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A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...
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Enhanced recovery from chronic ischemic injury by bone marrow cells in a rat model of ischemic stroke.
Yoo, Jongman; Seo, Jin-Ju; Eom, Jang-Hyeon; Hwang, Dong-Youn
Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Thrombolytic drugs effectively treat the very acute stage of stroke, and several neuroprotectants that are designed to treat secondary injury following stroke are being tested in clinical trials. However, these pharmacological approaches primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In recent years, stem cell-mediated regenerative approaches have emerged as promising therapeutic strategies for treating the chronic stage of stroke. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. Our transplantation experiments using BMCs obtained from ischemic donor rats showed functional and structural recovery during the chronic stage of stroke. BMC-mediated neural proliferation was prominent in the brains of rats with chronic stroke, and most of the new cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neural proliferation coincided with a significant reduction (∼50%) in the number of activated microglia, which is consistent with previous reports of enhanced neural proliferation being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic ischemic brain were CD25(+) cells, suggesting that these cells may exert the beneficial effects associated with BMC transplantation. Based on the reported anti-inflammatory role of CD25(+) regulatory T-cells in acute experimental stroke, we propose a working model delineating the positive effects of BMC transplantation during the chronic phase of stroke; infiltrating BMCs (mostly CD25(+) cells) reduce activated microglia, which leads to enhanced neural proliferation and enhanced recovery from neuronal damage in this rat model of chronic stroke. This study provides valuable insights into the effect
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Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.
Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari
Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. PMID:23725345
Capriotti, Teri; Murphy, Teresa
Each year, more than 795,000 people in the United States suffer a stroke and by 2030, it is estimated that 4% of the U.S. population will have had a stroke. Home healthcare clinicians will be increasingly called upon to assist stroke survivors and their caregivers adjust to disability and assist the survivor during their reintegration into the community. Therapeutic modalities are changing with advanced technology. Great strides are being made in the treatment of acute stroke; particularly endovascular interventions. More patients are surviving the acute stroke event and therefore will need to learn how to live with various degrees of disability. It is important for home healthcare clinicians to understand the process from acute event to medical stabilization, and from rehabilitation to long-term adaptation. PMID:27145407
Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke
Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk
Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761
Influence of Kinesitherapy on Gait in Patients with Ischemic Stroke in the Chronic Period
Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Dimitrova, Antoaneta; Grigorova-Petrova, Kristin
AIM: The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on gait in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: The study was conducted with 56 patients with ISChP (duration of the disease up to 1 year). For determining changes in gait before and after the treatment a cadence of gait and maximum movement speed were taken into consideration. To determine the cadence, steps are counted for covering 6 meters and 10 meters respectively. The maximum speed of the gait is determined in m / min by dividing undergone distance (m) and time (min). RESULTS: Patients were found to significantly normalize the parameters of gait. Compared to the initial data, there is a significant reduction in the number of steps on 6 and 10 meters and a tendency to increase the speed of gait, with the significant change during the 1st month with a level of significance of p <0.001. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as exercise program at home, which significantly improved gait cadence and speed of movement in patients with ischemic stroke in the chronic period and is with a supportive prolonged exposure. PMID:27275297
Influence of Kinesitherapy on Balance Reactions in Patients with Ischemic Stroke in the Chronic Period
Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Dimitrova, Antoaneta; Grigorova-Petrova, Kristin
AIM: The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on balance reactions in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: A prospective, multicenter study with 56 patients with ISChP. Evaluation of balance reactions using Berg Balance Scale - BBS, includes implementation of 14 tasks with increasing difficulty reflecting the usual activities of everyday life. The first 5 assignments are used to assess the main balance potential and the remaining 9 (6th to 14th task) include more sophisticated balance tasks. RESULTS: The patients were found with a significant improvement in balance opportunities, according to the scale of Berg. Compared to initial data there is a significant increase in the number of points in the measured indicators for functional and static balance. In absolute terms, positive change is most pronounced during the 1st month with a level of significance of p <0.001. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as adapted exercise program at home, and significantly improved equilibrium reactions in patients with postural disorders because of ischemic stroke and is with a supportive prolonged exposure. PMID:27275294
Imaging acute ischemic stroke.
González, R Gilberto; Schwamm, Lee H
Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672
Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage
Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.
Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730
Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period
Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Grigorova-Petrova, Kristin; Dimitrova, Antoaneta
AIM: This study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on orthostatic reactivity in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: An active orthostatic test is used for the evaluation of the orthostatic reactions. The arterial blood pressure and heart rate were defined in the 10 minutes of supine position, before and after 1, 5 and 10 minutes of active upright position. The orthostatic autoregulation is evaluated four times - at the beginning of the study, on the 10th day, on the 1st month and three months after the start of the KT. The classification by Thulesius was used to separate the patients into two groups depending on the type of their orthostatic reactivity. RESULTS: At the beginning of the study of infringements symptomatic type orthostatic reactivity (SOR) was observed in 24 patients and hypertensive type orthostatic reactivity (HOR) was observed in the remaining 32 patients. Once applied SKTM establish improvement of orthostatic autoregulation for the groups SOR and HOR at the 10th day and the 1st month with a level of significance p <0.05. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as an adapted exercise program at home, has significantly improved the orthostatic reactivity in patients with orthostatic dysregulation due to the ISChP.
Acute Ischemic Stroke Intervention.
Khandelwal, Priyank; Yavagal, Dileep R; Sacco, Ralph L
Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID:27256835
Ischemic Stroke after Heart Transplantation.
Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe
Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504
Ischemic Stroke after Heart Transplantation
Acampa, Maurizio; Lazzerini, Pietro Enea; Guideri, Francesca; Tassi, Rossana; Martini, Giuseppe
Cerebrovascular complications after orthotopic heart transplantation (OHT) are more common in comparison with neurological sequelae subsequent to routine cardiac surgery. Ischemic stroke and transient ischemic attack (TIA) are more common (with an incidence of up to 13%) than intracranial hemorrhage (2.5%). Clinically, ischemic stroke is manifested by the appearance of focal neurologic deficits, although sometimes a stroke may be silent or manifests itself by the appearance of encephalopathy, reflecting a diffuse brain disorder. Ischemic stroke subtypes distribution in perioperative and postoperative period after OHT is very different from classical distribution, with different pathogenic mechanisms. Infact, ischemic stroke may be caused by less common and unusual mechanisms, linked to surgical procedures and to postoperative inflammation, peculiar to this group of patients. However, many strokes (40%) occur without a well-defined etiology (cryptogenic strokes). A silent atrial fibrillation (AF) may play a role in pathogenesis of these strokes and P wave dispersion may represent a predictor of AF. In OHT patients, P wave dispersion correlates with homocysteine plasma levels and hyperhomocysteinemia could play a role in the pathogenesis of these strokes with multiple mechanisms increasing the risk of AF. In conclusion, stroke after heart transplantation represents a complication with considerable impact not only on mortality but also on subsequent poor functional outcome. PMID:26915504
[Cerebrolysin for acute ischemic stroke].
iganshina, L E; Abakumova, T R
The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke. PMID:23805635
Between 2.2% and 17% of all strokes have symptom onset during hospitalization in a patient originally admitted for another diagnosis or procedure. These in-hospital strokes represent a unique population with different risk factors, more mimics, and substantially worsened outcomes compared to community-onset strokes. The fact that these strokes manifest during the acute care hospitalization, in patients with higher rates of thrombolytic contraindications, creates distinct challenges for treatment. However, the best evidence suggests benefit to treating appropriately selected in-hospital ischemic strokes with thrombolysis. Evidence points toward a "quality gap" for in-hospital stroke with longer in-hospital delays to evaluation and treatment, lower rates of evaluation for etiology, and decreased adherence to consensus quality process measures of care. This quality gap for in-hospital stroke represents a focused opportunity for quality improvement. PMID:26288675
Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study
Pelicioni, Maristela C. X.; Novaes, Morgana M.; Peres, Andre S. C.; Lino de Souza, Altay A.; Minelli, Cesar; Fabio, Soraia R. C.; Pontes-Neto, Octavio M.; Santos, Antonio C.; de Araujo, Draulio B.
Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS. PMID:26839716
Arterial ischemic stroke in HIV
Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom
HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505
Growth factors in ischemic stroke
Lanfranconi, S; Locatelli, F; Corti, S; Candelise, L; Comi, G P; Baron, P L; Strazzer, S; Bresolin, N; Bersano, A
Abstract Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects. PMID:20015202
Phytochemicals in Ischemic Stroke.
Kim, Joonki; Fann, David Yang-Wei; Seet, Raymond Chee Seong; Jo, Dong-Gyu; Mattson, Mark P; Arumugam, Thiruma V
Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments for stroke has failed to progress much in over 20 years since the introduction of the thrombolytic drug, recombinant tissue plasminogen activator. These alarming circumstances caused many research groups to search for alternative treatments in the form of neuroprotectants. Here, we consider the potential use of phytochemicals in the treatment of stroke. Their historical use in traditional medicine and their excellent safety profile make phytochemicals attractive for the development of therapeutics in human diseases. Emerging findings suggest that some phytochemicals have the ability to target multiple pathophysiological processes involved in stroke including oxidative stress, inflammation and apoptotic cell death. Furthermore, epidemiological studies suggest that the consumption of plant sources rich in phytochemicals may reduce stroke risk, and so reinforce the possibility of developing preventative or neuroprotectant therapies for stroke. In this review, we describe results of preclinical studies that demonstrate beneficial effects of phytochemicals in experimental models relevant to stroke pathogenesis, and we consider their possible mechanisms of action. PMID:27193940
Intravenous thrombolytics for ischemic stroke.
Barreto, Andrew D
For many decades, intravenous (IV) thrombolytics have been delivered to treat acute thrombosis. Although these medications were originally effective for coronary thrombosis, their mechanisms have proven beneficial for many other disease processes, including ischemic stroke. Treatment paradigms for acute ischemic stroke have largely followed those of cardiology. Specifically, the aim has been to recanalize the occluded artery and to restore perfusion to the brain that remains salvageable. To that end, rapid clot lysis was sought using thrombolytic medicines already proven effective in the coronary arteries. IV-thrombolysis for ischemic stroke began its widespread adoption in the late 1990s after the publication of the National Institute of Neurological Disorders and Stroke study. Since that time, other promising IV-thrombolytics have been developed and tested in human trials, but as of yet, none have been proven better than a placebo. Adjunctive treatments are also being evaluated. The challenge remains balancing reperfusion and salvaging brain tissue with the potential risks of brain hemorrhage. PMID:21638138
Ischemic perinatal stroke: challenge and opportunities.
Raju, Tonse N K
The second highest risk group for developing a cerebral stroke is the perinatal period, generally defined as 20 weeks of gestation through 28th postnatal day of age. In this commentary, a brief overview of ischemic perinatal strokes is presented. Ischemic perinatal stroke (IPS) occurs at a rate of 1 : 2300 to 1 : 5000 births, accounting for 30% of children with hemiplegic cerebral palsy (CP). Thus, IPS is the most common known cause for CP [1-3]. Although they occur frequently, much remains to be studied about perinatal strokes in general and the ischemic variety in particular. PMID:18705894
Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke
Arboix, Adrià
Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516
Management of Acute Hypertensive Response in Patients With Ischemic Stroke.
AlSibai, Ahmad; Qureshi, Adnan I
High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction. PMID:27366297
An overview of antithrombotics in ischemic stroke.
Schweickert, Patricia A; Gaughen, John R; Kreitel, Elizabeth M; Shephard, Timothy J; Solenski, Nina J; Jensen, Mary E
The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke. PMID:27153001
Heart Failure in Acute Ischemic Stroke
Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume
Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at
Stem cell therapy in ischemic stroke
Misra, Vivek; Ritchie, Michael M.; Stone, Laura L.; Low, Walter C.
Objective: Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. Method: We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. Result: The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Conclusions: Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke. PMID:23008400
Neuroprotective Mechanisms of Taurine against Ischemic Stroke
Menzie, Janet; Prentice, Howard; Wu, Jang-Yen
Ischemic stroke exhibits a multiplicity of pathophysiological mechanisms. To address the diverse pathophysiological mechanisms observed in ischemic stroke investigators seek to find therapeutic strategies that are multifaceted in their action by either investigating multipotential compounds or by using a combination of compounds. Taurine, an endogenous amino acid, exhibits a plethora of physiological functions. It exhibits antioxidative properties, stabilizes membrane, functions as an osmoregulator, modulates ionic movements, reduces the level of pro-inflammators, regulates intracellular calcium concentration; all of which contributes to its neuroprotective effect. Data are accumulating that show the neuroprotective mechanisms of taurine against stroke pathophysiology. In this review, we describe the neuroprotective mechanisms employed by taurine against ischemic stroke and its use in clinical trial for ischemic stroke. PMID:24961429
The Ischemic Stroke Genetics Study (ISGS) Protocol
Meschia, James F; Brott, Thomas G; Brown, Robert D; Crook, Richard JP; Frankel, Michael; Hardy, John; Merino, José G; Rich, Stephen S; Silliman, Scott; Worrall, Bradford Burke
Background The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. Methods/Design The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. Discussion The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes. PMID:12848902
Chinese Herbal Products for Ischemic Stroke.
Hung, I-Ling; Hung, Yu-Chiang; Wang, Lin-Yi; Hsu, Sheng-Feng; Chen, Hsuan-Ju; Tseng, Ying-Jung; Kuo, Chun-En; Hu, Wen-Long; Li, Tsai-Chung
Traditional Chinese herbal products (CHPs) have been described in ancient medicine systems as treatments for various stroke-associated ailments. This study is aimed to investigate the prescription patterns and combinations of CHPs for ischemic stroke in Taiwan. Prescriptions of CHPs for ischemic stroke were obtained from the National Health Insurance Research Database (NHIRD) of Taiwan. Every prescription with a leading diagnosis of ischemic stroke made during 2000-2010 was analyzed. Descriptive statistics were applied to the pattern of co-prescriptions. Multiple logistic regression models were used to assess demographic and risk factors that are correlated with CHP use. The dataset of inpatient claims data contained information on 15,896 subjects who experienced ischemic stroke from 2000 to 2010. There was an average of 5.82 CHPs in a single prescription for subjects with ischemic stroke. Bu-yang-huan-wu-tang (BYHWT) (40.32%) was by far the most frequently prescribed formula CHP for ischemic stroke, and the most commonly used combination of two-formula-CHP was BYHWT with Shu-jin-huo-xue-tang (SJHXT) (4.40%). Dan Shen (16.50%) was the most commonly used single CHP for ischemic stroke, and the most commonly used combination of two single CHPs was Shi Chang Pua with Yuan Zhi (4.79%). We found that BYHWT and Dan Shen were the most frequently prescribed formula and single CHP for ischemic stroke, respectively. These results provide information about individualized therapy and may contribute to further pharmacologic experiments and clinical trials. PMID:26477801
Angiotensinogen polymorphism and ischemic stroke risk
Bao, Huan; Hao, Jun-Jie; Yang, Yu-Mei; Xu, Xia-Hong; Wang, Yue; Zuo, Lian; Lu, Jing; Zhang, Jing; Zhang, Yue; Xu, Si-Yi; Wang, Xuan; Li, Ying; Li, Gang
The angiotensinogen M235T polymorphism was associated with ischemic stroke risk. However, the results were controversial. Thus, a meta-analysis was conducted. NCBI, Medline, Web of Science and Embase databases were systematically searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. There was a significant association between angiotensinogen M235T polymorphism and ischemic stroke risk (OR = 1.69; 95% CI, 1.35-2.11; P < 0.001). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with ischemic stroke in Asian (OR = 1.85; 95% CI, 1.45-2.35; P < 0.001). In the age subgroup, we found that angiotensinogen M235T polymorphism could increase both early-onset ischemic stroke risk (OR = 1.88; 95% CI, 1.33-2.43; P < 0.001) and late-onset ischemic stroke risk (OR = 1.20; 95% CI, 1.01-1.39; P = 0.04). This meta-analysis suggested that angiotensinogen M235T polymorphism was associated with ischemic stroke. PMID:26550208
Evolving Treatments for Acute Ischemic Stroke.
Zerna, Charlotte; Hegedus, Janka; Hill, Michael D
The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment. PMID:27126651
Therapeutic hypothermia for acute ischemic stroke.
Froehler, Michael T; Ovbiagele, Bruce
Intravenous recombinant tissue plasminogen activator remains the only US FDA-approved treatment for acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for stroke patients. Although no clinical trials have yet investigated the efficacy of therapeutic hypothermia in focal cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of cardiac arrest and newborns with hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of hypothermia in the treatment of acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of hypothermia, methodologies employed for the induction of hypothermia, results from animal models of cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of hypothermia is key and is best accomplished with a combination of ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including meperidine, buspirone and surface warming. We await the results of clinical trials to determine the utility of therapeutic hypothermia in acute ischemic stroke. If proven efficacious, hypothermia would be a welcome complement to established reperfusion therapies for ischemic stroke patients. PMID:20397832
[Secondary prevention of ischemic non cardioembolic stroke].
Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere
Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. PMID:25771074
Endothelial progenitor cells in acute ischemic stroke
Martí-Fàbregas, Joan; Crespo, Javier; Delgado-Mederos, Raquel; Martínez-Ramírez, Sergi; Peña, Esther; Marín, Rebeca; Dinia, Lavinia; Jiménez-Xarrié, Elena; Fernández-Arcos, Ana; Pérez-Pérez, Jesús; Querol, Luis; Suárez-Calvet, Marc; Badimon, Lina
Objectives The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points. Material and methods We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0–2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry. Results We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes. Conclusions After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months. PMID:24363968
White matter injury in ischemic stroke.
Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong
Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions. PMID:27090751
Flow Augmentation in Acute Ischemic Stroke.
Yadollahikhales, Golnaz; Borhani-Haghighi, Afshin; Torabi-Nami, Mohammad; Edgell, Randall; Cruz-Flores, Salvador
There is an urgent need for additional therapeutic options for acute ischemic stroke considering the major pitfalls of the options available. Herein, we briefly review the role of cerebral blood flow, collaterals, vasoreactivity, and reperfusion injury in acute ischemic stroke. Then, we reviewed pharmacological and interventional measures such as volume expansion and induced hypertension, intra-aortic balloon counterpulsation, partial aortic occlusion, extracranial-intracranial carotid bypass surgery, sphenopalatine ganglion stimulation, and transcranial laser therapy with regard to their effects on flow augmentation and neuroprotection. PMID:25475112
[Therapy of acute ischemic stroke].
Sobesky, J
New diagnostic and therapeutic developments have led to an innovative approach to stroke therapy. The slogan "time is brain" emphasizes that stroke is a medical emergency comparable to myocardial infarction. The stroke unit conception is an evidence based therapy for all stroke patients and improves outcome significantly. The monitoring of vital signs and the management of stroke specific complications are highly effective. Early secondary prophylaxis reduces the risk of recurrence. The effect of CT based thrombolysis within the time window of 4,5 h has been substantiated by current data. Stroke MRI holds the promise for an improved therapy by patient stratification and by opening the time window. Interventional recanalisation, vascular interventions and hemicraniectomy complement the therapeutic options in the acute phase of stroke. PMID:19838656
Risk factors for perioperative ischemic stroke in cardiac surgery
da Costa, Mário Augusto Cray; Gauer, Maria Fernanda; Gomes, Ricardo Zaneti; Schafranski, Marcelo Derbli
Objective The purpose of this study was to evaluate the risk factors for ischemic stroke in patients undergoing cardiac surgery. Methods From January 2010 to December 2012, 519 consecutive patients undergoing cardiac surgery were analyzed prospectively. The sample was divided into two groups: patients with stroke per and postoperative were allocated in Group GS (n=22) and the other patients in the group CCONTROL (n=497). The following variables were compared between the groups: gender, age, carotid stenosis ≥ 70%, diabetes on insulin, chronic obstructive pulmonary disease, peripheral arteriopathy, unstable angina, kidney function, left ventricular function, acute myocardial infarction, pulmonary arterial hypertension, use of cardiopulmonary bypass. Ischemic stroke was defined as symptoms lasting over 24 hours associated with changes in brain computed tomography scan. The variables were compared using Fisher's exact test, Chi square, Student's t-test and logistic regression. Results Stroke occurred in 4.2% of patients and the risk factors statistically significant were: carotid stenosis of 70% or more (P=0.03; OR 5.07; IC 95%: 1.35 to 19.02), diabetes on insulin (P=0.04; OR 2.61; IC 95%: 1.10 to 6.21) and peripheral arteriopathy (P=0.03; OR 2.61; 95% CI: 1.08 to 6.28). Conclusion Risk factors for ischemic stroke were carotid stenosis of 70% or more, diabetes on insulin and peripheral arteriopathy. PMID:26313728
Ischemic Stroke during Pregnancy and Puerperium
Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Padovani, Alessandro; Pezzini, Alessandro
Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy. PMID:21331336
Ischemic stroke: carotid and vertebral artery disease.
Vilela, P; Goulão, A
Ischemic strokes may have distinct aetiologies, including several different intrinsic arterial pathological disorders. The diagnosis and understanding of these arterial diseases is critical for the correct management of stroke as different treatment approaches are undertaken according to the aetiology. Atherosclerosis is by far the most common arterial disease among adults, and other pathological processes include arterial dissection, small vessel disease, inflammatory and non-inflammatory vasculopathy and vasomotor disorders. In children, there are several vasculopathies responsible for vaso-occlusive disease such as sickle-cell anemia, acute regressive angiopathy and Moya-Moya disease, neurofibromatosis, dissections, vasculitis associated with intracranial and systemic infections. An overview of the major carotid and vertebral pathological diseases responsible for ischemic stroke in adults and children, highlighting the accuracy of the different imaging modalities for its diagnosis and the imaging appearance of these diseases, is given. PMID:15657789
Errata Corrige. Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period. http://dx.doi.org/10.3889/oamjms.2015.090
Vasileva, Danche; Lubenova, Daniela; Mihova, Marija; Grigorova-Petrova, Kristin; Dimitrova, Antoaneta
AIM: This study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on orthostatic reactivity in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: An active orthostatic test is used for the evaluation of the orthostatic reactions. The arterial blood pressure and heart rate were defined in the 10 minutes of supine position, before and after 1, 5 and 10 minutes of active upright position. The orthostatic autoregulation is evaluated four times - at the beginning of the study, on the 10th day, on the 1st month and three months after the start of the KT. The classification by Thulesius was used to separate the patients into two groups depending on the type of their orthostatic reactivity. RESULTS: At the beginning of the study of infringements symptomatic type orthostatic reactivity (SOR) was observed in 24 patients and hypertensive type orthostatic reactivity (HOR) was observed in the remaining 32 patients. Once applied SKTM establish improvement of orthostatic autoregulation for the groups SOR and HOR at the 10th day and the 1st month with a level of significance p <0.05. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as an adapted exercise program at home, has significantly improved the orthostatic reactivity in patients with orthostatic dysregulation due to the ISChP.
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke
Lansberg, Maarten G.; O'Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.
Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273
Endovascular treatment of acute ischemic stroke.
Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A
Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469
Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke.
Martynov, Mikhail Yu; Gusev, Eugeny I
Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood-brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142
Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke
Martynov, Mikhail Yu; Gusev, Eugeny I
Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142
Predicting Hemorrhagic Transformation of Acute Ischemic Stroke
Marsh, Elisabeth B.; Llinas, Rafael H.; Schneider, Andrea L.C.; Hillis, Argye E.; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F.
Abstract Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe. The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation. PMID:26765425
Remote ischemic conditioning for acute ischemic stroke: dawn in the darkness.
Pan, Jingrui; Li, Xiangpen; Peng, Ying
Stroke is a leading cause of disability with high morbidity and mortality worldwide. Of all strokes, 87% are ischemic. The only approved treatments for acute ischemic stroke are intravenous thrombolysis with alteplase within 4.5 h and thrombectomy within 8 h after symptom onset, which can be applied to just a few patients. During the past decades, ischemic preconditioning has been widely studied to confirm its neuroprotection against subsequent ischemia/reperfusion injury in the brain, including preconditioning in situ or in a remote organ (such as a limb) before onset of brain ischemia, the latter of which is termed as remote ischemic preconditioning. Because acute stroke is unpredicted, ischemic preconditioning is actually not suitable for clinical application. So remote ischemic conditioning performed during or after the ischemic duration of the brain was then designed to study its neuroprotection alone or in combination with alteplase in animals and patients, which is named as remote ischemic perconditioning or remote ischemic postconditioning. As expected, animal experiments and clinical trials both showed exciting results, indicating that an evolution in the treatment for acute ischemic stroke may not be far away. However, some problems or disputes still exist. This review summarizes the research progress and unresolved issues of remote ischemic conditioning (pre-, per-, and post-conditioning) in treating acute ischemic stroke, with the hope of advancing our understanding of this promising neuroprotective strategy for ischemic stroke in the near future. PMID:26812782
Human Data Supporting Glyburide in Ischemic Stroke.
Sheth, Kevin N; Simard, J Marc; Elm, Jordan; Kronenberg, Golo; Kunte, Hagen; Kimberly, W Taylor
The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative. PMID:26463916
Personalized approach to primary and secondary prevention of ischemic stroke
Primary and secondary prevention of ischemic stroke represents a significant part of stroke management and health care. Although there are official guidelines concerning stroke management, new knowledge are introduced to them with a slight delay. This article provides an overview of current information on primary and secondary prevention of ischemic stroke. It summarizes information especially in the field of cardioembolic stroke, the use of new anticoagulants and the management of carotid stenosis based on the results of recent clinical studies. The optimal approach in stroke management is to follow these recommendations, to know new strategies and to apply an individual personalized approach in our clinical decisions. PMID:24949113
Green Space and Mortality Following Ischemic Stroke
Wilker, Elissa H.; Wu, Chih-Da; McNeely, Eileen; Mostofsky, Elizabeth; Spengler, John; Wellenius, Gregory A.; Mittleman, Murray A.
Background Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival has not been studied. Methods Patients ≥21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and 2008 with acute ischemic stroke were identified. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. Addresses were linked to average Normalized Difference Vegetation Index, distance to roadways with more than 10,000 cars/day, and US census block group. Deaths were identified through June 2012 using the Social Security Death Index. Results There were 929 deaths among 1,645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history, demographic and socioeconomic factors, the hazard ratio for patients living in locations in the highest quartile of green space compared to the lowest quartile was 0.78 (95% Confidence Interval: 0.63 to 0.97) (p-trend=0.009). This association remained statistically significant after adjustment for residential proximity to a high traffic road. Conclusions Residential proximity to green space is associated with higher survival rates after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association, and to better understand the exposure-response relationships and susceptibility factors that may contribute to higher mortality in low green space areas. PMID:24906067
Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke
Hayakawa, Kazuhide; Mishima, Kenichi; Fujiwara, Michihiro
Cannabis contains the psychoactive component delta9-tetrahydrocannabinol (delta9-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta9-THC and other cannabinoid CB1 receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta9-THC also mediates psychological effects through the activation of the CB1 receptor in the central nervous system. In addition to the CB1 receptor agonists, cannabis also contains therapeutically active components which are CB1 receptor independent. Of the CB1 receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB1 receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.
Polygenic risk of ischemic stroke is associated with cognitive ability
Malik, Rainer; Marioni, Riccardo; Campbell, Archie; Seshadri, Sudha; Worrall, Bradford B.; Sudlow, Cathie L.M.; Hayward, Caroline; Bastin, Mark E.; Starr, John M.; Porteous, David J.; Wardlaw, Joanna M.; Deary, Ian J.
Objectives: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). Methods: Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. Results: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = −0.070, p = 1.95 × 10−8). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. Conclusions: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability. PMID:26695942
Sexual dimorphism in ischemic stroke: lessons from the laboratory
Manwani, Bharti; McCullough, Louise D
Ischemic stroke is emerging as a major health problem for elderly women. Women have lower stroke incidence than men until an advanced age, when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women. Experimental models of rodent stroke have replicated this clinical epidemiology, with exacerbated injury in older compared with young female rodents Many of the detrimental effects of aging on ischemic stroke outcome in females can be replicated by ovariectomy, suggesting that hormones such as estrogen play a neuroprotective role. However, emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes, and these effects may be independent of circulating hormone levels. This article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms. PMID:21612353
Premature Cardiac Contractions and Risk of Incident Ischemic Stroke
Ofoma, Uchenna; He, Fan; Shaffer, Michele L.; Naccarelli, Gerard V.; Liao, Duanping
Background The etiologies of ischemic stroke remain undetermined in 15% to 40% of patients. Apart from atrial fibrillation, other arrhythmias are less well-characterized as risk factors. Premature cardiac contractions are known to confer long-term cardiovascular risks, like myocardial infarction. Ischemic stroke as cardiovascular risk outcome remains a topic of interest. We examined the prospective relationships in the Atherosclerosis Risk in Communities (ARIC) study, to determine whether premature atrial (PAC) or ventricular (PVC) contractions are associated with increased risk for incident ischemic stroke. Methods and Results We analyzed 14 493 baseline stroke-free middle-aged individuals in the ARIC public-use data. The presence of PAC or PVC at baseline was assessed from 2-minute electrocardiogram. A physician-panel confirmed and classified all stroke cases. Average follow-up time was 13 years. Proportional hazards models assessed associations between premature contractions and incident stroke. PACs and PVCs were identified in 717 (4.9%) and 793 (5.5%) participants, respectively. In all, 509(3.5%) participants developed ischemic stroke. The hazard ratio (HR) (95% confidence interval [CI]) associated with PVC was 1.77 (1.30, 2.41), attenuated to 1.25 (0.91, 1.71) after adjusting for baseline stroke risk factors. The interaction between PVC and baseline hypertension was marginally significant (P=0.08). Among normotensives, having PVCs was associated with nearly 2-fold increase in the rate of incident ischemic stroke (HR 1.69; 95% CI 1.02, 2.78), adjusting for stroke risk factors. The adjusted risk of ischemic stroke associated with PACs was 1.30 (95% CI 0.92, 1.83). Conclusions Presence of PVCs may indicate an increased risk of ischemic stroke, especially in normotensives. This risk approximates risk of stroke from being black, male, or obese in normotensives from this cohort. PMID:23316293
Therapy Effects of Bone Marrow Stromal Cells on Ischemic Stroke
Ye, Xinchun; Hu, Jinxia; Cui, Guiyun
Stroke is the second most common cause of death and major cause of disability worldwide. Recently, bone marrow stromal cells (BMSCs) have been shown to improve functional outcome after stroke. In this review, we will focus on the protective effects of BMSCs on ischemic brain and the relative molecular mechanisms underlying the protective effects of BMSCs on stroke. PMID:27069533
Sensitivity of the neuroimaging techniques in ischemic stroke.
Smajlović, Dzevdet; Sinanović, Osman
The aim of this study was to investigate and compare the sensitivity and effectiveness of neuroimaging techniques in 190 patients with acute ischemic stroke. The first computed tomography (CT) scan for all patients was performed within the first 12 hours of the stroke symptoms onset. For each patient, between the third and fifth day of the hospitalization, at least one more neuroimaging procedure (CT and/or magnetic resonance imaging--MRI, and/or diffusion weighted imaging--DWI) was done. The CT scan in the first 12 hours of the stroke onset was positive in 32% of the patients; the highest number of the positive findings was in the patients with total anterior circulation infarct (52%). After 48 hours of the stroke onset second CT was positive in 85% (75/89), MRI in 93.5% (115/123), and DWI in 98.8% (79/80) patients. MRI was significantly more sensitive than CT in detection of ischemic lesion (88% vs. 72%, P=0.01), particularly in the patients with lacunar infarcts (75% vs. 50%, P=0.005). In detection of ischemic stroke 48 hours of the stroke onset the slightly higher number of strokes were detected on DWI in comparison with MRI (98.6% vs. 88.7%). According to our results, within the first 12 hours after the stroke onset, CT is reliable only for detection of considerable number of cortical ischemic strokes of the anterior cerebral circulation. After 48 hours from the stroke onset CT, MRI and DWI show high sensitivity in the detection of ischemic lesion of all clinical stroke subtypes. MRI is more sensitive in comparison with CT in detection of ischemic lesion, while DWI does not show dominance in comparison with MRI in identification of ischemic stroke after 48 hours of the symptoms onset. PMID:15628251
The Migraine-Ischemic Stroke Relation in Young Adults
Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro
In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470
The Paradox Role of Regulatory T Cells in Ischemic Stroke
Li, Min; Jiang, Yongjun
The underlying mechanism of ischemic stroke is not completely known. Regulatory T cells (Tregs), a subset of T cells, play a pivotal role in the pathophysiological process of ischemic stroke. However, there is also controversy over the role of Tregs in stroke. Hence, the function of Tregs in ischemic stroke has triggered a heated discussion recently. In this paper, we reviewed the current lines of evidence to describe the full view of Tregs in stroke. We would like to introduce the basic concepts of Tregs and then discuss their paradox function in ischemic stroke. On one side, Tregs could protect brain against ischemic injury via modulating the inflammation process. On the other side, they exaggerated the insult by causing microvascular dysfunction. They also interfered with the neurological function recovery. In addition, the reasons for this paradox role would be discussed in the review and the prospective of the clinical application of Tregs was also included. In conclusion, Tregs contributed to the outcome of ischemic stroke, while more lines of evidence are needed to understand how Tregs regulate the immune system and influence the outcome of stroke. PMID:24288462
Therapeutic hypothermia and ischemic stroke: A literature review
Tahir, Rizwan A.; Pabaney, Aqueel H.
Background: Ischemic stroke is the fifth leading cause of death in the US. Clinical techniques aimed at helping to reduce the morbidity associated with stroke have been studied extensively, including therapeutic hypothermia. In this study, the authors review the literature regarding the role of therapeutic hypothermia in ischemic stroke to appreciate the evolution of hypothermia technology over several decades and to critically analyze several early clinical studies to validate its use in ischemic stroke. Methods: A comprehensive literature search was performed using PubMed and Google Scholar databases. Search terms included "hypothermia and ischemic stroke" and "therapeutic hypothermia." A comprehensive search of the current clinical trials using clinicaltrials.gov was conducted using the keywords "stroke and hypothermia" to evaluate early and ongoing clinical trials utilizing hypothermia in ischemic stroke. Results: A comprehensive review of the evolution of hypothermia in stroke and the current status of this treatment was performed. Clinical studies were critically analyzed to appreciate their strengths and pitfalls. Ongoing and future registered clinical studies were highlighted and analyzed compared to the reported results of previous trials. Conclusion: Although hypothermia has been used for various purposes over several decades, its efficacy in the treatment of ischemic stroke is debatable. Several trials have proven its safety and feasibility; however, more robust, randomized clinical trials with large volumes of patients are needed to fully establish its utility in the clinical setting. PMID:27313963
[Ischemic stroke following a scorpion sting].
Elkhayari, M; Hachimi, A; Ziadi, A; Abdenasser Samkaoui, M
Scorpion envenomation is caused by an accidental scorpion sting. In its severe form, it involves life-threatening respiratory or cardiac damage; it may also cause the neurological severity of systemic manifestations. We report the case of a young 35-year-old woman stung by an Androctonus mauretanicus scorpion, who developed impaired consciousness, hemiplegia and respiratory distress. At admission, the brain computed tomography showed a hypodense area in the right parietal region; the chest radiograph revealed a bilateral alveolar syndrome. Troponin was elevated and hemostasis disorders were present. The clinical course was remarkable: cardiogenic shock with multiple organ failure followed by death on day 3. This case illustrates a rare complication of scorpion envenomation: ischemic stroke due to an undetermined mechanism, which in addition to the cardiac and respiratory injuries, led to the serious complications and fatal outcome. PMID:23648127
Oxidative stress--assassin behind the ischemic stroke.
Pradeep, Hanumanthappa; Diya, Joseph B; Shashikumar, Shivaiah; Rajanikant, Golgodu K
Ischemic stroke is the second leading cause of death and disability worldwide and is associated with significant clinical and socioeconomic implications, emphasizing the need for effective therapies. Several neuroprotective strategies have failed in clinical trials because of poor knowledge of the molecular processes flanked with ischemic stroke. Therefore, uncovering the molecular processes involved in ischemic brain injury is of critical importance. Therapeutic strategies for ischemic stroke remain ineffective, though rapid advances occur in understanding the pathophysiology of the disease. The oxidative stress is one such high-potential phenomenon, the precise role of which needs to be understood during ischemic events. Nevertheless, the studies carried out in preclinical models of ischemic stroke have pointed to the major role of oxidative stress in exacerbating the ischemic injury. Oxidative stress leading to cell death requires generation of free radicals through multiple mechanisms, such as respiratory inhibition, Ca(2+) imbalance, excitotoxicity, reperfusion injury and inflammation. Free radicals are highly reactive to all the molecular targets: lipids, proteins and nucleic acids, modifying their chemical structure and generating oxidation-derived products. This review discusses molecular aspects of oxidative stress in ischemic stroke and catastrophes that set up as an aftermath of the trauma. PMID:23023336
Clinical and morphological correlations in acute ischemic stroke.
Slujitoru, Anca Stefania; Enache, Andreea Lorena; Pintea, Irina Lavinia; Rolea, Elisabeta; Stocheci, Cristina Mariana; Pop, O T; Predescu, Anca
We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made. PMID:23303014
Dimethylarginine levels in cerebrospinal fluid of hyperacute ischemic stroke patients are associated with stroke severity.
Brouns, Raf; Marescau, Bart; Possemiers, Ilse; Sheorajpanday, Rishi; De Deyn, Peter P
We hypothesise that asymmetric and symmetric dimethylarginine (ADMA, SDMA) are released in cerebrospinal fluid (CSF) due to ischemia-induced proteolysis and that CSF dimethylarginines are related to stroke severity. ADMA and SDMA were measured in CSF of 88 patients with ischemic stroke or TIA within 24 h after stroke onset (mean 8.6 h) and in 24 controls. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score at admission. Outcome was evaluated by institutionalization due to stroke and the modified Rankin scale. Dimethylarginine levels were higher in patients with stroke than in TIA patients, who had higher levels than controls and correlated with the NIHSS. Logistic regression analysis confirmed that dimethylarginines were independently associated with stroke severity. The SDMA/ADMA ratio did not differ significantly between controls and stroke patients. CSF dimethylarginine levels are increased in hyperacute ischemic stroke and are associated with stroke severity. PMID:19296217
Sex differences in predictors of ischemic stroke: current perspectives
Samai, Alyana A; Martin-Schild, Sheryl
Globally, stroke is a significant public health concern affecting more than 33 million individuals. Of growing importance are the differences between males and females in the predictors and overall risk of stroke. Given that women have a higher lifetime risk for stoke and account for more than half of all stroke deaths, sex-specific stroke risk factors merit investigation and may help target public health interventions. This review aims to discuss the current body of knowledge regarding sex-specific predictors of ischemic stroke including both modifiable and non-modifiable risk factors, as well as specific pathologies known to increase stroke risk. PMID:26251609
IL1RN VNTR Polymorphism in Ischemic Stroke
Worrall, Bradford B.; Brott, Thomas G.; Brown, Robert D.; Brown, W. Mark; Rich, Stephen S.; Arepalli, Sampath; Wavrant-De Vrièze, Fabienne; Duckworth, Jaime; Singleton, Andrew B.; Hardy, John; Meschia, James F.
Background and Purpose Genetic factors influence risk for ischemic stroke and likely do so at multiple steps in the pathogenic process. Variants in genes related to inflammation contribute to risk of stroke. The purpose of this study was to confirm our earlier finding of an association between allele 2 of a variable number tandem repeat of the IL-1 receptor antagonist gene (IL1RN) and cerebrovascular disease. Methods An association study of the variable number tandem repeat genotype with ischemic stroke and stroke subtypes was performed on samples from a North American study of affected sibling pairs concordant for ischemic stroke and 2 North American cohorts of prospectively ascertained ischemic stroke cases and unrelated controls. DNA analysis was performed on cases and controls, stratified by race. Results After adjustment for age, sex, and stroke risk factors, the odds ratio for association of allele 2 and ischemic stroke was 2.80 (95% confidence interval, 1.29 to 6.11; P=0.03) for the white participants. The effect of allele 2 of IL1RN on stroke risk most closely fits a recessive genetic model (P=0.009). For the smaller sample of nonwhite participants, the results were not significant. Conclusions Allele 2 of IL1RN, present in nearly one-quarter of stroke patients, may contribute to genetic risk for ischemic stroke and confirm the previously identified association with cerebrovascular disease. These results are driven by the association in the white participants. Further exploration in a larger nonwhite sample is warranted. PMID:17332449
Trans Fat, Aspirin, and Ischemic Stroke in Postmenopausal Women
Yaemsiri, Sirin; Sen, Souvik; Tinker, Lesley; Rosamond, Wayne; Wassertheil-Smoller, Sylvia; He, Ka
Objective To examine the associations between dietary fat intake and ischemic stroke among postmenopausal women. Methods We conducted a prospective cohort study of 87,025 generally healthy postmenopausal women (age 50–79 years) enrolled in the Women's Health Initiative Observational Study. Repeated and validated dietary assessments were done using a self-administered food frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HR) of ischemic stroke based on quintiles of the cumulative average of fat intake. Results We documented 1,049 incident cases of ischemic stroke over 663,041 person-years of follow-up. Women in the highest quintile of trans fat intake had a significantly higher incidence of ischemic stroke (HR 1.39, 95% confidence interval [CI] 1.08–1.79, P-trend = 0.048) compared with women in the lowest quintile, while controlling for multiple covariates. The observed association was modified by aspirin use (P-interaction=0.02). The HR was 1.66 (95% CI 1.21–2.36, P-trend<0.01) among baseline non-aspirin users (n=67,288) and 0.95 (95% CI 0.60–1.48, P-trend=0.43) among aspirin users (n=19,736). No significant associations were found between intakes of saturated, monounsaturated, or polyunsaturated fat and ischemic stroke or any ischemic stroke subtypes. Interpretation In this large cohort of postmenopausal women, higher intake of trans fat was associated with incident ischemic stroke independent of major lifestyle/dietary factors. Aspirin use may attenuate the potential adverse effect of trans fat intake on ischemic stroke. PMID:22383309
Systemic chemokine levels, coronary heart disease, and ischemic stroke events
Canouï-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.
Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors. PMID:21849651
Review of current and emerging therapies in acute ischemic stroke.
Novakovic, R; Toth, G; Purdy, P D
The statistics for stroke in the USA reads like a familiar ad slogan cited in most papers pertaining to acute ischemic stroke (AIS). Stroke is the third leading cause of death in the USA. While stroke ranks third among all causes of death, behind diseases of the heart and cancer, it is the leading cause of serious long-term disability in the USA.(1) Approximately 795 000 people, 87% of whom are ischemic, suffer from stroke each year in the USA.(2) That means that on average, every 40 seconds someone within the USA develops a stroke. For 2009 the combined direct and indirect cost of stroke, from hospitalization and rehabilitation to institutionalization, is estimated at $68.9 billion within the USA.(2). PMID:21994100
Circadian rhythm of onset of stroke - in 50 cases of ischemic stroke.
Uddin, M S; Hoque, M I; Uddin, M K; Kamol, S A; Chowdhury, R H
Stroke is a leading cause of death and disability worldwide. While the immediate consequence of stroke include permanent cognitive deficits, paralysis, visual impairment and sensory disturbances; stroke also results in long term dysregulation of sleep and mood, which may be equally disabling. The influence of ischemic stroke on circadian rhythm regulation, which is strongly linked to sleep and mood, may thus potentially influence long term recovery in stroke patients. Stroke induces immediate changes in the timing of pineal melatonin secretion, indicating that cortical and basal ganglia infarction impacts the timing of melatonin rhythms. This study was done to find out the time of onset of most of the ischemic stroke attack and to determine the outcome of ischemic stroke during hospital stay. All ischemic stroke patients admitted in Medicine wards in Comilla Medical College Hospital during the period of 1st November 2010 to 30th April 2011 included in this study. After admission, a careful history and a thorough clinical examination was carried out. Data collection was done on a preset questionnaire which involved to identify the risk factors, the time of onset of ischemic stroke, and outcome during hospital stay. All the cases were investigated. Among the 50 ischemic stroke patients, 68% were male and 32% female. Maximum age groups were 61-70 years (50%). By occupational category, maximum were retired persons (46%); 68% were hypertensive, 38% smoker and 16% had diabetes. Dyslipidemia was present in 44% patients. Most of the ischemic stroke (44%) occurred in the morning to late morning (6:01AM-12:00PM) and majority (80%) of the patients was discharged with residual neurological dysfunction. This study supports the presence of a circadian pattern in the onset of ischemic stroke, with higher risk in the morning to late morning. Most of the patients were discharged with residual neurological dysfunction. PMID:25725678
The Many Roles of Statins in Ischemic Stroke
Zhao, Jingru; Zhang, Xiangjian; Dong, Lipeng; Wen, Ya; Cui, Lili
Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke. PMID:25977681
Effects of ischemic stroke on dynamics of cerebral autoregulation
NASA Astrophysics Data System (ADS)
Chen, Zhi; Ivanov, Plamen Ch; Hu, Kun; Stanley, Eugene; Novak, Vera
Cerebral vasoregulation involves several complex mechanisms adapting blood flow to fluctuations of systemic blood pressure (BP). Autonomic BP and metabolic vasoregulation are impaired after stroke and cerebral blood flow depends on systemic BP. To probe the mechanisms of cerebral autoregulation we study levels of nonlinear synchronization between cerebral blood flow velocity (BFV) and peripheral BP. We quantify the instantaneous phase of each signal employing analytic signal approach and Hilbert transform. As a marker of synchronization, we introduce a measure of cross-correlation between the instantaneous phase increments of the BFV and BP signals at different time lags. We have studied 12 subjects with minor chronic ischemic stroke and 11 matched normotensive controls (age<65years). BFV and BP of these subjects are continuously recorded during supine baseline, head-up tilt, hyperventilation and CO2 rebreathing. For control subjects we find significant synchronization between cerebral BFV and peripheral BP only for short time lags of up to 5-6 seconds, suggesting a rapid return to a steady cerebral blood flow after initial blood pressure perturbations. In contrast, for stroke subjects BFV/BP we find enhanced synchronization over longer time lags of up to 20 seconds, suggesting entrainment of cerebral blood flow velocity by slow vasomotor rhythms. These findings suggest that cerebral vasoregulation is impaired and cerebral blood flow follows the fluctuations of systemic BP in a synchronous manner. Our analysis shows that cerebral autoregulation is impaired in 10 out of the 12 stroke subjects, which is typically difficult to diagnose with conventional methods. Thus, our novel synchronization approach offers a new tool sensitive for evaluation of changes in the dynamics of cerebral autoregulation under stroke.
Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages
Shaafi, Sheyda; Mahmoudi, Javad; Pashapour, Ali; Farhoudi, Mehdi; Sadigh-eteghad, Saeed; Akbari, Hossein
Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries. PMID:25671178
Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke
Piggott, Damani A.; Carroll, Karen C.; Lim, Michael; Melia, Michael T.
Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176
[Ischemic stroke as reaction to an acute stressful event].
Ibrahimagić, Omer C; Sinanović, Osman; Cickusić, Amra; Smajlović, Dzevdet
The period following ischemic stroke can be considered as a reaction to a stressful event. Changes in cortisol secretion are one of the indicators of stress reaction. The aim of the study was to determine morning serum levels of cortisol in stroke patients within 48 hours and 15 days of ischemic stroke onset. Study group included 40 patients, 20 of them were females, mean age 65.3 +/- 10.3 years. The patients did not receive any corticosteroid agents or spironolactone, and did not suffer from Cushing's or Addison's syndrome. Ischemic stroke was verified by computed tomography of the brain. The fluorometric method with DELFIA Cortisol immunoassay was used to determine morning serum cortisol levels. Reference values of the measured hormone were 201-681 nmol/l. The mean level of serum cortisol within 48 hours of stroke was 560.9 +/- 318.9 nmol/l, and on day 15 it was 426.2 +/- 159.3 nmol/l, i.e. significantly lower (p < 0.02). On the first measurement, the level of serum cortisol was elevated in 32%, and on the second measurement in only 7.5% patients, which was also significantly lower (p < 0.001). It was concluded that the stress reaction in ischemic stroke patients was more pronounced within the first 48 hours of stroke onset. Judging from the morning cortisol levels, the reaction to stress was considerably less pronounced 15 days after stroke onset. PMID:15875466
Nontyphoidal Salmonellosis, Human Immunodeficiency Virus Infection, and Ischemic Stroke.
