Reduced Rate of Diagnostic Positive Detection of JC Virus DNA in Cerebrospinal Fluid in Cases of Suspected Progressive Multifocal Leukoencephalopathy in the Era of Potent Antiretroviral Therapy

Marzocchetti, Angela; Giambenedetto, Simona Di; Cingolani, Antonella; Ammassari, Adriana; Cauda, Roberto; Luca, Andrea De

doi:10.1128/jcm.43.8.4175-4177.2005

Cited by 120 publications

(75 citation statements)

References 17 publications

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“…This low detection rate may be due to non-specificity of radiological findings (Antinori et al, 1997) or insensitivity of PCR, or perhaps due to highly active antiretroviral therapy (HAART) re-establishing host immune function and reducing JCV below detectable levels (Koralnik, 2006). These possibilities are supported by the findings that PML is often difficult to distinguish radiographically from lesions caused by HIV encephalopathy (Olsen et al, 1988;Koralnik et al, 1999) and that the sensitivity of JCV PCR dropped from 89.5 % in the pre-HAART era (1992)(1993)(1994)(1995) to 57.5 % in the HAART era (1996)(1997)(1998)(1999)(2000)(2001)(2002) (Marzocchetti et al, 2005). Interestingly, JCV PCR was also positive in 19 % of patients with abnormal white matter radiology findings suggestive of infection but not characteristic of PML.…”

Section: Resultssupporting

confidence: 58%

Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy

Wang

Qian

2009

Journal of Medical Microbiology

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In a retrospective review of data from 168 patients with suspected progressive multifocal leukoencephalopathy (PML) between 1996 and 2006, JC virus (JCV) PCR on cerebrospinal fluid (CSF) samples was positive only in human immunodeficiency virus (HIV)-infected patients with low CD4 cell counts and in severely immunocompromised patients with radiographic lesions consistent with PML or infectious processes generally. Of note, one HIV patient with a very low CD4 cell count had a positive JCV PCR despite a normal magnetic resonance imaging exam. We concluded that JCV PCR testing on CSF specimens should therefore be targeted to these high-risk patients.

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Section: Resultssupporting

confidence: 58%

Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy

Wang

Qian

2009

Journal of Medical Microbiology

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“…42 As a result of this, the sensitivity of PCR testing for JCV DNA has dropped to 58%. 81,82 Imaging has become very important in the diagnosis of PML in the post-HAART era. In fact, most recently published diagnostic criteria classify PML as "definite PML" or "presumptive PML" on the basis of clinical presentation and imaging appearances with or without positive brain biopsy/PCR (Table 2).…”

Section: Diagnosismentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

115

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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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“…29 As a result of this, the sensitivity of PCR testing for JCV-DNA is now estimated to be around 58%. 30,31 Berger et al 2013 have also proposed that PML diagnosis should be considered 'possible' when there is evidence of typical imaging and clinical findings with no documentation of JCV either in brain biopsy or in the CSF. 6 In our series, detection of JCV-DNA by PCR in CSF was positive in 20 patients (95%).…”

mentioning

confidence: 99%

Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

Augusto¹,

Neves

Reis³

et al. 2015

Acta Med Port

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Acta Med Port 2015 May-Jun;28(3):286-296 RESUMOIntrodução: A leucoencefalopatia multifocal progressiva é uma patologia desmielinizante causada pelo vírus John Cunningham, geralmente associada a estados de imunodepressão, em particular a infeção pelo vírus da imunodeficiência humana. Pode apresentar múltiplas manifestações clínicas e tem habitualmente um padrão imagiológico típico. A evolução clínica é geralmente progressiva, podendo ocorrer uma melhoria do prognóstico associada à recuperação imunológica. Results: Twenty-one patients were included in our study, mostly men (n = 20, 95.2%). Mean age at diagnosis was 39 years. Motor deficits were the most common clinical finding. John Cunningham virus-DNA was detected in the cerebral spinal fluid in 20 patients (95.2%). Brain imaging studies most commonly disclosed bilateral supratentorial, asymmetric lesions. Four (19%) patients developed immune reconstitution inflammatory syndrome in the follow-up. Therapeutic approach included initiation and continuation/optimization of antiretroviral therapy, with adjunctive therapy with corticosteroids in four patients. Seventeen (81%) patients died during the study period; median survival time following progressive multifocal leukoencephalopathy diagnosis was 3 months (range 1 -13). Discussion:The results of our study are in accordance with the data previously published on progressive multifocal leukoencephalopathy in human immunodeficiency virus patients. Progressive multifocal leukoencephalopathy is predominantly associated with severe immunosuppression, particularly in patients who are not under anti-retroviral therapy, and usually presents with motor and cognitive symptoms and signs. A typical bilateral asymmetric pattern in conventional magnetic resonance imaging is present in the majority of the patients. There is no specific therapy for progressive multifocal leukoencephalopathy and it is usually fatal, although outcomes can improve with highly active anti-retroviral therapy. Immune reconstitution inflammatory syndrome is also an important complication related with progressive multifocal leukoencephalopathy, usually associated with anti-retroviral therapy. Progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome presents with different imaging characteristics from progressive multifocal leukoencephalopathy and treatment with steroids can improve survival. Conclusion:The mortality rate and long-term neurological morbidity associated with progressive multifocal leukoencephalopathy are quite high. These data should increase clinician awareness to the occurrence of progressive multifocal leukoencephalopathy among human immunodeficiency virus patients and highlight the important role of magnetic resonance imaging, as early diagnosis may be associated with better outcome.

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Reduced Rate of Diagnostic Positive Detection of JC Virus DNA in Cerebrospinal Fluid in Cases of Suspected Progressive Multifocal Leukoencephalopathy in the Era of Potent Antiretroviral Therapy

Cited by 120 publications

References 17 publications

Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy

Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy

JC Virus Infection of the Brain

Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

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