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Progressive multifocal leukoencephalopathy in chronic lymphocytic leukemia: a report of three cases and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus, a DNA papovavirus. It is usually associated with conditions causing profound immunodeficiency, classically seen in patients with HIV/AIDS. Since its first description in 1958, PML has also been associated with various lymphoproliferative malignancies, including chronic lymphocytic leukemia (CLL). With the use of newer chemotherapeutic agents such as the purine analogue fludarabine and various monoclonal antibodies in the treatment of CLL, more case

Progressive multifocal leukoencephalopathy following heightened immunosuppression after lung transplant.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the JC virus that occurs in the setting of immunosuppression. A 38-year-old female lung transplant recipient at our institution received treatment for episodes of acute rejection with steroids, anti-thymocyte globulin and alemtuzumab, in addition to maintenance immunosuppression. She was diagnosed with PML 13 months after the last episode of rejection, for which she had received alemtuzumab. Despite attempted treatment with cidofovir followed by mirtazapine, PML progressed, …

Прогрессивная многофукальная лейкоэнцефалопатия, напоминающая центральную нервную систему системная волчанка эритематос.

21-летняя женщина с 6-летней историей SLE с нарушениями речи и неуклюжестью правой руки, а также проявлениями активной болезни, что говорит о центральной нервной системе SLE. Несмотря на агрессивное лечение SLE, ее неврологическое состояние ухудшилось. МРТ продемонстрировала низкую интенсивность в изображениях, взвешенных по Т1, и высокую интенсивность в изображениях, взвешенных по Т2 в белом материи двустороннего церебрального и мозжечного мозга, совместимых с прогрессивной многофукальной лейкоэнцефалопатией (ПМЛ). Внутреннее управление интерферон-бетой, казалось, замедлило ухудшение ее МРТ и

Совпадение в аннотации оригинала
A 21-year-old woman with a 6-year history of SLE presented with a speech disturbance and right hand clumsiness along with manifestations of … ings. However, she eventually developed decerebrate rigidity and died due to candidemia. DNA of the JC virus was detected in the autopsied brain by the polymerase chain reaction technique. PML should always be borne in mind when examining patients with SLE showing neurological abnormalities.

Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.

Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells de…

Natalizumab therapy for highly active pediatric multiple sclerosis.

IMPORTANCE: Given the high frequency of failure of first-line therapies, there is an urgent need for second-line treatment strategies for pe … number of adverse events, the prevalence of neutralizing antibodies against natalizumab, and serum JC virus-antibody status. RESULTS Treatment with natalizumab was associated with reductions in mean annualized relapse rates (3.7 without treatment vs 0.4 with treatment; P < .001), median Expanded Disability Status Scale scores (2 without treatment vs 1 wit …

Natalizumab: Perspectives from the Bench to Bedside.

Probably no other disease-modifying drug for multiple sclerosis has a more fascinating story than natalizumab from both the bench to bedside perspective and the postmarketing experience standpoint. Natalizumab is a monoclonal antibody that inhibits the trafficking of lymphocytes from the blood into the central nervous system by blocking the adhesion molecule α4-integrin. Natalizumab was approved as a disease-modifying drug for relapsing remitting multiple sclerosis only 12 years after the discovery of its target molecule-a time line that is rather fast for drug development. However, a few mont

Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV

Prevalence of JC Polyomavirus in Patients with Neuroinvasive Disease of Unknown Etiology in Croatia.

Background and Objectives: John Cunningham polyomavirus (JCPyV) is a highly prevalent virus in the human population. The prevalence of JCPyV in patients with central nervous system disorders has not been examined extensively. The aim of this study was to analyze the prevalence of JCPyV DNA/antibodies in patients with neuroinvasive diseases (NID) of unknown etiology. Materials and Methods: The study included 132 patients with NID (febrile headache, meningitis, encephalitis) tested from January 2021 to December 2022. The control group consisted of 47 asymptomatic individuals. In patients with NI

Detection of JCPyV microRNA in blood and urine samples of multiple sclerosis patients under natalizumab therapy.

Polyomavirus JC (JCPyV) reactivation and development of progressive multifocal leukoencephalopathy is a health concern in multiple sclerosis patients under natalizumab therapy. Here, the JCPyV microRNA-J1-3p and microRNA-J1-5p expressions and genomic variability were investigated in blood and urine samples of multiple sclerosis patients before and under natalizumab therapy and in healthy controls. The two JCPyV microRNAs were detected in the JCPyV-DNA-positive peripheral blood mononuclear cell samples and in the exosomes derived from plasma and urine obtained from JCPyV-DNA-positive and JCPyV-

Oncogenic Viruses in Skull Base Chordomas.