Piggott, Damani A; Carroll, Karen C; Lim, Michael; Melia, Michael T
Nontyphoidal Salmonella infection and stroke are major causes of morbidity and mortality worldwide, with increased risk in the human immunodeficiency virus (HIV)-infected population. We report a rare case of ischemic stroke associated with Salmonella enteritidis subdural empyema in an older HIV-infected patient with multimorbidity, despite surgery and treatment with susceptible antimicrobial drugs. PMID:27419176
Association of integrin α2 gene variants with ischemic stroke
Matarin, Mar; Brown, W Mark; Hardy, John A; Rich, Stephen S; Singleton, Andrew B; Brown, Robert D; Brott, Thomas G; Worrall, Bradford B; Meschia, James F
Genetic variants in the gene encoding integrin α2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P = 0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P= 0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes. PMID:17534386
Hepatitis C and recurrent treatment-resistant acute ischemic stroke
Tarsia, Joseph; Dunn, Casey; Aysenne, Aimee; Shah, Basil; Moore, David F.
Since the introduction of recombinant tissue plasminogen activator and thrombolysis, acute ischemic stroke has become a treatable disorder if the patient presents within the 4.5-hour time window. Typically, sporadic stroke is caused by atherosclerotic disease involving large or small cerebral arteries or secondary to a cardioembolic source often associated with atrial fibrillation. In the over-65-year age group, more rare causes of stroke, such as antiphospholipid syndromes, are unusual; such stroke etiologies are mostly seen in a younger age group (<55 years). Here we describe acute ischemic stroke in three patients >65 years with hepatitis C–associated antiphospholipid antibodies. We suggest that screening for antiphospholipid disorders in the older patient might be warranted, with potential implications for therapeutic management and secondary stroke prevention. PMID:23543984
Perfusion Angiography in Acute Ischemic Stroke.
Scalzo, Fabien; Liebeskind, David S
Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and T max, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232
Perfusion Angiography in Acute Ischemic Stroke
Liebeskind, David S.
Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232
Factoring in Factor VIII With Acute Ischemic Stroke
Siegler, James E.; Samai, Alyana; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl
There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. PMID:25669199
Epidermoid Causing Ischemic Stroke in the Brainstem
Mahore, Amit; Kulkarni, Abhijeet; Rangarajan, Vithal; Patil, Manoj; Kawale, Juhi
Intracranial tumors may rarely cause stroke. We report an epidermoid cyst causing stroke in a pediatric patient. We have also reviewed the literature and pathogenesis of stroke caused by intracranial tumors. PMID:25580320
Ischemic Stroke and Its Risk Factors in a Registry-Based Large Cross-Sectional Diabetic Cohort in a Country Facing a Diabetes Epidemic
Al-Rubeaan, Khalid; Al-Hussain, Fawaz; Youssef, Amira M.; Subhani, Shazia N.; Al-Sharqawi, Ahmad H.; Ibrahim, Heba M.
The main aim of this study is to determine the prevalence and risk factors of ischemic stroke among diabetic patients registered in the Saudi National Diabetes Registry (SNDR) database. A cross-sectional sample of 62,681 diabetic patients aged ≥25 years was used to calculate ischemic stroke prevalence and its risk factors. Univariate and multivariate logistic regression analyses were used to assess the roles of different risk factors. The prevalence of ischemic stroke was 4.42% and was higher in the older age group with longer diabetes duration. Poor glycemic control and the presence of chronic diabetes complications were associated with a high risk of ischemic stroke. History of smoking and type 2 diabetes were more frequent among stroke patients. Obesity significantly decreased the risk for ischemic stroke. Regression analysis for ischemic stroke risk factors proved that age ≥45 years, male gender, hypertension, coronary artery disease (CAD), diabetes duration ≥10 years, insulin use, and hyperlipidemia were significant independent risk factors for ischemic stroke. We conclude that ischemic stroke is prevalent among diabetic individuals, particularly among those with type 2 diabetes. Good glycemic, hypertension, and hyperlipidemia control, in addition to smoking cessation, are the cornerstones to achieve a significant reduction in ischemic stroke risk. PMID:26989695
Autonomic dysfunction in acute ischemic stroke: an underexplored therapeutic area?
De Raedt, Sylvie; De Vos, Aurelie; De Keyser, Jacques
Impaired autonomic function, characterized by a predominance of sympathetic activity, is common in patients with acute ischemic stroke. This review describes methods to measure autonomic dysfunction in stroke patients. It summarizes a potential relationship between ischemic stroke-associated autonomic dysfunction and factors that have been associated with worse outcome, including cardiac complications, blood pressure variability changes, hyperglycemia, immune depression, sleep disordered breathing, thrombotic effects, and malignant edema. Involvement of the insular cortex has been suspected to play an important role in causing sympathovagal imbalance, but its exact role and that of other brain regions remain unclear. Although sympathetic overactivity in patients with ischemic stroke appears to be a negative prognostic factor, it remains to be seen whether therapeutic strategies that reduce sympathetic activity or increase parasympathetic activity might improve outcome. PMID:25541326
The effects of citicoline on acute ischemic stroke: a review.
Overgaard, Karsten
Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11,000 patients with various neurologic disorders, including acute ischemic stroke (AIS). The conclusion is that citicoline is safe to use and may have a beneficial effect in AIS patients and most beneficial in less severe stroke in older patients not treated with recombinant tissue plasminogen activator. No other neuroprotective agent had any beneficial effect in confirmative clinical trials or had any positive effect in the subgroup analysis. Citicoline is the only drug that in a number of different clinical stroke trials continuously had some neuroprotective benefit. PMID:24739589
Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke.
Hsieh, Fang-I; Jeng, Jiann-Shing; Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming
In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010-2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190
Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke
Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A.; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming
In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010–2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006–08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190
Angiogenesis-regulating microRNAs and ischemic stroke
Yin, Ke-Jie; Hamblin, Milton; Chen, Y. Eugene
Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis. PMID:26156265
Potential microRNA biomarkers for acute ischemic stroke.
Zeng, Ye; Liu, Jing-Xia; Yan, Zhi-Ping; Yao, Xing-Hong; Liu, Xiao-Heng
Acute ischemic stroke is a significant cause of high morbidity and mortality in the aging population globally. However, current therapeutic strategies for acute ischemic stroke are limited. Atherosclerotic plaque is considered an independent risk factor for acute ischemic stroke. To identify biomarkers for carotid atheromatous plaque, bioinformatics analysis of the gene microarray data of plaque and intact tissue from individuals was performed. Differentially expressed genes (DEGs) were identified using the Multtest and Limma packages of R language, including 56 downregulated and 69 upregulated DEGs. Enriched microRNA (miRNA or miR) DEGs networks were generated using WebGestalt software and the STRING databases, and the miRNAs were validated using serum from acute ischemic stroke patients with reverse transcription quantitative PCR (RT‑qPCR). Four confirmed differentially expressed miRNAs (miR‑9, ‑22, ‑23 and ‑125) were associated with 28 upregulated DEGs, and 7 miRNAs (miR‑9, ‑30, ‑33, ‑124, ‑181, ‑218 and ‑330) were associated with 25 downregulated DEGs. Gene ontology (GO) function suggested that the confirmed miRNA‑targeted DEGs predominantly associated with signal transduction, the circulatory system, biological adhesion, striated muscle contraction, wound healing and the immune system. The confirmed miRNA‑targeted genes identified serve as potential therapeutic targets for acute ischemic stroke. PMID:26459744
Melatonin and Ischemic Stroke: Mechanistic Roles and Action
Andrabi, Syed Suhail; Parvez, Suhel; Tabassum, Heena
Stroke is one of the most devastating neurological disabilities and brain's vulnerability towards it proves to be fatal and socio-economic loss of millions of people worldwide. Ischemic stroke remains at the center stage of it, because of its prevalence amongst the several other types attacking the brain. The various cascades of events that have been associated with stroke involve oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of Ca2+ level, and so forth. Melatonin is a neurohormone secreted by pineal and extra pineal tissues responsible for various physiological processes like sleep and mood behaviour. Melatonin has been implicated in various neurological diseases because of its antioxidative, antiapoptotic, and anti-inflammatory properties. We have previously reviewed the neuroprotective effect of melatonin in various models of brain injury like traumatic brain injury and spinal cord injury. In this review, we have put together the various causes and consequence of stroke and protective role of melatonin in ischemic stroke. PMID:26435711
Pre-ischemic exercise alleviates oxidative damage following ischemic stroke in rats.
Feng, Rui; Zhang, Min; Wang, Xiao; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng
Physical exercise has been proved to be neuroprotective in clinical trials and animal experiments. However, the exact mechanism underlying this neuroprotective effect remains unclear. The aim of the present study was to explore whether pre-ischemic treadmill training could act as a form of ischemic preconditioning in a rat following ischemic stroke by reducing oxidative damage. Fifty-four rats were randomly divided into three groups (n=18 per group): Sham surgery, middle cerebral artery occlusion (MCAO) without exercise and MCAO with exercise. Subsequent to treadmill training, ischemic stroke was induced by occluding the MCA for 1.5 h, followed by reperfusion. Six rats in each group were evaluated for neurological deficits and then sacrificed by decapitation to calculate the infarct volume. The remaining rats in each group were sacrificed to detect the level of superoxide dismutase (SOD) activity (n=6) and malondialdehyde (MDA) concentration (n=6). The results indicated that pre-ischemic exercise training reduced brain infarct volume and neurological deficits, increased SOD activity and decreased the concentration of MDA following ischemic stroke. In conclusion, treadmill exercise training prior to MCAO/reperfusion increased the antioxidant ability and decreased the oxidative damage in the brain subsequent to ischemic stroke. PMID:25187848
Genome wide analysis of blood pressure variability and ischemic stroke
Khan, Muhammad S; Nalls, Michael A; Bevan, Steve; Cheng, Yu-Ching; Chen, Wei-Min; Malik, Rainer; McCarthy, Nina S; Holliday, Elizabeth G; Speed, Douglas; Hasan, Nazeeha; Pucek, Mateusz; Rinne, Paul E.; Sever, Peter; Stanton, Alice; Shields, Denis C; Maguire, Jane M; McEvoy, Mark; Scott, Rodney J; Ferrucci, Luigi; Macleod, Mary J; Attia, John; Markus, Hugh S; Sale, Michele M; Worrall, Bradford B; Mitchell, Braxton D; Dichgans, Martin; Sudlow, Cathy; Meschia, James F; Rothwell, Peter M
Background and Purpose Visit-to-visit variability in BP is associated with ischemic stroke. We sought to determine whether such variability has a genetic aetiology and whether genetic variants associated with BP variability are also associated with ischemic stroke. Methods A GWAS for loci influencing BP variability was undertaken in 3,802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study where long-term visit-to-visit and within visit BP measures were available. Since BP variability is strongly associated with ischemic stroke, we genotyped the sentinel SNP in an independent ischemic stroke population comprising of 8,624 cases and 12,722 controls and in 3,900 additional (Scandinavian) participants from the ASCOT study in order to replicate our findings. Results The ASCOT discovery GWAS identified a cluster of 17 correlated SNPs within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (p=1.4×10−8). Conditional analysis on rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in ischemic stroke patients found no association for overall stroke (OR 1.02; 95% CI 0.97-1.07; p=0.52) or its sub-types: CE (OR 1.07; 95% CI 0.97-1.16; p=0.17), LVD (OR 0.98; 95% 0.89-1.07; p=0.60) and SVD (OR 1.07; 95% CI 0.97-1.17; p=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (p=0.18). Conclusions We identified a cluster of SNPs at the NLGN1 locus showing significant association with BP variability. Follow up analyses did not support an association with risk of ischemic stroke and its subtypes. PMID:23929743
Kurth, Tobias; Everett, Brendan M.; Buring, Julie E.; Kase, Carlos S.; Ridker, Paul M; Gaziano, J. Michael
Objective To evaluate the association between total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, and non-HDL-C with the risk of ischemic stroke in a large cohort of apparently healthy women. Methods Prospective cohort study among 27,937 US women aged ≥45 years participating in the Women's Health Study who provided baseline blood samples. Stroke occurrence was self-reported and confirmed by medical record review. We categorized plasma lipid measurements into quintiles. We used Cox proportional hazards models to evaluate the association between lipids and risk of ischemic stroke. Results During 11 years of follow-up, 282 ischemic strokes occurred. All lipid levels were strongly associated with increased risk of ischemic stroke in age-adjusted models. The association attenuated particularly for HDL-C after adjustment for potential confounders. For the comparison of the highest to the lowest quintile, the multivariable-adjusted hazard ratios (95% confidence intervals; P for trend across mean quintile values) of ischemic stroke were 2.27 (1.43-3.60; Ptrend<0.001) for total cholesterol; 1.74 (1.14-2.66; Ptrend=0.003) for LDL-C; 0.78 (0.52-1.17; Ptrend=0.27) for HDL-C; 1.65 (1.06-2.58; Ptrend=0.02) for total cholesterol to HDL-C ratio; and 2.45 (1.54-3.91; Ptrend<0.001) for non-HDL-C. Conclusions In this large cohort of apparently healthy women, total cholesterol, low-density lipoprotein cholesterol, the total cholesterol to high-density lipoprotein cholesterol ratio, and non-high-density lipoprotein cholesterol were significantly associated with increased risk of ischemic stroke. PMID:17310025
The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke.
Chang, Jason J; Stanfill, Ansley; Pourmotabbed, Tayebeh
Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins. PMID:27529234
The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke
Chang, Jason J.; Stanfill, Ansley; Pourmotabbed, Tayebeh
Stroke remains the fifth leading cause of mortality in the United States with an annual rate of over 128,000 deaths per year. Differences in incidence, pathogenesis, and clinical outcome have long been noted when comparing ischemic stroke among different ethnicities. The observation that racial disparities exist in clinical outcomes after stroke has resulted in genetic studies focusing on specific polymorphisms. Some studies have focused on matrix metalloproteinases (MMPs). MMPs are a ubiquitous group of proteins with extensive roles that include extracellular matrix remodeling and blood-brain barrier disruption. MMPs play an important role in ischemic stroke pathophysiology and clinical outcome. This review will evaluate the evidence for associations between polymorphisms in MMP-1, 2, 3, 9, and 12 with ischemic stroke incidence, pathophysiology, and clinical outcome. The role of polymorphisms in MMP genes may influence the presentation of ischemic stroke and be influenced by racial and ethnic background. However, contradictory evidence for the role of MMP polymorphisms does exist in the literature, and further studies will be necessary to consolidate our understanding of these multi-faceted proteins. PMID:27529234
Inflammatory mechanisms in ischemic stroke: role of inflammatory cells
Jin, Rong; Yang, Guojun; Li, Guohong
Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219
Adolescent ischemic stroke associated with anabolic steroid and cannabis abuse.
El Scheich, Tarik; Weber, Artur-Aron; Klee, Dirk; Schweiger, Daniel; Mayatepek, Ertan; Karenfort, Michael
We report on a 16-year-old body builder who suffered from an acute ischemic stroke. In the urine, cannabis metabolites as well as metabolites of the oral androgenic-anabolic steroid methandrostenolone were detected, both known to be associated with stroke events. This report highlights the role of cannabis and steroid abuse that induce strokes in the absence of arteriopathy, cardioembolism or thrombophilia. Owing to new upcoming socio-behavioral aspects of late childhood and early adolescent life, this formally rare abuse of cannabis and/or anabolic steroids as well as their associations with strokes becomes more current than ever. PMID:23382306
Biomarkers Associated with Ischemic Stroke in Diabetes Mellitus Patients.
Yang, Shuisheng; Zhao, Jingfeng; Chen, Yuxiang; Lei, Minxiang
Diabetes is an established risk factor for ischemic stroke, but the associated molecular mechanisms remain to be fully elucidated. This study investigated the role of plasma and platelet microRNAs and their targeting proteins in the activation of platelets and their association with the occurrence of ischemic stroke in patients with type 2 diabetes mellitus (T2DM). Results showed that the expressions of platelet and plasma miR-144 and miR-223 were significantly altered in T2DM patients with or without ischemic stroke compared to that in healthy controls, but these changes were more significant in T2DM patients with ischemic stroke. The expressions of P2Y12 and IRS-1 as well as phosphorylation levels of IRS-1, PI3K, and Akt in platelets were significantly altered in T2DM patients with or without ischemic stroke. The expression of platelet miR-144 and miR-223 significantly correlated with their plasma levels, P2Y12 and IRS-1 expression, blood glucose concentration, and platelet activation rate. High glucose concentration significantly elevated P-selectin, miR-144 and P2Y12 expression and significantly reduced miR-223 and IRS-1 expression in UT-7 cells. Overexpression of miR-223 and blocking of miR-144 expression significantly normalized the effects of high glucose concentration in UT-7 cells. In conclusion, hyperglycemia may activate platelets through miR-144 and miR-223 to downregulate IRS-1 and upregulate P2Y12 expression in the platelets of T2DM patients through an IRS-1-PI3K-Akt signaling. Low platelet and plasma miR-223 expression in addition to high platelet and plasma miR-144 expression are risk factors for ischemic stroke in T2DM patients. PMID:26175178
Hurdles in stroke thrombolysis: Experience from 100 consecutive ischemic stroke patients
Badachi, Sagar; Mathew, Thomas; Prabhu, Arvind; Nadig, Raghunandan; Sarma, Gosala R. K.
Background: Acute management of ischemic stroke involves thrombolysis within 4.5 h. For a successful outcome, early recognition of stroke, transportation to the hospital emergency department immediately after stroke, timely imaging, proper diagnosis, and thrombolysis within 4.5 h is of paramount importance. Aim: To analyze the obstacles for thrombolysis in acute stroke patients. Materials and Methods: The study was conducted in a tertiary care center in South India. A total of hundred consecutive patients of acute ischemic stroke who were not thrombolysed, but otherwise fulfilled the criteria for thrombolysis were evaluated prospectively for various factors that prevented thrombolysis. The constraints to thrombolysis were categorized into: i) Failure of patient to recognize stroke symptoms, ii) patient's awareness of thrombolysis as a treatment modality for stroke, iii) failure of patient's relative to recognize stroke, iv) failure of primary care physician to recognize stroke, v) transport delays, vi) lack of neuroimaging and thrombolysis facility, and vii) nonaffordability. Results: The biggest hurdle for early hospital presentation is failure of patients to recognize stroke (73%), followed by lack of neuroimaging facility (58%), nonaffordability (56%), failure of patient's relative to recognize stroke (38%), failure of the primary care physician to recognize stroke (21%), and transport problems (13%). Awareness of thrombolysis as a treatment modality for stroke was seen only in 2%. Conclusion: Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for improvement to overcome various hurdles that prevent thrombolysis. PMID:26713013
Anesthesia for Endovascular Approaches to Acute Ischemic Stroke.
Avitsian, Rafi; Machado, Sandra B
Involvement of the Anesthesiologist in the early stages of care for acute ischemic stroke patient undergoing endovascular treatment is essential. Anesthetic management includes the anesthetic technique (general anesthesia vs sedation), a matter of much debate and an area in need of well-designed prospective studies. The large numbers of confounding factors make the design of such studies a difficult process. A universally agreed point in the endovascular management of acute ischemic stroke is the importance of decreasing the time to revascularization. Hemodynamic and ventilatory management and implementation of neuroprotective modalities and treatment of acute procedural complications are important components of the anesthetic plan. PMID:27521194
Siblings with Ischemic Stroke Study (SWISS): Results of a Genome-wide Scan for Stroke Loci
Meschia, James F.; Nalls, Michael; Matarin, Mar; Brott, Thomas G.; Brown, Robert D.; Hardy, John; Kissela, Brett; Rich, Stephen S.; Singleton, Andrew; Hernandez, Dena; Ferrucci, Luigi; Pearce, Kerra; Keller, Margaret; Worrall, Bradford B.
Background and Purpose Ischemic stroke has a strong familial component to risk. The Siblings with Ischemic Stroke Study (SWISS) is a genome-wide family-based analysis that included use of imputed genotypes. SWISS was conducted to examine associations between SNPs and risk of stroke and stroke subtypes within pairs. Methods SWISS enrolled 312 probands with ischemic stroke across 70 US and Canadian centers. Affected siblings were ascertained by centers and confirmed by central record review; unaffected siblings were ascertained by telephone contact. Ischemic stroke was subtyped using TOAST criteria. Genotyping was performed using an Illumina 610 quad array (probands) and an Illumina linkage V array (affected siblings). SNPs were imputed using 1000 Genomes Project data and MACH software. Family-based association analyses were conducted using the sibling-transmission disequilibrium test. Results For all pairs, the correlation of age at stroke within pairs of affected siblings was r = 0.83 (95%CI, 0.78 to 0.86; P < 2.2×10−16). The correlation did not differ substantially by subtype. The concordance of stroke subtypes among affected pairs was 33.8% (kappa = 0.13; P = 5.06×10−4) and did not differ by age at stroke in the proband. Although no SNP achieved genome-wide significance for risk of ischemic stroke, there was clustering of the most associated SNPs on chromosomes 3p (NOS1) and 6p. Conclusions Stroke subtype and age at stroke in affected sibling pairs exhibit significant clustering. No individual SNP reached genome-wide significance. However, two promising candidate loci were identified, including one that contains NOS1, though these risk loci warrant further examination in larger sample collections. PMID:21940970
Risk factors and outcomes of childhood ischemic stroke in Taiwan.
Lee, Ying-Ying; Lin, Kuang-Lin; Wang, Huei-Shyong; Chou, Min-Liang; Hung, Po-Cheng; Hsieh, Meng-Ying; Lin, Jainn-Jim; Wong, Alex Mun-Ching
In this retrospective study, we reviewed the charts and collected clinical and radiographic data on children (age range, 1 month to 18 years) with symptoms and radiographic confirmation of ischemic stroke for the period of January 1996 to July 2006. Ninety-four children were enrolled. Eighty-eight had arterial ischemic stroke and six had sinovenous thrombosis. Twenty-nine percent of the children had seizures. Twenty-six percent had diffuse neurological signs and 76% had focal neurological signs. Risk factors included vascular disease (33%), infection (27%), metabolic disorders (18%), trauma (11%), prothrombotic states (13%), cardiac disease (10%), and mitochondrial disease (6%). Ten percent (n=9) had no identifiable cause. Twenty-two percent of the children had more than one risk factor. Anterior territory (70%) was more involved than posterior territory (18%) in arterial ischemic stroke. Unilateral infarctions were more common on the left side (51%) than on the right (24.5%). Neurological deficits were present in 45% (n=34/75) of the children; the most frequent deficit was motor impairment (24%). Seven children (9%) died in the acute stage. There were 12 children (16%) who had recurrent stroke and 8 children (8/12) who had underlying vascular disease. The vascular disease included moyamoya disease (5), CNS lupus (1) and ill-defined vasculopathy (2). The etiology pattern in Taiwan was different from that in Western countries. Vascular disease was a significant risk factor for recurrence in childhood ischemic stroke. PMID:17573220
Arterial Ischemic Stroke in Children: Risk Factors and Etiologies
Numis, Adam L.
Stroke is increasingly recognized as a significant cause of morbidity or mortality in children and as a financial burden for families and society. Recent studies have identified and confirmed presumptive risk factors and have identified novel associations with childhood arterial ischemic stroke. A better understanding of these risk factors for stroke in children, which differ from the atherosclerotic risk factors in adults, is the first step needed to improve strategies for stroke prevention and intervention and ultimately minimize the physical, mental and financial burden of AIS. Here, we discuss recent advances in research for selected childhood stroke risk factors, highlighting the progress made in our understanding of etiologic mechanisms and pathophysiology, and address the future directions for acute and long-term treatment strategies for pediatric stroke. PMID:24384876
Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats
Moldthan, Huong L.; Hirko, Aaron C.; Thinschmidt, Jeffrey S.; Grant, Maria; Li, Zhimin; Peris, Joanna; Lu, Yuanqing; Elshikha, Ahmed; King, Michael A.; Hughes, Jeffrey A.; Song, Sihong
Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. PMID:24582784
Minor Stroke and Transient Ischemic Attack: Research and Practice
Yakhkind, Aleksandra; McTaggart, Ryan A.; Jayaraman, Mahesh V.; Siket, Matthew S.; Silver, Brian; Yaghi, Shadi
A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID:27375548
Minor Stroke and Transient Ischemic Attack: Research and Practice.
Yakhkind, Aleksandra; McTaggart, Ryan A; Jayaraman, Mahesh V; Siket, Matthew S; Silver, Brian; Yaghi, Shadi
A majority of patients with ischemic stroke present with mild deficits for which aggressive management is not often pursued. Comprehensive work-up and appropriate intervention for minor strokes and transient ischemic attacks (TIAs) point toward better patient outcomes, lower costs, and fewer cases of disability. Imaging is a key modality to guide treatment and predict stroke recurrence. Patients with large vessel occlusions have been found to suffer worse outcomes and could benefit from intervention. Whether intravenous thrombolytic therapy decreases disability in minor stroke patients and whether acute endovascular intervention improves functional outcomes in patients with minor stroke and known large vessel occlusion remain controversial. Studies are ongoing to determine ideal antiplatelet therapy for stroke and TIA, while ongoing statin therapy, surgical management for patients with carotid stenosis, and anticoagulation for patients with atrial fibrillation have all been proven to decrease the rate of stroke recurrence and improve outcomes. This review summarizes the current evidence and discusses the standard of care for patients with minor stroke and TIA. PMID:27375548
Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients
Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung
Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.
Transient central diabetes insipidus following ischemic stroke.
Jayaraman, Muthukrishnan; Kumar, Sandeep; Ahmad, F M H
Central Diabetes Insipidus (CDI) following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery. PMID:24251140
[Ischemic stroke: A rare complication of liver hydatid cyst].
Ghadhoune, H; Chaari, A; Baccouche, N; Chelly, H; Bouaziz, M
Hydatid cyst of the liver (HCL) is a widespread disease in North African countries. We report the case of a 39-year-old patient who was admitted in our intensive care unit because of anaphylactic shock due to a cracked HCL fortuitously discovered. This accident was also complicated by an ischemic stroke witch underline mechanisms are discussed. PMID:24075197
Brainstem ischemic stroke after to Bothrops atrox snakebite.
Cañas, Carlos A
We report case of a 48 years old woman bitten on her right foot by a Bothrops atrox viper. As a result, she developed a severe coagulopathy which improved with application of polyvalent antivenom. Four days after bite she suffered a devastating brainstem ischemic stroke. Possible pathogenetic mechanisms are discussed. PMID:27527269
Glibenclamide for the treatment of ischemic and hemorrhagic stroke.
Caffes, Nicholas; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc
Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. PMID:25749474
[Development of Researches on Scalp Acupuncture for Ischemic Stroke].
Tian, Liang; Wang, Jin-hai; Sun, Run-jie; Zhang, Xing-hua; Yuan, Bo; Du, Xiao-zheng
Ischemic stroke is one of the commonly met diseases in clinical practice nowadays. Acupuncture therapy is widly used in the treatment of sequela of ischemic stroke in China and its mechanisms have been extensively studied in recen years. In the present paper, the authors focus on the development of studies on the mechanism of scalp acupuncture therapy in the treatment of ischemic stroke. Results indicate that scalp acupuncture intervention can 1) improve cerebral blood circulation to promote regional energy metabolism, 2) up-regulate expression of glial cell-line derived neurotrophic factor (GDNF), etc., possibly promoting proliferation and differentiation of neural stem cells in the focal cerebral cortex and hippocampus, 3) reduce contents of excitatory amino acid and increase level of gamma-aminobutyric acid (GABA) to lower neurogenic toxicity, and relieve cerebral injury, 4) ease cerebral vascular immunoinflammatory reactions, 5) regulate blood lipid metabolism to resist cerebral free radical damage, and 6) inhibit cerebral cortical apoptosis. However, these results only revealed very limited intrinsic mechanisms of scalp acupuncture in improving ischemic stroke. Further studies using comprehensive techniques of multi-disciplines as molecular biology, electrophysiology, etc. are definitely needed. PMID:27141629
Update on the Role of Cannabinoid Receptors after Ischemic Stroke
Capettini, Luciano S. A.; Savergnini, Silvia Q.; da Silva, Rafaela F.; Stergiopulos, Nikos; Santos, Robson A. S.; Mach, François; Montecucco, Fabrizio
Cannabinoids are considered as key mediators in the pathophysiology of inflammatory diseases, including atherosclerosis. In particular, they have been shown to reduce the ischemic injury after acute cardiovascular events, such as acute myocardial infarction and ischemic stroke. These protective and anti-inflammatory properties on peripheral tissues and circulating inflammatory have been demonstrated to involve their binding with both selective cannabinoid type 1 (CB1) and type 2 (CB2) transmembrane receptors. On the other hands, the recent discoveries of novel different classes of cannabinoids and receptors have increased the complexity of this system in atherosclerosis. Although only preliminary data have been reported on the activities of novel cannabinoid receptors, several studies have already investigated the role of CB1 and CB2 receptors in ischemic stroke. While CB1 receptor activation has been shown to directly reduce atherosclerotic plaque inflammation, controversial data have been shown on neurotransmission and neuroprotection after stroke. Given its potent anti-inflammatory activities on circulating leukocytes, the CB2 activation has been proven to produce protective effects against acute poststroke inflammation. In this paper, we will update evidence on different cannabinoid-triggered avenues to reduce inflammation and neuronal injury in acute ischemic stroke. PMID:22577257
Intermittent fasting attenuates inflammasome activity in ischemic stroke.
Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V
Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. PMID:24805069
Correlation Analysis of Sleep Quality and Youth Ischemic Stroke
Zhang, Shunqing; Chang, Cheng; Zhang, Juan; Song, Bo; Fang, Hui; Xu, YuMing
Objective. To study risk factors related to ischemic stroke (IS) in youth and the influence of sleep quality on youth ischemic stroke incidence. Methods. 223 patients aged 18 to 45 years who were admitted to Puyang People's Hospital from June 2011 to February 2013 with a first-ever ischemic stroke were selected as the research cases. 158 young people with a normal physical examination were selected as the control group. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to analyse the correlation between sleep quality and youth IS incidence. The US National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (MRS) scores were used to assess cases' state of illness and prognosis three months after IS. Results. Univariate and multivariate logistic regression analysis showed that the association of these risk factors with youth IS incidence, from highest to lowest, was hypertension, hyperlipidaemia, smoking history, high homocysteine, the quality of sleep, family history of stroke, and alcoholism. Poor sleep quality ranked fifth among all risk factors and was positively correlated with poor prognosis for youth IS patients. Conclusion. The results of this study showed that sleep quality is an important factor in the pathogenesis and prognosis of youth IS. PMID:25161340
Stroke and the "stroke belt" in dialysis: contribution of patient characteristics to ischemic stroke rate and its geographic variation.
Wetmore, James B; Ellerbeck, Edward F; Mahnken, Jonathan D; Phadnis, Milind A; Rigler, Sally K; Spertus, John A; Zhou, Xinhua; Mukhopadhyay, Purna; Shireman, Theresa I
Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m(2) was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the "stroke belt" or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients. PMID:23990675
Bone Fracture Pre-Ischemic Stroke Exacerbates Ischemic Cerebral Injury in Mice
Zou, Dingquan; Zhan, Lei; Li, Zhengxi; Zhu, Wan; Su, Hua
Ischemic stroke is a devastating complication of bone fracture. Bone fracture shortly after stroke enhances stroke injury by augmenting inflammation. We hypothesize that bone fracture shortly before ischemic stroke also exacerbates ischemic cerebral injury. Tibia fracture was performed 6 or 24 hours before permanent middle cerebral artery occlusion (pMCAO) on C57BL/6J mice or Ccr2RFP/+Cx3cr1GFP/+ mice that have the RFP gene knocked into one allele of Ccr2 gene and GFP gene knocked into one allele of Cx3cr1 gene. Behavior was tested 3 days after pMCAO. Infarct volume, the number of CD68+ cells, apoptotic neurons, bone marrow-derived macrophages (RFP+), and microgila (GFP+) in the peri-infarct region were quantified. Compared to mice subjected to pMCAO only, bone fracture 6 or 24 hours before pMCAO increased behavioral deficits, the infarct volume, and the number of CD68+ cells and apoptotic neurons in the peri-infarct area. Both bone marrow-derived macrophages (CCR2+) and microglia (CX3CR1+) increased in the peri-infarct regions of mice subjected to bone fracture before pMCAO compared to stroke-only mice. The mice subjected to bone fracture 6 hours before pMCAO had more severe injury than mice that had bone fracture 24 hours before pMCAO. Our data showed that bone fracture shortly before stroke also increases neuroinflammation and exacerbates ischemic cerebral injury. Our findings suggest that inhibition of neuroinflammation or management of stroke risk factors before major bone surgery would be beneficial for patients who are likely to suffer from stroke. PMID:27089041
Drug repurposing for immune modulation in acute ischemic stroke.
Amantea, Diana; Bagetta, Giacinto
Innate immune cells play a dualistic role in the evolution of ischemic brain damage, with classic phenotypes promoting injury, and alternatively activated M2 microglia/macrophages or N2 neutrophils providing tissue remodelling and repair. Recently, a number of drugs commonly used for other indications (i.e., azithromycin, minocycline, bexarotene, rosiglitazone, metformin) was reported to provide neuroprotection in preclinical stroke models by promoting immune polarization towards non-inflammatory, protective phenotypes. Repurposing drugs with a well-established safety profile should allow a reduction in the risk of clinical trial failure that has dominated the unsuccessful development of neuroprotective drugs in stroke during the last decades. The clinical validation of the proof of concept, followed by the assessment of safety and efficacy of immune-polarizing repurposed drugs will definitively offer new opportunities for the acute treatment of ischemic stroke. PMID:26657075
The Siblings With Ischemic Stroke Study (SWISS): A Progress Report
Meschia, James F.; Kissela, Brett M.; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Beck, Jeanne; Skarp, Alexa N.
There is increasing evidence that genetic factors are associated with ischemic stroke, including multiple recent reports of association with the gene PDE4D, encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are important but can be logistically difficult to perform. This article reviews the design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems in performing a sibling-based pedigree study where proband-initiated consent is used to enroll pedigree members. Proband-initiated enrollment optimizes privacy protections for family members, but it is associated with a substantial pedigree non-completion rate such that 3 to 4 probands must be identified to obtain one completed sibling pedigree. This report updates the progress of enrollment in the SWISS protocol, discusses barriers to pedigree completion and describes innovative approaches used by the SWISS investigators to enhance enrollment. PMID:16595789
Optical-resolution photoacoustic microscopy of ischemic stroke
NASA Astrophysics Data System (ADS)
Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.
A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.
MR Perfusion Imaging in Acute Ischemic Stroke
Copen, William A.; Schaefer, Pamela W.; Wu, Ona
MR perfusion imaging offers the potential for measuring brain perfusion in acute stroke patients, at a time when treatment decisions based upon these measurements may affect outcomes dramatically. Rapid advancements in both acute stroke therapy and perfusion imaging techniques have resulted in continuing redefinition of the role that perfusion imaging should play in patient management. This review first discusses the basic pathophysiology of acute stroke, with specific attention to alterations in the various perfusion-related parameters that can be studied by MR perfusion imaging. Although these parameters are sometimes treated as somewhat interchangeable, they reveal greatly different information about brain perfusion. Therefore, subsequent discussion of the utility of different kinds of perfusion images focuses on the differences between them, as well as important artifacts that can complicate their interpretation. Finally, research on the continually evolving role of MR perfusion imaging in acute stroke care is summarized. PMID:21640299
Neurological outcome after arterial ischemic stroke in children
Nasiri, Jafar; Ariyana, Alireza; Yaghini, Omid; Ghazavi, Mohammad Reza; Keikhah, Mojtaba; Salari, Mehri
Background: Stroke is an important cause of disability in children. Pediatric stroke may be due to significant permanent cognitive and motor handicap in children. In this study, we evaluated long-term outcomes of stroke in pediatric patients who have been discharged with definite diagnosis of stroke in Tehran Mofid children's Hospital and Imam Hossein children's Hospital located in Isfahan, Iran, from 2005 to 2012. Materials and Methods: A total of 53 children with stroke were included in the study. Stroke outcomes as motor disability, seizures, and cognitive dysfunctions were assessed. Results: After a median follow-up of 4 years, 15 (29%) patients experienced full recovery. Thirty-eight (71%) patients had some degree of neurological handicap. Conclusion: Approximately 70% of children with arterial ischemic stroke suffer from long-term neurological disabilities including motor deficits, cognitive impairment, and late seizures. Stroke recurrence is the most important risk factor responsible for severe adverse neurological outcomes in pediatric stroke. PMID:27376046
Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke
Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.
Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. Materials and Methods This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Results Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. Conclusion For all patients a considerable region of the CTP ischemic core
Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice
Copin, Jean-Christophe; da Silva, Rafaela F; Fraga-Silva, Rodrigo A; Capettini, Luciano; Quintao, Silvia; Lenglet, Sébastien; Pelli, Graziano; Galan, Katia; Burger, Fabienne; Braunersreuther, Vincent; Schaller, Karl; Deruaz, Maud; Proudfoot, Amanda E; Dallegri, Franco; Stergiopulos, Nikolaos; Santos, Robson A S; Gasche, Yvan; Mach, François; Montecucco, Fabrizio
Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a 'cast' carotid device. In the second model, acute Evasin-3 treatment (5 minutes after cerebral ischemia onset) was assessed in mice subjected to transient left middle cerebral artery occlusion. Although CXCL1 and CXCL2 were upregulated in both atherosclerotic plaques and infarcted brain, only CXCL1 was detectable in serum. In carotid atherosclerosis, treatment with Evasin-3 was associated with reduction in intraplaque neutrophil and matrix metalloproteinase-9 content and weak increase in collagen as compared with Vehicle. In ischemic stroke, treatment with Evasin-3 was associated with reduction in ischemic brain neutrophil infiltration and protective oxidants. No other effects in clinical and histological outcomes were observed. We concluded that Evasin-3 treatment was associated with reduction in neutrophilic inflammation in both mouse models. However, Evasin-3 administration after cerebral ischemia onset failed to improve poststroke outcomes. PMID:23250107
Protein methionine oxidation augments reperfusion injury in acute ischemic stroke
Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.
Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204
Dual targeted nanocarrier for brain ischemic stroke treatment.
Zhao, Yue; Jiang, Yan; Lv, Wei; Wang, Zhongyuan; Lv, Lingyan; Wang, Baoyan; Liu, Xin; Liu, Yang; Hu, Quanyin; Sun, Wujin; Xu, Qunwei; Xin, Hongliang; Gu, Zhen
Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment. PMID:27142584
Physical exercise training and neurovascular unit in ischemic stroke.
Wang, X; Zhang, M; Feng, R; Li, W B; Ren, S Q; Zhang, J; Zhang, F
Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. In this review, we summarized the protective effects of physical exercise on neurovascular unit (NVU), including neurons, astrocytes, pericytes and the extracellular matrix. Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke. PMID:24780769
Magnetic resonance imaging in acute ischemic stroke treatment.
Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven; Kang, Dong-Wha
Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872
Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment
Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven
Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872
Acute vertebrobasilar ischemic stroke due to electric injury.
Singh Jain, Rajendra; Kumar, Sunil; Suresh, Desai Tushar; Agarwal, Rakesh
Electrical injuries are most commonly due to household accidents.Various factors determine the severity of electric injury, including type of current, amperage, voltage, tissue resistance, pathway of current,and duration of contact with the body. Various types of neurologic damage due to electrical injury have been described in literature. It may manifest as peripheral nerve injury, spinal cord damage, seizures, cerebellarataxia, hypoxic encephalopathy, and intracerebral hemorrhage. Acute ischemic stroke is an infrequent complication of electrical injury. Herein,we report a case of middle-aged man, who accidentally sustained high voltage electrical injury followed by acute vertebrobasilar ischemic stroke. Magnetic resonance imaging of the brain showed acute infarctin bilateral cerebellar and medial occipital regions. Computed tomographic angiogram of the brain and neck vessels was normal. Possibly,in our patient, the mechanism could be related to direct vascular injury due to electric current. PMID:25684743
Comparison of Performance Achievement Award Recognition With Primary Stroke Center Certification for Acute Ischemic Stroke Care
Fonarow, Gregg C.; Liang, Li; Smith, Eric E.; Reeves, Mathew J.; Saver, Jeffrey L.; Xian, Ying; Hernandez, Adrian F.; Peterson, Eric D.; Schwamm, Lee H.
Background Hospital certification and recognition programs represent 2 independent but commonly used systems to distinguish hospitals, yet they have not been directly compared. This study assessed acute ischemic stroke quality of care measure conformity by hospitals receiving Primary Stroke Center (PSC) certification and those receiving the American Heart Association's Get With The Guidelines‐Stroke (GWTG‐Stroke) Performance Achievement Award (PAA) recognition. Methods and Results The patient and hospital characteristics as well as performance/quality measures for acute ischemic stroke from 1356 hospitals participating in the GWTG‐Stroke Program 2010–2012 were compared. Hospitals were classified as PAA+/PSC+ (hospitals n=410, patients n=169 302), PAA+/PSC− (n=415, n=129 454), PAA−/PSC+ (n=88, n=26 386), and PAA−/PSC− (n=443, n=75 565). A comprehensive set of stroke measures were compared with adjustment for patient and hospital characteristics. Patient characteristics were similar by PAA and PSC status but PAA−/PSC− hospitals were more likely to be smaller and nonteaching. Measure conformity was highest for PAA+/PSC+ and PAA+/PSC− hospitals, intermediate for PAA−/PSC+ hospitals, and lowest for PAA−/PSC− hospitals (all‐or‐none care measure 91.2%, 91.2%, 84.3%, and 76.9%, respectively). After adjustment for patient and hospital characteristics, PAA+/PSC+, PAA+/PSC−, and PAA−/PSC+ hospitals had 3.15 (95% CIs 2.86 to 3.47); 3.23 (2.93 to 3.56) and 1.72 (1.47 to 2.00), higher odds for providing all indicated stroke performance measures to patients compared with PAA−/PSC− hospitals. Conclusions While both PSC certification and GWTG‐Stroke PAA recognition identified hospitals providing higher conformity with care measures for patients hospitalized with acute ischemic stroke, PAA recognition was a more robust identifier of hospitals with better performance. PMID:24125846
Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats.
Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio
Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke. PMID:25821957
Copolymer-1 Promotes Neurogenesis and Improves Functional Recovery after Acute Ischemic Stroke in Rats
Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio
Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke. PMID:25821957
Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.
Lambrinos, Anna; Schaink, Alexis K; Dhalla, Irfan; Krings, Timo; Casaubon, Leanne K; Sikich, Nancy; Lum, Cheemun; Bharatha, Aditya; Pereira, Vitor Mendes; Stotts, Grant; Saposnik, Gustavo; Kelloway, Linda; Xie, Xuanqian; Hill, Michael D
Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke. PMID:27071728
Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study
Maier, Oskar; Schröder, Christoph; Forkert, Nils Daniel; Martinetz, Thomas; Handels, Heinz
Motivation Ischemic stroke, triggered by an obstruction in the cerebral blood supply, leads to infarction of the affected brain tissue. An accurate and reproducible automatic segmentation is of high interest, since the lesion volume is an important end-point for clinical trials. However, various factors, such as the high variance in lesion shape, location and appearance, render it a difficult task. Methods In this article, nine classification methods (e.g. Generalized Linear Models, Random Decision Forests and Convolutional Neural Networks) are evaluated and compared with each other using 37 multiparametric MRI datasets of ischemic stroke patients in the sub-acute phase in terms of their accuracy and reliability for ischemic stroke lesion segmentation. Within this context, a multi-spectral classification approach is compared against mono-spectral classification performance using only FLAIR MRI datasets and two sets of expert segmentations are used for inter-observer agreement evaluation. Results and Conclusion The results of this study reveal that high-level machine learning methods lead to significantly better segmentation results compared to the rather simple classification methods, pointing towards a difficult non-linear problem. The overall best segmentation results were achieved by a Random Decision Forest and a Convolutional Neural Networks classification approach, even outperforming all previously published results. However, none of the methods tested in this work are capable of achieving results in the range of the human observer agreement and the automatic ischemic stroke lesion segmentation remains a complicated problem that needs to be explored in more detail to improve the segmentation results. PMID:26672989
Ginsenoside Rd and ischemic stroke; a short review of literatures☆
Nabavi, Seyed Fazel; Sureda, Antoni; Habtemariam, Solomon; Nabavi, Seyed Mohammad
Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID:26869821
Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.
Chou, Ping Song; Lin, Chien Hung; Chao, Hai Lun; Chao, A Ching
Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy. It suggested a central embolic source. Because the patient has paroxysmal atrial fibrillation (Af), the possible embolic sources may come from fragmentation of pre-existing intra-atrial clot. Although Af and the presence of cardiac thrombus are not contraindication for IV rt-PA in acute ischemic stroke, our case and review suggested that the administration of IV rt-PA to patients with known Af and intracardiac thrombus could represent a particular risk situation and should be carefully evaluated. PMID:22205004
Do energy drinks cause epileptic seizure and ischemic stroke?
Dikici, Suber; Saritas, Ayhan; Besir, Fahri Halit; Tasci, Ahmet Hakan; Kandis, Hayati
Energy drinks are popular among young individuals and marketed to college students, athletes, and active individuals between the ages of 21 and 35 years. We report a case that had ischemic stroke and epileptic seizure after intake of energy drink with alcohol. To the best of our knowledge, the following case is the first report of ischemic stroke after intake of energy drink. A previously healthy 37-year-old man was brought to the emergency department after a witnessed tonic-clonic seizure. According to his wife's testimony, just before loss of consciousness, the patient had been drinking 3 boxes of energy drinks (Redbull, Istanbul, Turkey, 250 mL) with vodka on an empty stomach. He did not have a history of seizures, head trauma, or family history of seizures or another disease. In cranial diffusion magnetic resonance imaging, there were hyperintense signal changes in bilateral occipital area (more pronounced in the left occipital lobe), right temporal lobe, frontal lobe, and posterior parietal lobe. All tests associated with possible etiologic causes of ischemic stroke in young patients were negative. Herein, we want to attract attention to adverse effect of energy drink usage. PMID:22867827
Effect and Safety of Rosuvastatin in Acute Ischemic Stroke
Heo, Ji Hoe; Song, Dongbeom; Nam, Hyo Suk; Kim, Eung Yeop; Kim, Young Dae; Lee, Kyung-Yul; Lee, Ki-Jeong; Yoo, Joonsang; Kim, Youn Nam; Lee, Byung Chul; Yoon, Byung-Woo; Kim, Jong S.
Background and Purpose The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. Methods This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naïve stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. Results This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53–1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2±1.0 mm3 vs. placebo: 0.3±1.3 mm3; P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. Conclusions The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation. PMID:26846760
History, Evolution, and Importance of Emergency Endovascular Treatment of Acute Ischemic Stroke.
Holodinsky, Jessalyn K; Yu, Amy Y X; Assis, Zarina A; Al Sultan, Abdulaziz S; Menon, Bijoy K; Demchuk, Andrew M; Goyal, Mayank; Hill, Michael D
More than 800,000 people in North America suffer a stroke each year, with ischemic stroke making up the majority of these cases. The outcomes of ischemic stroke range from complete functional and cognitive recovery to severe disability and death; outcome is strongly associated with timely reperfusion treatment. Historically, ischemic stroke has been treated with intravenous thrombolytic agents with moderate success. However, five recently published positive trials have established the efficacy of endovascular treatment in acute ischemic stroke. In this review, we will discuss the history of stroke treatments moving from various intravenous thrombolytic drugs to intra-arterial thrombolysis, early mechanical thrombectomy devices, and finally modern endovascular devices. Early endovascular therapy failures, recent successes, and implications for current ischemic stroke management and future research directions are discussed. PMID:27021771
Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials
Liu, Jialing; Wang, Yongting; Akamatsu, Yosuke; Lee, Chih Cheng; Stetler, R Anne; Lawton, Michael T.; Yang, Guo-Yuan
The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke. PMID:24291532
Ambient air pollution and risk of ischemic stroke and TIA
Lisabeth, LD; Escobar, JD; Dvonch, JT; Sanchez, BN; Majersik, JJ; Brown, DL; Smith, MA; Morgenstern, LB
Background Data on the association between air pollution and cerebrovascular disease in the US are limited. The objective of this study was to investigate the association between short-term exposure to ambient air pollution and risk of ischemic cerebrovascular events in a US community. Methods Daily counts of ischemic strokes/TIAs (2001–2005) were obtained from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) Project. Daily particulate matter <2.5μm in diameter (PM2.5), ozone (O3), and meteorological data were obtained from Texas Commission on Environmental Quality. To examine the association between PM2.5 and stroke/TIA risk, Poisson regression was used. Separate models included same day PM2.5, PM2.5 lagged 1–5 days, and an averaged lag effect. All models were adjusted for temperature, day of week and temporal trends in stroke/TIA. The effects of O3 were also investigated. Results Median PM2.5 was 7.0 μg/m3 (Inter Quartile Range (IQR): 4.8–10.0). There were borderline significant associations between same day (RR=1.03, 95% CI:0.99–1.07 for an IQR increase in PM2.5) and previous day (RR=1.03, 95% CI:1.00–1.07) PM2.5 and stroke/TIA risk. These associations were independent of O3, which demonstrated similar associations with stroke/TIA risk (same day RR=1.02, 95% CI: 0.97–1.08 and previous day RR=1.04, 95% CI: 0.99–1.09) in two pollutant models. Inference We observed associations between recent PM2.5 and O3 exposure and ischemic stroke/TIA risk even in this community with relatively low pollutant levels. This study provides data on environmental exposures and stroke risk in the US and suggests future research on ambient air pollution and stroke is warranted. PMID:18508356
Imaging of occlusive thrombi in acute ischemic stroke
Gasparian, GG; Sanossian, N; Shiroishi, MS; Liebeskind, DS
Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal CT and MRI, angiography and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management. PMID:25545291
Impact of baseline characteristics on outcomes of carotid artery stenting in acute ischemic stroke patients
Yu, Cheng-Sheng; Lin, Chih-Ming; Liu, Chi-Kuang; Lu, Henry Horng-Shing
Carotid artery stenting is an effective treatment for ischemic stroke patients with moderate-to-severe carotid artery stenosis. However, the midterm outcome for patients undergoing this procedure varies considerably with baseline characteristics. To determine the impact of baseline characteristics on outcomes following carotid artery stenting, data from 107 eligible patients with a first episode of ischemic stroke were collected by retrospective chart review. A modified Rankin Scale (mRS) was used to divide patients into two baseline groups, mRS ≤2 and mRS >2. A three-step decision-tree statistical analysis was conducted. After weighting the decision-tree parameters, the following impact hierarchy was obtained: admission low-density lipoprotein, gouty arthritis, chronic kidney disease, ipsilateral common carotid artery resistance index, contralateral ophthalmic artery resistance index, sex, and dyslipidemia. The finite-state machine model demonstrated that, in patients with baseline mRS ≤2, 46% had an improved mRS score at follow-up, whereas 54% had a stable mRS score. In patients with baseline mRS >2, a stable mRS score was observed in 75%, improved score in 23%, and a poorer score in 2%. Admission low-density lipoprotein was the strongest predictive factor influencing poststenting outcome. In addition, our study provides further evidence that carotid artery stenting can be of benefit in first-time ischemic stroke patients with baseline mRS scores >2. PMID:27099508
Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke.
