Brain Biopsy Is More Reliable than the DNA test for JC Virus in Cerebrospinal Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy

Ikeda, Junji; Matsushima, Akira; Ishii, Wataru; Goto, Tetuya; Takahashi, Keiichi; Nakamichi, Kazuo; Saijo, Masayuki; Sekijima, Yoshiki; Ikeda, Shu‐ichi

doi:10.2169/internalmedicine.56.7689

Cited by 21 publications

(23 citation statements)

References 20 publications

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“…Previous cases have been described where CSF PCR testing . This SV40 immunohistochemical stain (×40) reveals the scattered pleomorphic glial cell nuclei to stain strongly due to a crossreactivity among the polyoma viruses for JC virus was negative, but brain biopsy supported the diagnosis of PML [3] . Typically this happens if the CSF testing is done very early, but this case was different in that patient D had several months of symptoms prior to his negative testing [4] .…”

Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalitis in a patient with sarcoidosis on hydroxychloroquine with negative cerebrospinal fluid testing for the John Cunningham virus

Inamullah¹,

Farin²,

Tran³

et al. 2018

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Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by the John Cunningham (JC) virus typically seen in immuno-compromised patients. Several drugs that suppress that immune system have already been known to cause PML such as natalizumab and rituximab. We present a patient with sarcoidosis who develops PML in the rare setting of minimal immunosuppression with only hydroxychloroquine. There was significant delay in the diagnosis due to negative cerebrospinal fluid testing for JC virus and concern for neuro-sarcoidosis, but eventually a diagnosis of PML was made via brain biopsy.

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Section: Discussionmentioning

confidence: 99%

Progressive multifocal leukoencephalitis in a patient with sarcoidosis on hydroxychloroquine with negative cerebrospinal fluid testing for the John Cunningham virus

Inamullah¹,

Farin²,

Tran³

et al. 2018

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“…In many cases, MQ was combined with mirtazapine, an antidepressant that, acting on the 5-HT2A serotonin receptor, is able to inhibit JCPyV entry into glial cells, preventing the diffusion of the infection in oligodendrocytes. The outcomes of this treatment are controversial, leading to the resolution of the infection, with a claimed effect of MQ and mirtazapine treatment [86,87,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105], and to the resolution of the infection probably due to other factors [96,[106][107][108][109] or to the death of the patient, which was not always directly related to the unsuccessful therapy [87,96,[110][111][112][113][114][115][116]. In one case, the suspension of the therapy was necessary due to the side effects [117].…”

Section: Mefloquine and Jcpyvmentioning

confidence: 99%

The Use of Antimalarial Drugs against Viral Infection

et al. 2020

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In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.

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“…In these cases, JCV DNA and/or protein were detected in brain tissues on pathological analyses, despite negative CSF samples on standard PCR testing. We also recently presented a case in which PML was only diagnosed by brain biopsy [28]. In this case, the patient was not positive for JCV in the CSF because the real-time PCR amplification signal was too faint and unstable, probably due to the extremely low copy number of the target DNA.…”

Section: Discussionmentioning

confidence: 99%

Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy

et al. 2019

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BackgroundProgressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by JC virus (JCV). Although detecting JCV DNA in the cerebrospinal fluid (CSF) by real-time polymerase chain reaction (PCR) is useful, diagnosis is difficult when JCV concentrations are low. We therefore aimed to lower the detection limit of real-time PCR testing by enriching JCV in the CSF via ultrafiltration.MethodsVirus suspensions and CSF specimens from 20 untreated patients with suspected PML were collected and total DNAs were extracted. The JCV large T gene was detected by quantitative real-time PCR under condition with and without prior centrifugal ultrafiltration.ResultsThe JCV DNA was reliably detected to a lower limit of 10 copies/mL of virus suspension by real-time PCR with ultrafiltration. When using this method, the quantity of JCV DNA per PCR reaction increased 3.2- to 8.7-fold compared with the standard procedure. Seven patients were positive for JCV when using the standard procedure, and an additional patient was positive when using ultrafiltration. All JCV-positive patients had neurological features and magnetic resonance imaging findings compatible with PML.ConclusionsThe detection limit of JCV DNA by real-time PCR can be lowered by viral enrichment using ultrafiltration. Our simple protocol offers a valuable tool for PML diagnosis when extremely low copy numbers of JCV are released into the CSF or when brain biopsy is not feasible.

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Brain Biopsy Is More Reliable than the DNA test for JC Virus in Cerebrospinal Fluid for the Diagnosis of Progressive Multifocal Leukoencephalopathy

Cited by 21 publications

References 20 publications

Progressive multifocal leukoencephalitis in a patient with sarcoidosis on hydroxychloroquine with negative cerebrospinal fluid testing for the John Cunningham virus

Progressive multifocal leukoencephalitis in a patient with sarcoidosis on hydroxychloroquine with negative cerebrospinal fluid testing for the John Cunningham virus

The Use of Antimalarial Drugs against Viral Infection

Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy

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