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Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy.

OBJECTIVE: Natalizumab, a therapy for multiple sclerosis (MS), has been associated with progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection of the CNS associated with the JC virus. We assessed clinical outcomes and identified variables associated with survival in 35 patients with natalizumab-associated PML. METHODS: Physicians provided Karnofsky scores and narrative descriptions of clinical status. Data were supplemented by the natalizumab global safety database. RESULTS: At the time of analysis, 25 patients (71%) had survived. Survivors were younger (median 40 v…

Immune system's role in viral encephalitis.

Viral infections can be a major thread for the central nervous system (CNS), therefore, the immune system must be able to mount a highly pro … an Herpes virus-1 encephalitis with the defect in innate immune response which favors this disease; JC virus-caused progressive multifocal leukoencephalopathy and the crucial role of adaptive immune response in this example; and finally, HIV infection with the accompanying low grade chronic inflammation in the CNS in some patients, which may be an explanat …

Distribution of JC polyomavirus genotypes in Tunisian renal transplant recipients between January 2008 and January 2011.

The polyomavirus JC (JCPyV) is a ubiquitous virus in humans, causing progressive multifocal leukoencephalopathy, a fatal demyelinating disease. JCPyV propagates in the adult kidney and excretes its progeny in urine, from which its DNA can be recovered readily. JCPyV isolates worldwide can be classified into 14 subtypes or genotypes, each associated with a specific geographical region. The European genotypes EU-a-b-c are spread throughout Europe and Mediterranean areas. The major African genotype Af2 is spread not only throughout Africa but also in West and South Asia. A minor African genotype

Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare.

Progressive multifocal leukoencephalopathy, a formerly rare disease that chiefly occurred in persons with underlying lymphoma and chronic ly … ukoencephalopathy currently requires brain biopsy. The application of polymerase chain reaction for JC virus amplification to cerebrospinal fluid samples suggests that it may provide an alternative means of diagnosis. Recent in vitro studies of cytosine arabinoside and camptothecin suggest that they, or similar agents, may prove useful in the treatment of …

Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients.

BACKGROUND: Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 or JC virus. METHODS…

Treatment of viral encephalitis.

Several viruses may cause central nervous system diseases with a broad range of clinical manifestations. The time course of the viral enceph … iology of some viral encephalitis [e.g. West-Nile virus, and Japanese B virus]. Citomegalovirus and JC virus are examples of infections of the brain that have been seen more frequently because they occur in immunocompromised patients. In the other hand many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory tr …

Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature.

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemipar…

Efficacy and side effects of natalizumab therapy in patients with multiple sclerosis.

Natalizumab (Nat) is a humanized monoclonal antibody used for the treatment of relapsing multiple sclerosis (MS). Nat inhibits lymphocyte migration via the blood brain barrier (BBB) by blockage of an integrin adhesion molecule, very late antigen 4. During the phase III clinical trials, it was shown that Nat reduces disease activity and prevents disability progression. In addition, several smaller studies indicate a positive influence of Nat on cognition, depression, fatigue, and quality of life (Qol). Therapeutic efficacy has to be weighed against the risk of developing potentially fatal progr

From injection therapies to natalizumab: views on the treatment of multiple sclerosis.

Discoveries of the mechanisms that underlie the pathogenesis of multiple sclerosis have been acquired at an impressive rate over the last fe … fer views on the risks associated with the use of natalizumab by underscoring the importance of the JC virus serology and by providing preliminary data on our experience with the extended interval dosing of natalizumab. This approach, which advocates individualized treatment plans, raises the question of the minimum effective natalizumab dose. Extended int …

Multifocal progressive leukoencephalopathy occurring after refractory anemia and multiple infectious disorders consecutive to severe lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is related to central nervous system infection with JC virus (JCV). This leukoencephalopathy occurs in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or lymphoid malignancies. We describe here a patient with myelodysplastic syndrome who developed several life-threatening infections including listeriosis, tuberculosis, and PML. Listeriosis and recurrence of tuberculosis preceded the occurrence of PML. Neurologic features associated with major ataxia, speech disorders, and PML were documented by cranial mag…

Связанная с Натализумабом прогрессивная многофукальная лейкоэнцефалопатия.

Прогрессивная многофукальная лейкоэнцефалопатия (PML) — демиелионирующая болезнь мозга, вызванная инфекцией олигодендроцитов вирусом JC (JCV), которая обычно происходит в связи с дефектами клеточного иммунитета. Клиническое представление PML зависит от области его воздействия в центральной нервной системе и может включать в себя широкий спектр недостатков, таких, как слабый фокус, трудности речи, визуальные изменения, когнитивные нарушения или атаксия. В то время как эта болезнь была впервые описана у пациентов с клеточными аномалиями B (лимфома Ходжкинса и хроническая лимфоцитная лейкемия), б

Совпадение в аннотации оригинала
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain resulting from infection of oligodendrocytes by JC virus (JCV) typically occurring in association with defects of cell-mediated immunity. The clinical presentation of PML depends on its area of effect in the central nervous system and can include a broad spectrum of defi…

[Pure alexia secondary to progressive multifocal leukoencephalopathy as first manifestation of HIV infection].