Seppälä, Ilkka; Kleber, Marcus E; Bevan, Steve; Lyytikäinen, Leo-Pekka; Oksala, Niku; Hernesniemi, Jussi A; Mäkelä, Kari-Matti; Rothwell, Peter M; Sudlow, Cathie; Dichgans, Martin; Mononen, Nina; Vlachopoulou, Efthymia; Sinisalo, Juha; Delgado, Graciela E; Laaksonen, Reijo; Koskinen, Tuomas; Scharnagl, Hubert; Kähönen, Mika; Markus, Hugh S; März, Winfried; Lehtimäki, Terho
Asymmetric and symmetric dimethylarginines (ADMA and SDMA) impair nitric oxide bioavailability and have been implicated in the pathogenesis of atrial fibrillation (AF). Alanine-glyoxylate aminotransferase 2 (AGXT2) is the only enzyme capable of metabolizing both of the dimethylarginines. We hypothesized that two functional AGXT2 missense variants (rs37369, V140I; rs16899974, V498L) are associated with AF and its cardioembolic complications. Association analyses were conducted using 1,834 individulas with AF and 7,159 unaffected individuals from two coronary angiography cohorts and a cohort comprising patients undergoing clinical exercise testing. In coronary angiography patients without structural heart disease, the minor A allele of rs16899974 was associated with any AF (OR = 2.07, 95% CI 1.59-2.68), and with paroxysmal AF (OR = 1.98, 95% CI 1.44-2.74) and chronic AF (OR = 2.03, 95% CI 1.35-3.06) separately. We could not replicate the association with AF in the other two cohorts. However, the A allele of rs16899974 was nominally associated with ischemic stroke risk in the meta-analysis of WTCCC2 ischemic stroke cohorts (3,548 cases, 5,972 controls) and with earlier onset of first-ever ischemic stroke (360 cases) in the cohort of clinical exercise test patients. In conclusion, AGXT2 variations may be involved in the pathogenesis of AF and its age-related thromboembolic complications. PMID:26984639
Impact of baseline characteristics on outcomes of carotid artery stenting in acute ischemic stroke patients.
Yu, Cheng-Sheng; Lin, Chih-Ming; Liu, Chi-Kuang; Lu, Henry Horng-Shing
Carotid artery stenting is an effective treatment for ischemic stroke patients with moderate-to-severe carotid artery stenosis. However, the midterm outcome for patients undergoing this procedure varies considerably with baseline characteristics. To determine the impact of baseline characteristics on outcomes following carotid artery stenting, data from 107 eligible patients with a first episode of ischemic stroke were collected by retrospective chart review. A modified Rankin Scale (mRS) was used to divide patients into two baseline groups, mRS ≤2 and mRS >2. A three-step decision-tree statistical analysis was conducted. After weighting the decision-tree parameters, the following impact hierarchy was obtained: admission low-density lipoprotein, gouty arthritis, chronic kidney disease, ipsilateral common carotid artery resistance index, contralateral ophthalmic artery resistance index, sex, and dyslipidemia. The finite-state machine model demonstrated that, in patients with baseline mRS ≤2, 46% had an improved mRS score at follow-up, whereas 54% had a stable mRS score. In patients with baseline mRS >2, a stable mRS score was observed in 75%, improved score in 23%, and a poorer score in 2%. Admission low-density lipoprotein was the strongest predictive factor influencing poststenting outcome. In addition, our study provides further evidence that carotid artery stenting can be of benefit in first-time ischemic stroke patients with baseline mRS scores >2. PMID:27099508
Association of selenoprotein S gene polymorphism with ischemic stroke in a Chinese case-control study.
Li, Xiao-Xia; Guan, Hong-Jun; Liu, Jian-Ping; Guo, Yu-Peng; Yang, Yong; Niu, Ying-Ying; Yao, Li-Yan; Yang, Yin-Dong; Yue, Hong-Yu; Meng, Li-Li; Cui, Xin-Yu; Yang, Xiao-Wei; Gao, Jin-Xiao
Previous studies showed that selenoprotein S (SELS) was associated with a range of inflammatory markers, and its gene expression was influenced by a polymorphism in the promoter region. The genetic basis of the ischemic stroke has now been largely determined, so the aim of the study was to examine the role of SELS genetic variants in the ischemic stroke risk in a Chinese population. We conducted a case-control study with 239 ischemic stroke patients and 240 controls. Two single-nucleotide polymorphisms (SNPs) in SELS genes were analyzed for association with the risk of ischemic stroke in the Chinese Han population. No evidence of ischemic stroke association was observed with the SNP rs34713741. Interestingly, the strongest evidence showed that SELS SNP rs4965814 was associated with ischemic stroke (P < 0.05). We found a significant association with increased ischemic stroke risk in women carrying the CC genotype of rs4965814 [hazard ratio: 2.43(1.03-5.75)]; a similar trend was also found in men carrying the TC genotype of rs4965814 [hazard ratio: 1.81(1.06-3.08)]. SNP rs4965814 of SELS may affect the susceptibility to ischemic stroke. Understanding the inflammatory mechanisms of ischemic stroke may give new therapeutic targets to pharmacologists. PMID:25390504
Mesenchymal Stem Cells for Ischemic Stroke: Progress and Possibilities.
Maria Ferri, Anna Lucia; Bersano, Anna; Lisini, Daniela; Boncoraglio, Giorgio; Frigerio, Simona; Parati, Eugenio
Stroke is the most common neurological cause of morbidity and mortality in industrialized countries, afflicting 15 million people every year. The numbers are expected to increase, mostly due to aging populations. One in five stroke patients dies, and one in three are left with permanent disabilities. Although some acute phase therapies such as intravenous recombinant tissue plasminogen activator (rt-PA) andendovascular treatment have been shown to improve ischemic stroke outcome, these therapies are available only for a small proportion of patients. The use of stem cells to replace brain cells lost during stroke is a long-term goal, and one which is difficult to achieve given that transplanted cells must integrate and restore neural pathways to regain function of damaged parts of the brain. Over the past decade the use of mesenchymal stromal cells (MSCs) as therapy has emerged as a particularly attractive option. MSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Herein, we present a review of the application of MSCs in ischemic stroke, including the source of MSCs, the route and timing of their delivery into the brain and the endpoints measured. Experimental data of transplantation of MSCs in animal stroke models suggest an improved functional recovery. The transplantation of MSCs influences a wide range of events by modulating the inflammatory environment, stimulating endogenous neurogenesis and angiogenesis and reducing the formation of glial scar, although the precise, underlying mechanism of this phenomenon remains unknown. The results from early clinical trials highlight the need to optimize variables such as cell selection and route of administration in order to translate these results into safe and successful clinical applications. PMID:26898654
Hemodilution increases cerebral blood flow in acute ischemic stroke
Vorstrup, S.; Andersen, A.; Juhler, M.; Brun, B.; Boysen, G.
We measured cerebral blood flow in 10 consecutive, but selected, patients with acute ischemic stroke (less than 48 hours after onset) before and after hemodilution. Cerebral blood flow was measured by xenon-133 inhalation and emission tomography, and only patients with focal hypoperfusion in clinically relevant areas were included. Hemodilution was done according to the hematocrit level: for a hematocrit greater than or equal to 42%, 500 ml whole blood was drawn and replaced by the same volume of dextran 40; for a hematocrit between 37% and 42%, only 250 ml whole blood was drawn and replaced by 500 cc of dextran 40. Mean hematocrit was reduced by 16%, from 46 +/- 5% (SD) to 39 +/- 5% (SD) (p less than 0.001). Cerebral blood flow increased in both hemispheres by an average of 20.9% (p less than 0.001). Regional cerebral blood flow increased in the ischemic areas in all cases, on an average of 21.4 +/- 12.0% (SD) (p less than 0.001). In three patients, a significant redistribution of flow in favor of the hypoperfused areas was observed, and in six patients, the fractional cerebral blood flow increase in the hypoperfused areas was of the same magnitude as in the remainder of the brain. In the last patient, cerebral blood flow increased relatively less in the ischemic areas. Our findings show that cerebral blood flow increases in the ischemic areas after hemodilution therapy in stroke patients. The marked regional cerebral blood flow increase seen in some patients could imply an improved oxygen delivery to the ischemic tissue.
Medical complications experienced by first-time ischemic stroke patients during inpatient, tertiary level stroke rehabilitation
Civelek, Gul Mete; Atalay, Ayce; Turhan, Nur
[Purpose] The aim of this study was to assess the medical complications in first-time ischemic stroke patients, to identify the factors related to occurrence of complications. [Subjects and Methods] First-time ischemic stroke patients (n=81) admitted to a tertiary level inpatient rehabilitation center during a 5 year period were included in the study. The attending physiatrist noted the presence of specific medical complications and complications that required transfer to the acute care facility from patient records. The Oxfordshire Community Stroke Project classification was used to define the clinical subtypes of the ischemic stroke patients. The Charlson comorbidity index was used to evaluate co-morbid conditions. Functional disability was assessed using the Functional Independence Measure at admission and discharge. [Results] We found that 88.9% of the patients had at least one complication. The five most common complications were urinary tract infection (48.1%), shoulder pain (37.0%), insomnia (37.0%), depression (32.1%), and musculoskeletal pain other than shoulder pain (32.1%) and 11.1% of patients were transferred to acute care facility during rehabilitation period. Functional Independence Measure scores both at admission and discharge were significantly lower in patients with at least one complication than in patients with no complications. [Conclusion] Medical complications are common among patients undergoing stroke rehabilitation. Close interdisciplinary collaboration between physiatrists and other medical specialities is necessary for optimal management. PMID:27065523
Medical complications experienced by first-time ischemic stroke patients during inpatient, tertiary level stroke rehabilitation.
Civelek, Gul Mete; Atalay, Ayce; Turhan, Nur
[Purpose] The aim of this study was to assess the medical complications in first-time ischemic stroke patients, to identify the factors related to occurrence of complications. [Subjects and Methods] First-time ischemic stroke patients (n=81) admitted to a tertiary level inpatient rehabilitation center during a 5 year period were included in the study. The attending physiatrist noted the presence of specific medical complications and complications that required transfer to the acute care facility from patient records. The Oxfordshire Community Stroke Project classification was used to define the clinical subtypes of the ischemic stroke patients. The Charlson comorbidity index was used to evaluate co-morbid conditions. Functional disability was assessed using the Functional Independence Measure at admission and discharge. [Results] We found that 88.9% of the patients had at least one complication. The five most common complications were urinary tract infection (48.1%), shoulder pain (37.0%), insomnia (37.0%), depression (32.1%), and musculoskeletal pain other than shoulder pain (32.1%) and 11.1% of patients were transferred to acute care facility during rehabilitation period. Functional Independence Measure scores both at admission and discharge were significantly lower in patients with at least one complication than in patients with no complications. [Conclusion] Medical complications are common among patients undergoing stroke rehabilitation. Close interdisciplinary collaboration between physiatrists and other medical specialities is necessary for optimal management. PMID:27065523
Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke
Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra
Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917
Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke.
Mehrpour, Masoud; Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra
Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917
Gender differences in patients with acute ischemic stroke.
Caso, Valeria; Paciaroni, Maurizio; Agnelli, Giancarlo; Corea, Francesco; Ageno, Walter; Alberti, Andrea; Lanari, Alessia; Micheli, Sara; Bertolani, Luca; Venti, Michele; Palmerini, Francesco; Billeci, Antonia M R; Comi, Giancarlo; Previdi, Paolo; Silvestrelli, Giorgio
Stroke has a greater effect on women than men owing to the fact that women have more stroke events and are less likely to recover. Age-specific stroke rates are higher in men; however, because of women's longer life expectancy and the much higher incidence of stroke at older ages, women have more stroke events than men overall. The aims of this prospective study in consecutive patients were to assess whether there are gender differences in stroke risk factors, treatment or outcome. Consecutive patients with ischemic stroke were included in this prospective study at four study centers. Disability was assessed using a modified Rankin Scale score (>or=3 indicating disabling stroke) in both genders at 90 days. Outcomes and risk factors in both genders were compared using the chi(2) test. Multiple logistic regression analysis was used to identify any independent predictors of outcome. A total of 1136 patients were included in this study; of these, 494 (46%) were female. Women were statistically older compared with men: 76.02 (+/- 12.93) and 72.68 (+/- 13.27) median years of age, respectively. At admission, females had higher NIH Stroke Scale scores compared with males (9.4 [+/- 6.94] vs 7.6 [+/- 6.28] for men; p = 0.0018). Furthermore, females tended to have more cardioembolic strokes (153 [30%] vs 147 [23%] for men; p = 0.004). Males had lacunar and atherosclerotic strokes more often (146 [29%] vs 249 [39%] for men; p = 0.002, and 68 [13%] vs 123 [19%] for men; p = 0.01, respectively). The mean modified Rankin Scale score at 3 months was also significantly different between genders, at 2.5 (+/- 2.05) for women and 2.1 (+/- 2.02) for men (p = 0.003). However, at multivariate analysis, female gender was not an indicator for negative outcome. It was concluded that female gender was not an independent factor for negative outcome. In addition, both genders demonstrated different stroke pathophysiologies. These findings should be taken into account when diagnostic workup and
Ischemic penumbra in acute stroke: Demonstration by PET with fluorine-18 fluoromisonidazole
Yeh, S.H.; Liu, R.S.; Hu, H.H.
Ischemic penumbra (IP) in acute stroke has gained clinical interest since tissue functions may be recovered if perfusion can be reestablished. However, such therapeutic intervention is {open_quotes}blind{close_quotes} since clinical examination can not distinguish IP from developing infarction. In vivo demonstration of IP may have significance for stroke patient management. This study was a preliminary evaluation of detecting IP in vivo by F-18 fluoromisonidazole ([F-18]-FMISO), a hypoxic imaging agent. Static PET imaging was performed after IV injection of 370 MBq of [F-18]-FMISO at 20 and 120 min. Tomograms were reconstructed and evaluated visually in correlation with CT or MR scans. In acute stroke, patients (pts) were called back for the second PET study one month after the initial study. CT was used for confirming infarction. In 6 pts with acute cerebral infarction, three of them had intense [F-18]-FMISO retention in the penumbra surrounding the central, eclipse-like zone of absent radio-activity (infarction) at 2 hr in the acute state, and the penumbra disappeared in association with increased area of infarction on CT in one case in the chronic state. In five pts with chronic infarction, all had no penumbra of [F-18]-FMISO retention. In summary, our preliminary results demonstrate the feasibility of using [F-18]-FMISO PET to detect ischemic penumbra in vivo.
Hyperbaric Oxygen Therapy in Acute Ischemic Stroke: A Review
Ding, Zheng; Tong, Wesley C.; Lu, Xiao-Xin; Peng, Hui-Ping
Stroke, also known as cerebrovascular disease, is a common and serious neurological disease, which is also the fourth leading cause of death in the United States so far. Hyperbaric medicine, as an emerging interdisciplinary subject, has been applied in the treatment of cerebral vascular diseases since the 1960s. Now it is widely used to treat a variety of clinical disorders, especially hypoxia-induced disorders. However, owing to the complex mechanisms of hyperbaric oxygen (HBO) treatment, the therapeutic time window and the undefined dose as well as some common clinical side effects (such as middle ear barotrauma), the widespread promotion and application of HBO was hindered, slowing down the hyperbaric medicine development. In August 2013, the US Food and Drug Administration declared artery occlusion as one of the 13 specific indications for HBO therapy. This provides opportunities, to some extent, for the further development of hyperbaric medicine. Currently, the mechanisms of HBO therapy for ischemic stroke are still not very clear. This review focuses on the potential mechanisms of HBO therapy in acute ischemic stroke as well as the time window. PMID:25337089
Neuroprotection in ischemic stroke: what does the future hold?
Korczyn, Amos D; Brainin, Michael; Guekht, Alla
Neurodegenerative and vascular disease processes are commonly found concurrently in the brains of elderly patients, highlighting the difficulty in determining which processes may be responsible for cognitive impairment. Therapeutically, it may be more sensible to assume that most patients have mixed dementia. Therefore, therapies with multimodal modes of action would be expected to confer neuronal protection. Ischemic stroke is also associated with a complex pathophysiology and a high incidence of post-stroke cognitive impairment, but evidence for the efficacy of neuroprotective treatments in humans is contradictory (mainly due to a failed translation from bench to bedside). Nevertheless, emerging drug therapies continue to undergo testing in prospective, randomized, controlled studies. Natural biologicals, such as Actovegin, or smaller biological molecules with multifaceted effects in the restorative phase of ischemia are likely candidates for efficacy testing. In addition, a number of non-pharmacological interventions, especially lifestyle interventions, are also the subject of current research and would eventually be expected to supplement the treatment and prevention of ischemic stroke. PMID:25708307
Profile of prothrombotic factors in Indian children with ischemic stroke.
Konanki, Ramesh; Gulati, Sheffali; Saxena, Renu; Gupta, Arun Kumar; Seith, Ashu; Kumar, Ashok; Saxena, Anita; Kabra, Madhulika; Kalra, Veena; Lakshmy, Ramakrishnan
This study was undertaken in view of paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities. PMID:24629397
A more consistent intraluminal rhesus monkey model of ischemic stroke
Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming
Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726
[Ischemic stroke in childhood. A complication of tonsillectomy].
Matilla Álvarez, A; García Serrano, E; González de la Huebra Labrador, T; Morales Martín, A C; Yusta Martín, G; Vaquero Roncero, L M
Tonsillectomy is one of the most frequently performed otorhinolaryngological procedures on children. The postoperative complications are classified into primary or intermediate, which generally appear within 24h, and as secondary or delayed, after 48 h. We present the case of an ischemic stroke after performing a tonsillectomy on a 3 year-old boy, which was diagnosed in the immediate postoperative period. Using brain echo-doppler and angio-CT, an intraluminal clot was observed in the left internal carotid artery, probably as a result of direct vessel injury during arterial ligature for hemostasis. PMID:26025286
Anton's Syndrome due to Bilateral Ischemic Occipital Lobe Strokes
Zukić, Sanela; Sinanović, Osman; Hodžić, Renata; Mujagić, Svjetlana; Smajlović, Edina
We present a case of a patient with Anton's syndrome (i.e., visual anosognosia with confabulations), who developed bilateral occipital lobe infarct. Bilateral occipital brain damage results in blindness, and patients start to confabulate to fill in the missing sensory input. In addition, the patient occasionally becomes agitated and talks to himself, which indicates that, besides Anton's syndrome, he might have had Charles Bonnet syndrome, characterized by both visual loss and hallucinations. Anton syndrome, is not so frequent condition and is most commonly caused by ischemic stroke. In this particular case, the patient had successive bilateral occipital ischemia as a result of massive stenoses of head and neck arteries. PMID:25530893
Anton's Syndrome due to Bilateral Ischemic Occipital Lobe Strokes.
Zukić, Sanela; Sinanović, Osman; Zonić, Lejla; Hodžić, Renata; Mujagić, Svjetlana; Smajlović, Edina
We present a case of a patient with Anton's syndrome (i.e., visual anosognosia with confabulations), who developed bilateral occipital lobe infarct. Bilateral occipital brain damage results in blindness, and patients start to confabulate to fill in the missing sensory input. In addition, the patient occasionally becomes agitated and talks to himself, which indicates that, besides Anton's syndrome, he might have had Charles Bonnet syndrome, characterized by both visual loss and hallucinations. Anton syndrome, is not so frequent condition and is most commonly caused by ischemic stroke. In this particular case, the patient had successive bilateral occipital ischemia as a result of massive stenoses of head and neck arteries. PMID:25530893
Novel Thrombolytics for Acute Ischemic Stroke: Challenges and Opportunities.
Logallo, Nicola; Kvistad, Christopher E; Nacu, Aliona; Thomassen, Lars
Progress in finding a better alternative to alteplase has been slow. Tenecteplase and desmoteplase have better pharmacological profiles compared with alteplase, but definite clinical evidence of their superiority is lacking. The two major phase III studies that have tested the efficacy and safety of desmoteplase in ischemic stroke patients have shown neutral results and a promising safety profile, but the trials compared desmoteplase with placebo only in late admitted patients. Future trials should focus on testing novel thrombolytics in the early time window either as the sole acute recanalizing treatment or combined with thrombectomy. PMID:26798040
... the blockages that lead to ischemic strokes. A hemorrhagic stroke occurs if an artery in the brain leaks ... risms) are examples of conditions that can cause hemorrhagic strokes. (Aneurysms are balloon-like bulges in an artery ...
Timing of blood pressure lowering in acute ischemic stroke.
Carcel, Cheryl; Anderson, Craig S
Whether there are any benefits without harm from early lowering of blood pressure (BP) in the setting of acute ischemic stroke (AIS) has been a longstanding controversy in medicine. Whilst most studies have consistently shown associations between elevated BP, particularly systolic BP, and poor outcome, some also report that very low BP (systolic <130 mmHg) and large reductions in systolic BP are associated with poor outcomes in AIS. However, despite these associations, the observed U- or J-shaped relationship between BP and outcome in these patients may not be causally related. Patients with more severe strokes may have a more prominent autonomic response and later lower BP as their condition worsens, often pre-terminally. Fortunately, substantial progress has been made in recent years with new evidence arising from well-conducted randomized trials. This review outlines new evidence and recommendations for clinical practice over BP management in AIS. PMID:26041479
Ischemic Stroke in Confederation with Trivial Head Trauma
Shegji, Vijaykumar
Minor head injuries in children are common, resulting in brain concussion, and these injuries mostly end up without complications. Usually head trauma results in hemorrhagic stroke. Here we present a case of ischemic stroke following a trivial head trauma. A 10-month-old girl presented with posttraumatic right sided hemiparesis with right sided facial palsy. MRI brain revealed an area of acute infarct in the left capsuloganglionic region. The child was initially managed conservatively, as the hematological parameters were normal, and was started on anticoagulant therapy. An improvement in the clinical condition was achieved in 12 hrs of treatment with gain in power and resolution of weakness in 10 days. The specific cause for hemiparesis in the child is not elicited; possibility of genetic and environmental factors can be attributable. PMID:27313936
NINJ2 polymorphism is associated with ischemic stroke in Chinese Han population.
Wan, Xin-hong; Li, Shu-juan; Cheng, Ping; Zhang, Qi; Yang, Xin-chun; Zhong, Guang-zhen; Hu, Wen-li; Jin, Li; Wang, Xiao-feng
Recently, a genome-wide association study reported an association between two single nucleotide polymorphisms (SNPs) rs11833579 and rs12425791 near NINJ2 gene and ischemic stroke in Caucasians. Therefore, NINJ2 gene is an important candidate locus in the prevalence of ischemic stroke. We performed a hospital based genetic association study in Chinese Han subjects to investigate the relationship between NINJ2 gene and ischemic stroke. We genotyped 14 tagging single nucleotide polymorphisms (tSNP) in 749 ischemic stroke subjects and 924 control subjects and conducted the association between these tSNPs and ischemic stroke. We detected a tSNP rs10849373 in the first intron of the NINJ2 gene significantly associated with ischemic stroke (both genotype and allelic p=0.0001). The minor A allele increased the risk of ischemic stroke with a per-allele OR of 1.37 for the additive genetic model in univariate analysis (p=0.0001). The significance remained after adjustment for the covariates of age, gender, BMI, cigarette smoking, alcohol drinking, hypertension, and diabetes. Therefore, we report a new genetic variant, rs10849373, located in the first intron of the NINJ2 gene, conferring risk of ischemic stroke in Chinese Han subjects. Further genetic association and functional studies are required to search the causal functional variant in linkage disequilibrium with this polymorphism. PMID:21722921
Neurotoxic lipid peroxidation species formed by ischemic stroke increase injury
Zeiger, Stephanie L. H.; Musiek, Erik S.; Zanoni, Giuseppe; Vidari, Giovanni; Morrow, Jason D.; Milne, Ginger J.; McLaughlin, BethAnn
Stroke is the third leading cause of death in the United States yet no neuroprotective agents for treatment are clinically available. There is a pressing need to understand the signaling molecules which mediate ischemic cell death and identify novel neuroprotective targets. Cyclopentenone isoprostanes (IsoP), formed following free radical mediated peroxidation of arachidonic acid, are used as markers of stress but their bioactivity is poorly understood. We have recently shown that 15-A2t-Isop is a potent neurotoxin in vitro and increases the free radical burden in neurons. In this work, we demonstrate that 15-A2t-IsoP is abundantly produced in stroke infarcted human cortical tissue. Using primary neuronal cultures we found that minimally toxic exposure to 15-A2t-IsoP does not alter ATP content, but in combination with oxygen glucose deprivation resulted in a significant hyperpolarization of the mitochondrial membrane and dramatically increased neuronal cell death. In the presence of Ca2+, 15-A2t-IsoP led to a rapid induction of the permeability transition pore and release of cytochrome c. Taken with our previous work, these data support a model in which ischemia causes generation of reactive oxygen species, calcium influx, lipid peroxidation and 15-A2t-IsoP formation. These factors combine to enhance opening of the permeability transition pore leading to cell death subsequent to mitochondrial cytochrome c release. This data is the first documentation of significant 15-A2t-IsoP formation following acute ischemic stroke and suggests addition of 15-A2t-IsoP to in vitro models of ischemia may help to more fully recapitulate stroke injury. PMID:19699297
Carotid Artery Stenosis with Acute Ischemic Stroke: Stenting versus Angioplasty
Villwock, Mark R.; Padalino, David J.; Deshaies, Eric M.
Background When a patient with carotid artery stenosis presents emergently with acute ischemic stroke, the optimum treatment plan is not clearly defined. If intervention is warranted, and open surgery is prohibitive, endovascular revascularization may be performed. The use of stents places the patient at additional risk due to their thrombogenic potential. The intent of this study was to compare outcomes following endovascular approaches (angioplasty alone vs. stent) in the setting of acute stroke. Methods We extracted a population from the National Inpatient Sample (2012) and the Nationwide Inpatient Sample (2003–2011) composed of patients with carotid artery stenosis with infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with mechanical thrombectomy or thrombolysis were excluded. Categorical variables were compared between treatment groups with Chi-squared tests. Binary logistic regression was performed to evaluate mortality and iatrogenic stroke while controlling for age, case severity, and comorbidity burden. Results About 6,333 admissions met our criteria. A majority were treated via stenting (89%, n = 5,608). The angioplasty-alone group had significantly higher mortality (9.0% vs. 3.8%, p < 0.001) and iatrogenic stroke rate (3.9% vs. 1.9%, p < 0.001) than the stent group. The adjusted odds ratios of mortality and iatrogenic stroke for patients treated with angioplasty alone were 1.953 (p < 0.001) and 1.451 (p = 0.105), respectively, in comparison to patients treated with carotid stenting. Conclusion Multivariate analysis found the risk of mortality to be elevated following angioplasty alone. This may represent selection bias, but it also may indicate that symptomatic patients with stroke suffer from severe stenosis and unstable plaques that would benefit from stent placement. These results would caution angioplasty alone as an arm of a future randomized trial involving this severely burdened patient
Dynamic changes in neuronal autophagy and apoptosis in the ischemic penumbra following permanent ischemic stroke
Deng, Yi-hao; He, Hong-yun; Yang, Li-qiang; Zhang, Peng-yue
The temporal dynamics of neuronal autophagy and apoptosis in the ischemic penumbra following stroke remains unclear. Therefore, in this study, we investigated the dynamic changes in autophagy and apoptosis in the penumbra to provide insight into potential therapeutic targets for stroke. An adult Sprague-Dawley rat model of permanent ischemic stroke was prepared by middle cerebral artery occlusion. Neuronal autophagy and apoptosis in the penumbra post-ischemia were evaluated by western blot assay and immunofluorescence staining with antibodies against LC3-II and cleaved caspase-3, respectively. Levels of both LC3-II and cleaved caspase-3 in the penumbra gradually increased within 5 hours post-ischemia. Thereafter, levels of both proteins declined, especially LC3-II. The cerebral infarct volume increased slowly 1–4 hours after ischemia, but subsequently increased rapidly until 5 hours after ischemia. The severity of the neurological deficit was positively correlated with infarct volume. LC3-II and cleaved caspase-3 levels were high in the penumbra within 5 hours after ischemia, and after that, levels of these proteins decreased at different rates. LC3-II levels were reduced to a very low level, but cleaved caspase-3 levels remained high 72 hours after ischemia. These results indicate that there are temporal differences in the activation status of the autophagic and apoptotic pathways. This suggests that therapeutic targeting of these pathways should take into consideration their unique temporal dynamics.
Ultrahigh-Field MRI in Human Ischemic Stroke – a 7 Tesla Study
Bauer, Miriam; Stengl, Katharina L.; Mutke, Matthias A.; Tovar-Martinez, Elena; Wuerfel, Jens; Endres, Matthias; Niendorf, Thoralf; Sobesky, Jan
Introduction Magnetic resonance imaging (MRI) using field strengths up to 3 Tesla (T) has proven to be a powerful tool for stroke diagnosis. Recently, ultrahigh-field (UHF) MRI at 7 T has shown relevant diagnostic benefits in imaging of neurological diseases, but its value for stroke imaging has not been investigated yet. We present the first evaluation of a clinically feasible stroke imaging protocol at 7 T. For comparison an established stroke imaging protocol was applied at 3 T. Methods In a prospective imaging study seven patients with subacute and chronic stroke were included. Imaging at 3 T was immediately followed by 7 T imaging. Both protocols included T1-weighted 3D Magnetization-Prepared Rapid-Acquired Gradient-Echo (3D-MPRAGE), T2-weighted 2D Fluid Attenuated Inversion Recovery (2D-FLAIR), T2-weighted 2D Fluid Attenuated Inversion Recovery (2D-T2-TSE), T2* weighted 2D Fast Low Angle Shot Gradient Echo (2D-HemoFLASH) and 3D Time-of-Flight angiography (3D-TOF). Results The diagnostic information relevant for clinical stroke imaging obtained at 3 T was equally available at 7 T. Higher spatial resolution at 7 T revealed more anatomical details precisely depicting ischemic lesions and periinfarct alterations. A clear benefit in anatomical resolution was also demonstrated for vessel imaging at 7 T. RF power deposition constraints induced scan time prolongation and reduced brain coverage for 2D-FLAIR, 2D-T2-TSE and 3D-TOF at 7 T versus 3 T. Conclusions The potential of 7 T MRI for human stroke imaging is shown. Our pilot study encourages a further evaluation of the diagnostic benefit of stroke imaging at 7 T in a larger study. PMID:22701525
Intravenous thrombolysis, mechanical embolectomy, and intracranial stenting for hyperacute ischemic stroke in a patient with moyamoya disease.
Argetsinger, Debora S; Miller, Jeffrey W; Fletcher, Jeffrey J
The Japanese translation of moyamoya means "puff of smoke" and refers to the angiographic appearance of dilated collateral vessels seen during chronic progressive narrowing of the intracranial supraclinoid portions of the internal carotid arteries. Despite cerebral ischemia being the most common presenting symptom, 20% to 40% of adults suffer a hemorrhagic stroke. Due to the lack of evidence and histopathologic findings, intravenous and endovascular reperfusion therapy is typically avoided. This case study presents a patient with moyamoya disease in the hyperacute phase of ischemic stroke. The patient received full dose (0.9mg/kg) tissue plasminogen activator and subsequently underwent a mechanical clot extraction and Wingspan stent (Stryker, Kalamazoo, MI, USA) placement. The use of these options in the setting of moyamoya disease is novel. This demonstrates that moyamoya disease may not be an absolute contraindication to revascularization in hyperacute ischemic stroke and underscores that many perceived contraindications to thrombolytic and mechanical revascularization therapies are relative. PMID:26896911
Circadian variation in stroke onset: identical temporal pattern in ischemic and hemorrhagic events.
Manfredini, Roberto; Boari, Benedetta; Smolensky, Michael H; Salmi, Raffaella; la Cecilia, Olga; Maria Malagoni, Anna; Haus, Erhard; Manfredini, Fabio
Stroke is the culmination of a heterogeneous group of cerebrovascular diseases that is manifested as ischemia or hemorrhage of one or more blood vessels of the brain. The occurrence of many acute cardiovascular events--such as myocardial infarction, sudden cardiac death, pulmonary embolism, critical limb ischemia, and aortic aneurysm rupture--exhibits prominent 24 h patterning, with a major morning peak and secondary early evening peak. The incidence of stroke exhibits the same 24 h pattern. Although ischemic and hemorrhagic strokes are different entities and are characterized by different pathophysiological mechanisms, they share an identical double-peak 24 h pattern. A constellation of endogenous circadian rhythms and exogenous cyclic factors are involved. The staging of the circadian rhythms in vascular tone, coagulative balance, and blood pressure plus temporal patterns in posture, physical activity, emotional stress, and medication effects play central and/or triggering roles. Features of the circadian rhythm of blood pressure, in terms of their chronic and acute effects on cerebral vessels, and of coagulation are especially important. Clinical medicine has been most concerned with the prevention of stroke in the morning, when population-based studies show it is of greatest risk during the 24 h; however, improved protection of at-risk patients against stroke in the early evening, the second most vulnerable time of cerebrovascular accidents, has received relatively little attention thus far. PMID:16076646
Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis
Low, Audrey S. L.; Lunt, Mark; Mercer, Louise K.; Watson, Kath D.; Dixon, William G.; Symmons, Deborah P. M.
Objective Patients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30‐day and 1‐year mortality after ischemic stroke. Methods Patients with RA starting therapy with TNFi and a biologics‐naive comparator group treated with synthetic disease‐modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever‐exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD–treated patients and TNFi‐treated patients using logistic regression, adjusted for age and sex. Results To April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD–treated patients and 106 in 11,642 TNFi‐treated patients) occurred during 11,973 and 61,226 person‐years of observation, respectively (incidence rate 175 versus 173 per 100,000 person‐years). After adjustment for confounders, there was no association between ever‐exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54–1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03–1.21] and 0.60 [95
Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats.
Chao, Xiaodong; Zhou, Jun; Chen, Tao; Liu, Wenbo; Dong, Wenpeng; Qu, Yan; Jiang, Xiaofan; Ji, Xituan; Zhen, Haining; Fei, Zhou
Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1β and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1β and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke. PMID:20869955
Ginsberg, Myron D.
Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safety-feasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4–6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials. This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany
Endothelial Dysfunction and Procoagulant Activity in Acute Ischemic Stroke
Blum, Arnon; Vaispapir, Vladimir; Keinan-Boker, Lital; Soboh, Soboh; Yehuda, Hila; Tamir, Snait
Endothelium-dependent vasodilator function may be regarded as an index of inflammation. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity, and outcome. Our aim was to measure systemic vascular function directly (using forearm flow mediated dilatation) in patients with acute ischemic stroke and to clarify whether recent acute ischemic stroke is associated with impaired vascular function. Patients who were not eligible for thrombolytic therapy because of delayed arrival were randomly recruited to the study after signing a consent form. All 43 patients were conscious and had an acute ischemic stroke. Brain CT was performed on admission, and clinical evaluation was carried out by a neurologist on admission and four days later. Vascular responsiveness was evaluated by ABI and by endothelial function measurements on admission. Levels of P-selectin were measured during the first 24 hrs and on day 4. Forty-three patients (28 men and 15 women) and 23 healthy men (control) were enrolled in the study. Patients were older (62.4±12.5 y vs 44.2±11.6 y, p=0.001), had worse endothelial dysfunction (–4.4±7.4% vs 16.6±7.6%, p=0.001), and had a higher BMI (28±6 vs 24±5, p=0.001). No gender effect was found in endothelial function (–5.1±7.8% vs –2.5±6.6%, p=0.25) and ABI (1.0±0.26 vs 1.0±0.5, p=0.29). However, men had lower BMIs compared to women (26.8±5.8 vs 31.4±5.5, p=0.01). The neurological scale decreased from 4.9±3.4 to 3.2±3.0 on day 4 (p=0.001). In men, it was 4.8±3.8 on admission, and decreased to 3.2±3.4 on day 4 (p=0.001). In women, it was 5.0±2.7, and decreased to 3.3±2.3 on day 4 (p=0.001). P-selectin levels were high on admission (68.0±55.5 pg/ml) and increased 4 days later (102.3±72.0 pg/ml) (p=0.01). Men had higher levels on admission (79.1± 66.7 pg/ml vs 48.9± 15.4 pg/ml, p=0.02) and rose on day 4 to 113.6±82.6 pg/ml (p=0.05); in women P
An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes
Muiño, Elena; Krupinski, Jurek; Carrera, Caty; Gallego-Fabrega, Cristina; Montaner, Joan; Fernández-Cadenas, Israel
Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. Methods. We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. Results. Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke (p value <0.05). The score generated was only associated with the cardioembolic stroke subtype (p value: 0.001) and was replicated in an independent cohort (p value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002). Conclusion. The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes. PMID:26355258
Mean platelet volume is related with ischemic stroke in patients with sinus rhythm.
Özkan, Buğra; Arik, Osman Z; Gözükara, Mehmet Y; Şahin, Durmuş Y; Topal, Salih; Uysal, Onur K; Elbasan, Zafer; Epçeliden, Tuncay; Çayli, Murat; Gür, Mustafa
Stroke is the leading cause of disability worldwide. It is known that atrial fibrillation and left atrial enlargement contribute ischemic stroke, and mean platelet volume (MPV) increases in patients with ischemic stroke and atrial fibrillation. We aimed to determine whether higher MPV is associated with ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched healthy individuals as control group (Group 2). After physical and echocardiographic examination, 24-48 h Holter monitoring and complete blood counts were studied. There were no statistically significant differences in age, sex rates, and comorbidities between groups. Left atrial diameter was higher in Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was significantly higher in Group 1 (P < 0.001) and was an independent determinant [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In conclusion, higher MPV is associated with acute ischemic stroke in patients with sinus rhythm and without heart failure or left atrial enlargement. MPV and left atrial diameter are independent predictors of ischemic stroke in this patient population. PMID:24686100
Variation in mortality of ischemic and hemorrhagic strokes in relation to high temperature
NASA Astrophysics Data System (ADS)
Lim, Youn-Hee; Kim, Ho; Hong, Yun-Chul
Outdoor temperature has been reported to have a significant influence on the seasonal variations of stroke mortality, but few studies have investigated the effect of high temperature on the mortality of ischemic and hemorrhagic strokes. The main study goal was to examine the effect of temperature, particularly high temperature, on ischemic and hemorrhagic strokes. We investigated the association between outdoor temperature and stroke mortality in four metropolitan cities in Korea during 1992-2007. We used time series analysis of the age-adjusted mortality rate for ischemic and hemorrhagic stroke deaths by using generalized additive and generalized linear models, and estimated the percentage change of mortality rate associated with a 1°C increase of mean temperature. The temperature-responses for the hemorrhagic and ischemic stroke mortality differed, particularly in the range of high temperature. The estimated percentage change of ischemic stroke mortality above a threshold temperature was 5.4 % (95 % CI, 3.9-6.9 %) in Seoul, 4.1 % (95 % CI, 1.6-6.6 %) in Incheon, 2.3 % (-0.2 to 5.0 %) in Daegu and 3.6 % (0.7-6.6 %) in Busan, after controlling for daily mean humidity, mean air pressure, day of the week, season, and year. Additional adjustment of air pollution concentrations in the model did not change the effects. Hemorrhagic stroke mortality risk significantly decreased with increasing temperature without a threshold in the four cities after adjusting for confounders. These findings suggest that the mortality of hemorrhagic and ischemic strokes show different patterns in relation to outdoor temperature. High temperature was harmful for ischemic stroke but not for hemorrhagic stroke. The risk of high temperature to ischemic stroke did not differ by age or gender.
Factors associated with unfavorable outcome in minor ischemic stroke
Uehara, Toshiyuki; Ohara, Tomoyuki; Suzuki, Rieko; Toyoda, Kazunori; Minematsu, Kazuo
Objectives: The purpose of this study was to elucidate the factors that correlate with unfavorable outcomes and to develop a simple validated model for assessing risk of unfavorable outcomes in patients with minor ischemic stroke. Methods: The derivation cohort included 1,313 patients hospitalized within 72 hours after onset with an initial NIH Stroke Scale score of 0 to 3 enrolled in a prospective, multicenter, observational study. Unfavorable outcome was defined as dependency (modified Rankin Scale score of 3–5) or death at 90 days. The predictive values of factors related to unfavorable outcome were evaluated. External validation was performed in 879 patients from a single-center stroke registry. Results: In the derivation cohort, a total of 203 patients (15%) had unfavorable outcomes. On multivariable analysis, women (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.30–2.94), age ≥72 years (OR 2.80, 95% CI 1.83–4.36), intra/extracranial vascular occlusive lesion (OR 2.80, 95% CI 1.82–4.28), leg weakness (OR 1.72, 95% CI 1.06–2.82), and extinction/inattention (OR 5.55, 95% CI 1.30–21.71) were independently associated with unfavorable outcome. Patients having both a vascular lesion and either leg weakness or extinction/inattention showed 4.63 (95% CI 2.23–9.33) times the risk of unfavorable outcome compared with those having neither. In the validation cohort, the risk was similar, at 3.77 (95% CI 1.64–8.37). Conclusions: Intra- and extracranial vascular imaging, NIH Stroke Scale items such as leg weakness and extinction/inattention, and their combination, as well as female sex and advanced age, may be useful for predicting unfavorable outcomes in patients with minor stroke. PMID:24907232
Withdrawal of Antithrombotic Agents and Its Impact on Ischemic Stroke Occurrence
Broderick, Joseph P.; Bonomo, Jordan B.; Kissela, Brett M.; Khoury, Jane C.; Moomaw, Charles J.; Alwell, Kathleen; Woo, Daniel; Flaherty, Matthew L.; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Kleindorfer, Dawn O.
Background Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication. Methods and Results Patient records from the population-based Greater Cincinnati / Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review. Results In 2005, 2,197 cases of ischemic stroke among residents of the region were identified via hospital discharge records. Of the 2,197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal: 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes following withdrawal, 71 (62.3%) were first-ever, and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period. Conclusions The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance. PMID:21719769
Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients.
Zhang, Xia; Huang, Zhi-Chao; Lu, Tao-Sheng; You, Shou-Jiang; Cao, Yong-Jun; Liu, Chun-Feng
The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (μmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 μmol/L) or lower UA levels (≤250 μmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 μmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 μmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 μmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 μmol/L were seven times more
A Retrospective Cohort Study Comparing Stroke Recurrence Rate in Ischemic Stroke Patients With and Without Acupuncture Treatment.
Shih, Chun-Chuan; Liao, Chien-Chang; Sun, Mao-Feng; Su, Yi-Chang; Wen, Chi-Pang; Morisky, Donald E; Sung, Fung-Chang; Hsu, Chung Y; Lin, Jaung-Geng
Little was known about the effects of acupuncture on stroke recurrence. The aim of this study is to investigate whether ischemic stroke patients receiving acupuncture treatment have a decreased risk of stroke recurrence. A retrospective cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004 was conducted based on the claims of Taiwan National Health Insurance Research Database. The use of acupuncture treatment and stroke recurrence were identified during the follow-up period from 2000 to 2009. This study compared the risk of stroke recurrence between ischemic stroke cohorts with and without acupuncture treatment by calculating adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acupuncture associated with stroke recurrence in the Cox proportional hazard model. The stroke recurrence rate per 1000 person-years decreased from 71.4 without to 69.9 with acupuncture treatment (P < 0.001). Acupuncture treatment was associated with reduced risk of stroke recurrence (HR 0.88; 95% CI 0.84-0.91). The acupuncture effect was noted in patients with or without medical treatment for stroke prevention but its impact decreased with aging of stroke patients. Compared with stroke patients without acupuncture treatment and medication therapy, the hazard ratios of stroke recurrence for those had medication therapy only, acupuncture only, and both were 0.42 (95% CI 0.38-0.46), 0.50 (95% CI 0.43-0.57), and 0.39 (95% CI 0.35-0.43), respectively. This study raises the possibility that acupuncture might be effective in lowering stroke recurrence rate even in those on medications for stroke prevention. Results suggest the need of prospective sham-controlled and randomized trials to establish the efficacy of acupuncture in preventing stroke. PMID:26426630
A Retrospective Cohort Study Comparing Stroke Recurrence Rate in Ischemic Stroke Patients With and Without Acupuncture Treatment
Shih, Chun-Chuan; Liao, Chien-Chang; Sun, Mao-Feng; Su, Yi-Chang; Wen, Chi-Pang; Morisky, Donald E.; Sung, Fung-Chang; Hsu, Chung Y.; Lin, Jaung-Geng
Abstract Little was known about the effects of acupuncture on stroke recurrence. The aim of this study is to investigate whether ischemic stroke patients receiving acupuncture treatment have a decreased risk of stroke recurrence. A retrospective cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004 was conducted based on the claims of Taiwan National Health Insurance Research Database. The use of acupuncture treatment and stroke recurrence were identified during the follow-up period from 2000 to 2009. This study compared the risk of stroke recurrence between ischemic stroke cohorts with and without acupuncture treatment by calculating adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acupuncture associated with stroke recurrence in the Cox proportional hazard model. The stroke recurrence rate per 1000 person-years decreased from 71.4 without to 69.9 with acupuncture treatment (P < 0.001). Acupuncture treatment was associated with reduced risk of stroke recurrence (HR 0.88; 95% CI 0.84–0.91). The acupuncture effect was noted in patients with or without medical treatment for stroke prevention but its impact decreased with aging of stroke patients. Compared with stroke patients without acupuncture treatment and medication therapy, the hazard ratios of stroke recurrence for those had medication therapy only, acupuncture only, and both were 0.42 (95% CI 0.38–0.46), 0.50 (95% CI 0.43–0.57), and 0.39 (95% CI 0.35–0.43), respectively. This study raises the possibility that acupuncture might be effective in lowering stroke recurrence rate even in those on medications for stroke prevention. Results suggest the need of prospective sham-controlled and randomized trials to establish the efficacy of acupuncture in preventing stroke. PMID:26426630
The Effects of Air Pollution on Ischemic Stroke Admission Rate
Alimohammadi, Hossein; Fakhri, Sara; Derakhshanfar, Hojjat; Hosseini-Zijoud, Seyed-Mostafa; Safari, Saeed
The present study aimed to determine the relationship between the level of air pollutants and the rate of ischemic stroke (IS) admissions to hospitals. In this retrospective cross-sectional study, stroke admissions (January-March 2012 and 2013) to an emergency department and air pollution and meteorological data were gathered. The relationship between air pollutant levels and hospital admission rates were evaluated using the generalize additive model. In all 379 patients with IS were referred to the hospital (52.5% male; mean age 68.2±13.3 years). Both transient (p<0.001) and long-term (p<0.001) rises in CO level increases the risk of IS. Increased weekly (p<0.001) and monthly (p<0.001) average O3 levels amplifies this risk, while a transient increase in NO2 (p<0.001) and SO2 (p<0.001) levels has the same effect. Long-term changes in PM10 (p<0.001) and PM2.5 (p<0.001) also increase the risk of IS. The findings showed that the level of air pollutants directly correlates with the number of stroke admissions to the emergency department. PMID:26866000
Critical Care for Patients with Massive Ischemic Stroke
Koh, Younsuck; Choi, H. Alex; Lee, Kiwon
Malignant cerebral edema following ischemic stroke is life threatening, as it can cause inadequate blood flow and perfusion leading to irreversible tissue hypoxia and metabolic crisis. Increased intracranial pressure and brain shift can cause herniation syndrome and finally brain death. Multiple randomized clinical trials have shown that preemptive decompressive hemicraniectomy effectively reduces mortality and morbidity in patients with malignant middle cerebral artery infarction. Another life-saving decompressive surgery is suboccipital craniectomy for patients with brainstem compression by edematous cerebellar infarction. In addition to decompressive surgery, cerebrospinal fluid drainage by ventriculostomy should be considered for patients with acute hydrocephalus following stroke. Medical treatment begins with sedation, analgesia, and general measures including ventilatory support, head elevation, maintaining a neutral neck position, and avoiding conditions associated with intracranial hypertension. Optimization of cerebral perfusion pressure and reduction of intracranial pressure should always be pursued simultaneously. Osmotherapy with mannitol is the standard treatment for intracranial hypertension, but hypertonic saline is also an effective alternative. Therapeutic hypothermia may also be considered for treatment of brain edema and intracranial hypertension, but its neuroprotective effects have not been demonstrated in stroke. Barbiturate coma therapy has been used to reduce metabolic demand, but has become less popular because of its systemic adverse effects. Furthermore, general medical care is critical because of the complex interactions between the brain and other organ systems. Some challenging aspects of critical care, including ventilator support, sedation and analgesia, and performing neurological examinations in the setting of a minimal stimulation protocol, are addressed in this review. PMID:25328873
The Effects of Air Pollution on Ischemic Stroke Admission Rate.
