut the rope and trap him in the subterranean realm. ATU 361, "Bearskin": a man makes a deal with devil: must not pray or bathe for a certain number of years. Later, the man meets a father with his three daughters; only the youngest sister promises to marry the man. After the time is up, the man grooms himself and goes to meet his bride, explaining the whole story. Her sisters seethe with rage and explode with jealousy; the devil takes two souls, instead of one. ATU 403, "The Black and the White Bride": a woman, dispised by her (step)family, marries a prince. Later, her step-mother conspires to replace the woman with her (step)sibling. ATU 432, "The Bird Lover" or "The Prince as Bird": a maiden is visited at night by a bird, which is a prince in disguise. Her family begin to suspect something and set up a trap by her window: they put spikes (nails, broken glass, thorns) to hurt the bird. The bird prince thinks her beloved betrayed him and flees, which prompts the heroine to seek him in parts unknown. ATU 480, "The Kind and Unkind Girls" or "The Spinning-Woman by the Spring": two sisters or stepsisters, one diligent and the other lazy, meet a supernatural entity in the woods or in a magical realm. The diligent sibling acts kindly and obeys the entitys orders, and is rewarded; the lazy one disobeys and is punished. ATU 510A, "Cinderella": the heroine is maltreated by her stepmother and stepsiblings. ATU 511, "One-Eye, Two-Eyes, and Three-Eyes": two women (the first one-eyed and the other three-eyed) mistreat their sibling, a woman with two eyes. ATU 530, "The Princess on the Glass Hill": a father sends his three sons to guard his crops or to hold a vigil on his grave. The older ones disobey and/or feel frightened, so they send their youngest brother, whom they call a fool or stupid, to fulfill their fathers orders. The foolish brother acquires three magical horses and uses them to reach a princess atop a glass hill for three times. ATU 530A, "The Pig With Golden Bristles": as a continuation of the story of The Glass Mountain, after the wedding, the tsar/king sends his sons-in-law on a quest for some creatures with marvellous attributes. The older brothers want to go on the quest to impress their father-in-law and further humiliate their youngest brother. ATU 550, "The Golden Bird": a king sends his three sons to find the golden bird and bring it home. The older ones fail, but the youngest is successful, capturing the bird and a horse and bringing with him a maiden as his wife. Spurred by intense jealousy, they murder their sibling or toss them in a ditch and take the prizes of the quest for themselves. ATU 551, "The Water of Life": a king is dying or blind, so he sends his sons for a magical cure (a magical bird, the water of life, etc.), which can only be found in a distant realm, in the hands of a princess or maiden. The youngest is successful and returns with the prize, but his brothers drop him in a ditch. The youngest prince survives and returns incognito to the city. The foreign maiden comes after the person who stole her property. ATU 554, "The Grateful Animals": in some variants, the youngest brother protects or helps three animals of different species, much to his brothers chagrin, who wanted to hunt them. When the three brothers are assigned tasks by a king, the youngest accomplishes the feats with the animals help. ATU 707, "The Dancing Water, the Singing Apple, and the Speaking Bird": one night, the prince (king, tsar, sultan) hears three sisters talking, the youngest promising that, if she were to marry the king, would bear him children (twins, triplets) with wonderful attributes. Her sisters are married to lowly officials or servants of the kings court and, bearing an intense jealousy toward the newly crowned queen, decide to get rid of the royal children. ATU 709, "Snow White": in some regional variants of the tale type, the rivalry isnt between mother and daughter or between step-mother and step-daughter. Instead, it is the heroines older sisters who get jealous over the youngests beauty and charm and conspire to kill her. ATU 780, "The Singing Bone": a person murders their sibling (brother or sister) and buries them in a shallow grave. A tree sprouts from it. Its wood is used to create an instrument (fiddle, violin, flute) that reveals the murder. In literature A number of Shakespeares plays display the incidences of sibling rivalry. King Lear provokes rivalry among his three daughters by asking them to describe their love for him; in the same play, Edmund contrives to force his half-brother Edgar into exile. In The Taming of the Shrew, sisters Kate and Bianca are shown fighting bitterly. In Richard III, the title character is at least partially motivated by rivalry with his brother, King Edward. In As You Like It, there is obvious sibling rivalry and antagonism between Orlando and Oliver, and also between Duke Frederick and Duke Senior. Most adaptations of Sherlock Holmes depict sibling rivalry with his brother, Mycroft Holmes. In John Steinbecks East of Eden, the brothers Cal and Aron Trask are counterparts to Cain and Abel of the Bible story. A Song of Ice and Fire contains numerous examples, such as that between Stannis Baratheon and Renly Baratheon. After their eldest brother Robert Baratheons death they contend for the Iron Throne, Stannis finally killing Renly through dark magic on the night before Renly intends to kill Stannis in battle, though it is left unclear whether he is aware of his role in Renlys death. The history of Westeros also contains "The Dance of the Dragons", in which Princess Rhaenyra Targaryen and her half-brother Aegon II Targaryen fought over the Iron Throne after their Father Viserys I Targaryens death, Aegon eventually killing Rhaenyra, but being poisoned shortly after, leading to Rhaenyras son Aegon III becoming king. In film and television Sibling rivalry is a common theme in media that features child characters, reflecting the importance of this issue in early life. These issues can include jealousy on the birth of a new baby, different sibling roles, frequent arguments, competitiveness for mothers affection, and tensions between step-siblings. Adult siblings can also be portrayed with a rivalrous relationship, often a continuation of childhood conflicts. Situation comedies exploit this to comic effect. Sibling relationships may be shown as alternately loving and argumentative. Brothers or sisters in a similar line of work may display professional rivalry. In serious drama, conflict between siblings can be fatal, as shown in crime dramas involving such rivalries. Real life Occasionally real life instances of sibling rivalry are publicized in the mass media. Siblings who play the same sport will often be compared with each other; for example, American football players Peyton and Eli Manning, or tennis players Venus and Serena Williams. Musicians Liam and Noel Gallagher of Oasis have a turbulent relationship, similar to that of Ray and Dave Davies of The Kinks. Politicians Ed and David Miliband are likewise portrayed as having a strained relationship, after Ed narrowly defeated David in the final round of the 2010 Labour Party leadership election (UK).Actresses Olivia de Havilland and Joan Fontaine had an uneasy relationship from childhood and in 1975 the sisters stopped speaking to each other completely. The incredibly popular singing Andrews Sisters maintained professional harmony in show business for more than 30 years, but clashed famously in their personal lives (after LaVernes death in 1967, Patty and Maxene stopped speaking in 1975 and never looked back). The rivalry between singers Lata Mangeshkar and Asha Bhosle is often talked about in the Indian media, in spite of their insistence that these are just tales. Twin sisters and advice columnists Ann Landers and Abigail Van Buren had a relationship that was alternately very close and publicly antagonistic. Journalists Christopher and Peter Hitchens had many public disagreements and at least one protracted falling-out due to their differing political and religious views. See also Dassler brothers feud Birthright Birth order Family Firstborn Sibling abuse Emotional intelligence References External links YourChild: Sibling Rivalry University of Michigan Health System YourChild: New Baby Sibling: Helping Your Older Child (or Children) Adjust University of Michigan Health System How to stop sibling rivalry by Virginia K. Molgaard Sibling rivalry: You vs. Them Living with your teenager: Dealing with Sibling rivalry Sibling Rivalry Raising Children Network Siblings in Conflict Film and Text (in German) Sibling Rivalry (Infographic)
Hepatitis B	Hepatitis B is an infectious disease caused by the Hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.Many people have no symptoms during an initial infection. For others, symptoms may appear 30 to 180 days after becoming infected and can include a rapid onset of sickness with nausea, vomiting, yellowish skin, fatigue, dark urine, and abdominal pain. Symptoms during acute infection typically last for a few weeks, though some people may feel sick for up to six months. Deaths resulting from acute stage HBV infections are rare. An HBV infection lasting longer than six months is usually considered chronic. The likelihood of developing chronic hepatitis B is higher for those who are infected with HBV at a younger age. About 90% of those infected during or shortly after birth develop chronic hepatitis B, while less than 10% of those infected after the age of five develop chronic cases. Most of those with chronic disease have no symptoms; however, cirrhosis and liver cancer eventually develop in about 25% of those with chronic HBV.The virus is transmitted by exposure to infectious blood or body fluids. In areas where the disease is common, infection around the time of birth or from contact with other peoples blood during childhood are the most frequent methods by which hepatitis B is acquired. In areas where the disease is rare, intravenous drug use and sexual intercourse are the most frequent routes of infection. Other risk factors include working in healthcare, blood transfusions, dialysis, living with an infected person, travel in countries with high infection rates, and living in an institution. Tattooing and acupuncture led to a significant number of cases in the 1980s; however, this has become less common with improved sterilization. The hepatitis B viruses cannot be spread by holding hands, sharing eating utensils, kissing, hugging, coughing, sneezing, or breastfeeding. The infection can be diagnosed 30 to 60 days after exposure. The diagnosis is usually confirmed by testing the blood for parts of the virus and for antibodies against the virus. It is one of five main hepatitis viruses: A, B, C, D, and E. During an initial infection, care is based on a persons symptoms. In those who develop chronic disease, antiviral medication such as tenofovir or interferon may be useful; however, these drugs are expensive. Liver transplantation is sometimes recommended for cases of cirrhosis or hepatocellular carcinoma.Hepatitis B infection has been preventable by vaccination since 1982. As of 2022, the hepatitis B vaccine is between 98% and 100% effective in preventing infection. The vaccine is administered in several doses; after an initial dose, two or three more vaccine doses are required at a later time for full effect. The World Health Organization (WHO) recommends infants receive the vaccine within 24 hours after birth when possible. National programs have made the hepatitis B vaccine available for infants in 190 countries as of the end of 2021. To further prevent infection, the WHO recommends testing all donated blood for hepatitis B before using it for transfusion. Using antiviral prophylaxis to prevent mother-to-child transmission is also recommended, as is following safe sex practices, including the use of condoms In 2016, the WHO set a goal of eliminating viral hepatitis as a threat to global public health by 2030. Achieving this goal would require the development of therapeutic treatments to cure chronic hepatitis B, as well as preventing its transmission and using vaccines to prevent new infections.An estimated 296 million people, or 3.8% of the global population, had chronic hepatitis B infections as of 2019. Another 1.5 million developed acute infections that year, and 820,000 deaths occurred as a result of HBV. Cirrhosis and liver cancer are responsible for most HBV-related deaths. The disease is most prevalent in Africa (affecting 7.5% of the continent’s population) and in the Western Pacific region (5.9%). Infection rates are 1.5% in Europe and 0.5% in the Americas. According to some estimates, about a third of the worlds population has been infected with hepatitis B at one point in their lives. Hepatitis B was originally known as "serum hepatitis". Signs and symptoms Acute infection with hepatitis B virus is associated with acute viral hepatitis, an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.Chronic infection with hepatitis B virus may be asymptomatic or may be associated with chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of membranous glomerulonephritis (MGN).Symptoms outside of the liver are present in 1–10% of HBV-infected people and include serum-sickness–like syndrome, acute necrotizing vasculitis (polyarteritis nodosa), membranous glomerulonephritis, and papular acrodermatitis of childhood (Gianotti–Crosti syndrome). The serum-sickness–like syndrome occurs in the setting of acute hepatitis B, often preceding the onset of jaundice. The clinical features are fever, skin rash, and polyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute hepatitis B. About 30–50% of people with acute necrotizing vasculitis (polyarteritis nodosa) are HBV carriers. HBV-associated nephropathy has been described in adults but is more common in children. Membranous glomerulonephritis is the most common form. Other immune-mediated hematological disorders, such as essential mixed cryoglobulinemia and aplastic anemia have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined; therefore, they probably should not be considered etiologically linked to HBV. Cause Transmission Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. HBV is 50 to 100 times more infectious than human immunodeficiency virus (HIV). HBV can be transmitted through several routes of infection. In vertical transmission, HBV is passed from mother to child (MTCT) during childbirth. Without intervention, a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg.Early life horizontal transmission can occur through bites, lesions, certain sanitary habits, or other contact with secretions or saliva containing HBV. Adult horizontal transmission is known to occur through sexual contact, blood transfusions and transfusion with other human blood products, re-use of contaminated needles and syringes. Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-transmission (MTCT) of HBV. Virology Structure Hepatitis B virus (HBV) is a member of the hepadnavirus family. The virus particle (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of core protein. These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses. The 42 nm virions, which are capable of infecting liver cells known as hepatocytes, are referred to as "Dane particles". In addition to the Dane particles, filamentous and spherical bodies lacking a core can be found in the serum of infected individuals. These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigens (HBsAg), and is produced in excess during the life cycle of the virus. Genome The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full-length strand) and 1700–2800 nucleotides long (for the short length-strand). The negative-sense (non-coding) is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (−) sense strand and a short sequence of RNA from the (+) sense strand. Non-coding bases are removed from the ends of the (−) sense strand and the ends are rejoined. There are four known genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. In some rare strains of the virus known as Hepatitis B virus precore mutants, no HBeAg is present. The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large (the order from surface to the inside: pre-S1, pre-S2, and S ), middle (pre-S2, S), and small (S) are produced. There is a myristyl group, which plays an important role in infection, on the amino-terminal end of the preS1 part of the large (L) protein. In addition to that, N terminus of the L protein have virus attachment and capsid binding sites. Because of that, the N termini of half of the L protein molecules are positioned outside the membrane and the other half positioned inside the membrane.The function of the protein coded for by gene X is not fully understood but it is associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth regulating molecules. Pathogenesis The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known pararetroviruses: non-retroviruses that still use reverse transcription in their replication process. The virus gains entry into the cell by binding to NTCP on the surface and being endocytosed. Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The partially double-stranded viral DNA is then made fully double stranded by a viral polymerase and transformed into covalently closed circular DNA (cccDNA). This cccDNA serves as a template for transcription of four viral mRNAs by host RNA polymerase. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase. These four viral transcripts undergo additional processing and go on to form progeny virions that are released from the cell or returned to the nucleus and re-cycled to produce even more copies. The long mRNA is then transported back to the cytoplasm where the virion P protein (the DNA polymerase) synthesizes DNA via its reverse transcriptase activity. Serotypes and genotypes The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins, and into eight major genotypes (A–H). The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination. There are two other genotypes I and J but they are not universally accepted as of 2015. The diversity of genotypes is not shown equally in the world. For example, A, D, and E genotypes have been seen in Africa prevalently while B and C genotypes are observed in Asia as widespread.Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A–F). Two further types have since been described (G and H). Most genotypes are now divided into subgenotypes with distinct properties. Mechanisms Hepatitis B virus primarily interferes with the functions of the liver by replicating in hepatocytes. A functional receptor is NTCP. There is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D. The virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS-specific receptors are expressed primarily on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells.During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus-specific cytotoxic T lymphocytes(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines, which are then used to purge HBV from viable hepatocytes. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver. Diagnosis The tests, called assays, for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex.The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of the core protein, alternatively known as hepatitis B core antigen, or HBcAg. During this window in which the host remains infected but is successfully clearing the virus, IgM antibodies specific to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease. Therefore, most hepatitis B diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG).Shortly after the appearance of the HBsAg, another antigen called hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a hosts serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the e antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the e antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication. If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen (anti-HBs and anti HBc IgG). The time between the removal of the HBsAg and the appearance of anti-HBs is called the window period. A person negative for HBsAg but positive for anti-HBs either has cleared an infection or has been vaccinated previously. Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase (ALT) levels and inflammation of the liver, if they are in the immune clearance phase of chronic infection. Carriers who have seroconverted to HBeAg negative status, in particular those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others. However, it is possible for individuals to enter an "immune escape" with HBeAg-negative hepatitis. PCR tests have been developed to detect and measure the amount of HBV DNA, called the viral load, in clinical specimens. These tests are used to assess a persons infection status and to monitor treatment. Individuals with high viral loads, characteristically have ground glass hepatocytes on biopsy. Prevention Vaccine Vaccines for the prevention of hepatitis B have been routinely recommended for babies since 1991 in the United States. The first dose is generally recommended within a day of birth. The hepatitis B vaccine was the first vaccine capable of preventing cancer, specifically liver cancer.Most vaccines are given in three doses over a course of days. A protective response to the vaccine is defined as an anti-HBs antibody concentration of at least 10 mIU/ml in the recipients serum. The vaccine is more effective in children and 95 percent of those vaccinated have protective levels of antibody. This drops to around 90% at 40 years of age and to around 75 percent in those over 60 years. The protection afforded by vaccination is long lasting even after antibody levels fall below 10 mIU/ml. For newborns of HBsAg-positive mothers: hepatitis B vaccine alone, hepatitis B immunoglobulin alone, or the combination of vaccine plus hepatitis B immunoglobulin, all prevent hepatitis B occurrence. Furthermore, the combination of vaccine plus hepatitis B immunoglobulin is superior to vaccine alone. This combination prevents HBV transmission around the time of birth in 86% to 99% of cases.Tenofovir given in the second or third trimester can reduce the risk of mother to child transmission by 77% when combined with hepatitis B immunoglobulin and the hepatitis B vaccine, especially for pregnant women with high hepatitis B virus DNA levels. However, there is no sufficient evidence that the administration of hepatitis B immunoglobulin alone during pregnancy, might reduce transmission rates to the newborn infant. No randomized control trial has been conducted to assess the effects of hepatitis B vaccine during pregnancy for preventing infant infection.All those with a risk of exposure to body fluids such as blood should be vaccinated, if not already. Testing to verify effective immunization is recommended and further doses of vaccine are given to those who are not sufficiently immunized.In 10- to 22-year follow-up studies there were no cases of hepatitis B among those with a normal immune system who were vaccinated. Only rare chronic infections have been documented. Vaccination is particularly recommended for high risk groups including: health workers, people with chronic kidney failure, and men who have sex with men.Both types of the hepatitis B vaccine, the plasma-derived vaccine (PDV) and recombinant vaccine (RV) are of similar effectiveness in preventing the infection in both healthcare workers and chronic kidney failure groups. With one difference noticed among health worker group, that the RV intramuscular route is significantly more effective compared with RV intradermal route of administration. Other In assisted reproductive technology, sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of transmission from mother to child with IVF is no different from the risk in spontaneous conception.Those at high risk of infection should be tested as there is effective treatment for those who have the disease. Groups that screening is recommended for include those who have not been vaccinated and one of the following: people from areas of the world where hepatitis B occurs in more than 2%, those with HIV, intravenous drug users, men who have sex with men, and those who live with someone with hepatitis B. Screening during pregnancy is recommended in the United States. Treatment Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype. Treatment duration when medication is taken by mouth, however, is more variable and usually longer than one year.Although none of the available medications can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2018, there are eight medications licensed for the treatment of hepatitis B infection in the United States. These include antiviral medications lamivudine, adefovir, tenofovir disoproxil, tenofovir alafenamide, telbivudine, and entecavir, and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a. In 2015 the World Health Organization recommended tenofovir or entecavir as first-line agents. Those with current cirrhosis are in most need of treatment.The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of the genotype of the infecting virus or the persons heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.It seems unlikely that the disease will be eliminated by 2030, the goal set in 2016 by WHO. However, progress is being made in developing therapeutic treatments. In 2010, the Hepatitis B Foundation reported that 3 preclinical and 11 clinical-stage drugs were under development, based on largely similar mechanisms. In 2020, they reported that there were 17 preclinical- and 32 clinical-stage drugs under development, using diverse mechanisms. Prognosis Hepatitis B virus infection may be either acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months. Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, this drops to 30% for younger children, and only 5% of newborns that acquire the infection from their mother at birth will clear the infection. This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma. Of those infected between the age of one to six, 70% will clear the infection.Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. Polyarteritis nodosa is more common in people with hepatitis B infection. Cirrhosis A number of different tests are available to determine the degree of cirrhosis present. Transient elastography (FibroScan) is the test of choice, but it is expensive. Aspartate aminotransferase to platelet ratio index may be used when cost is an issue. Reactivation Hepatitis B virus DNA remains in the body after infection, and in some people, including those that do not have detectable HBsAg, the disease recurs. Although rare, reactivation is seen most often following alcohol or drug use, or in people with impaired immunity. HBV goes through cycles of replication and non-replication. Approximately 50% of overt carriers experience acute reactivation. Males with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than people with lower levels. Although reactivation can occur spontaneously, people who undergo chemotherapy have a higher risk. Immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver. The risk of reactivation varies depending on the serological profile; those with detectable HBsAg in their blood are at the greatest risk, but those with only antibodies to the core antigen are also at risk. The presence of antibodies to the surface antigen, which are considered to be a marker of immunity, does not preclude reactivation. Treatment with prophylactic antiviral drugs can prevent the serious morbidity associated with HBV disease reactivation. Epidemiology At least 296 million people, or 3.8% of the worlds population, had chronic HBV infection as of 2019. Another 1.5 million cases of acute HBV infection also occurred that year. Regional prevalences across the globe range from around 7.5% in Africa to 0.5% in the Americas.The primary method of HBV transmission and the prevalence of chronic HBV infection in specific regions often correspond with one another. In populations where HBV infection rates are 8% or higher, which are classified as high prevalence, vertical transmission (usually occurring during birth) is most common, though rates of early childhood transmission can also be significant among these populations. In 2021, 19 African countries had infection rates ranging between 8-19%, placing them in the high prevalence category.In moderate prevalence areas where 2–7% of the population is chronically infected, the disease is predominantly spread horizontally, often among children, or vertically. China’s HBV infection rate is at the higher end of the moderate prevalence classification with an infection rate of 6.89% as of 2019. HBV prevalence in India is also moderate, with studies placing India’s infection rate between 2-4%.Countries with low HBV prevalence include Australia (0.9%), those in the WHO European Region (which average 1.5%), and most countries in North and South America (which average 0.28%). In the United States, an estimated 0.26% of the population was living with HBV infection as of 2018. History Findings of HBV DNA in ancient human remains have shown that HBV has infected humans since at least ten millennia, both in Eurasia and in the Americas. This disproved the belief that hepatitis B originated in the New World and spread to Europe around 16th century. Hepatitis B virus subgenotype C4 is exclusively present in Australian aborigines, suggesting an ancient origin as much as 50,000 years old. However, analyses of ancient HBV genomes suggested that the most recent common ancestor of all known human HBV strains was dated to between 20,000 and 12,000 years ago, pointing
Hepatitis B	to a more recent origin for all HBV genotypes. The evolution of HBV in humans was shown to reflect known events of human history such as the first peopling of the Americas during the late Pleistocene and the Neolithic transition in Europe. Ancient DNA studies have also showed that some ancient hepatitis viral strains still infect humans, while other became extinct.The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885. An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed with serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Lurmans paper, now regarded as a classical example of an epidemiological study, proved that contaminated lymph was the source of the outbreak. Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used, and, more importantly, reused, for administering Salvarsan for the treatment of syphilis. The largest outbreak of Hepatitis B ever recorded was the infection of up to 330,000 American soldiers during World War II. The outbreak has been blamed on a yellow fever vaccine made with contaminated human blood serum, and after receiving the vaccinations about 50,000 soldiers developed jaundice.The virus was not discovered until 1966 when Baruch Blumberg, then working at the National Institutes of Health (NIH), discovered the Australia antigen (later known to be hepatitis B surface antigen, or HBsAg) in the blood of Aboriginal Australian people. Although a virus had been suspected since the research published by Frederick MacCallum in 1947, David Dane and others discovered the virus particle in 1970 by electron microscopy. In 1971, the FDA issued its first-ever blood supply screening order to blood banks. By the early 1980s the genome of the virus had been sequenced, and the first vaccines were being tested. Society and culture World Hepatitis Day, observed 28 July, aims to raise global awareness of hepatitis B and hepatitis C and encourage prevention, diagnosis, and treatment. It has been led by the World Hepatitis Alliance since 2007 and in May 2010, it received global endorsement from the World Health Organization. See also Infectious causes of cancer Oncovirus References External links Hepatitis B at Curlie
Omphalomesenteric duct cyst	Omphalomesenteric duct cysts (ODC, also known as an omphalomesenteric duct remnant or vitelline cyst) are developmental defects relating to the closure of the omphalomesenteric duct. It usually disintegrates within six weeks of gestation, but remnants of the cyst can sometimes be found along the intestines or umbilicus. Any remnants can be removed via surgical means. See also Pilomatricoma List of cutaneous conditions == References ==
