progressive multifocal leukoencephalopathy ( pml ) is a rapidly progressive , potentially fatal , demyelinating disease affecting immunosuppressed patients . pml is rarely reported in cases with no underlying disease or immunosuppression - associated condition . we present a 72-year - old previously healthy woman who developed a progressive neurological condition affecting the entire nervous system which led to her death within 5 months . pml should be considered in patients with progressive neurological disorders involving the white matter , even in the absence of previous immunomodulatory treatment or immunosuppression . progressive multifocal encephalopathy ( pml ) is a potentially fatal , demyelinating disease of the central nervous system caused by a papillomavirus called jc virus . this entity presents with a wide clinical spectrum and is pathologically characterized by multiple demyelinating lesions , oligodendrocytes with enlarged nuclei , inclusions and bizarre astrocytes . a possible diagnosis is based on clinical manifestations , imaging findings and jc - virus - positive pcr in the cerebrospinal fluid ( csf ) , but the definite diagnosis is made by biopsy or at autopsy . the exact pathogenesis is still unclear , but an initial infection without apparent illness is assumed to occur in adolescence . the virus might become latent and then , under certain immunosuppressed conditions , reactivate and cause pml . pml mainly occurs as a complication in hematological malignancies , in lymphoproliferative disorders , in immunosuppressed patients and most commonly in patients with aids . the increasing use of various immunosuppressive and immunomodulatory agents has led to a higher incidence of pml . numerous reports have been published on the association between pml and the use of monoclonal antibodies , such as efalizumab , natalizumab and rituximab in patients with psoriasis , crohn 's disease and multiple sclerosis . autoimmune disorders with various chronic organ failures can be complicated by this fatal demyelinating disease , but it is rarely seen in immunocompetent subjects without underlying disease . we present a case of pml with no underlying disease where the diagnosis was made at autopsy . a 72-year - old female was admitted to her local hospital because of right - sided hemiparesis and dysphasia . she had a history of well - regulated hypertension and total alopecia at age 40 years with spontaneous improvement . her mother had suffered a stroke at the age of 70 years and no other family history of disease was reported . three months prior to admission , the patient noted fluctuating small , red , itchy skin eruptions without fever or other accompanying infection signs . ct of the brain showed a hypodense lesion in the left parietal region , considered to be of vascular genesis . three months after the initial neurological signs , a new ct scan revealed an enlarged hypodense lesion in the left parietal region and a minor lesion in the right dorsal parietal region . the patient 's condition deteriorated considerably with increasing neurological symptoms , personality changes , aphasia , apraxia and right - sided hemiplegia . the lymphocyte count was low ( 1215% ; normal range 2143 ) with low levels of serum igg ( 4.7 g / l ; normal range 0.42.1 ) , but a normal iga level and no monoclonal component were seen . c - reactive protein , sr level , antinuclear antibodies , antineutrophil cytoplasmic antibody , double - stranded dna , cardiolipin antibodies and rheumatoid factors were normal . serological tests for epstein - barr virus , cytomegalovirus , borrelia and syphilis were all negative . an hiv test was not performed . csf analysis revealed a normal cell count and normal protein and glucose levels ; there was no sign of intrathecal immunoglobulin synthesis . pcr for neurotropic viruses ( herpes simplex virus , varicella zoster virus , cytomegalovirus , epstein - barr virus and enterovirus ) and borrelia were negative . a whole - body ct scan revealed bilateral kidney cysts , but no sign of malignancy or other pathological findings . mri of the brain showed widespread white - matter lesions in both hemispheres , more extensively on the left side involving the frontal , parietal and occipital lobes ( fig . magnetic resonance spectroscopy performed with multivoxal chemical shift technique over the right frontoparietal lobe showed unspecific changes with an elevated choline - to - creatine ratio and reduced n - acetylaspartate levels . the patient deteriorated and the planned stereotactic brain biopsy was not performed because of her poor condition . she passed away from the cardiopulmonary complications of bilateral bronchopneumonia 5 months after the first signs of disease . the bilateral bronchopneumonia , moderate coronary atherosclerosis , bilateral kidney cysts and cholecystolithiasis were confirmed . multiple confluent demyelination foci were described in both hemispheres , but not in the brainstem or the cerebellum . the