Alimohammadi, Hossein; Fakhri, Sara; Derakhshanfar, Hojjat; Hosseini-Zijoud, Seyed-Mostafa; Safari, Saeed; Hatamabadi, Hamid Reza
The present study aimed to determine the relationship between the level of air pollutants and the rate of ischemic stroke (IS) admissions to hospitals. In this retrospective cross-sectional study, stroke admissions (January-March 2012 and 2013) to an emergency department and air pollution and meteorological data were gathered. The relationship between air pollutant levels and hospital admission rates were evaluated using the generalize additive model. In all 379 patients with IS were referred to the hospital (52.5% male; mean age 68.2±13.3 years). Both transient (p<0.001) and long-term (p<0.001) rises in CO level increases the risk of IS. Increased weekly (p<0.001) and monthly (p<0.001) average O3 levels amplifies this risk, while a transient increase in NO2 (p<0.001) and SO2 (p<0.001) levels has the same effect. Long-term changes in PM10 (p<0.001) and PM2.5 (p<0.001) also increase the risk of IS. The findings showed that the level of air pollutants directly correlates with the number of stroke admissions to the emergency department. PMID:26866000
Shared genetic basis for migraine and ischemic stroke
Malik, Rainer; Freilinger, Tobias; Winsvold, Bendik S.; Anttila, Verneri; Vander Heiden, Jason; Traylor, Matthew; de Vries, Boukje; Holliday, Elizabeth G.; Terwindt, Gisela M.; Sturm, Jonathan; Bis, Joshua C.; Hopewell, Jemma C.; Ferrari, Michel D.; Rannikmae, Kristiina; Wessman, Maija; Kallela, Mikko; Kubisch, Christian; Fornage, Myriam; Meschia, James F.; Lehtimäki, Terho; Sudlow, Cathie; Clarke, Robert; Chasman, Daniel I.; Mitchell, Braxton D.; Maguire, Jane; Kaprio, Jaakko; Farrall, Martin; Raitakari, Olli T.; Kurth, Tobias; Ikram, M. Arfan; Reiner, Alex P.; Longstreth, W.T.; Rothwell, Peter M.; Strachan, David P.; Sharma, Pankaj; Seshadri, Sudha; Quaye, Lydia; Cherkas, Lynn; Schürks, Markus; Rosand, Jonathan; Ligthart, Lannie; Boncoraglio, Giorgio B.; Davey Smith, George; van Duijn, Cornelia M.; Stefansson, Kari; Worrall, Bradford B.; Nyholt, Dale R.; Markus, Hugh S.; van den Maagdenberg, Arn M.J.M.; Cotsapas, Chris; Zwart, John A.; Palotie, Aarno
Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10−28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10−20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype. PMID:25934857
Serum activity of angiotensin converting enzyme 2 is decreased in patients with acute ischemic stroke.
Bennion, Douglas M; Rosado, Christian A; Haltigan, Emily A; Regenhardt, Robert W; Sumners, Colin; Waters, Michael F
Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective carboxypeptidase, are dynamically altered after stroke in preclinical models. We sought to characterize the previously unexplored changes in serum ACE2 activity of stroke patients and the mechanism of these changes. Serum samples were obtained from patients during acute ischemic stroke (n=39), conditions mimicking stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity levels were analyzed by fluorometric assay and correlated with clinical variables by regression analyses. Serum ACE2 activity was significantly lower in acute ischemic stroke as compared to both control and stroke-alert patients, followed by an increase to control levels at three days. Serum ACE2 activity significantly correlated with the presence of ischemic stroke after controlling for other factors (P=0.01). Additional associations with ACE2 activity included a positive correlation with systolic blood pressure at presentation in stroke-alert (R(2)=0.24, P=0.03), while stroke levels showed no correlation (R(2)=0.01, P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic changes in serum ACE2 activity in stroke, which concur with preclinical studies, are not likely to be driven primarily by acute changes in blood pressure or sheddase activity. These findings provide new insight for developing therapies targeting this protective system in ischemic stroke. PMID:27488276
Shared genetic contribution to ischemic stroke and Alzheimer's disease
Adib‐Samii, Poneh; Harold, Denise; Dichgans, Martin; Williams, Julie; Lewis, Cathryn M.; Markus, Hugh S.; Fornage, Myriam; Holliday, Elizabeth G; Sharma, Pankaj; Bis, Joshua C; Psaty, Bruce M; Seshadri, Sudha; Nalls, Mike A; Devan, William J; Boncoraglio, Giorgio; Malik, Rainer; Mitchell, Braxton D; Kittner, Steven J; Ikram, M Arfan; Clarke, Robert; Rosand, Jonathan; Meschia, James F; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Bevan, Steve; Kilarski, Laura L; Walters, Matthew; Thijs, Vincent; Slowik, Agnieszka; Lindgren, Arne; de Bakker, Paul I W; Lambert, Jean‐Charles; Ibrahim‐Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier‐Boley, Benjamin; Russo, Giancarlo; Thornton‐Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao‐Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie‐Thçrèse; Choi, Seung‐Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiçvet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger‐Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George‐Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez‐Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton‐Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li‐San; Dartigues, Jean‐François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak‐Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe
Objective Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases. Methods Using genome‐wide association study (GWAS) data from METASTROKE + (15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype‐level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome‐wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome‐wide single‐nucleotide polymorphism (SNP) data. We then performed a meta‐analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred. Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG [standard error] = 0.37 [0.17]; p = 0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta‐analysis of AD IGAP and METASTROKE + small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1) associated with both diseases (p = 1.8 × 10−8). A pathway analysis identified four associated pathways involving cholesterol transport and immune response. Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739–747 PMID:26913989
Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine
Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen
Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837
Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine.
Seto, Sai-Wang; Chang, Dennis; Jenkins, Anita; Bensoussan, Alan; Kiat, Hosen
Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID:27275837
Associations of functional alanine-glyoxylate aminotransferase 2 gene variants with atrial fibrillation and ischemic stroke
Seppälä, Ilkka; Kleber, Marcus E.; Bevan, Steve; Lyytikäinen, Leo-Pekka; Oksala, Niku; Hernesniemi, Jussi A.; Mäkelä, Kari-Matti; Rothwell, Peter M.; Sudlow, Cathie; Dichgans, Martin; Mononen, Nina; Vlachopoulou, Efthymia; Sinisalo, Juha; Delgado, Graciela E.; Laaksonen, Reijo; Koskinen, Tuomas; Scharnagl, Hubert; Kähönen, Mika; Markus, Hugh S.; März, Winfried; Lehtimäki, Terho
Asymmetric and symmetric dimethylarginines (ADMA and SDMA) impair nitric oxide bioavailability and have been implicated in the pathogenesis of atrial fibrillation (AF). Alanine–glyoxylate aminotransferase 2 (AGXT2) is the only enzyme capable of metabolizing both of the dimethylarginines. We hypothesized that two functional AGXT2 missense variants (rs37369, V140I; rs16899974, V498L) are associated with AF and its cardioembolic complications. Association analyses were conducted using 1,834 individulas with AF and 7,159 unaffected individuals from two coronary angiography cohorts and a cohort comprising patients undergoing clinical exercise testing. In coronary angiography patients without structural heart disease, the minor A allele of rs16899974 was associated with any AF (OR = 2.07, 95% CI 1.59-2.68), and with paroxysmal AF (OR = 1.98, 95% CI 1.44–2.74) and chronic AF (OR = 2.03, 95% CI 1.35–3.06) separately. We could not replicate the association with AF in the other two cohorts. However, the A allele of rs16899974 was nominally associated with ischemic stroke risk in the meta-analysis of WTCCC2 ischemic stroke cohorts (3,548 cases, 5,972 controls) and with earlier onset of first-ever ischemic stroke (360 cases) in the cohort of clinical exercise test patients. In conclusion, AGXT2 variations may be involved in the pathogenesis of AF and its age-related thromboembolic complications. PMID:26984639
Statins in Acute Ischemic Stroke: A Systematic Review
Hong, Keun-Sik; Lee, Ji Sung
Background and Purpose Statins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS. Methods From literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates. Results In total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). Conclusions The current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence. PMID:26437994
Platelets Proteomic Profiles of Acute Ischemic Stroke Patients
Baykal, Ahmet Tarik; Sener, Azize
Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight
Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke
Azab, Seham F.; Akeel, Nagwa E.; Abdalhady, Mohamed A.; Elhewala, Ahmed A.; Ali, Al Shymaa A.; Amin, Ezzat K.; Sarhan, Dina T.; Almalky, Mohamed A.A.; Elhindawy, Eman M.; Salam, Mohamed M.A.; Soliman, Attia A.; Abdellatif, Sawsan H.; Ismail, Sanaa M.; Elsamad, Nahla A.; Hashem, Mustafa I.A.; Aziz, Khalid A.; Elazouni, Osama M.A.; Arafat, Manal S.
Abstract Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched. In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients. This was a case–control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects' serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases. We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15–73]ng/mL) compared to the control group (median, 24[10–41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0
Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.
Cevik, Ozge; Baykal, Ahmet Tarik; Sener, Azize
Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into
[NDT-Bobath method used in the rehabilitation of patients with a history of ischemic stroke].
Klimkiewicz, Paulina; Kubsik, Anna; Woldańska-Okońska, Marta
Ischemic stroke is the third leading cause of death and disability in human. The vitally important problem after ischemic stroke is hemiparesis of the body. The most common methods used in improving the mobility of patients after ischemic stroke is a Bobath-NDT (Neuro-Developmental Treatment - Bobath), which initiated the Berta and Karel Bobath for children with cerebral palsy. It is a method designed to neurophysiological recovery of these vital functions that the patient was lost due to illness, and wants it back. PMID:23289255
[The neurovascular unit in health and ischemic stroke].
Ago, Tetsuro
The neurovascular unit (NVU), a minimal unit to exert neurological functions, is composed of neurons, astrocytes, endothelial cells, pericytes, and extracellular matrix proteins forming basal membranes. The cell components interact with one another and function cooperatively under both physiological and pathological conditions. Pericytes and astrocytes participate crucially in the formation and maintenance of the blood-brain barrier (BBB), the tight junction formed by endothelial cells, and regulate cerebral blood flow in response to neurological activities. The BBB actively regulate molecular import and export. The concept of the NVU is also useful for understanding pathogenesis and exploring therapeutic targets in various CNS disorders. In this review, recent research advances regarding the NVU and its components in health and ischemic stroke are summarized. PMID:27333744
Diagnosis and acute management of perinatal arterial ischemic stroke
Ferriero, Donna M.
Summary Perinatal arterial ischemic stroke (PAIS) can be an unrecognized cause of short- and long-term neurologic disability. Focal clonic seizure in the newborn period is the most common clinical presentation of PAIS. MRI is optimal in diagnosing PAIS; negative cranial ultrasound or CT does not rule out PAIS. Given the low rate of recurrence in combination with risk factors thought to be isolated to the maternal-fetal unit, anticoagulation or antiplatelet treatment is usually not recommended. The majority of newborns with PAIS do not go on to develop epilepsy, although further research is warranted in this area. Long-term morbidity, including motor, cognitive, and behavioral disabilities, can follow PAIS, necessitating early recognition, diagnosis, and therapy initiation. PMID:25317375
Elevation of troponin I in acute ischemic stroke
Su, Yu-Chin; Huang, Kuo-Feng; Yang, Fu-Yi
Background. Cardiac morbidities account for 20% of deaths after ischemic stroke and is the second commonest cause of death in acute stroke population. Elevation of cardiac troponin has been regarded as a prognostic biomarker of poor outcome in patients with acute stroke. Methods. This retrospective study enrolled 871 patients with acute ischemic stroke from August 2010 to March 2015. Data included vital signs, laboratory parameters collected in the emergency department, and clinical features during hospitalization. National Institutes of Health Stroke Scale (NIHSS), Barthel index, and modified Rankin Scale (mRS) were used to assess stroke severity and outcome. Results. Elevated troponin I (TnI) > 0.01 µg/L was observed in 146 (16.8%) patients. Comparing to patients with normal TnI, patients with elevated TnI were older (median age 77.6 years vs. 73.8 years), had higher median heart rates (80 bpm vs. 78 bpm), higher median white blood cells (8.40 vs. 7.50 1,000/m3) and creatinine levels (1.40 mg/dL vs. 1.10 mg/dL), lower median hemoglobin (13.0 g/dL vs. 13.7 g/dL) and hematocrit (39% vs. 40%) levels, higher median NIHSS scores on admission (11 vs. 4) and at discharge (8 vs. 3), higher median mRS scores (4 vs3) but lower Barthel index scores (20 vs. 75) at discharge (p < 0.001). Multivariate analysis revealed that age ≥ 76 years (OR 2.25, CI [1.59–3.18]), heart rate ≥ 82 bpm (OR 1.47, CI [1.05–2.05]), evidence of clinical deterioration (OR 9.45, CI [4.27–20.94]), NIHSS score ≥ 12 on admission (OR 19.52, CI [9.59–39.73]), and abnormal TnI (OR 1.98, CI [1.18–3.33]) were associated with poor outcome. Significant factors for in-hospital mortality included male gender (OR 3.69, CI [1.45–9.44]), evidence of clinical deterioration (OR 10.78, CI [4.59–25.33]), NIHSS score ≥ 12 on admission (OR 8.08, CI [3.04–21.48]), and elevated TnI level (OR 5.59, CI [2.36–13.27]). C-statistics revealed that abnormal TnI improved the predictive power of both poor
Gait improvement after treadmill training in ischemic stroke survivors: A critical review of functional MRI studies☆
Xiao, Xiang; Huang, Dongfeng; O'Young, Bryan
Stroke survivors often present with abnormal gait, movement training can improve the walking performance post-stroke, and functional MRI can objectively evaluate the brain functions before and after movement training. This paper analyzes the functional MRI changes in patients with ischemic stroke after treadmill training with voluntary and passive ankle dorsiflexion. Functional MRI showed that there are some changes in some regions of patients with ischemic stroke including primary sensorimotor cortex, supplementary motor area and cingulate motor area after treadmill training. These findings suggest that treadmill training likely improves ischemic stroke patients' lower limb functions and gait performance and promotes stroke recovery by changing patients' brain plasticity; meanwhile, the novel treadmill training methods can better training effects. PMID:25337096
Pioglitazone for Secondary Prevention after Ischemic Stroke and Transient Ischemic Attack: Rationale and Design of the Insulin Resistance Intervention after Stroke (IRIS) Trial
Viscoli, Catherine M.; Brass, Lawrence M.; Carolei, Antonio; Conwit, Robin; Ford, Gary A.; Furie, Karen L.; Gorman, Mark; Guarino, Peter D.; Inzucchi, Silvio E.; Lovejoy, Anne M.; Parsons, Mark W.; Peduzzi, Peter N.; Ringleb, Peter; Schwartz, Gregory G.; Spence, J. David; Tanne, David; Young, Lawrence H.; Kernan, Walter N.
Background: Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack (TIA). The Insulin Resistance Intervention after Stroke (IRIS) trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events. Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, non-diabetic patients with a recent ischemic stroke or TIA. Design: Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment-Insulin Resistance greater than 3.0 without meeting criteria for diabetes. Within 6 months of the index stroke or TIA, patients were randomly assigned to pioglitazone (titrated from 15mg to 45mg/day) or matching placebo and followed for up to 5 years. The primary outcome is time to stroke or MI. Secondary outcomes include time to stroke alone, acute coronary syndrome, diabetes, cognitive decline and all-cause mortality. Enrollment of 3876 participants from 179 sites in seven countries was completed in January, 2013. Participant follow-up will continue until July, 2015. Summary: The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of non-diabetic, insulin-resistant patients with stroke or TIA. Results are expected in early 2016. PMID:25458644
Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis.
Wang, Wen; Zhang, Lu; Liu, Weiming; Zhu, Qin; Lan, Qing; Zhao, Jizong
Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta-analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta-analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients. PMID:26856461
Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target
Jin, Zhen; Wu, Jinzi; Yan, Liang-Jun
It is well established that the brain can be prepared to resist or tolerate ischemic stroke injury, and mitochondrion is a major target for this tolerance. The preparation of ischemic stroke tolerance can be achieved by three major approaches: ischemic conditioning, hypoxic conditioning and chemical conditioning. In each conditioning approach, there are often two strategies that can be used to achieve the conditioning effects, namely preconditioning (Pre-C) and postconditioning (Post-C). In this review, we focus on chemical conditioning of mitochondrial proteins as targets for neuroprotection against ischemic stroke injury. Mitochondrial targets covered include complexes I, II, IV, the ATP-sensitive potassium channel (mitoKATP), adenine dinucleotide translocase (ANT) and the mitochondrial permeability transition pore (mPTP). While numerous mitochondrial proteins have not been evaluated in the context of chemical conditioning and ischemic stroke tolerance, the paradigms and approaches reviewed in this article should provide general guidelines on testing those mitochondrial components that have not been investigated. A deep understanding of mitochondria as the target of chemical conditioning for ischemic stroke tolerance should provide valuable insights into strategies for fighting ischemic stroke, a leading cause of death in the world. PMID:27005615
The Relation Between GABA and L-Arginine Levels With Some Stroke Risk Factors in Acute Ischemic Stroke Patients
Hosinian, Mohsen; Qujeq, Durdi; Ahmadi Ahangar, Alijan
Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. PMID:27478806
The Relation Between GABA and L-Arginine Levels With Some Stroke Risk Factors in Acute Ischemic Stroke Patients.
Hosinian, Mohsen; Qujeq, Durdi; Ahmadi Ahangar, Alijan
Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. PMID:27478806
Ischemic stroke and incidental finding of a right atrial lipoma.
Censi, Stefano; Squeri, Angelo; Baldelli, Marco; Parizi, Sepideh Torabi
A young man presented with recurrent ischemic stroke under antiplatelet therapy. A patent foramen ovale (PFO) was diagnosed by transesophageal echocardiography (TEE) and the patient was referred to our institution for percutaneous closure. An echogenic mass in the right atrium was detected during the intraprocedural TEE. The interventional team decided to perform transcatheter closure of PFO under fluoroscopy and TEE guide, without complications. Subsequent cardiac magnetic resonance (CMR) imaging confirmed an encapsulated and hyperintense mass located in the roof of the right atrium. The signal intensity pattern and the absence of gadolinium contrast uptake allowed a confident diagnosis of lipoma. Cardiac lipoma accounts for about 10% of primary cardiac tumors and frequently rises from the epicardial fat tissue. Echocardiographic images can remain equivocal about the nature of the mass and CMR offers a substantial contribution to a correct diagnosis. The tumor usually appears encapsulated and asymptomatic, but dyspnea, atrial and ventricular arrhythmias and, rarely, peripheral embolization have been reported. To our knowledge, this is the second case reported on paradoxical embolization associated with right atrial lipoma. Although the relationship of cardiac lipoma with stroke is not well defined, the potential proembolic significance of this lesion cannot be excluded, especially when a PFO coexists. PMID:24149062
Acute development of collateral circulation and therapeutic prospects in ischemic stroke
Iwasawa, Eri; Ichijo, Masahiko; Ishibashi, Satoru; Yokota, Takanori
In acute ischemic stroke, collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia, and in increasing the successful recanalization rate without hemorrhagic transformation. We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome, and it disappears promptly once the effective recanalization is achieved. Contrary to the belief that collateral vessels develop over time in chronic stenotic condition, there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress, which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries. We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1, which is a known shear-stress mechanosensing protein. PMID:27127459
Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system.
Aaron, Sanjith; Shyamkumar, N K; Alexander, Sunithi; Babu, P Suresh; Prabhakar, A T; Moses, Vinu; Murthy, T V; Alexander, Mathew
Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343
Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system
Aaron, Sanjith; Shyamkumar, N. K.; Alexander, Sunithi; Babu, P. Suresh; Prabhakar, A. T.; Moses, Vinu; Murthy, T. V.; Alexander, Mathew
Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343
Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke
Hochmeister, Sonja; Engel, Odilo; Adzemovic, Milena Z.; Pekar, Thomas; Kendlbacher, Paul; Zeitelhofer, Manuel; Haindl, Michaela; Meisel, Andreas; Fazekas, Franz; Seifert-Held, Thomas
Objectives From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. Methods In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. Results Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. Conclusions LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections. PMID:27152948
Polymorphisms of IGFI contribute to the development of ischemic stroke.
Kim, Hak Jae; Kim, Su Kang; Park, Hae Jeong; Chung, Joo-Ho; Chun, Jinman; Yun, Dong Hwan; Kim, Young Ock
Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the IFG1 gene are associated with the development and clinical features of IS in a Korean population. A total of 119 patients with IS and 289 control subjects were recruited. Stroke patients were classified into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and ≥6) and the Modified Barthel Index (MBI; <60 and ≥60). Among the SNPs of the IFG1 gene, five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron), rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3' untranslated region; 3'UTR). Multiple logistic regression models were conducted to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After Bonferroni correction (p(c)), the A and G alleles of rs2162679 and rs6214 had significant differences between patients with IS and the controls [rs2162679, OR (95% CI) = 1.64 (1.17-2.31), p=0.004, p(c)=0.02; rs6214, OR (95% CI) = 1.52 (1.12-2.07), p=0.007, p(c)=0.035], respectively. However, the five selected SNPs were not related to the NIHSS and MBI scores. These results suggest that IGF1 may be associated with the development of IS. PMID:22969851
Polymorphisms of IGFI contribute to the development of ischemic stroke
Insulin-like growth factor 1 (IFG1) is neuroprotective in animal models of focal brain ischemia and correlates with ischemic stroke (IS) outcome in the elderly. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the IFG1 gene are associated with the development and clinical features of IS in a Korean population. A total of 119 patients with IS and 289 control subjects were recruited. Stroke patients were classified into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS; <6 and ≥6) and the Modified Barthel Index (MBI; <60 and ≥60). Among the SNPs of the IFG1 gene, five SNPs were selected and analyzed by direct sequencing: rs2162679 (intron), rs2195239 (intron), rs978458 (intron), rs1520220 (intron) and rs6214 (3′ untranslated region; 3′UTR). Multiple logistic regression models were conducted to analyze genetic data. SNPStats, SNPAnalyzer Pro and Helixtree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. Two SNPs, rs2162679 and rs6214, were associated with the development of IS. After Bonferroni correction (pc), the A and G alleles of rs2162679 and rs6214 had significant differences between patients with IS and the controls [rs2162679, OR (95% CI) = 1.64 (1.17–2.31), p=0.004, pc=0.02; rs6214, OR (95% CI) = 1.52 (1.12–2.07), p=0.007, pc=0.035], respectively. However, the five selected SNPs were not related to the NIHSS and MBI scores. These results suggest that IGF1 may be associated with the development of IS. PMID:22969851
Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities (ARIC) Study
Caughey, Melissa C.; Loehr, Laura R.; Key, Nigel S.; Derebail, Vimal K.; Gottesman, Rebecca F.; Kshirsagar, Abhijit V.; Grove, Megan L.; Heiss, Gerardo
Background and Purpose Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. Methods A population-based sample of African Americans (N=3,497, mean age=54, female=62%) was followed from 1987–2011 in the Atherosclerosis Risk in Communities Study (ARIC), contributing a total of 65,371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A (HbAA). Models were adjusted for age, sex, smoking, diabetes, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. Results SCT was identified in 223 (6.4%) participants. Over a median follow up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than HbAA (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0 – 2.0), and an incidence rate difference amounting to 1.9 (0.4 – 3.8) extra strokes per 1000 person-years. Conclusion We observed an increased risk of ischemic stroke in African Americans with SCT. Further investigation of the incidence and pathophysiology of stroke in SCT patients is warranted. PMID:25139879
Two children with both arm ischemia and arterial ischemic stroke during the perinatal period.
McKasson, Marilyn J; Golomb, Meredith R
It is rare for both limb ischemia and arterial ischemic stroke to occur in the same child during the perinatal period. Two children who appear to have had perinatal emboli to both an arm and a middle cerebral artery territory are presented here. One child required amputation of the ischemic limb below the shoulder, and the other required skin grafts to the distal ischemic fingers. Each of these children later received cerebral magnetic resonance imaging for evaluation of developmental delay and was found to have what appeared to be old perinatal arterial ischemic stroke. Both children were homozygous for the methylenetetrahydrofolate reductase C677T gene variant. Eight other children with perinatal limb ischemia and stroke were found on literature review; several also had delayed diagnosis of perinatal stroke. This report examines the approach to diagnosis and treatment in each of these and makes suggestions for the similar cases in the future. PMID:21862833
Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients
La, C.; Nair, V.A.; Mossahebi, P.; Stamm, J.; Birn, R.; Meyerand, M.E.; Prabhakaran, V.
Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01–0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery. PMID:27077023
Recovery of slow-5 oscillations in a longitudinal study of ischemic stroke patients.
La, C; Nair, V A; Mossahebi, P; Stamm, J; Birn, R; Meyerand, M E; Prabhakaran, V
Functional networks in resting-state fMRI are identified by characteristics of their intrinsic low-frequency oscillations, more specifically in terms of their synchronicity. With advanced aging and in clinical populations, this synchronicity among functionally linked regions is known to decrease and become disrupted, which may be associated with observed cognitive and behavioral changes. Previous work from our group has revealed that oscillations within the slow-5 frequency range (0.01-0.027 Hz) are particularly susceptible to disruptions in aging and following a stroke. In this study, we characterized longitudinally the changes in the slow-5 oscillations in stroke patients across two different time-points. We followed a group of ischemic stroke patients (n = 20) and another group of healthy older adults (n = 14) over two visits separated by a minimum of three months (average of 9 months). For the stroke patients, one visit occurred in their subacute window (10 days to 6 months after stroke onset), the other took place in their chronic window (> 6 months after stroke). Using a mid-order group ICA method on 10-minutes eyes-closed resting-state fMRI data, we assessed the frequency distributions of a component's representative time-courses for differences in regards to slow-5 spectral power. First, our stroke patients, in their subacute stage, exhibited lower amplitude slow-5 oscillations in comparison to their healthy counterparts. Second, over time in their chronic stage, those same patients showed a recovery of those oscillations, reaching near equivalence to the healthy older adult group. Our results indicate the possibility of an eventual recovery of those initially disrupted network oscillations to a near-normal level, providing potentially a biomarker for stroke recovery of the cortical system. This finding opens new avenues in infra-slow oscillation research and could serve as a useful biomarker in future treatments aimed at recovery. PMID:27077023
Dose-Response Relationship Between Cigarette Smoking and Risk of Ischemic Stroke in Young Women
Bhat, Viveca M.; Cole, John W.; Sorkin, John D.; Wozniak, Marcella A.; Malarcher, Ann M.; Giles, Wayne H.; Stern, Barney J.; Kittner, Steven J.
Background and Purpose Although cigarette smoking is known to be a risk factor for ischemic stroke, there are few data on the dose-response relationship between smoking and stroke risk in a young ethnically diverse population. Methods We used data from the Stroke Prevention in Young Women Study, a population-based case-control study of risk factors for ischemic stroke in women aged 15 to 49 years to examine the relationship between cigarette smoking and ischemic stroke. Historical data, including smoking history, was obtained through standardized interviews. Odds ratios (OR) were estimated using logistic regression. Cases (n=466) were women with stroke in the greater Baltimore-Washington area, and controls (n=604) were women free of a stroke history identified by random digit dialing. Results After multivariable adjustment, the OR comparing current smokers to never smokers was 2.6 (P<0.0001); no difference in stroke risk was observed between former smokers and never smokers. Adjusted OR increased with increasing number of cigarettes smoked per day (OR=2.2 for 1 to 10 cigs/d; 2.5 for 11 to 20 cigs/d; 4.3 for 21 to 39 cigs/d; 9.1 for 40 or more cigs/d). Conclusion These results suggest a strong dose-response relationship between cigarette smoking and ischemic stroke risk in young women and reinforce the need for aggressive smoking cessation efforts in young adults. PMID:18703815
Relation of Paraoxonase1, Arylesterase and Lipid Profile in Ischemic Stroke Patients
Mogarekar, Mukund R; Wagh, Reena V; Das, Rajkumar R; Pramanik, Sanjay S; Sonune, Sanjay M; Chawhan, Sanjay M
Background Paraoxonase 1 (PON1) is an enzyme associated with High density lipoprotein (HDL) in blood and it is considered to have antioxidant and antiatherogenic properties. PON1 plays an important role in protecting HDL and especially low density lipoprotein (LDL) from oxidative modification by hydrolyzing lipid peroxides which are known to be associated with many vascular diseases including atherosclerosis and ischemic stroke. Aim The aim of the study was to evaluate and correlate serum paraoxonase (PON1) and arylesterase (ARE) activities as well as lipid profile levels in patients with ischemic stroke. Materials and Methods The study population was comprised of 50 ischemic stroke patients and 50 healthy controls. The serum PON1 and ARE activities were measured spectrophotometrically by using paraoxon and phenylacetate as substrate respectively by Eckerson method. Serum lipid was measured using routine biochemical method. Results The normality of the distribution of the parameters are assessed by Shapiro-Wilk test. Two sample t-test is applied for hypothesis testing. The serum PONI and arylesterase ARE decreased significantly in ischemic stroke patients (p<0.001). The PON1 was positively correlated with HDL. Conclusion This study strongly suggests that the estimation of HDL-C associated PON1 enzyme gives valuable information for prediction of risk of ischemic stroke due to cerebrovascular thromboembolism. The result shows that PON1 and ARE could be considered as a risk factors for ischemic stroke. PMID:26673997
Ischemic stroke incidence in Santa Coloma de Gramenet (ISISCOG), Spain. A community-based study
Alzamora, María Teresa; Sorribes, Marta; Heras, Antonio; Vila, Nicolás; Vicheto, Marisa; Forés, Rosa; Sánchez-Ojanguren, José; Sancho, Amparo; Pera, Guillem
Background In Spain, stroke is one of the major causes of death and the main cause of severe disability in people over 65 years. We analyzed the incidence of ischemic stroke, stroke subtypes, case fatality and disability at 90 days after the event in a Spanish population. Methods A prospective community-based register of ischemic strokes was established in Santa Coloma de Gramenet (Barcelona) [116,220 inhabitants of all ages, according to the municipal census of December 31,2001], from January 1 to December 31, 2003. Standard definitions and case finding methods were used to identify all cases in all age groups. Every patient underwent a complete clinical evaluation and systematic tests including neuroimaging (CT/MRI) and vascular studies (carotid duplex ultrasound intra and extracranial and MR angiography). Results Over a one year period, 196 ischemic strokes were registered [107 men; median age = 76 years (range 39–98)], being the first event in 159 patients (81.1%) and a recurrent stroke in 37 (18.9%). After age-adjustment to the European population, the incidence of ischemic stroke per 100,000 inhabitants was 172 (95% CI, 148–196); 219 (176–261) in men and 133 (105–160) in women, with an annual incidence for first ischemic stroke of 139 (118–161); 165 (128–201) in men and 115 (89–140) in women. The incidence of stroke increased with age. Stroke subtypes (TOAST classification criteria) were lacunar in 28.8%, atherothrombotic in 18.6%, cardioembolic in 26.6% and undetermined in 26.0% of patients. At 90 days, the case-fatality was 12%, and among survivors, moderate-to-severe disability was present in 45 % at 3 months. Conclusion This prospective community-based study shows one of the lowest incidences of stroke in Europe, as well as one of the lowest case fatality and disability rates at 90 days after stroke. PMID:18371212
Quality of Life after Intra-arterial Therapy for Acute Ischemic Stroke
Cortez, Melissa M.; Wilder, Michael; McFadden, Molly; Majersik, Jennifer J.
Few data exist about health-related quality of life outcomes after intra-arterial therapy for acute ischemic stroke. We assessed stroke-specific quality of life in stroke survivors after intra-arterial therapy. Consecutive patients undergoing intra-arterial therapy for acute ischemic stroke from 2005-2010 were retrospectively identified via an institutional database. Stroke-specific quality of life (using the Stroke-Specific Quality of Life Score) and disability status (modified Rankin Scale) were prospectively assessed via mailed questionnaire. We analyzed quality of life scores by domain and summary score, with a summary score of ≥ 4 defined as a good outcome. Analysis of variance was used to model the effect of final recanalization status, stroke severity, and modified Rankin Scale on total quality of life score. ANOVA and Pearson's correlations were used to test the association between stroke severity/modified Rankin Scale and quality of life/time since stroke respectively. Of ninety-nine acute ischemic stroke patients, 61 responded yielding: 11 interim deaths, 7 incomplete surveys, and 43 complete surveys for analysis. Among responding survivors, overall quality of life score was 3.9 (SD 0.7); 77% of these reported good quality of life. Scores were higher in recanalized patients in 11 of 12 domains, but was significant only for mood. Although modified Rankin Scale was associated with stroke severity, quality of life was independent of both. Seventy-seven percent of acute ischemic stroke survivors who received intra-arterial therapy reported good quality of life. Furthermore, these data suggest that stroke-specific quality of life is an independent outcome from stroke severity and disability status. PMID:24813258
Subtotal Gastrectomy With Billroth II Anastomosis Is Associated With a Low Risk of Ischemic Stroke in Peptic Ulcer Disease Patients
Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung
Abstract Duodenal diversion can ameliorate lipid and glucose metabolism. We assessed the risk of stroke after subtotal gastrectomy with Billroth II anastomosis (SGBIIA) in peptic ulcer disease (PUD). We identified 6425 patients who received SGBIIA for PUD between 1998 and 2010 from the Taiwan National Health Insurance Research Database as the study cohort; we frequency-matched them with 25,602 randomly selected controls from the PUD population who did not receive SGBIIA according to age, sex, index year, and comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), and obesity. All patients were followed until the end of 2011 to determine the incidence of stroke. The incidence of stroke was lower in patients in the SGBIIA cohort than in those in the non-SGBIIA cohort (18.9 vs 22.9 per 1000 person-years, adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.72–0.89, P < 0.001). The risk of ischemic stroke (aHR 0.77, 95% CI 0.69–0.86, P < 0.001), rather than hemorrhagic stroke (aHR 1.00, 95% CI 0.78–1.28), was lower for the SGBIIA cohort than for the non-SGBIIA cohort according to the multivariable Cox proportional hazard regression analysis. The relative risk of ischemic stroke after SGBIIA was lower in men (aHR 0.77, 95% CI 0.69–0.86) than in women (aHR 0.80, 95% CI 0.65–0.99) and in patients aged ≥65 years (aHR 0.72, 95% CI 0.63–0.81) than in those of other age groups (≤49 years, aHR 0.82, 95% CI 0.48–1.39; 50–64 years, aHR 1.01, 95% CI 0.79–1.28). The relative risk of ischemic stroke after SGBIIA was also reduced in patients with comorbidities (aHR 0.84, 5% CI 0.75–0.95) rather than in those without comorbidities (aHR 0.81, 95% CI 0.59–1.12). SGBIIA is associated with a low risk of ischemic stroke for PUD patients, and its protective effect is prominent in men, patients aged ≥65
Does computed tomography permeability predict hemorrhagic transformation after ischemic stroke?
Yen, Peggy; Cobb, Allison; Shankar, Jai Jai Shiva
AIM: To use perfusion-derived permeability-surface area product maps to predict hemorrhagic transformation following thrombolytic treatment for acute ischemic stroke. METHODS: We retrospectively analyzed our prospectively kept acute stroke database over five consecutive months for patients with symptoms of acute ischemic stroke (AIS) who had computed tomography (CT) perfusion (CTP) done at arrival. Patients included in the analyses also had to have a follow-up CT. The permeability-surface area product maps (PS) was calculated for the side of the ischemia and/or infarction and for the contralateral unaffected side at the same level. The cerebral blood flow map was used to delineate the ischemic territory. Next, a region of interest was drawn at the centre of this territory on the PS parametric map. Finally, a mirror region of interest was created on the contralateral side at the same level. The relative permeability-surface area product maps (rPS) provided an internal control and was calculated as the ratio of the PS on the side of the AIS to the PS on the contralateral side. A student t-test was performed after log conversion of rPS between patients with and without hemorrhagic transformation. Log conversion was used to convert the data into normal distribution to use t-test. For the group of patients who experienced intracranial bleed, a student t-test was performed between those with only petechial hemorrhage and those with more severe parenchymal hematoma with subarachnoid haemorrhage. RESULTS: Of 84 patients with AIS and CTP at admission, only 42 patients had a follow-up CT. The rPS derived using the normal side as the internal control was significantly higher (P = 0.003) for the 15 cases of hemorrhagic transformation (1.71 + 1.64) compared to 27 cases that did not have any (1.07 + 1.30). Patients with values above the overall mean rPS of 1.3 had an increased likelihood of subsequent hemorrhagic transformation. The sensitivity of using this score to predict
Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke
Zhao, Xu; Yu, Yue; Xu, Wenlong; Dong, Lei; Wang, Yuan; Gao, Bing; Li, Guangyu; Zhang, Wentao
Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage. PMID:27043525
Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke.
Zhao, Xu; Yu, Yue; Xu, Wenlong; Dong, Lei; Wang, Yuan; Gao, Bing; Li, Guangyu; Zhang, Wentao
Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage. PMID:27043525
The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future
L.L.Yeo, Leonard; Sharma, Vijay K
Ischemic stroke is one of the major causes of mortality and long-term disability. In the recent past, only very few treatment options were available and a considerable proportion of stroke survivors remained permanently disabled. However, over the last 2 decades rapid advances in acute stroke care have resulted in a corresponding improvement in mortality rates and functional outcomes. In this review, we describe the evolution of systemic thrombolytic agents and various interventional devices, their current status as well as some of the future prospects. We reviewed literature pertaining to acute ischemic stroke reperfusion treatment. We explored the current accepted treatment strategies to attain cerebral reperfusion via intravenous modalities and compare and contrast them within the boundaries of their clinical trials. Subsequently we reviewed the trials for interventional devices for acute ischemic stroke, categorizing them into thrombectomy devices, aspiration devices, clot disruption devices and thrombus entrapment devices. Finally we surveyed several of the alternative reperfusion strategies available. We also shed some light on the controversies surrounding the current strategies of treatment of acute ischemic stroke. Acute invasive interventional strategies continue to improve along with the noninvasive modalities. Both approaches appear promising. We conducted a comprehensive chronological review of the existing treatments as well as upcoming remedies for acute ischemic stroke. PMID:23864913
Stroke and the "Stroke Belt" in Dialysis: Contribution of Patient Characteristics to Ischemic Stroke Rate and Its Geographic Variation
Ellerbeck, Edward F.; Mahnken, Jonathan D.; Phadnis, Milind A.; Rigler, Sally K.; Spertus, John A.; Zhou, Xinhua; Mukhopadhyay, Purna; Shireman, Theresa I.
Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m2 was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the "stroke belt" or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients. PMID:23990675
Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages
Weiner, Daniel E.; Dad, Taimur
Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250
Telomere Length and Ischemic Stroke in Women: A Nested Case-Control Study
Schürks, Markus; Prescott, Jennifer; Dushkes, Rimma; De Vivo, Immaculata; Rexrode, Kathryn M.
Background Telomere shortening has been implicated in cardiovascular disease. However, prospective data on the association between relative telomere length (RTL) and ischemic stroke are scarce and inconclusive. Methods We used a nested case-control design among women participating in the prospective Nurses' Health Study. Participants provided blood samples in 1990 and were followed through 2006. Women with confirmed incident ischemic stroke were matched to controls by age, smoking, postmenopausal status, and postmenopausal hormone use. Quantitative PCR was used to determine RTL in genomic DNA extracted from peripheral blood leukocytes. Conditional logistic regression was used to determine the risk of ischemic stroke associated with RTL, using RTL quartiles and as dichotomous according to the median. Results Data on RTL were available from 504 case-control pairs. Results did not suggest an association between RTL and ischemic stroke. The odds ratio for ischemic stroke was 0.82 (95% confidence interval [CI] 0.52–1.32) comparing lowest to the highest RTL quartile and 0.90 (95% CI 0.65–1.24) comparing RTL below the median to RTL above the median. Associations were unchanged after additional adjustment for cardiovascular risk factors. Further analyses suggested an association between RTL and fatal ischemic stroke (54 case-control pairs; lowest vs. highest quartile OR=1.99, 95%CI 0.26–14.9); however, results were statistically insignificant. Conclusion In this large nested case-control study among women RTL was not associated with ischemic stroke. In light of the varying study results in the literature on the association between telomere length and stroke additional research is warranted. PMID:23521613
Sitagliptin After Ischemic Stroke in Type 2 Diabetic Patients: A Nationwide Cohort Study
Chen, Dong-Yi; Wang, Szu-Heng; Mao, Chun-Tai; Tsai, Ming-Lung; Lin, Yu-Sheng; Su, Feng-Chieh; Chou, Chung-Chuan; Wen, Ming-Shien; Wang, Chun-Chieh; Hsieh, I-Chang; Hung, Kuo-Chun; Cherng, Wen-Jin; Chen, Tien-Hsing
Abstract The cerebrovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) with ischemic stroke remains uncertain. The aim of this study was to assess the efficacy and safety of sitagliptin in patients with T2DM with recent ischemic stroke. We analyzed data from the Taiwan National Health Insurance Research Database between March 1, 2009, and December 31, 2011. Ischemic stroke patients were identified from individuals with T2DM. Patients who received sitagliptin were compared with those who did not to evaluate the cardiovascular safety and efficacy of sitagliptin. The primary outcome was a composite of ischemic stroke, myocardial infarction, or cardiovascular death. A total of 5145 type 2 diabetic patients with ischemic stroke met our inclusion criteria and were followed for up to 2.83 years (mean, 1.17 years). Overall, 1715 patients (33.3%) received sitagliptin and 3430 patients (66.7%) did not. The primary composite outcome occurred in 190 patients in the sitagliptin group (11.1%) and in 370 patients in the comparison group (10.8%) (hazard ratio [HR] = 1.02; 95% confidence interval [CI], 0.85–1.21). Patients treated with sitagliptin had a similar risk of ischemic stroke, hemorrhagic stroke, and all-cause mortality with an HR of 0.95 (95% CI, 0.78–1.16, P = 0.612), 1.07 (95% CI, 0.55–2.11, P = 0.834), and 1.00 (95% CI, 0.82–1.22, P = 0.989), respectively, compared with patients not treated with sitagliptin. Treatment with sitagliptin in type 2 diabetic patients with recent ischemic stroke was not associated with increased or decreased risks of adverse cerebrovascular outcomes. PMID:26181549
Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population
Yoo, Seung Don; Yun, Dong Hwan; Kim, Hee-Sang; Kim, Su Kang; Kim, Dong Hwan; Chon, Jinmann; Je, Goun; Kim, Yoon-Seong; Chung, Joo-Ho; Chung, Seung Joon; Yeo, Jin Ah
Objective To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke. Methods We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data. Results No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models. Conclusion These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population. PMID:26949676
Association of genetic variants with coronary artery disease and ischemic stroke in a longitudinal population-based genetic epidemiological study
Our previous studies identified nine genes and chromosomal region 3q28 as susceptibility loci for myocardial infarction, ischemic stroke or chronic kidney disease by genome-wide or candidate gene association studies. As coronary artery disease (CAD) and ischemic stroke may share genetic architecture, certain genetic variants may confer susceptibility to the two diseases. The present study examined the association of 13 polymorphisms at these 10 loci with the prevalence of CAD or ischemic stroke in community-dwelling individuals, with the aim of identifying genetic variants that confer susceptibility to the two conditions. Study subjects (170 with CAD, 117 with ischemic stroke and 5,718 controls) were recruited to the Inabe Health and Longevity Study, a longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The subjects were recruited from individuals who visited for an annual health checkup and they were followed up each year (mean follow-up period, 5 years). Longitudinal analysis with a generalized estimating equation, and with adjustment for age, gender, body mass index, smoking status, the prevalence of hypertension, diabetes mellitus and dyslipidemia and the serum concentration of creatinine, revealed that rs2074380 (G→A) and rs2074381 (A→G) of the α-kinase 1 (ALPK1) gene and rs8089 (T→G) of the thrombospondin 2 (THBS2) gene were significantly (P<2×10−16) associated with the prevalence of CAD, with the AA genotype of rs2074380 and GG genotypes of rs2074381 and rs8089 being protective against this condition. Similar analysis revealed that rs9846911 (A→G) at chromosome 3q28, rs2074381 of ALPK1, rs8089 of THBS2 and rs6046 (G→A) of the coagulation factor VII gene were significantly (P<2×10−16) associated with the prevalence of ischemic stroke, with the GG genotypes of rs9846911, rs2074381 and rs8089 and the AA genotype of rs6046 being protective against this condition. ALPK1 and THBS2 may thus be
The Association Between Peptic Ulcer Disease and Ischemic Stroke
Cheng, Tain-Junn; Guo, How-Ran; Chang, Chia-Yu; Weng, Shih-Feng; Li, Pi-I; Wang, Jhi-Joung; Wu, Wen-Shiann
Abstract Stroke is a common cause of death worldwide, but about 30% of ischemic stroke (IS) patients have no identifiable contributing risk factors. Because peptic ulcer disease (PUD) and vascular events share some common risk factors, we conducted a population-based study to evaluate the association between PUD and IS. We followed up a representative sample of 1 million residents of Taiwan using the National Health Insurance Research Database from 1997 to 2011. We defined patients who received medications for PUD and had related diagnosis codes as the PUD group, and a reference group matched by age and sex was sampled from those who did not have PUD. We also collected data on medical history and monthly income. The events of IS occurred after enrollment were compared between the 2 groups. The data were analyzed using Cox proportional hazard models at the 2-tailed significant level of 0.05. The PUD group had higher income and prevalence of hypertension, diabetes mellitus (DM), heart disease, and hyperlipidemia. They also had a higher risk of developing IS with an adjusted hazard ratio of 1.31 (95% confidence interval: 1.20–1.41). Other independent risk factors included male sex, older age, lower income, and co-morbidity of hypertension, diabetes mellitus (DM), and heart disease. PUD is a risk factor for IS, independent of conventional risk factors such as male sex, older age, lower income, and co-morbidity of hypertension, DM, and heart disease. Prevention strategies taking into account PUD should be developed and evaluated. PMID:27258514
Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke.