Abdomen	The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. The area occupied by the abdomen is called the abdominal cavity. In arthropods it is the posterior tagma of the body; it follows the thorax or cephalothorax.In humans, the abdomen stretches from the thorax at the thoracic diaphragm to the pelvis at the pelvic brim. The pelvic brim stretches from the lumbosacral joint (the intervertebral disc between L5 and S1) to the pubic symphysis and is the edge of the pelvic inlet. The space above this inlet and under the thoracic diaphragm is termed the abdominal cavity. The boundary of the abdominal cavity is the abdominal wall in the front and the peritoneal surface at the rear. In vertebrates, the abdomen is a large body cavity enclosed by the abdominal muscles, at front and to the sides, and by part of the vertebral column at the back. Lower ribs can also enclose ventral and lateral walls. The abdominal cavity is continuous with, and above, the pelvic cavity. It is attached to the thoracic cavity by the diaphragm. Structures such as the aorta, inferior vena cava and esophagus pass through the diaphragm. Both the abdominal and pelvic cavities are lined by a serous membrane known as the parietal peritoneum. This membrane is continuous with the visceral peritoneum lining the organs. The abdomen in vertebrates contains a number of organs belonging to, for instance, the digestive system, urinary system, and muscular system. Contents The abdominal cavity contains most organs of the digestive system, including the stomach, the small intestine, and the colon with its attached appendix. Other digestive organs are known as the accessory digestive organs and include the liver, its attached gallbladder, and the pancreas, and these communicate with the rest of the system via various ducts. The spleen, and organs of the urinary system including the kidneys, and adrenal glands also lie within the abdomen, along with many blood vessels including the aorta and inferior vena cava. The urinary bladder, uterus, fallopian tubes, and ovaries may be seen as either abdominal organs or as pelvic organs. Finally, the abdomen contains an extensive membrane called the peritoneum. A fold of peritoneum may completely cover certain organs, whereas it may cover only one side of organs that usually lie closer to the abdominal wall. This is called the retroperitoneum, and the kidneys and ureters are known as retroperitoneal organs. Abdominal organs can be highly specialized in some animals. For example, the stomach of ruminants, (a suborder of mammals that includes cattle and sheep), is divided into four chambers – rumen, reticulum, omasum and abomasum. Muscles There are three layers of muscles in the abdominal wall. They are, from the outside to the inside: external oblique, internal oblique, and transverse abdominal. The first three layers extend between the vertebral column, the lower ribs, the iliac crest and pubis of the hip. All of their fibers merge towards the midline and surround the rectus abdominis in a sheath before joining up on the opposite side at the linea alba. Strength is gained by the criss-crossing of fibers, such that the external oblique runs downward and forward, the internal oblique upward and forward, and the transverse abdominal horizontally forward.The transverse abdominal muscle is flat and triangular, with its fibers running horizontally. It lies between the internal oblique and the underlying transverse fascia. It originates from the inguinal ligament, costal cartilages 7-12, the iliac crest and thoracolumbar fascia. Inserts into the conjoint tendon, xiphoid process, linea alba and the pubic crest. The rectus abdominis muscles are long and flat. The muscle is crossed by three fibrous bands called the tendinous intersections. The rectus abdominis is enclosed in a thick sheath, formed as described above, by fibers from each of the three muscles of the lateral abdominal wall. They originate at the pubis bone, run up the abdomen on either side of the linea alba, and insert into the cartilages of the fifth, sixth, and seventh ribs. In the region of the groin, the inguinal canal, is a passage through the layers. This gap is where the testes can drop through the wall and where the fibrous cord from the uterus in the female runs. This is also where weakness can form, and cause inguinal hernias.The pyramidalis muscle is small and triangular. It is located in the lower abdomen in front of the rectus abdominis. It originates at the pubic bone and is inserted into the linea alba halfway up to the navel. Function Functionally, the human abdomen is where most of the digestive tract is placed and so most of the absorption and digestion of food occurs here. The alimentary tract in the abdomen consists of the lower esophagus, the stomach, the duodenum, the jejunum, ileum, the cecum and the appendix, the ascending, transverse and descending colons, the sigmoid colon and the rectum. Other vital organs inside the abdomen include the liver, the kidneys, the pancreas and the spleen. The abdominal wall is split into the posterior (back), lateral (sides), and anterior (front) walls. Movement, breathing and other functions The abdominal muscles have different important functions. They assist as muscles of exhalation in the breathing process during forceful exhalation. Moreover, these muscles serve as protection for the inner organs. Furthermore, together with the back muscles they provide postural support and are important in defining the form. When the glottis is closed and the thorax and pelvis are fixed, they are integral in the cough, urination, defecation, childbirth, vomit, and singing functions. When the pelvis is fixed, they can initiate the movement of the trunk in a forward motion. They also prevent hyperextension. When the thorax is fixed, they can pull up the pelvis and finally, they can bend the vertebral column sideways and assist in the trunks rotation. Posture The transverse abdominis muscle is the deepest muscle, therefore, it cannot be touched from the outside. It can greatly affect the bodys posture. The internal obliques are also deep and also affect body posture. Both of them are involved in rotation and lateral flexion of the spine and are used to bend and support the spine from the front. The external obliques are more superficial and they are also involved in rotation and lateral flexion of the spine. Also they stabilize the spine when upright. The rectus abdominis muscle is not the most superficial abdominal muscle. The tendonous sheath extending from the external obliques cover the rectus abdominis. The rectus abdominis is the muscle that very fit people develop into the 6-pack ab look. Although it should really be a 10 pack as there are 5 vertical sections on each side. The 2 bottom sections are just above the pubic bone and usually not visible, hence, the 6 pack abs. The rectus abdominals function is to bend ones back forward (flexion). The main work of the abdominal muscles is to bend the spine forward when contracting concentrically. Society and culture Social and cultural perceptions of the outward appearance of the abdomen has varying significance around the world. Depending on the type of society, excess weight can be perceived as an indicator of wealth and prestige due to excess food, or as a sign of poor health due to lack of exercise. In many cultures, bare abdomens are distinctly sexualized and perceived similarly to breast cleavage. Exercise Being key elements of spinal support, and contributors to good posture, it is important to properly exercise the abdominal muscles together with the back muscles because when these are weak or overly tight they can suffer painful spasms and injuries. When properly exercised, abdominal muscles contribute to improved posture and balance, reduce the likelihood of back pain episodes, reduce the severity of back pain, protect against injury by responding efficiently to stresses, help avoid some back surgeries, and help with the healing of back problems, or after spine surgery. When strengthened, the abdominal muscles provide flexibility as well. The abdominal muscles can be worked by practicing disciplines of general body strength such as Pilates, yoga, Tai chi, and jogging. There are also specific routines which target each of these muscles. Clinical significance Abdominal obesity is a condition where abdominal fat or visceral fat, has built up excessively between the abdominal organs. This is associated with a higher risk of heart disease, asthma and type 2 diabetes. Abdominal trauma is an injury to the abdomen and can involve damage to the abdominal organs. There is an associated risk of severe blood loss and infection. Injury to the lower chest can cause injuries to the spleen and liver.A scaphoid abdomen is when the abdomen is sucked inwards. In a newborn, it may represent a diaphragmatic hernia. In general, it is indicative of malnutrition. Disease Many gastrointestinal diseases affect the abdominal organs. These include stomach disease, liver disease, pancreatic disease, gallbladder and bile duct disease; intestinal diseases include enteritis, coeliac disease, diverticulitis, and IBS. Examination Different medical procedures can be used to examine the organs of the gastrointestinal tract. These include endoscopy, colonoscopy, sigmoidoscopy, enteroscopy, oesophagogastroduodenoscopy and virtual colonoscopy. There are also a number of medical imaging techniques that can be used. Surface landmarks are important in the examination of the abdomen. Surface landmarks In the mid-line a slight furrow extends from the xiphoid process above to the pubic symphysis below, representing the linea alba in the abdominal wall. At about its midpoint sits the umbilicus or navel. The rectus abdominis on each side of the linea alba stands out in muscular people. The outline of these muscles is interrupted by three or more transverse depressions indicating the tendinous intersections. There is usually one about the xiphoid process, one at the navel, and one in between. It is the combination of the linea alba and the tendinous intersections which form the abdominal "six-pack" sought after by many people. The upper lateral limit of the abdomen is the subcostal margin (at or near the subcostal plane) formed by the cartilages of the false ribs (8, 9, 10) joining one another. The lower lateral limit is the anterior crest of the ilium and Pouparts ligament, which runs from the anterior superior spine of the ilium to the spine of the pubis. These lower limits are marked by visible grooves. Just above the pubic spines on either side are the external abdominal rings, which are openings in the muscular wall of the abdomen through which the spermatic cord emerges in the male, and through which an inguinal hernia may rupture. One method by which the location of the abdominal contents can be appreciated is to draw three horizontal and two vertical lines. Horizontal lines The highest of the former is the transpyloric line of C. Addison, which is situated halfway between the suprasternal notch and the top of the pubic symphysis, and often cuts the pyloric opening of the stomach an inch to the right of the mid-line. The hilum of each kidney is a little below it, while its left end approximately touches the lower limit of the spleen. It corresponds to the first lumbar vertebra behind. The second line is the subcostal line, drawn from the lowest point of the subcostal arch (tenth rib). It corresponds to the upper part of the third lumbar vertebra, and it is an inch or so above the umbilicus. It indicates roughly the transverse colon, the lower ends of the kidneys, and the upper limit of the transverse (3rd) part of the duodenum. The third line is called the intertubercular line, and runs across between the two rough tubercles, which can be felt on the outer lip of the crest of the ilium about two and a half inches (64 mm) from the anterior superior spine. This line corresponds to the body of the fifth lumbar vertebra, and passes through or just above the ileo-caecal valve, where the small intestine joins the large intestine. Vertical lines The two vertical or mid-Poupart lines are drawn from the point midway between the anterior superior spine and the pubic symphysis on each side, vertically upward to the costal margin. The right one is the most valuable, as the ileo-caecal valve is situated where it cuts the intertubercular line. The orifice of the appendix lies an inch lower, at McBurneys point. In its upper part, the vertical line meets the transpyloric line at the lower margin of the ribs, usually the ninth, and here the gallbladder is situated. The left mid-Poupart line corresponds in its upper three-quarters to the inner edge of the descending colon.The right subcostal margin corresponds to the lower limit of the liver, while the right nipple is about half an inch above its upper limit. Quadrants and regions The abdomen can be divided into quadrants or regions to describe the location of an organ or structure. Classically, quadrants are described as the left upper, left lower, right upper, and right lower. Quadrants are also often used in describing the site of an abdominal pain.The abdomen can also be divided into nine regions. These terms stem from "hypo" meaning "below" and "epi" means "above", while "chondron" means "cartilage" (in this case, the cartilage of the rib) and "gaster" means stomach. The reversal of "left" and "right" is intentional, because the anatomical designations reflect the patients own right and left.) The "right iliac fossa" (RIF) is a common site of pain and tenderness in patients who have appendicitis. The fossa is named for the underlying iliac fossa of the hip bone, and thus is somewhat imprecise. Most of the anatomical structures that will produce pain and tenderness in this region are not in fact in the concavity of the ileum. However, the term is in common usage. Other animals In arthropods the abdomen is built up of a series of upper plates known as tergites and lower plates known as sternites, the whole being held together by a tough yet stretchable membrane. The abdomen contains the insects digestive tract and reproductive organs, it consists of eleven segments in most orders of insects though the eleventh segment is absent in the adult of most higher orders. The number of these segments does vary from species to species with the number of segments visible reduced to only seven in the common honeybee. In the Collembola (Springtails) the abdomen has only six segments. The abdomen is sometimes highly modified. In Apocrita (bees, ants and wasps), the first segment of the abdomen is fused to the thorax and is called the propodeum. In ants the second segment forms the narrow petiole. Some ants have an additional postpetiole segment, and the remaining segments form the bulbous gaster. The petiole and gaster (abdominal segments 2 and onward) are collectively called the metasoma. Unlike other arthropods, insects possess no legs on the abdomen in adult form, though the Protura do have rudimentary leg-like appendages on the first three abdominal segments, and Archaeognatha possess small, articulated "styli" which are sometimes considered to be rudimentary appendages. Many larval insects including the Lepidoptera and the Symphyta (Sawflies) have fleshy appendages called prolegs on their abdominal segments (as well as their more familiar thoracic legs), which allow them to grip onto the edges of plant leaves as they walk around. In arachnids (spiders, scorpions and relatives), the term "abdomen" is used interchangeably with "opisthosoma" ("hind body"), which is the body section posterior to that bearing the legs and head (the prosoma or cephalothorax). See also Abdominal fat References External links "Abdomen" . Colliers New Encyclopedia. 1921.
Solitary fibrous tumor	Solitary fibrous tumor (SFT), also known as fibrous tumor of the pleura, is a rare mesenchymal tumor originating in the pleura or at virtually any site in the soft tissue including seminal vesicle. Approximately 78% to 88% of SFTs are benign and 12% to 22% are malignant. The World Health Organization (2020) classified SET as specific type of tumor in the category of malignant fibroblastic and myofibroblastic tumors. Signs and symptoms About 80% of pleural SFTs originate in the visceral pleura, while 20% arise from parietal pleura. Although they are often very large tumors (up to 40 cm. in diameter), over half are asymptomatic at diagnosis. While some researchers have proposed that a SFT occupying at least 40% of the affected hemithorax be considered a "giant solitary fibrous tumor", no such "giant" variant has yet been recognized within the most widely used pleural tumor classification scheme.Some SFTs are associated with the paraneoplastic Doege–Potter syndrome, which is caused by tumor production of IGF-2. Pathophysiology Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors. Treatment The treatment of choice for both benign and malignant SFT is complete en bloc surgical resection. Prognosis Prognosis in benign SFTs is excellent. About 8% will recur after first resection, with the recurrence usually cured after additional surgery.The prognosis in malignant SFTs is much more guarded. Approximately 63% of patients will have a recurrence of their tumor, of which more than half will succumb to disease progression within 2 years. Adjuvant chemotherapy and/or radiotherapy in malignant SFT remains controversial. History SFT was first mentioned in the scientific literature by Wagner. The first discussion of its clinical and pathological properties was by Klemperer and Rabin. SFTs have also been known as hemangiopericytomas although this term has now been discontinued from WHO tumor classifications.Over the years pleural SFTs acquired a number of synonyms, including localized fibrous tumor, benign mesothelioma, localized fibrous mesothelioma, submesothelial fibroma, and pleural fibroma. The use of names that include ‘mesothelioma’ for this tumor is discouraged because of potential confusion with diffuse malignant mesothelioma, a much more serious disease. See also Hemangiopericytoma Myopericytoma Additional images References External links [1] World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. (Download Page)
Spastic hemiplegia	Spastic hemiplegia is a neuromuscular condition of spasticity that results in the muscles on one side of the body being in a constant state of contraction. It is the "one-sided version" of spastic diplegia. It falls under the mobility impairment umbrella of cerebral palsy. About 20–30% of people with cerebral palsy have spastic hemiplegia. Due to brain or nerve damage, the brain is constantly sending action potentials to the neuromuscular junctions on the affected side of the body. Similar to strokes, damage on the left side of the brain affects the right side of the body and damage on the right side of the brain affects the left side of the body. Other side can be effected for lesser extent. The affected side of the body is rigid, weak and has low functional abilities. In most cases, the upper extremity is much more affected than the lower extremity. This could be due to preference of hand usage during early development. If both arms are affected, the condition is referred to as double hemiplegia. Some patients with spastic hemiplegia only experience minor impairments, where in severe cases one side of the body could be completely paralyzed. The severity of spastic hemiplegia is dependent upon the degree of the brain or nerve damage. Presentation Complications The muscle spasticity can cause gait patterns to be awkward and jerky. The constant spastic state of the muscle can lead to bone and tendon deformation, further complicating the patients mobility. Many patients with spastic hemiplegia are subjected to canes, walkers and even wheelchairs. Due to the decrease in weight bearing, patients are at a higher risk of developing osteoporosis. An unhealthy weight can further complicate mobility. Patients with spastic hemiplegia are a high risk for experiencing seizures. Oromotor dysfunction puts patients at risk for aspiration pneumonia. Visual field deficits can cause impaired two-point discrimination. Many patients experience the loss of sensation in the arms and legs on the affected side of the body. Nutrition is essential for the proper growth and development for a child with spastic hemiplegia. Causes There are many different brain dysfunctions that can account for the cause for spastic hemiplegia. Spastic hemiplegia occurs either at birth or in the womb. The cause can be all types of strokes, cerebral palsy head injuries, hereditary diseases, brain injuries and infections. Malformations of the veins or arteries in any part of the body can lead to spastic hemiplegia. The artery most commonly affected is the middle cerebral artery. Unborn and newborn babies are susceptible to strokes. Leukodystrophies are a group of hereditary diseases that are known to cause spastic hemiplegia. Brain infections that cause spastic hemiplegia are meningitis, multiple sclerosis, and encephalitis. The spasticity occurs when the afferent pathways in the brain are compromised and the communication between the brain to the motor fibers is lost. When the inhibitory signals to deactivate the stretch reflex is lost the muscle remains in a constantly contracted state. With spastic hemiplegia, one upper extremity and one lower extremity is affected, so cervical, lumbar and sacral segments of the spinal column can be affected. Diagnosis Infants with spastic hemiplegia may develop a hand preference earlier than is typical. Treatment There is no known cure for cerebral palsy, however, there is a large array of treatments proven effective at improving quality of life and relieving some of the symptoms associated with CP, especially SHCP. Some treatments are aimed at improving mobility, strengthening muscle and improving coordination. Although CP is due to permanent damage and is not progressive in nature, without treatment the symptoms can become worse, intensifying in pain and severity, and create complications that were not initially present. Some treatments are preventative measures to help prevent further complications, such as complete paralysis of the arm due to non-use and subsequent worsening hypertonia and joint contracture. Others forms of treatment are corrective in nature. Many treatments target symptoms that are indirectly related to or caused by the SHCP. Many of these treatments are common for other forms of CP as well. Treatment is individualized based on each case and the specific needs of the patient. Treatments are often combined with other forms of treatment and a long-term treatment plan is created and continuously evaluated. Treatment can include the following: Physical therapy – Physical therapy is the most common form of treatment (source needed). It may include sensory stimulation, stretching, strengthening and positioning. Constraint-induced movement therapy is a newer form of physical therapy for SHCP that involves casting or splinting the unaffected arm to promote the use of the affected arm (Taub). The theory behind constraint-induced movement therapy is that new neural pathways are created. Alternative forms of physical therapy include yoga and dance. Physical therapy may also include the use of braces while not actively involved with the therapist. Occupational therapy – Occupational therapy evaluates and treats patients through selected activities in order to enable people to function as effectively and independently as possible in daily life. Occupational therapy is geared toward the individual to achieve optimal results and performance while learning to cope with their disability. Speech therapy – Due to difficulties in speech, speech therapy is often necessary. Aside from helping with understanding language and increasing communication skills, speech therapists can also assist children that have difficulty eating and drinking. Behavioral therapy — Psychotherapy and counseling are heavily used in the treatment of individuals with SHPD to help them cope emotionally with their needs and frustrations. Counseling through social work can be very beneficial for social issues and adjustments to society. Psychotherapy becomes a more important aspect of therapy when more serious issues such as depression become problematic. Play therapy is a common treatment for all young children with or without disabilities but can be very useful in helping children with SHCP. This therapy again is individualized geared to improve emotional and social development; reduce aggression; improve cooperation with others; assist a child in processing a traumatic event or prepare for an upcoming event such as surgery. Surgery – Although surgery may become necessary in some cases, physical therapy and the consistent use of braces can help mitigate the need for surgery. Surgical procedures are painful with long and difficult recoveries and do not cure the condition. Most common is a surgery that effectively lengthens the muscle. This type of surgery is usually performed on the legs, but can be performed on the arms as well. Surgeries also may be necessary to realign joints. Other, less popular surgical techniques try to reduce spasticity by severing selected overactive nerves that control muscles. This procedure, known as selective dorsal root rhizotomy, is still somewhat controversial and is generally used only on the lower extremities of severe cases. Other experimental surgical techniques are also being investigated. The benefits of surgery can also be negated or reversed if the patient does not participate in physical therapy and braces (or casts) are not worn regularly. Medicinal – Medication targeting symptoms associated with spasticity is also a relatively new treatment that is utilized but is still in the early stages of development. Drugs such as baclofen, benzodiazepines (e.g., diazepam), tizanidine, and sometimes dantrolene have shown promise in the effort to diminish spasticity. Botulinum toxin ("Botox") type A may reduce spasticity a few months at a time and has frequently been considered a beneficial treatment for children with SHCP and other forms of CP. Botox has been shown to be especially beneficial to reducing spasticity in the gastrocnemius (calf) muscle. This therapy can improve range of motion, reduce deformity, improve response to occupational and physical therapy, and delay the need for surgery. Botulinum toxin type A injections have also shown advantages for upper extremities. There is still some doubt about its use to improve upper limb function as it may induce muscle weakness temporary. Casting and occupational therapy used in conjunction with Botox injections, may be an additional option for better results. Research is constantly investing in new improvements and more experimental therapy and treatment. Epidemiology The incidence of cerebral palsy has increased in the past 40 years. It has been estimated that in the United States cerebral palsy occurs in 4 out every 1000 births. Of these births about 20–30% of them have spastic hemiplegia. Spasticity overall, is the more common type of cerebral palsy, whereas non-spastic cerebral palsy is less common. Studies show that spastic cerebral palsy is on the rise, and the occurrence of diplegia type is decreasing. The prevalence of cerebral palsy is higher in areas of low socioeconomic status. This could potentially be because cerebral palsy incidence increases as birth weight decreases. == References ==
Gynecomastia	Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.Gynecomastia can be normal in newborn babies due to exposure to estrogen from the mother, in adolescents going through puberty, in older men over age 50, and/or in obese men. Most occurrences of gynecomastia do not require diagnostic tests. Gynecomastia may be caused by abnormal hormone changes, any condition that leads to an increase in the ratio of estrogens/androgens such as liver disease, kidney failure, thyroid disease and some non-breast tumors. Alcohol and some drugs can also cause breast enlargement. Other causes may include Klinefelter syndrome, metabolic dysfunction, or a natural decline in testosterone production. This may occur even if the levels of estrogens and androgens are both appropriate, but the ratio is altered.Gynecomastia is the most common benign disorder of the male breast tissue and affects 35% of men, being most prevalent between the ages of 50 and 69. It is normal for up to 70% of adolescent boys to develop gynecomastia. Of these, 75% resolve within two years of onset without treatment. If the condition does not resolve within 2 years, or if it causes embarrassment, pain or tenderness, treatment is warranted. Medical treatment of gynecomastia that has persisted beyond two years is often ineffective. Gynecomastia is different from "pseudogynecomastia", which is commonly present in men with obesity.Medications such as aromatase inhibitors have been found to be effective and even in rare cases of gynecomastia from disorders such as aromatase excess syndrome or Peutz–Jeghers syndrome, but surgical removal of the excess tissue can be needed to correct the condition. In 2019, 24,123 male patients underwent the procedure in the United States, accounting for a 19% increase since 2000. Definition Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogen and androgen. Gynecomastia is different from "pseudogynecomastia", which is defined as an excess of skin and/or adipose tissue in the male breasts without the growth of true glandular breast tissue; this is commonly associated with obesity and can be ruled out by physical exam. Signs and symptoms In gynecomastia there is typically enlargement of one or both breasts, symmetrically or asymmetrically, in a man. A soft, compressible, and mobile mass of breast tissue is felt under the nipple and its surrounding skin in contrast to softer fatty tissue which is not associated with a mass. It may also be accompanied by breast tenderness or nipple sensitivity, which is commonly associated with gynecomastia observed in adolescents, typically early in development. Gynecomastia that is painful, bothersome, rapidly-growing, associated with masses in other areas of the body, or persistent should be evaluated by a clinician for potential causes. Dimpling of the skin, nipple discharge, and nipple retraction are not typical features of gynecomastia and may be associated with other disorders. Milky discharge from the nipple is not a typical finding, but may be seen in a gynecomastic individual with a prolactin secreting tumor. An increase in the diameter of the areola and asymmetry of the chest are other possible signs of gynecomastia.Gynecomastia has psychosocial implications that may be particularly challenging for adolescents who are experiencing physical maturation and self-identity formation, which includes body image disturbances, negative attitudes towards eating, self-esteem problems, social withdrawal, anxiety, and shame. Men with gynecomastia may appear anxious or stressed due to concerns about its appearance and the possibility of having breast cancer. Causes Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen action, a decrease in androgen action, or a combination of these two factors. Estrogen and androgens have opposing actions on breast tissue: estrogens stimulate proliferation while androgens inhibit proliferation. The cause of gynecomastia is unknown in around 25% of cases. Known causes can be physiologic (occurring normally) or non-physiologic due to underlying pathologies such as drug use, chronic disease, tumors, or malnutrition. Physiologic Physiologic or normal gynecomastia can occur at three timepoints in life: shortly after birth in both female and male infants, during puberty in adolescent males, and in older adults over the age of 60. Newborns 60-90% of male and female newborns may show breast development at birth or in the first weeks of life. During pregnancy, the placenta converts the androgenic hormones dehydroepiandrosterone (DHEA) and DHEA sulfate to the estrogenic hormones estrone and estradiol, respectively; after these estrogens are produced by the placenta, they are transferred into the babys circulation, thereby leading to temporary gynecomastia in the baby. In some infants, neonatal milk (also known as "witchs milk") can leak from the nipples. The temporary gynecomastia seen in newborn babies usually resolves after two or three weeks. Adolescents Hormonal imbalance (elevated ratio of estrogen to androgen) during early puberty, either due to decreased androgen production from the adrenals and/or increased conversion of androgens to estrogens, leads to transient gynecomastia in adolescent males. It can occur in up to 65% of adolescents as early as age 10 and peaks at ages 13 and 14. It is self-limited in 75-90% of adolescents and usually resolves spontaneously within 1 to 3 years as pubertal progression increases testosterone levels and cause regression of breast tissue. By age 17, only 10% of adolescent males have persistent gynecomastia. Older adults Declining testosterone levels and an increase in the level of subcutaneous fatty tissue seen as part of the normal aging process can lead to gynecomastia in older males. Increased fatty tissue, a major site of aromatase activity, leads to increased conversion of androgenic hormones such as testosterone to estrogens. Additionally, levels of sex hormone binding globulin (SHBG) increase with age and bind with less affinity to estrogen than androgens. Put together, the elevated ratio of estrogen to androgen leads to gynecomastia, also known as senile gynecomastia in this group. There is a 24-65% prevalence of senile gynecomastia in older males. Non-physiologic Drugs About 10–25% of gynecomastia cases are estimated to result from the use of medications or exogenous chemicals. Drugs can increase estrogen activity or increase the estrogen to androgen ratio through various mechanisms, such as binding to estrogen receptors, promoting estrogen synthesis, providing precursors that can be aromatized into estrogen, causing damage to the testes, inhibiting testosterone synthesis, inhibiting the action of androgens, or displacing estrogen from SHBG. Drugs with good evidence for association with gynecomastia include cimetidine, ketoconazole, gonadotropin-releasing hormone analogues, human growth hormone, human chorionic gonadotropin, 5α-reductase inhibitors such as finasteride and dutasteride, certain estrogens used for prostate cancer, and antiandrogens such as bicalutamide, flutamide, and spironolactone.Drugs with fair evidence for association with gynecomastia include calcium channel blockers such as verapamil, amlodipine, and nifedipine; risperidone, olanzapine, anabolic steroids, alcohol, opioids, efavirenz, alkylating agents, and omeprazole. Certain components of personal skin care products such as lavender or tea tree oil have been reported to cause prepubertal gynecomastia due to its estrogenic and anti-androgenic effects. Certain dietary supplements such as dong quai and Tribulus terrestris have also been associated with gynecomastia. Refeeding gynecomastia Malnutrition and significant loss of body fat suppress gonadotropin secretion, leading to hypogonadism. This is reversible when adequate nutrition resumes, where the return of gonadotropin secretion and gonadal function cause a transient imbalance of estrogen and androgen that mimics puberty, resulting in transient gynecomastia. This phenomenon, also known as refeeding gynecomastia, was first observed when men returning home from prison camps during World War II developed gynecomastia after resuming a normal diet. Similar to pubertal gynecomastia, refeeding gynecomastia resolves on its own in 1–2 years. Chronic disease Many kidney failure patients experience a hormonal imbalance due to the suppression of testosterone production and testicular damage from high levels of urea also known as uremia-associated hypogonadism. Additionally, gynecomastia has been observed in 50% of patients with chronic kidney disease undergoing dialysis. Similar to the mechanism behind refeeding gynecomastia, dialysis allows patients with renal failure who were previously malnourished to expand their diets and regain weight. Dialysis-associated gynecomastia resolves spontaneously within 1–2 years.In individuals with liver failure or cirrhosis, the livers ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcoholic drinks may also contribute to a higher estrogen to testosterone ratio. Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia.A small proportion of male gynecomastia cases may be seen with rare inherited disorders such as spinal and bulbar muscular atrophy and the very rare aromatase excess syndrome. Hypogonadism Gynecomastia can be caused by absolute deficiency in androgen production due to primary or secondary hypogonadism. Primary hypogonadism results when there is damage to the testes (due to radiation, chemotherapy, infections, trauma, etc), leading to impaired androgen production. It can also be caused by chromosomal abnormality seen in Klinefelter syndrome, which is associated with gynecomastia in about 80% of cases. Secondary hypogonadism results when there is damage to the hypothalamus or pituitary (due to radiation, chemotherapy, infection, trauma, etc), and similarly lead to impaired androgen production. The net effect is reduced androgen production while serum estrogen levels (from peripheral aromatization of androgens) remain unaffected. The lack of androgen-mediated inhibition of breast tissue proliferation combined with relative estrogen excess result in gynecomastia. Tumors Testicular tumors such as Leydig cell tumors, Sertoli cell tumors (such as in Peutz–Jeghers syndrome) and hCG-secreting choriocarcinoma may result in rapid-onset gynecomastia by causing excess production of estrogen. Other tumors such as adrenal tumors, pituitary gland tumors (such as a prolactinoma), or lung cancer, can produce hormones that alter the male–female hormone balance and cause gynecomastia.Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia. Pathophysiology The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen, which stimulates breast tissue growth, and androgens, which inhibit breast tissue growth. Breast prominence can result from enlargement of glandular breast tissue, chest adipose tissue (fat) and skin, and is typically a combination. As in females, estrogen stimulates the growth of breast tissue in males. In addition to directly stimulating breast tissue growth, estrogens indirectly decrease secretion of testosterone by suppressing luteinizing hormone secretion, resulting in decreased testicular secretion of testosterone. Estrogen excess One of the main mechanisms for imbalance between estrogens and androgens is the overproduction of estrogens. A possible cause may be a neoplasm that originates from estrogen-secreting cells. Tumors that produce hCG stimulate production of estradiol while reducing other testicular hormone production. Obesity is another common cause of excess serum estrogens due to the presence of aromatase in peripheral tissue, which is a protein that converts androgens into estrogens. Peutz-Jeghers syndrome is a rare cause of testicular tumors that affect aromatase expression, which results in elevated serum estrogen levels. Aromatase excess syndrome is a rare genetic disorder that leads to increased conversion of androgens to estrogens in the body. Androgen deficiency Primary hypogonadism (indicating an intrinsic problem with the testes in males) leads to decreased testosterone synthesis and increased conversion of testosterone to estradiol potentially leading to a gynecomastic appearance. Klinefelter syndrome is a notable example of a disorder that causes hypogonadism and gynecomastia, and has a higher risk of breast cancer in males (20–50 times higher than males without the disorder). Secondary hypogonadism (indicating a problem with the brain) leads to decreased production and release of luteinizing hormone (LH, a stimulatory signal for endogenous steroid hormone synthesis) which leads to decreased production of testosterone and estradiol in the testes. Increased levels of sex hormone-binding globulin Estrogens can increase blood levels of the protein sex hormone-binding globulin (SHBG), which binds free testosterone (the active form) more strongly than estrogen, leading to decreased action of testosterone in male breast tissue. Conditions such as hyperthyroidism and chronic liver disease affect levels of SHBG, leading to symptomatic gynecomastia. Androgen resistance Dysfunction in the androgen receptor prevents the effects of testosterone from acting on its target tissues. Androgen insensitivity syndromes result from the different degrees of resistance to the effects of androgens, and can cause external genitalia that may not be aligned with the genotype of the individuals sex chromosomes. Complete androgen insensitivity syndrome results in the failure to develop external genitalia such as the penis and scrotum along with development of breasts in an individual with testes. Partial androgen insensitivity syndrome may result in a variety of presentations. Minimal androgen insensitivity syndrome may present as gynecomastia in adolescence and may additionally be associated with infertility. Medications Medications are known to cause gynecomastia through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means. Potential sources of estrogen include oral contraceptive pills, spironolactone, and anabolic steroids.High levels of prolactin in the blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia. A high level of prolactin in the blood can inhibit the release of gonadotropin-releasing hormone and therefore cause secondary hypogonadism. Receptors for prolactin and other hormones including insulin-like growth factor 1, insulin-like growth factor 2, luteinizing hormone, progesterone, and human chorionic gonadotropin have been found in male breast tissue, but the impact of these various hormones on gynecomastia development is not well understood. Chronic disease Individuals who have cirrhosis or chronic liver disease may develop gynecomastia for several reasons. Those diagnosed with cirrhosis tend to have increased secretion of the androgenic hormone androstenedione from the adrenal glands, increased conversion of this hormone into various types of estrogen, and increased levels of SHBG, which leads to decreased blood levels of free testosterone. Around 10–40% of males with Graves disease (a common form of hyperthyroidism) experience gynecomastia. Increased conversion of testosterone to estrogen by increased aromatase activity, increased levels of SHBG and increased production of testosterone and estradiol by the testes due to elevated levels of LH cause the gynecomastia. Proper treatment of the hyperthyroidism can lead to the resolution of the gynecomastia. Diagnosis To diagnose gynecomastia, a thorough history and physical examination are obtained by a physician. Important aspects of the physical examination include evaluation of the male breast tissue with palpation to evaluate for breast cancer and pseudogynecomastia (male breast tissue enlargement solely due to excess fatty tissue), evaluation of penile size and development, evaluation of testicular development and an assessment for masses that raise suspicion for testicular cancer, and proper development of secondary sex characteristics such as the amount and distribution of pubic and underarm hair. Gynecomastia usually presents with bilateral involvement of the breast tissue but may occur unilaterally as well.Diagnosis of men with breast enlargement can be evaluated using an algorithm. A review of the medications or substances an individual takes may reveal the cause of gynecomastia. Recommended laboratory investigations to find the underlying cause of gynecomastia include tests for aspartate transaminase and alanine transaminase to rule out liver disease, serum creatinine to determine if kidney damage is present, and thyroid-stimulating hormone levels to evaluate for hyperthyroidism. If these initial laboratory tests fail to uncover the cause of gynecomastia, then additional tests to evaluate for an underlying hormonal balance due to hypogonadism or a testicular tumor should be checked including total and free levels of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, serum beta human chorionic gonadotropin (β-hCG), and prolactin.High levels of prolactin are uncommon in people with gynecomastia. If β-hCG levels are abnormally high, then ultrasound of the testicles should be performed to check for signs of a hormone-secreting testicular tumor. Markers of testicular, adrenal, or other tumors such as urinary 17-ketosteroid or serum dehydroepiandrosterone may also be checked if there is evidence of hormonal imbalance on physical examination. If this evaluation does not reveal the cause of gynecomastia, then it is considered to be idiopathic gynecomastia (of unclear cause). Differential diagnosis While there can be many potential causes of male patients that present with increased breast tissue, differential diagnoses are most concerning for gynecomastia, pseudogynecomastia, and breast cancer (which is rare in men). Other potential causes of male breast enlargement such as mastitis, lipoma, sebaceous cyst, dermoid cyst, hematoma, metastasis, ductal ectasia, fat necrosis, or a hamartoma are typically excluded before making the diagnosis. Imaging Mammography is the method of choice for radiologic examination of male breast tissue in the diagnosis of gynecomastia when breast cancer is suspected on physical examination. If a mass/lump is felt during a physical exam some features of the lump that would point to malignancy would be painless, non moveable (fixed), irregularly shaped, and skin changes. Mammography is rarely indicated for men since breast cancer is an unlikely diagnosis. If mammography is performed and does not reveal findings suggestive of breast cancer, further imaging is not typically necessary. If a tumor of the adrenal glands or the testes is thought to be responsible for the gynecomastia, ultrasound examination of these structures may be performed. Histology Early histological features expected to be seen on examination of gynecomastic tissue attained by fine-needle aspiration biopsy include the following: proliferation and lengthening of the ducts, an increase in connective tissue, an increase in inflammation, and swelling surrounding the ducts, and an increase in fibroblasts in the connective tissue. Chronic gynecomastia may show different histological features such as increased connective tissue fibrosis, an increase in the number of ducts, less inflammation than in the acute stage of gynecomastia, increased subareolar fat, and hyalinization of the stroma. When surgery is performed, the gland is routinely sent to the lab to confirm the presence of gynecomastia and to check for tumors under a microscope. The utility of pathologic examination of breast tissue removed from male adolescent gynecomastia patients has recently been questioned due to the rarity of breast cancer in this population. Classification The spectrum of gynecomastia severity has been categorized into a grading system: Grade I: Minor enlargement, no skin excess Grade II: Moderate enlargement, no skin excess Grade III: Moderate enlargement, skin excess Grade IV: Marked enlargement, skin excess Treatment Mild cases of gynecomastia in adolescence may be treated with advice on lifestyle habits such as proper diet and exercise with reassurance. In more severe cases, medical treatment may be offered including medication or surgical intervention. Medication Gynecomastia can respond well to medical treatment although it is usually only effective when done within the first two years after the start of male breast enlargement. Selective estrogen receptor modulators (SERMs) such as tamoxifen, raloxifene, and clomifene may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia. Clomifene seems to be less effective than tamoxifen or raloxifene. Tamoxifen may be used to treat gynecomastia in adults and of the medical treatments used, tamoxifen is the most effective. Recent studies have shown that treatment with tamoxifen may represent a safe and effective mode of treatment in cases of cosmetically disturbing or painful gynecomastia. Aromatase inhibitors (AIs) such as anastrozole have been used off-label for cases of gynecomastia occurring during puberty but are less effective than SERMs.A few cases of gynecomastia caused by the rare disorders aromatase excess syndrome and Peutz–Jeghers syndrome have responded to treatment with AIs such as anastrozole. Androgens/anabolic steroids may be effective for gynecomastia. Testosterone itself may not be suitable to treat gynecomastia as it can be aromatized into estradiol, but nonaromatizable androgens like topical androstanolone (dihydrotestosterone) can be useful. Surgery If chronic gynecomastia does not respond to medical treatment, surgical removal of glandular breast tissue is usually required. The American Board of Cosmetic Surgery reports surgery is the "most effective known treatment for gynecomastia." Surgical treatment should be considered if the gynecomastia persists for more than 12 months, causes distress (ie physical discomfort or psychological distress), and is in the fibrotic stage. In adolescent males, it is recommended that surgery is postponed until puberty is completed (penile and testicular development should reach Tanner scale Stage V).Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities. In 2019, 24,123 male patients underwent surgical treatment for gynecomastia in the United States, accounting for a 19% increase since 2000. Thirty-five percent of those patients were between the ages of 20 and 29, and 60% were younger than age 29 at the time of the operation. At an average surgeons fee of $4,123, gynecomastia surgery was also the 11th most costly male cosmetic surgery of 2019. Others Radiation therapy and tamoxifen have been shown to help prevent gynecomastia and breast pain from developing in prostate cancer patients who will be receiving androgen deprivation therapy. The efficacy of these treatments is limited once gynecomastia has occurred and are therefore most effective when used prophylactically.In the United States, many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on the basis that it is a cosmetic procedure. Prognosis Gynecomastia itself is a benign finding. It does not confer a poor prognosis, for some patients with underlying pathologies such as testicular cancer the prognosis may be worse. The glandular tissue typically grows under the influence of hormonal stimulation and is often tender or painful. Furthermore, gynecomastia frequently presents social and psychological difficulties such as low self-esteem, depression or shame. Epidemiology Gynecomastia is the most common benign disorder of the male breast tissue and affects 35 percent of men, being most prevalent between the ages of 50 and 69.New cases of gynecomastia are common in three age populations: newborns, adolescents, and men older than 50 years. Newborn gynecomastia occurs in about 60–90 percent of male babies and most cases resolve on their own in about 2–3 weeks after delivery. During adolescence, on average 33 percent of males are estimated to exhibit signs of gynecomastia. Gynecomastia in older men is estimated to be present in 24–65 percent of men between the ages of 50 and 80. Estimates on asymptomatic gynecomastia is about up to 70% in men aged 50 to 69 years.The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of the disorder is not fully understood. The use of anabolic steroids and exposure to chemicals that mimic estrogen in cosmetic products, organochlorine pesticides, and industrial chemicals have been suggested as possible factors driving this increase. According to the American Society of Plastic Surgeons, breast reduction surgeries to correct gynecomastia are fairly common but has been a recent decline. In 2020, there were over 18,000 procedures of this type performed in the United States which is down 11% compared to in 2019. Society and culture Gynecomastia can result in psychological distress for those with the condition. Support groups exist to help improve the self-esteem of affected people.In 2019, a 12-person Philadelphia jury awarded $8 billion in punitive damages to plaintiffs tied to the use of risperidone. Risperidone is an atypical antipsychotic that was originally approved to treat psychosis, but its use in children, including those with autism, ADHD, and schizophrenia diagnoses, has grown over the last two decades.In Murray v. Janssen Pharmaceuticals, Murray was a Risperidone user who was prescribed the medication at age nine and developed male breasts. A jury decided in Murrays favor in November 2015 and awarded him $1.75 million. The $1.75 million jury verdict represented damages for "disfigurement and mental anguish," though it was later reduced to $680,000. In the second portion of the bifurcated trial, the plaintiffs sought to prove that the companies knew and deliberately disregarded evidence that Risperidone could lead to gynecomastia in young males, and nonetheless promoted the medication off-label and released the medication into the open market for prescription and use by patients without disclosing the side effects. The jury found for the plaintiffs in the second portion of the trial and awarded $8 billion in punitive damages. The amount was later reduced to $6.8 million
Gynecomastia	by Judge Kenneth Powell Jr. Etymology The term comes from Greek γυνή gyné (stem gynaik-) female and μαστός mastós breast. See also Breast hypertrophy Male bra Male lactation Mammoplasia References Explanatory notes Citations External links Media related to Gynecomastia at Wikimedia Commons
Duct ectasia of breast	Duct ectasia of the breast, mammary duct ectasia or plasma cell mastitis is a condition that occurs when a milk duct beneath the nipple widens, the duct walls thicken, and the duct fills with fluid. This is the most common cause of greenish discharge. Mammary duct ectasia can mimic breast cancer. It is a disorder of peri- or post-menopausal age.Duct ectasia syndrome is a synonym for nonpuerperal mastitis, but the term has also been occasionally used to describe special cases of fibrocystic diseases or mastalgia or as a wastebasket definition of benign breast disease. Correlation of duct widening with the "classical" symptoms of duct ectasia syndrome is unclear. However, duct widening was recently very strongly correlated with noncyclic breast pain.Duct diameter is naturally variable, subject to hormonal interactions. Duct ectasia syndrome in the classical meaning is associated with additional histological changes. Symptoms Signs of duct ectasia can include nipple retraction, inversion, pain, and classic green-brown discharge. Causes Breasts are made up of fibrous connective tissues, which are made up of cells, fibers and a gel-like substance. Pathogenesis The duct widening is commonly believed to be a result of secretory stasis, including stagnant colostrum, which also causes periductal inflammation and fibrosis. However, because nonspecific duct widening is common it might be also coincidental finding in many processes. Smokers seem more often affected by duct ectasia syndrome although the reported results are not entirely consistent. The correlation with smoking status appears weaker than for subareolar abscess. Correlation with the actual duct widening is not known. Both duct widening and duct ectasia syndrome are frequently bilateral, hence systemic causes are likely involved. Diagnosis Noninvasive methods to determine duct diameter in live patients are available only recently and it is not clear how the results should be compared with older results from biopsies. Histologically, dilation of the large duct is prominent. Duct widening with associated periductal fibrosis is frequently included in the wastebasket definition of fibrocystic disease. In plasma cell rich lesions diagnosed on core biopsies, steroid-responsive IgG4-related mastitis can be identified by IgG/IgG4 immunostaining. Duct Ectasia Syndrome The term duct ectasia syndrome has been used to describe symptoms of nonpuerperal mastitis, possibly associated with nipple inversion and nipple discharge. In some contexts, it was used to describe a particular form of nonpuerperal mastitis coincident with fibrocystic disease, frequently involving pasty (coloured) nipple discharge, nipple retraction, retroareolar abscess and blue dome cysts. Abscessation is not very frequent but by some definitions recurrent subareolar abscess is merely a variant of duct ectasia syndrome - abscessation would be obviously more frequent with this definition. Duct ectasia syndrome has been associated with histopathological findings that are distinct from a simple duct widening. In addition to nonspecific duct widening the myoepithelial cell layer is atrophic, missing or replaced by fibrous tissue. The original cuboidal epithelial layer may be also severely impaired or missing. Characteristic calcifications are often visible on mammographic images. Periductal mastitis, comedo mastitis, secretory disease of the breast, plasma cell mastitis and mastitis obliterans are sometimes considered special cases or synonyms of duct ectasia syndrome. Prognosis The condition is usually self-limiting, and thus not indicated for surgery. Terminology The term has several meanings on histological and symptomatic levels and on both levels usage overlaps with mastalgia, fibrocystic disease and specific sub- or superclasses of nonpuerperal mastitis. While this is not ideal for a definition it results from actual usage in international literature. Because research literature regarding duct ectasia is anything but abundant it is probably easiest to determine the exact meaning(s) intended by the respective authors on a case-by-case basis and this section can offer only a few hints. Typical usage in North America is a synonym of nonpuerperal mastitis, including the special cases of granulomatous mastitis, comedo mastitis, subareolar abscess with or without squamous metaplasia of lactiferous ducts and fistulation.Simple duct widening should be carefully distinguished from more complex histological changes. References == External links ==
Ocular albinism	Ocular albinism is a form of albinism which, in contrast to oculocutaneous albinism, presents primarily in the eyes. There are multiple forms of ocular albinism, which are clinically similar.: 865 Both known genes are on the X chromosome. When the term "autosomal recessive ocular albinism" ("AROA") is used, it usually refers to mild variants of oculocutaneous albinism rather than ocular albinism, which is X-linked. Types References External links GeneReviews/NCBI/NIH/UW entry on Ocular Albinism, X-Linked
Simple-type schizophrenia	Simple-type schizophrenia is a sub-type of schizophrenia included in the International Classification of Diseases (ICD-10), in which it is classified as a mental and behaviour disorder. It is not included in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the upcoming ICD-11, effective on the 1st of January 2022. Simple-type schizophrenia is characterized by negative ("deficit") symptoms, such as avolition, apathy, anhedonia, reduced affect display, lack of initiative, lack of motivation, low activity; with absence of hallucinations or delusions of any kind. Simple schizophrenia was included as a proposed diagnosis for further study in the appendix of the former DSM-IV. Signs and symptoms It has possibly the earliest onset compared to all other schizophrenias, considered to begin in some within childhood. Symptoms of schizophrenia simplex include an absence of will, impoverished thinking and flattening of affect. There is a gradual deterioration of functioning with increased amotivation and reduced socialization. It is considered to be rarely diagnosed and is a schizophrenia without psychotic symptoms.In a study of patients in a Massachusetts hospital, persons with simple schizophrenia were found to make attempts at reality fulfillment with respect to the more primitive needs; tending toward the achievement of fulfillment of these needs rather than engaging in fantasy as is typically found as a reaction to environmental stimuli by the psychotic person. Causes A progressive state of simple schizophrenia results often in cases of adolescent onset juvenile general paresis. Paresis is caused by placental-foetal transfer of infection and results in intellectual (mental) subnormality. Occurrence of this type of paresis is altogether uncommon (Lishman 1998). Diagnosis Classification ICD The WHO first listed the condition in the 6th revision of the International Classification of Diseases ICD-6 (1949) and it stayed in the manual until the present version ICD-10. ICD-9 The ICD-9 simple-type schizophrenia description: A psychosis in which there is insidious development of oddities of conduct, inability to meet the demands of society, and decline in total performance. Delusions and hallucinations are not in evidence and the condition is less obviously psychotic than are the hebephrenic, catatonic and paranoid types of schizophrenia. With increasing social impoverishment vagrancy may ensue and the patient becomes self-absorbed, idle and aimless. Because the schizophrenic symptoms are not clear-cut, diagnosis of this form should be made sparingly, if at all. ICD-10 These are the current criteria: Slowly progressive development over a period of at least one year, of all three of the following: (a) A significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of drive and interests, aimlessness, idleness, a self-absorbed attitude and social withdrawal. (b) Gradual appearance and deepening of negative symptoms such as marked apathy, paucity of speech, underactivity, blunting of affect, passivity and lack of initiative, and poor non-verbal communication. (c) Marked decline in social, scholastic or occupational performance. 2. Absence, at any time, of any symptoms referred to in G1 in F20.0 - F20.3 and of hallucinations or well formed delusions of any kind, i.e. the subject must never have met the criteria for any other type of schizophrenia, or any other psychotic disorder. 3. Absence of evidence of dementia or any other organic mental disorder. The ICD is currently in revision 10, and the ICD-11 was accepted in May 2019 will come into effect in 2022. In the ICD-11, there is no longer a diagnostic category of simple schizophrenia, and all subtypes of schizophrenia have been eliminated. DSM Simple-type schizophrenia also appeared in the first two editions of the DSM as an official diagnosis: This psychosis is characterized chiefly by a slow and insidious reduction of external attachments and interests and by apathy and indifference leading to impoverishment of interpersonal relations, mental deterioration, and adjustment on a lower level of functioning. In general, the condition is less dramatically psychotic than are the hebephrenic, catatonic, and paranoid types of schizophrenia. Also, it contrasts with schizoid personality, in which there is little or no progression of the disorder. But after that, it was omitted in later versions and has since then never returned as a formal diagnosis in any DSM. However, DSM-IV (1994) and DSM-IV-TR (2000) included Simple Schizophrenia in the appendix under the proposed category of simple deteriorative disorder. The provisional research criteria for it were: Progressive development over a period of at least a year of all of the following: (1) marked decline in occupational or academic functioning (2) gradual appearance and deepening of negative symptoms such as affective flattening, alogia, and avolition (3) poor interpersonal rapport, social isolation or social withdrawal B. Criterion A for Schizophrenia has never been met. C. The symptoms are not better accounted for by Schizotypal or Schizoid Personality Disorder, a Psychotic Disorder, a Mood Disorder, an Anxiety Disorder, a dementia, or Mental Retardation and are not due to the direct physiological effects of a substance or a general medical condition. Treatment The use of antipsychotic medication is commonly the first line of treatment; however, the effectiveness after treatment is in question. L-DOPA is effective against reduced affect display and emotional withdrawal, aloofness from society, apathy. History The early idea that a person with schizophrenia might present solely with symptoms and indications of deterioration (i.e. presenting with no accessory symptoms) was identified as dementia simplex.ICD-10 specifies the continuation of symptoms for a period of two years in the diagnosis of simple schizophrenia. This is because of disagreement on the classification validity of the sub-type, that having been retained by the ICD classification, has been omitted from DSM classifications. Symptoms identified earlier to dementia simplex are now DSM-attributed by way of improvements in diagnostic technique to other classifications such as neurodegenerative disorders.Early observations that concur with symptoms of the dementia praecox of the form classified later as simplex began in 1838 with Jean Esquirol. In 1860, Bénédict Morel introduced the term dementia précoce and Langdon Down provided in 1887 the most complete description to that date of the clinical manifestation that Charpentier described in 1890 as dementia précoce simple des enfant normaux.The description of simple schizophrenia is inter-changeable with describing symptoms as a form of dementia praecox known as simple dementing, at least in the time when the Swiss psychiatrists Otto Diem and Eugen Bleuler were studying it. In 1893, Emil Kraepelin considered there were four types of schizophrenia, and was amongst the first to identify three of them (dementia hebephrenica, dementia paranoides, dementia catatonica). The simplex type was added by Eugen Bleuler to the earlier ones identified by Kraepelin in 1899 and subsequently given a basic outline in 1903 by Otto Diem publishing a monograph on dementia praecox in the simple dementing form. This was based on a survey of two males having had a relatively normal childhood but who then fell into patterns of living tending towards vagrancy.A description of a cerebral disorder in relation to organic factors and in the context of general paralysis of the insane only; with no reference to schizophrenia, shows a disorder with features of generalized dementia (Lishman 1998). In 1951, a film was made showing the clinical characteristics of simple-type schizophrenia. Controversy Definition of this type of schizophrenia is without unity or is controversial. The diagnosis was discontinued in the DSM system, although it was recommended for reinclusion in 1989. It was subsequently confirmed as having imprecise diagnostic criteria based on collective descriptions lacking in agreement.However, in an experiment with a small sample size, five patients with a diagnosis of simple deteriorative disorder (DSM-IV) were found to have grey matter deficits, atrophy and reduced cerebral perfusion in the frontal areas. Whitwell et al. found justification to retain the classification on the basis of fulfillment of "dimensional" considerations of classification, as opposed to criticisms resulting from disagreement in considerations of classification using orientation from other categories. References == External links ==
