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Progressive multifocal leukoencephalopathy: a review of the pathology and pathogenesis.

Progressive multifocal leukoencephalopathy is an important viral opportunistic infection of oligodendrocytes leading to direct demyelination. Virus is likely disseminated to the brain via the blood. However, the timing of that dissemination with relationship to clinical disease is unknown. Important clues about viral pathogenesis have been learned by applying molecular in situ techniques to diseased brain. The oligodendrocyte is the primary target for JC virus infection, and its death is the primary reason for demyelination. Bizarre astrocytes show limited viral DNA replication but are abortiv…

Favorable Response to Mirtazapine in John Cunningham Virus-related Gray Matter Lesion in a Patient with Human Immunodeficiency Virus.

Mirtazapine has recently emerged as a promising agent for the treatment of progressive multifocal leukoencephalopathy (PML). While there is no Class I evidence for its use, numerous case reports have illustrated mirtazapine's efficacy. True to its name, PML is known to occur mostly in the white matter of the brain as its causative agent, John Cunningham virus (JC virus), has a predilection for infecting glial cells. The virus replicates vigorously in oligodendrocytes and causes lysis of the glial cell culminating in demyelination. Therefore, gray matter involvement is rare. Mirtazapine's 5HT2A…

Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients.

The alpha(4) integrin antagonist natalizumab was shown to be effective in patients with immune-mediated disorders but was unexpectedly assoc … ut natalizumab were examined for evidence of HHV-6. In addition, we also superinfected a persistent JC virus infected glial cell with HHV-6A to determine if JC virus can be increased. Elevated serum HHV6 IgG and HHV-6A DNA was detected in the CSF of a subset of patients but not controls. We confirmed that superinfection with HHV-6 of a JC virus infected gl …

Pathogenesis of progressive multifocal leukoencephalopathy--revisited.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is rare even though the proven etiological agent of PML, the polyomavirus JC (JC virus), is ubiquitous within the human population. The common feature of PML cases appears to be underlying immunosuppression, and PML has gained clinical visibility because of its association with human immunodeficiency virus and AIDS and its occurrence as a side effect of certain immunomodulatory drugs. A hypothesis has gained general acceptance that JC virus causes a primary infection in childhood and …

New insights into progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Progressive multifocal leukoencephalopathy is a deadly demyelinating disease of the central nervous system, which occurs in immunosuppressed individuals. It is caused by a reactivation of the polyomavirus JC, which induces a lytic infection of oligodendrocytes. This review covers recent developments in the clinical and pathological presentations of progressive multifocal leukoencephalopathy, and advances in the understanding of JC virus biology. RECENT FINDINGS: The availability of highly active antiretroviral therapy has changed the clinical spectrum of progressive multifo…

Mefloquine in the treatment of progressive multifocal leukoencephalopathy.

Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. A 54-year-old woman with sarcoidosis presented with a progressive cerebellar syndrome. MRI showed lesions affecting the right cerebellum that progressed over time to the brainstem. JC virus was found in the cerebrospinal fluid (CSF), and brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy. Mefloquine 1000 mg/week was initiated 6 months after symptom onset. Clinical progression stopped immediately, and JC virus became undetectable in…

[Progressive Multifocal Leukoencephalopathy with Inflammatory Reactions].

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by reactivation of the JC virus associated with impaired host immunity. However, PML may occur even without an evident cause of immunosuppression. In such cases, JC virus DNA in cerebrospinal fluid (CSF) may not be detectable with polymerase chain reactions (PCR), and a brain biopsy may be performed. Pathology may exhibit marked inflammatory reactions around the JC virus-infected cells, although typical intranuclear viral inclusions would rarely be seen. Atypical inflammation in patients with PML likely an indi…

Two cases of progressive multifocal leukoencephalopathy after allogeneic hematopoietic cell transplantation and a review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a rare subacute demyelinating disorder of the central nervous system (CNS) caused by the … chain reaction (PCR) of the cerebrospinal fluid (CSF) has emerged as a promising tool for detecting JC virus, a negative result does not rule out PML. Brain biopsy remains the most reliable and accurate method for diagnosing JC virus-associated PML. Presently, there is no universally effective antiviral therapy against JC virus and outcome is fatal in the …

JC human papovavirus replication in human amnion cells.