Raju, Tonse N K; Nelson, Karin B; Ferriero, Donna; Lynch, John Kylan
Ischemic perinatal stroke is a disorder associated with significant long-term neurologic morbidity. With an estimated incidence of 1 in 2300 to 5000 births, stroke is more likely to occur in the perinatal period than at any time in childhood. The incidence of ischemic perinatal stroke ranks second only to that of strokes in the elderly population. Although ischemic perinatal stroke is a well-recognized disorder, many aspects remain to be studied. There is no consensus on its terminology, definition, or classification. Several risk factors have been identified, but their precise roles in causing stroke are not well understood. There are no reliable predictors of ischemic perinatal stroke on which to base prevention or treatment strategies. To review these important issues and propose a research agenda, the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke convened a workshop in August 2006. This article provides a summary of the workshop. PMID:17766535
Selective neuronal loss in ischemic stroke and cerebrovascular disease
Baron, Jean-Claude; Yamauchi, Hiroshi; Fujioka, Masayuki; Endres, Matthias
As a sequel of brain ischemia, selective neuronal loss (SNL)—as opposed to pannecrosis (i.e. infarction)—is attracting growing interest, particularly because it is now detectable in vivo. In acute stroke, SNL may affect the salvaged penumbra and hamper functional recovery following reperfusion. Rodent occlusion models can generate SNL predominantly in the striatum or cortex, showing that it can affect behavior for weeks despite normal magnetic resonance imaging. In humans, SNL in the salvaged penumbra has been documented in vivo mainly using positron emission tomography and 11C-flumazenil, a neuronal tracer validated against immunohistochemistry in rodent stroke models. Cortical SNL has also been documented using this approach in chronic carotid disease in association with misery perfusion and behavioral deficits, suggesting that it can result from chronic or unstable hemodynamic compromise. Given these consequences, SNL may constitute a novel therapeutic target. Selective neuronal loss may also develop at sites remote from infarcts, representing secondary 'exofocal' phenomena akin to degeneration, potentially related to poststroke behavioral or mood impairments again amenable to therapy. Further work should aim to better characterize the time course, behavioral consequences—including the impact on neurological recovery and contribution to vascular cognitive impairment—association with possible causal processes such as microglial activation, and preventability of SNL. PMID:24192635
A Population-Based Study of 30-day Incidence of Ischemic Stroke Following Surgical Neck Dissection
MacNeil, S. Danielle; Liu, Kuan; Garg, Amit X.; Tam, Samantha; Palma, David; Thind, Amardeep; Winquist, Eric; Yoo, John; Nichols, Anthony; Fung, Kevin; Hall, Stephen; Shariff, Salimah Z.
Abstract The objective of this study was to determine the 30-day incidence of ischemic stroke following neck dissection compared to matched patients undergoing non-head and neck surgeries. A surgical dissection of the neck is a common procedure performed for many types of cancer. Whether such dissections increase the risk of ischemic stroke is uncertain. A retrospective cohort study using data from linked administrative and registry databases (1995–2012) in the province of Ontario, Canada was performed. Patients were matched 1-to-1 on age, sex, date of surgery, and comorbidities to patients undergoing non-head and neck surgeries. The primary outcome was ischemic stroke assessed in hospitalized patients using validated database codes. A total of 14,837 patients underwent surgical neck dissection. The 30-day incidence of ischemic stroke following the dissection was 0.7%. This incidence decreased in recent years (1.1% in 1995 to 2000; 0.8% in 2001 to 2006; 0.3% in 2007 to 2012; P for trend <0.0001). The 30-day incidence of ischemic stroke in patients undergoing neck dissection is similar to matched patients undergoing thoracic surgery (0.5%, P = 0.26) and colectomy (0.5%, P = 0.1). Factors independently associated with a higher risk of stroke in 30 days following neck dissection surgery were of age ≥75 years (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05–2.53), and a history of diabetes (OR 1.60, 95% CI 1.02–2.49), hypertension (OR 2.64, 95% CI 1.64–4.25), or prior stroke (OR 4.06, 95% CI 2.29–7.18). Less than 1% of patients undergoing surgical neck dissection will experience an ischemic stroke in the following 30 days. This incidence of stroke is similar to thoracic surgery and colectomy. PMID:26287406
Adjuvant Chinese Herbal Products for Preventing Ischemic Stroke in Patients with Atrial Fibrillation
Muo, Chih-Hsin; Chiu, Hsienhsueh Elley; Liu, Chun-Ting
Objective Chinese herbal products (CHPs) are widely used for atrial fibrillation (AF) in Taiwan. We investigated the effect of adjuvant CHPs in preventing ischemic stroke in patients with AF. Methods Taiwanese patients in the Health Insurance Database newly diagnosed with AF during 2000–2011 were enrolled. Medication treatment with/without CHPs was administered within 7 days after the AF diagnosis. The clinical endpoint was an ischemic stroke. The Chi-square test, Fisher's exact test, and Student t test were used to examine differences between the traditional Chinese medicine (TCM) and non-TCM cohorts. Cox proportional hazard regression was used to assess the risk for ischemic stroke between two cohorts. Results Three hundred and eleven patients underwent TCM treatment and 1715 patients did not. Compared to non-TCM users, TCM users had a lower incidence of stroke (12.59% vs. 1.93%, respectively) and lower risk of stroke [CHA2DS2-VASc score = 0–2 (hazard ratio = 0.20; 95% confidence interval = 0.06–0.65)]. Compared to non-TCM users, the stroke risk was significantly lower in TCM users with AF who were female or younger than 65 years, but not in males, people more than 65 years old, or people with comorbidities. Compared to TCM users, non-TCM users who received conventional treatment had a higher ischemic stroke risk. The risk for AF-related hospitalization was significantly lower in TCM users (0.64%) than in non-TCM users (38.1%). Conclusions Users of TCM with AF have a lower risk of new-onset ischemic stroke. Therefore, adjuvant CHP therapy may have a protective effect and may be used in AF patients to prevent ischemic stroke. PMID:27428543
Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.
Hamatani, Yasuhiro; Iguchi, Moritake; Nakamura, Michikazu; Ohtani, Ryo; Yamashita, Yugo; Takagi, Daisuke; Unoki, Takashi; Ishii, Mitsuru; Masunaga, Nobutoyo; Ogawa, Hisashi; Hamatani, Mio; Abe, Mitsuru; Akao, Masaharu
Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke. PMID:26219729
Animal models of ischemic stroke and their application in clinical research
Fluri, Felix; Schuhmann, Michael K; Kleinschnitz, Christoph
This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models. PMID:26170628
Association of dementia with death after ischemic stroke: A two-year prospective study
Gao, Chang-Yue; Lian, Yan; Zhang, Meng; Zhang, Li-Li; Fang, Chuan-Qing; Deng, Juan; Li, Jing; Xu, Zhi-Qiang; Zhou, Hua-Dong; Wang, Yan-Jiang
The association between dementia and the risk of death after ischemic stroke was investigated. Neurological, neuropsychological and functional assessments were evaluated in 619 patients with acute ischemic stroke. Dementia was diagnosed at admission and at three months after stroke onset. The patients were scheduled for a two-year follow-up after the index stroke. The Kaplan-Meier survival and Cox proportional hazards regression analyses were used to estimate the cumulative proportion of survival, and the association between dementia and risk of death after stroke. In total, 146 patients (23.6%) were diagnosed with dementia after stroke. The cumulative proportion of surviving cases was 49.3% in patients with dementia after a median follow-up of 21.2±5.6 months, and 92.5% in patients without dementia. Multivariate analysis revealed that dementia (HR, 7.21; 95% CI, 3.85–13.49) was associated with death, independent of age, atrial fibrillation, previous stroke and NIH stroke scale. In conclusion, the mortality rate is increased in stroke patients with dementia. Dementia is an important risk factor for death after stroke, independent of age, atrial fibrillation, previous stroke, and the severity of the stroke. PMID:27588095
Developing drug strategies for the neuroprotective treatment of acute ischemic stroke.
Tuttolomondo, Antonino; Pecoraro, Rosaria; Arnao, Valentina; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio
Developing new treatment strategies for acute ischemic stroke in the last twenty years has offered some important successes, but also several failures. Most trials of neuroprotective therapies have been uniformly negative to date. Recent research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies. PMID:26469760
Ischemic stroke management in West Scotland: a chart review
Verpillat, Patrice; Dorey, Julie; Guilhaume-Goulant, Chantal; Dabbous, Firas; Aballéa, Samuel
Background Little information is available about the long-term management of ischemic stroke (IS) in West Scotland. In this study we aim to describe the management of IS at onset, admission, and during follow-up among patients who survived an IS event. Methods General practitioners (GPs) (n=20) were randomly selected to recruit IS patients and extract data about patient characteristics, hospitalizations, discharge, and ambulatory care from GP databases, hospital letters, and direct contact with patients and their relatives. Descriptive analyses were conducted. Results One hundred and one patients were included, with a mean age of 65.6±13.4. About half of the patients contacted their GPs at the time of onset (45.4%). Cardiovascular history was prevalent in 29.7% of cases, and 14% of all cases were recurrences. Of the patients, 89 (88%) were hospitalized with mean length of stay (LOS) 11.8 days. Treatment was administered on average within 12.9 hours of admission and 23.6% of the admitted patients received thrombolytic treatment. During the 1-year follow-up period, 33.6% of patients were rehospitalized and the mean LOS was 15.1±29.5 days. Further, patients on average sought nursing care (10.9%), physical therapy (45.5%), occupational therapy (27.7%), speech therapy (12.9%), and professional caregivers (12%). Conclusion The health-care resource utilization of IS patients is a major driver of economic burden. PMID:27123179
Force control in chronic stroke.
Kang, Nyeonju; Cauraugh, James H
Force control deficits are common dysfunctions after a stroke. This review concentrates on various force control variables associated with motor impairments and suggests new approaches to quantifying force control production and modulation. Moreover, related neurophysiological mechanisms were addressed to determine variables that affect force control capabilities. Typically, post stroke force control impairments include: (a) decreased force magnitude and asymmetrical forces between hands, (b) higher task error, (c) greater force variability, (d) increased force regularity, and (e) greater time-lag between muscular forces. Recent advances in force control analyses post stroke indicated less bimanual motor synergies and impaired low-force frequency structure. Brain imaging studies demonstrate possible neurophysiological mechanisms underlying force control impairments: (a) decreased activation in motor areas of the ipsilesional hemisphere, (b) increased activation in secondary motor areas between hemispheres, (c) cerebellum involvement, and (d) relatively greater interhemispheric inhibition from the contralesional hemisphere. Consistent with identifying neurophysiological mechanisms, analyzing bimanual motor synergies as well as low-force frequency structure will advance our understanding of post stroke force control. PMID:25704075
Clopidogrel responsiveness in stroke patients on a chronic aspirin regimen.
Sternberg, Zohara; Ching, Marilou; Sawyer, Robert N; Chichelli, Trevor; Li, Fan; Janicke, David; Radovic, Vladan; Mehta, Bijal; Farooq, Osman; Munschauer, Frederick E
This study evaluated the antiplatelet effects of clopidogrel (CPG) in patients sustaining acute ischemic stroke who were already receiving chronic outpatient aspirin therapy (81-325 mg/day). Platelet function was measured using 3 different "point-of-care" platelet function analyzers: the Thrombelastograph hemostasis system, the Accumetrics VerifyNow system, and the Chronolog 570VS impedance aggregometer. Platelet function was assessed before administration of a 300-mg CPG loading dose and again at 26 hours and 64 hours after this loading dose along with a 75-mg daily maintenance dose. All 3 instruments detected marked inhibition of platelet function at 26 hours and 64 hours after CPG administration. There were significant variations among the 3 instruments in monitoring antiplatelet responses to aspirin and CPG; however, these variations were eliminated when the platelet function results were corrected for baseline platelet variability. The percentage of patients who were poor responders to CPG after switching from aspirin depended on the measurement instrument used, but was higher at 26 hours after CPG administration than at 64 hours after CPG administration. Our findings indicate that poor response to antiplatelet agents in general, and to CPG in particular, is a function of the measuring instrument. The correction for baseline platelet variability results in similar levels of platelet inhibition measured by the 3 platelet function analyzers. Future studies are warranted to examine the association between ex vivo CPG-induced platelet inhibition and clinical outcomes in patients with ischemic stroke. PMID:22209644
Atrial fibrillation is a predictor of in-hospital mortality in ischemic stroke patients
Ong, Cheung-Ter; Wong, Yi-Sin; Wu, Chi-Shun; Su, Yu-Hsiang
Background/purpose In-hospital mortality rate of acute ischemic stroke patients remains between 3% and 18%. For improving the quality of stroke care, we investigated the factors that contribute to the risk of in-hospital mortality in acute ischemic stroke patients. Materials and methods Between January 1, 2007, and December 31, 2011, 2,556 acute ischemic stroke patients admitted to a stroke unit were included in this study. Factors such as demographic characteristics, clinical characteristics, comorbidities, and complications related to in-hospital mortality were assessed. Results Of the 2,556 ischemic stroke patients, 157 received thrombolytic therapy. Eighty of the 2,556 patients (3.1%) died during hospitalization. Of the 157 patients who received thrombolytic therapy, 14 (8.9%) died during hospitalization. History of atrial fibrillation (AF, P<0.01) and stroke severity (P<0.01) were independent risk factors of in-hospital mortality. AF, stroke severity, cardioembolism stroke, and diabetes mellitus were independent risk factors of hemorrhagic transformation. Herniation and sepsis were the most common complications of stroke that were attributed to in-hospital mortality. Approximately 70% of in-hospital mortality was related to stroke severity (total middle cerebral artery occlusion with herniation, basilar artery occlusion, and hemorrhagic transformation). The other 30% of in-hospital mortality was related to sepsis, heart disease, and other complications. Conclusion AF is associated with higher in-hospital mortality rate than in patients without AF. For improving outcome of stroke patients, we also need to focus to reduce serious neurological or medical complications. PMID:27418830
Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke
Lakhan, Shaheen E.; Kirchgessner, Annette; Tepper, Deborah; Leonard, Aidan
Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs' role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined. PMID:23565108
Serum C-reactive protein level as a biomarker for differentiation of ischemic from hemorrhagic stroke.
Roudbary, Seyed Ali; Saadat, Farshid; Forghanparast, Kambiz; Sohrabnejad, Reza
Cerebrovascular accidents rank first in the frequency and importance among all neurological disease. Although a number of studies had shown increased level of the high sensitive C-reactive protein (hs-CRP) in patients with ischemic stroke, the association of increased hs-CRP with various type of stroke especially the assessment hs-CRP level in ischemic and hemorrhagic stroke have not been investigated. In the present study, we assessed the concentration of hs-CRP in patients with documented ischemic and hemorrhagic stroke in the first 24 hours of the onset of symptoms. Thirty-two patients with Ischemic and hemorrhagic stroke were evaluated at neurology department of Poursina Hospital. The presence of baseline vascular risk factors, including hypertension, diabetes mellitus, hypercholesterolemia, obesity, and smoking, was determined. The blood samples were then collected and routine hematology and biochemistry tests were done. hs-CRP levels were determined using a highly sensitive immunonephelometric method. In this cross sectional study, the age of patient varied from 45-85 years (Mean 70.9 ± 9.4). Serum level of hs-CRP in Ischemic patients were 18.92 ± 11.28 and in hemorrhagic group was 2.65 ± 1.7. This relationship was statistically significant (P<0.0001). It might be concluded that hs-CRP might be considered as a usefully adjunct method for the initial diagnosis of the type of stroke. PMID:21681701
Sex differences in patients with acute ischemic stroke in Tuzla region, Bosnia and Herzegovina.
Salihović, Denisa; Smajlović, Dzevdet; Sinanović, Osman; Kojić, Biljana
Although many aspects of stroke are similar at both sexes, however, there are some differences and characteristics as well. The aim of this study was to analyze sex differences in patients with acute ischemic stroke (IS) regarding to risk factors, subtypes, stroke severity and outcome. From January 1st 2001 to December 31st 2005 at the Department of Neurology Tuzla 2833 patients were admitted with acute ischemic stroke (IS). We were analyzed risk factors, subtypes, stroke severity (Scandinavian Stroke Scale), and thirty-day outcome. There were 1484 (52.3%) female, and they were older than male (67.8 +/- 10.6 vs. 65.7 +/- 10.5, p<0.0001). Hypertension (78% vs. 67%, p<0.0001), heart diseases (50% vs. 45%, p=0.009), atrial fibrillation (22% vs. 14%, p<0.0001) and diabetes mellitus (33% vs. 21%, p<0.0001) were frequently in female, while smoking (45% vs. 14%) and alcohol overuse (18% vs. 0,6%) in male (p<0.0001). Atherothrombotic type of ischemic stroke was frequently in male (37.4% vs. 31.6%, p=0.0013) and cardioembolic in female (21.7% vs. 15.5%, p<0.0001). At admission female had lower SS (SS 31.0 +/- 15 vs. 34.0 +/- 15, p<0.0001). Thirty-day mortality was significantly higher in female (23.3% vs. 18.4%, p=0.0015), and favourable outcome within one month (Rankin Scale
KALRN Rare and Common Variants and Susceptibility to Ischemic Stroke in Chinese Han Population.
Dang, Meizheng; Wang, Zhenzhen; Zhang, Ruyou; Li, Xiaoying; Peng, Yanqing; Han, Xuesong; Sun, Litao; Tian, Jiawei
Stroke is the second most common cause of mortality worldwide, and it is a major cause of physical disability. Several genome-wide association studies have yielded numerous common variants which increase the risk of ischemic stroke, including the Kalirin-coding gene, KALRN. KALRN strongly associates with early-onset coronary artery disease and atherosclerosis and plays an important role in stroke in the European population. In this study, we analyzed four KALRN gene SNPs in 503 ischemic stroke patients and 493 control subjects, separating the patients into separate research groups based on comorbidity with hypertension or diabetes and stroke type (atherosis or lacunar and combination type). We found a rare variant of KALRN, rs11712619, that associated with lacunar stroke in the northern Chinese Han population with an average-risk allele frequency 0.009 (OR 2.95, 95 % CI 1.08-8.01, p = 0.028). However, after adjusting for relevant factors, including sex, age, body mass index, dyslipidemia, alcohol consumption, and smoking, this association was not evident. Additionally, the KALRN variant rs6438833 was associated with ischemic stroke, ischemic stroke comorbid with diabetes, and lacunar stroke after adjusting for the relevant factors (p = 0.046, p = 0.019 and p = 0.046, respectively), which remained significant after 10,000 permutation procedure test (p' = 0.047, p' = 0.018 and p' = 0.048, respectively). The association of these rare and common variants of KALRN with ischemic stroke in northern Chinese Han population offers insight for potential therapeutic research. PMID:25917671
Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke.
Rodhe, Johanna; Burguillos, Miguel A; de Pablos, Rocio M; Kavanagh, Edel; Persson, Annette; Englund, Elisabet; Deierborg, Tomas; Venero, Jose L; Joseph, Bertrand
Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work. PMID:27566702
Building a "brain attack" team to administer thrombolytic therapy for acute ischemic stroke
Hill, M D; Barber, P A; Demchuk, A M; Sevick, R J; Newcommon, N J; Green, T; Buchan, A M
Before tissue plasminogen activator (tPA) was licensed for use in Canada, in February 1999, the Calgary Regional Stroke Program spearheaded the development and organization of local resources to use thrombolytic therapy in patients who had experienced acute ischemic stroke. In 1996 special permission was obtained from the Calgary Regional Health Authority to use intravenously administered tPA for acute ischemic stroke, and ethical and scientific review boards approved the protocols. After 3 years our efforts have resulted in improved patient outcomes, shorter times from symptom onset to treatment and acceptable adverse event rates. Areas for continued improvement include the door-to-needle time and broader education of the public about the symptoms of acute ischemic stroke. PMID:10862236
Lesion segmentation from multimodal MRI using random forest following ischemic stroke.
Mitra, Jhimli; Bourgeat, Pierrick; Fripp, Jurgen; Ghose, Soumya; Rose, Stephen; Salvado, Olivier; Connelly, Alan; Campbell, Bruce; Palmer, Susan; Sharma, Gagan; Christensen, Soren; Carey, Leeanne
Understanding structure-function relationships in the brain after stroke is reliant not only on the accurate anatomical delineation of the focal ischemic lesion, but also on previous infarcts, remote changes and the presence of white matter hyperintensities. The robust definition of primary stroke boundaries and secondary brain lesions will have significant impact on investigation of brain-behavior relationships and lesion volume correlations with clinical measures after stroke. Here we present an automated approach to identify chronic ischemic infarcts in addition to other white matter pathologies, that may be used to aid the development of post-stroke management strategies. Our approach uses Bayesian-Markov Random Field (MRF) classification to segment probable lesion volumes present on fluid attenuated inversion recovery (FLAIR) MRI. Thereafter, a random forest classification of the information from multimodal (T1-weighted, T2-weighted, FLAIR, and apparent diffusion coefficient (ADC)) MRI images and other context-aware features (within the probable lesion areas) was used to extract areas with high likelihood of being classified as lesions. The final segmentation of the lesion was obtained by thresholding the random forest probabilistic maps. The accuracy of the automated lesion delineation method was assessed in a total of 36 patients (24 male, 12 female, mean age: 64.57±14.23yrs) at 3months after stroke onset and compared with manually segmented lesion volumes by an expert. Accuracy assessment of the automated lesion identification method was performed using the commonly used evaluation metrics. The mean sensitivity of segmentation was measured to be 0.53±0.13 with a mean positive predictive value of 0.75±0.18. The mean lesion volume difference was observed to be 32.32%±21.643% with a high Pearson's correlation of r=0.76 (p<0.0001). The lesion overlap accuracy was measured in terms of Dice similarity coefficient with a mean of 0.60±0.12, while the contour
Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with ischemic stroke in the Eastern Chinese Han population.
Lv, Q-Q; Lu, J; Sun, H; Zhang, J-S
The association between the MTHFR genetic polymorphism and ischemic stroke has been reported by a number of investigators. However, the results have been controversial and conflicting. The aim of this study was to explore the association between the MTHFR variants C677T and A1298C and the risk of ischemic stroke in an Eastern Chinese Han population. A total of 199 patients with ischemic stroke and 241 controls were recruited. Genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using the Taqman 7900HT Sequence Detection System. The overall estimates (odds ratio: OR) for the allele (C) and genotype (AC+CC) of the A1298C polymorphism were 1.57 [95% confidence interval (CI) = 1.16-2.10], and 2.36 (95%CI = 1.39-4.00), respectively, establishing significant association of the MTHFR A1298C polymorphism with ischemic stroke. In contrast, there were no statistically significant differences compared to controls between MTHFR C677T polymorphic variants in the association ischemic stroke risk. Furthermore, haplotype-based analysis demonstrated that compared with the C-677-A-1298 haplotype, the C-677-C-1298 and T-677-C-1298 haplotypes showed significant increased risk of ischemic stroke (OR = 1.56; 95%CI = 1.07- 2.2; P = 0.02; OR = 1.76; 95%CI = 1.17-2.65; P < 0.01, respectively). We concluded that the A1298C polymorphism and the haplotypes C-677-C-1298 and T-677-C-1298 in MTHFR might modulate the risk of ischemic stroke in the Eastern Chinese Han population. PMID:25966188
Inducible Glutamate Oxaloacetate Transaminase as a Therapeutic Target Against Ischemic Stroke
Khanna, Savita; Briggs, Zachary
Abstract Significance: Glutamate serves multi-faceted (patho)physiological functions in the central nervous system as the most abundant excitatory neurotransmitter and under pathological conditions as a potent neurotoxin. Regarding the latter, elevated extracellular glutamate is known to play a central role in ischemic stroke brain injury. Recent Advances: Glutamate oxaloacetate transaminase (GOT) has emerged as a new therapeutic target in protecting against ischemic stroke injury. Oxygen-sensitive induction of GOT expression and activity during ischemic stroke lowers glutamate levels at the stroke site while sustaining adenosine triphosphate levels in brain. The energy demands of the brain are among the highest of all organs underscoring the need to quickly mobilize alternative carbon skeletons for metabolism in the absence of glucose during ischemic stroke. Recent work builds on the important observation of Hans Krebs that GOT-mediated metabolism of glutamate generates tri-carboxylic acid (TCA) cycle intermediates in brain tissue. Taken together, outcomes suggest GOT may enable the transformative switch of otherwise excitotoxic glutamate into life-sustaining TCA cycle intermediates during ischemic stroke. Critical Issues: Neuroprotective strategies that focus solely on blocking mechanisms of glutamate-mediated excitotoxicity have historically failed in clinical trials. That GOT can enable glutamate to assume the role of a survival factor represents a paradigm shift necessary to develop the overall significance of glutamate in stroke biology. Future Directions: Ongoing efforts are focused to develop the therapeutic significance of GOT in stroke-affected brain. Small molecules that target induction of GOT expression and activity in the ischemic penumbra are the focus of ongoing studies. Antioxid. Redox Signal. 22, 175–186. PMID:25343301
Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden.
Margaglione, M; D'Andrea, G; Giuliani, N; Brancaccio, V; De Lucia, D; Grandone, E; De Stefano, V; Tonali, P A; Di Minno, G
At a young age, ischemic stroke is an uncommon event in which prothrombotic factors are likely to play an important role. In 202 referred cases, 105 men and 97 women, median age 39 years (range, 3 to 50), with a history of ischemic stroke and in 1036 age frequency-matched apparently healthy individuals from the same ethnic background, we have investigated whether inherited prothrombotic conditions increase the risk of ischemic stroke. Neither abnormal plasma levels of natural anticoagulants and fibrinogen nor significant increase of the prothrombin A20210 allele was found in stroke cases compared with controls. Hypertension (odds ratio [OR], 22.61), male sex (OR, 2.30), smoking (OR, 2.78) and alcohol habits (OR, 0.14), a personal history of venous thromboembolism (OR, 4.53), a family history of stroke (OR, 1.93), high circulating levels of fibrinogen (P=0.0190), and total cholesterol (P=0.101) were all independently associated with ischemic stroke. Compared with noncarriers, carriers of the factor V (FV) Leiden mutation (OR, 2.56), and to a lesser extent, of the methylenetetrahydrofolate reductase (MTHFR) TT genotype (OR, 1.60), had an independent higher estimated risk of having a history of ischemic stroke. The relationship with the FV Leiden mutation was greater in women (OR, 3.95). Thus, in addition to established determinants, FV Leiden mutation is independently associated with the occurrence of ischemic stroke in this setting. The greater association in women suggests the possibility of an interaction of this genotype with female hormones. PMID:10397694
Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.
Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun
Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke. PMID:25659099
Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.
Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K
Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716
Vagus Nerve Stimulation in Ischemic Stroke: Old Wine in a New Bottle
Cai, Peter Y.; Bodhit, Aakash; Derequito, Roselle; Ansari, Saeed; Abukhalil, Fawzi; Thenkabail, Spandana; Ganji, Sarah; Saravanapavan, Pradeepan; Shekar, Chandana C.; Bidari, Sharatchandra; Waters, Michael F.; Hedna, Vishnumurthy Shushrutha
Vagus nerve stimulation (VNS) is currently Food and Drug Administration-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression, which has failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966–2014) with keywords "VNS AND stroke" in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of VNS in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation. PMID:25009531
Citalopram Enhances Neurovascular Regeneration and Sensorimotor Functional Recovery after Ischemic Stroke in Mice
Espinera, Alyssa R.; Ogle, Molly E.; Gu, Xiaohuan; Wei, Ling
Recent clinical trials have demonstrated that treatment with selective serotonin reuptake inhibitors (SSRIs) after stroke enhances motor functional recovery; however, the underlying mechanisms remain to be further elucidated. We hypothesized that daily administration of the clinical drug citalopram would produce these functional benefits via enhancing neurovascular repair in the ischemic peri-infarct region. To test this hypothesis, focal ischemic stroke was induced in male C57/B6 mice by permanent ligation of distal branches of the middle cerebral artery to the barrel cortex and 7-min occlusion of the bilateral common carotid arteries. Citalopram (10 mg/kg, i.p.) was injected 24 hrs after stroke and daily thereafter. To label proliferating cells, bromo-deoxyuridine was injected daily beginning 3 days after stroke. Immunohistochemical and functional assays were performed to elucidate citalopram-mediated cellular and sensorimotor changes after stroke. Citalopram treatment had no significant effect on infarct formation or edema 3 days after stroke; however, citalopram-treated mice had better functional recovery than saline-treated controls 3 and 14 days after stroke in the adhesive removal test. Increased expression of brain derived neurotrophic factor was detected in the peri-infarct region 7 days after stroke in citalopram-treated animals. The number of proliferating neural progenitor cells and the distance of neuroblast migration from the sub-ventricular zone towards the ischemic cortex were significantly greater in citalopram-treated mice at 7 days after stroke. Immunohistochemical staining and co-localization analysis showed that citalopram-treated animals generated more new neurons and microvessels in the peri-infarct region 21 and 28 days after stroke. Taken together, these results suggest that citalopram promotes post-stroke sensorimotor recovery likely via enhancing neurogenesis, neural cell migration and the microvessel support in the peri-infarct region of
Effect of stem cell-based therapy for ischemic stroke treatment: A meta-analysis.
Wang, Qian; Duan, Feng; Wang, Ming-Xin; Wang, Xiao-Dong; Liu, Peng; Ma, Li-Zhi
Stroke is a major cause of death and long-term disability worldwide. Cell-based therapies improve neural functional recovery in pre-clinical studies, but clinical results require evaluation. We aimed to assess the effects of mesenchymal stem cells on ischemic stroke treatment. We searched the PubMed, Embase and Cochrane databases until July 2015 and selected the controlled trials using mesenchymal stem cells for ischemic stroke treatment compared with cell-free treatment. We assessed the results by meta-analysis using the error matrix approach, and we assessed the association of mesenchymal stem cell counts with treatment effect by dose-response meta-analysis. Seven trials were included. Manhattan plots revealed no obvious advantage of the application of stem cells to treat ischemic stroke. For the comprehensive evaluation index, stem cell treatment did not significantly reduce the mortality of ischemic stroke patients (relative risk (RR) 0.59, 95% confidence interval (CI) 0.29-1.19; ln(RR) 0.54, 95% CI -0.18 to 1.25, p=0.141). The National Institutes of Health Stroke Scale was also not significantly improved by stem cell treatment (standardized mean difference (SMD) 0.94, 95% CI -0.13 to 2.01, p=0.072). The European Stroke Scale was significantly improved using the stem cell treatment (SMD 1.15, 95% CI 0.37-1.92). The dose-response meta-analysis did not reveal a significant linear regression relationship between the number of stem cells and therapeutic effect, except regarding the National Institutes of Health Stroke Scale index. In conclusion, our assessments indicated no significant difference between stem cell and cell-free treatments. Further research is needed to discover more effective stem cell-based therapies for ischemic stroke treatment. PMID:27131124
Neuronal deficiency of HIF prolyl 4-hydroxylase 2 in mice improves ischemic stroke recovery in an HIF dependent manner.
Li, Lexiao; Saliba, Pamela; Reischl, Stefan; Marti, Hugo H; Kunze, Reiner
Hypoxia inducible factors (HIFs) mediate the endogenous adaptive responses to hypoxia. HIF prolyl 4-hydroxylase domain proteins (PHD) are important suppressors of the HIF pathway. Recently, we demonstrated that neuron-specific deletion of Phd2 reduces cerebral tissue damage in the very acute phase of ischemic stroke. In the present study, we investigated whether neuronal Phd2 ablation is likewise beneficial for stroke recovery, and aimed to identify underlying cellular mechanisms. Mice underwent permanent occlusion of the distal middle cerebral artery (pdMCAO) for either 7days (sub-acute stage) or 30days (chronic stage). One week after pdMCAO the infarct size of Phd2-deficient mice was significantly reduced as compared to wild-type (WT) mice. Accordingly, Phd2-deficient animals showed less impaired sensorimotor function. Neuronal loss of Phd2 upregulated vascular endothelial growth factor (VEGF) and significantly increased microvascular density along the infarct border in the sub-acute stage of stroke. Phd2-deficient mice showed reduced expression of pro-inflammatory cytokines and increased numbers of resting microglia/macrophages and reactive astrocytes within peri-infarct regions in comparison to WT littermates. Finally, brain tissue protection and increased angiogenesis upon sub-acute ischemic stroke was completely absent in Phd2 knockout mice that were additionally deficient for both Hif1a and Hif2a. Our findings suggest that lack of PHD2 in neurons improves histological and functional long-term outcome from ischemic stroke at least partly by amplifying endogenous adaptive neovascularization through activation of the HIF-VEGF axis. PMID:27001147
Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke.
Glueck, C J; Fontaine, R N; Wang, P
Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband's mother and brother had deep venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband's brother was heterozygous for the G20210A prothrombin gene mutation. The proband's niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband's heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogen-progestin oral contraceptives were given to the proband's niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke. PMID:11246543
Ionic Regulation of Cell Volume Changes and Cell Death after Ischemic Stroke
Song, Mingke; Yu, Shan Ping
Stroke is a leading cause of human death and disability in the US and around the world. Shortly after the cerebral ischemia, cell swelling is the earliest morphological change in injured neuronal, glial and endothelial cells. Cytotoxic swelling directly results from increased Na+ (with H2O) and Ca2+ influx into cells via ionic mechanisms evoked by membrane depolarization and a number of harmful factors such as glutamate accumulation and the production of oxygen reactive species (ROS). During the sub-acute and chronic phases after ischemia, injured cells may show a phenotype of cell shrinkage due to complex processes involving membrane receptors/channels and programmed cell death signals. This review will introduce some progress in the understanding of the regulation of pathological cell volume changes and the involved receptors and channels, including NMDA and AMPA receptors, acid-sensing ion channels (ASIC), hemichannels, transient receptor potential (TRP) channels and KCNQ channels. Moreover, accumulating evidence supports a key role of energy deficiency and dysfunction of Na+/K+-ATPase in ischemia-induced cell volume changes and cell death. Specifically, the Na+ pump failure is a prerequisite for disruption of ionic homeostasis including a pro-apoptotic disruption of the K+ homeostasis. Finally, we will introduce the concept of hybrid cell death as a result of the Na+ pump failure in cultured cells and the ischemic brain. The goal of this review is to outline recent understanding of the ionic mechanism of ischemic cytoxicity and suggest innovative ideas for future translational research. PMID:24323733
Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke
NASA Astrophysics Data System (ADS)
Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.
Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.
Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives.
Feldstein, Carlos A
Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID:24220549
Hypoxia Inducible Factor 1 as a Therapeutic Target in Ischemic Stroke
Shi, H
In stroke research, a significant focus is to develop therapeutic strategies that prevent neuronal death and improve recovery. Yet, few successful therapeutic strategies have emerged. Hypoxia-inducible factor 1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be an important player in neurological outcomes following ischemic stroke due to the functions of its downstream genes. These include genes that promote glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Many lines of evidence have shown that HIF-1 is induced in ischemic brains. Importantly, it seems that HIF-1 is primarily induced in the salvageable tissue of an ischemic brain, penumbra. However, the effect of HIF-1 on neuronal tissue injuries is still debatable based on evidence from in vitro and preclinical studies. Furthermore, it is of importance to understand the mechanism of HIF-1 degradation after its induction in ischemic brain. This review provides a present understanding of the mechanism of HIF-1 induction in ischemic neurons and the potential effect of HIF-1 on ischemic brain tissue. The author also elaborates on potential therapeutic approaches through understanding of the induction mechanism and of the potential role of HIF-1 in ischemic stroke. PMID:19903149
Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study
Matsuo, Ryu; Ago, Tetsuro; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kuwashiro, Takahiro; Kitazono, Takanari; Kamouchi, Masahiro
Background and Purpose Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. Methods We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis. Results Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65–0.97] for neurological improvement, 1.72 [1.26–2.34] for neurological deterioration, and 2.03 [1.55–2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). Conclusions High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke. PMID:27258004
Categorization of Ischemic Stroke Patients Compared with National Institutes of Health Stroke Scale
Marendic, Mario; Bulicic, Ana Repic; Borovina, Tonka; Mise, Nikolina Ivica; Romac, Rinaldo; Suljic, Enra; Titlic, Marina; Milosevic, Marina
Introduction: Scientific guidelines recommend the National Institutes of Health Stroke Scale (NIHSS) for ischemic stroke (IS) assessment. In Clinical Department of Neurology of Split University Hospital Center nurses use the categorization of patients (COP) according to individual needs for health care. Aim: The aim of this study was to demonstrate that there is a positive correlation between the COP and the NIHSS in IS patients. Methods: We analyzed NIHSS scores and COP findings in 325 participants (median age 77 years, min-max: 37-95 years) with acute ISs. Results: There is a statistically significant correlation between the NIHSS score at admission and COP at admission (ρ=0.717; P<0.001). There is a statistically significant correlation between the NIHSS score at discharge and COP at discharge (ρ=0.762; P<0.001). Median of NIHSS scores at admission is higher in females than in males for 2 (Z=4.45, P<0.001) and at discharge is higher for 2 (Z = 4.1, P<0.001). Median of COP at admission is higher in females than in males for 1 (Z=4.7, P<0.001) and at discharge is the same (Z=4.7, P<0.001). Conclusion: There is a significant association of NIHSS scores and COP in IS patients. This association exists at admission and at discharge from the hospital. PMID:27147786
Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack
Patel, Priyesh A.; Zhao, Xin; Fonarow, Gregg C.; Lytle, Barbara L.; Smith, Eric E.; Xian, Ying; Bhatt, Deepak L.; Peterson, Eric D.; Schwamm, Lee H.; Hernandez, Adrian F.
Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized. Methods and Results Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc). Conclusions NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin. PMID:26058721
Molecular Basis of Impaired Glycogen Metabolism during Ischemic Stroke and Hypoxia
Hossain, Mohammed Iqbal; Roulston, Carli Lorraine; Stapleton, David Ian
Background Ischemic stroke is the combinatorial effect of many pathological processes including the loss of energy supplies, excessive intracellular calcium accumulation, oxidative stress, and inflammatory responses. The brain's ability to maintain energy demand through this process involves metabolism of glycogen, which is critical for release of stored glucose. However, regulation of glycogen metabolism in ischemic stroke remains unknown. In the present study, we investigate the role and regulation of glycogen metabolizing enzymes and their effects on the fate of glycogen during ischemic stroke. Results Ischemic stroke was induced in rats by peri-vascular application of the vasoconstrictor endothelin-1 and forebrains were collected at 1, 3, 6 and 24 hours post-stroke. Glycogen levels and the expression and activity of enzymes involved in glycogen metabolism were analyzed. We found elevated glycogen levels in the ipsilateral hemispheres compared with contralateral hemispheres at 6 and 24 hours (25% and 39% increase respectively; P<0.05). Glycogen synthase activity and glycogen branching enzyme expression were found to be similar between the ipsilateral, contralateral, and sham control hemispheres. In contrast, the rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 58% lower activity (P<0.01) in the ipsilateral hemisphere (24 hours post-stroke), which corresponded with a 48% reduction in cAMP-dependent protein kinase A (PKA) activity (P<0.01). In addition, glycogen debranching enzyme expression 24 hours post-stroke was 77% (P<0.01) and 72% lower (P<0.01) at the protein and mRNA level, respectively. In cultured rat primary cerebellar astrocytes, hypoxia and inhibition of PKA activity significantly reduced glycogen phosphorylase activity and increased glycogen accumulation but did not alter glycogen synthase activity. Furthermore, elevated glycogen levels provided metabolic support to astrocytes during hypoxia. Conclusion Our study has
Endovascular Interventions in Acute Ischemic Stroke: Recent Evidence, Current Challenges, and Future Prospects.
Appireddy, Ramana; Zerna, Charlotte; Menon, Bijoy K; Goyal, Mayank
After many years of clinical research, endovascular thrombectomy has been conclusively proven to be an effective treatment in acute ischemic stroke. The evidence is compelling; however, it is generated in high volume stroke centers with stroke expertise. Challenges remain ahead on translating and implementing this evidence in routine clinical care across the world. The current evidence has opened up avenues for further research and innovation in this field. In this review, we will discuss the evolution of evidence on endovascular thrombectomy followed by a discussion of challenges and future prospects in this exciting field of stroke care. PMID:27221502
[Dynamics of intracranial pressure in patients with massive ischemic stroke after decompressive craniotomy].
Nikitin, A S; Burov, S A; Petrikov, S S; Asratian, S A; Gorshkov, K M; Krylov, V V
The goal of the study was assessment of the value of ICP monitoring in patients with massive ischemic stroke after decompressive craniotomy. 12 patients with massive ischemic stroke were performed ICP monitoring after decompressive craniotomy. We identified 3 types of ICP dynamics: a) normal ICP, which no need to treat; b) ICP elevation to 20 mm Hg and more in postoperative period, which can be treated by nonsurgical therapy; c) refractory to therapy ICP elevation to 20 mm Hg and more with development of intracranial hypertension. We consider that ICP monitoring in patients with massive ischemic stroke after decompressive craniotomy can be useful for optimization of the therapy and correction of intracranial hypertension. PMID:24341041
Cost - effectiveness analysis of the antiplatelet treatment administered on ischemic stroke patients using goal programming approach
NASA Astrophysics Data System (ADS)
Rajendran, Rasvini; Zainuddin, Zaitul Marlizawati; Idris, Badrisyah
There are numerous ways to prevent or treat ischemic stroke and each of these competing alternatives is associated with a different effectiveness and a cost. In circumstances where health funds are budgeted and thus fixed, cost-effectiveness analysis (CEA) can provide information on how to comprehend the largest health gains with that limited fund as CEA is used to compare different strategies for preventing or treating a single disease. The most common medications for ischemic stroke are the anti-platelet drugs. While some drugs are more effective than others, they are also more expensive. This paper will thus assess the CEA of anti-platelet drug available for ischemic stroke patients using goal programming (GP) approach subject to in-patients days and patients' quality-of-life. GP presents a way of striving towards several objectives simultaneously whereby in this case we will consider minimizing the cost and maximizing the effectiveness.
Deep vein thrombosis after ischemic stroke: rationale for a therapeutic trial
Bornstein, N.M.; Norris, J.W.
Deep venous thrombosis (DVT) in the legs occurs in 23% to 75% of patients with acute ischemic stroke, and pulmonary embolism accounts for about 5% of deaths. New heparinoid substances, lacking the hazards of more established anticoagulants, raise the question of DVT prophylaxis for these patients. Two hundred fifty consecutive acute ischemic stroke patients were evaluated for the presence of DVT of the legs in a feasibility study for a trial of low-molecular-weight heparin prophylaxis. Forty-nine patients were found suitable for the study, of whom 11 (22.5%) developed DVT. All patients underwent clinical examination, I-125 fibrinogen leg scanning, and impedance plethysmography. Five patients were sufficiently alert and without serious neurologic deficits to justify DVT prophylaxis. Recent advances in noninvasive diagnostic techniques to detect DVT early and the development of relatively safe heparinoid compounds increase the need for a prophylactic study in patients with ischemic stroke.
[Comparative aspects of using neuroprotectors in the management of patients with ischemic stroke].
Ershov, V I
Comparative efficacy of neuroprotective preparations: actovegin, cerebrolysin and ceraxon was studied in 73 patients in the most acute phase of ischemic stroke. A control group included 33 patients in the most acute phase of ischemic stroke who received only basic treatment without neuroprotectors. Patient's state was assessed with the NIHSS, the original scale of E.I. Gusev and V.I. Skvortsova and the Barthel index. Ceraxon in daily dosage 2 g and cerebrolysin in daily dosage 10 ml during 10 days after the development of ischemic stroke led to the significantly better regression of neurological symptoms to the 21st day of disease compared to the control group. Barthel index scores did not differ in the groups studied. PMID:22224244
Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.
Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F
Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (p<0.05). The over-expression of mGluR5 and NR2B mRNA was also inhibited by pre-ischemic exercise (p<0.05). In summary, exercise preconditioning ameliorated brain damage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate. PMID:24907601
Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke
Khanna, Savita; Heigel, Mallory; Weist, Jessica; Gnyawali, Surya; Teplitsky, Seth; Roy, Sashwati; Sen, Chandan K.; Rink, Cameron
The vitamin E family includes both tocopherols and tocotrienols, where α-tocopherol (αTOC) is the most bioavailable form. Clinical trials testing the therapeutic efficacy of high-dose αTOC against stroke have largely failed or reported negative outcomes when a "more is better" approach to supplementation (>400 IU/d) was used. This work addresses mechanisms by which supraphysiologic αTOC may contribute to stroke-induced brain injury. Ischemic stroke injury and the neuroinflammatory response were studied in tocopherol transfer protein-deficient mice maintained on a diet containing αTOC vitamin E at the equivalent human dose of 1680 IU/d. Ischemic stroke-induced brain injury was exacerbated in the presence of supraphysiologic brain αTOC levels. At 48 h after stroke, S100B and RAGE expression was increased in stroke-affected cortex of mice with elevated brain αTOC levels. Such increases were concomitant with aggravated microglial activation and neuroinflammatory signaling. A poststroke increase in markers of oxidative injury and neurodegeneration in the presence of elevated brain αTOC establish that at supraphysiologic levels, αTOC potentiates neuroinflammatory responses to acute ischemic stroke. Exacerbation of microglial activation by excessive αTOC likely depends on its unique cell signaling regulatory properties independent of antioxidant function. Against the background of clinical failure for high-dose αTOC, outcomes of this work identify risk for exacerbating stroke-induced brain injury as a result of supplementing diet with excessive levels of αTOC.—Khanna, S., Heigel,M., Weist, J., Gnyawali, S., Teplitsky, S., Roy, S., Sen, C. K., Rink, C. Excessive α-tocopherol exacerbates microglial activation and brain injury caused by acute ischemic stroke. PMID:25411436
Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.
Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola
The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. PMID
Ginsenoside Rd Is Efficacious Against Acute Ischemic Stroke by Suppressing Microglial Proteasome-Mediated Inflammation.
Zhang, Guangyun; Xia, Feng; Zhang, Yunxia; Zhang, Xiao; Cao, Yuhong; Wang, Ling; Liu, Xuedong; Zhao, Gang; Shi, Ming
A great deal of attention has been paid to neuroprotective therapies for cerebral ischemic stroke. Our two recent clinical trials showed that ginsenoside Rd (Rd), a kind of monomeric compound extracted from Chinese herbs, Panax ginseng and Panax notoginseng, was safe and efficacious for the treatment of ischemic stroke. In this study, we conducted a pooled analysis of the data from 199 patients with acute ischemic stroke in the first trial and 390 in the second to reanalyze the efficacy and safety of Rd. Moreover, animal stroke models were carried out to explore the possible molecular mechanisms underlying Rd neuroprotection. The pooled analysis showed that compared with placebo group, Rd could improve patients' disability as assessed by modified Rankin Scale (mRS) score on day 90 post-stroke and reduce neurologic deficits on day 15 or day 90 post-stroke as assessed by NIH Stroke Scale (NIHSS) and Barthel Index (BI) scores. For neuroprotective mechanisms, administration of Rd 4 h after stroke could inhibit ischemia-induced microglial activation, decrease the expression levels of various proinflammatory cytokines, and suppress nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (IκBα) phosphorylation and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nuclear translocation. An in vitro proteasome activity assay revealed a significant inhibitory effect of Rd on proteasome activity in microglia. Interestingly, Rd was showed to have less side effects than glucocorticoid. Therefore, our study demonstrated that Rd could safely improve the outcome of patients with ischemic stroke, and this therapeutic effect may result from its capability of suppressing microglial proteasome activity and sequential inflammation. PMID:26081140
[Analysis of a disturbance of trace element balance in patients with ischemic stroke with arterial hypertension].
Kuramshina, D B; Novikova, L B; Nikonov, A A; Torshin, I Iu; Gromova, O A
Disturbance of trace element balance increases the risk of cerebrovascular disease and, above all, ischemic stroke (IS). A comparative analysis of clinical and demographic parameters and trace element composition of hair was performed in the group of 30 ischemic stroke patients with arterial hypertension (AH) and 30 stroke patients without hypertension (mean age 55±7 years). The stroke patients with hypertension were characterized by the elevated body mass index (28.5±4.1 kg/m2, AI, 26.0±2.9 kg/m2, p=0.006), higher incidence of coronary heart disease (p=0.04). Alcohol consumption more than 3 drinks a week was associated with a 5-fold increase of the risk of stroke with hypertension (95% CI 1.0-27, p=0.035). The results revealed a number of statistically significant differences in trace element profile in the studied groups of patients: deficits of essential magnesium, manganese, cobalt, copper, zinc, a statistically significant increase in sodium levels, toxic and conditionally toxic trace elements (cadmium, mercury, bismuth, barium, etc.). One of the probable factors that lead to the accumulation of toxic trace elements in stroke patients is the increased consumption of alcohol including that of substandard quality. The data obtained also show the feasibility of implementing screening programs to assess micronutrient status (including trace elements) for early detection of pathological abnormalities in the elemental homeostasis that might lead to an increased risk of ischemic stroke and hypertension. PMID:22677769
Systemic neutrophil activation in a mouse model of ischemic stroke and reperfusion.
