JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathy

Koralnik, Igor J.; Wüthrich, Christian; Dang, Xin; Rottnek, Matthew; Gurtman, Alejandra; Simpson, David M.; Morgello, Susan

doi:10.1002/ana.20431

Cited by 176 publications

(143 citation statements)

References 18 publications

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“…Other JCPyV-associated central nervous system disorders -JCPyV-mediated granule cell neuronopathy describes the cytopathic replication of JCPyV in granule cell neurons of the cerebellum (227,228). Clinically, this entity is characterized by a cerebellar syndrome with ataxia and progressive cerebellar atrophy.…”

Section: Jcpyv Diseasementioning

confidence: 99%

The human JC polyomavirus (JCPyV): virological background and clinical implications

Hirsch

Kardas

Kranz

et al. 2013

APMIS

147

169

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JC polyomavirus (JCPyV) was the first of now 12 PyVs detected in humans, when in 1964, PyV particles were revealed by electron microscopy in progressive multifocal leukoencephalopathy (PML) tissues. JCPyV infection is common in 35–70% of the general population, and the virus thereafter persists in the renourinary tract. One third of healthy adults asymptomatically shed JCPyV at approximately 50 000 copies/mL urine. PML is rare having an incidence of <0.3 per 100 000 person years in the general population. This increased to 2.4 per 1000 person years in HIV‐AIDS patients without combination antiretroviral therapy (cART). Recently, PML emerged in multiple sclerosis patients treated with natalizumab to 2.13 cases per 1000 patients. Natalizumab blocks α4‐integrin‐dependent lymphocyte homing to the brain suggesting that not the overall cellular immunodeficiency but local failure of brain immune surveillance is a pivotal factor for PML. Recovering JCPyV‐specific immune control, e.g., by starting cART or discontinuing natalizumab, significantly improves PML survival, but is challenged by the immune reconstitution inflammatory syndrome. Important steps of PML pathogenesis are undefined, and antiviral therapies are lacking. New clues might come from molecular and functional profiling of JCPyV and PML pathology and comparison with other replicative pathologies such as granule cell neuronopathy and (meningo‐)encephalitis, and non‐replicative JCPyV pathology possibly contributing to some malignancies. Given the increasing number of immunologically vulnerable patients, a critical reappraisal of JCPyV infection, replication and disease seems warranted.

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Section: Jcpyv Diseasementioning

confidence: 99%

The human JC polyomavirus (JCPyV): virological background and clinical implications

Hirsch

Kardas

Kranz

et al. 2013

APMIS

147

169

View full text Add to dashboard Cite

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“…Posterior fossa lesions typically affect the middle cerebellar peduncles and adjacent pons and/or cerebellar hemispheres. There is another cerebellar manifestation of JCV, the JCVGCN, 55 which infects only cerebellar granule cell neurons, sparing the oligodendrocytes. The classic histopathologic appearances of PML with oligodendrocytic and astrocytic changes are, therefore, not present in this condition.…”

Section: Jcvgcnmentioning

confidence: 99%

“…In JCVGCN, 55 there is isolated involvement of the internal granular cell layer of the cerebellum without white matter involvement. In the early stage of the disease, there is no specific MR finding.…”

Section: Jcvgcnmentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

118

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SUMMARY:Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE, JCVGCN, and JCM. Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency. IRIS may develop secondary to restoration of immunity in HIV-positive patients with PML receiving antiretroviral therapy. This is of profound clinical significance and needs to be diagnosed promptly. Imaging plays a crucial role in the diagnosis of the disease, monitoring of treatment response, identifying disease progression, and predicting prognosis. In this article, current understanding of the epidemiology, pathogenesis, clinical presentations, and all aspects of imaging of JCV infection of the brain have been comprehensively reviewed.ABBREVIATIONS: ADC ϭ apparent diffusion coefficient; CNS ϭ central nervous system; cPML ϭ classic PML; Cr ϭ creatine; CTL ϭ cytotoxic T-lymphocytes; DWI ϭ diffusion-weighted imaging; FLAIR ϭ fluid-attenuated inversion recovery; HAART ϭ highly active antiretroviral therapy; HIV ϭ human immunodeficiency virus; ICL ϭ idiopathic CD4 lymphocytopenia; iPML ϭ inflammatory PML; IRIS ϭ immune reconstitution inflammatory syndrome; JCE ϭ JCV encephalopathy; JCM ϭ JCV meningitis; JCV ϭ JC virus; JCVGCN ϭ JCV granular cell neuronopathy; mAb ϭ monoclonal antibody; mIns ϭ myo-inositol; MS ϭ multiple sclerosis; MTR ϭ magnetization transfer ratio; NAA ϭ N-acetylaspartate; NIRIS ϭ neuro-IRIS; PCR ϭ polymerase chain reaction; PML ϭ progressive multifocal leukoencephalopathy; PML-IRIS ϭ PML associated with IRIS; RR ϭregulatory region; SLE ϭ systemic lupus erythematosus

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“…The most frequent visual deficits are homonymous hemianopsia or quadrantanopsia due to lesions in the optic radiations or occipital cortex. Nondemyelinating cerebellar granule cell neuronopathy can present with a cerebellar syndrome (70). Optic nerve involvement is not seen, and spinal cord involvement is extremely rare.…”

Section: Clinical and Laboratory Manifestations Of Pmlmentioning

confidence: 99%

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

Calabrese¹,

Molloy²,

Huang³

et al. 2007

Arthritis & Rheumatism

169

102

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JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathy

Cited by 176 publications

References 18 publications

The human JC polyomavirus (JCPyV): virological background and clinical implications

The human JC polyomavirus (JCPyV): virological background and clinical implications

JC Virus Infection of the Brain

Progressive multifocal leukoencephalopathy in rheumatic diseases: Evolving clinical and pathologic patterns of disease

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