JC human papovavirus was found to replicate in primary human amnion cells. The virus has undergone eight passages in amnion cells and was identified by serological methods as JC virus. By restriction endonuclease analysis of the viral DNA, the fragments observed were identical to those previously reported for the prototype strain.

Frequent infection of neurons by SV40 virus in SIV-infected macaque monkeys with progressive multifocal leukoencephalopathy and meningoencephalitis.

Simian virus 40 (SV40), family Polyomaviridae, in immunocompromised macaques can cause fatal demyelinating central nervous system disease analogous to progressive multifocal leukoencephalopathy caused by John Cunningham (JC) virus in immunocompromised humans. Recently, we have demonstrated that JC virus can infect cerebellar granule cell neurons and cortical pyramidal neurons in immunosuppressed people. To examine whether SV40 neuronal infection occurs spontaneously in immunosuppressed macaques, we analyzed archival brain specimens from 20 simian immunodeficiency virus-infected rhesus with AID…

Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease affecting the central nervous system as a result of reactivation … r programmed cell death protein 1 (PD-1) inhibitors, such as pembrolizumab, to contain and/or clear JC virus. Herein, we discuss the first reported Australian case of a 61-year-old female with PML secondary to chemoimmunotherapy demonstrating complete clearance of JC virus as well as clinical and radiological stabilisation following pembrolizumab treatment …

Diagnosis of progressive multifocal leukoencephalopathy by brain biopsy with biotin labeled DNA:DNA in situ hybridization.

DNA:DNA in situ hybridization using a cloned JC virus (JCV) DNA probe labeled with biotin confirmed the presence of JCV DNA in formalin-fixed, paraffin-embedded brain biopsies from four cases of progressive multifocal leukoencephalopathy (PML). Only small pieces of tissue were available in each case. Detection of the JC DNA:DNA hybrids was carried out by affinity cytochemistry. JCV DNA was identified predominantly in the nuclei of interfascicular oligodendrocytes in demyelinated areas of the biopsies. JC virus was isolated from one case, and the diagnosis of PML was substantiated in all cases …

Application of "Mentzer's PML case definition" to natalizumab-treated patients in the setting of strict MRI-based pharmacovigilance.

OBJECTIVE: To compare the available diagnostic criteria for progressive multifocal leukoencephalopathy (PML) diagnosis in a real-world cohor … TS: The "Mentzers case definition" resulted in a level of certainty 1-3 in patients with a positive JC virus PCR, termed 'definite' and 'probable' PML according to the AAN diagnostic criteria. Patients that tested negative for JC virus in CSF (29%) were classified level 4 by the "Mentzers case definition", neglecting the longitudinal clinical and radiologi …

An atypical case of progressive multifocal leukoencephalopathy in a patient with high grade B-cell lymphoma causing diagnostic delay.

Progressive multifocal leukoencephalopathy (PML) is a rare disease of the central nervous system caused by opportunistic infection with JC virus. It presents in patients who are immunocompromised, and diagnosis is made by correlating clinical findings and radiological changes with the detection of JC virus in cerebrospinal fluid. Rarely, a brain biopsy is needed. A 72 year old with high grade B-cell lymphoma developed right arm weakness and limb ataxia shortly after his diagnosis. CNS involvement was excluded with a normal CT head, MRI brain/spine, and CSF examination. A paraneoplastic cause w…

Case report of a patient with progressive multifocal leukoencephalopathy under treatment with dimethyl fumarate.

