{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:36:51Z","timestamp":1788907011433,"version":"build-2803163510"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":277,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220659\/Z\/20\/Z"],"award-info":[{"award-number":["220659\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008721","name":"University College London Hospitals NHS Foundation Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018942","name":"Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018942","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Encephalitis lethargica, an epidemic neurological illness, typically involved a severe sleep disorder and progressive parkinsonism. A century later, our understanding relies on seminal descriptions, more recent historical research and the study of small numbers of possible sporadic cases. Theories around infection, environmental toxins, catatonia and autoimmune encephalitis have been proposed. We aimed to describe the presentation of encephalitis lethargica and test these diagnostic and aetiological theories. Subjects with encephalitis lethargica were identified in the archives of the National Hospital for Neurology and Neurosurgery, UK between 1918 and 1946. Case notes were examined to establish illness temporality, clinical features and cerebrospinal fluid results. Controls from the archives were identified for 10% of cases, matching on discharge year, sex and neurologist. Clinical presentation was compared to modern diagnostic criteria for encephalitis lethargica, catatonia and autoimmune encephalitis. In a case\u2013control design, a multilevel logistic regression was conducted to ascertain whether cases of encephalitis lethargica were associated with febrile illnesses and with environmental exposures. Six hundred and fourteen cases of encephalitis lethargica and 65 controls were identified. Cases had a median age of 29 years (interquartile range 18) and a median time since symptomatic onset of 3.00 years (interquartile range 3.52). Motor features were present in 97.6%, cranial nerve findings in 91.0%, ophthalmological features in 77.4%, sleep disorders in 66.1%, gastrointestinal or nutritional features in 62.1%, speech disorders in 60.8% and psychiatric features in 53.9%. Of the 167 cases who underwent lumbar puncture, 20 (12.0%) had a pleocytosis. The Howard and Lees criteria for encephalitis lethargica had a sensitivity of 28.5% and specificity of 96.9%. Among the cases, 195 (31.8%, 95% confidence interval 28.1\u201335.6%) had a history of febrile illness within one calendar year prior to illness onset, which was more common than among the controls (odds ratio 2.70, 95% confidence interval 1.02\u20137.20, P = 0.05), but there was substantial reporting bias. There was no evidence that occupational exposure to solvents or heavy metals was associated with encephalitis lethargica. Two hundred and seventy-six (45.0%) of the cases might meet criteria for possible autoimmune encephalitis, but only 3 (0.5%) might meet criteria for probable NMDA receptor encephalitis. Only 11 cases (1.8%) met criteria for catatonia. Encephalitis lethargica has a distinct identity as a neuropsychiatric condition with a wide range of clinical features. Evidence for a relationship with infectious or occupational exposures was weak. Autoimmune encephalitis may be an explanation, but typical cases were inconsistent with NMDA receptor encephalitis.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae347","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T13:57:19Z","timestamp":1728050239000},"source":"Crossref","is-referenced-by-count":8,"title":["Encephalitis lethargica: clinical features and aetiology"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-5410","authenticated-orcid":false,"given":"Jonathan P","family":"Rogers","sequence":"first","affiliation":[{"name":"Division of Psychiatry, University College London , London W1T 7NF ,","place":["UK"]},{"name":"Department of Neuropsychiatry, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Mastellari","sequence":"additional","affiliation":[{"name":"University Lille, Inserm, CHU Lille, U1172\u2014LilNCog\u2014Lille Neuroscience & Cognition , F-59000 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex J","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieron","family":"Kumar","sequence":"additional","affiliation":[{"name":"South London and Maudsley NHS Foundation Trust , London BR3 3BX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Burchill","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University College London , London W1T 7NF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S","family":"David","sequence":"additional","affiliation":[{"name":"Institute of Mental Health, University College London , London W1T 7NF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glyn","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University College London , London W1T 7NF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-4385","authenticated-orcid":false,"given":"Andrew","family":"Lees","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-9401","authenticated-orcid":false,"given":"Michael S","family":"Zandi","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]},{"name":"Department of Neuroinflammation, University College London , London, WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"2024102214364568200_fcae347-B1","first-page":"581","article-title":"Die encephalitis lethargica","volume":"30","author":"von Economo","year":"1917","journal-title":"Wien Klin Wochenschr"},{"issue":"8","key":"2024102214364568200_fcae347-B2","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1093\/brain\/awx177","article-title":"Encephalitis lethargica: 100 years after the epidemic","volume":"140","author":"Hoffman","year":"2017","journal-title":"Brain"},{"issue":"Suppl","key":"2024102214364568200_fcae347-B3","first-page":"1.1","article-title":"A note on the history of epidemic encephalomyelitis","volume":"12","author":"Crookshank","year":"1919","journal-title":"Proc R Soc Med"},{"issue":"8303","key":"2024102214364568200_fcae347-B4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0140-6736(82)90820-0","article-title":"1918 influenza, encephalitis lethargica, parkinsonism","volume":"2","author":"Ravenholt","year":"1982","journal-title":"Lancet (London, England)"},{"key":"2024102214364568200_fcae347-B5","first-page":"839","article-title":"The fading trail of the sleepy wraith","author":"Foley","year":"2015","journal-title":"Encephalitis Lethargica"},{"issue":"Pt 1","key":"2024102214364568200_fcae347-B6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/brain\/110.1.19","article-title":"Encephalitis lethargica. 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