INTRODUCTION: Pure alexia, or alexia without agraphia, is usually caused by disconnection between the gyrus angularis and visual areas of both hemispheres. Cerebrovascular disease is the most frequent cause of this syndrome. CLINICAL CASE: We report the first case of a patient with pure alexia secondary to progressive multifocal leukoencephalopathy (PML) as the first manifestation of Human Immunodeficiency Virus (HIV) infection. Polymerase chain reaction in cerebrospinal fluid was positive for JC virus. Despite favorable immunological and virological response to highly active antiretroviral t…

[A Patient with Progressive Multifocal Leukoencephalopathy Who Developed Bálint Syndrome Improved by Combination Therapy Using Mefloquine and Mirtazapine].

We describe a 62-year-old man who developed subacute visual loss after cord blood stem cell transplantation for malignant lymphoma. Brain magnetic resonance imaging (MRI) showed bilateral hyperintense lesions in the occipital and parietal lobes. A diagnosis of progressive multifocal encephalopathy (PML) was established following brain biopsy and detection of JC virus (JCV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). He developed optic ataxia and visual inattention, and was then diagnosed as having Bálint syndrome. After he was treated with mefloquine and mirtazapine, his Báli…

Продольный анализ индекса антител, противостолбняка, для оценки риска прогрессивной многофукальной лейкоэнцефалопатии.

Оценка риска прогрессивной многофукальной лейкоэнцефалопатии (Nat-PML) в связи с натальным вирусом (JCV) включает антителный индекс (AI). Продольное определение антиJCV AI было дано в группе MS, обработанной натализумабом (Nat-MS, n = 468), и в образцах пациентов Nat-PML (n = 15). В Nat-MS средний показатель АИ составлял 0,8 (25-75-й процентиль, 0,2-2.8) при внутрииндивидуальном коэффициенте вариации (CV) 9,8% (4.8-17,6). Пациенты с AI ≤ 0,9 продемонстрировали более высокое значение CV. МА была выше (3.4 (3.1-3.6) в пробах до диагностирования Nat-PML, чем в серопозитивных Nat-MS (2.4 (1.0-3.4)

Совпадение в аннотации оригинала
Risk assessment for natalizumab-associated progressive multifocal leukoencephalopathy (Nat-PML) comprises the anti-JC virus (JCV) antibody index (AI). The anti-JCV AI was longitudinally determined in a natalizumab-treated MS cohort (Nat-MS, n = 468) and samples of Nat-PML patients (n = 15). In Nat-MS, the median AI was 0.8 (25th to 75th percentile, 0.2-2.8) …

NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.

Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neuro

Successful Treatment of Progressive Multifocal Leukoencephalopathy With Tenofovir Alafenamide Fumarate.

OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal CNS infection caused by reactivation of JC virus, typically in immunocompromised patients. No effective antiviral therapy has been established. We report a case of PML in a patient with multiple sclerosis (MS) treated with fingolimod, who received oral tenofovir alafenamide fumarate (TAF). METHODS: This is a single-patient case report from Stavanger University Hospital, Norway. A 67-year-old woman with secondary progressive MS developed progressive neurologic symptoms during fingolimod treatment. MRI and CSF a…

Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far

Transient biopsy-proven progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) in an elderly woman without known immunodeficiency: a case report.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe opportunistic brain disease caused by lytic JC polyomavirus (JCPyV) replication in oligodendrocytes. Although JCPyV infection is common in the general population, PML almost exclusively occurs in patients immunocompromised due to untreated HIV/AIDS, haematological malignancies, primary immunodeficiencies, solid organ transplantation, or immunomodulatory treatment of autoimmune diseases. There is no effective antiviral treatment, and recovery depends on immune reconstitution. Paradoxically, initiation of antiretroviral the

The spectrum of progressive multifocal leukoencephalopathy: a practical approach.

John Cunningham virus (JCV) infection of the central nervous system causes progressive multifocal leukoencephalopathy (PML) in patients with systemic immunosuppression. With the increased application of modern immunotherapy and biologics in various immune-mediated disorders, the PML risk spectrum has changed. Thus, new tools and strategies for risk assessment and stratification in drug-associated PML such as the JCV antibody indices have been introduced. Imaging studies have highlighted atypical presentations of cerebral JCV disease such as granule cell neuronopathy. Imaging markers have been