Sarcosinemia	Sarcosinemia (SAR), also called hypersarcosinemia and SARDH deficiency, is a rare autosomal recessive metabolic disorder characterized by an increased concentration of sarcosine in blood plasma and urine ("sarcosinuria"). It can result from an inborn error of sarcosine metabolism, or from severe folate deficiency related to the folate requirement for the conversion of sarcosine to glycine. It is thought to be a relatively benign condition. Cause Sarcosinemia is thought to be caused by a mutation in the sarcosine dehydrogenase (SARDH) gene, which is located at human chromosome 9q34.The disease is inherited in an autosomal recessive manner, which means the defective gene responsible for the disorder is located on an autosome (chromosome 9 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. Diagnosis Treatment See also Inborn errors of metabolism References External links Sarcosinemia at NIHs Office of Rare Diseases
Drug tolerance	Drug tolerance or drug insensitivity is a pharmacological concept describing subjects reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drugs effects; however, this may accelerate tolerance, further reducing the drugs effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease ones allergic reactions) is called drug desensitization.The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subjects reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient. Tachyphylaxis Tachyphylaxis is a subcategory of drug tolerance referring to cases of sudden, short-term onset of tolerance following the administration of a drug. Pharmacodynamic tolerance Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use. A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the receptor, desensitizing it through constant interaction. Other possibilities include a reduction in receptor density (usually associated with receptor agonists), or other mechanisms leading to changes in action potential firing rate. Pharmacodynamic tolerance to a receptor antagonist involves the reverse, i.e., increased receptor firing rate, an increase in receptor density, or other mechanisms. While most occurrences of pharmacodynamic tolerance occur after sustained exposure to a drug, instances of acute or instant tolerance (tachyphylaxis) can occur. Pharmacokinetic (metabolic) tolerance Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs (ADME). All psychoactive drugs are first absorbed into the bloodstream, carried in the blood to various parts of the body including the site of action (distribution), broken down in some fashion (metabolism), and ultimately removed from the body (excretion). All of these factors are very important determinants of crucial pharmacological properties of a drug, including its potency, side effects, and duration of action. Pharmacokinetic tolerance (dispositional tolerance) occurs because of a decreased quantity of the substance reaching the site it affects. This may be caused by an increase in induction of the enzymes required for degradation of the drug e.g. CYP450 enzymes. This is most commonly seen with substances such as ethanol. This type of tolerance is most evident with oral ingestion, because other routes of drug administration bypass first-pass metabolism. Enzyme induction is partly responsible for the phenomenon of tolerance, in which repeated use of a drug leads to a reduction of the drugs effect. However, it is only one of several mechanisms leading to tolerance. Behavioral tolerance Behavioral tolerance occurs with the use of certain psychoactive drugs, where tolerance to a behavioral effect of a drug, such as increased motor activity by methamphetamine, occurs with repeated use. It may occur through drug-independent learning or as a form of pharmacodynamic tolerance in the brain; the former mechanism of behavioral tolerance occurs when one learns how to actively overcome drug-induced impairment through practice. Behavioral tolerance is often context-dependent, meaning tolerance depends on the environment in which the drug is administered, and not on the drug itself. Behavioral sensitization describes the opposite phenomenon. See also == References ==
Loin pain hematuria syndrome	Loin pain hematuria syndrome (LPHS) is the combination of debilitating unilateral or bilateral flank pain and microscopic or macroscopic amounts of blood in the urine that is otherwise unexplained.Loin pain-hematuria syndrome (LPHS) is a poorly defined disorder characterized by recurrent or persistent loin (flank) pain and hematuria that appears to represent glomerular bleeding. Most patients present with both manifestations, but some present with loin pain or hematuria alone. Pain episodes are rarely associated with low-grade fever and dysuria, but urinary tract infection is not present. The major causes of flank pain and hematuria, such as nephrolithiasis and blood clot, are typically not present. Renal arteriography may suggest focally impaired cortical perfusion, while renal biopsy may show interstitial fibrosis and arterial sclerosis.The pain is typically severe, and narcotic therapy is often prescribed as a way to manage chronic pain. Sleep can be difficult because the supine position increases pressure on the flank. The onset of pain is often associated with nausea and vomiting, making pain management by oral opiates complicated. Cause The cause of LPHS is not known. One theory proposes that it is caused by a thin glomerular basement membrane and red blood cell (RBC) renal tubular congestion that leads to swelling of the kidney and distension of the renal fascia resulting in pain.Researchers have hypothesized that the syndrome may be due to blood vessel diseases of the kidney, spasms of the kidney vessels, or other bleeding disorders (coagulopathy). The hematuria in LPHS may be due to an abnormal (thick or thin) glomerular basement membrane. The glomerular basement membrane is a tissue in the kidney that filters the blood. An abnormal glomerular basement membrane may allow red blood cells into the urinary space. Because kidney stones are so common in people with LPHS, crystals in the kidney tubules may also play a part in bleeding and pain.Other speculations on cause include IgA nephropathy. This is a condition in which small amount of a type of normal antibody (called IgA) get stuck in the kidney as it passes through in the bloodstream. This is a chronic condition, which sometimes goes away on its own but occasionally can cause damage to the kidneys. A related condition called IgM nephropathy can sometimes cause pain. Thin membrane disease. In this condition the membrane that filters the blood to make urine is too thin, and blood can pass across it in very small amounts. In a few cases of this condition, there is pain in the kidneys, usually occurring in attacks every so often. Although this condition can be painful, kidney failure does not seem to occur in the long term, so that the only real problem is the symptoms. Infection. In some cases, loin pain-haematuria syndrome occurs after a bladder infection with involvement of the kidney. Even when the infection has been treated and bugs can no longer be found in the urine, pain may persist for 6 months, or even longer in some cases. "Classic loin pain-haematuria syndrome". Some patients have none of the above diagnoses. In these cases there may be minor abnormalities on a kidney biopsy. Angiogram tests to look at the blood vessels in the kidney may show abnormal blood flow, perhaps causing a cramp like pain. The cause is not fully understood. It certainly is [more common] in women than in men, and there may be hormonal influences. Some women find the pain is worse at different times of their menstrual cycle, or comes on during pregnancy, or if they are taking [oral contraceptives].It has also been reported to be caused by microscopic granules of calcium oxylate into the glomerulus itself, causing blood vessels to rupture and increase the distention of the renal capsule.This condition may persist for some years, and can be lifelong. Damage to the kidneys leading to kidney failure does not occur. However, because LPHS is unusual in patients older than 60 years, some clinicians believe that LPHS eventually resolves.At this time no cure has been found for this disease. LPHS is a debilitating disease due to chronic pain and the inability to know how to control the glomerular aspect. The pain of LPHS can be worsened by acts as simple as riding in the car and undertaking daily activities. Many people with this disease are unable to maintain employment due to the debilitating pain. Unpublished research by Dr. Ahmed Ghanem (who has cared for well over 100 women with LPHS found that untreated Symptomatic Nephroptosis - SN (Hypermobile kidney) can lead to LPHS. Nephropexy can help to relieve symptoms. Severe renal colic caused by kinking ureter. Pain classically relieved a little by going on all fours with hips higher than head. Diagnosis LPHS is considered a diagnosis of exclusion. The syndrome presents with hematuria (blood in the urine) and flank (a region of the lower back beneath the ribs and above the ilium) pain which can result from a number of causes. Nonglomerular causes of bleeding (e.g., urinary infection, tumor, or nephrolithiasis) must be excluded. Obstruction of the urinary tract should not be present, confirmed by at least two imaging procedures while pain is present. Diagnosis of loin pain-hematuria syndrome (LPHS) occurs when hematuria is present, recurrent or persistent pain is severe, and other causes of bleeding are excluded. Urine testing can be performed to detect microscopic levels of hematuria. Protein is also commonly found in the urine of patients with LPHS. Kidney biopsies are sometimes performed to look for evidence of glomerular hematuria, excess red blood cells in the kidney tubules, and to assess the width of the glomerular basement membrane. Hematuria (more than 5 red blood cells per high power field) should be present in virtually every urinalysis and is typically characterized by dysmorphic red cells. Recurrent or persistent severe pain for six months or more, occurring in the costovertebral angles. Relation to chronic pelvic pain LPHS has considerable overlap with chronic pelvic pain syndrome. Relation to thin basement membrane disease A thin glomerular basement membrane, as in thin basement membrane disease, is proposed to be the characteristic finding on renal biopsy, but not part of the syndrome definition. Differential diagnosis Kidney stones Nutcracker syndrome IgA nephropathy Cancer of the genitourinary tract Chronic pelvic pain Endometriosis Pyelonephritis Treatment The treatment of LPHS varies considerably from centre to centre. As the condition is rare and poorly understood, a widely adopted standard of care is not existent.Treatment of loin pain-hematuria syndrome (LPHS) typically consists of pain management. Narcotics or oral opioids may be prescribed to help control pain. Patients with severe pain may need high-dose opioids daily or almost daily. Occasionally, people with LPHS require hospitalization for intravenous opioid therapy and control of nausea. Other treatments may include denervation, autotransplantation, renal neurectomy, or nephrectomy. Unfortunately symptoms often recur following these procedures. Limited evidence suggests that drugs that inhibit angiotensin may reduce the frequency and severity of episodes of loin pain and gross hematuria.Pain management with opiate and non-opiate analgesia is common. Angiotensin converting enzyme inhibitors are thought to be beneficial, as they reduce intraglomerular pressure and, presumably, reduce renal tubular congestion with RBCs.Possible treatment regimens General Angiotensin inhibition Reduce the risk of nephrolithiasis Pain control Opioid therapy Inpatient therapy Intravenous opioid regimen Antiemetic drugs Pruritus management Maintenance therapy between pain exacerbations Invasive therapy Implantable drug delivery system Surgical renal denervation Renal autotransplantation Nephrectomy (NOT recommended) Other invasive therapies (but not proven effective) Pulse radio frequency Celiac plexus block Intraureteric capsaicin infusionSurgery (autotransplantation) is thought by some to be of benefit in selected individuals and advocated in some centres, but usually considered the last resort.Physicians discourage surgery, as LPHS symptoms often re-occur after autotransplantation. Epidemiology LPHS is listed as a rare disease in the US National Institute of Health Rare Diseases database. While exact numbers worldwide are not available, the primary LPHS research clinic located in Ohio has over 200 patients. In addition, several hundred other patients have been reported in one study as of 2006. The prevalence of LPHS is estimated at about 0.012 percent, which qualifies LPHS as a rare disease (prevalence less than 0.07 percent) according to the Rare Diseases Act of 2002. Those affected are usually young, with an average age of 31 years, and 70% to 80% are women. See also Pelvic pain References External links Loin Pain - Patient UK
Arterial embolism	Arterial embolism is a sudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood, the major type of embolus being a blood clot (thromboembolism). Sometimes, pulmonary embolism is classified as arterial embolism as well, in the sense that the clot follows the pulmonary artery carrying deoxygenated blood away from the heart. However, pulmonary embolism is generally classified as a form of venous embolism, because the embolus forms in veins. Arterial embolism is the major cause of infarction (which may also be caused by e.g. arterial compression, rupture or pathological vasoconstriction). Signs and symptoms Symptoms may begin quickly or slowly depending on the size of the embolus and how much it blocks the blood flow. Symptoms of embolisation in an organ vary with the organ involved but commonly include: Pain in the involved body part Temporarily decreased organ functionLater symptoms are closely related to infarction of the affected tissue. This may cause permanently decreased organ function.For example, symptoms of myocardial infarction mainly include chest pain, dyspnea, diaphoresis (an excessive form of sweating), weakness, light-headedness, nausea, vomiting, and palpitations.Symptoms of limb infarction include coldness, decreased or no pulse beyond the site of blockage, pain, muscle spasm, numbness and tingling, pallor and muscle weakness, possibly to the grade of paralysis in the affected limb. Commonly occluded sites Arterial emboli often occur in the legs and feet. Some may occur in the brain, causing a stroke, or in the heart, causing a heart attack. Less common sites include the kidneys, intestines, and eyes. Risk factors Risk factors for thromboembolism, the major cause of arterial embolism, include disturbed blood flow (such as in atrial fibrillation and mitral stenosis), injury or damage to an artery wall, and hypercoagulability (such as increased platelet count). Mitral stenosis poses a high risk of forming emboli which may travel to the brain and cause stroke. Endocarditis increases the risk for thromboembolism, by a mixture of the factors above. Atherosclerosis in the aorta and other large blood vessels is a common risk factor, both for thromboembolism and cholesterol embolism. The legs and feet are major impact sites for these types. Thus, risk factors for atherosclerosis are risk factors for arterial embolisation as well: advanced age cigarette smoking hypertension (high blood pressure) obesity hyperlipidemia, e.g. hypercholesterolemia, hypertriglyceridemia, elevated lipoprotein (a) or apolipoprotein B, or decreased levels of HDL cholesterol) diabetes mellitus Sedentary lifestyle stressOther important risk factors for arterial embolism include: recent surgery (both for thromboembolism and air embolism) previous stroke or cardiovascular disease a history of long-term intravenous therapy (for air embolism) Bone fracture (for fat embolism)A septal defect of the heart makes it possible for paradoxical embolization, which happens when a clot in a vein enters the right side of the heart and passes through a hole into the left side. The clot can then move to an artery and cause arterial embolisation. Pathophysiology An arterial embolism is caused by one or more emboli getting stuck in an artery and blocking blood flow, causing ischemia, possibly resulting in infarction with tissue death (necrosis). Individuals with arterial thrombosis or embolism often develop collateral circulation to compensate for the loss of arterial flow. However, it takes time for sufficient collateral circulation to develop, making affected areas more vulnerable for sudden occlusion by embolisation than for e.g. gradual occlusion as in atherosclerosis. Materials Arterial embolisms can consist of various materials, including: Thromboembolism – embolism of thrombus or blood clot. Cholesterol embolism - embolism of cholesterol, often from atherosclerotic plaque inside a vessel. Fat embolism – embolism of bone fracture or fat droplets. Air embolism (also known as a gas embolism) – embolism of air bubbles. Septic embolism – embolism of pus containing bacteria. Cancer embolismIn contrast, amniotic fluid embolism almost exclusively affects the venous side. Diagnosis In addition to evaluating the symptoms above, the health care provider may find decreased or no blood pressure in the arm or leg.Tests to determine any underlying cause for thrombosis or embolism and to confirm presence of the obstruction may include: Doppler ultrasound, especially duplex ultrasonography. It may also involve transcranial doppler exam of arteries to the brain Echocardiography, sometimes involving more specialized techniques such as Transesophageal echocardiography (TEE) or myocardial contrast echocardiography (MCE) to diagnose myocardial infarction Arteriography of the affected extremity or organ Digital subtraction angiography is useful in individuals where administration of radiopaque contrast material must be kept to a minimum. Magnetic resonance imaging (MRI) Blood tests for measuring elevated enzymes in the blood, including cardiac-specific troponin T and/or troponin I, myoglobins, and creatine kinase isoenzymes. These indicate embolisation to the heart that has caused myocardial infarction. Myoglobins and creatine kinase are also elevated in the blood in embolisation in other locations. Blood cultures may be done to identify the organism responsible for any causative infection Electrocardiography (ECG) for detecting myocardial infarction Angioscopy using a flexible fiberoptic catheter inserted directly into an artery. Prevention Prevention of atherosclerosis, which is a major risk factor of arterial embolism, can be performed e.g. by dieting, physical exercise and smoking cessation.In case of high risk for developing thromboembolism, antithrombotic medication such as warfarin or coumadin may be taken prophylactically. Antiplatelet drugs may also be needed. Treatment Treatment is aimed at controlling symptoms and improving the interrupted blood flow to the affected area of the body.Medications include: Antithrombotic medication. These are commonly given because thromboembolism is the major cause of arterial embolism. Examples are: Anticoagulants (such as warfarin or heparin) and antiplatelet medication (such as aspirin, ticlopidine, and clopidogrel) can prevent new clots from forming Thrombolytics (such as streptokinase) can dissolve clots Painkillers given intravenously Vasodilators to relax and dilate blood vessels.Appropriate drug treatments successfully produce thrombolysis and removal of the clot in 50% to 80% of all cases.Antithrombotic agents may be administered directly onto the clot in the vessel using a flexible catheter (intra-arterial thrombolysis). Intra-arterial thrombolysis reduces thromboembolic occlusion by 95% in 50% of cases, and restores adequate blood flow in 50% to 80% of cases.Surgical procedures include: Arterial bypass surgery to create another source of blood supply Embolectomy, to remove the embolus, with various techniques available: Thromboaspiration Angioplasty with balloon catheterization with or without implanting a stent Balloon catheterization or open embolectomy surgery reduces mortality by nearly 50% and the need for limb amputation by approximately 35%. Embolectomy by open surgery on the arteryIf extensive necrosis and gangrene has set in an arm or leg, the limb may have to be amputated. Limb amputation is in itself usually remarkably well-tolerated, but is associated with substantial mortality (~50%), primarily because of the severity of the diseases in patients where it is indicated. Prognosis How well a patient does depends on the location of the clot and to what extent the clot has blocked blood flow. Arterial embolism can be serious if not treated promptly.Without treatment, it has a 25% to 30% mortality rate. The affected area can be permanently damaged, and up to approximately 25% of cases require amputation of an affected extremity. Arterial emboli may recur even after successful treatment. Complications Possible complications of arterial embolism depend on the site of the obstruction: In the heart it can cause myocardial infarction In the brain, it can cause a transient ischemic attack (TIA), and, in prolonged blood obstruction, stroke. Blockage of arteries that supply arms or legs may result in necrosis and gangrene Temporary or permanent decrease or loss of other organ functions In septic embolism, there can be infection of the affected tissue or even septic shock, potentially leading to gangrene and sepsis Epidemiology In the United States, approximately 550,000 people die each year from heart-related arterial embolism and thrombosis. Approximately 250,000 of these individuals are female, and approximately 100,000 of all these deaths are considered premature, that is, prior to the age of average life expectancy. References == External links ==
Amyotrophic lateral sclerosis	Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrigs disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common type of motor neuron disease. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty speaking or swallowing. Half of the people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Most people experience pain. The affected muscles are responsible for chewing food, speaking, and walking. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. ALS eventually causes paralysis and early death, usually from respiratory failure.Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause linked to a history of the disease in the family, and these are known as familial ALS. About half of these genetic cases are due to one of two specific genes. ALS and frontotemporal dementia (FTD) are considered to be part of a common disease continuum (ALS-FTD) because of genetic, clinical, and pathological similarities. The underlying mechanism involves damage to both upper and lower motor neurons; in ALS-FTD, neurons in the frontal and temporal lobes of the brain die as well. The diagnosis is based on a persons signs and symptoms, with testing done to rule out other potential causes.There is no known cure for ALS. The goal of treatment is to improve symptoms. A medication called riluzole may extend life by about two to three months. Non-invasive ventilation may result in both improved quality and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help. The disease can affect people of any age, but usually starts around the age of 60 and in inherited cases around the age of 50. The average survival from onset to death is two to four years, though this can vary, and about 10% survive longer than 10 years, and death is usually due to respiratory failure. In Europe, the disease affects about two to three people per 100,000 per year. Rates in much of the world are unclear. In the United States, it most commonly occurs in whites.Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis. It became well known in the United States in the 20th century when in 1939 it affected baseball player Lou Gehrig (leading to his death two years later), and later worldwide, following the 1963 diagnosis of then 21 year old cosmologist Stephen Hawking. However, unlike most individuals with ALS, Hawking managed to survive his illness for another 55 years. The first ALS gene was discovered in 1993 while the first animal model was developed in 1994. In 2014, videos of the Ice Bucket Challenge went viral on the Internet and increased public awareness of the condition. Classification ALS is a motor neuron disease, also spelled "motor neurone disease", which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. Other motor neuron diseases include primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy, pseudobulbar palsy, and monomelic amyotrophy (MMA).ALS itself can be classified in a few different ways: by how fast the disease progresses which is related to the age of onset; by whether it is familial or sporadic, and by the region first affected. In about 25% of cases, muscles in the face, mouth, and throat are affected first because motor neurons in the part of the brainstem called the medulla oblongata (formerly called the "bulb") start to die first along with lower motor neurons. This form is called "bulbar-onset ALS". In about 5% of cases, muscles in the trunk of the body are affected first. In most cases the disease spreads and affects other spinal cord regions. A few people with ALS have symptoms that are limited to one spinal cord region for at least 12 to 24 months before spreading to a second region; these regional variants of ALS are associated with a better prognosis. Classical ALS, PLS, and PMA ALS can be classified by the types of motor neurons that are affected. Typical or "classical" ALS involves upper motor neurons in the brain and lower motor neurons in the spinal cord. Primary lateral sclerosis (PLS) involves only upper motor neurons, and progressive muscular atrophy (PMA) involves only lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS.Classic ALS accounts for about 70% of all cases of ALS and can be subdivided into limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the arms and legs and accounts for about two-thirds of all classic ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for the other one-third of cases. Bulbar onset is associated with a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS has a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS has a median survival of 2.6 years and a 10-year survival rate of 13%. A rare variant is respiratory-onset ALS that accounts for about 3% of all cases of ALS, in which the initial symptoms are difficulty breathing (dyspnea) with exertion, at rest, or while lying down (orthopnea). Spinal and bulbar symptoms tend to be mild or absent at the beginning. It is more common in males. Respiratory-onset ALS has the worst prognosis of any ALS variant; in a population-based study, those with respiratory-onset had a median survival of 1.4 years and 0% survival at 10 years.Primary lateral sclerosis (PLS) accounts for about 5% of all cases of ALS and affects upper motor neurons in the arms and legs. However, more than 75% of people with apparent PLS develop lower motor neuron signs within four years of symptom onset, meaning that a definite diagnosis of PLS cannot be made until then. PLS has a better prognosis than classic ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss.Progressive muscular atrophy (PMA) accounts for about 5% of all cases of ALS and affects lower motor neurons in the arms and legs. While PMA is associated with longer survival on average than classic ALS, it still progresses to other spinal cord regions over time, eventually leading to respiratory failure and death. Upper motor neuron signs can develop late in the course of PMA, in which case the diagnosis might be changed to classic ALS. Regional variants Regional variants of ALS have symptoms that are limited to a single spinal cord region for at least a year; they progress more slowly than classic ALS and are associated with longer survival. Examples include flail arm syndrome, flail leg syndrome, and isolated bulbar ALS. Flail arm syndrome and flail leg syndrome are often considered to be regional variants of PMA because they only involve lower motor neurons. Isolated bulbar ALS can involve upper or lower motor neurons. These regional variants of ALS cannot be diagnosed at the onset of symptoms; a failure of the disease to spread to other spinal cord regions for an extended period of time (at least 12 months) must be observed.Flail arm syndrome, also called brachial amyotrophic diplegia, is characterized by lower motor neuron damage in the cervical spinal cord only, leading to gradual onset of weakness in the proximal arm muscles and decreased or absent reflexes. Flail leg syndrome, also called leg amyotrophic diplegia, is characterized by lower motor neuron damage in the lumbosacral spinal cord only, leading to gradual onset of weakness in the legs and decreased or absent reflexes. Isolated bulbar ALS is characterized by upper or lower motor neuron damage in the bulbar region only, leading to gradual onset of difficulty with speech (dysarthria) and swallowing (dysphagia); breathing (respiration) is generally preserved, at least initially. Two small studies have shown that people with isolated bulbar ALS may live longer than people with bulbar-onset ALS. Age of onset ALS can also be classified based on the age of onset. While the peak age of onset is 58 to 63 for sporadic ALS and 47 to 52 for familial ALS, about 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 (juvenile ALS). People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of disease. Juvenile ALS is more likely to be familial than adult-onset ALS; genes known to be associated with juvenile ALS include ALS2, SETX, SPG11, FUS, and SIGMAR1. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is associated with a more rapid functional decline and shorter survival. Signs and symptoms The disorder causes muscle weakness, atrophy, and muscle spasms throughout the body due to the degeneration of the upper motor and lower motor neurons. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel function and the extraocular muscles (the muscles responsible for eye movement) are usually spared until the final stages of the disease.Cognitive or behavioral dysfunction is present in 30–50% of individuals with ALS. Around half of people with ALS will experience mild changes in cognition and behavior, and 10–15% will show signs of frontotemporal dementia (FTD). Most people with ALS who have normal cognition at the time of diagnosis have preserved cognition throughout the course of their disease; the development of cognitive impairment in those with normal cognition at baseline is associated with a worse prognosis. Repeating phrases or gestures, apathy, and loss of inhibition are frequently reported behavioral features of ALS. Language dysfunction, executive dysfunction, and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS; a meta-analysis found no relationship between dysfunction and disease severity. However, cognitive and behavioral dysfunctions have been found to correlate with reduced survival in people with ALS and increased caregiver burden; this may be due in part to deficits in social cognition. About half the people who have ALS experience emotional lability, in which they cry or laugh for no reason; it is more common in those with bulbar-onset ALS.Pain is a symptom experienced by most people with ALS and can take the form of neuropathic pain (pain caused by nerve damage), spasticity, muscle cramps, and nociceptive pain caused by reduced mobility and muscle weakness; examples of nociceptive pain in ALS include contractures (permanent shortening of a muscle or joint), neck pain, back pain, shoulder pain, and pressure ulcers.Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, and taste. Initial symptoms The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a "dropped foot" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock.In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the intercostal muscles that support breathing are affected first.Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex. An abnormal reflex commonly called Babinskis sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). However, twitching is more of a side effect than a diagnostic symptom; it either occurs after or accompanies weakness and atrophy. Progression Although the initial symptoms and rate of progression vary from person to person, the disease eventually spreads to unaffected regions and the affected regions become more affected. Most people eventually are not able to walk or use their hands and arms, lose the ability to speak and swallow food and their own saliva, and begin to lose the ability to cough and to breathe on their own.The rate of progression can be measured using the ALS Functional Rating Scale - Revised (ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability); it is the most commonly used outcome measure in clinical trials and is used by doctors to track disease progression. Though the degree of variability is high and a small percentage of people have a much slower disorder, on average, people with ALS lose about 0.9 FRS points per month. A survey-based study among clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful.Disease progression tends to be slower in people who are younger than 40 at onset, are mildly obese, have symptoms restricted primarily to one limb, and those with primarily upper motor neuron symptoms. Conversely, progression is faster and prognosis poorer in people with bulbar-onset ALS, respiratory-onset ALS and frontotemporal dementia. Late stages Difficulties with chewing and swallowing make eating very difficult and increase the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. The most common cause of death among people with ALS are respiratory failure or pneumonia and most people with ALS die in their own home from the former cause, with their breath stopping while they sleep.Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die between two and four years after the diagnosis. Around half of people with ALS die within 30 months of their symptoms beginning, and about 20% of people with ALS live between five and ten years after symptoms begin. Guitarist Jason Becker has lived since 1989 with the disorder, while cosmologist Stephen Hawking lived for 55 more years following his diagnosis, but they are considered unusual cases. Cause Though the exact cause of ALS is unknown, genetic and environmental factors are thought to be of roughly equal importance. The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. Genetics ALS can be classified as familial or sporadic, depending on whether or not there is a family history of the disease. There is no consensus among neurologists on the exact definition of familial ALS. The strictest definition is that a person with ALS must have two or more first-degree relatives (children, siblings, or parents) who also have ALS. A less strict definition is that a person with ALS must have at least one first-degree or second-degree relative (grandparents, grandchildren, aunts, uncles, nephews, nieces or half-siblings) who also has ALS. Familial ALS is usually said to account for 10% of all cases of ALS, though estimates range from 5% to 20%. Higher estimates use a broader definition of familial ALS and examine the family history of people with ALS more thoroughly.In sporadic ALS, there is no family history of the disease. Sporadic ALS and familial ALS appear identical clinically and pathologically and are similar genetically; about 10% of people with sporadic ALS have mutations in genes that are known to cause familial ALS. In light of these parallels, the term "sporadic ALS" has been criticized as misleading because it implies that cases of sporadic ALS are only caused by environmental factors; the term "isolated ALS" has been suggested as a more accurate alternative.More than 20 genes have been associated with familial ALS, of which four account for the majority of familial cases: C9orf72 (40%), SOD1 (20%), FUS (1–5%), and TARDBP (1–5%). The genetics of familial ALS are better understood than the genetics of sporadic ALS; as of 2016, the known ALS genes explained about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance, meaning that mutations in two or more genes are required to cause disease.ALS and frontotemporal dementia (FTD) are now considered to be part of a common disease spectrum (FTD–ALS) because of genetic, clinical, and pathological similarities. Genetically, C9orf72 repeat expansions account for about 40% of familial ALS and 25% of familial FTD. Clinically, 50% of people with ALS have some cognitive or behavioral impairments and 5–15% have FTD, while 40% of people with FTD have some motor neuron symptoms and 12.5% have ALS. Pathologically, abnormal aggregations of TDP-43 protein are seen in up to 97% of ALS patients and up to 50% of FTD patients. In December 2021 a paper found the TDP-43 proteinopathy is in turn caused by defective cyclophilin A which regulates TARDBP gene expression. Other genes known to cause FTD-ALS include CHCHD10, SQSTM1, and TBK1. Environmental factors Where no family history of the disease is present – around 90% of cases – no cause is known. Possible associations for which evidence is inconclusive include military service and smoking. Although studies on military history and ALS frequency are inconsistent, there is weak evidence for a positive correlation. Various proposed factors include exposure to environmental toxins (inferred from geographical deployment studies), as well as alcohol and tobacco use during military service.A 2016 review of 16 meta-analyses concluded that there was convincing evidence for an association with chronic occupational exposure to lead; suggestive evidence for farming, exposure to heavy metals other than lead, beta-carotene intake, and head injury; and weak evidence for omega-3 fatty acid intake, exposure to extremely low frequency electromagnetic fields, pesticides, and serum uric acid.In a 2017 study by the United States Centers for Disease Control and Prevention analyzing U.S. deaths from 1985 to 2011, occupations correlated with ALS deaths were white collar, such as in management, financial, architectural, computing, legal, and education jobs. Other potential risk factors remain unconfirmed, including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock. There is a tentative association with exposure to various pesticides, including the organochlorine insecticides aldrin, dieldrin, DDT, and toxaphene. Head injury A 2015 review found that moderate to severe traumatic brain injury is a risk factor for ALS, but whether mild traumatic brain injury increases rates was unclear. A 2017 meta-analysis found an association between head injuries and ALS; however, this association disappeared when the authors considered the possibility of reverse causation, which is the idea that head injuries are an early symptom of undiagnosed ALS, rather than the cause of ALS. Physical activity A number of reviews prior to 2021 found no relationship between the amount of physical activity and the risk of developing ALS. A 2009 review found that the evidence for physical activity as a risk factor for ALS was limited, conflicting, and of insufficient quality to come to a firm conclusion. A 2014 review concluded that physical activity in general is not a risk factor for ALS, that soccer and American football are possibly associated with ALS, and that there was not enough evidence to say whether or not physically demanding occupations are associated with ALS. A 2016 review found the evidence inconclusive and noted that differences in study design make it difficult to compare studies, as they do not use the same measures of physical activity or the same diagnostic criteria for ALS. However, research published in 2021 suggested that there was a positive causal relationship between ALS and intense physical exercise in those with a risk genotype. Sports Both football and American football have been identified as risk factors for ALS in several studies, although this association is based on small numbers of ALS cases. A 2012 retrospective cohort study of 3,439 former NFL players found that their risk of dying from neurodegenerative causes was three times higher than the general US population, and their risk of dying from ALS or Alzheimers disease was four times higher. However, this increased risk was calculated on the basis of two deaths from Alzheimers disease and six deaths from ALS out of 334 deaths total in this cohort, meaning that this study does not definitively prove that playing American football is a risk factor for ALS. Some NFL players thought to have died from ALS may have actually had chronic traumatic encephalopathy (CTE), a neurodegenerative disorder associated with multiple head injuries that can present with symptoms that are very similar to ALS.Football was identified as a possible risk factor for ALS in a retrospective cohort study of 24,000 Italian footballers who played between 1960 and 1996. There were 375 deaths in this group, including eight from ALS. Based on this information and the incidence of ALS, it was calculated that the soccer players were 11 times more likely to die from ALS than the general Italian population. However, this calculation has been criticized for relying on an inappropriately low number of expected cases of ALS in the cohort. When the lifetime risk of developing ALS was used to predict the number of expected cases, soccer players were no more likely to die of ALS than the general population. Smoking Smoking is possibly associated with ALS. A 2009 review concluded that smoking was an established risk factor for ALS. A 2010 systematic review and meta-analysis concluded that there was not a strong association between smoking and ALS, but that smoking might be associated with a higher risk of ALS in women. A 2011 meta-analysis concluded that smoking increases the risk of ALS versus never smoking. Among smokers, the younger they started smoking, the more likely they were to get ALS; however, neither the number of years smoked nor the number of cigarettes smoked per day affected their risk of developing ALS. Risk factor ALS can strike at any age, but it increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but the difference will disappear after age 70. It has also been suggested that military veterans are about 1.5 to 2 times more likely to develop ALS, though the reason is unclear. Pathophysiology Neuropathology The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies (abnormal aggregations of protein) known as Bunina bodies in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is TDP-43 protein; however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively. The gross pathology of ALS, which are features of the disease that can be seen with the naked eye, include skeletal muscle atrophy, motor cortex atrophy, sclerosis of the corticospinal and corticobulbar tracts, thinning of the hypoglossal nerves (which control the tongue), and thinning of the anterior roots of the spinal cord. Aside from the death of motor neurons, two other characteristics common to most ALS variants are focal initial pathology, meaning that symptoms start in a single spinal cord region, and progressive continuous spread, meaning that symptoms spread to additional regions over time. Prion-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The glymphatic system may also be involved in the pathogenesis of ALS. Biochemistry It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1, PFN1, and TUBA4A.There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal protein both within and between cells in a prion-like manner. This also leads to decreased levels of RNA-binding protein in the nucleus, which may mean that their target RNA transcripts do not undergo the normal processing. Other RNA metabolism genes associated with ALS include ANG, SETX, and MATR3.C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is
Amyotrophic lateral sclerosis	a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); people with up to 30 repeats are considered normal, while people with hundreds or thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these C9orf72 repeats are deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein. Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal length and fast axonal transport of mitochondrial cargo) has been shown to occur in C9orf72-ALS using human induced pluripotent stem cell (iPSC) technologies coupled with CRISPR/Cas9 gene-editing, and human post-mortem spinal cord tissue examination.Excitotoxicity, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory neurotransmitter glutamate, is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the AMPA receptor) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (EAAT2), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect. Diagnosis No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the person and a series of tests to rule out other diseases. Physicians obtain the persons full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are worsening. A number of biomarkers are being studied for the condition, but so far are not in general medical use. Diagnostic criteria The diagnosis of ALS is based on the El Escorial Revised criteria and the Awaji criteria. The original El Escorial criteria had four levels of diagnostic certainty, based on how many of the four spinal cord regions were involved: bulbar, cervical, thoracic, and lumbar. Definite ALS was defined as upper motor neuron (UMN) and lower motor neuron (LMN) signs in three spinal cord regions, probable ALS as UMN and LMN signs in two regions, possible ALS as UMN and LMN signs in only one region, and suspected ALS as LMN signs only. The El Escorial Revised criteria, also known as the Airlie House criteria, dropped the "suspected ALS" category and added a "laboratory-supported probable ALS" category. The Awaji criteria give abnormal EMG tests the same weight as clinical signs of LMN dysfunction in making the diagnosis of ALS, thus making the "laboratory-supported probable ALS" category unnecessary. The only three categories in the Awaji criteria are definite ALS, probable ALS, and possible ALS.The El Escorial Revised criteria are specific for ALS, which means that someone who meets the criteria is very likely to have ALS; however, they are not especially sensitive for ALS, which means that someone who does not meet the criteria can still have ALS. Their sensitivity is particularly poor in the early stages of ALS. The Awaji criteria have better sensitivity than the El Escorial Revised criteria, especially for bulbar-onset ALS. A 2012 meta-analysis found that the El Escorial Revised criteria had a sensitivity of 62.2%, while the Awaji criteria had a sensitivity of 81.1%; both sets of criteria had a specificity of about 98%. The El Escorial criteria were designed to standardize patient groups for clinical trials but are not as useful in clinical practice; possible ALS as described by the El Escorial criteria is almost always clinically ALS. Differential diagnosis Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging (MRI) is often normal in people with early stage ALS, it can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disc in the neck, syringomyelia, or cervical spondylosis.Based on the persons symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), Lyme disease, and syphilis. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy, and spinal and bulbar muscular atrophy can also mimic certain aspects of the disease and should be considered.ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because the prognosis of ALS and closely related subtypes of motor neurone disease are generally poor, neurologists may carry out investigations to evaluate and exclude other diagnostic possibilities. Disorders of the neuromuscular junction, such as myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome, may also mimic ALS, although this rarely presents diagnostic difficulty over time. Benign fasciculation syndrome and cramp fasciculation syndrome may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time, the distinction will not present any difficulty to the experienced neurologist; where doubt remains, EMG may be helpful.Most cases of ALS, however, are correctly diagnosed, with the error rate of diagnosis in large ALS clinics being less than 10%. One study examined 190 people who met the MND/ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these people (16%) had their diagnosis completely changed during the clinical observation development period. In the same study, three people had a false negative diagnosis of MG, which can mimic ALS and other neurological disorders, leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not. Management There is no cure for ALS. Management focuses on treating symptoms and providing supportive care, with the goal of improving quality of life and prolonging survival. This care is best provided by multidisciplinary teams of healthcare professionals; attending a multidisciplinary ALS clinic is associated with longer survival, fewer hospitalizations, and improved quality of life. Riluzole prolongs survival by about 2–3 months. Edaravone slows functional decline slightly in a small number of people with ALS; it is expensive and must be administered by daily IV infusions that may decrease quality of life. Other medications may be used to manage other symptoms.Non-invasive ventilation (NIV) is the main treatment for respiratory failure in ALS. In people with normal bulbar function, it prolongs survival by about seven months and improves quality of life. One study found that NIV is ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression and functional decline continue. It may decrease the quality of life of people with ALS or their caregivers. Invasive ventilation is more commonly used in Japan than North America or Europe.Physical therapy can promote functional independence through aerobic, range of motion, and stretching exercises. Occupational therapy can assist with activities of daily living through adaptive equipment. Speech therapy can assist people with ALS who have difficulty speaking. Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. The feeding tube is usually inserted by percutaneous endoscopic gastrostomy (PEG). There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life.Palliative care should begin shortly after someone is diagnosed with ALS. Discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Hospice care can improve symptom management at the end of life and increases the likelihood of a peaceful death. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety. Medications Riluzole has been found to modestly prolong survival by about 2–3 months. It may have a greater survival benefit for those with bulbar-onset ALS. It may work by decreasing release of the excitatory neurotransmitter glutamate from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (asthenia). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis.Edaravone has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from oxidative stress. The most common side effects are bruising and gait disturbance. Treatment with edaravone is expensive and requires daily hour-long IV infusions for 10 days in a two-week period.Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Gabapentin, pregabalin, and tricyclic antidepressants (e.g., amitriptyline) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids can be used for nociceptive pain.Depression can be treated with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, while benzodiazepines can be used for anxiety. There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD. Baclofen and tizanidine are the most commonly used oral drugs for treating spasticity; an intrathecal baclofen pump can be used for severe spasticity. Atropine, scopolamine, amitriptyline or glycopyrrolate may be prescribed when people with ALS begin having trouble swallowing their saliva (sialorrhea).A 2017 review concluded that mexiletine was safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016. In a study from 2020, AMX0035, a combination of sodium phenylbutyrate and taurursodiol, was shown to prolong the survival of patients by several months. In March 2022, an independent advisory panel to the FDA voted 6–4 that data was insufficient to show the drug slowed progression of ALS. Breathing support Non-invasive ventilation Non-invasive ventilation (NIV) is the primary treatment for respiratory failure in ALS and was the first treatment shown to improve both survival and quality of life. NIV uses a face or nasal mask connected to a ventilator that provides intermittent positive pressure to support breathing. Continuous positive pressure is not recommended for people with ALS because it makes breathing more difficult. Initially, NIV is used only at night because the first sign of respiratory failure is decreased gas exchange (hypoventilation) during sleep; symptoms associated with this nocturnal hypoventilation include interrupted sleep, anxiety, morning headaches, and daytime fatigue. As the disease progresses, people with ALS develop shortness of breath when lying down, during physical activity or talking, and eventually at rest. Other symptoms include poor concentration, poor memory, confusion, respiratory tract infections, and a weak cough. Respiratory failure is the most common cause of death in ALS.It is important to monitor the respiratory function of people with ALS every three months, because beginning NIV soon after the start of respiratory symptoms is associated with increased survival. This involves asking the person with ALS if they have any respiratory symptoms and measuring their respiratory function. The most commonly used measurement is upright forced vital capacity (FVC), but it is a poor detector of early respiratory failure and is not a good choice for those with bulbar symptoms, as they have difficulty maintaining a tight seal around the mouthpiece. Measuring FVC while the person is lying on their back (supine FVC) is a more accurate measure of diaphragm weakness than upright FVC. Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of diaphragm strength that is not affected by bulbar muscle weakness. If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime blood gas analysis to look for hypoxemia (low oxygen in the blood) and hypercapnia (too much carbon dioxide in the blood). If their daytime blood gas analysis is normal, they should then have nocturnal pulse oximetry to look for hypoxemia during sleep.Non-invasive ventilation prolongs survival longer than riluzole. A 2006 randomized controlled trial found that NIV prolongs survival by about 48 days and improves quality of life; however, it also found that some people with ALS benefit more from this intervention than others. For those with normal or only moderately impaired bulbar function, NIV prolongs survival by about seven months and significantly improves quality of life. For those with poor bulbar function, NIV neither prolongs survival nor improves quality of life, though it does improve some sleep-related symptoms. Despite the clear benefits of NIV, about 25–30% of all people with ALS are unable to tolerate it, especially those with cognitive impairment or bulbar dysfunction. Results from a large 2015 cohort study suggest that NIV may prolong survival in those with bulbar weakness, and so NIV should be offered to all people with ALS, even if it is likely that they will have difficulty tolerating it. Invasive ventilation Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (tracheostomy) and inserting a tube connected to a ventilator. It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use. While invasive ventilation prolongs survival, especially for those younger than 60, it does not treat the underlying neurodegenerative process. The person with ALS will continue to lose motor function, making communication increasingly difficult and sometimes leading to locked-in syndrome, in which they are completely paralyzed except for their eye muscles. About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life but most still consider it to be satisfactory. However, invasive ventilation imposes a heavy burden on caregivers and may decrease their quality of life. Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe. Therapy Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.Occupational therapy and special equipment such as assistive technology can also enhance peoples independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles, because muscle exhaustion can lead to worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. This includes inspiratory muscle training, lung volume recruitment training, and manual assisted cough therapy aimed at increasing respiratory muscle strength as well as increasing survival rates.People with ALS who have difficulty speaking or swallowing may benefit from working with a speech-language pathologist. These health professionals can teach people adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) or low-tech communication techniques such as head mounted laser pointers, alphabet boards or yes/no signals.In a study published in 2022, a completely locked-in ALS patient was fitted with two 64-bit brain implant microarrays in his motor cortex in 2020. Using audible feedback from his own intentional neural firing rates, he was able to communicate letters to form phrases. This is the first example of communication at length with a fully locked-in ALS patient. Nutrition Preventing weight loss and malnutrition in people with ALS improves both survival and quality of life. Weight loss in ALS is caused by muscle wasting due to motor neuron death, increased resting energy expenditure, and decreased food intake. Difficulty swallowing (dysphagia) develops in about 85% of people with ALS at some point over the course of their disease and is a major cause of decreased food intake, leading to malnutrition and weight loss. It is important to regularly assess the weight and swallowing ability of people with ALS. Initially, dysphagia may be managed by dietary changes and modified swallowing techniques. Difficulty swallowing liquids usually develops first and can be managed by switching to thicker liquids like fruit nectar or smoothies, or by adding fluid thickeners to thin fluids like water and coffee. People with ALS should eat soft, moist foods, which tend to be easier to swallow than dry, crumbly, or chewy foods. They should also be instructed on proper head posture during swallowing, which can make swallowing easier. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival.A feeding tube should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. This can take the form of a gastrostomy tube, in which a tube is placed through the wall of the abdomen into the stomach, or a nasogastric tube, in which a tube is placed through the nose and down the esophagus into the stomach. A gastrostomy tube is more appropriate for long-term use than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers. The feeding tube is usually inserted by percutaneous endoscopic gastrostomy (PEG). There is some evidence that a PEG tube should be inserted before vital capacity drops below 50% of expected, as a low vital capacity may be associated with a higher risk of complications. However, a large 2015 study showed that PEG insertion is safe in people with advanced ALS and low vital capacities, as long as they are on NIV during the procedure.There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life by sustaining nutrition and medication intake. This reduces the risk of weight loss and dehydration, and can decrease anxiety from extended mealtimes and decreased oral food intake. End-of-life care Palliative care, which relieves symptoms and improves quality of life without treating the underlying disease, should begin shortly after someone is diagnosed with ALS. Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out advance directives indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes. Late in the disease course, difficulty speaking due to muscle weakness (dysarthria) and cognitive dysfunction may impair their ability to communicate their wishes regarding care. Continued failure to solicit the preferences of the person with ALS may lead to unplanned and potentially unwanted emergency interventions, such as invasive ventilation. If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject.Hospice care, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death. It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, about 0–3% of the time. About 90% of people with ALS die peacefully. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety. Epidemiology ALS is the most common motor neuron disease in adults and the third most common neurodegenerative disease after Alzheimers disease and Parkinsons disease. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women. The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old. The number of new cases is about 0.8 people per 100,000 per year in east Asia and about 0.7 people per 100,000 per year in south Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent. There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America. There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than the rest of the world, including Guam, the Kii Peninsula of Japan, and Western New Guinea. The incidence in these areas has decreased since the 1960s; the cause remains unknown.People of all races and ethnic backgrounds may be affected by ALS, but it is more common in whites than in Africans, Asians, or Hispanics. In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West. Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks. There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is C9orf72, followed by SOD1, TARDBP, and FUS, while the most common ALS gene in Asia is SOD1, followed by FUS, C9orf72, and TARDBP. ALS can affect people at any age, but the peak incidence is between 50 and 75 years and decreases dramatically after 80 years. The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS; alternatively, ALS in the elderly might go undiagnosed because of comorbidities (other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS. In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group. Sporadic ALS usually starts around the ages of 58 to 63 years, while familial ALS starts earlier, usually around 47 to 52 years. The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the worlds population, especially in developing countries. History Descriptions of the disease date back to at least 1824 by Charles Bell. In 1850, François-Amilcar Aran was the first to describe a disorder he named "progressive muscular atrophy", a form of ALS in which only the lower motor neurons are affected. In 1869, the connection between the symptoms and the underlying neurological problems were first described by Jean-Martin Charcot, who initially introduced the term amyotrophic lateral sclerosis in his 1874 paper. Flail arm syndrome, a regional variant of ALS, was first described by Alfred Vulpian in 1886. Flail leg syndrome, another regional variant of ALS, was first described by Pierre Marie and his student Patrikios in 1918.In 1945, American naval doctors reported that ALS was 100 times more prevalent among the Chamorro people of Guam than in the rest of the world. In 1956 the variant of ALS endemic to Guam was named "amyotrophic lateral sclerosis/parkinsonism dementia complex" (ALS/PDC), as it had the typical symptoms of ALS accompanied by parkinsonism-like symptoms; the name in the local language is lytico-bodig disease. Despite a number of genetic and environmental studies, the cause of ALS/PDC remains unknown. Rates peaked in the early 1950s and steadily declined thereafter, and by 1985 the incidence of ALS/PDC in Guam was about the same as the rest of the world.The first gene to be associated with ALS was SOD1, which was identified in 1993. This led to the development of the first animal model of ALS, the transgenic SOD1 mouse, in 1994. In December 1995, riluzole became the first FDA-approved drug for ALS. It was then approved in Europe in 1996 and in Japan in 1998. In 1996, the ALS Functional Rating Scale (ALSFRS) was first published; it was a