Morrison, Helena; McKee, Dana; Ritter, Leslie
As a natural response to injury and disease, neutrophils activate, adhere to the microvasculature, migrate into brain tissue, and release toxic substances such as reactive oxygen species and proteases. This neutrophil response occurs when blood flow is returned to brain tissue (reperfusion) after ischemic stroke. Thus, the presence of activated systemic neutrophils increases the potential for tissue injury during reperfusion after ischemic stroke. Although experiments in rat models suggest that activated neutrophils play a pivotal role in cerebral ischemia reperfusion injury, little is known about systemic neutrophil activation during reperfusion following ischemic stroke in a mouse model. The purpose of this study was to characterize systemic leukocyte responses and neutrophil CD11b expression 15-min and 24-hr post-reperfusion in a mouse model of ischemic stroke. The intraluminal filament method of transient middle cerebral artery occlusion (tMCAO) with reperfusion or a sham procedure was performed in male C57Bl/6 mice. Automated leukocyte counts and manual white blood cell (WBC) differential counts were measured. Flow cytometry was used to assess systemic neutrophil surface CD11b expression. The data suggest that the damaging potential of systemic neutrophil activation begins as early as 15 min and remains evident at 24 hr after the initiation of reperfusion. In addition, because transgenic mouse models, bred on a C57Bl/6 background, are increasingly used to elucidate single mechanisms of reperfusion injury after ischemic stroke, findings from this study are foundational for future investigations examining the damaging potential of neutrophil responses post-reperfusion after ischemic stroke in genetically altered mouse models within this background strain. PMID:21044968
Lack of associations between rs2910164 and rs11614913 polymorphisms and the risk of ischemic stroke
Qin, Biyong; Zheng, Yan; Zhang, Wenjun; Wang, Chengmou; Wang, Jian; Cai, Zhiyou
Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA genes may play a role in the development of cerebrovascular diseases including ischemic stroke through functionally modulating the expression of microRNA target genes. However, the current studies regarding the associations of the common microRNA polymorphisms with susceptibility to ischemic stroke have obtained discrepant results, which prompted us to perform a meta-analysis for a more precise estimation of the concerned associations. Relevant studies evaluating the associations between two common polymorphisms (miR-146a rs2910164 and miR-196a2 rs11614913) and the risk of ischemic stroke were retrieved from the PubMed, Embase, Cochrane Library, Google Scholar, Chinese Wanfang, Chinese Biomedical Database, and Chinese National Knowledge Infrastructure databases. The odds ratio (OR) with its 95% confidence interval (95% CI) were pooled to assess the strength of the associations using RevMan 5.2 and Stata 12.0 software. A total of 5 case-control studies with 2069 cases and 2061 controls on rs2910164, 4 case-control studies with 1873 cases and 1856 controls on rs11614913 polymorphisms were enrolled in the meta-analysis. Overall, neither allele frequency nor genotype distribution of the two common polymorphisms was found to be associated with risk for ischemic stroke in all genetic models. The subgroup analysis revealed a significant association between miR-146a rs2910164 polymorphism and increased risk of ischemic stroke in large sample size group and in Koreans under homozygous, allele, dominant and recessive models. The present meta-analysis suggests that the two common polymorphisms (rs2910164, rs11614913) may not contribute to the susceptibility to ischemic stroke. However, more well-designed studies with large sample size are warranted to further validate the results in different ethnicities. PMID:26770439
Stroke Genetics Network (SiGN) Study: Design and rationale for a genome-wide association study of ischemic stroke subtypes
Meschia, James F.; Arnett, Donna K.; Ay, Hakan; Brown, Robert D.; Benavente, Oscar; Cole, John W.; de Bakker, Paul I.W.; Dichgans, Martin; Doheny, Kimberly F.; Fornage, Myriam; Grewal, Raji; Gwinn, Katrina; Jern, Christina; Conde, Jordi Jimenez; Johnson, Julie A.; Jood, Katarina; Laurie, Cathy C.; Lee, Jin-Moo; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; McClure, Leslie A.; Mitchell, Braxton D.; Schmidt, Reinhold; Rexrode, Kathryn M.; Rich, Stephen S.; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Sharma, Pankaj; Shuldiner, Alan R.; Slowik, Agnieszka; Wassertheil-Smoller, Sylvia; Sudlow, Cathie; Thijs, Vincent; Woo, Daniel; Worrall, Bradford B.; Wu, Ona; Kittner, Steven J.
Background and Purpose Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The NINDS Stroke Genetics Network (SiGN) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods The NINDS Stroke Genetics Network (SiGN) includes ischemic stroke cases from 24 Genetic Research Centers (GRCs), 13 from the US and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the web-based Causative Classification of Stroke (CCS) system, with data entered by trained and certified adjudicators at participating GRCs. Through the Center for Inherited Diseases Research (CIDR), SiGN plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide SNP arrays, and add to these another 4,253 previously genotyped cases for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. CIDR-generated genotypes and corresponding phenotypic data will be shared with the scientific community through dbGaP, and brain MRI studies will be centrally archived. Conclusions The SiGN consortium, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke. PMID:24021684
Differentiating the effects of characteristics of PM pollution on mortality from ischemic and hemorrhagic strokes.
Lin, Hualiang; Tao, Jun; Du, Yaodong; Liu, Tao; Qian, Zhengmin; Tian, Linwei; Di, Qian; Zeng, Weilin; Xiao, Jianpeng; Guo, Lingchuan; Li, Xing; Xu, Yanjun; Ma, Wenjun
Though increasing evidence supports significant association between particulate matter (PM) air pollution and stroke, it remains unclear what characteristics, such as particle size and chemical constituents, are responsible for this association. A time-series model with quasi-Poisson function was applied to assess the association of PM pollution with different particle sizes and chemical constituents with mortalities from ischemic and hemorrhagic strokes in Guangzhou, China, we controlled for potential confounding factors in the model, such as temporal trends, day of the week, public holidays, meteorological factors and influenza epidemic. We found significant association between stroke mortality and various PM fractions, such as PM10, PM2.5 and PM1, with generally larger magnitudes for smaller particles. For the PM2.5 chemical constituents, we found that organic carbon (OC), elemental carbon (EC), sulfate, nitrate and ammonium were significantly associated with stroke mortality. The analysis for specific types of stroke suggested that it was hemorrhagic stroke, rather than ischemic stroke, that was significantly associated with PM pollution. Our study shows that various PM pollution fractions are associated with stroke mortality, and constituents primarily from combustion and secondary aerosols might be the harmful components of PM2.5 in Guangzhou, and this study suggests that PM pollution is more relevant to hemorrhagic stroke in the study area, however, more studies are warranted due to the underlying limitations of this study. PMID:26652230
Pathophysiology, treatment, and animal and cellular models of human ischemic stroke
Stroke is the world's second leading cause of mortality, with a high incidence of severe morbidity in surviving victims. There are currently relatively few treatment options available to minimize tissue death following a stroke. As such, there is a pressing need to explore, at a molecular, cellular, tissue, and whole body level, the mechanisms leading to damage and death of CNS tissue following an ischemic brain event. This review explores the etiology and pathogenesis of ischemic stroke, and provides a general model of such. The pathophysiology of cerebral ischemic injury is explained, and experimental animal models of global and focal ischemic stroke, and in vitro cellular stroke models, are described in detail along with experimental strategies to analyze the injuries. In particular, the technical aspects of these stroke models are assessed and critically evaluated, along with detailed descriptions of the current best-practice murine models of ischemic stroke. Finally, we review preclinical studies using different strategies in experimental models, followed by an evaluation of results of recent, and failed attempts of neuroprotection in human clinical trials. We also explore new and emerging approaches for the prevention and treatment of stroke. In this regard, we note that single-target drug therapies for stroke therapy, have thus far universally failed in clinical trials. The need to investigate new targets for stroke treatments, which have pleiotropic therapeutic effects in the brain, is explored as an alternate strategy, and some such possible targets are elaborated. Developing therapeutic treatments for ischemic stroke is an intrinsically difficult endeavour. The heterogeneity of the causes, the anatomical complexity of the brain, and the practicalities of the victim receiving both timely and effective treatment, conspire against developing effective drug therapies. This should in no way be a disincentive to research, but instead, a clarion call to
Evaluation of mean diffusion and kurtosis MRI mismatch in subacute ischemic stroke: Comparison with NIHSS score.
Guo, Yue-Lin; Zhang, Zhong-Ping; Zhang, Gui-Shan; Kong, Ling-Mei; Rao, Hai-Bing; Chen, Wei; Wang, Guang-Wen; Shen, Zhi-Wei; Zheng, Wen-Bin; Wu, Ren-Hua
Neurological deterioration (ND) is a devastating complication following ischemic stroke. This study aimed to identify the differences in lesion characteristics in subacute ischemic stroke patients with and without ND using diffusional kurtosis imaging (DKI), as well as to confirm the responsible lesions that may lead to ND, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Seventy-nine patients with subacute cerebral infarction were allocated to the ND (-) and ND (+) groups according to the NIHSS score and lesion number. The mean diffusion (MD) lesions were significantly larger than the mean kurtosis (MK) deficits in the ND (+) group (P<0.05); however, there was no significant difference in the ND (-) group (P>0.05). The MD and MK in the lesion recovered to normal levels over time; however, the recovery trends in the ND (+) group were substantially slower than the ND (-) group. The differences between the two groups were only significant regarding the MK (p<0.05). Furthermore, multiple infarction lesions exhibited good consistency in the ND (-) group, but were non-homogeneous in the ND (+) group. To the best of our knowledge, this is the first study to demonstrate that a significant MD/MK mismatch and heterogeneity of multiple ischemic lesions on MK in subacute ischemic stroke may represent a new expansion of an ischemic lesion or acute reinfarction, which is closely related to ND. PMID:27208488
Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke
Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2 test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 of TOMM40 (P=0.0443; recessive model; odds ratio=0.50) and rs273909 of SLC22A4 (P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition. TOMM40 and SLC22A4 may thus be susceptibility loci for ischemic stroke in Japanese individuals. PMID:26171154
Evaluation of transesophageal echocardiography in detecting cardiac sources of emboli in ischemic stroke patients
Toodeji, Mohammad Amin; Izadi, Sadegh; Shariat, Abdolhamid; Nikoo, Mohamad Hosin
Background: Embolus is one of the causes of ischemic stroke that can be due to cardiac sources such as valvular heart diseases and atrial fibrillation and atheroma of the aorta. Transesophageal echocardiography (TEE) is superior in identifying potential cardiac sources of emboli. Due to insufficient data on TEE findings in ischemic stroke in Iran, the present study was done to evaluate TEE in detecting cardiac sources of emboli. The main aim of this study was to describe the cardiogenic sources of emboli using TEE in the ischemic stroke patients. Methods: This is a cross-sectional study conducted during a 13-month period from January 2012 to February 2013 in Shiraz Nemazee teaching hospital. Patients admitted with stroke diagnosis were included; but hemorrhagic stroke cases were excluded. 229 patients with ischemic stroke diagnosis were included and underwent TEE. Results: Causes of cardiac emboli were detected in 65 cases (40.7%) and categorized to high-risk (29.7%) and potential risk (11%). High risk cardiac sources included atrial fibrillation (8.7%), mitral valve disease (MS or MI) 11 cases (4.75%), aortic valve disease (AS or AI) 8 (3.5%), prosthetic valve 3 (1.35%), dilated cardiomyopathy 45 (19.65%) and congestive heart failure with ejection fraction < 30% in 8 cases (3.5%). Potential cardiac sources of emboli comprised 7 cases (3.05%) of septal aneurysm, 4 (1.75%) left ventricular hypokinesia, 13 (5.7%) mitral annular calcification and 9 cases (3.95%) complex atheroma in the ascending aorta or proximal arch. Conclusion: Our study showed that high risk cardiac sources of emboli can be detected using TEE in a considerable percentage of ischemic stroke patients. The most common high risk cardiac etiologies were dilated cardiomyopathy and valvular heart diseases. PMID:26793628
Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever.
Savastano, Luis; Gemmete, Joseph J; Pandey, Aditya S; Roark, Christopher; Chaudhary, Neeraj
Ischemic strokes in childhood are rare. Thrombolytic therapy with intravenous (IV) tissue plasminogen activator (tPA) has been the main intervention for the management of pediatric stroke patients, but safety data are lacking and efficacy has been questioned. Recently, successful endovascular treatments for acute ischemic stroke in children have been reported with increasing frequency, suggesting that mechanical thrombectomy can be a safe and effective treatment. We present the case of a 22-month-old child with acute ischemic stroke due to basilar artery occlusion that was successfully treated with a stent retriever. PMID:26156170
Next-generation antithrombotics in ischemic stroke: preclinical perspective on 'bleeding-free antithrombosis'
Kraft, Peter; De Meyer, Simon F; Kleinschnitz, Christoph
The present antithrombotic drugs used to treat or prevent ischemic stroke have significant limitations: either they show only moderate efficacy (platelet inhibitors), or they significantly increase the risk for hemorrhages (thrombolytics, anticoagulants). Although most strokes are caused by thrombotic or embolic vessel occlusions, the pathophysiological role of platelets and coagulation is largely unclear. The introduction of novel transgenic mouse models and specific coagulation inhibitors facilitated a detailed analysis of molecular pathways mediating thrombus formation in models of acute ischemic stroke. Prevention of early platelet adhesion to the damaged vessel wall by blocking platelet surface receptors glycoprotein Ib alpha (GPIbα) or glycoprotein VI (GPVI) protects from stroke without provoking bleeding complications. In addition, downstream signaling of GPIbα and GPVI has a key role in platelet calcium homeostasis and activation. Finally, the intrinsic coagulation cascade, activated by coagulation factor XII (FXII), has only recently been identified as another important mediator of thrombosis in cerebrovascular disease, thereby disproving established concepts. This review summarizes the latest insights into the pathophysiology of thrombus formation in the ischemic brain. Potential clinical merits of novel platelet inhibitors and anticoagulants as powerful and safe tools to combat ischemic stroke are discussed. PMID:22805877
Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.
Zhang, Linjie; Yang, Li
Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke. PMID:25549058
Acute ischemic non-embolic stroke and serum level of uric acid
Sheykholeslami, Nazanin Zia; Gadari, Faranak; Ahmady, Jafar
Background Impact of high level of uric acid on stroke is still controversial. We conducted this study to investigate the relationship between acute ischemic non-embolic stroke and serum levels of uric acid. Methods This was a case-control study on patients with acute ischemic non-embolic stroke in Rafsanjan, Iran. The control group consisted of normal persons who were similar to the case group in terms of age and gender. Serum level of uric acid in the first 24 hours of admission was measured with photometry method. Results In a total of 130 patients (59 mens), hyperuricemia was seen in 13.0% of subjects in the control group and 10.7% of subjects in the case group. Nine patients in case group and 7 patients in control group with hyperuricemia were women. No significant relationship was found between acute ischemic non-embolic stroke and serum level of uric acid. Conclusion There was no relationship between uric acid and acute ischemic non-embolic stroke. PMID:24250850
Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke
Rabinstein, Alejandro A.
Most of the contraindications to the administration of intravenous (IV) recombinant tissue plasminogen activator (rtPA) originated as exclusion criteria in major stroke trials. These were derived from expert consensus for the National Institute of Neurological Disorders and Stroke (NINDS) trial. Despite the fact that the safety and efficacy of IV rtPA has been repeatedly confirmed in large international observational studies over the past 20 years, most patients with acute ischemic stroke disappointingly still do not receive thrombolytic treatment. Some of the original exclusion criteria have proven to be unnecessarily restrictive in real-world clinical practice. It has been suggested that application of relaxed exclusion criteria might increase the IV thrombolysis rate up to 20% with comparable outcomes to thrombolysis with more conventional criteria. We review the absolute and relative contraindications to IV rtPA for acute ischemic stroke, discussing the underlying rationale and evidence supporting these exclusion criteria. PMID:26288669
Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke
Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke. PMID:26610894
Intravenous thrombolysis in a patient with left atrial myxoma with acute ischemic stroke
Kulkarni, Girish Baburao; Yadav, Ravi; Mustare, Veerendrakumar; Modi, Sailesh
Intravenous thrombolysis (IVT) is an accepted therapy in patients with acute ischemic stroke presenting within 3-4.5 hours of symptom onset. Selection of the patient for thrombolysis depends on the careful assessment for the risk of post thrombolysis symptomatic haemorrhage (6.2-8.9%) which may be fatal. Atrial myxomas which are the commonest tumors of the heart are associated with stroke due to tumor/clot embolism. There are very few case reports of IVT and its outcome in patients with atrial myxoma with stroke. Some have reported successful thrombolysis, while others have reported intracerebral bleeding. In this report we describe our experience of IVT in atrial myxoma patient with ischemic stroke and review the relevant literature. PMID:25506173
Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies.
Benjamin, Laura A; Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L; Nath, Avindra; Heyderman, Robert S; Connor, Myles D; Solomon, Tom
HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505
Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non-lacunar stroke: preliminary results.
Chen, Y F; Luo, C H; Liu, Y J; Lu, W H; Su, B R
Stroke is a non-communicable disease of increasing socioeconomic importance in aging populations. This study compared the risk factors implicated in two subtypes of ischemic stroke: lacunar stroke (LS) and non-lacunar stroke (NLS). A retrospective case control study was conducted on a total of 368 patients [220 cases (59.8%) of NLS and 148 cases (40.2%) of LS] with first-time onset of ischemic stroke. Multivariate logistic regression was performed to compare multiple non-cerebrovascular risk factors between the two groups. More patients with a history of diabetes were found in the NLS than the LS group (40.5 vs 26.4%), and that both fasting glucose and HbA1C levels before the onset of stroke were higher in NLS than LS patients. Multivariate analysis revealed that patients with a history of diabetes were 1.57 times more likely to have NLS than LS (OR = 1.57, 95%CI = 0.95-3.26). Moreover, male patients were more likely to develop NLS than females (OR = 1.46, 95%CI = 0.79-2.69), and patients with elevated fibrinogen levels were 1.4 times more likely to develop NLS than LS (OR = 1.40, 95%CI = 1.09-1.80). Additionally, patients who were heavy drinkers (OR = 1.39, 95%CI = 0.68-2.84) or smokers (OR = 1.62, 95%CI = 0.91-2.89) were more likely to develop NLS than LS. Other risk factors, such as hypertension, dyslipidemia, age, and average blood pressure, did not differ between the two types of stroke. Thus, distinct non-cerebrovascular risk factors (male gender, long history of diabetes, elevated fibrinogen, heavy smoking, and heavy drinking) are associated with a higher risk of developing non-lacunar stroke than lacunar stroke. PMID:25966082
Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report
Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de
Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.
Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review.
O'Donnell, Martin J; Hankey, Graeme J; Eikelboom, John W
For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348). PMID:18369175
Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke
Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong
Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202
A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke
Kim, Hyung Jik; Kim, Jwa-Kyung; Oh, Mi Sun; Kim, Sung Gyun; Yu, Kyung-Ho
Background and Purpose Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study. Methods This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. The primary endpoint of poor functional outcome was defined as 3-month death or dependency (modified Rankin Scale score ≥3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of ≥4 at discharge compared to baseline) during hospitalization and in-hospital mortality. Results The overall eGFR was 84.5±20.8 mL/min/1.73 m2 (mean±SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality. Conclusions A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization. PMID
Ischemic Stroke Is Associated with the ABO Locus: The EuroCLOT Study
Williams, Frances M K; Carter, Angela M; Hysi, Pirro G; Surdulescu, Gabriela; Hodgkiss, Dylan; Soranzo, Nicole; Traylor, Matthew; Bevan, Steve; Dichgans, Martin; Rothwell, Peter M W; Sudlow, Cathie; Farrall, Martin; Silander, Kaisa; Kaunisto, Mari; Wagner, Peter; Saarela, Olli; Kuulasmaa, Kari; Virtamo, Jarmo; Salomaa, Veikko; Amouyel, Philippe; Arveiler, Dominique; Ferrieres, Jean; Wiklund, Per-Gunnar; Arfan Ikram, M; Hofman, Albert; Boncoraglio, Giorgio B; Parati, Eugenio A; Helgadottir, Anna; Gretarsdottir, Solveig; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; Seshadri, Sudha; DeStefano, Anita; Gschwendtner, Andreas; Psaty, Bruce; Longstreth, Will; Mitchell, Braxton D; Cheng, Yu-Ching; Clarke, Robert; Ferrario, Marco; Bis, Joshua C; Levi, Christopher; Attia, John; Holliday, Elizabeth G; Scott, Rodney J; Fornage, Myriam; Sharma, Pankaj; Furie, Karen L; Rosand, Jonathan; Nalls, Mike; Meschia, James; Mosely, Thomas H; Evans, Alun; Palotie, Aarno; Markus, Hugh S; Grant, Peter J; Spector, Tim D
Objective End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy REFVIDunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. Methods Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). Results Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10–8) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10–186), rs10665 with FVII (p = 2.4 × 10–47), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10–57) and factor VIII (p = 1.2 × 10–36). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88–0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). Interpretation ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic
Disparities among Asians and Native Hawaiians and Pacific Islanders with ischemic stroke
Koenig, Matthew A.; Asai, Susan M.; Chang, Cherylee W.; Seto, Todd B.
Objectives: To evaluate disparities in cardiovascular risk factors among Asians and Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with ischemic stroke. Methods: We performed a retrospective study on consecutive patients hospitalized for ischemic stroke at a single tertiary center in Honolulu between 2004 and 2010. The prevalence of cardiovascular risk factors was compared for NHPI, Asians, and whites who were hospitalized for ischemic stroke. Results: A total of 1,921 patients hospitalized for ischemic stroke were studied. NHPI were less likely to be older (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.94–0.96), more likely to be female (OR 1.55, 95% CI 1.07–2.24), and more likely to have diabetes (OR 2.74, 95% CI 1.87–4.00), hypertension (OR 1.98, 95% CI 1.27–3.10), and obesity (OR 1.82, 95% CI 1.25–2.65) than whites. NHPI had higher low-density lipoprotein levels (114 ± 50 mg/dL vs 103 ± 45 mg/dL, p = 0.001) and lower high-density lipoprotein levels (38 ± 11 mg/dL vs 45 ± 15 mg/dL, p < 0.0001) than whites. Compared with Asians, NHPI were less likely to be older (OR 0.95, 95% CI 0.94–0.97) and more likely to have diabetes (OR 1.88, 95% CI 1.35–2.61), previous stroke or TIA (OR 1.57, 95% CI 1.09–2.25), and obesity (OR 6.05, 95% CI 4.31–8.48). Conclusions: Asians, NHPI, and whites with ischemic stroke have substantially different cardiovascular risk factors. Targeted secondary prevention will be important in reducing disparities among these racial groups. PMID:23365055
Incremental Value of Left Atrial Global Longitudinal Strain for Prediction of Post Stroke Atrial Fibrillation in Patients with Acute Ischemic Stroke
Kim, Darae; Cho, In Jeong; Kim, Young Dae; Nam, Hyo Suk; Chang, Hyuk-Jae; Hong, Geu-Ru; Ha, Jong-Won; Heo, Ji Hoe; Chung, Namsik
Background Atrial fibrillation (AF) is a well-established risk factor for stroke. Interestingly, ischemic stroke increases risk of incident AF in patients without prior diagnosed AF. For better risk stratification for post-stroke AF, we studied left atrial (LA) size and mechanical function using two-dimensional (2D) speckle tracking imaging in patients with acute ischemic stroke. Methods A total of 227 patients (132 males, age 67 ± 12) with acute ischemic stroke without a history of AF underwent 2D transthoracic echocardiography and speckle tracking imaging for the assessment of LA volume index and global LA longitudinal strain (LALS). From clinical variables, the CHA2DS2-VASc score and National Institute of Health Stroke Scale (NIHSS) were calculated in each patient. Post-stroke AF was defined as newly diagnosed AF during the course after ischemic stroke. Results Post-stroke AF occurred in 25 patients (11%). Patients with post-stroke AF were older and showed a higher tendency of CHA2DS2-VASc score, significantly higher log NIHSS, larger LA volume index and lower global LALS than those without. In multivariate analysis, global LALS was an independent predictor for post-stroke AF (hazard ratio 0.90, 95% confidence interval 0.83.0.97, p < 0.01) after controlling for confounding factors. Furthermore, global LALS provided incremental predictive value for post-stroke AF over the CHA2DS2-VASc score, NIHSS, and LA volume index. The global LALS < 14.5% better distinguished post-stroke AF (area under the curve 0.837, sensitivity 60%, specificity 95%, p < 0.01) than CHA2DS2-VASc score. Conclusion Global LALS as a marker of LA mechanical function has incremental predictive value for post-stroke AF in patients with acute ischemic stroke. PMID:27081440
Association of the Single Nucleotide Polymorphisms in microRNAs 130b, 200b, and 495 with Ischemic Stroke Susceptibility and Post-Stroke Mortality.
Kim, Jinkwon; Choi, Gun Ho; Ko, Ki Han; Kim, Jung Oh; Oh, Seung Hun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun
The microRNA (miRNA) is a small non-coding RNA molecule that modulates gene expression at the posttranscriptional level. Platelets have a crucial role in both hemostasis and thrombosis, a condition that can occlude a cerebral artery and cause ischemic stroke. miR-130b, miR-200b, and miR-495 are potential genetic modulators involving platelet production and activation. We hypothesized that single nucleotide polymorphisms (SNPs) in these miRNAs might potentially contribute to the susceptibility to ischemic stroke and post-stroke mortality. This study included 523 ischemic stroke patients and 400 control subjects. We investigated the association of three miRNA SNPs (miR-130bT>C, miR-200bT>C, and miR-495A>C) with ischemic stroke prevalence and post-stroke mortality. In the multivariate logistic regression, there was no statistically significant difference in the distribution of miR-130bT>C, miR-200bT>C, or miR-495A>C between the ischemic stroke and control groups. In the subgroup analysis based on ischemic stroke subtype, the miR-200b CC genotype was less frequently found in the large-artery atherosclerosis stroke subtype compared with controls (TT+CT vs CC; adjusted odds ratio for CC, 0.506; 95% confidence interval, 0.265-0.965). During a mean follow-up period of 4.80 ± 2.11 years after stroke onset, there were 106 all-cause deaths among the 523 stroke patients. Multivariate Cox regression analysis did not find a significant association between post-stroke mortality and three miRNA SNPs. Our findings suggest that the functional SNP of miR-200b might be responsible for the susceptibility to large-artery atherosclerotic stroke. PMID:27603512
A Family History of Stroke Is Associated with Increased Intima-Media Thickness in Young Ischemic Stroke - The Norwegian Stroke in the Young Study (NOR-SYS)
Øygarden, Halvor; Fromm, Annette; Sand, Kristin Modalsli; Kvistad, Christopher Elnan; Eide, Geir Egil; Thomassen, Lars; Naess, Halvor; Waje-Andreassen, Ulrike
Background and Purpose Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients. Methods First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT. Results During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD. Conclusions FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients. Trial Registration ClinicalTrials.gov NCT01597453 PMID:27504830
Supratentorial arterial ischemic stroke following cerebellar tumor resection in two children.
Catsman-Berrevoets, Coriene E; van Breemen, Melanie; van Veelen, Marie Lise; Appel, Inge M; Lequin, Maarten H
We describe two children who developed ischemic strokes in the territory of the middle cerebral artery, one 7 days and one 11 days after resection of a cerebellar tumor. In the first child, another infarction occurred in the territory of the contralateral middle cerebral artery 5 days after the first stroke. No specific cause or underlying risk factor other than the surgical procedure was found. The subacute clinical course at stroke onset resembled that of the 'posterior fossa syndrome', suggesting a common underlying mechanism. PMID:16088257
Angiogenesis and stem cell transplantation as potential treatments of cerebral ischemic stroke.
Wei, Ling; Keogh, Christine L; Whitaker, Vivian Riley; Theus, Michelle Hedrick; Yu, Shan Ping
Ischemic stroke is a leading cause of human death and disability. Although stroke survivors may gain spontaneous partial functional recovery, they often suffer from sensory-motor dysfunctions, behavioral/neurological alterations, and various degrees of paralysis. Currently, limited clinical intervention is available to prevent ischemic damage and restore lost function in stroke victims. In addition to the extensive research on protective maneuvers against ischemia-induced cell death, increasing attention has been focused on potential strategies of promoting tissue repair and functional recovery in the damaged post-ischemic brain. Angiogenesis, or the growth of new blood vessels, may contribute to cell survival and functional recovery of the area of insult. The study of angiogenesis will increase the understanding of the mechanism underlying post-ischemia neurovascular plasticity and regeneration. Additionally, stem cell transplantation has emerged in the last few years as a potential therapy for ischemic stroke, because of their capability to differentiate into multiple cell types and the possibility that they may provide trophic support for cell survival, tissue repair, and functional recovery. PMID:15927824
Current Opinion of Bone Marrow Stromal Cell Transplantation for Ischemic Stroke
KURODA, Satoshi
This article reviews recent advancement and perspective of bone marrow stromal cell (BMSC) transplantation for ischemic stroke, based on current information of basic and translational research. The author would like to emphasize that scientific approach would enable us to apply BMSC transplantation into clinical situation in near future. PMID:26984453
Technology Transfer Automated Retrieval System (TEKTRAN)
BACKGROUND AND PURPOSE: A relationship between the apolipoprotein E (apoE) genotype and ischemic stroke has been inconsistently reported. We explored this relation in the Atherosclerosis Risk in Communities Study (ARIC). METHODS: The ARIC cohort involves 15,792 men and women, aged 45 to 64 years at ...
Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model
Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.
Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488
Metabolic Syndrome and its Profound Effect on Prevalence of Ischemic Stroke
Lucke-Wold, Brandon P.; DiPasquale, Kenneth; Logsdon, Aric F.; Nguyen, Linda; Lucke-Wold, A. Noelle; Turner, Ryan C.; Huber, Jason D.; Rosen, Charles L.
Ischemic stroke represents a leading cause of death worldwide and the leading cause of disability in the United States. Greater than 8% of all deaths are attributed to ischemic stroke. This rate is consistent with the heightened burden of cardiovascular disease deaths. Treatments for acute ischemic stroke remain limited to tissue plasminogen activator and mechanical thrombolysis, both of which require significant medical expertise and can only be applied to a select number of patients based on time of presentation, imaging, and absence of contraindications. Over 1,000 compounds that were successful in treating ischemic stroke in animal models have failed to correlate to success in clinical trials. The search for alternative treatments is ongoing, drawing greater attention to the importance of preclinical models that more accurately represent the clinical population through incorporation of common risk factors. This work reviews the contribution of these commonly observed risk factors in the clinical population highlighting both the pathophysiology as well as current clinical diagnosis and treatment standards. We also highlight future potential therapeutic targets, areas requiring further investigation, and recent changes in best-practice clinical care.
Epigenetic Regulation of Oxidative Stress in Ischemic Stroke
Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin
The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844
Outdoor air pollution, subtypes and severity of ischemic stroke – a small-area level ecological study
Background Evidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke. Methods We used a small-area level ecological study design and a stroke register set up to capture all incident cases of first ever stroke (1995–2007) occurring in a defined geographical area in South London (948 census output areas; population of 267839). Modeled PM10 and NO2 concentrations were available at a very fine spatial scale (20 meter by 20 meter grid point resolution) and were aggregated to output area level using postcode population weighted averages. Ischemic stroke was classified using the Oxford clinical classification, the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification, National Institutes of Health Stroke Scale (NIHSS) score and a pragmatic clinical severity classification based on Glasgow coma score, ability to swallow, urinary continence and death <2 days of stroke onset. Results Mean (SD) concentrations were 25.1 (1.2) ug/m3 (range 23.3-36.4) for PM10 and 41.4 (3.0) ug/m3 (range 35.4-68.0) for NO2. There were 2492 incident cases of ischemic stroke. We found no evidence of association between these pollutants and the incidence of ischemic stroke subtypes classified using the Oxford and TOAST classifications. We found no significant association with stroke severity using NIHSS severity categories. However, we found that outdoor concentrations of both PM10 and NO2 appeared to be associated with increased incidence of mild but not severe ischemic stroke, classified using the pragmatic clinical severity classification. For mild ischemic stroke, the rate ratio in the highest PM10 category by tertile was 1.20 (1.05-1.38) relative to the lowest category. The rate ratio in the highest NO2 category was 1.22 (1
Neuroprotection for Ischemic Stroke: Moving Past Shortcomings and Identifying Promising Directions
Turner, Ryan C.; Lucke-Wold, Brandon; Lucke-Wold, Noelle; Elliott, Alisa S.; Logsdon, Aric F.; Rosen, Charles L.; Huber, Jason D.
The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics. PMID:23344061
Ischemic stroke following abuse of Marijuana in a Nigerian adult male.
Oyinloye, Olalekan; Nzeh, Donald; Yusuf, Ayodeji; Sanya, Emmanuel
Cannabis is the most widely used illicit drug among adolescents and young adults. Despite its widespread use, only a few reports exist on the association of cannabis use and stroke. A 26-year-old Nigerian male, developed right-sided ischemic stroke few hours after smoking three wraps of cannabis. He had smoked cannabis consistently for the past 4 years prior to the development of the stroke. Known stroke etiology and abuse of other illicit drugs were ruled out from history and investigations. Neuroimaging studies of the brain revealed infarcts in basal ganglia secondary to occlusion of blood flow in the left anterior and middle cerebral arteries. The mechanism of stroke in this patient was thought to be a cannabis-induced vasculopathy. Many cases of stroke in the young are increasingly being seen in hospitals in resource scarce countries. There seems to be a predilection for the basal ganglia in ischemic stroke following cannabis abuse. Therefore, cannabis abuse should be considered in young adults with basal ganglia infarcts, after excluding other known etiologies. PMID:25288854
Automated segmentation of brain ventricles in unenhanced CT of patients with ischemic stroke
NASA Astrophysics Data System (ADS)
Qian, Xiaohua; Wang, Jiahui; Li, Qiang
We are developing an automated method for detection and quantification of ischemic stroke in computed tomography (CT). Ischemic stroke often connects to brain ventricle, therefore, ventricular segmentation is an important and difficult task when stroke is present, and is the topic of this study. We first corrected inclination angle of brain by aligning midline of brain with the vertical centerline of a slice. We then estimated the intensity range of the ventricles by use of the k-means method. Two segmentation of the ventricle were obtained by use of thresholding technique. One segmentation contains ventricle and nearby stroke. The other mainly contains ventricle. Therefore, the stroke regions can be extracted and removed using image difference technique. An adaptive template-matching algorithm was employed to identify objects in the fore-mentioned segmentation. The largest connected component was identified and considered as the ventricle. We applied our method to 25 unenhanced CT scans with stroke. Our method achieved average Dice index, sensitivity, and specificity of 95.1%, 97.0%, and 99.8% for the entire ventricular regions. The experimental results demonstrated that the proposed method has great potential in detection and quantification of stroke and other neurologic diseases.
The Taxonomy Statistic Uncovers Novel Clinical Patterns in a Population of Ischemic Stroke Patients
Tukiendorf, Andrzej; Kaźmierski, Radosław; Michalak, Sławomir
In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S), whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M) algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen's coefficient of agreement was κ = 0.766(P < 0.0001). The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus' taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS), and diabetes mellitus (DM) status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED) and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems. PMID:23875000
Charlson comorbidity index as a predictor of in-hospital death in acute ischemic stroke among very old patients: a single-cohort perspective study.
Falsetti, Lorenzo; Viticchi, Giovanna; Tarquinio, Nicola; Silvestrini, Mauro; Capeci, William; Catozzo, Vania; Fioranelli, Agnese; Buratti, Laura; Pellegrini, Francesco
Chronic diseases are increasing worldwide. Association of two or more chronic conditions is related with poor health status and reduced life expectancy, particularly among elderly patients. Comorbidities represent a risk factor for adverse events in several critical illnesses. We aimed to evaluate if elderly patients are affected by multiple chronic pathologies, assessed by Charlson comorbidity index (CCI), showed a reduced in-hospital survival after ischemic stroke. In a 3-year period, we evaluated all the subjects admitted to our internal medicine department for ischemic stroke. Age, sex, NIHSS score and all the comorbidities were recorded. Days of hospitalization, hospital-related infections and in-hospital mortality were also assessed. For each patient, we evaluated CCI, obtaining four classes: group 1 (CCI: 2-3), group 2 (CCI: 4-5), group 3 (CCI: 6-7) and group 4 (CCI: ≥8). Survival was evaluated with Kaplan-Meier and Cox regression analyses. The complete model considered in-hospital death as the main outcome, days of hospitalization as the time variable and CCI as the main predictor, adjusting for NIHSS, sex and nosocomial infections. Patients in CCI group 3 and 4 had an increased risk of in-hospital mortality, independently of NIHSS, sex and nosocomial infections. Elderly patients with multiple comorbidities have higher risk of in-hospital death when affected by ischemic stroke. PMID:27166707
Diagnostic Potential of the NMDA Receptor Peptide Assay for Acute Ischemic Stroke
Dambinova, Svetlana A.; Bettermann, Kerstin; Glynn, Theodore; Tews, Matthew; Olson, David; Weissman, Joseph D.; Sowell, Richard L.
Background The acute assessment of patients with suspected ischemic stroke remains challenging. The use of brain biomarker assays may improve the early diagnosis of ischemic stroke. The main goal of the study was to evaluate whether the NR2 peptide, a product of the proteolytic degradation of N-methyl-D-aspartate (NMDA) receptors, can differentiate acute ischemic stroke (IS) from stroke mimics and persons with vascular risk factors/healthy controls. A possible correlation between biomarker values and lesion sizes was investigated as the secondary objective. Methods and Findings A total of 192 patients with suspected stroke who presented within 72 h of symptom onset were prospectively enrolled. The final diagnosis was determined based on clinical observations and radiological findings. Additionally gender- and age-matched healthy controls (n = 52) and persons with controlled vascular risk factors (n = 48) were recruited to compare NR2 peptide levels. Blinded plasma was assayed by rapid magnetic particles (MP) ELISA for NR2 peptide within 30 min and results for different groups compared using univariate and multivariate statistical analyses. There was a clinical diagnosis of IS in 101 of 192 (53%) and non-stroke in 91 (47%) subjects. The non-stroke group included presented with acute stroke symptoms who had no stroke (n = 71) and stroke mimics (n = 20). The highest NR2 peptide elevations where found in patients with IS that peaked at 12 h following symptom onset. When the biomarker cut off was set at 1.0 ug/L, this resulted in a sensitivity of 92% and a specificity of 96% to detect IS. A moderate correlation (rs = 0.73) between NR2 peptide values and acute ischemic cortical lesions (<200 mL) was found. Conclusions This study suggests that the NR2 peptide may be a brain specific biomarker to diagnose acute IS and may allow the differentiation of IS from stroke mimics and controls. Additional larger scale clinical validation studies are required
Noninvasive ventilatory correction as an adjunct to an experimental systemic reperfusion therapy in acute ischemic stroke.
Barlinn, Kristian; Balucani, Clotilde; Palazzo, Paola; Zhao, Limin; Sisson, April; Alexandrov, Andrei V
Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies. PMID:21052540
[Promising new treatment for acute ischemic stroke--Sonothrombolysis can enhance the effect of intravenous thrombolysis].
Gu, Thomas; Wester, Per; Johansson, Elias
Intravenous thrombolysis has been a break-through for treatment of acute ischemic stroke. However, total recanalization is only achieved in 18%. Sonothrombolysis aims at enhancing the recanalization effect by adding continuous transcranial ultrasound. Sonothrombolysis may facilitate the recanalization rate without increased risk of intracerebral hemorrhage. This further results in decreased risk of disability compared with only intravenous thrombolysis. Intravenously applied micro-bubbles is an additive treatment to sonothrombolysis which might further increase the recanalization rate but perhaps at the expense of increased risk of intracerebral hemorrhage. In a case-series at Umeå Stroke Center, we report the results of the first 20 ischemic stroke patients treated with sonothrombolysis in Sweden. Our initial results look promising with recanalization rates similar to earlier published data. No intracerebral hemorrhage occurred among our sonothrombolysed patients. PMID:25647105
Mechanical thrombectomy in pediatric acute ischemic stroke: Clinical outcomes and literature review.
Madaelil, Thomas P; Kansagra, Akash P; Cross, DeWitte T; Moran, Christopher J; Derdeyn, Colin P
There are limited data on outcomes of mechanical thrombectomy for pediatric stroke using modern devices. In this study, we report two cases of pediatric acute ischemic stroke treated with mechanical thrombectomy, both with good angiographic result (TICI 3) and clinical outcome (no neurological deficits at 90 days). In addition, we conducted a literature review of all previously reported cases describing the use of modern thrombectomy devices. Including our two cases, the aggregate rate of partial or complete vessel recanalization was 100% (22/22), and the aggregate rate of favorable clinical outcome was 91% (20/22). This preliminary evidence suggests that mechanical thrombectomy with modern devices may be a safe and effective treatment option in pediatric patients with acute ischemic stroke. PMID:26945589
Perinatal ischemic stroke: a five-year retrospective study in a level-III maternity
Machado, Virgínia; Pimentel, Sónia; Pinto, Filomena; Nona, José
Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies. PMID:25993071
Predicting discharge mortality after acute ischemic stroke using balanced data.
Ho, King Chung; Speier, William; El-Saden, Suzie; Liebeskind, David S; Saver, Jeffery L; Bui, Alex A T; Arnold, Corey W
Several models have been developed to predict stroke outcomes (e.g., stroke mortality, patient dependence, etc.) in recent decades. However, there is little discussion regarding the problem of between-class imbalance in stroke datasets, which leads to prediction bias and decreased performance. In this paper, we demonstrate the use of the Synthetic Minority Over-sampling Technique to overcome such problems. We also compare state of the art machine learning methods and construct a six-variable support vector machine (SVM) model to predict stroke mortality at discharge. Finally, we discuss how the identification of a reduced feature set allowed us to identify additional cases in our research database for validation testing. Our classifier achieved a c-statistic of 0.865 on the cross-validated dataset, demonstrating good classification performance using a reduced set of variables. PMID:25954451
Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke.
Tahir, Hassan; Daruwalla, Vistasp; Meisel, Jeremy; Kodsi, Samir E
Pseudoperipheral palsy has been used to characterize isolated monoparesis secondary to stroke. Isolated hand nerve palsy is a rare presentation for acute cerebral stroke. Our patient presented with clinical features of typical peripheral radial nerve palsy and a normal computed tomography scan of the head, which, without a detailed history and neurological examination, could have been easily misdiagnosed as a peripheral nerve lesion deferring further investigation for a stroke. We stress the importance of including cerebral infarction as a critical differential diagnosis in patients presenting with sensory-motor deficit in an isolated peripheral nerve pattern. A good history and physical exam can differentiate stroke from peripheral neuropathy as the cause of radial nerve palsy. PMID:27493976
Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke
Tahir, Hassan; Daruwalla, Vistasp; Meisel, Jeremy; Kodsi, Samir E.
Pseudoperipheral palsy has been used to characterize isolated monoparesis secondary to stroke. Isolated hand nerve palsy is a rare presentation for acute cerebral stroke. Our patient presented with clinical features of typical peripheral radial nerve palsy and a normal computed tomography scan of the head, which, without a detailed history and neurological examination, could have been easily misdiagnosed as a peripheral nerve lesion deferring further investigation for a stroke. We stress the importance of including cerebral infarction as a critical differential diagnosis in patients presenting with sensory-motor deficit in an isolated peripheral nerve pattern. A good history and physical exam can differentiate stroke from peripheral neuropathy as the cause of radial nerve palsy. PMID:27493976
Methylene blue treatment in experimental ischemic stroke: a mini review
Jiang, Zhao; Duong, Timothy Q
Stroke is a leading cause of death and long-term disability. Methylene blue, a drug grandfathered by the Food and Drug Administration with a long history of safe usage in humans for treating methemoglobinemia and cyanide poisoning, has recently been shown to be neuroprotective in neurodegenerative diseases and brain injuries. The goal of this paper is to review studies on methylene blue in experimental stroke models. PMID:27042692
Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke
Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio
Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681
Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke
Pierce, David; Dixit, Anand; Kimberley, Teresa J.; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P.; Rennaker, Robert L.; Cramer, Steven C.; Walters, Matthew; Engineer, Navzer
Background and Purpose— Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Methods— Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity). Results— Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). Conclusions— This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. PMID:26645257
Analysis of the risk factors for the short-term prognosis of acute ischemic stroke
Liang, Jin; Liu, Wenbo; Sun, Jianping; Gu, Xinyi; Ma, Qiang; Tong, Weijun
This study investigated the risk factors for the short-term prognosis of acute ischemic stroke to provide a scientific evidence for improving prevention and treatment. A total of 2557 cases of acute ischemic stroke were included in the study. We collected the data on demographic characteristics, life style-related risk factors, clinical feature, and other clinical characteristics for all the participants. The outcomes were assessed using the modified Rankin scale (mRs) on day 14 or at discharge. According to the mRs score, the subjects were divided into three groups, namely, the control group (0≤ mRs ≤2), the disability group (3≤ mRs ≤5), and the death group (mRs = 6). The general conditions of these three groups were compared. An mRs score of 3≤ mRs ≤6 belonged to the composite outcome group. Logistic regression was also applied to analyze the risk factors of short-term prognosis. Monovariant logistic regression showed that age, on-set admission, hospital stays, temperature, heart rate, stroke subtype, hypertension, hyperglycemia, history of heart disease, history of atrial fibrillation, history of cerebral stroke, drinking, count of WBC, count of mononuclear leucocyte, and rate of neutrophile granulocyte were statically significant. To further control the confounding factors, multivariant logistic regression analysis was carried out. The result showed that age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were related to the short-term prognosis. Age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were the risk factors of the short-term prognosis of acute ischemic stroke. PMID:26885162
Determinants of outcome in patients eligible for thrombolysis for ischemic stroke
Caso, Valeria; Paciaroni, Maurizio; Venti, Michele; Palmerini, Francesco; Silvestrelli, Giorgio; Milia, Paolo; Biagini, Sergio; Agnelli, Giancarlo
Objectives Eligibility criteria for thrombolysis in ischemic stroke have been clearly defined. However, not all eligible patients benefit from this treatment. This study aimed to assess the determinants for clinical outcome in consecutive, eligible patients with ischemic stroke treated with thrombolysis in a single-center study. Methods Consecutive patients with ischemic stroke were treated with tissue plasminogen activator (t-PA) following the established eligibility National Institute of Neurological Disorders and Stroke (NINDS) and European Stroke Initiative (EUSI) criteria. Risk factors including blood pressure and pre-treatment glycemia were properly managed. Death and disability at 3 months were the study outcomes. Disability was evaluated by the Rankin-scale. Favorable outcome was defined as 0–2 and adverse outcome as 3–6 including death. Results Seventy-eight patients were included in the study in a single stroke unit. The mean age was 70.9 ± 13.2 years (range 36–94). Follow-up at 3 months was completed in 73 patients. A favorable outcome was observed in 37 patients (50%) and adverse outcome in 36 (36%). Nine patients (12.3%) died within 3 months. The presence of an occluded carotid artery was a strong predictor for adverse outcome (p < 0.0001). A low NIH Stroke Scale-Score (NIHSS) at admission was a associated with a favorable outcome, while history of diabetes mellitus led to an unfavorable outcome. Conclusion Among patients eligible for thrombolysis, many do not benefit from this treatment. These include patients with carotid occlusion and diabetes. PMID:18078026
Antigen-specific immune reactions to ischemic stroke
Urra, Xabier; Miró, Francesc; Chamorro, Angel; Planas, Anna M.
Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke. PMID:25309322
Rapid weather changes are associated with increased ischemic stroke risk: a case-crossover study.
Rakers, Florian; Schiffner, Rene; Rupprecht, Sven; Brandstädt, Antje; Witte, Otto W; Walther, Mario; Schlattmann, Peter; Schwab, Matthias
Observational studies focusing on absolute meteorological values suggest an association between meteorological parameters and stroke risk but these results are inconsistent and conflicting. Since changes in weather can provoke atrial fibrillation, we examined the association between rapid weather changes and stroke risk in 1694 patients with determinable onset of stroke symptoms in a case-crossover study in central Germany. Days one to three before stroke onset were classified as hazard periods and day seven as the respective control period. Risk of ischemic stroke in relation to 24 h differences in mean ambient temperature, relative humidity and atmospheric pressure was determined. The association between temperature and stroke risk appears to be close to linear with an increase in stroke risk of 11 % (odds ratio 1.11, 95 % confidence interval 1.01-1.22) for each 2.9 °C temperature decrease over 24 h. In individuals with a higher cardiovascular risk, stroke risk increased by 30 % (1.30, 1.06-1.61). Risk for cardioembolic strokes increased by 26 % (1.26, 1.06-1.50). Rapid positive or negative changes in relative humidity (>5 %) and atmospheric pressure (>10 hPa) increased stroke risk by a maximum of 30 % (1.30, 1.02-1.66) and 63 % (1.63, 1.10-2.42). In individuals with a higher cardiovascular risk, rapid changes in atmospheric pressure were associated with a four-times higher stroke risk (4.56, 1.26-16.43). Our results suggest that rapid decreases in ambient temperature and rapid changes in relative humidity and atmospheric pressure increase stroke risk under temperate climate conditions. Individuals with a high cardiovascular risk profile seem to be at greater risk. PMID:26148559
Age, subjective stress, and depression after ischemic stroke.