BACKGROUND: Progressive multifocal leukoencephalopathy is a severe demyelinating disease caused by the polyoma JC virus in patients with reduced immunocompetence. A few cases of progressive multifocal leukoencephalopathy have been reported in patients treated with fumaric acid esters. CASE PRESENTATION: A 53-year-old Caucasian woman reported to our clinic with a first focal epileptic seizure and mild cognitive impairment. Since 1.5 years, she was treated with fumaderm for her psoriasis. During that time, her lymphocyte counts ranged between 450 and 700/μl. Cerebral magnet resonance imaging sh…

Progressive multifocal leukoencephalopathy after natalizumab monotherapy.

We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared after 14 monthly infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain-reaction (PCR) assay of cerebrospinal fluid. The patient's symptoms worsened, and the diagnosis of PML was established with a more sensitive quantitative PCR assay after 16 infusions of natalizumab. Plasma excha…

Natalizumab-treated patients at high risk for PML persistently excrete JC polyomavirus.

Sixty-three natalizumab-treated patients with relapsing multiple sclerosis were screened for JC polyomavirus (JCV) viruria. Urinary-positive patients were longitudinally sampled for up to 24 weeks. Using methods that distinguish encapsidated virus from naked viral DNA, 17.5 % of patients were found to excrete virus, consistent with the prevalence of urinary excretion in the general population. Unexpectedly, urinary excretion was predominantly seen (>73 %) in patients with high JC antibody index (≥2.0). Active JCV infection, therefore, tends to occur in natalizumab patients that carry a high ri

The pathogenesis of progressive multifocal leukoencephalopathy.

Interest in pathogenesis of progressive multifocal leukoencephalopathy (PML) followed the observation of the high risk for the disease in HIV infection and the recent observation of an association with a variety of newer therapeutic modalities, e.g., natalizumab, an α4β1 integrin inhibitor, and efalizumab, an anti-CD11a monoclonal antibody. Any hypothesis of PML pathogenesis must account for a number of facts. Firstly, the causative agent JC virus is ubiquitously present, yet only a vanishingly small number of infected persons develop the disease. Secondly, disorders of cell-mediated immunity …

The basis for modeling progressive multifocal leukoencephalopathy pathogenesis.

PURPOSE OF REVIEW: The appearance of progressive multifocal leukoencephalopathy (PML) in association with newer, highly effective biological agents has increased the importance of understanding the mechanisms by which they and other underlying predisposing causes give rise to the disorder. This review attempts to describe what is currently known about the pathogenesis of PML. RECENT FINDINGS: JC virus is a ubiquitous polyoma virus that infects at least 50% of the human population by adulthood. Despite this high prevalence of infection PML remains exceptionally rare, suggesting the presence of…

Прогрессивная многофукальная лейкоэнцефалопатия у пациента с хронической миэлогенной лейкемией.

42-летний мужчина с хронической миэлевой лейкемией попал в больницу с болью в бедре. После хирургического ремонта после перелома бедра у него появились афазия, слюня и лихорадка. Первоначально у него был диагностирован инсульт. Поясничный прокол исключал обычные инфекции, а тест на ВИЧ ELISA был отрицательным. Серийные снимки МРТ выявили прогрессивный демиелинизирующий эффект. Полимеразная цепная реакция, проведенная на цереброспиновой жидкости, была положительной для вируса JC (JC - инициалы первого лица, диагностированного этим вирусом). Пациентка лечилась цидофовиром, но умерла, не получив

Совпадение в аннотации оригинала
A 42-year-old man with chronic myelogenous leukemia presented to the hospital with hip pain. After undergoing surgical repair for a hip frac … yelinating pattern. Polymerase chain reaction performed on cerebrospinal fluid was positive for the JC virus (JC are the initials of the first person diagnosed with this virus). The patient was treated with cidofovir but died before a full course could be administered. JC virus is present in most adult hosts but is only harmful in immuno-compromised hosts. …