JC Virus PCR Detection Is Not Infallible: A Fulminant Case of Progressive Multifocal Leukoencephalopathy with False-Negative Cerebrospinal Fluid Studies despite Progressive Clinical Course and Radiological Findings.

Mohamed-Ali Babi,William Pendlebury,Steven Braff,Waqar Waheed

doi:10.1155/2015/643216

Abstract

We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (CSF) in a patient with clinical and radiological findings suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly progressive global decline with clinical and radiographic findings suggestive of PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML with presence of JC-polyoma virus by immunohistochemical staining. This case highlights the potential of false-negative JC virus PCR in CSF when radiographic and clinical features are suggestive of “possible PML.” We review the plausible causes of potential false-negative CSF results and suggest that when the clinical presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive PCR assay and subsequent brain biopsy should be considered if CSF remains negative. Additionally, appropriate exclusion of other neurologic conditions is essential.

Highlights

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disorder of the CNS caused by infection of the JC-polyoma virus
PML has classically been described in immune-compromised individuals, such as acquired immune deficiency syndrome (AIDS), but it occurs in people on chronic immunosuppressive therapy for solid organ transplants, in people with hematological malignancies receiving antineoplastic therapy, and in individuals with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus with or without immunosuppressive or immunomodulatory therapies that depress the immune response and allow JC virus reactivation [1,2,3]
We describe a case of PML with false-negative cerebrospinal fluid (CSF) JC virus polymerase chain reaction (PCR), reinforcing the importance of obtaining histological confirmation when clinicoradiological findings are suggestive of PML, even with initially normal CSF studies

Summary

Introduction

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disorder of the CNS caused by infection of the JC-polyoma virus. To the best of our knowledge, only one case report in the literature described association of adalimumab therapy with PML and none implicated concurrent adalimumab and methotrexate therapy with PML [6, 11].

Results

Conclusion