McCarthy, Michael J; Sucharew, Heidi J; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Ferioli, Simona; Adeoye, Opeolu; Kleindorfer, Dawn O; Kissela, Brett M
The incidence of stroke among younger adults in the United States is increasing. Few studies have investigated the prevalence of depressive symptoms after stroke among different age groups or the extent to which subjective stress at the time of stroke interacts with age to contribute to post-stroke depression. The present study examined whether there exists an age gradient in survivors' level of depressive symptoms and explored the extent to which financial, family, and health-related stress may also impact on depression. Bivariate analyses (N = 322) indicated significant differences in depression and stress by age group, as well as differences in age and stress by 3-month depression status. Linear regression analyses indicated that survivors between the ages of 25-54 and 55-64 years old had, on average, significantly higher depressive symptom scores. Those with financial, family, and health-related stress at the time of stroke, irrespective of age, also had significantly higher scores. PMID:26245159
Effective mechanical thrombectomy in a patient with hyperacute ischemic stroke associated with cardiac myxoma.
Baek, Seol-Hee; Park, Soonchan; Lee, Nam Joon; Kang, Youngjin; Cho, Kyung-Hee
Ischemic stroke is the most common neurologic manifestation of cardiac myxoma. However, there has been no current guideline on the treatment of hyperacute ischemic stroke due to cardiac myxoma. We describe a patient with hyperacute stroke caused by cardiac myxoma who had a good outcome with rapid recanalization through mechanical thrombectomy. A 46-year-old man was admitted with acute symptoms of right side hemiplegia and global aphasia. Brain computed tomography (CT) angiography showed a T occlusion of the left internal carotid artery. Intravenous recombinant tissue plasminogen activator was administered. However, his clinical symptoms did not improve. Thus, we performed endovascular treatment and had a successful outcome. A pathologic examination of the retrieved clot revealed a tumor emboli from a cardiac myxoma. Transthoracic echocardiogram revealed a left atrial myxoma in which a large mass was attached to the posterior wall of the aorta. The patient's neurologic deficits recovered with the exception of left eye blindness. Reperfusion therapy with mechanical thrombectomy might be safe and effective for the rapid revascularization of large vessel occlusions in hyperacute ischemic stroke, from which the tumor thrombi can be retrieved. PMID:25174564
Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke
NASA Astrophysics Data System (ADS)
Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut
The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.
[Hereditary thrombophilia with ischemiC stroke and sinus thrombosis. Diagnosis, therapy and meta-analysis].
Weih, M; Junge-Hülsing, J; Mehraein, S; Ziemer, S; Einhäupl, K M
Hereditary thrombophilias are a heterogenous group of genetic coagulation disorders which, particularly in combination with acquired prothrombotic factors, induce a predisposition to thrombosis. After characterization of frequent thrombophilic syndromes like factor V-Leiden or the prothrombin 20210GA mutation, a number of case-control studies screened for the prevalence of these mutations in ischemic stroke and cerebral venous thrombosis (CVT). Our meta-analysis shows that factor V-Leiden and prothrombin are frequent and significantly associated with CVT (16.4% vs. 4.9% or 4.3, P < 0.001, and 12.1% vs. 1.9% or 5.8, P < 0.001). In ischemic stroke, only factor V-Leiden and not prothrombin is a weak but significant risk factor (5.9% vs. 2.6% or 1.6, P < 0.001, and 4.1% vs. 3.3% or 1.4, P = 0.1). The C677T homozygous point mutation in the MTHFR, a homocysteine-degrading enzyme, was also associated with arterial stroke (16% vs. 15% or 1.5, P < 0.001). For CVT, sufficient data are lacking. We therefore recommend screening for thrombophilia in CVT. In ischemic stroke, atrial premature complex (APC) resistance should be considered. As long as controlled studies are lacking, individual anticoagulant therapy must take hereditary and precipitating factors into account to assess potential thrombotic risk. PMID:11139989
[The fetal proteins in prognosis of development of pneumonia in patients with ischemic stroke].
Arkhipkin, A A; Liang, O V; Kochetov, A G
The searching of laboratory predictors of pneumonia in patients with ischemic stroke is an actual issue. The fetal proteins can be such biomarkers. The study was carried out to determine significance of such fetal proteins as alpha-fetoprotein, cancerous embryonic antigen, CA 19-9, CA 125, CA 15-3, CA 72-4, CYFRA 21-1 for prognosis of development of pneumonia in patients with ischemic stroke. The study included sampling of 216 patients in acute period of ischemic stroke. All patients were measured level of fetal proteins in first day from onset of disease using electrochemiluminescence immunoassay. It is demonstrated that CA 72-4 has the most significance for prognosis of development of pneumonia from all analyzed proteins and complications of ischemic stroke. The probability ratio relatively to other fetal proteins added up to 0.460 (CL 95% 0.267-0.791, p=0.011), to other complications--0.629 (CL 95% 0.433-0.913, p=0.015). The threshold value of CA 72-4 for development of pneumonia added up to 0.82 (CL 95% 0.68-0.96, p=0.011) U/ml. Under lower level of CA 72-4 the risk of development of pneumonia increases. Under higher level of CA 72-4 there is statistical probability of absence of developmnent of pneumonia. The threshold value was lower than reference interval which in the study added up to 0.85-1.42 U/ml. The detection of level of CA 72-4 on first day after onset of stroke in patients can be recommended for establishing of group of high risk of development of pneumonia and implementation of therapeutic activities. PMID:25872261
Outcome Predictors in First-Ever Ischemic Stroke Patients: A Population-Based Study
Corso, Giovanni; Bottacchi, Edo; Tosi, Piera; Caligiana, Laura; Lia, Chiara; Veronese Morosini, Massimo; Dalmasso, Paola
Background. There is scant population-based information regarding predictors of stroke severity and long-term mortality for first-ever ischemic strokes. The aims of this study were to determine the characteristics of patients who initially presented with first-ever ischemic stroke and to identify predictors of severity and long-term mortality. Methods. Data were collected from the population-based Cerebrovascular Aosta Registry. Between 2004 and 2008, 1057 patients with first-ever ischemic stroke were included. Variables analysed included comorbidities, sociodemographic factors, prior-to-stroke risk factors, therapy at admission and pathophysiologic and metabolic factors. Multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional Hazards model were used to assess predictors. Results. Predictors of stroke severity at admission were very old age (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.75–5.06), female gender (OR 1.73, 95% CI 1.21–2.40), atrial fibrillation (OR 2.76, 95% CI 1.72–4.44), low ejection fraction (OR 2.22, CI 95% 1.13–4.32), and cardioembolism (OR 2.0, 95% CI 1.36–2.93). Predictors of long-term mortality were very old age (hazard ratio [HR] 2.02, 95% CI 1.65–2.47), prestroke modified Rankin scale 3–5 (HR 1.82; 95% CI 1.46–2.26), Charlson Index ≥2 (HR 1.97; 95% CI 1.62–2.42), atrial fibrillation (HR 1.43, 95% CI 1.04–1.98), and stroke severity (HR 3.54, 95% CI 2.87–4.36). Conclusions. Very old age and cardiac embolism risk factors are the independent predictors of stroke severity. Moreover, these factors associated with other comorbid medical conditions influence independently long-term mortality after ischemic stroke.
Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke
Vani, Javad Rasouli; Mohammadi, Mohammad Taghi; Foroshani, Mahsa Sarami; Jafari, Mahvash
Oxidative stress is the common underlying mechanism of damage in ischemic stroke. Therefore, we aimed to evaluate the possible protective effects of polyhydroxylated fullerene derivatives on brain infarction and oxidative/nitrosative stress in a rat model of ischemic stroke. The experiment was performed by four groups of rats (each; n=12); Sham, Control ischemia, and ischemic treatment groups (Pretreatment and Posttreatment). Brain ischemia was induced by 90 min middle cerebral artery occlusion (MCAO) followed by 24 hours reperfusion. Rats received fullerene nanoparticles at dose of 1 mg/kg 30 min before MCAO and immediately after beginning of reperfusion. Infarct volume, contents of malondialdehyde (MDA), glutathione (GSH) and nitrate as well as superoxide dismutase (SOD) activity were assessed 24 hours after termination of MCAO. Brain infarct volume was 310 ± 21 mm3 in control group. Administration of fullerene nanoparticles before and after MCAO significantly decreased the infarct volume by 53 % (145 ± 45 mm3) and 81 % (59 ± 13 mm3), respectively. Ischemia also enhanced MDA and nitrate contents of ischemic hemispheres by 45 % and 25 % , respectively. Fullerene nanoparticles considerably reduced the MDA and nitrate contents of ischemic hemispheres before MCAO by 58 % and 17 % , respectively, and after MCAO by 38 % and 21 % , respectively. Induction of MCAO significantly decreased GSH content (19 % ) and SOD activity (52 % ) of ischemic hemispheres, whereas fullerene nanoparticles increased the GSH content and SOD activity of ischemic hemispheres by 19 % and 52 % before MCAO, respectively, and 21 % and 55 % after MCAO, respectively. Our findings indicate that fullerene nanoparticles, as a potent scavenger of free radicals, protect the brain cells against ischemia/reperfusion injury and inhibit brain oxidative/nitrosative damage. PMID:27540350
First-ever Ischemic Stroke after a Flight in a Patient with Prior Poliomyelitis
Chang, Cheng-Chiang; Chang, Shin-Tsu; Ku, Chih-Hung; Chiang, Shang-Lin; Chang, Hsiao-Ying; Lai, Min-Hsin; Tsai, Kao-Chung; Chen, Liang-Cheng
Survivors of poliomyelitis sometimes travel by air with mobility assistance. However, prolonged seating during long-haul flights may also possibly produce stroke events on polio-inflicted patients. A 48-year-old polio-inflicted male suffered a stroke after an extended flight. A two-dimensional echocardiography was normal without detected patent foramen ovale or dyskinetic segment. The venodynamic variables were all within normal limits. MR Imaging studies revealed acute cerebral infarction in the distribution of the right middle cerebral artery and posterior watershed area. Hematological examination revealed positive anti-cardiolipin IgG antibody which might contribute to the risk of thrombosis as an underlying condition in addition to immobilization. This is the first presentation of ischemic stroke after a flight in a patient with prior poliomyelitis. In addition to decompression sickness, economy class stroke syndrome and postpoliomyelitis syndrome, the physician should also take other coagulation disorders into consideration during the investigation. PMID:21876645
Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke
Turner, Renée J.; Sharp, Frank R.
Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke. PMID:26973468
Translational strategies for neuroprotection in ischemic stroke - focusing on Acid Sensing Ion Channel 1a
O'Bryant, Zaven; Vann, Kiara T.; Xiong, Zhi-Gang
Ischemic stroke contributes to the majority of brain injuries and remains to be a leading cause of death and long-term disability. Despite the devastating pathology and high incidence of disease, there remain only few treatment options (tPA and endovascular procedures), which may be hampered by time dependent administration among a variety of other factors. Promising research of glutamate receptor antagonists has been unsuccessful in clinical trial. But, the mechanism by which glutamate receptors initiate injury by excessive calcium overload has spurred investigation of new and potentially successful candidates for stroke therapy. Acid sensing ion channels (ASICs) may contribute to poor stroke prognosis due to localized drop in brain pH, resulting in excessive calcium overload, independent of glutamate activation. Accumulating studies targeting ASICs have underscored the importance of understanding inhibition, regulation, desensitization and trafficking of this channel and its role in disease. This review will discuss potential directions in translational ASIC research for future stroke therapies. PMID:24390970
Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice
Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Wei, Ling
Apelin is a peptide originally isolated from bovine stomach tissue extracts and identified as an endogenous ligand of the APJ receptor; recent work showed that apelin ameliorates the ischemic injury in the heart and the brain. Being an analogue to the angiotensin II receptor, the apelin/APJ signaling may mediate angiogenesis process. We explored the noninvasive intranasal brain delivery method and investigated therapeutic effects of apelin-13 in a focal ischemic stroke model of mice. Intranasal administration of apelin-13 (4 mg/kg) was given 30 min after the onset of stroke and repeated once daily. Three days after stroke, mice received apelin-13 had significantly reduced infarct volume and less neuronal death in the penumbra. Western blot analyses showed upregulated levels of apelin, apelin receptor APLNR, and Bcl-2 and decreased caspase-3 activation in the apelin-13-treated brain. The proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1β, and chemokine monocyte chemoattractant protein-1 mRNA increased in the ischemic brain, which were significantly attenuated by apelin-13. Apelin-13 remarkably reduced microglia recruitment and activation in the penumbra according to morphological features of Iba-1-positive cells 3 days after ischemia. Apelin-13 significantly increased the expression of angiogenic factor vascular endothelial growth factor and matrix metalloproteinase-9 14 days after stroke. Angiogenesis illustrated by collagen IV + /5-bromo-2′-deoxyuridin + colabeled cells was significantly increased by the apelin-13 treatment 21 days after stroke. Finally, apelin-13 promoted the local cerebral blood flow restoration and long-term functional recovery. This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13. PMID:26391329
Paradoxical Association of Smoking With In‐Hospital Mortality Among Patients Admitted With Acute Ischemic Stroke
Ali, Syed F.; Smith, Eric E.; Bhatt, Deepak L.; Fonarow, Gregg C.; Schwamm, Lee H.
Background Compared to those who never smoked, a paradoxical effect of smoking on reducing mortality in patients admitted with myocardial ischemia has been reported. We sought to determine if this effect was present in patients hospitalized with ischemic stroke. Methods and Results Using the local Get with the Guidelines‐Stroke registry, we analyzed 4305 consecutively admitted ischemic stroke patients (March 2002–December 2011). The sample was divided into smokers versus nonsmokers. The main outcome of interest was the overall inpatient mortality. Compared to nonsmokers, tobacco smokers were younger, more frequently male and presented with fewer stroke risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, and atrial fibrillation. Smokers also had a lower average NIH Stroke Scale (NIHSS) and fewer received tissue plasminogen activator (tPA). Patients in both groups had similar adherence to early antithrombotics, dysphagia screening prior to oral intake, and deep vein thrombosis (DVT) prophylaxis. Smoking was associated with lower all‐cause in‐hospital mortality (6.6% versus 12.4%; unadjusted OR 0.46; CI [0.34 to 0.63]; P<0.001). In multivariable analysis, adjusted for age, gender, ethnicity, hypertension, diabetes mellitus, hyperlipidemia, CAD, atrial fibrillation, NIHSS, and tPA, smoking remained independently associated with lower mortality (adjusted OR 0.64; CI [0.42 to 0.96]; P=0.03). Conclusions Similar to myocardial ischemia, smoking was independently associated with lower inpatient mortality in acute ischemic stroke. This effect may be due to tobacco‐induced changes in cerebrovascular vasoreactivity, or may be due in part to residual confounding. Larger, multicenter studies are needed to confirm the finding and the effect on 30‐day and 1‐year mortality. PMID:23782919
Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice.
Chen, Dongdong; Lee, Jinhwan; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping
Apelin is a peptide originally isolated from bovine stomach tissue extracts and identified as an endogenous ligand of the APJ receptor; recent work showed that apelin ameliorates the ischemic injury in the heart and the brain. Being an analogue to the angiotensin II receptor, the apelin/APJ signaling may mediate angiogenesis process. We explored the noninvasive intranasal brain delivery method and investigated therapeutic effects of apelin-13 in a focal ischemic stroke model of mice. Intranasal administration of apelin-13 (4 mg/kg) was given 30 min after the onset of stroke and repeated once daily. Three days after stroke, mice received apelin-13 had significantly reduced infarct volume and less neuronal death in the penumbra. Western blot analyses showed upregulated levels of apelin, apelin receptor APLNR, and Bcl-2 and decreased caspase-3 activation in the apelin-13-treated brain. The proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1β, and chemokine monocyte chemoattractant protein-1 mRNA increased in the ischemic brain, which were significantly attenuated by apelin-13. Apelin-13 remarkably reduced microglia recruitment and activation in the penumbra according to morphological features of Iba-1-positive cells 3 days after ischemia. Apelin-13 significantly increased the expression of angiogenic factor vascular endothelial growth factor and matrix metalloproteinase-9 14 days after stroke. Angiogenesis illustrated by collagen IV + /5-bromo-2'-deoxyuridin + colabeled cells was significantly increased by the apelin-13 treatment 21 days after stroke. Finally, apelin-13 promoted the local cerebral blood flow restoration and long-term functional recovery. This study demonstrates a noninvasive intranasal delivery of apelin-13 after stroke, suggesting that the reduced inflammatory activities, decreased cell death, and increased angiogenesis contribute to the therapeutic benefits of apelin-13. PMID:26391329
Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2
Carbone, Federico; Teixeira, Priscila Camillo; Braunersreuther, Vincent; Mach, François; Vuilleumier, Nicolas
Abstract Significance: Phagocytes play a key role in promoting the oxidative stress after ischemic stroke occurrence. The phagocytic NADPH oxidase (NOX) 2 is a membrane-bound enzyme complex involved in the antimicrobial respiratory burst and free radical production in these cells. Recent Advances: Different oxidants have been shown to induce opposite effects on neuronal homeostasis after a stroke. However, several experimental models support the detrimental effects of NOX activity (especially the phagocytic isoform) on brain recovery after stroke. Therapeutic strategies selectively targeting the neurotoxic ROS and increasing neuroprotective oxidants have recently produced promising results. Critical Issues: NOX2 might promote carotid plaque rupture and stroke occurrence. In addition, NOX2-derived reactive oxygen species (ROS) released by resident and recruited phagocytes enhance cerebral ischemic injury, activating the inflammatory apoptotic pathways. The aim of this review is to update evidence on phagocyte-related oxidative stress, focusing on the role of NOX2 as a potential therapeutic target to reduce ROS-related cerebral injury after stroke. Future Directions: Radical scavenger compounds (such as Ebselen and Edaravone) are under clinical investigation as a therapeutic approach against stroke. On the other hand, NOX inhibition might represent a promising strategy to prevent the stroke-related injury. Although selective NOX inhibitors are not yet available, nonselective compounds (such as apocynin and fasudil) provided encouraging results in preclinical studies. Whereas additional studies are needed to better evaluate this therapeutic potential in human beings, the development of specific NOX inhibitors (such as monoclonal antibodies, small-molecule inhibitors, or aptamers) might further improve brain recovery after stroke. Antioxid. Redox Signal. 23, 460–489. PMID:24635113
Epidemiology of non-fatal cerebrovascular stroke and transient ischemic attacks in Al Quseir, Egypt
El-Tallawy, Hamdy N; Farghaly, Wafaa MA; Shehata, Ghaydaa A; Abdel-Hakeem, Nabil M; Rageh, Tarek A; Badry, Reda; Kandil, Mahmoud R
Background and purpose Stroke is a medical emergency that can cause permanent neurological damage, complications, and disability. We aim to determine the epidemiology of non-fatal cerebrovascular stroke (CVS) and transient ischemic attacks (TIAs) in Al Quseir City, Red Sea, Egypt. Methods The total population (n=33,285) was screened through a door to door study by three specialists of neurology and 15 female social workers (for demographic data collection). All suspected stroke patients were subjected to a full clinical examination, computerized tomography (CT) and/or magnetic resonance imaging (MRI) of their brain, blood sugar, lipogram, serum uric acid, complete blood cells, blood urea, and serum creatinine, as well as evaluated by Barthel Index and Scandinavian Stroke Scale. Carotid doppler, echocardiography, and thyroid functions were done for selected cases. Results CVS was recorded among 130 patients out of 19,848 subjects aged 20 years and more, yielding a total prevalence of 6.55/1,000 population. From June 1, 2010 to May 31, 2011, 36 patients were recorded to have stroke within 1-year, yielding an incidence rate of 1.81/1,000. Prevalence and incidence rates were higher among males than females, and both indices increased steadily with advancing age to reach the highest prevalence (37.02/1,000) and incidence rate (9.5/1,000) among aged persons 60 years and more. Conclusion The prevalence of non-fatal stroke in Al Quseir city (6.55/1,000) was at the lower range of that recorded in developing countries (5–10/1,000) and slightly higher than that recorded in industrialized countries (5/1,000 population). Ischemic stroke is the most common type of stroke. The prevalence of TIAs was 0.15/1,000. PMID:24293992
Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells.
Gómez-Úriz, Ana M; Milagro, Fermín I; Mansego, María L; Cordero, Paúl; Abete, Itziar; De Arce, Ana; Goyenechea, Estíbaliz; Blázquez, Vanessa; Martínez-Zabaleta, Maite; Martínez, José Alfredo; López De Munain, Adolfo; Campión, Javier
Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers. PMID:25429063
Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.
Lioutas, Vasileios-Arsenios; Alfaro-Martinez, Freddy; Bedoya, Francisco; Chung, Chen-Chih; Pimentel, Daniela A; Novak, Vera
Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood-brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS. PMID:26040423
Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study
Wang, Yingying; Cai, Yunpeng
Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID:27407070
Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study.
Wang, Yingying; Cai, Yunpeng
Recent studies have revealed the systematic altering of gene expression in human peripheral blood during the early stages of ischemic stroke, which suggests a new potential approach for the rapid diagnosis or prediction of stroke onset. Nevertheless, due to the difficulties of collecting human samples during proper disease stages, related studies are rather restricted. Many studies have instead been performed on manipulated animal models for investigating the regulation patterns of biomarkers during different stroke stages. An important inquiry is how well the findings of animal models can be replicated in human cases. Here, a method is proposed based on PageRank scores of miRNA-mRNA interaction network to select ischemic stroke biomarkers derived from rat brain samples, and biomarkers are validated with two human peripheral blood gene expression datasets. Hierarchical clustering results revealed that the achieved biomarkers clearly separate the blood gene expression of stroke patients and healthy people. Literature searches and functional analyses further validated the biological significance of these biomarkers. Compared to the traditional methods, such as differential expression, the proposed approach is more stable and accurate in detecting cross-species biomarkers with biological relevance, thereby suggesting an efficient approach of re-using gene biomarkers obtained from animal-model studies for human diseases. PMID:27407070
Multipotent bone marrow stromal cell therapy promotes endogenous cell proliferation following ischemic stroke.
Pirzad Jahromi, Gila; Shabanzadeh Pirsaraei, Alireza; Sadr, Seyed Shahabeddin; Kaka, Golamreza; Jafari, Mahvash; Seidi, Sadegh; Charish, Jason
Despite extensive research over the years, there still exists some debate as to what constitutes the optimal therapeutic strategy to promote recovery following stroke. Due to the complexity of injured brain pathophysiology, treatment approaches should ideally address numerous factors, ultimately aiming to promote tissue protection, axonal regrowth and functional recovery. This study extends the understanding of the effects of bone marrow stromal cell (BMSC) treatment following experimentally induced ischemic stroke in rats. Focal ischemic brain injury was experimentally induced in rats by placing a preformed clot into the middle cerebral artery. Animals were injected intravenously with BMSCs at 24 h after stroke and were killed 7 days post injury. When administered BMSCs following stroke, the neurological outcome was significantly improved relative to controls. There was an increase in the number of BMSCs labelled with BrdU present in the injured hemisphere of the brain compared to the non-injured side. Furthermore, administration of BMSCs also led to increases in astrocytosis, vascularization and endogenous proliferation. These findings provide insight into the mechanisms of action of BMSC treatment and further argue for the therapeutic potential of BMSCs as an effective treatment following cerebral stroke. PMID:26218989
A Young Woman with Ischemic Stroke: Should We Pay More Attention to Varicella Zoster Infection?
Borbinha, Cláudia; Marto, João Pedro; Calado, Sofia; Viana-Baptista, Miguel
Ischemic and hemorrhagic stroke are recognized complications of Varicella zoster virus (VZV) infections, although uncommon and poorly documented. The authors report the case of a 31-year-old woman admitted with acute ischemic stroke of the right posterior cerebral artery and a history of a thoracic rash 1 month before. Aspirin and simvastatin were prescribed, but the patient suffered a stepwise deterioration the following days, with new areas of infarction on brain imaging. Despite no evidence of cardiac or large vessel embolic sources, anticoagulation was started empirically 6 days after stroke onset. One week later, symptomatic hemorrhagic transformation occurred. The diagnosis of VZV vasculopathy was then considered, and treatment with acyclovir and prednisolone was started with no further vascular events. Cerebrospinal fluid analysis and digital subtraction angiography findings corroborated the diagnosis. The patient was discharged to the rehabilitation center with a modified Rankin scale (mRS) score of 4. On the 6-month follow-up, she presented only a slight disability (mRS score 2). In conclusion, VZV vasculopathy needs to be considered in young adults with stroke. A high index of suspicion and early treatment seem to be important to minimize morbidity and mortality. Anticoagulation should probably be avoided in stroke associated with VZV vasculopathy. PMID:27504091
Ischemic stroke due to paradoxical embolism arising from a popliteal vein aneurysm.
Auboire, Laurent; Palcau, Laura; Mackowiak, Elise; Viader, Fausto; Le Hello, Claire; Berger, Ludovic
Popliteal vein aneurysm (PVA) is a very uncommon cause of stroke. We present the case of a 63-year-old, right-handed man who presented to the emergency department with transitory ischemic accident (left superior extremity regressive monoplegia). Complete etiologic work-up led to the discovery of both a patent foramen ovale associated with an septum interauricular aneurysm, and of a PVA without mural thrombus. The diagnosis of brain paradoxical embolism was retained. The unique potentially embolic cause was the presence of the PVA. We decided to treat the PVA surgically to avoid a further cerebral vascular episode. Although uncommon, venous etiology must be considered for stroke. PMID:24360944
Sporadic Carney complex without PRKAR1A mutation in a young patient with ischemic stroke.
Aguiar de Sousa, Diana; Gouveia, Ana Isabel; Wessling, Ana; Geraldes, Ruth; Canhão, Patrícia
We describe a 29-year-old male, with a previous history of testicular tumor, who presented with a posterior circulation ischemic stroke associated to an atrial myxoma. Dermatologic observation disclosed spotty skin and mucosal pigmentation (lentigines), and a cutaneous myxoma was histopathologically confirmed. Although there was no family history of any of the Carney complex (CNC) features and no mutations in the PRKAR1A gene were found, these findings lead to the diagnosis of CNC. We emphasize the importance of recognizing this entity in young patients with stroke. PMID:25576349
Aspirin Resistance in the Acute Stages of Acute Ischemic Stroke Is Associated with the Development of New Ischemic Lesions
Kim, Joon-Tae; Heo, Suk-Hee; Lee, Ji Sung; Choi, Min-Ji; Choi, Kang-Ho; Nam, Tai-Seung; Lee, Seung-Han; Park, Man-Seok; Kim, Byeong C.; Kim, Myeong-Kyu; Cho, Ki-Hyun
Background Aspirin is a primary antiplatelet agent for the secondary prevention of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is expected in acute ischemic stroke (AIS), it may increase the rate of early clinical events. Therefore, we sought to determine whether aspirin resistance in the acute stage was associated with early radiological events, including new ischemic lesions (NILs). Methods This study was a single-center, prospective, observational study conducted between April 2012 and May 2013. Aspirin 300 mg was initially administered followed by maintenance doses of 100 mg daily. The acute aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin loading. An aARU value ≥550 IU was defined as biological aspirin resistance (BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions separate from index lesions, which were not detected on the initial DWI. Results A total of 367 patients were analyzed in this study. BAR in aARU was detected in 60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were frequently in the same territory as the index lesions (79%), pial infarcts (61.7%), and located within the cortex (59.3%). BAR was independently associated with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01–3.96; p = 0.047). Conclusion In conclusion, BAR in aARU could be associated with NILs on follow-up DWI in AIS. Therefore, a further prospective study with a longer follow-up period is necessary to evaluate the clinical implications of aARU in AIS. PMID:25849632
Cytochrome 4A11 Genetic Polymorphisms Increase Susceptibility to Ischemic Stroke and Associate with Atherothrombotic Events After Stroke in Chinese
Zhang, Biao; Wang, Chun; Liao, Duanxiu; Lin, Jing; Chi, Lifen
To evaluate the associations between four single-nucleotide polymorphisms (SNPs) in CYP4A11 and CYP4F2 and ischemic stroke (IS), and between these variants and atherothrombotic events after stroke. IS patients (n=396) and controls (n=378) were genotyped for two CYP4A11 SNPs (rs2269231 and rs9333025) and two CYP4F2 SNPs (rs2108622 and rs3093135). Patients were followed up for 12 months after the stroke for the atherothrombotic events. The frequency of the rs9333025 GG genotype was significantly higher in IS patients than in controls. Logistic regression analysis showed that the presence of rs9333025 GG in patients was associated with significantly higher risk of IS. Cox regression analysis revealed that the rs9333025 GG genotype was an independent risk factor for atherothrombotic events after stroke. The rs9333025 GG genotype increases patients' susceptibility to IS and is associated with high frequencies of atherothrombotic events in stroke patients. PMID:25734770
Hemorrhagic and ischemic stroke secondary to herpes simplex virus type 2 meningitis and vasculopathy.
Snider, Samuel B; Jacobs, Claire S; Scripko, Patricia S; Klein, Joshua P; Lyons, Jennifer L
Herpes simplex virus type 2 (HSV-2) meningitis dogmatically is benign and self-limited in the immune competent patient. However, we describe how left untreated HSV-2 meningitis can be complicated by vasculitis and both ischemic and hemorrhagic stroke. We report a 57-year-old woman with lymphocytic meningitis complicated by ischemic stroke and intracerebral hemorrhage in the setting of vasculopathy and HSV-2 DNA detected in CSF successfully treated with acyclovir and corticosteroids. Subsequent angiographic magnetic resonance imaging revealed improvement in the vasculopathy after treatment. This case demonstrates that HSV-2 meningitis may take a less benign course and further provides the first evidence of angiographic improvement in addition to clinical improvement after definitive treatment. PMID:24806272
[Intervention effect of Tibetan patent medicine Ruyi Zhenbao pills in acute ischemic stroke in rats].
Liu, Rui-ying; Wu, Wei-jie; Tan, Rui; Xie, Bin; Zhong, Zhen-dong; He, Jing-ping; Chen, Yao; Kang, Xin-li
Ischemic stroke is a primary cause of death and long-term disability all over the world. This disease is resulted from ischemia and hypoxia in brain tissues because of insufficient blood supply and causes a series of physiochemical metabolism disorders and physiological dysfunction. Its high disability ratio has bright huge burdens to society, governments and families. However, there is not efficacious medicine to treat it. In this study, a right middle cerebral artery occlusion was established in rats to observe the multi-path and multi-aspect intervention effects of Tibetan patent medicine Ruyi Zhenbao pills in reducing injuries to Nissl bodies, cerebral edema and inflammatory reactions and preventing cellular apoptosis, in order to lay a foundation for defining its therapeutic mechanism in acute ischemic stroke. PMID:26084187
Meta-Analysis of Local Endovascular Therapy for Acute Ischemic Stroke.
Kennedy, Sean A; Baerlocher, Mark O; Baerlocher, Felix; Socko, Daniel; Sacks, David; Nikolic, Boris; Wojak, Joan C; Haskal, Ziv J
A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care. PMID:26803573
[Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke].
Li, De-chuan; Bao, Xiu-qi; Sun, Hua; Zhang, Dan
Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA. PMID:26521431
Mild Sensory Stimulation Completely Protects the Adult Rodent Cortex from Ischemic Stroke
Chen-Bee, Cynthia H.; Frostig, Ron D.
Despite progress in reducing ischemic stroke damage, complete protection remains elusive. Here we demonstrate that, after permanent occlusion of a major cortical artery (middle cerebral artery; MCA), single whisker stimulation can induce complete protection of the adult rat cortex, but only if administered within a critical time window. Animals that receive early treatment are histologically and behaviorally equivalent to healthy controls and have normal neuronal function. Protection of the cortex clearly requires reperfusion to the ischemic area despite permanent occlusion. Using blood flow imaging and other techniques we found evidence of reversed blood flow into MCA branches from an alternate arterial source via collateral vessels (inter-arterial connections), a potential mechanism for reperfusion. These findings suggest that the cortex is capable of extensive blood flow reorganization and more importantly that mild sensory stimulation can provide complete protection from impending stroke given early intervention. Such non-invasive, non-pharmacological intervention has clear translational potential. PMID:20585659
Successful intravenous thrombolysis in a patient with antiphospholipid syndrome, acute ischemic stroke and severe thrombocytopenia.
Camara-Lemarroy, Carlos R; Infante-Valenzuela, Adrian; Andrade-Vazquez, Catalina J; Enriquez-Noyola, Raul V; Garcia-Valadez, Erick A; Gongora-Rivera, Fernando
Alteplase is the only approved drug for the treatment of acute ischemic stroke, but it is offered to a minority of patients, not only because of the short therapeutic window but also because of the numerous contraindications associated with thrombolysis, such as thrombocytopenia. There is some controversy on the true risk associated with thrombolysis in patients with thrombocytopenia. Here we report the case of a young patient, who developed an in-hospital acute ischemic stroke involving a large territory of the right middle cerebral artery, who was successfully treated with intravenous alteplase, despite having thrombocytopenia and prolonged prothrombin times due to systemic lupus erythematosus and antiphospholipid syndrome. This case exemplifies the need to reassess contraindications for thrombolysis, many based on expert opinion and not clinical evidence, especially in complex clinical situations. PMID:26575492
Subtotal Gastrectomy With Billroth II Anastomosis Is Associated With a Low Risk of Ischemic Stroke in Peptic Ulcer Disease Patients: A Nationwide Population-Based Study.
Chen, Chien-Hua; Lin, Cheng-Li; Kao, Chia-Hung
Duodenal diversion can ameliorate lipid and glucose metabolism. We assessed the risk of stroke after subtotal gastrectomy with Billroth II anastomosis (SGBIIA) in peptic ulcer disease (PUD).We identified 6425 patients who received SGBIIA for PUD between 1998 and 2010 from the Taiwan National Health Insurance Research Database as the study cohort; we frequency-matched them with 25,602 randomly selected controls from the PUD population who did not receive SGBIIA according to age, sex, index year, and comorbidities including hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, congestive heart failure, chronic kidney disease, chronic obstructive pulmonary disease (COPD), and obesity. All patients were followed until the end of 2011 to determine the incidence of stroke.The incidence of stroke was lower in patients in the SGBIIA cohort than in those in the non-SGBIIA cohort (18.9 vs 22.9 per 1000 person-years, adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.72-0.89, P < 0.001). The risk of ischemic stroke (aHR 0.77, 95% CI 0.69-0.86, P < 0.001), rather than hemorrhagic stroke (aHR 1.00, 95% CI 0.78-1.28), was lower for the SGBIIA cohort than for the non-SGBIIA cohort according to the multivariable Cox proportional hazard regression analysis. The relative risk of ischemic stroke after SGBIIA was lower in men (aHR 0.77, 95% CI 0.69-0.86) than in women (aHR 0.80, 95% CI 0.65-0.99) and in patients aged ≥65 years (aHR 0.72, 95% CI 0.63-0.81) than in those of other age groups (≤49 years, aHR 0.82, 95% CI 0.48-1.39; 50-64 years, aHR 1.01, 95% CI 0.79-1.28). The relative risk of ischemic stroke after SGBIIA was also reduced in patients with comorbidities (aHR 0.84, 5% CI 0.75-0.95) rather than in those without comorbidities (aHR 0.81, 95% CI 0.59-1.12).SGBIIA is associated with a low risk of ischemic stroke for PUD patients, and its protective effect is prominent in men, patients aged ≥65 years, and those with comorbidities
Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population
Huang, Suli; Zhou, Shiquan; Zhang, Yanwei; Lv, Ziquan; Li, Shanshan; Xie, Changhui; Ke, Yuebin; Deng, Pingjian; Geng, Yijie; Zhang, Qian; Chu, Xiaofan; Yi, Zhaohui; Zhang, Ying; Wu, Tangchun; Cheng, Jinquan
microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis. PMID:25658319
Delayed Ischemic Stroke after Flow Diversion of Large Posterior Communicating Artery Aneurysm
Kim, Si On; Chung, Yeon Gu; Won, Yu Sam
For securing large, giant, and wide-neck aneurysms, conventional coil embolization has substantial limitations, such as incomplete occlusion, recanalization, and a high recurrence rate. To overcome these limitations, a novel paradigm was suggested and, as a result, flow-diverting device was developed. The flow-diverting device is an innovative and effective technique to allow securing of large, giant, and wide-neck aneurysms. In numerous studies, the flow-diverting device has shown better outcomes than coil embolization. However, the flow-diverting device has also some risks, including rupture of aneurysm, intracerebral hemorrhage, and ischemic stroke. In addition, with more experience, unexpected complications are also reported.5)7) In the present case, we experienced a delayed ischemic stroke at 27 days after endovascular treatment. The patient had multiple aneurysms and, among them, we treated a large posterior communicating artery aneurysm using Pipeline™ Embolization Device. The patient was tolerable for 25 days, but then suddenly presented intermittent right hemiparesis. In the initial diffusion magnetic resonance imaging (MRI), there was no acute lesion; however, in the follow-up MRI, an acute ischemic stroke was found in the territory of anterior choroidal artery which was covered by Pipeline Embolization Device. We suspect that neo-intimal overgrowth or a tiny thrombus have led to this delayed complication. Through our case, we learned that the neurosurgeon should be aware of the possibility of delayed ischemic stroke after flow diversion, as well as, long-term close observation and follow-up angiography are necessary even in the event of no acute complications. PMID:27114962
Delayed Ischemic Stroke after Flow Diversion of Large Posterior Communicating Artery Aneurysm.
Kim, Si On; Chung, Yeon Gu; Won, Yu Sam; Rho, Myung Ho
For securing large, giant, and wide-neck aneurysms, conventional coil embolization has substantial limitations, such as incomplete occlusion, recanalization, and a high recurrence rate. To overcome these limitations, a novel paradigm was suggested and, as a result, flow-diverting device was developed. The flow-diverting device is an innovative and effective technique to allow securing of large, giant, and wide-neck aneurysms. In numerous studies, the flow-diverting device has shown better outcomes than coil embolization. However, the flow-diverting device has also some risks, including rupture of aneurysm, intracerebral hemorrhage, and ischemic stroke. In addition, with more experience, unexpected complications are also reported.5)7) In the present case, we experienced a delayed ischemic stroke at 27 days after endovascular treatment. The patient had multiple aneurysms and, among them, we treated a large posterior communicating artery aneurysm using Pipeline™ Embolization Device. The patient was tolerable for 25 days, but then suddenly presented intermittent right hemiparesis. In the initial diffusion magnetic resonance imaging (MRI), there was no acute lesion; however, in the follow-up MRI, an acute ischemic stroke was found in the territory of anterior choroidal artery which was covered by Pipeline Embolization Device. We suspect that neo-intimal overgrowth or a tiny thrombus have led to this delayed complication. Through our case, we learned that the neurosurgeon should be aware of the possibility of delayed ischemic stroke after flow diversion, as well as, long-term close observation and follow-up angiography are necessary even in the event of no acute complications. PMID:27114962
Effect of IMOD™ on the inflammatory process after acute ischemic stroke: a randomized clinical trial
Background and purpose of the study Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke. Methods In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n = 49) and control (n = 50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared. Results and major conclusion 58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00 ± 8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p = 0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p = 0.02). There was an insignificant decrease in TNF-α and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy. PMID:23514014
A novel effect of Noscapine on patients with massive ischemic stroke: A pseudo-randomized clinical trial
Mahmoudian, Massoud; Rezvani, Mohammad; Rohani, Mohammad; Benaissa, Foozya; Jalili, Mehdi; Ghourchian, Shadi
Background: Massive ischemic stroke causes significant mortality and morbidity in stroke patients. The main treatments for massive ischemic stroke are recombinant tissue plasminogen activator (rtPA), craniotomy, and endovascular interventions. Due to destructive effects of bradykinin on the nervous system in ischemic stroke, it seems reasonable that using Noscapine as a Bradykinin antagonist may improve patients' outcome after ischemic stroke. The effect of Noscapine on massive ischemic stroke was shown by the previous pilot study by our group. This pseudo-randomized clinical trial study was designed to assess the result of the pilot study. Methods: Patients who had clinical symptoms or computed tomography scan indicative of massive stroke (in full middle cerebral artery territory) were entered to the study. The cases received the drugs according to their turns in emergency ward (pseudo-randomized). The patient group received Noscapine, and the control group received common supportive treatments. The patients and data analyzer were blinded about the data. At the end of the study, to adjust confounding variables we used logistic regression. Results: After 1-month follow-up, 16 patients in the control group and 11 patients in the case group expired (P = 0.193). Analyzing the data extracted from Rankin scale and Barthel index check lists, revealed no significant differences in the two groups. Conclusion: Despite the absence of significant statistical results in our study, the reduction rate of 16% for mortality rate in Noscapine recipients is clinically remarkable and motivates future studies with larger sample sizes. PMID:25874051
Fire-Heat and Qi Deficiency Syndromes as Predictors of Short-term Prognosis of Acute Ischemic Stroke
Cheng, Shu-Chen; Lin, Chien-Hsiung; Chang, Yeu-Jhy; Lee, Tsong-Hai; Ryu, Shan-Jin; Chen, Chun-Hsien; Chang, Her-Kun; Chang, Chee-Jen
Abstract Objectives To explore the relationships between traditional Chinese medicine (TCM) syndromes and disease severity and prognoses after ischemic stroke, such as neurologic deficits and decline in activities of daily living (ADLs). Methods The study included 211 patients who met the inclusion criteria of acute ischemic stroke based on clinical manifestations, computed tomography or magnetic resonance imaging findings, and onset of ischemic stroke within 72 hours with clear consciousness. To assess neurologic function and ADLs in patients with different TCM syndromes, the TCM Syndrome Differentiation Diagnostic Criteria for Apoplexy scale (containing assessments of wind, phlegm, blood stasis, fire-heat, qi deficiency, and yin deficiency with yang hyperactivity syndromes) was used within 72 hours of stroke onset, and Western medicine–based National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) assessments were performed at both admission and discharge. Results The most frequent TCM syndromes associated with acute ischemic stroke were wind syndrome, phlegm syndrome, and blood stasis syndrome. Improvement according to the BI at discharge and days of admission were significantly different between patients with and those without fire-heat syndrome. Patients with qi deficiency syndrome had longer hospital stays and worse NIHSS and BI assessments at discharge than patients without qi deficiency syndrome. All the reported differences reached statistical significance. Conclusions These results provide evidence that fire-heat syndrome and qi deficiency syndrome are essential elements that can predict short-term prognosis of acute ischemic stroke. PMID:23600945
Metabolic syndrome associated with Ischemic Stroke among the Mexican Hispanic Population in the El Paso/Border Region
Osborn, Michael F; Miller, Charles C; Badr, Ahmed; Zhang, Jun
The Hispanic population caries a disproportionate burden of stroke compared to the non-Hispanic White population. Most studies have been conducted on Caribbean Hispanics, indicating a need to better understand the characteristics of stroke and its prevalence among the Hispanic populations of Mexican descent. In this report, data were collected in the El Paso/US-Mexico border region, where 82% of the population is Mexican Hispanic, through a retrospective study of ischemic stroke from 2005 to 2010. Odds ratios (OR), 95% confidence intervals (CI), logistic regression and multivariate analysis of the odds ratios adjusted for other variables, were used to analyze the effects of various risk factors on ischemic stroke. The metabolic syndrome and its components, specifically hypertension, diabetes, and dyslipidemia appeared to be strongly associated with ischemic stroke in the Mexican Hispanic population. Mexican Hispanic ischemic stroke patients were nearly seven times more likely to have this syndrome, compared to Mexican Hispanic controls from the National Health and Nutrition Examination Survey. Likewise, the patients were nearly forty times more likely to have hypertension and eleven times more likely to have diabetes. Efforts to prevent ischemic stroke and limit its impact in the Mexican Hispanic population should focus on controlling hypertension and diabetes. PMID:24548371
Factors preventing African Americans from seeking early intervention in the treatment of ischemic strokes.
King, D. F.; Trouth, A. J.; Adams, A. O.
The most widely advocated drug that has been developed to decrease and possibly reverse the crippling effect of stroke is recombinant tissue plasminogen activator (rt-PA). In the treatment of ischemic stroke, rt-PA must be administered within the first 3 hr after the onset of symptoms for optimal efficacy and avoidance of life-threatening cerebral hemorrhage. This study sought to determine whether African-American stroke victims presented for treatment within the first 3 hr. In the study, we identified some of the more common reasons for the lack of prompt presentation. A prospective survey of 103 randomly selected acute stroke patients was performed. We found that less than half of this population sought assistance in the emergency department in time to take advantage of rt-PA therapy. When confronted with symptoms that were consistent with acute stroke, many patients either chose to ignore them or thought that they were experiencing transient phenomena. Three factors were identified as possible reasons for the lack of prompt response: (a) a lack of information about available treatment options; (b) the inability to recognize the early warning signs of an impending stroke; and (c) denial of illness. This study may help to evolve strategies that must be instituted to better educate the community about the early recognition of stroke and available treatment alternatives. PMID:12653381
Association between PDE4D gene and ischemic stroke: recent advancements.
Das, Satrupa; Roy, Sitara; Munshi, Anjana
Stroke is a severe complication and a leading cause of death worldwide and genetic studies among different ethnicities has provided the basis for involvement of phosphodiesterase 4D (PDE4D) gene in cerebrovascular diseases. Recent advancements have evaluated the role of this gene in stroke and these studies have provided a stronger support for the involvement of this gene in stroke development and few studies also suggest that it may influence outcome. Furthermore, case-control studies and meta-analysis studies have provided strong evidence for certain variants in PDE4D to predispose to stroke only among certain ethnicities. Thus, this review focuses on recent progress made in PDE4D gene research involving genetic, molecular and pharmacological aspect. A strong conclusion has emerged that clearly indicates a pivotal role played by this gene in ischemic stroke globally. Studies have also noticeably highlighted that PDE4D gene/pathway can be a suitable drug target for managing stroke; however, a more comprehensive research is still required to understand the molecular and cellular intricacies this gene plays in stroke development, progression and its outcome. PMID:26004910
Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype.
Amantea, Diana; Certo, Michelangelo; Petrelli, Francesco; Tassorelli, Cristina; Micieli, Giuseppe; Corasaniti, Maria Tiziana; Puccetti, Paolo; Fallarino, Francesca; Bagetta, Giacinto
To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype. PMID:26518285
Ischemic stroke related to an amniotic fluid embolism during labor.
Woo, Yeon-Sun; Hong, Soon-Cheol; Park, Seong-Mi; Cho, Kyung-Hee
We report a young woman who survived multiple cerebral infarctions related to an amniotic fluid embolism (AFE) during labor. To our knowledge, an embolic stroke due to the coexistence of an AFE and patent foramen ovale (PFO) has not been reported. We describe the patient's clinical and radiological features and discuss the stroke mechanism in relation to our AFE hypothesis. A 32-year-old woman presented to the emergency room after experiencing convulsions during labor (blood pressure, 64/28mmHg; oxygen saturation, 67%). She was in a stupor, and her response to painful stimuli on the right side was weaker than on the left side. Acute stroke was considered as a possible cause. Additionally, an AFE was suspected due to cardiopulmonary arrest during labor. Brain MRI revealed multiple territory embolic infarctions. The transcranial Doppler with bubble study demonstrated a right-to-left shunt during the Valsalva maneuver. A transesophageal echocardiogram revealed a PFO with a right-to-left shunt. The elevated intrathoracic pressure during labor may have caused blood to flow backward through the heart, shunting blood from the right side to the left through the PFO. In cases such as this, an amniotic fluid embolus may travel directly from the venous to the arterial circulation via the PFO, leading to multiple cerebral infarctions. PMID:25709056
Optimal Combination Treatment and Vascular Outcomes in Recent Ischemic Stroke Patients by Premorbid Risk Level
Park, Jong-Ho; Ovbiagele, Bruce
Background Optimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. Methods We analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness level 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. Results Compared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20–1.28) and 0.32 (0.14–0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16–1.77) and 0.25 (0.08–0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09–5.00) and 0.22 (0.06–0.78) in the high-risk group. Conclusion Optimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke. PMID:26044963
Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke
Lv, Wen; Li, Wen-yu; Xu, Xiao-yan; Jiang, Hong; Bang, Oh Yong
This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke. PMID:26487854
[Ischemic Stroke, Excitatory Amino Acids Toxicity and the Adjustment of Acupuncture Intervention].
Li, Xiao-xiao; Lu, Sheng-feng; Zhu, Bing-mei; Fu, Shu-ping
Excitatory amino acids toxicity is an onset causation of cerebral ischemia injury cascade reaction, and eventually leading to brain cell necrosis and apoptosis. Acupuncture is reported to be effective for ischemic stroke in clinical practice and animal experiments, but its mechanism is still under exploring. In this paper the authors introduce the research status of antiexcitatory amino acids toxicity effect of acupuncture in ischemic stroke animals by summarizing its effects on subunits of ionotropic glutamate receptor (NMDA/AMPA) and metabotropic glutamate receptors (mGluRs), and on astrocyte activities. Results indicated that acupuncture intervention may down-regulate the expression levels of cerebral multi-types (NR 1, NR 2 B) of glutamate NMDA receptors, up-regulate expression of glutamate transporter-1, NR 2 A, cannabinoid receptor (CBR) type 1 and 2, and suppress activities of cerebral astrocytes, reduce the content of extracellular glutamate to lower its toxicity and to improve stroke at last. The present paper may provide a reference for acupuncture research on ischemic brain injury. PMID:27323449
Left ventricular geometry and white matter lesions in ischemic stroke patients.