microscopic examination revealed areas with demyelination , a variable number of macrophages , enlarged purple - stained oligodendroglial nuclei and massive gliosis with gemistocytic astrocytes , some with bizarre nuclei ( fig . the patient reported here only had a history of hypertension . her initial neurological symptoms and the first ct scan led to the misdiagnosis of stroke . gradual worsening a few months later and mri findings were not consistent with vascular or tumor etiology . a whole - body ct scan and cancer markers in the blood did not show signs of malignancy . no malignant cells were detected by cytological examination of the csf which meant that a lymphoma of the central nervous system was not likely . as the patient did not have any underlying cause for immunosuppression and had not undergone immunosuppressive therapy , she was not tested for jc virus in the csf . another weakness of the testing was the missing hiv status , although an elderly , nontravelling female farmer with no blood transfusion history was not suspected of carrying the retrovirus . as early as the 1970s , several reports were published on pml in patients with no known underlying causes and these cases were defined as primary or spontaneous pml [ 5 , 6 ] . reviewed the literature of pml cases with minimal or occult immunosuppression and found 33 cases between 1966 and 2009 and 5 cases from their own series . twenty - two of these 38 patients did not have any chronic diseases or ongoing immunosuppressive treatment , but 5 ( 22.7% ) were diagnosed with idiopathic cd4 + t - lymphocytopenia . in many cases , organ failure such as liver cirrhosis , kidney failure or autoimmune disorders including sjgren syndrome , systemic lupus erythematosis , polymyositis , dermatomyositis and sarcoidosis were mentioned in the medical histories [ 4 , 7 ] . in the following years , an increasing number of publications made it more obvious that most probably both the cellular system and the humoral immune system are involved in pml . many chronic diseases or organ failures might be associated with a transient immunodysfunction which might promote the reactivation of the jc virus . idiopathic cd4 + t - lymphocytopenia has been described in pml   and hypogammaglobulinemia can very rarely be an underlying cause . a recent report on a patient treated with fumaric acid demonstrated medication - induced lymphocytopenia and this was considered to be the most probable cause of pml . these findings indicate the necessity of continuous monitoring of the immune system to avoid the reactivation of an opportunistic infection . in many cases , pml was not suspected prior to death and diagnosis was uncovered by autopsy , as in the case in this study . a thorough work - up including an hiv test and lymphocyte subsets should have been made to uncover possible immunosuppression . patients on immunomodulatory treatment should have regular screening of their immune system before and during therapy to decrease the risk of pml . to date , there is no established therapy for pml . in cases associated with immunomodulatory agents like natalizumab , the withdrawal of the drug and further elimination by plasma exchange is the most important therapy for immune system recovery . various medical regimes , for instance antimalaria medication , mefloquine and the antiviral medication cidofovir , have been applied with doubtful results . jc virus has been described as using serotonin receptors to infect glial cells , and mirtazapine , an ht2a receptor antagonist , has therefore been tried to inhibit this infection . in a case of hypogammaglobulinemia , the use of intravenous immunoglobulin therapy has been proposed as a possible treatment , but this needs further investigation . pml may occur in patients with no known underlying conditions associated with immunosuppression . in cases with a relatively rapid , progressive neurological disorder affecting the entire nervous system , mainly involving the white matter transient immunodysfunction such as idiopathic cd4 + t - lymphocytopenia or hypogammaglobulinemia might be associated with pml . the humoral and cellular immune system should be screened to detect a possible common immunodeficiency disorder that might be an underlying cause in patients who are assumed to be immunocompetent .
backgroundprogressive multifocal leukoencephalopathy ( pml ) is a rapidly progressive , potentially fatal , demyelinating disease affecting immunosuppressed patients . 
 pml is rarely reported in cases with no underlying disease or immunosuppression - associated condition.case reportwe present a 72-year - old previously healthy woman who developed a progressive neurological condition affecting the entire nervous system which led to her death within 5 months . 
 pml was diagnosed at autopsy.conclusionpml should be considered in patients with progressive neurological disorders involving the white matter , even in the absence of previous immunomodulatory treatment or immunosuppression .