Abstract
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system with a poor prognosis and is primarily caused by JC virus (JCV) with a mutation called prototype. We encountered a case of PML with moderate progression and analyzed the mutational patterns of JCV in the cerebrospinal fluid (CSF). A 19-year-old Japanese woman with mild neurological symptoms was diagnosed with combined immunodeficiency following pneumocystis pneumonia. Brain magnetic resonance imaging scan showed multiple brain lesions, and real-time polymerase chain reaction testing detected JCV in the CSF, leading to the diagnosis of PML. The disease course of PML was stable after administration of mefloquine and mirtazapine with immunoglobulin replacement therapy. In the JCV genome cloned from the patient CSF, DNA sequences of the gene encoding the capsid protein (VP1) and the non-coding control region exhibited small mutations. However, they were quite similar to those of the archetype JCV, which persists asymptomatically in healthy individuals. These findings provide insight into the mutational characteristics of JCV in PML with mild symptoms and progression.
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The authors would like to thank the patient in this study.
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This work was supported by the Research Committee of Prion Disease and Slow Virus Infection, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health and Labour Sciences Research Grants, The Ministry of Health, Labour and Welfare, Japan, and by JSPS KAKENHI (Grant Number 21K07450). We would like to thank Editage (www.editage.com) for English language editing.
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Kosuke Iwami, Masaaki Matsushima, Azusa Nagai, Shinichi Shirai, Sho Nakakubo, Ikuko Takahashi-Iwata, Masafumi Yamada, and Ichiro Yabe collected and interpreted the clinical data. Kazuo Nakamichi completed virological analyses. Kosuke Iwami and Kazuo Nakamichi wrote the manuscript and prepared the figures. Kosuke Iwami and Kazuo Nakamichi contributed equally to this work. All authors have critically revised and approved the manuscript.
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The CSF was collected for clinical care, and written informed consent was obtained from the patient and her family for the use of the specimen for research purposes. The study was performed in accordance with the ethical standards of the Declaration of Helsinki after approval from the research institution.
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Iwami, K., Nakamichi, K., Matsushima, M. et al. Progressive multifocal leukoencephalopathy with mild clinical conditions and detection of archetype-like JC virus in cerebrospinal fluid. J. Neurovirol. 27, 917–922 (2021). https://doi.org/10.1007/s13365-021-01017-4
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DOI: https://doi.org/10.1007/s13365-021-01017-4