Amyotrophic lateral sclerosis	10-item questionnaire that measured the ability of people with ALS to perform activities of daily living. In 1999, the scale was changed to give more weight to respiratory symptoms. The resulting ALS Functional Rating Scale - Revised (ALSFRS-R) is a 12-item questionnaire that replaces the single question about breathing with a question each about dyspnea, orthopnea, and respiratory insufficiency.In 2006, it was discovered that the protein TDP-43 is a major component of the inclusion bodies seen in both ALS and frontotemporal dementia (FTD), which provided evidence that ALS and FTD are part of a common disease spectrum. This led to the discovery in 2008 that mutations in TARDBP, the gene that codes for TDP-43, are a cause of familial ALS. In 2011, noncoding repeat expansions in C9orf72 were found to be a major cause of ALS and FTD. Edaravone was approved to treat ALS in Japan and South Korea in 2015 and in the United States in 2017. As of 2017, it has not been approved to treat ALS in Europe. Diagnostic criteria In the 1950s, electrodiagnostic testing (EMG and NCV) began to be used to evaluate clinically suspected ALS. In 1969 Edward H. Lambert published the first EMG/NCS diagnostic criteria for ALS, consisting of four findings he considered to strongly support the diagnosis. In 1990, the World Federation of Neurology (WFN) held a meeting at El Escorial, Spain, to come up with precise diagnostic criteria for ALS to help standardize clinical trials; the resulting "El Escorial" criteria were published in 1994. In 1998, the WFN held another meeting to revise the criteria at Airlie House in Warrenton, Virginia; the resulting "Airlie House" or "El Escorial Revised" criteria were published in 2000. In 2006, a meeting was held on Awaji Island in Japan to discuss how to use EMG and NCV tests to help diagnose ALS earlier; the resulting "Awaji" criteria were published in 2008. Name Amyotrophic comes from Greek: a- means "no", myo- (from mûs) refers to "muscle", and trophḗ means "nourishment". Therefore, amyotrophy means "muscle malnourishment" or the wasting of muscle tissue. Lateral identifies the areas in a persons spinal cord where the affected motor neurons that control muscle are located. Sclerosis means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.ALS is sometimes referred to as Charcots disease (not to be confused with Charcot–Marie–Tooth disease and Charcot joint disease), because Jean-Martin Charcot was the first to connect the clinical symptoms with the pathology seen at autopsy. The British neurologist Russell Brain coined the term motor neurone disease in 1933 to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease, neurone being a historically incorrect form of neuron. In some countries, especially the United States, ALS is called Lou Gehrigs disease after the American baseball player Lou Gehrig who developed ALS in 1938.In the United States and continental Europe, the term ALS (as well as Lou Gehrigs disease in the US) refers to all forms of the disease, including "classical" ALS, progressive bulbar palsy, progressive muscular atrophy, and primary lateral sclerosis. In the United Kingdom and Australia, the term motor neurone disease refers to all forms of the disease while ALS only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement. Society and culture In August 2014, a challenge went viral online, commonly known as the "ALS Ice Bucket Challenge". Contestants fill a bucket full of ice and water, then state who nominated them to do the challenge, and nominate three other individuals of their choice to take part in it. The contestants then dump the buckets of ice and water onto themselves. However, it can be done in a different order. The contestants then donate at least US$10 (or a similar amount in their local currency) to ALS research at the ALS Association, the ALS Therapy Development Institute, ALS Society of Canada or Motor Neurone Disease Association in the UK. Any contestants who refuse to have the ice and water dumped on them are expected to donate at least US$100 to ALS research. As of July 2015, the Ice Bucket Challenge had raised $115 million for the ALS Association. Many celebrities have taken part in the challenge. The Ice Bucket Challenge was credited with helping to raise funds that contributed to the discovery that the gene NEK1 may potentially contribute to the development for ALS. Research Model organisms Many different organisms are used as models for studying ALS, including Saccharomyces cerevisiae (a species of yeast), Caenorhabditis elegans (a roundworm), Drosophila melanogaster (the common fruit fly), Danio rerio (the zebrafish), Mus musculus (the house mouse), and Rattus norvegicus (the common rat). None of these models perfectly represents ALS in humans, partly because most animal models are based on gene overexpression, meaning that multiple copies of the mutant human gene are inserted into the transgenic model, and partly because the human nervous system is very different from that of other animals.The first animal model for ALS was the SOD1G93A transgenic mouse, which was developed in 1994. It expresses about 20–24 copies of the mutant human SOD1 gene and reproduces most of the clinical and pathological findings seen in ALS. Although there are now over 20 different SOD1 mouse models, the SOD1G93A model remains both the most widely used SOD1 mouse model and the most widely used ALS mouse model overall. Much of the present understanding of ALS pathophysiology came from studying mouse models that overexpress mutant SOD1, especially SOD1G93A mice. However, many drug targets that were shown to be effective in the SOD1G93A transgenic mouse failed in clinical trials in humans; other SOD1 models have had similar problems. Most of these drugs were identified as potentially effective based on a single study in a rodent SOD1 model and then failed in clinical trials in patients who primarily had sporadic ALS. It is thought that these clinical trials failed because SOD1 mutations account for only 2% of all ALS cases and because the pathology of SOD1 ALS is thought to be distinct from all other types of ALS; it lacks the abnormal aggregations of TDP-43 protein or FUS protein seen in nearly all other cases of ALS.As of 2018, there are about 20 TARDBP mouse models, a dozen FUS mouse models, and a number of C9orf72, PFN1, and UBQLN2 mouse models. There are also new methods of developing animal models, including viral transgenesis, in which viruses are used to deliver mutant genes to an animal model, and CRISPR/Cas9, which can be used to give an animal model multiple mutated genes. Both of these methods are faster and cheaper than traditional methods of genetically engineering mice; they also allow scientists to study the effects of a mutation in mice of different genetic backgrounds, which better represents the genetic diversity seen in humans.Cellular models used to study ALS include the yeast Saccharomyces cerevisiae and rat or mouse motor neurons in culture. Small-animal models include the fruit fly, the roundworm C. elegans, and the zebrafish. Of the three, the fruit fly is the most widely used; it has a rapid life-cycle, short lifespan, a sophisticated nervous system, and many genetic tools available. C. elegans has a short life-cycle, is easy to manipulate genetically, and has a simple but well-understood nervous system. The zebrafish has transparent embryos that can be injected with DNA or RNA and has a lifespan of up to two years. Induced pluripotent stem cells (iPSCs) can be used to convert skin fibroblasts into motor neurons. It is now possible to generate iPSCs from people with ALS, which can then be converted into spinal motor neurons, which are useful for studying disease mechanisms and for testing potential drugs for ALS. iPSCs allow sporadic ALS to be modelled, which cannot be done with animal models. Treatments From the 1960s until 2014, about 50 drugs for ALS were tested in randomized controlled trials (RCTs); of these, riluzole was the only one that showed a slight benefit in improving survival. Drugs tested and not shown to be effective in clinical trials in humans include antiviral drugs, anti-excitotoxic drugs, growth factors, neurotrophic factors, anti-inflammatory drugs, antioxidants, anti-apoptotic drugs, and drugs to improve mitochondria function.An analysis of 23 large phase II and phase III RCTs that failed between 2004 and 2014 concluded that there were many potential reasons for their lack of success. These trials in humans went ahead on the basis of positive results in SOD1 transgenic mice, which are not a good animal model for sporadic ALS. In most preclinical studies the SOD1 mice were given the drug during the presymptomatic stage, which makes the results less likely to apply to people with ALS, who begin treatment well after their symptoms begin. Positive results in small phase II studies in humans could also be misleading and lead to failure in phase III trials. Other potential issues included the drug not reaching its intended site of action in the central nervous system and drug interactions between the study drug and riluzole.Repetitive transcranial magnetic stimulation had been studied in ALS in small and poorly designed clinical trials; as of 2013, evidence was insufficient to know whether rTMS is safe or effective for ALS. One 2016 review of stem-cell therapy trials found tentative evidence that intraspinal stem cell implantation was relatively safe and possibly effective. A 2019 Cochrane review of cell-based therapies found that there was insufficient evidence to speculate about efficacy. Masitinib has been approved as an orphan drug in Europe and the United States, with studies ongoing as of 2016. Beta-adrenergic agonist drugs have been proposed as a treatment for their effects on muscle growth and neuroprotection, but research in humans is insufficient to determine their efficacy. Cause With the discovery that TDP-43, FUS, and C9orf72 can cause ALS as well as related forms of frontotemporal dementia (FTD/ALS) there has been intense effort to understand how these mutations cause disease, and whether other protein dysfunction may be important. As of 2013, it appeared that differences in the methylation of arginine residues in FUS protein may be relevant, and methylation status may be a way to distinguish some forms of FTD from ALS. See also Transportin 1 Notes References External links ALS Association Official Website Amyotrophic lateral sclerosis at Curlie
Latah	Latah, from Southeast Asia, is a condition in which abnormal behaviors result from a person experiencing a sudden shock. When surprised, the affected person typically engages in such behaviors as screaming, cursing, dance movements, and uncontrollable laughter, and will typically mimic the words or actions of those around them. Physical symptoms include an increased heart rate and profuse sweating, but no clear physiological source has been identified. Latah is considered a culture-specific startle disorder that was historically regarded as personal difference rather than an illness. Similar conditions have been recorded within other cultures and locations. For example, there are the so-called Jumping Frenchmen of Maine, imu among women of the Ainu people of Japan, mali-mali or silok among Filipinos, and bat-schi (บ้าจี้) among Thais; however, the connection among these syndromes is controversial. Earliest record The earliest mention of latah is in J. R. Logans journal from 1849 when he traveled from Melaka to Naning. Though this is only a possible reference, by the 1860s, latah had been clearly identified in Malaya and Java. Seen first as merely a "cerebral affection", little was understood about latah during this time. OBriens notes from the early– to mid–1880s are the first gathering of information on latah recorded. He observed that latah was more common in women than men, and more likely to occur in more mature, rather than younger, women. From many of the original accounts of European travelers, latah does not seem to have changed much in either affected demographic population nor in symptoms.The British colonial administrator Frank Swettenham wrote about latah in his volume of essays Malay Sketches (1895). Swettenham describes how two policemen from Ambon Island stationed in Selangor in 1874 who were affected with the condition were made the victims of pranks by their colleagues. Signs and symptoms Latah can affect people differently; someone can have a very strong reaction or a slight reaction during a latah episode. Every instance of latah has been acquired over time. Those who are affected, which by an overwhelming number are middle-aged to older women, are not born latah. It typically occurs around the time of menopause. There is a lack of latah in the higher social strata of Malay and Java, which suggests they are more likely to suppress their responses than those who belong to lower social classes. A latah episode occurs after being startled (poking, shouting, something falling). During an episode, a latah person will begin to shout obscenities, imitate words or gestures of those around them or even those on TV, and will often obey any commands given to them – no matter how outrageous or against cultural norms they are. Persons with latah make movements reminiscent of behaviors normally peculiar to certain childhood developmental stages. The person is unlikely to remember anything occurring during the episode. Malay perspective When Malays were asked why they thought that women were more likely to suffer from latah, they responded with the cultural explanation that women have less "semangat" or soul substance. They also said women are simply easier to tease than men, and coupling these two together, latah becomes more readily observable and developed throughout recurrent provocation in women than in men. This also accounts for the higher prevalence of latah in lower status persons, as they are more vulnerable to abuse than others. The Malay also believe women are more susceptible because they lose more blood than men, through menstruation. Some Malay believe that excess tickling of a child will predispose them to latah later in life. In the DSM Latah was included in Diagnostic and Statistical Manual of Mental Disorders (DSM) IV under the "Dissociative Disorder: Not Otherwise Specified" section as a culture–bound syndrome. DSM IV describes latah as a hypersensitivity to sudden fright, often with echopraxia, echolalia, command obedience, and dissociative or trancelike behavior. It mentions other cultures where latah is found, but the only further information the DSM-IV provides is that in Malaysia, it is more often found in middle–aged women. It has been removed from DSM-5, and rather than the DSM-5 expanding upon the DSM IVs list of culture–bound syndromes, it has instead provided cross-lists for more commonly known disorders that a culture-bound syndrome might be classified as. DSM-5 has taken out the "culture–bound syndrome" language and replaced it with more "sensitive" language, and the glossary where the now shortened list of previously recognized culture–bound syndromes is titled "Other Specified" and "Unspecified" dissociative disorders. A more general discussion, involving the formation of a cultural identity, explanation, and assessment, has been added. In popular culture William S. Burroughs mentions latah several times in his 1959 novel Naked Lunch, "a parody of modern mass man under modern conditioning programmes of advertising and public[ly] induced morality", according to Eric Mottram. Burroughs described latah as involving echopraxia, as well as being forcibly induced rather than spontaneously occurring. Latah is also mentioned in Burroughs 1963 novel The Yage Letters. Possible causes The onset of latah is often associated with stress. In a study done by Tanner and Chamberland in 2001, a significant number of research participants had experienced a life stressor (such as a child or husband dying) just before becoming latah. Additionally, a large number of participants from many research studies have reported strange dreams occurring just before the onset of latah. These dreams usually had a sexual element to them, often involving penises. According to Tanner and Chamberland, perhaps the dreams, although with variation, indicate some sort of dysfunction in a specific anatomical area. Exploring this further might lead to more insights as to the cause and/or cure of latah.: 526–529 Osborne (2001) states that latah is a possible emotional outlet in a stifling culture. Winzelers believes that latah is less demeaning for women than it is for men, and that women actually have more freedom in society because they are not held to as strict of standards as men are. He argues that as men age, they become more concerned with personal dignity and poise while women become less so. Because of this, women feel more freedom to engage in latah behavior, while men do not. See also Hyperekplexia Tourette syndrome Tic References Further reading Kenny, MG (1978). "LATAH: The symbolism of a putative mental disorder". Culture, Medicine and Psychiatry. 2 (3): 209–231. doi:10.1007/BF00051005. PMID 710172. S2CID 29736522. Simons, RC (November 2001). "Introduction to Culture-Bound Syndromes". Psychiatric Times. XVIII (11). "Nova et Vetera". British Medical Journal. 1 (2669): 438–46. 24 February 1912. doi:10.1136/bmj.1.2669.438-a. PMC 2345217. PMID 20766030. "Special Correspondence". British Medical Journal. 1 (1423): 763–765. 7 April 1888. doi:10.1136/bmj.1.1423.763. PMC 2197720.
Frasier syndrome	Frasier syndrome is a urogenital anomaly associated with the WT1 (Wilms tumor 1 gene) gene.It was first characterized in 1964. Presentation Both males and females can have Frasier syndrome but their presentations can be different. Affected females usually have normal genitalia and gonads and have only the features of impaired renal function, which may not present until early childhood or even adolescence. Because females do not have all the features of the condition (e.g. gonadal dysgenesis), females are usually given the diagnosis of isolated nephrotic syndrome Medline ref. Frasier syndrome in some infants may therefore go unrecognized until the affected child presents with signs of renal impairment and further testing is undertaken to evaluate the cause. In infants with XY genotype it causes an intersex condition as a result of gonadal dysgenesis. Although males with Frasier syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia may not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The internal reproductive organs (gonads) are typically undeveloped and referred to as streak gonads.Source These abnormal gonads are nonfunctional and often become cancerous, so they are usually removed surgically early in life. Renal features of the condition include progressive glomerulonephropathy (focal segmental glomerulosclerosis). Patients are also at increased risk of genito-urinary tumors (usually gonadoblastoma).The glomerulonephropathy presents later than in Denys-Drash syndrome, and the tumour risk phenotype is different; whilst Denys-Drash syndrome is associated with Wilms tumour, Frasier syndrome is associated with gonadoblastoma. Differentiating between the two syndromes can be challenging. Genetics The WT1 gene exists on chromosome 11 (at 11p13), and codes for a four zinc finger transcription factor. Its role as a transcription factor is related to proper kidney and gonadal development. The link between kidney and gonadal development and WT1 was highlighted in past studies looking at the related Denys-Drash syndrome. Results of various investigations identified the loss of function of WT1 to be a prerequisite of Wilms tumour development, and also a key trait of individuals with genital abnormalities.Mutations responsible for Frasier syndrome predominantly occur in intron 9 of the WT1 gene, specifically nucleotide substitutions that influence an intron splice site. Mutations in this region proved for the absence of three amino acids—K T S—between the third and fourth WT1 zinc fingers. Referring to the autosomal dominant expressive nature of this disease, it is only necessary for an individual to have one complement of the mutated intronic sequence to appear affected. Differing from the similar Denys-Drash syndrome, where a mutated form of the WT1 protein exists, Frasier syndrome expression works solely on the existence of a changed ratio of KTS isoforms: normal WT1 proteins including the KTS site (+KTS), and mutated, shortened proteins lacking the KTS site (–KTS). Through alternative splicing, a specific ratio of the two isoforms normally exists, though the mutation in the intron 9 splice site severely lowers levels of the +KTS isoform; this leads to Frasier syndrome. Inheritance pattern Frasier syndrome is inherited in an autosomal dominant fashion, indicating the need for only one mutated allele in a cell to lead to expression of the disease. Mutations predominantly occur de novo, allowing for expression in an individual that has no family history of it. The mutations occur during gamete formation or early in embryogenesis. Diagnosis Genetic screening of children experiencing amenorrhea and steroid resistant nephrotic syndrome can diagnose Fraiser syndrome early, although the slow progression of renal failure makes diagnosis difficult. Treatment Reconstructive surgery is an option for this condition References == External links ==
Stress ulcer	A stress ulcer is a single or multiple mucosal defect which can become complicated by upper gastrointestinal bleeding or physiologic stress. Ordinary peptic ulcers are found commonly in the gastric antrum and the duodenum whereas stress ulcers are found commonly in fundic mucosa and can be located anywhere within the stomach and proximal duodenum. Signs and symptoms Stress ulcers, as defined by overt bleeding and hemodynamic instability, decreased hemoglobin, and/or need for transfusion, were seen in 1.5% of patients in the 2252 patients in the Canadian Critical Care Trials group study. People with stress ulcers have a longer ICU length of stay (up to 8 days) and a higher mortality (up to 4 fold) than patients who do not have stress ulceration and bleeding. While the bleeding and transfusions associated with the stress ulcerations contribute to the increased mortality, the contribution of factors like low blood pressure, sepsis, and respiratory failure to the mortality independently of the stress ulceration cannot be ignored. Risk factors Risk factors for stress ulcer formation that have been identified are numerous and varied. However, two landmark studies and one position paper exist that addresses the topic of risk factors for stress ulcer formation: Non-critically ill medical patients with 2 or more of the following: respiratory failure, sepsis, heart failure, hepatic encephalopathy, jaundice, kidney failure, stroke, hypertension, previous gastrointestinal disease and treatment with corticosteroids, NSAIDS, heparin, or warfarin. In surgical critically ill patients, only those patients who are on a mechanical ventilator for more than 48 hours and/or those with a coagulopathy. The American Society of Health-System Pharmacists guideline recommends against the practice of stress ulcer prophylaxis in non-critically ill patients. Mechanisms Location The ulcerations may be superficial and confined to the mucosa, in which case they are more appropriately called erosions, or they may penetrate deeper into the submucosa. The former may cause diffuse mucosal oozing of blood, whereas the latter may erode into a submucosal vessel and produce frank hemorrhage. Lesions The characteristic lesions may be multiple, superficial mucosal erosions similar to erosive gastroduodenitis. Occasionally, there may be a large acute ulcer in the duodenum (Curling’s ulcer).Generally, there are multiple lesions located mainly in the stomach and occasionally in the duodenum. They range in depth from mere shedding of the superficial epithelium (erosion) to deeper lesions that involve the entire mucosal thickness (ulceration). Formation The pathogenic mechanisms are similar to those of erosive gastritis.The pathogenesis of stress ulcer is unclear but probably is related to a reduction in mucosal blood flow or a breakdown in other normal mucosal defense mechanisms in conjunction with the injurious effects of acid and pepsin on the gastroduodenal mucosa. Diagnosis Stress ulcer is suspected when there is upper gastrointestinal bleeding in the appropriate clinical setting, for example, when there is upper gastrointestinal bleeding in elderly patients in a surgical intensive care unit (ICU) with heart and lung disease, or when there is upper gastrointestinal bleeding in patients in a medical ICU who require respirators.Stress ulcer can be diagnosed after the initial management of gastrointestinal bleeding, the diagnosis can be confirmed by upper GI endoscopy. Prevention The need for medications to prevent stress ulcer among those in the intensive care unit is unclear. As of 2014, the quality of the evidence is poor. It is unclear which agent is best or if prevention is needed at all. Benefit may only occur in those who are not being fed. Possible agents include antacids, H2-receptor blockers, sucralfate, and proton pump inhibitors (PPIs). Tentative evidence supports that PPIs may be better than H2 blockers.Concerns with the use of stress ulcer prophylaxis agents include increased rates of pneumonia and Clostridium difficile colitis. Treatment The principles of management are the same as for the chronic ulcer. The steps of management are similar as in erosive gastritis.Endoscopic means of treating stress ulceration may be ineffective and operation required. It is believed that shunting blood away from the mucosa makes the mucous membrane ischaemic and more susceptible to injury.Treatment of stress ulceration usually begins with prevention. Careful attention to respiratory status, acid-base balance, and treatment of other illnesses help prevent the conditions under which stress ulcers occur. Patients who develop stress ulcers typically do not secrete large quantities of gastric acid; however, acid does appear to be involved in the pathogenesis of the lesions. Thus it is reasonable either to neutralize acid or to inhibit its secretion in patients at high risk.In case of severe hemorrhagic or erosive gastritis and stress ulcers, a combination of antacids and H2-blockers may stop active bleeding and prevent bleeding from happening again. In selected patients, either endoscopic therapy or selective infusion of vasopressin into the left gastric artery may help control the hemorrhage. Epidemiology Among those in the intensive care unit, ulceration resulting in bleeding is very rare. == References ==
Neurodegenerative disease	A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinsons disease, Alzheimers disease, Huntingtons disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people. Specific disorders Alzheimers disease Alzheimers disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe, parietal lobe, and parts of the frontal cortex and cingulate gyrus. It is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimers disease, no effective treatments have been found. However, clinical trials have developed certain compounds that could potentially change the future of Alzheimers disease treatments. Currently, diagnoses of Alzheimers is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimers has a 20% misdiagnosis rate.AD pathology is primarily characterized by the presence of amyloid plaques and neurofibrillary tangles. Plaques are made up of small peptides, typically 39–43 amino acids in length, called amyloid beta (also written as A-beta or Aβ). Amyloid beta is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neurons membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase. One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into the dense extracellular amyloid plaques. Parkinsons disease Parkinsons disease (PD) is the second most common neurodegenerative disorder. It typically manifests as bradykinesia, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. PD is primarily characterized by death of dopaminergic neurons in the substantia nigra, a region of the midbrain. The cause of this selective cell death is unknown. Notably, alpha-synuclein-ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. It is thought that defects in protein transport machinery and regulation, such as RAB1, may play a role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinsons disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinsons disease mechanism.The main known risk factor is age. Mutations in genes such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and tau protein (MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinsons disease (PD), however, some neurologists question its efficacy. This assessment method is a source of controversy among medical professionals. The gut microbiome might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment. Huntingtons disease Huntingtons disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin gene (HTT). HD is characterized by loss of medium spiny neurons and astrogliosis. The first brain region to be substantially affected is the striatum, followed by degeneration of the frontal and temporal cortices. The striatums subthalamic nuclei send control signals to the globus pallidus, which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea. Huntingtons disease presents itself later in life even though the proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment.HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as inclusion bodies in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal axonal transport, leading to impaired transport of important cargoes such as BDNF. Huntingtons disease currently has no effective treatments that would modify the disease. Multiple sclerosis Multiple sclerosis (MS) is a chronic debilitating demyelinating disease of the central nervous system, caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which is proposed to be due to the release of antigens such as myelin oligodendrocyte glycoprotein, myelin basic protein, and proteolipid protein, causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and Macrophages to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as a spectrum based on the degree of inflammation, a majority of patients experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of Multiple sclerosis. The inflammatory response contributes to the loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the HLA-DRB1*15:01 allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS. Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) or Lou Gehrigs disease is a disease in which motor neurons are selectively targeted for degeneration. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that negatively impacts the upper motor neurons (UMNs) and lower motor neurons (LMNs). In 1993, missense mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase 1 (SOD1) were discovered in a subsets of patients with familial ALS. This discovery led researchers to focus on unlocking the mechanisms for SOD1-mediated diseases. However, the pathogenic mechanism underlying SOD1 mutant toxicity has yet to be resolved. More recently, TDP-43 and FUS protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 (C9orf72) is thought to be the most common known cause of sporadic ALS. It is diagnosed by skeletal muscle weakness that progresses gradually. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0-32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients.Independent research provided in vitro evidence that the primary cellular sites where SOD1 mutations act are located on astrocytes. Astrocytes then cause the toxic effects on the motor neurons. The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. Batten disease Batten disease is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease is the common name for a group of lysosomal storage disorders known as neuronal ceroid lipofuscinoses (NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, CLN3 disease (juvenile NCL) typically manifests between the ages of 4 to 7. Batten disease is characterized by motor impairment, epilepsy, dementia, vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on a conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite the research process for methods to treat Batten disease. Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD) is a prion disease that is characterized by rapidly progressive dementia. Abnormal proteins called prions aggregate in brain tissue leading to nerve cell death. Prions are misfolded PRNP proteins. They are also infectious. Variant Creutzfeldt–Jakob disease (vCJD) is the infectious form that comes from the meat of a cow that was infected with bovine spongiform encephalopathy, also called mad cow disease. Risk factor The greatest risk factor for neurodegenerative diseases is aging. Mitochondrial DNA mutations as well as oxidative stress both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that DNA damage accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing speed. Mechanisms Genetics Many neurodegenerative diseases are caused by genetic mutations, most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid glutamine. A repeat of CAG results in a polyglutamine (polyQ) tract. Diseases associated with such mutations are known as trinucleotide repeat disorders.Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ studies often use a variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the models of nematode (C. elegans), and fruit fly (Drosophila), mice, and non-human primates.Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including Huntingtons disease and the spinocerebellar ataxias. Epigenetics The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example is FKBP5 gene, which progressively increases its expression with age and has been related to Braak staging and increased tau pathology both in vitro and in mouse models of AD. Protein misfolding Several neurodegenerative diseases are classified as proteopathies as they are associated with the aggregation of misfolded proteins. Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. alpha-synuclein: can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinsons disease, dementia with Lewy bodies, and multiple system atrophy. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC), is found in amyloid plaques in Alzheimers disease. tau: hyperphosphorylated tau protein is the main component of neurofibrillary tangles in Alzheimers disease; tau fibrils are the main component of Pick bodies found in behavioral variant frontotemporal dementia. amyloid beta: the major component of amyloid plaques in Alzheimers disease. prion: main component of prion diseases and transmissible spongiform encephalopathy. Intracellular mechanisms Protein degradation pathways Parkinsons disease and Huntingtons disease are both late-onset and associated with the accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as proteopathies, and they are primarily caused by aggregates in the following structures: cytosol, e.g. Parkinsons and Huntingtons nucleus, e.g. Spinocerebellar ataxia type 1 (SCA1) endoplasmic reticulum (ER), (as seen with neuroserpin mutations that cause familial encephalopathy with neuroserpin inclusion bodies) extracellularly excreted proteins, amyloid-beta in Alzheimers diseaseThere are two main avenues eukaryotic cells use to remove troublesome proteins or organelles: ubiquitin–proteasome: protein ubiquitin along with enzymes is key for the degradation of many proteins that cause proteopathies including polyQ expansions and alpha-synucleins. Research indicates proteasome enzymes may not be able to correctly cleave these irregular proteins, which could possibly result in a more toxic species. This is the primary route cells use to degrade proteins.Decreased proteasome activity is consistent with models in which intracellular protein aggregates form. It is still unknown whether or not these aggregates are a cause or a result of neurodegeneration. autophagy–lysosome pathways: a form of programmed cell death (PCD), this becomes the favorable route when a protein is aggregate-prone meaning it is a poor proteasome substrate. This can be split into two forms of autophagy: macroautophagy and chaperone-mediated autophagy (CMA).macroautophagy is involved with nutrient recycling of macromolecules under conditions of starvation, certain apoptotic pathways, and if absent, leads to the formation of ubiquinated inclusions. Experiments in mice with neuronally confined macroautophagy-gene knockouts develop intraneuronal aggregates leading to neurodegeneration. chaperone-mediated autophagy defects may also lead to neurodegeneration. Research has shown that mutant proteins bind to the CMA-pathway receptors on lysosomal membrane and in doing so block their own degradation as well as the degradation of other substrates. Membrane damage Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles.The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. Mitochondrial dysfunction The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial intermembrane space. Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase. Over production of ROS (oxidative stress) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion, lipid concentration of the mitochondrial membranes, and the mitochondrial permeability transition. Mitochondrial disease leading to neurodegeneration is likely, at least on some level, to involve all of these functions.There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases Alzheimers, Parkinsons, Huntingtons, and amyotrophic lateral sclerosis.Neurons are particularly vulnerable to oxidative damage due to their strong metabolic activity associated with high transcription levels, high oxygen consumption, and weak antioxidant defense. DNA damage The brain metabolizes as much as a fifth of consumed oxygen, and reactive oxygen species produced by oxidative metabolism are a major source of DNA damage in the brain. Damage to a cells DNA is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with a gradual decline in the activities of repair mechanisms, could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia-oculomotor apraxia. Increased oxidative DNA damage in the brain is associated with Alzheimers disease and Parkinsons disease. Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimers disease, amyotrophic lateral sclerosis, ataxia telangiectasia, Cockayne syndrome, Parkinsons disease and xeroderma pigmentosum. Axonal transport Axonal swelling, and axonal spheroids have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles. Axonal transport can be disrupted by a variety of mechanisms including damage to: kinesin and cytoplasmic dynein, microtubules, cargoes, and mitochondria. When axonal transport is severely disrupted a degenerative pathway known as Wallerian-like degeneration is often triggered. Programmed cell death Programmed cell death (PCD) is death of a cell in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinsons disease, amytrophic lateral sclerosis, Alzheimers disease and Huntingtons disease. PCD observed in neurodegenerative diseases may be directly pathogenic; alternatively, PCD may occur in response to other injury or disease processes. Apoptosis (type I) Apoptosis is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death. Extrinsic apoptotic pathways: Occur when factors outside the cell activate cell surface death receptors (e.g., Fas) that result in the activation of caspases-8 or -10. Intrinsic apoptotic pathways: Result from mitochondrial release of cytochrome c or endoplasmic reticulum malfunctions, each leading to the activation of caspase-9. The nucleus and Golgi apparatus are other organelles that have damage sensors, which can lead the cells down apoptotic pathways.Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This activates the effectors that in turn cleave other proteins resulting in apoptotic initiation. Autophagic (type II) Autophagy is a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an autophagosome, which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. Cytoplasmic (type III) PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause necrosis at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis. Transglutaminase Transglutaminases are human enzymes ubiquitously present in the human body and in the brain in particular.The main function of transglutaminases is bind proteins and peptides intra- and intermolecularly, by a type of covalent bonds termed isopeptide bonds, in a reaction termed transamidation or crosslinking.Transglutaminase binding of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption.Most relevant human neurodegenerative diseases share the property of having abnormal structures made up of proteins and peptides.Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In Alzheimers disease, these are amyloid-beta and tau. In Parkinsons disease, it is alpha-synuclein. In Huntingtons disease, it is huntingtin.Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of transglutaminases in vitro or in vivo, that is, they can be bonded by trasglutaminases by covalent bonds to each other and potentially to any other transglutaminase substrate in the brain.Transglutaminase augmented expression: It has been proved that in these neurodegenerative diseases (Alzheimers disease, Parkinsons disease, and Huntingtons disease) the expression of the transglutaminase enzyme is increased.Presence of isopeptide bonds in these structures: The presence of isopeptide bonds (the result of the transglutaminase reaction) have been detected in the abnormal structures that are characteristic of these neurodegenerative diseases.Co-localization: Co-localization of transglutaminase mediated isopeptide bonds with these abnormal structures has been detected in the autopsy of brains of patients with these diseases. Management The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. Animal models in research In the search for effective treatments (as opposed to palliative care), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimers disease, and also phase II clinical trials for use in Huntingtons disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimers disease drug Dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimers disease failed in 2012, effectively ending the development in this indication.In another experiment using a rat model of Alzheimers disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 25–35. This suggests that there could be therapeutic value to PRP-1. Other avenues of investigation Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand.The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimers disease and other conditions; however, more research must be done to prove safety and efficacy in humans.A current therapeutic target for the treatment of Alzheimers disease is the protease β-secretase, which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent the neuronal death that is responsible for the symptoms of Alzheimers disease. See also Amyloid JUNQ and IPOD Neurodegeneration with brain iron accumulation Prevention of dementia == References ==
Moyamoya disease	Moyamoya disease is a disease in which certain arteries in the brain are constricted. Blood flow is blocked by constriction and blood clots (thrombosis). A collateral circulation develops around the blocked vessels to compensate for the blockage, but the collateral vessels are small, weak, and prone to bleeding, aneurysm and thrombosis. On conventional angiography, these collateral vessels have the appearance of a "puff of smoke" (described as "もやもや (moyamoya)" in Japanese).When moyamoya is diagnosed by itself, with no underlying correlational conditions, it is diagnosed as moyamoya disease. This is also the case when the arterial constriction and collateral circulation are bilateral. Moyamoya syndrome is unilateral arterial constriction, or occurs when one of the several specified conditions is also present. This may also be considered as moyamoya being secondary to the primary condition. Mainly, occlusion of the distal internal carotid artery occurs. On angiography, a "puff of smoke" appearance is seen, and the treatment of choice is surgical bypass. Presentation Patients usually present with TIA, ischemic/hemorrhagic stroke, or seizure. The age distribution is bimodal being either young adolescence or mid-forties. Cause About 10% of cases of moyamoya disease are familial, and some cases result from specific genetic mutations. Susceptibility to moyamoya disease-2 (MYMY2; 607151) is caused by variation in the RNF213 gene (613768) on the long arm of chromosome 17 (17q25). Moyamoya disease-5 (MYMY5; 614042) is caused by mutation in the ACTA2 gene (102620) on the long arm of chromosome 10 (10q23.3); and moyamoya disease-6 with achalasia (MYMY6; 615750) is caused by mutation in the GUCY1A3 gene (139396) on the long arm of chromosome 4 (4q32). Loci for the disorder have been mapped to the short arm of chromosome 3 (MYMY1) and the long arm of chromosome 8 (8q23) (MYMY3; 608796). See also MYMY4 (300845), an X-linked recessive syndromic disorder characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism, and linked to q25.3, on chromosome 17.In Japan the overall incidence is higher (0.35 per 100,000). In North America, women in the third or fourth decade of life are most often affected, but the condition may also occur during infancy or childhood. These women frequently experience transient ischaemic attacks (TIA), cerebral hemorrhage, or may not experience any symptoms at all. They have a higher risk of recurrent stroke and may be experiencing a distinct underlying pathophysiology compared to patients from Japan.Moyamoya disease can be either congenital or acquired. Patients with Down syndrome, sickle cell anemia, neurofibromatosis type 1, congenital heart disease, fibromuscular dysplasia, activated protein C resistance, or head trauma can develop moyamoya malformations. It is more common in women than in men, although about a third of those affected are male. Pathophysiology The disease moyamoya, which is a Japanese mimetic word, gets its characteristic name due to the appearance of smoke on relevant angiographs resultant from the tangle of tiny vessels in response to stenosis. This makes the blood leak out of the arteries, causing pressure to the brain and subsequent headaches. Over the last six decades since the disease was first described, pathogenesis of moyamoya disease remained elusive, although the gene ring finger protein 213 (RNF213) has been implicated. In September 2021, a south Indian researcher has proposed a pathbreaking theory on moyamoya pathogenesis. Coined the "Mechano-biological theory", the disease has a multifactorial pathogenesis. The authors provide a tangible explanation of the occurrence of moyamoya phenomenon in the idiopathic and syndromic variants of the disease. In short, the authors report that moyamoya disease likely occurs due to a number of factors (e.g., differences in vascular anatomy) that ultimately contribute to broad cerebral blood vessel occlusion and consequent shifts in vessel connections to try to provide blood for the compromised brain.Once it begins, the vascular occlusion tends to continue despite any known medical management. In some people this leads to transient ischemic attacks or repeated strokes with severe functional impairment or even death. In others, the blockage may not cause any symptoms.The disease causes constrictions primarily in the internal carotid artery, and often extends to the middle and anterior cerebral arteries, branches of the internal carotid artery inside the skull. When the internal carotid artery becomes completely blocked, the fine collateral circulation that it supplies is obliterated. Patients often survive on the collateral circulation from the back (posterior) of the circle of Willis, arising from the basilar artery.The arterial constrictions in moyamoya disease are unlike the constrictions in atherosclerosis. In atherosclerosis, the walls of arteries are damaged, leading to the deposition of fat and immune cells, and ultimately the accumulation of immune cells laden with fat. In moyamoya, the inner layer of the carotid artery proliferates within the arterial lumen. The artery also fills with blood clots, which may cause strokes.Moyamoya disease tends to affect adults in the third to fourth decade of life. In children it tends to cause strokes or seizures. In adults it tends to cause strokes or bleeding. The clinical features are strokes, recurrent transient ischemic attacks (TIAs), sensorimotor paralysis (numbness and paralysis of the extremities), convulsions and/or migraine-like headaches. Moreover, following a stroke, secondary bleeding may occur. Such bleeding, called hemorrhagic strokes, may also stem from rupture of the weak neovascular vessel walls. Diagnosis Cerebral angiography is the gold standard of diagnosing moyamoya disease and its progression. According to Suzukis system, it can be classified into six stages: Stage 1 Narrowing of carotid fork Stage 2 Initiation of the moyamoya and dilatation of intracranial main arteries Stage 3 Intensification of the moyamoya and defects of the anterior cerebral artery and middle cerebral artery Stage 4 Minimization of the moyamoya and defects of the posterior cerebral artery Stage 5 Reduction of the moyamoya and development of external carotid artery collaterals Stage 6 Disappearance of the moyamoya and circulation only via external cerebral artery and vertebral arteryMagnetic resonance angiography (MRA) is also useful in diagnosing the disease with good correlation with Suzukis grading system.Proliferation of smooth muscle cells in the walls of the moyamoya-affected arteries has been found to be representative of the disease. A study of six autopsies of six patients who died from moyamoya disease lead to the finding that there is evidence that supports the theory that there is a thickening, or proliferation, of the innermost layer of the vessels affected by moyamoya. These vessels are the ACA (anterior cerebral artery), MCA (middle cerebral artery), and ICA (internal carotid artery). The occlusion of the ICA results in concomitant diminution of the "puff-of-smoke" collaterals, as they are supplied by the ICA.Often nuclear medicine studies such as SPECT (single photon emission computerized tomography) are used to demonstrate the decreased blood and oxygen supply to areas of the brain involved with moyamoya disease. Conventional angiography provides the conclusive diagnosis of moyamoya disease in most cases and should be performed before any surgical considerations.Darren B. Orbach explains how the disease progresses as well as the role angiography plays in detecting the progression of moyamoya in a short video. In 2019, author and artist Sarah Lippett published a graphic novel about her decade-long struggle to get a diagnosis and treatment for moyamoya disease, called A Puff of Smoke (published with Jonathan Cape). The book was praised in the newspaper The Guardian as a "wonderfully drawn memoir of a serious childhood illness." It was one of the papers "graphic novels of the year" in 2019 and The Observer newspapers graphic novel of the month in November 2019. Associated biomarkers Smith (2015) conducted a study that looked into specific biological markers that correlate to moyamoya disease. Some of the categories of these biomarkers include phenotypes - conditions commonly related to moyamoya, radiographical markers for the diagnosis of moyamoya, and proteins as well as cellular changes that occur in cases of moyamoya.Similar to moyamoya disease, there are conditions that are closely associated with moyamoya disease. Some of the more common medical conditions that are closely associated with moyamoya disease include trisomy 21 (Down Syndrome), sickle cell disease, and neurofibromatosis type 1. There is also evidence that identifies hyperthyroidism and congenital dwarfing syndromes as two of the more loosely associated syndromes that correlate with the possibility of being diagnosed with moyamoya disease later in life.There is also research that has shown that certain radiographic biomarkers that lead to the diagnosis of moyamoya disease have been identified. The specific radiographic markers are now considered an acceptable key component to moyamoya disease and have been added to the International Classification of Diseases (ICD). These biomarkers of moyamoya are "stenosis of the distal ICAs up to and including the bifurcation, along with segments of the proximal ACA and MCA...dilated basal collateral vessels must be present" Some other common findings that have not been added to the classification index of those with moyamoya disease which are found using radiography involve very distinct changes in the vessels of the brain. These changes include newly formed vessels made to compensate for another change noted, ischemia and cerebrovascular reserve, both found on MRI. Functional changes include evidence of ischemia in vessels of the brain (ICA, ACA, MCA, specifically). It is important to also note that the radiographic biomarkers, in order to be classified as moyamoya disease, all findings must be bilateral. If this is not the case and the findings are unilateral, it is diagnosed as moyamoya syndrome.There are also several protein biomarkers that have been linked to the moyamoya disease diagnosis. Although the sample size of the studies performed are small due to the rarity of the disease, the findings are indicative of a correlation between the disease and several specific protein biomarkers. Other studies have confirmed the correlation of moyamoya and adhesion molecule 1 (ICAM-1) being increased as compared to normal vascular function counterparts. Furthermore, it has been concluded that the localization of inflammatory cells suggests that the inflammation stimulus itself may be responsible for the proliferation and occlusion in the ICA, ACA, and MCA found in those with moyamoya disease. Treatment Drugs such as antiplatelet agents (including aspirin) are usually given to prevent clots, but surgery is usually recommended. Because moyamoya tends to affect only the internal carotid artery and nearby sections of the adjacent anterior and middle cerebral arteries, surgeons can direct other arteries, such as the external carotid artery or the superficial temporal artery to replace its circulation. The arteries are either sewn directly into the brain circulation, or placed on the surface of the brain to reestablish new circulation after a few weeks.There are many operations that have been developed for the condition, but currently the most favored are the in-direct procedures EDAS, EMS, and multiple burr holes and the direct procedure STA-MCA. Combined revascularisation procedure, which includes both the direct superficial temporal artery (STA) to middle cerebral artery (MCA) bypass performed with a combination of in-direct procedures, is considered the treatment of choice. Although its efficacy, particularly for hemorrhagic disease, remains uncertain, the procedure is thought to reduce the hemodynamic burden on the engorged collateral blood vessels. Multiple burr holes have been used in frontal and parietal lobes with good neovascularisation achieved.The EDAS (encephaloduroarteriosynangiosis) procedure is a synangiosis procedure that requires dissection of a scalp artery over a course of several centimeters and then making a small temporary opening in the skull directly beneath the artery. The artery is then sutured to a branch of the middle cerebral artery on the surface of the brain and the bone is replaced.In the EMS (encephalomyosynangiosis) procedure, the temporalis muscle, which is in the temple region of the forehead, is dissected and through an opening in the skull placed onto the surface of the brain.In the multiple burr holes procedure, multiple small holes (burr holes) are placed in the skull to allow for growth of new vessels into the brain from the scalp.In the STA-MCA procedure, the scalp artery (superficial temporal artery or STA) is directly sutured to an artery on the surface of the brain (middle cerebral artery or MCA). This procedure is also commonly referred to as an EC-IC (External Carotid-Internal Carotid) bypass.All of these operations have in common the concept of a blood and oxygen "starved" brain reaching out to grasp and develop new and more efficient means of bringing blood to the brain and bypassing the areas of blockage. The modified direct anastomosis and encephalo-myo-arterio-synangiosis play a role in this improvement by increasing cerebral blood flow (CBF) after the operation. A significant correlation is found between the postoperative effect and the stages of preoperative angiograms. It is crucial for surgery that the anesthesiologist have experience in managing children being treated for moyamoya, as the type of anesthesia they require is very different from the standard anesthetic children get for almost any other type of neurosurgical procedure. Prognosis The natural history of this disorder is not well known. The long term outlook for patients with treated moyamoya seems to be good when direct bypass is used. Although symptoms may seem to improve almost immediately after the in-direct EDAS, EMS, and multiple burr holes surgeries, it will take probably 6 to 12 months before new vessels can develop to give a sufficient blood supply. With the direct STA-MCA surgery, increased blood supply is immediate.Once a major stroke or bleeding takes place, even with treatment, the patient may be left with permanent loss of function so it is very important to treat this condition promptly. Research Recent investigations have established that both moyamoya disease and arteriovenous fistulas (AVFs) of the lining of the brain, the dura, are associated with dural angiogenesis. These factors may represent a mechanism for ischemia contributing to the formation of dural AVFs. At least one case of simultaneous unilateral moyamoya syndrome and ipsilateral dural arteriovenous fistula has been reported at the Barrow Neurological Institute. In this case a 44-year-old man presented with headache, tinnitus, and an intraventricular hemorrhage, as seen on computed tomographic scans. Cerebral angiography showed a right moyamoya pattern and an ipsilateral dural AVF fed by branches of the external carotid artery and draining into the transverse sinus. This extremely rare coincidental presentation may have deeper pathogenic implications.The research into the pathogenesis of moyamoya disease has found a breakthrough with the proposal of a "Mechano-biological theory" of pathogenesis of this disease. A research group in southern India have proposed this unifying theory based on computational fluid dynamics studies and longitudinal data. This proposal unifies the pathogenesis of moyamoya disease and moyamoya syndromes described in literature under a single mechanism. References External links moyamoya.eu—International website for information about diagnostics and treatment of moyamoya patients Orphanets disease page on moyamoya disease Moyamoya Disease Portal—Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum (SCTIMST)
Osteopoikilosis	Osteopoikilosis is a benign, autosomal dominant sclerosing dysplasia of bone characterized by the presence of numerous bone islands in the skeleton. Presentation The radiographic appearance of osteopoikilosis on an X-ray is characterized by a pattern of numerous white densities of similar size spread throughout all the bones. This is a systemic condition. It must be differentiated from blastic metastasis, which can also present radiographically as white densities interspersed throughout bone. Blastic metastasis tends to present with larger and more irregular densities in less of a uniform pattern. Another differentiating factor is age, with blastic metastasis mostly affecting older people, and osteopoikilosis being found in people 20 years of age and younger. The distribution is variable, though it does not tend to affect the ribs, spine, or skull. Cause Epidemiology Men and women are affected in equal number, reflecting the fact that osteopoikilosis attacks indiscriminately. Additionally, the disease is often associated with melorheostosis, despite the apparent lack of correlation between melorheostosis and genetic heritability. It has been tied to LEMD3. Buschke–Ollendorff syndrome is a similar condition, which is also associated with LEMD3. See also List of radiographic findings associated with cutaneous conditions References == External links ==
