{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:05:07Z","timestamp":1740146707199,"version":"3.37.3"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2155"],"award-info":[{"award-number":["EXC 2155"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.<\/jats:p>","DOI":"10.1371\/journal.pone.0242321","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T19:11:25Z","timestamp":1606245085000},"page":"e0242321","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy"],"prefix":"10.1371","volume":"15","author":[{"given":"Yi","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"M\u00f6hn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amani","family":"Al-Mekhlafi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Schuchardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Skripuletz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram","family":"S\u00fchs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Pessler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Stangel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"pone.0242321.ref001","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1474-4422(10)70040-5","article-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis","volume":"9","author":"CS Tan","year":"2010","journal-title":"Lancet Neurol"},{"key":"pone.0242321.ref002","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.ncl.2008.03.007","article-title":"Progressive multifocal leukoencephalopathy","volume":"26","author":"T Weber","year":"2008","journal-title":"Neurol Clin"},{"key":"pone.0242321.ref003","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1086\/595299","article-title":"Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study","volume":"199","author":"M Touma","year":"2009","journal-title":"J Infect Dis"},{"key":"pone.0242321.ref004","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1002\/art.24966","article-title":"Progressive multifocal leukoencephalopathy: a national estimate of frequency in systemic lupus erythematosus and other rheumatic diseases","volume":"60","author":"ES Molloy","year":"2009","journal-title":"Arthritis Rheum"},{"key":"pone.0242321.ref005","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/1756285615602832","article-title":"Progressive multifocal leukoencephalopathy: current treatment options and future perspectives","volume":"8","author":"D Pavlovic","year":"2015","journal-title":"Ther Adv Neurol Disord"},{"key":"pone.0242321.ref006","first-page":"109","article-title":"Progressive Multifocal Leukoencephalopathy: Current Insights","volume":"9","author":"M Kartau","year":"2019","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"pone.0242321.ref007","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1086\/374048","article-title":"Clinical course and prognostic factors of progressive multifocal leukoencephalopathy in patients treated with highly active antiretroviral therapy","volume":"36","author":"J Berenguer","year":"2003","journal-title":"Clin Infect Dis"},{"key":"pone.0242321.ref008","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.med.080708.082655","article-title":"Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies","volume":"61","author":"EO Major","year":"2010","journal-title":"Annu Rev Med"},{"key":"pone.0242321.ref009","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1212\/WNL.0b013e31828c2fa1","article-title":"PML diagnostic criteria: consensus statement from the AAN. 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