Butenaerts, Demian; Chrzanowska-Wasko, Joanna; Slowik, Agnieszka; Dziedzic, Tomasz
Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26-12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24-10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72-8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry. PMID:26581453
Thrombolysis for acute ischemic stroke by tenecteplase in the emergency department of a Moroccan hospital
Belkouch, Ahmed; Jidane, Said; Chouaib, Naoufal; Elbouti, Anass; Nebhani, Tahir; Sirbou, Rachid; Bakkali, Hicham; Belyamani, Lahcen
Introduction Thrombolysis has radically changed the prognosis of acute ischemic stroke. Tenecteplase is a modified form of rt-PA with greater specificity for fibrin and a longer half-life. We report the experience of a Moroccan tertiary hospital in thrombolysis using Tenecteplase. Methods We conducted an open prospective study of all patients who were treated with Tenecteplase for an acute ischemic stroke admitted to our emergency department. Tenecteplase was administered intravenously at a dose of 0.4 mg/kg single bolus. The primary outcome measure was the proportion of patients achieving significant early neurological recovery defined as an improvement of 4 or more points on the NIHSS score at 24h. Results 13 patients had been treated by intravenous thrombolysis. 31% were women. Mean age was 63 years old. The mean NIHSS score at admission was 14.3 and 24h after was at 9.1. The right middle cerebral artery was involved in 69% of cases. The carotid atherosclerosis was predominant 63.3% and the cardio embolic etiology 27%. The mean time to the first medical contact after the onset of symptoms was 3h 30 min. One patient presented a capsulo-lenticular hematoma of 5 mm3 in the same side of the ischemic stroke. Conclusion Tenecteplase is a more interesting thrombolytic than alteplase, it seems to be more suitable for thrombolysis in our center. PMID:26405473
Role of imaging in current acute ischemic stroke workflow for endovascular therapy.
Menon, Bijoy K; Campbell, Bruce C V; Levi, Christopher; Goyal, Mayank
Ischemic stroke is caused by a thrombus that blocks an intracranial artery. Brain tissue beyond the blocked artery survives for a variable period of time because of blood and nutrients received through tiny vessels called collaterals. Imaging the brain and the vasculature that supplies it is therefore a vital first step in treating patients with acute ischemic stroke. In this review, we focus on current evidence for imaging selection of patients for endovascular therapy in the context of the recently positive clinical trials, such as Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing Computed Tomography to Recanalization Times (ESCAPE), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA). We discuss evidence for and use of the various imaging paradigms available. We discuss how to set up quick and efficient imaging protocols for patient selection and address common concerns about the use of imaging, including time spent, contrast, radiation, and other advantages and disadvantages. Finally, we briefly comment on how imaging can integrate itself within various health systems of care in the future, thereby potentially improving patient outcomes further. PMID:25944319
Role of erythrocyte sedimentation rate in ischemic stroke as an inflammatory marker of carotid atherosclerosis
Singh, Amit Shankar; Atam, Virendra; Yathish, Besthenahalli Erappa; Das, Liza; Koonwar, Seiddhartha
Background: Inflammation mediates a key role in the pathogenesis of atherosclerosis which is an important cause of ischemic stroke. An elevated erythrocyte sedimentation rate (ESR) may, therefore, be a marker of the extent andor intensity of a general atherosclerotic process and thus a marker for advanced atherosclerosis heralding increased risk of arterial thrombosis leading to ischemic stroke. Materials and Methods: ESR was calculated in ischemic stroke patients by Westergren's method along with carotid sonography using high resolution 7.5 MHz techniques to find the prevalence of increased carotid intima-media thickness (CIMT) and presence of plaque according to Mannheim Carotid Intima-Media Thickness Consensus. Results: Average value of ESR in all patients was 27.89 ± 9.73 mm/h. A significant association was found between ESR and markers of carotid atherosclerosis, that is, high CIMT of more than 0.8 mm (P < 0.0001) and presence of plaque (P-0.026) in univariate analysis. Also, a significant positive correlation was found between ESR and serum fibrinogen, another inflammatory marker. (r = 0.88, P < 0.0001). Conclusion: The extent of inflammation may reflect in part the propensity of atherosclerotic lesions to lead to clinical disease. Study shows the association of ESR with markers of atherosclerosis confirming the strength of the inflammatory response associated with carotid atherosclerosis and might conceivably carry important prognostic information regarding occurrence of such catastrophic events in future. PMID:24741248
Oxidative stress in post-acute ischemic stroke patients after intensive neurorehabilitation.
Ciancarelli, Irene; De Amicis, Daniela; Di Massimo, Caterina; Carolei, Antonio; Ciancarelli, Maria Giuliana Tozzi
We investigated in post-acute ischemic stroke patients the influence of intensive neurorehabilitation on oxidative stress balance during recovery of neurological deficits. For this purpose, fourteen patients were included in the study within 30 days of stroke onset. Outcome measures were the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index, and the Katz Index. Redox balance was assessed by measuring plasma peroxidative by-products, nitrite/nitrate metabolites (NOx), as an index of nitric oxide (NO), Cu/Zn Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration, autoantibodies against ox-LDL (OLAB) serum level and plasma antioxidant capacity. Assessments were made before and after neurorehabilitation. Fifteen apparently healthy controls were investigated to compare redox markers. Intensive neurorehabilitation was associated with an improvement of all the outcome measures (P < 0.05). Decreased values of peroxidative by-products and of NOx (P < 0.05) were observed after neurorehabilitation in stroke patients even though their values were higher than in controls (P < 0.05). Changes observed before and after neurorehabilitation in NIHSS scores (Δ NIHSS scores) and in plasma NOx amount (Δ NOx) correlated positively (r=0.79; P < 0.005). No differences in EC-SOD activity, OLAB and serum urate concentrations were found between stroke patients and controls, before and after neurorehabilitation. Total plasma antioxidant capacity, lower in stroke patients than in controls before neurorehabilitation, was unchanged thereafter. Our data provide evidence of the effectiveness of neurorehabilitation on reducing redox unbalance in stroke patients and hints the role of NO as a messenger involved in post-ischemic neuronal plasticity influencing recovery of neurological deficits. PMID:22873723
Comparative Effectiveness of Standard Care With IV Thrombolysis Versus Without IV Thrombolysis for Mild Ischemic Stroke
Choi, Jay Chol; Jang, Min Uk; Kang, Kyusik; Park, Jong‐Moo; Ko, Youngchai; Lee, Soo‐Joo; Cha, Jae‐Kwan; Kim, Dae‐Hyun; Park, Sang Soon; Park, Tai Hwan; Lee, Kyung Bok; Lee, Jun; Kim, Joon‐Tae; Cho, Ki‐Hyun; Yu, Kyung‐Ho; Oh, Mi‐Sun; Lee, Byung‐Chul; Cho, Yong‐Jin; Kim, Dong‐Eog; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B.; Bae, Hee‐Joon
Background One third of patients presenting with initially mild strokes have unfavorable outcomes, and the efficacy of intravenous thrombolysis (IVT) in this population has not been proven. This study aimed to evaluate the comparative effectiveness of standard care with IVT versus without IVT in mild stroke patients. Methods and Results Using a multicenter stroke registry database, we identified patients with acute ischemic stroke who presented within 4.5 hours of symptom onset and had initial National Institutes of Health Stroke Scale scores ≤5. Multivariable logistic analysis and propensity score matching were used to adjust for baseline imbalances between the patients who did and did not receive IVT. Adjusted odds ratios and 95% CIs of IVT were estimated for 3‐month modified Rankin Scale scores of 0 to 1 and symptomatic. Of 13 117 patients with stroke who were hospitalized between April 2008 and May 2012, 1386 met the eligibility criteria, and 194 (14.0%) were treated with IVT. For a modified Rankin Scale of 0 to 1 at 3 months, the adjusted odds ratios were 1.96 (95% CI, 1.28 to 3.00; P=0.002) by multivariable logistic analysis and 1.68 (1.10 to 2.56; P=0.02) by propensity score matching analysis, respectively. There was a statistically nonsignificant excess of symptomatic hemorrhagic transformation (odds ratios=3.76 [0.95 to 16.42; P=0.06] and 4.81 [0.84 to 49.34; P=0.09]), respectively. Conclusions In this observational registry‐based study, standard care with IVT is more effective than not receiving IVT in mild ischemic stroke patients, and there is a statistically nonsignificant risk of symptomatic hemorrhagic transformation. PMID:25628404
Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide
Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642
Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population.
Das, Satrupa; Kaul, Subhash; Jyothy, Akka; Munshi, Anjana
In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n=620), its subtypes and hemorrhagic stroke (n=250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p=0.01), cardioembolic stroke (p=0.001 and p=0.0004) and lacunar stroke (p=0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P=0.000) and for triglyceride (P=0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes. PMID:27329241
Dietary Habits in Patients with Ischemic Stroke: A Case-Control Study
Rodríguez-Campello, Ana; Jiménez-Conde, Jordi; Ois, Ángel; Cuadrado-Godia, Elisa; Giralt-Steinhauer, Eva; Schroeder, Helmut; Romeral, Gemma; Llop, Mireia; Soriano-Tárraga, Carolina; Garralda-Anaya, Montserrat; Roquer, Jaume
Background and Aims Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed. Methods A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups. Results A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8–3244.5) vs 2208.7(1753.1–2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p<0.001; OR 1.02), total cholesterol (p = 0.001; OR 1.04), and breaded foods (p = 0.001; OR 1.94) and lower consumption of probiotic yogurt (p = 0.002; OR 0.88). Compared to patients, control participants indicated greater intention to eat vegetables (p = 0.002; OR 1.5) and whole foods (p = 0.000; OR 2.4) and reduce their intake of salt (p = 0.002; OR 1.7), fat (p = 0.000; OR 3.7) and sweets (p = 0.004; OR 1.7) than patients. Conclusion We observed different dietary patterns between stroke patients and controls. Stroke patients have a higher caloric intake and are less concerned about maintaining healthy nutritional habits. PMID:25506934
Administration of Uric Acid in the Emergency Treatment of Acute Ischemic Stroke.
Llull, Laura; Amaro, Sergio; Chamorro, Ángel
Oxidative stress is one of the main mechanisms implicated in the pathophysiology of inflammatory and neurodegenerative diseases of the central nervous system (CNS). Uric acid (UA) is the end product of purine catabolism in humans, and it is the main endogenous antioxidant in blood. Low circulating UA levels have been associated with an increased prevalence and worse clinical course of several neurodegenerative and inflammatory diseases of the CNS, including Parkinson's disease and multiple sclerosis. Moreover, the exogenous administration of UA exerts robust neuroprotective properties in experimental models of CNS disease, including brain ischemia, spinal cord injury, meningitis, and experimental allergic encephalitis. In experimental brain ischemia, exogenous UA and the thrombolytic agent alteplase exert additive neuroprotective effects when administered in combination. UA is rapidly consumed following acute ischemic stroke, and higher UA levels at stroke admission are associated with a better outcome and reduced infarct growth at follow-up. A recent phase II trial demonstrated that the combined intravenous administration of UA and alteplase is safe and prevents an early decrease of circulating UA levels in acute ischemic stroke patients. Moreover, UA prevents the increase in the circulating levels of the lipid peroxidation marker malondialdehyde and of active matrix metalloproteinase (MMP) 9, a marker of blood-brain barrier disruption. The moderately sized URICOICTUS phase 2b trial showed that the addition of UA to thrombolytic therapy resulted in a 6% absolute increase in the rate of excellent outcome at 90 days compared to placebo. The trial also showed that UA administration resulted in a significant increment of excellent outcome in patients with pretreatment hyperglycemia, in females and in patients with moderate strokes. Overall, the encouraging neuroprotective effects of UA therapy in acute ischemic stroke warrants further investigation in adequately
Non-Gaussian Diffusion Imaging for Enhanced Contrast of Brain Tissue Affected by Ischemic Stroke
Geffroy, Françoise; Le Bihan, Denis; Shah, N. Jon
Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the "gold standard". The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes. PMID:24586610
Early Sitting in Ischemic Stroke Patients (SEVEL): A Randomized Controlled Trial
Herisson, Fanny; Godard, Sophie; Volteau, Christelle; Le Blanc, Emilie; Guillon, Benoit; Gaudron, Marie
Background Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients. Objective As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome. Methods This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0–2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure. Results One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0–2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms. Conclusion Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke
Searching for patent foramen ovale in a 44-year-old female patient after ischemic stroke – diagnostic problems
Kralisz, Paweł; Bachórzewska-Gajewska, Hanna; Dobrzycki, Sławomir
Patent foramen ovale (PFO) is associated with the occurrence of cryptogenic strokes in young patients. Transesophageal echocardiography with contrast is the established standard in PFO diagnostics. We present the case of a 44-year-old female patient after ischemic stroke, in whom PFO was not detected by echocardiography; the defect was ultimately diagnosed by right heart catheterization. PMID:27516797
Searching for patent foramen ovale in a 44-year-old female patient after ischemic stroke - diagnostic problems.
Zalewska-Adamiec, Małgorzata; Kralisz, Paweł; Bachórzewska-Gajewska, Hanna; Dobrzycki, Sławomir
Patent foramen ovale (PFO) is associated with the occurrence of cryptogenic strokes in young patients. Transesophageal echocardiography with contrast is the established standard in PFO diagnostics. We present the case of a 44-year-old female patient after ischemic stroke, in whom PFO was not detected by echocardiography; the defect was ultimately diagnosed by right heart catheterization. PMID:27516797
Technology Transfer Automated Retrieval System (TEKTRAN)
Stroke is the leading cause of severe disability and the third leading cause of death, accounting for one of every 15 deaths in the USA. We investigated the association of polymorphisms in the soluble epoxide hydrolase gene (EPHX2) with incident ischemic stroke in African-Americans and Whites. Twelv...
Nonprogressive Unilateral Intracranial Arteriopathy in Children with Arterial Ischemic Stroke
Yeon, Je Young
The nonprogressive unilateral intracranial arteriopathy known as transient (focal) cerebral arteriopathy is not a well-recognized arteriopathy among practitioners of Korea and Japan, although it cannot be easily differentiated from early moyamoya disease. This review summarizes the nomenclature, pathophysiology, diagnostic evaluation, clinico-radiological features, and management of nonprogressive (reversible or stable) unilateral arteriopathy based on the relevant literature and our own experiences. Nonprogressive unilateral arteriopathy should be strongly suspected in children presenting with basal ganglia infarction and arterial beading. The early identification of patients likely to have nonprogressive or progressive arteriopathy would ensure proper management and guide further research for secondary stroke prevention. PMID:26180606
Monocyte Subsets and Related Chemokines in Carotid Artery Stenosis and Ischemic Stroke
Grosse, Gerrit M.; Schulz-Schaeffer, Walter J.; Teebken, Omke E.; Schuppner, Ramona; Dirks, Meike; Worthmann, Hans; Lichtinghagen, Ralf; Maye, Gerrit; Limbourg, Florian P.; Weissenborn, Karin
Carotid stenosis (CS) is an important cause of ischemic stroke. However, reliable markers for the purpose of identification of high-risk, so-called vulnerable carotid plaques, are still lacking. Monocyte subsets are crucial players in atherosclerosis and might also contribute to plaque rupture. In this study we, therefore, aimed to investigate the potential role of monocyte subsets and associated chemokines as clinical biomarkers for vulnerability of CS. Patients with symptomatic and asymptomatic CS (n = 21), patients with cardioembolic ischemic strokes (n = 11), and controls without any cardiovascular disorder (n = 11) were examined. Cardiovascular risk was quantified using the Essen Stroke Risk Score (ESRS). Monocyte subsets in peripheral blood were measured by quantitative flow cytometry. Plaque specimens were histologically analyzed. Furthermore, plasma levels of monocyte chemotactic protein 1 (MCP-1) and fractalkine were measured. Intermediate monocytes (Mon2) were significantly elevated in symptomatic and asymptomatic CS-patients compared to controls. Mon2 counts positively correlated with the ESRS. Moreover, stroke patients showed an elevation of Mon2 compared to controls, independent of the ESRS. MCP-1 levels were significantly higher in patients with symptomatic than in those with asymptomatic CS. Several histological criteria significantly differed between symptomatic and asymptomatic plaques. However, there was no association of monocyte subsets or chemokines with histological features of plaque vulnerability. Due to the multifactorial influence on monocyte subsets, the usability as clinical markers for plaque vulnerability seems to be limited. However, monocyte subsets may be critically involved in the pathology of CS. PMID:27023515
Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine) Treatment
Jaideep, Sriranjini Sitaram; Nagaraja, Dindagur; Pal, Pramod Kumar; Sudhakara, D.; Talakad, Sathyaprabha N.
Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine) describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory) (mean age 39.26 ± 9.88 years; male 43, female 7) were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I) or Ayurveda treatment (Group II) for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS). Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F = 8.16, P = 0.007, F = 9.73, P = 0.004, F = 13.51, and P = 0.001, resp.). The BRS too increased following the treatment period (F = 10.129, P = 0.004). Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted. PMID:24971149
Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke
Schuhmann, Michael K.; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter
Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082
Monocyte Subsets and Related Chemokines in Carotid Artery Stenosis and Ischemic Stroke.
Grosse, Gerrit M; Schulz-Schaeffer, Walter J; Teebken, Omke E; Schuppner, Ramona; Dirks, Meike; Worthmann, Hans; Lichtinghagen, Ralf; Maye, Gerrit; Limbourg, Florian P; Weissenborn, Karin
Carotid stenosis (CS) is an important cause of ischemic stroke. However, reliable markers for the purpose of identification of high-risk, so-called vulnerable carotid plaques, are still lacking. Monocyte subsets are crucial players in atherosclerosis and might also contribute to plaque rupture. In this study we, therefore, aimed to investigate the potential role of monocyte subsets and associated chemokines as clinical biomarkers for vulnerability of CS. Patients with symptomatic and asymptomatic CS (n = 21), patients with cardioembolic ischemic strokes (n = 11), and controls without any cardiovascular disorder (n = 11) were examined. Cardiovascular risk was quantified using the Essen Stroke Risk Score (ESRS). Monocyte subsets in peripheral blood were measured by quantitative flow cytometry. Plaque specimens were histologically analyzed. Furthermore, plasma levels of monocyte chemotactic protein 1 (MCP-1) and fractalkine were measured. Intermediate monocytes (Mon2) were significantly elevated in symptomatic and asymptomatic CS-patients compared to controls. Mon2 counts positively correlated with the ESRS. Moreover, stroke patients showed an elevation of Mon2 compared to controls, independent of the ESRS. MCP-1 levels were significantly higher in patients with symptomatic than in those with asymptomatic CS. Several histological criteria significantly differed between symptomatic and asymptomatic plaques. However, there was no association of monocyte subsets or chemokines with histological features of plaque vulnerability. Due to the multifactorial influence on monocyte subsets, the usability as clinical markers for plaque vulnerability seems to be limited. However, monocyte subsets may be critically involved in the pathology of CS. PMID:27023515
Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke.
Schuhmann, Michael K; Gunreben, Ignaz; Kleinschnitz, Christoph; Kraft, Peter
Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. PMID:26927082
Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality
Shi, Zhihong; Guan, Yalin; Huo, Ya Ruth; Liu, Shuling; Zhang, Meilin; Lu, Hui; Yue, Wei; Wang, Jinhuan
Background and Purpose— Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality. Methods— A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months. Results— During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels. Conclusions— Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype. PMID:26199315
Differing Patterns of Altered Slow-5 Oscillations in Healthy Aging and Ischemic Stroke
La, Christian; Mossahebi, Pouria; Nair, Veena A.; Young, Brittany M.; Stamm, Julie; Birn, Rasmus; Meyerand, Mary E.; Prabhakaran, Vivek
The 'default-mode' network (DMN) has been investigated in the presence of various disorders, such as Alzheimer's disease and Autism spectrum disorders. More recently, this investigation has expanded to include patients with ischemic injury. Here, we characterized the effects of ischemic injury in terms of its spectral distribution of resting-state low-frequency oscillations and further investigated whether those specific disruptions were unique to the DMN, or rather more general, affecting the global cortical system. With 43 young healthy adults, 42 older healthy adults, 14 stroke patients in their early stage (<7 days after stroke onset), and 16 stroke patients in their later stage (between 1 to 6 months after stroke onset), this study showed that patterns of cortical system disruption may differ between healthy aging and following the event of an ischemic stroke. The stroke group in the later stage demonstrated a global reduction in the amplitude of the slow-5 oscillations (0.01–0.027 Hz) in the DMN as well as in the primary visual and sensorimotor networks, two 'task-positive' networks. In comparison to the young healthy group, the older healthy subjects presented a decrease in the amplitude of the slow-5 oscillations specific to the components of the DMN, while exhibiting an increase in oscillation power in the task-positive networks. These two processes of a decrease DMN and an increase in 'task-positive' slow-5 oscillations may potentially be related, with a deficit in DMN inhibition, leading to an elevation of oscillations in non-DMN systems. These findings also suggest that disruptions of the slow-5 oscillations in healthy aging may be more specific to the DMN while the disruptions of those oscillations following a stroke through remote (diaschisis) effects may be more widespread, highlighting a non-specificity of disruption on the DMN in stroke population. The mechanisms underlying those differing modes of network disruption need to be
Sonothrombolysis in the management of acute ischemic stroke.
Rubiera, Marta; Alexandrov, Andrei V
Multiple in vitro and animal models have demonstrated the efficacy of ultrasound to enhance fibrinolysis. Mechanical pressure waves produced by ultrasound energy improve the delivery and penetration of alteplase (recombinant tissue plasminogen activator [tPA]) inside the clot. In human stroke, the CLOTBUST phase II trial showed that the combination of alteplase plus 2 hours of continuous transcranial Doppler (TCD) increased recanalization rates, producing a trend toward better functional outcomes compared with alteplase alone. Other small clinical trials also showed an improvement in clot lysis when transcranial color-coded sonography was combined with alteplase. In contrast, low-frequency ultrasound increased the symptomatic intracranial hemorrhage rate in a clinical trial. Administration of microbubbles (MBs) may further enhance the effect of ultrasound on thrombolysis by lowering the ultrasound-energy threshold needed to induce acoustic cavitation. Initial clinical trials have been encouraging, and a multicenter international study, TUCSON, determined a dose of newly developed MBs that can be safely administered with alteplase and TCD. Even in the absence of alteplase, the ultrasound energy, with or without MBs, could increase intrinsic fibrinolysis. The intra-arterial administration of ultrasound with the EKOS NeuroWave catheter is another ultrasound application for acute stroke that is currently being studied in the IMS III trial. Operator-independent devices, different MB-related techniques, and other ultrasound parameters for improving and spreading sonothrombolysis are being tested. PMID:20104930
Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke
Tajiri, Naoki; Acosta, Sandra; Portillo-Gonzales, Gabriel S.; Aguirre, Daniela; Reyes, Stephanny; Lozano, Diego; Pabon, Mibel; Dela Peña, Ike; Ji, Xunming; Yasuhara, Takao; Date, Isao; Solomita, Marianna A.; Antonucci, Ivana; Stuppia, Liborio; Kaneko, Yuji; Borlongan, Cesar V.
Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells' therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investigations have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights the need for investigations of mechanisms underlying AFS cells' therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of the cell transplantation for stroke. PMID:25165432
Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.
Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P
Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. PMID:23954448
Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke.
Previch, Lauren E; Ma, Linlin; Wright, Joshua C; Singh, Sunpreet; Geng, Xiaokun; Ding, Yuchuan
Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs) are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system. PMID:27438832
Progress in AQP Research and New Developments in Therapeutic Approaches to Ischemic and Hemorrhagic Stroke
Previch, Lauren E.; Ma, Linlin; Wright, Joshua C.; Singh, Sunpreet; Geng, Xiaokun; Ding, Yuchuan
Cerebral edema often manifests after the development of cerebrovascular disease, particularly in the case of stroke, both ischemic and hemorrhagic. Without clinical intervention, the influx of water into brain tissues leads to increased intracranial pressure, cerebral herniation, and ultimately death. Strategies to manage the development of edema constitute a major unmet therapeutic need. However, despite its major clinical significance, the mechanisms underlying cerebral water transport and edema formation remain elusive. Aquaporins (AQPs) are a class of water channel proteins which have been implicated in the regulation of water homeostasis and cerebral edema formation, and thus represent a promising target for alleviating stroke-induced cerebral edema. This review examines the significance of relevant AQPs in stroke injury and subsequently explores neuroprotective strategies aimed at modulating AQP expression, with a particular focus on AQP4, the most abundant AQP in the central nervous system. PMID:27438832
Review of technology development and clinical trials of transcranial laser therapy for acute ischemic stroke treatment
NASA Astrophysics Data System (ADS)
Catanzaro, Brian E.; Streeter, Jackson; de Taboada, Luis
Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.
A Potential Epigenetic Marker Mediating Serum Folate and Vitamin B12 Levels Contributes to the Risk of Ischemic Stroke
Keat Wei, Loo; Sutherland, Heidi; Au, Anthony; Camilleri, Emily; Haupt, Larisa M.; Gan, Siew Hua; Griffiths, Lyn R.
Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles. We investigated epigenetic dysregulation for the methylenetetrahydrofolate reductase (MTHFR) gene among ischemic stroke patients. Cases and controls were recruited after obtaining signed written informed consents following a screening process against the inclusion/exclusion criteria. Serum vitamin profiles (folate, vitamin B12, and homocysteine) were determined using immunoassays. Methylation profiles for CpGs A and B in the MTHFR gene were determined using a bisulfite-pyrosequencing method. Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating serum folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73-fold. However, both CpGs A and B were not associated with serum homocysteine levels or ischemic stroke severity. CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke. PMID:25705649
The Relationship between C-Reactive Protein Level and Discharge Outcome in Patients with Acute Ischemic Stroke
Geng, He-Hong; Wang, Xin-Wang; Fu, Rong-Li; Jing, Meng-Juan; Huang, Ling-Ling; Zhang, Qing; Wang, Xiao-Xiao; Wang, Pei-Xi
Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients' demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094–4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436–6.032), DBIL (OR, 1.795; 95% CI, 1.311–2.458), and CRP (OR, 4.890; 95% CI, 3.063–7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge
H₂S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke.
Wen, Xiangru; Qi, Dashi; Sun, Ying; Huang, Xiaojing; Zhang, Fang; Wu, Jian; Fu, Yanyan; Ma, Kai; Du, Yang; Dong, Hongyan; Liu, YongHai; Liu, Hongzhi; Song, Yuanjian
Neuronal damage in the hippocampal formation which is more sensitive to ischemic stimulation and easily injured will cause severe learning and memory impairment. Therefore, inhibiting hippocampal neuron injuries is the main contributor for learning and memory impairment during cerebral ischemia. Hydrogen sulfide (H2S) is a new type of neurotransmitter that regulates the nervous, circulatory and immune systems as well as various adverse factors that can reduce cerebral vascular or brain parenchyma injury. During an ischemic stroke, H2S inhibits hippocampal neuronal damage, reducing learning and memory impairment. However, this molecular mechanism has not been elucidated clearly. In this study, we established four-vessel occlusion model in rats with cerebral ischemia. We found that NaHS (28 mmol/kg, intraperitoneally, for 7 days before ischemia), donor of H2S, significantly shortened the distance and time of loading onto the hidden platform in the positioning navigation process, decreased the latency in the space exploration process when cognitive testing with Morris water maze was performed during ischemic stroke in rats. NaHS also significantly shortened latency and reduced the number of errors in the platform diving experiment. The survival rate of neurons in the CA1 area of the hippocampus and the phosphorylation of Akt in the neurons were increased, the phosphorylation ASK1 and JNK3 were inhibited by NaHS. After an intracerebroventricular injection of LY294002 (inhibitor of PI3K/Akt, 10 μL, 100 nmol in 25% DMSO in PBS), the above effects of NaHS were attenuated. These findings suggest that H2S may improve the survival rate of hippocampal neurons and reduce the impairment of learning and memory by increasing the phosphorylation of Akt, inhibiting the phosphorylation of ASK1 and JNK3 in rats with induced ischemic stroke. PMID:24768640
Impact of 5A/6A polymorphism of matrix metalloproteinase-3 on recurrent atherosclerotic ischemic stroke in Chinese.
Huang, Xiao-Ya; Han, Li-Ya; Huang, Xiang-Dong; Guan, Chao-Hong; Mao, Xin-Lei; Ye, Zu-Sen
Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy. PMID:26314579
The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis
Au, Anthony; Griffiths, Lyn R.; Cheng, Kian-Kai; Wee Kooi, Cheah; Irene, Looi; Keat Wei, Loo
Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95% CI:1.11–1.58) and co-dominant models (OR = 1.24, 95% CI:1.02–1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95% CI:1.01–1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke. PMID:26666837
Upside Down Crossed Cerebellar Diaschisis: Proposing Chronic Stimulation of the Dentatothalamocortical Pathway for Post-Stroke Motor Recovery
Machado, Andre; Baker, Kenneth B.
Background: Stroke remains the leading cause for long-term motor impairment in the industrialized world. New techniques are needed to improve outcomes. Objective: To propose chronic electrical stimulation of the dentatothalamocortical pathway as a method for enhancing cortical excitability and improving motor recovery following stroke. Method: In previous studies, motor evoked potentials were derived from intracortical microstimulation and used to index cortical excitability in rats undergoing continuous, asynchronous deep cerebellar stimulation. In a separate set of experiments, the effect of chronic deep cerebellar stimulation on motor recovery was tested in rats following large ischemic strokes. Results: Deep cerebellar stimulation modulated cortical excitability in a frequency-dependent fashion. Beta band stimulation yielded sustained increment in excitability and was associated with enhanced motor recovery compared to sham stimulation. Conclusion: Chronic deep cerebellar stimulation enhances recovery of motor function following large ischemic strokes in the rat, an effect that may be associated with increased cortical excitability. Given that deep brain stimulation is already a well established method, this new approach to motor recovery may be a viable option for human translation in stroke rehabilitation. PMID:22661933
Early and intermediate prognosis of intravenous thrombolytic therapy in acute ischemic stroke subtypes according to the causative classification of stroke system
Pashapour, Ali; Atalu, Abolfazl; Farhoudi, Mehdi; Taheraghdam, Ali-Akbar; Sadeghi Hokmabadi, Elyar; Sharifipour, Ehsan; NajafiNeshli, Mehdi
Objectives: Intravenous thrombolytic therapy has established acceptable results in treating ischemic stroke. However, there is little information on treatment outcome especially in different subtypes. The aim of current study was to evaluate early and intermediate prognosis in intravenous thrombolytic therapy for acute ischemic stroke subtypes. Methodology: Forty eligible patients (57.5% male with mean age of 63.18±13.49 years) with definite ischemic stroke who were admitted to emergency department of Imam Reza University Hospital, in the first 180 minutes after occurrence received recombinant tissue plasminogen activator. All investigation findings were recorded and stroke subtypes were determined according to the Causative Classification of Stroke System. Stroke severity forms including modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores were recorded for all patients in first, seven and 90 days after stroke and disease outcome was evaluated. Results: The etiology of stroke was large artery atherosclerosis in 20%, cardio-aortic embolism in 45%, small artery occlusion in 17.5% and undetermined causes in 17.5%. NIHSS and mRS scores were significantly improved during time (P < 0.001 in both cases). Three months mortality rate was 25%. Among the etiologies, patients with small artery occlusion and then cardio-aortic embolism had lower NIHSS score at arrival (P = 0.04). Caplan-meier analysis showed that age, sex and symptom to needle time could predict disease outcome. Conclusion: Intravenous thrombolytic therapy is accompanied by good early and intermediate outcome in most patients with ischemic stroke. Small artery occlusion subtype had less disease severity and higher improvement. PMID:24353536
The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke
Chmielewski, Henryk; Kaczorowska, Beata; Przybyła, Monika; Baj, Zbigniew
Introduction Low-density lipoprotein cholesterol (LDL-C) has been reported to increase platelet activation. Reducing the level of LDL-C with statins induces important pleiotropic effects such as platelet inhibition. This association between platelet activity and statin therapy may be clinically important in reducing the risk of ischemic stroke. We investigated the effect of simvastatin therapy on platelet activation markers (platelet CD62P, sP-selectin, and platelet-derived microparticles (PDMPs)) in hyperlipidemic patients after ischemic stroke. Material and methods The study group consisted of 21 hyperlipidemic patients after ischemic stroke confirmed by CT, and 20 healthy subjects served as controls. We assessed the CD62P expression on resting and thrombin-activated blood platelets. CD62P and PDMPs were analyzed by the use of monoclonal antibodies anti-CD61 and anti-CD62 on a flow cytometer. The level of sP-selectin in serum was measured by the ELISA (enzyme-linked immunosorbent assay) method. All markers were re-analyzed after 6 months of treatment with simvastatin (20 mg/day). Results Hyperlipidemic patients presented a significantly higher percentage of CD62+ platelets and higher reactivity to thrombin compared to control subjects. After simvastatin therapy hyperlipidemic patients showed a reduction of the percentage of resting CD62P(+) platelets (p = 0.005) and a reduction of expression and percentage of CD62P(+) platelets after activation by thrombin (median p < 0.05; percentage: p = 0.001). A decrease of sP-selectin levels (p = 0.001) and percentage of PDMPs (p < 0.05) in this group was also observed. Conclusions HMG-CoA reductase inhibitor therapy in stroke patients with hyperlipidemia may be useful not only due to the lipid-lowering effect but also because of a significant role in reduction of platelet activation and reactivity. PMID:25861297
Prothrombotic risk factors and antithrombotic therapy in children with ischemic stroke
Askar, Gamal A.; Abu Faddan, Naglaa H.; Kamal, Taghreed M.
Objective: Congenital and acquired prothrombotic disorders have been highlighted in a recent series of cerebrovascular stroke (CVS), with a controversial role in pathogenesis. The aim is to study some prothrombotic risk factors [activated protein C (APC) resistance, von Willebrand factor (vWF), anticardiolpin (ACL) antibodies and plasma homocysteine] in children with ischemic stroke, and to evaluate the role of aspirin and low molecular weight heparin (LMWH) in its management in relation to outcome. Methods: A total of 37 cases aged from 1 month to 15 years ( mean ± standard deviation 26.2 ± 35.7 months), diagnosed as ischemic stroke (>24 hours) were recruited. Complete blood count, prothrombin time and concentration, partial thromboplastin time, serum electrolytes, random blood sugar, C-reactive protein, electrocardiogram and echocardiography were done. Levels of APC resistance, vWF, ACL antibodies [immunoglobulin G (IgG) and immunoglobulin M (IgM)] and plasma homocysteine were estimated. A total of 25 cases received aspirin 3–5 mg /kg/d and 12 patients received LMWH as initial dose at 75 international units (IU)/kg subcutaneously (SC) then 10–25 IU/kg/day for 15 days in a nonrandomized fashion. Results: The levels of APC resistance, vWF, ACL antibodies (IgG and IgM) and plasma homocysteine were significantly higher in stroke cases than in controls. There was no significant difference between cases treated with aspirin and those with LMWH in all prothrombotic factors. Significant positive correlations were found between vWF and ACL antibodies (IgG and IgM) levels before treatment. Significant decrease in cognitive function was detected between cases treated with LMWH and those treated with aspirin. Conclusion: Ischemic CVS in children is multifactorial. Thrombophilia testing should be performed in any child with CVS. Early use of aspirin improves the prognosis and has less effect on cognitive function. PMID:25922619
Left Ventricular Diastolic Dysfunction in Ischemic Stroke: Functional and Vascular Outcomes
Park, Hong-Kyun; Kim, Beom Joon; Yoon, Chang-Hwan; Yang, Mi Hwa; Han, Moon-Ku; Bae, Hee-Joon
Background and Purpose Left ventricular (LV) diastolic dysfunction, developed in relation to myocardial dysfunction and remodeling, is documented in 15%-25% of the population. However, its role in functional recovery and recurrent vascular events after acute ischemic stroke has not been thoroughly investigated. Methods In this retrospective observational study, we identified 2,827 ischemic stroke cases with adequate echocardiographic evaluations to assess LV diastolic dysfunction within 1 month after the index stroke. The peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e') was used to estimate LV diastolic dysfunction. We divided patients into 3 groups according to E/e' as follows: <8, 8-15, and ≥15. Recurrent vascular events and functional recovery were prospectively collected at 3 months and 1 year. Results Among included patients, E/e' was 10.6±6.4: E/e' <8 in 993 (35%), 8-15 in 1,444 (51%), and ≥15 in 378 (13%) cases. Functional dependency or death (modified Rankin Scale score ≥2) and composite vascular events were documented in 1,298 (46%) and 187 (7%) patients, respectively, at 3 months. In multivariable analyses, ischemic stroke cases with E/e' ≥15 had increased odds of functional dependence or death at 3 months (adjusted OR [95% CI]: 1.73 [1.27-2.35]) or 1 year (1.47 [1.06-2.06]) and vascular events within 1 year (1.65 [1.08-2.51]). Subgroups with normal ejection fraction or sinus rhythm exhibited a similar overall pattern and direction. Conclusions LV diastolic dysfunction was associated with poor functional outcomes and composite vascular events up to 1 year. PMID:27283279
Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China
Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun
Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Conclusions Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China. PMID:25329637
Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial
Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.
Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387
Sleep characteristics of individuals with chronic stroke: a pilot study
Al-Dughmi, Mayis; Al-Sharman, Alham; Stevens, Suzanne; Siengsukon, Catherine F
Changes in sleep characteristics in individuals with chronic stroke are not well described, particularly compared with healthy individuals. Therefore, the aim of this pilot study was to explore the sleep characteristics in individuals with chronic stroke compared to age- and sex-matched controls. Sixteen individuals with chronic stroke and ten age- and sex-matched controls underwent two nights of polysomnographic recording. The sleep characteristics of interest included total sleep time, sleep efficiency, and percent time, as well as time in minutes spent in stages N1, N2, and N3 and stage R sleep. The individuals with chronic stroke spent less percent time in stage N3 compared with controls (P=0.048). No significant differences in the other sleep characteristics were found between the stroke and control groups. Individuals with chronic stroke present with altered stage N3 sleep compared with healthy controls. These alterations in stage N3 sleep might be a sign of neuronal dysfunction and may impact recovery following stroke. A larger scale study is needed to confirm these findings. PMID:26543384
Do Cardiometabolic Risk Factors Relative Risks Differ for the Occurrence of Ischemic Heart Disease and Stroke?
Aalami Harandi, Samaneh; Sarrafzadegan, Nizal; Sadeghi, Masoumeh; Talaei, Mohammad; Dianatkhah, Mino; Oveisgharan, Shahram; Pourmoghaddas, Ali; Salehi, Asma; Sedighifard, Zohre
Background: The effects of the risk factors of ischemic heart disease (IHD) and stroke on the occurrence of these diseases differ between different populations. Objectives: To study the difference in the effects of different cardiovascular (CVD) risk factors on the incidence of IHD and stroke in an Iranian adult population. Patients and Methods: The Isfahan Cohort Study (ICS) is a longitudinal study that followed up 6323 subjects older than 35 years with no history of CVD since 2001. Of the original sample, only 5431 participants were contacted and followed up until 2011. The end points were the occurrence of IHD (defined as fatal and non-fatal myocardial infarction, unstable angina, and sudden cardiac death) and stroke. After 10 years of follow-up, 564 new cases of IHD and 141 new cases of stroke were detected. The relative risks (RRs) of cardiometabolic risk factors such as hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C) level, low high-density lipoprotein cholesterol (HDL-C) level, current smoking, obesity, high waist-to-hip ratio, family history of CVD, and metabolic syndrome were compared between IHD and stroke patients. The ratio of relative risks (RRR) was calculated for comparing two RRs and estimated adjusted RRR was calculated by using generalized linear regression with a log link and binomial distribution. Results: The RRs of the occurrence of IHD and stroke in diabetic patients were 1.94 and 3.26, respectively, and the difference was statistically different (P = 0.016). The RR of high LDL-C was significantly higher for IHD than for stroke (P = 0.045), while all the other risk factors showed similar RRs for IHD and stroke, with no significant difference in their RRR, including hypertension. Diabetes and hypertension had the highest RRs for IHD, followed by diabetes, metabolic syndrome, and hypertension for stroke. Conclusions: The effect of diabetes mellitus on stroke was more
T2*-weighted fMRI time-to-peak of oxygen challenge in ischemic stroke.
Shen, Qiang; Huang, Shiliang; Duong, Timothy Q
T2 (*)-weighted MRI of transient oxygen challenge (OC) showed exaggerated OC percent changes in the ischemic tissue at risk compared to normal tissue. One ambiguity is that regions with high vascular density also showed exaggerated OC percent changes. This study explored time-to-peak (TTP) of the OC percent changes to improve the utility of T2 (*)-weighted OC MRI. Experiments were performed longitudinally at 30 min, 150 min and 24 h after transient (60-min) stroke in rats. Ischemic core, normal, and mismatch tissue were classified pixel-by-pixel based on apparent diffusion coefficient and cerebral blood flow. Major findings were: (i) Delayed OC TTP was localized to and corresponded well with the perfusion-diffusion mismatch. (ii) By contrast, the exaggerated OC percent changes were less localized, with changes not only in the at-risk tissue but also in some areas of the contralesional hemisphere with venous vessel origins. (iii) The OC time-course of the mismatch tissue was biphasic, with a faster initial increase followed by a slower increase. (iv) At-risk tissue with delayed TTP and exaggerated OC was normal after reperfusion and the at-risk tissue was mostly (83 ± 18%) rescued by reperfusion as indicated by normal 24-h T2. OC TTP offers unique information toward better characterization of at-risk tissue in ischemic stroke. PMID:26661164
Early identification of potentially salvageable tissue with MRI-based predictive algorithms after experimental ischemic stroke
Bouts, Mark J R J; Tiebosch, Ivo A C W; van der Toorn, Annette; Viergever, Max A; Wu, Ona; Dijkhuizen, Rick M
Individualized stroke treatment decisions can be improved by accurate identification of the extent of salvageable tissue. Magnetic resonance imaging (MRI)-based approaches, including measurement of a 'perfusion-diffusion mismatch' and calculation of infarction probability, allow assessment of tissue-at-risk; however, the ability to explicitly depict potentially salvageable tissue remains uncertain. In this study, five predictive algorithms (generalized linear model (GLM), generalized additive model, support vector machine, adaptive boosting, and random forest) were tested in their potency to depict acute cerebral ischemic tissue that can recover after reperfusion. Acute T2-, diffusion-, and perfusion-weighted MRI, and follow-up T2 maps were collected from rats subjected to right-sided middle cerebral artery occlusion without subsequent reperfusion, for training of algorithms (Group I), and with spontaneous (Group II) or thrombolysis-induced reperfusion (Group III), to determine infarction probability-based viability thresholds and prediction accuracies. The infarction probability difference between irreversible—i.e., infarcted after reperfusion—and salvageable tissue injury—i.e., noninfarcted after reperfusion—was largest for GLM (20±7%) with highest accuracy of risk-based identification of acutely ischemic tissue that could recover on subsequent reperfusion (Dice's similarity index=0.79±0.14). Our study shows that assessment of the heterogeneity of infarction probability with MRI-based algorithms enables estimation of the extent of potentially salvageable tissue after acute ischemic stroke. PMID:23571283
Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?
van der Worp, H Bart; Macleod, Malcolm R; Kollmar, Rainer
Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke. PMID:20354545
Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration
Lucke-Wold, Brandon P.; Turner, Ryan C.; Logsdon, Aric F.; Simpkins, James W.; Alkon, Daniel L.; Smith, Kelly E.; Chen, Yi-Wen; Tan, Zhenjun; Huber, Jason D.; Rosen, Charles L.
Ischemic stroke and Alzheimer's disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury. PMID:25114088
Long-Term Survival in Older Critically Ill Patients with Acute Ischemic Stroke
Liou, Jinn-Ing; Smith, Maureen A.
Objective To compare survival in older patients with acute ischemic stroke admitted to intensive care units (ICU) with those not requiring ICU care and to assess the impact of mechanical ventilation (MV) and percutaneous gastrostomy tubes (PEG) on long-term mortality. Design Multi-center retrospective cohort study. Setting Administrative data from the Centers for Medicare and Medicaid Services covering 93 metropolitan counties primarily in the Eastern half of the United States. Patients 31,301 patients discharged with acute ischemic stroke in 2000. Interventions None Measurements Mortality from the time of index hospitalization up to the end of the follow-up period of 12 months. Information was also gathered on use of mechanical ventilation, percutaneous gastrostomy, sociodemographic variables and a host of comorbid conditions. Main Results 26% of all patients with acute ischemic stroke required ICU admission. The crude death rate for ICU stroke patients was 21% at 30 days and 40% at 1-year follow-up. At 30 days, after adjustment of sociodemographic variables and comorbidities, ICU patients had a 29% higher mortality hazard compared to non-ICU patients. Mechanical ventilation was associated with a five-fold higher mortality hazard (hazard ratio 5.59, confidence interval 4.93–6.34). The use of PEG was not associated with mortality at 30 days. By contrast, at 1-year follow up in 30-day survivors, ICU admission was not associated with mortality hazard (hazard ratio 1.01; 95% confidence interval 0.93–1.09). Mechanical ventilation still had a higher risk of death (hazard ratio 1.88, 95% confidence interval 1.57–2.25), and PEG patients had a 2.59 fold greater mortality hazard (95% confidence interval 2.38–2.82). Conclusions Both short-term and long-term mortality in older patients with acute ischemic stroke admitted to ICUs is lower than previously reported. The need for MV and PEG are markers for poor long-term outcome. Future research should focus on the
Metabolomics predicts stroke recurrence after transient ischemic attack
Jové, Mariona; Mauri-Capdevila, Gerard; Suárez, Idalmis; Cambray, Serafi; Sanahuja, Jordi; Quílez, Alejandro; Farré, Joan; Benabdelhak, Ikram; Pamplona, Reinald; Portero-Otín, Manuel
Objective: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones. Methods: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort. Results: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described. Conclusions: The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases. PMID:25471397
Strategies to improve recovery in acute ischemic stroke patients: Iberoamerican Stroke Group Consensus.
Alonso de Leciñana, M; Gutiérrez-Fernández, M; Romano, M; Cantú-Brito, C; Arauz, A; Olmos, L E; Ameriso, S F; Díez-Tejedor, E
Stroke is not only a leading cause of death worldwide but also a main cause of disability. In developing countries, its burden is increasing as a consequence of a higher life expectancy. Whereas stroke mortality has decreased in developed countries, in Latin America, stroke mortality rates continue to rise as well as its socioeconomic dramatic consequences. Therefore, it is necessary to implement stroke care and surveillance programs to better describe the epidemiology of stroke in these countries in order to improve therapeutic strategies. Advances in the understanding of the pathogenic processes of brain ischemia have resulted in development of effective therapies during the acute phase. These include reperfusion therapies (both intravenous thrombolysis and interventional endovascular approaches) and treatment in stroke units that, through application of management protocols directed to maintain homeostasis and avoid complications, helps to exert effective brain protection that decreases further cerebral damage. Some drugs may enhance protection, and besides, there is increasing knowledge about brain plasticity and repair mechanisms that take place for longer periods beyond the acute phase. These mechanisms are responsible for recovery in certain patients and are the focus of basic and clinical research at present. This paper discusses recovery strategies that have demonstrated clinical effect, or that are promising and need further study. This rapidly evolving field needs to be carefully and critically evaluated so that investment in patient care is grounded on well-proven strategies. PMID:23802573
Current management of acute ischemic stroke. Part 2: Antithrombotics, neuroprotectives, and stroke units.
Herd, A. M.
OBJECTIVE: To help family physicians who care for patients with acute stroke or who are involved in planning service delivery or resource allocation to understand recent developments in acute stroke care. QUALITY OF EVIDENCE: A MEDLINE search indicated that most data were derived from well designed, randomized, double-blind, placebo-controlled trials, including all the largest international studies and large systematic reviews. MAIN MESSAGE: Routine anticoagulation is not recommended except for circumstances such as cardioembolic stroke or deep vein thrombosis prophylaxis. Antiplatelet therapy with low-dose acetylsalicylic acid (or another antiplatelet agent if ASA is contraindicated) should be initiated within 48 hours of stroke onset, although benefit is modest. Dedicated care for stroke patients reduces morbidity and mortality and can be cost effective. Recent research into defibrinogenating and neuroprotective agents suggests some benefit, although none are currently licensed for use. Combination therapy might be the answer. CONCLUSION: Management of acute stroke is an emerging discipline; many potential therapies are still experimental. PMID:11570305