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It is caused by the John Cunningham virus (JCV), a ubiquitous polyomavirus that only rarely leads to neurological complications. Prompt diagnosis of PML is essential for patient management, but can be complicated by disease development in individuals who are relatively immunocompetent, the lack of highly specific clinical symptoms, unfamiliarity with recently described neuroimaging signs and the imperfect sensitivity of assays used to detect JCV in cerebrospinal fluid (CSF). We review the supportive clinical features, neuroimaging findings and confirmatory testing for PML and propose an algorithm to facilitate accurate diagnosis in clinical practice.<\/jats:p>","DOI":"10.1136\/pn-2025-004648","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T18:20:29Z","timestamp":1768846829000},"page":"pn-2025-004648","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Diagnosing progressive multifocal leukoencephalopathy: clinical features, neuroimaging findings, confirmatory testing and proposed diagnostic algorithm"],"prefix":"10.1136","author":[{"given":"Katherine M","family":"Sawicka","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Houpt","sequence":"additional","affiliation":[{"name":"Department 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London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Budhram","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre, London, Ontario, Canada"},{"name":"Department of Clinical Neurological Sciences and Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"2026011910201528000_pn-2025-004648v1.1","doi-asserted-by":"crossref","DOI":"10.4178\/epih.e2018001","article-title":"Systematic review of the published data on the worldwide prevalence of John Cunningham virus in patients with multiple sclerosis and neuromyelitis optica","volume":"40","author":"Paz","year":"2018","journal-title":"Epidemiol 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