Update on PML: Lessons from the HIV uninfected and new insights in pathogenesis and treatment

Hartman, Elizabeth A.; Huang, De Ren

doi:10.1007/s11904-008-0018-0

Cited by 12 publications

(6 citation statements)

References 59 publications

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“…Although HIV accounts for approximately 80% of the PML cases, there is increasing incidence of the disease in non-HIV settings. 3 JCV is a ubiquitous human pathogen, and both inhalation and ingestion of contaminated water have been suggested as major modes of transmission of the virus. 4,5 The primary infection is presumably asymptomatic, and 85% of the adult population has antibodies against JCV, implying previous exposure and potentially latent infection.…”

Section: Epidemiology: Population At Riskmentioning

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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Section: Epidemiology: Population At Riskmentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

118

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“…The median survival of patients without HIV infection is only a few months. Previous animal studies have shown that several therapeutic agents may be effective in the treatment of PML [10]. More recent case reports suggest that cidofovir and a 5-HT 2A blocker could be effective against PML [3, 7].…”

Section: Discussionmentioning

confidence: 99%

Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

et al. 2011

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Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating central nervous system disease caused by JC virus (JCV) reactivation in immunocompromised patients. The disease course of PML is often progressive, fatal and at present, there are few reports on successful treatment outcomes. Case Report: A 45-year-old man with systemic sarcoidosis presented with rapidly progressive dementia and right hemiparesis. The patient was diagnosed with PML as confirmed via brain biopsy and JCV PCR. With a combination treatment of cidofovir and mirtazapine, there was significant improvement of neurological symptoms without measurable functional deficit. Conclusion: This case suggests that dual therapy with cidofovir and mirtazapine might be an effective treatment option in PML patients with sarcoidosis.

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“…The polyomavirus, JC virus, is the causative agent of PML, a rapidly progressive demyelinating disorder in immunocompromised patients [243][244][245]. JC virus infection is common, with adult seroprevalence exceeding 50 % [246].…”

Section: Jc Virusmentioning

confidence: 99%

Central Nervous System Infections in Cancer Patients and Hematopoietic Stem Cell Transplant Recipients

Hoffman

Stosor

2014

Cancer Treatment and Research

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Central nervous system (CNS) infections in cancer patients present a diagnostic and therapeutic challenge for clinicians. While CNS infections are not frequent complications of cancer, its therapies, or hematopoietic stem cell transplantation, the importance of CNS infections lies in their propensity to result in profound morbidity and substantial mortality in this vulnerable patient population. With an expanding population of patients with malignant disease undergoing more potent and aggressive therapies and with the advent of newer immunomodulatory agents, the incidence of CNS infectious complications is likely to rise. This chapter will summarize the clinical and diagnostic evaluation of potential infections of the CNS in these patients and will discuss particular pathogens of interest with regard to this at-risk patient population.

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Update on PML: Lessons from the HIV uninfected and new insights in pathogenesis and treatment

Cited by 12 publications

References 59 publications

JC Virus Infection of the Brain

JC Virus Infection of the Brain

Dual Therapy with Cidofovir and Mirtazapine for Progressive Multifocal Leukoencephalopathy in a Sarcoidosis Patient

Central Nervous System Infections in Cancer Patients and Hematopoietic Stem Cell Transplant Recipients

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