{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:06:32Z","timestamp":1790661992514,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012628","name":"Japan Epilepsy Research Foundation","doi-asserted-by":"crossref","award":["JERFTENKAN 17002"],"award-info":[{"award-number":["JERFTENKAN 17002"]}],"id":[{"id":"10.13039\/501100012628","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the nature of prodromal headache in anti\u2010<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content> receptor (<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>) encephalitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective review of the clinical information of 39 patients with anti\u2010<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27\u00a0years [range, 12\u201347\u00a0years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010two patients (65%) reported headache either transiently (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>5) or continuously (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5\u00a0days (range, 1\u201029\u00a0days) after headache onset. In one patient, <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> antibodies were detected in <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> 3\u00a0days after headache onset. Patients with headache had more frequently fever (14\/22 [64%] vs. 2\/12 [17%] <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.013) and higher <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> pleocytosis (median white blood cells 79\/\u03bcl [range, 6\u2010311\/\u03bcl] vs. 30\/\u03bcl [range, 2\u201069\/\u03bcl], <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> oligoclonal band detection, elevated IgG index, tumor association, or brain <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> abnormalities between them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody\u2010mediated mechanisms that cause a decrease of synaptic <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> through crosslinking and internalization leading to a state mimicking \u201cdissociative anesthesia,\u201d we speculated that prodromal headache is not likely caused by direct effect of the autoantibodies but rather meningeal inflammation (noninfectious aseptic meningitis) that occurs in parallel to intrathecal antibody synthesis as an epiphenomenon of <jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content> autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1012","type":"journal-article","created":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T09:21:20Z","timestamp":1527844880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Prodromal headache in anti\u2010<scp>NMDAR<\/scp> encephalitis: An epiphenomenon of <scp>NMDAR<\/scp> autoimmunity"],"prefix":"10.1002","volume":"8","author":[{"given":"Naomi","family":"Tominaga","sequence":"first","affiliation":[{"name":"Department of Neurology Kitasato University School of Medicine  Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Kitasato University School of Medicine  Sagamihara 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