{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:21:38Z","timestamp":1791829298855,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>To assess the clinical spectrum of central nervous system (CNS) involvement as well as cerebrospinal fluid (CSF) and neuroimaging findings in patients with Whipple's disease (WD) and to analyze the association of neurological symptoms with CSF and imaging findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neurological involvement was retrospectively analyzed in a series of 36 patients diagnosed with WD at a single center between 1992 and 2019. Findings of 81 comprehensive CSF examinations from 36 patients, including polymerase chain reaction (PCR) tests for <jats:italic>Tropheryma whipplei<\/jats:italic> (TW) in CSF from 35 patients, were systematically evaluated. The prevalence of ischemic stroke in patients with WD was compared to a matched control cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neurological symptoms occurred in 23 of 36 (63.9%) patients, with cognitive, motor, and oculomotor dysfunction being most frequent. TW was detected by PCR in CSF of 13 of 22 (59.1%) patients with and four of 13 (30.8%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0496) patients without neurological symptoms. Total CSF protein (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.044) and lactate (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.035) were moderately elevated in WD with neurologic symptoms compared with WD without. No intrathecal immunoglobulin synthesis was observed. Three of 36 (8.3%) patients had hydrocephalus due to aqueductal stenosis. Patients with WD had an unexpectedly high prevalence of ischemic stroke (10\/36, 27.7%) compared to matched controls (10\/360, 3.2%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Neurological involvement in patients with WD is common. Detection of TW DNA in CSF is only partly associated with neurological symptoms. Elevated CSF parameters suggest CNS parenchymal infection. Stroke is a hitherto underrecognized manifestation of WD. These findings suggest that mechanisms beyond CNS infection contribute to the spectrum of CNS involvement in WD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15511","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T13:47:58Z","timestamp":1658238478000},"page":"3417-3429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The spectrum of central nervous system involvement in Whipple's disease"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-0038","authenticated-orcid":false,"given":"Jasper","family":"Mecklenburg","sequence":"first","affiliation":[{"name":"Department of Neurology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Moos","sequence":"additional","affiliation":[{"name":"Medical Department of Gastroenterology, Rheumatology and Infectious Diseases, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Moter","sequence":"additional","affiliation":[{"name":"Institute for Microbiology, Infectious Diseases and Immunology, Biofilmcenter, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"MoKi Analytics and Moter Diagnostics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Siebert","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Heinrich","family":"Nave","sequence":"additional","affiliation":[{"name":"Department of Neurology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Stroke Research Berlin (CSB)  Berlin Germany"},{"name":"Deutsches Zentrum f\u00fcr Herz\u2010Kreislauferkrankungen (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schneider","sequence":"additional","affiliation":[{"name":"Medical Department of Gastroenterology, Rheumatology and Infectious Diseases, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemens","family":"Ruprecht","sequence":"additional","affiliation":[{"name":"Department of Neurology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-805X","authenticated-orcid":false,"given":"Philipp","family":"Euskirchen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra062477"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.01.048"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-015-2357-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199705000-00003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0b013e3181f204a8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.130328"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5033-4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcl081"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00537-X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.01.051"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-7-48"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.2015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400404"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410220325"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870030211"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.66.4.532"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00685145"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-197611000-00003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-11-171"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000010"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1902.120709"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202171"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000714"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-153-11-201012070-00004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_10_27_1","first-page":"640","article-title":"SNOMED RT: a reference terminology for health care","author":"Spackman KA","year":"1997","journal-title":"Proc AMIA Annu Fall Symp"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01703-13"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.24.1.35"},{"key":"e_1_2_10_30_1","unstructured":"Robert Koch\u2010Institut AfEuG.Gesundheit in Deutschland aktuell 2014\/2015\u2010EHIS (GEDA 2014\/2015\u2010EHIS).Scientific Use File 1 Version. doi:10.7797\/19-201415-1-1-1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v042.i08"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-021-05844-5"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27419"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.40.9.901"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2089"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.05.029"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1086\/604717"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0528-0"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02427566"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2010.04.021"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.5334\/jbr-btr.527"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-802395-2.00005-5"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1911.121356"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-2-199907200-00007"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.05531-11"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-019-1257-2"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001835"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy664"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00503-4"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520510015494"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.3.336"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-008-0597-0"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2008.03.007"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/326174"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-eular.4985"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15511","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T05:42:01Z","timestamp":1697262121000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":54,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/ene.15511"],"URL":"https:\/\/doi.org\/10.1111\/ene.15511","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,9]]},"assertion":[{"value":"2022-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}