BACKGROUND: Chordomas are rare tumors assumed to derive from notochordal remnants. We believe that a molecular switch is responsible for the … -7, and Kaposi's sarcoma-associated herpesvirus), polyomaviridea (parvovirus B19 [PVB19], BK virus, JC virus, Simian virus 40, Merkel cell polyomavirus, human polyomavirus [HPyV]-6, and HPyV-7), papillomaviridae, and respiratory viruses. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to validate the positive results. RESULTS: PVB19 D …

PD-1 regulates CD4+ T cell-mediated CD8+ T cell responses in the brain to balance viral control and neuroinflammation.

Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus. Why PD-1 blockade finds variable success in PML patients is unclear. Brain CD4+ and CD8+ T cells are PD-1high during mouse polyomavirus (MuPyV) encephalitis. Here, we show that PD-1 loss during MuPyV infection acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4+ and CD8+ T cells and the function of virus-specific CD8+ T cells; in concert, brain virus levels decline and

PD-1 regulates CD4+ T cell-mediated CD8+ T cell responses in the brain to balance viral control and neuroinflammation.

Programmed cell death protein 1 (PD-1) is expressed by T cells during progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by the human-only JC polyomavirus. Why PD-1 blockade finds variable success in PML patients is unclear. Brain CD4+ and CD8+ T cells are PD-1high during mouse polyomavirus (MuPyV) encephalitis. Here, we show that PD-1 loss during MuPyV infection acts in a brain-autonomous manner to increase the magnitude of brain-infiltrating CD4+ and CD8+ T cells and the function of virus-specific CD8+ T cells; in concert, brain virus levels decline and

Clinical and magnetic resonance imaging regression of progressive multifocal leukoencephalopathy in an AIDS patient after intensive antiretroviral therapy.

A 36-year-old homosexual man with 6 months of visual symptoms and headaches had right homonymous hemianopia, mild new learning impairment, and alexia with agraphia. The initial brain magnetic resonance imaging (MRI) scan was reported consistent with left occipital infarction. Subsequent MRI demonstrated abnormal demyelination in subcortical white matter and deep parieto-occipital white matter bilaterally, but primarily left. Human immunodeficiency virus testing and cerebrospinal fluid polymerase chain reaction for JC virus DNA were both positive, consistent with progressive multifocal leukoenc…

Antiviral T-Cell Frequencies in a Healthy Population: Reference Values for Evaluating Antiviral Immune Cell Profiles in Immunocompromised Patients.

Viral infections and reactivations are major causes of morbidity and mortality after hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) as well as in patients with immunodeficiencies. Latent herpesviruses (e.g., cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6), lytic viruses (e.g., adenovirus), and polyomaviruses (e.g., BK virus, JC virus) can cause severe complications. Antiviral drugs form the mainstay of treatment for viral infections and reactivations after transplantation, but they have side effects and cannot achieve complete viral clearance without prior r…

Distinguishing Progressive Multifocal Leukoencephalopathy From Cerebral Toxoplasmosis in HIV: A Case Report.

Progressive multifocal leukoencephalopathy and cerebral toxoplasmosis are serious opportunistic infections in patients with advanced HIV infection. Diagnosis is often challenging due to overlapping clinical and radiological features. We present the case of a 40-year-old woman with a three-week history of expressive dysphasia, headache, and right arm weakness. Imaging revealed multiple enhancing brain lesions, initially raising concern for metastatic cancer. An extensive malignancy workup was unrevealing. Lumbar puncture confirmed JC virus in the CSF, and further testing identified previously u…

Immune profiling of a patient with alemtuzumab-associated progressive multifocal leukoencephalopathy.

A 31-year-old woman affected by multiple sclerosis (MS) experienced generalized tonic-clonic seizures 2 months after the second alemtuzumab cycle. Positive JC virus (JCV)-DNA in cerebrospinal fluid (CSF) and lesion iconography at magnetic resonance imaging (MRI) were suggestive of progressive multifocal leukoencephalopathy (PML). After 1 month, during full-blown immune reconstitution inflammatory syndrome, JCV-DNA became negative and symptoms gradually improved. New T- and B-cell output and T- and B-cell diversity were low and lymphocytes poorly responded to stimulation. This is the first case…

A Punctate Magnetic Resonance Imaging Pattern in a Patient with Systemic Lupus Erythematosus Is an Early Sign of Progressive Multifocal Leukoencephalopathy: A Clinicopathological Study.

A 37-year-old woman with systemic lupus erythematosus presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis. After tapering…

Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy.

Progressive multifocal leukoencephalopathy (PML), a frequently fatal demyelinating disease caused by JC virus, occurs as an opportunistic infection in patients with acquired immunodeficiency syndrome. Curative therapy has been elusive, but recent reports suggest its improvement after institution of highly active antiretroviral therapy (HAART). We describe a case of PML that developed 6 months after the patient, a 55-year-old man, began to receive HAART. The PML progressed despite good virologic and immunologic response to HAART. Substantial symptomatic and radiographic improvement occurred aft…