Semantic dementia	Semantic dementia (SD), also known as semantic variant primary progressive aphasia (svPPA), is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. However, the most common presenting symptoms are in the verbal domain (with loss of word meaning). Semantic dementia is a disorder of semantic memory that causes patients to lose the ability to match words or images to their meanings. However, it is fairly rare for patients with semantic dementia to develop category specific impairments, though there have been documented cases of it occurring. Typically, a more generalized semantic impairment results from dimmed semantic representations in the brain.SD is one of the three canonical clinical syndromes associated with frontotemporal lobar degeneration (FTLD), with the other two being frontotemporal dementia and progressive nonfluent aphasia. SD is a clinically defined syndrome but is associated with predominantly temporal lobe atrophy (left greater than right) and hence is sometimes called temporal variant FTLD (tvFTLD). SD is one of the three variants of primary progressive aphasia (PPA), which results from neurodegenerative disorders such as FTLD or Alzheimers disease. It is important to note the distinctions between Alzheimers disease and semantic dementia with regard to types of memory affected. In general, Alzheimers disease is referred to as a disorder affecting mainly episodic memory, defined as the memory related to specific, personal events distinct for each individual. Semantic dementia generally affects semantic memory, which refers to long-term memory that deals with common knowledge and facts. SD was first described by Arnold Pick in 1904 and in modern times was characterized by Professor Elizabeth Warrington in 1975, but it was not given the name semantic dementia until 1989. The clinical and neuropsychological features, and their association with temporal lobe atrophy were described by Professor John Hodges and colleagues in 1992. Presentation The defining characteristic of SD is decreased performance on tasks that require semantic memory. This includes difficulty with naming pictures and objects, single word comprehension, categorizing, and knowing uses and features of objects. SD patients also have difficulty with spontaneous speech creation, using words such as "this" or "things" where more specific and meaningful words can be used. Syntax is spared, and SD patients have the ability to discern syntactic violations and comprehend sentences with minimal lexical demands. SD patients have selectively worse concrete word knowledge and association, but retain knowledge and understanding of abstract words. SD patients are able to retain knowledge of numbers and music, but have more difficulty with concrete concepts with visual associations. Impairments of processing of phonemic structure and prosodic predictability have also been observed. Genetics The majority of SD patients have ubiquitin-positive, TDP-43 positive, tau-negative inclusions, although other pathologies have been described more infrequently, namely tau-positive Picks disease and Alzheimers pathology. Of all the FTLD syndromes, SD is least likely to run in families and is usually sporadic. Alzheimers Disease and Semantic Dementia Alzheimers disease is related to semantic dementia, which both have similar symptoms. The main difference between the two being that Alzheimers is categorized by atrophy to both sides of the brain while semantic dementia is categorized by loss of brain tissue in the front portion of the left temporal lobe. With Alzheimers disease in particular, interactions with semantic memory produce different patterns in deficits between patients and categories over time which is caused by distorted representations in the brain. For example, in the initial onset of Alzheimers disease, patients have mild difficulty with the artifacts category. As the disease progresses, the category specific semantic deficits progress as well, and patients see a more concrete deficit with natural categories. In other words, the deficit tends to be worse with living things as opposed to non-living things. Diagnosis SD patients generally have difficulty generating familiar words or recognizing familiar objects and faces. Clinical signs include fluent aphasia, anomia, impaired comprehension of word meaning, and associative visual agnosia (inability to match semantically related pictures or objects). As the disease progresses, behavioral and personality changes are often seen similar to those seen in frontotemporal dementia.SD patients perform poorly on tests of semantic knowledge. Published tests include both verbal and non-verbal tasks, e.g., The Warrington Concrete and Abstract Word Synonym Test, and The Pyramids and Palm Trees task. Testing also reveals deficits in picture naming (e.g. "dog" for a picture of a hippopotamus) and decreased category fluency. The question "What is a Stapler?" has been used as a primary diagnostic technique for discerning how SD patients understand word meaning.Speech of SD patients is marked by word-finding pauses, reduced frequency of content words, semantic paraphasias, circumlocutions, increased ratios of verbs to nouns, increased numbers of adverbs, and multiple repeats.SD patients sometimes show symptoms of surface dyslexia, a relatively selective impairment in reading low-frequency words with exceptional or atypical spelling-to-sound correspondences.It is currently unknown why semantic memory is impaired and semantic knowledge deteriorates in SD patients, though the cause may be due to damage to an amodal semantic system. This theory is supported by the atrophy of the anterior temporal lobe, which is believed to contain a component of the semantic system that integrates conceptual information. Others hypothesize that the damage is predominantly to the ventral temporal cortex, since SD patients remember numbers and music, but have trouble associating visual cues to concrete words.Due to the variety of symptoms dementia patients present, it becomes more difficult to assess semantic memory capability especially with regard to musical elements. In order to circumvent the explicit verbal learning tests for dementia, semantic melodic matching is a useful technique for detecting the semantic memory of semantic dementia patients. Moreover, it is important to maintain that these tests must be compared to nonmusical domain tests, as music cognition is not often measured in semantic dementia patients (less data available). Physical changes Structural and functional MRI imaging show a characteristic pattern of atrophy in the temporal lobes (predominantly on the left), with inferior greater than superior involvement and anterior temporal lobe atrophy greater than posterior. This distinguishes it from Alzheimers disease. Meta-analyses on MRI and FDG-PET studies confirmed these findings by identifying alterations in the inferior temporal poles and amygdalae as the hotspots of disease - brain regions that have been discussed in the context of conceptual knowledge, semantic information processing, and social cognition. Based on these imaging methods, semantic dementia can be regionally dissociated from the other subtypes of frontotemporal lobar degeneration, frontotemporal dementia, and progressive nonfluent aphasia.Selective hypometabolism of glucose has been observed in the anterior temporal lobe, as well as the medial temporal lobe and limbic areas.Damage to white matter tracts connecting the anterior temporal cortex to the inferior longitudinal, arcuate, and uncinate fasciculi, which are regions of the language network, is also seen using diffusion tensor imaging. Imaging also shows the integrity of the axonal connections from the anterior temporal cortex to frontal and posterior associative areas to be altered.Functional abnormalities have also been observed in hippocampal structures, the ventromedial prefrontal cortex, and the cingulate cortex. Memory in dementia: musical objects, musical concepts, and semantic memory Melodies are a key aspect of musical objects that are thought to form the contents of semantic memory for music. Melodies are defined as familiar tunes that become associated with musical or extra musical meaning. Using familiar songs, such as Christmas carols, were used to test whether SD patients were able to recognize the tones and melodies of the songs if the patients were just given the words of the song. In the analysis of semantic memory using melodies as stimuli, the contents of semantic memory can include many other aspects aside from recognition of the melody, such as the general information about the music (composer, genre, year of release). Results have shown that musicians who have semantic dementia are able to identify and recognize certain melodic tones.Further exploring the tests of music and semantic memory, results of a study that centered on the comprehension of emotion in music indicated that Alzheimers Disease (AD) patients retained the ability to discern emotions from a song while non-AD degenerative disease patients, such as those with semantic dementia (SD), show impaired comprehension of these emotions. Moreover, several dementia patients, all with varied musical experience and knowledge, all demonstrated an understanding of the fundamental governing rules of western music. Essentially, it was found that superordinate knowledge of music, such as the rules of composition, may be more robust than knowledge of specific music.Regarding the neurobiological correlates for this study, it was determined, via lesion studies, that bilateral (but especially the left-side of the brain) fronto-temporoparietal areas are significant in the associative processing of melodies. Based on the data of imaging studies that looked at the localization of processing melodies, it can be inferred that the anatomical location of the processes in consistent with the findings that some SD patients have intact melody recognition. Additionally, the neurobiological basis for musical emotion identification implicated the limbic and paralimbic structures in this process. Overall, the results of these studies suggest that the neurobiological basis of musical semantic memory is bilaterally located in the cerebral hemispheres, likely around the fronto-temporal areas of the brain. Unfortunately, due to the lack of studies studying musical semantic memory, conclusions cannot be more specific. Treatment There is currently no known curative treatment for SD. The average duration of illness is 8–10 years, and its progression cannot be slowed. Progression of SD can lead to behavioral and social difficulties, thus supportive care is essential for improving quality of life in SD patients as they grow more incomprehensible. Continuous practice in lexical learning has been shown to improve semantic memory in SD patients. No preventative measures for SD are recognized. References Reference 20: Rohani Omar, Julia C. Halistone, and Jason D. Warren, "Semantic Memory for Music in Dementia," Music Perception 29, no. 5 (June 2012):, doi:10.1525/mp.2012.29.5.467.Reference 21:Lise Gagnon, Isabelle Peretz, and Tamàs Fülöp, "Musical structural determinants of emotional judgments in dementia of the Alzheimer type.," Neuropsychology 23, no. 1 (2009): doi:10.1037/a0013790.Reference 22: J. C. Hailstone, R. Omar, and J. D. Warren, "Relatively preserved knowledge of music in semantic dementia," Journal of Neurology, Neurosurgery & Psychiatry 80, no. 7 (2009): doi:10.1136/jnnp.2008.153130. Further reading Gliebus, G. (March 2010). "Primary progressive aphasia: clinical, imaging, and neuropathological findings". Am J Alzheimers Dis Other Demen. 25 (2): 125–7. doi:10.1177/1533317509356691. PMID 20124255. S2CID 29195502. Henry, M.L.; Beeson, P.M.; Rapcsak, S.Z. (February 2008). "Treatment for anomia in semantic dementia". Semin Speech Lang. 29 (1): 60–70. doi:10.1055/s-2008-1061625. PMC 2699352. PMID 18348092. Henry, M.L.; Gorno-Tempini, M.L. (December 2010). "The logopenic variant of primary progressive aphasia". Current Opinion in Neurology. 23 (6): 633–7. doi:10.1097/WCO.0b013e32833fb93e. PMC 3201824. PMID 20852419. Reilly, J.; Rodriguez, A.D.; Lamy, M.; Neils-Strunjas, J. (2010). "Cognition, language, and clinical pathological features of non-Alzheimers dementias: an overview". J Commun Disord. 43 (5): 438–52. doi:10.1016/j.jcomdis.2010.04.011. PMC 2922444. PMID 20493496. Rohrer, J.D.; Knight, W.D.; Warren, J.E.; Fox, N.C.; Rossor, M.N.; Warren, J.D. (January 2008). "Word-finding difficulty: a clinical analysis of the progressive aphasias". Brain. 131 (Pt 1): 8–38. doi:10.1093/brain/awm251. PMC 2373641. PMID 17947337. == External links ==
Ischiopagi	Ischiopagi comes from the Greek word ischio- meaning hip (ilium) and -pagus meaning fixed or united. It is the medical term used for conjoined twins (Class V) who are united at the pelvis. The twins are classically joined with the vertebral axis at 180°. However, the most frequent cases usually structures the ischiopagus twins with two separate spines forming a lateral angle smaller than 90°. The conjoined twins usually have four arms; two, three or four legs; and typically one external genitalia and anus.It is mostly confused with pygopagus where the twins are joined dorsally at the buttocks facing away from each other, whereas ischiopagus twins are joined ventrally and caudally at the sacrum and coccyx. Parapagus is also similar to ischiopagus; however, parapagus twins are joined side-by-side whereas ischiopagus twins typically have spines connected at a 180° angle, facing away from one another. Classification Ischiopagus Dipus: This is the rarest variety with the twins sharing two legs with no lower extremities on one side. Ischiopagus Tripus: This is the most common variety. These twins share three legs, the third leg is often two fused legs, or is non-functioning. The twins also usually share only one set of external genitalia. Ischiopagus Tetrapus/Quadripus: This variety has the twins at a symmetrical continuous longitudinal axis with their area of union not broken anteriorly. The axes extends in a straight line but in opposite directions. The lower extremities are oriented at right angles to the axes of the thorax and the adjacent limbs near the union of the ischium belong to the opposite twin. Embryology During embryonic development, twins can form from the splitting of a single embryo (monozygotic) which forms identical twins or the twins can arise from separate oocytes in the same menstrual cycle (dizygotic) which forms fraternal twins. Although the latter is more frequent, monozygotic is the reason conjoined twins can develop. In monozygotic twinning for conjoined twins such as ischiopagi, the twins form by the splitting of a bi-laminar embryonic disc after the formation of the inner cell masses. Thus, making the twins occupy the same amnion which can lead to a conjoining of the twins as a result of the twins not separating properly during the twinning process. Separation occurring between the seventh and thirteenth days should result in a monochorionic, monoamniotic identical twins sharing a yolk sac. If separation of the twins occur in the later stages of development prior to the appearance of the primitive streak and axial orientation, then it can be predicted that conjoined twins will develop. The origin of exactly what goes wrong to produce ischiopagus or any conjoined twin is a result by either incomplete fission or double overlapping inducing centers on the same germ disc. Various studies suggest that mechanical disturbances such as shaking of the blastomeres, exposure of the embryo to cold or insufficient oxygen during the early process of cleavage, grafting organizer onto gastrula or half a gastrula together, or constricting the blastula or early gastrula can cause the incomplete separation of monozygotic twins. However, studies have shown that these disturbances must happen at critical times in the pregnancy for the conjoined twins to develop. Complications Conjoined twins are at high risk to being stillborn or dying shortly after birth. In some cases, a healthy twin and a parasitic twin are born. The parasitic twin has no hope for survival and dies and is then surgically separated from its twin. Depending upon how the twins are attached and what is shared among them, complications can arise from surgically separating the live twin from the dead twin. In Ischiopagus cases, the children share a pelvic region along with the gastrointestinal tract and genital region. Ischiopagus twins need reconstructive surgery for the genitals and gastrointestinal tract in order for normal bowel movements and reproductive possibilities in adulthood. For the Ischiopagus twins that both survive from birth, complications and risks also arise. Usually if both twins survive labor, one twin will be healthy and strong, while the other is malnourished and weak. Thus, surgery would have to be planned in advance to understand the best option and how to keep both children alive during surgery as well as afterwards. Treatment Separation is the only treatment for Ischiopagus. The rarity of the condition as well as the challenge it presents in separating the twins has been difficult to understand. In recent years, with advancing medical technology, physicians have been able to successfully separate Ischiopagus twins. However, it depends on the organs shared, how closely joined the twins are, and what risks could rise from separating the twins during surgery. Since Ischiopagus twins usually share a gastrointestinal tract and other organs in the pelvic region, it takes months of planning to decide whether or not separation of the twins outweighs the complications and risks associated with surgery and reconstruction of organs. Surgery to separate conjoined twins has allowed surgeons to be able to study the mechanisms of embryogenesis as well as the physiological consequences of parabiosis.Separating ischiopagus tripus conjoined twins usually leaves the twins with one leg each. Prognosis Depending upon what organs are shared among the twins and if they are surgically separable, usually only one of the twins makes it through the surgery or they both die due to complications either before or during the surgery. Now that successful surgery has been reported and more findings are becoming available due to research and pre-surgery evaluation, better surgery techniques and procedures will be available in the future to help increase the survival rate of ischiopagus twins as well as other conjoined twins. Epidemiology Ischiopagus is a rare anomaly occurring in about 1 in every 100,000 live births and occurring in 1 out of 10 conjoined twin births. Most Ischiopagus cases are common in the areas of India and Africa. Of the varieties of Ischiopagus twins, Ischiopagus Tetrapus is more prevalent, happening in 68.75% of all Ischiopagus cases. Ischiopagus Tripus occurs in 31.25% of cases while Ischiopagus Dipus occurs in only 6.25% of all Ischiopagus cases. == References ==
Tertiary hyperparathyroidism	Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone. Anatomically, these glands are located in the neck, para-lateral to the thyroid gland, which does not have any influence in the production of parathyroid hormone. Parathyroid hormone is released by the parathyroid glands in response to low blood calcium circulation. Persistent low levels of circulating calcium are thought to be the catalyst in the progressive development of adenoma, in the parathyroid glands resulting in primary hyperparathyroidism. While primary hyperparathyroidism is the most common form of this condition, secondary and tertiary are thought to result due to chronic kidney disease (CKD). Estimates of CKD prevalence in the global community range from 11 to 13% which translate to a large portion of the global population at risk of developing tertiary hyperparathyroidism. Tertiary hyperparathyroidism was first described in the late 1960s and had been misdiagnosed as primary prior to this. Unlike primary hyperparathyroidism, the tertiary form presents as a progressive stage of resolved secondary hyperparathyroidism with biochemical hallmarks that include elevated calcium ion levels in the blood, hypercalcemia, along with autonomous production of parathyroid hormone and adenoma in all four parathyroid glands. Upon diagnosis treatment of tertiary hyperparathyroidism usually leads to a surgical intervention. Presentation Symptoms in tertiary hyperparathyroidism are generally those seen in relation to elevated blood calcium levels. Tertiary hyperparathyroidism shares many symptomatic features with that of primary hyperparathyroidism, as the two are defined by hypercalcemia. These symptoms can vary greatly from asymptomatic to conditions leading to decreased quality of life. Non-specific symptoms include feeling tired and thirsty, mood changes including, feeling blue, weak and irritable along with other symptoms like itching, headache, joint pain, forgetfulness and abdominal pain have also been noted. More specific symptoms related to elevated blood calcium and phosphate levels include bone pain or osteodynia and tenderness which are common and related to proximal muscle tenderness. Other signs can include pancreatitis, kidney stones, corneal calcifications, thinning of long bones, and hypodermic calcifications which may be palpable in some patients.Calciphylaxis, though uncommon, can develop in patients with tertiary hyperparathyroidism. The product of elevated calcium and phosphate, forming crystal structures, that are then deposited in blood vessels. These crystals cause an inflammatory response and can lead to the occlusion of smaller vessels. Further complications like secondary infections and necrosis can develop from this and can be fatal for some, making the monitoring of blood calcium and phosphate levels necessary.Conditions due to bone loss such as osteopenia and osteoporosis are common in tertiary hyperparathyroidism along with pathologic fractures. Pseudoclubbing of the digits can also be indicative of a severe tertiary hyperparathyroidism due to excess resorption at the distal phalanges.Diagnosis includes both clinical and laboratory investigations. Radiological investigations include looking for signs of bone loss in both the hands and pelvis which is characteristic of tertiary hyperparathyroidism. Other clinical examination can include grading of muscle weakness, which is done by asking the patient to stand from a seated position with their hands folded across their chest. Laboratory investigations include evaluating blood calcium and alkaline phosphatase, which are always increased in tertiary hyperparathyroidism. Other common results from laboratory investigations would include decreased vitamin D levels, elevated blood parathyroid hormone and hyperphosphatemia. Etiology Hyperparathyroidism, in general, is caused by either tumorous growth in one or more parathyroid glands or a prolonged decrease in blood calcium levels or hypocalcaemia which in turn stimulates the production of parathyroid hormone release from the parathyroid gland. The parathyroid gland is located beside the thyroid gland in the neck, below and in front of the larynx and above the trachea. It is composed of four glands in total that monitor blood calcium levels via the calcium sensing receptors, a g-coupled protein receptor. The parathyroid glands main role is calcium homeostasis. Histologically, these glands are composed of chief cells and oxyphil cells with the chief cell primarily responsible for the storing and release of parathyroid hormone. These cells are arranged in a pseudo-follicular pattern similar to the thyroid follicles. Keratin staining is used to image the parathyroid hormone granules. Parathyroid hormone is responsible for the induction of increased calcium absorption in the gastrointestinal tract or gut and in the kidney. It also induces calcium and phosphate resorption from the bone by osteoclasts. Parathyroid hormone also plays a role in activating vitamin D from its pro form to its active form. Vitamin D is also responsible for increased blood calcium levels and works in conjunction with parathyroid hormone. Vitamin D is also partly responsible for the inhibition of parathyroid hormone release by binding Vitamin D receptors at the parathyroid gland. Tertiary hyperparathyroidism is defined by autonomous release of parathyroid hormone while in a hypercalcaemic state. Unlike primary hyperparathyroidism, hypercalcemia in the tertiary form is thought to be the result of resolution of secondary hyperparathyroidism rather than adenoma formation alone.Many of the mechanisms that drive the formation of tertiary hyperparathyroidism are due to outcomes of secondary hyperparathyroidism and so the tertiary from is said to be a continued progressive hyperparathyroidism. Secondary hyperparathyroidism occurs mainly in those who have chronic kidney disease or vitamin D deficiencies both of which lead to malabsorption of calcium and phosphate leading to decreased blood calcium levels inducing a hyperparathyroidism. Hyperphosphatemia in secondary hyperparathyroidism, due to increased parathyroid hormone, is thought to act directly on parathyroid glands and induce a hyperplasia or increased growth of the chief cells in particular. At the same time the hyperplasic parathyroid glands have reduced fibroblast-growth-factor-23 (FGF-23) and vitamin D receptor expression. FGF-23 is partly responsible for phosphate homeostasis and provides negative feedback to the parathyroid gland as does vitamin D.During prolonged secondary hyperparathyroidism increased blood phosphate levels drive hyperplasia of the parathyroid gland and this acts to reset calcium sensitivity at the calcium sensing receptors leading to tertiary hyperparathyroidism after resolution of the secondary form with the continued release of parathyroid hormone in the presence of hypercalcemia. Risk Factors and genetics An elevated risk of developing tertiary hyperparathyroidism exists when late stage kidney disease is not corrected timely. This is due to a hyperphosphatemia acting directly on the parathyroid glands. Genetically, those who have an X-linked dominant disorder that disrupts phosphate transport at the renal tubules (X-Linked hypophosphatemic rickets) and are receiving oral phosphate treatment have shown to be at high risk of developing tertiary hyperparathyroidism in the absence of secondary hyperparathyroidism. Recurring tertiary hyperparathyroidism is generally seen to be caused by incomplete parathyroidectomy without renal transplant and the risk is increased when the parathyroid tissue left after surgery is that of a nodular type.Other risk factors of tertiary hyperparathyroidism include an elevated risk of developing acute pancreatitis, mainly due to the hypercalcemia associated with the hyperparathyroidism. Other studies have shown a significant increase in the risk of developing malignancies of the urinary tract and renal system with women being more at risk. Though there is some conjecture as to the correlation between hyperparathyroidism and thyroid carcinoma development, there is however a correlation between the two, which is thought to be due to prolonged irradiation of the neck and head for parathyroid adenomas and increased parathyroid hormone.Other studies have found some correlation in the development of renal disease following parathyroidectomy. However, the mechanism for this effect remains unknown. Pathophysiology Tertiary Hyperparathyroidism is almost always related to end stage kidney disease and a secondary hyperparathyroidism. Physiological changes due to the kidney damage adversely affect feedback loops that control secretion of parathyroid hormone. Renal management of phosphate is impaired in secondary hyperparathyroidism which results in hyperphosphatemia.Primary hyperplasia of the parathyroid gland, results from both hypocalcaemia and increased phosphate levels by decreasing expression of calcium sensing receptors and vitamin D receptors at the parathyroid gland. These decreases in receptor expression lead to hyperfunctioning of the parathyroid. Hyperfunction of the parathyroid gland is thought to exacerbate primary hyperplasia which evolves further to a secondary more aggressive hyperplasia. Histologically, these hyperplasic glands can be either diffuse or nodular. Primary hyperplasia, usually resulting in diffuse polyclonal growth is manly related to reversible secondary hyperparathyroidism. Secondary hyperplasia of the parathyroid gland is more often a nodular, monoclonal growth that sustains secondary hyperparathyroidism and is the catalyst in the progression to tertiary hyperparathyroidism. Nodular hyperplastic glands in tertiary hyperparathyroidism are distinctly larger in both absolute size and weight up to 20-40-fold increases have been reported. Parathyroid glands are normally composed of chief cells, adipocytes and scattered oxyphil cells. Chief cells are thought to be responsible for the production, storage and secretion of parathyroid hormone. These cells appear light and dark with a prominent Golgi body and endoplasmic reticulum. In electron micrographs, secretory vesicles can be seen in and around the Golgi and at the cell membrane. These cells also contain prominent cytoplasmic adipose. Upon onset of hyperplasia these cells are described as having a nodular pattern with enlargement of protein synthesis machinery such as the endoplasmic reticulum and Golgi. Increased secretory vesicles are seen and decreased intercellular fat is characteristic. Oxyphil cells also appear hyperplasic however, these cells are much less prominent. Biochemically, there are changes in function between normal and nodular hyperplastic parathyroid glands. These changes involve proto-oncogene expression and activation of proliferative pathways while inactivating apoptotic pathways. In nodular parathyroid tissue increased expression of TGF-a, a growth factor, and EGFR, its receptor, results in aggressive proliferation and further downregulation of vitamin D receptors, which act to suppress hormone secretions. Furthermore, the proliferative marker, Ki67 is seen to be highly expressed in the secondary nodular hyperplastic state. Tumour suppressor genes have also been highlighted as being silenced or degraded in nodular hyperplastic parathyroid tissue. One such gene, p53, has been shown to regulate multiple tumour suppressor pathways and in tumorigenesis can be degraded by b-catenin. This pathway, in some aspect, is mediated by CACYBP, which is highly expressed in nodular parathyroid hyperplasia. Treatment Early pharmaceutical treatment for tertiary hyperparathyroidism may include supplementing vitamin D and the use of cinacalcet. Cinacalcet acts to increase the sensitivity of the calcium sensing receptors to calcium leading to a reduction in parathyroid hormone release, however, its use has limited impact in those with tertiary hyperparathyroidism. These treatments are more likely only transient therapies before parathyroidectomy is performed. Indications for surgery in tertiary hyperparathyroidism commonly involve the development of chronic, severe conditions including osteopenia, persistent severe hypercalcemia, bone pain and pathologic fracture. Other indications include development of conditions such calciphylaxis. Surgical options for tertiary hyperparathyroidism include subtotal parathyroidectomy (three and one half of total tissue) and total parathyroidectomy with autotransplatation of resected tissue. Outcomes from surgery are generally favourable and a return to normalised blood calcium levels and parathyroid function is seen. History In 1962, Dr C.E Dent reported that autonomous hyperparathyroidism may result from malabsorption syndromes and chronic kidney disease. The term tertiary hyperparathyroidism was first used in 1963 by Dr Walter St. Gaur to describe a case reported on at Massachusetts General hospital. This case involved a patient who had presented with autonomous parathyroid adenoma causing hypercalcemia with a background of parathyroid hyperplasia. Further reports were recorded in 1964, 65 and 67 of suspected tertiary hyperparathyroidism.In 1968 Davies, Dent and Watson produced a historic case study where they reviewed 200 cases of previously diagnosed primary hyperparathyroidism and found the majority of these cases should be reclassified as tertiary. These were important findings as it allowed an understanding into distinguishing features of primary, secondary and tertiary hyperparathyroidism which then allows appropriate medical treatment.It is now understood that tertiary hyperparathyroidism is defined as the presence of hypercalcemia, hyperphosphatemia and parathyroid hormone due to terminally biased parathyroid-bone-kidney feedback loop. Although there is still conjecture as to whether tertiary hyperparathyroidism is also due to adenomatous growth or hyperplasia it is clear that tertiary hyperparathyroidism presents with some form of tissue enlargement in all four parathyroid glands. See also Hyperparathyroidism Primary hyperparathyroidism Secondary hyperparathyroidism References == External links ==
Blue rubber bleb nevus syndrome	Blue rubber bleb nevus syndrome is a rare disorder that consists mainly of abnormal blood vessels affecting the skin or internal organs – usually the gastrointestinal tract. The disease is characterized by the presence of fluid-filled blisters (blebs) as visible, circumscribed, chronic lesions (nevi). BRBNS is caused by somatic mutations in the TEK (TIE2) gene. It was described by William Bennett Bean in 1958. Presentation BRBNS is a venous malformation, formerly, though incorrectly, thought to be related to the hemangioma. It sometimes causes serious bleeding. Lesions are most commonly found on the skin and in the small intestine and distal large bowel. The lesions can also be found in the central nervous system, liver, and muscles. It usually presents soon after birth or during early infancy. Causes The cause of blue rubber bleb nevus syndrome is currently unknown. The syndrome is considered sporadic. A patient who is diagnosed with BRBNS likely has a family history of other multifocal venous malformations which are a symptom of the disease. Autosomal inheritance of BRBNS has been found in familial cases associated with chromosome 9p, but the majority of cases are sporadic. The disease correlates with an onset of GI complications. It is reported that GI bleeding is the most common cause of death in most cases. Diagnosis Blue rubber bleb nevus syndrome is difficult to diagnose because of how rare the disease is. Diagnosis is usually based on the presence of cutaneous lesions with or without gastrointestinal bleeding and/or involvement of other organs. Cutaneous angiomas are found on the surface of the skin and from the scalp to the soles of feet. The lesions are rubbery, soft, tender and hemorrhagic, easily compressible and promptly refill after compression. A physical examination is mostly used to diagnosis cutaneous angiomas on the surface of the skin. Endoscopy has been the leading diagnostic tool for diagnosing BRBNS for those who have lesions in the gastrointestinal tract. The GI tract is illuminated and visualized in endoscopy. Endoscopy also allows immediate therapeutic measures like argon plasma, coagulation, laser photocoagulation, sclerotherapy, or band ligation. Besides physical examination and endoscopy, ultrasonography, radiographic images, CT and magnetic resonance imaging are helpful for detection of affected visceral organs. Treatment There are several methods to treat BRBNS, although it is not a curable disease. Treatment depends on the severity and location of affected areas. The cutaneous lesions can be effectively treated by laser, surgical removal, electrodesiccation, cryotherapy, and sclerotherapy. In other cases, iron therapy (such as iron supplementation) and blood transfusions are used to conservatively manage BRBNS because of the amount of blood that is lost from the GI bleeding. It is not necessary to remove the lesions in the gastrointestinal system unless the bleeding leads to anemia and repeated blood transfusions. It is safe to remove GI lesions surgically, but one or more lengthy procedures may be required. If there is a recurrence with new angioma in the gastrointestinal tract, laser-steroid therapy is needed. Treatment is not required for those with skin spots, but some individuals with BRBNS may want treatment for cosmetic reasons or if the affected location causes discomfort or affects normal function. Incidence Blue Rubber Bleb Nevus Syndrome affects males and females in equal numbers. According to a review of literature, 20% of patients with BRBNS were from the United States, 15% from Japan, 9% from Spain, 9% from Germany, 6% from China, and 6% from France; and a lower number of cases from other countries. This indicates that any race can be affected by BRBNS. See also Bart syndrome List of cutaneous conditions References Further reading Bean WB (1958). Vascular spiders and related lesions of the skin. Springfield, Illinois: Charles C.Thomas. pp. 178–85. External links Blue rubber bleb nevus; Bean syndrome at NIHs Office of Rare Diseases

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