Open AccessProdromal headache in anti‐ NMDAR encephalitis: An epiphenomenon of NMDAR autoimmunity
Author(s) -
Tominaga Naomi,
Kanazawa Naomi,
Kaneko Atsushi,
Kaneko Juntaro,
Kitamura Eiji,
Nakagawa Hiroto,
Nishiyama Kazutoshi,
Iizuka Takahiro
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.1012
Subject(s) - csf pleocytosis , medicine , pleocytosis , encephalitis , migraine , nmda receptor , lymphocytic pleocytosis , prodrome , anesthesia , gastroenterology , pediatrics , cerebrospinal fluid , immunology , psychiatry , receptor , virus , psychosis
Objective To investigate the nature of prodromal headache in anti‐ NMDA receptor ( NMDAR ) encephalitis. Methods Retrospective review of the clinical information of 39 patients with anti‐ NMDAR encephalitis admitted between January 1999 and September 2017. Five patients with an atypical presentation were excluded. Thus, in 34 patients (median 27 years [range, 12–47 years]; 28 [82%] female), the clinical features were compared between patients who initially reported headache and those who did not report. Results Twenty‐two patients (65%) reported headache either transiently ( n = 5) or continuously ( n = 17). Encephalitic symptoms (psychobehavioral memory alterations, seizure, dyskinesias, or altered level of consciousness) developed in 20 patients with median 5.5 days (range, 1‐29 days) after headache onset. In one patient, NMDAR antibodies were detected in CSF 3 days after headache onset. Patients with headache had more frequently fever (14/22 [64%] vs. 2/12 [17%] p = 0.013) and higher CSF pleocytosis (median white blood cells 79/μl [range, 6‐311/μl] vs. 30/μl [range, 2‐69/μl], p = 0.035) than those without headache, but there was no difference in gender, age at onset, seizure, migraine, CSF oligoclonal band detection, elevated IgG index, tumor association, or brain MRI abnormalities between them. Conclusions Headache often developed with fever and pleocytosis, but it was rapidly replaced by psychiatric symptoms. Based on current knowledge on the antibody‐mediated mechanisms that cause a decrease of synaptic NMDAR through crosslinking and internalization leading to a state mimicking “dissociative anesthesia,” 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 NMDAR autoimmunity. Psychobehavioral alterations following headache is an important clue to the diagnosis.