Antibodies to neuronal surface antigens in possible autoimmune encephalitis and new-onset refractory status epilepticus (NORSE)

Objective: To determine the frequency of antibodies to neuronal surface antigens (NSA-abs) in patients with possible autoimmune encephalitis (AE) or new-onset refractory status epilepticus (NORSE). Background: The frequency of NSA-abs in patients with possible AE or NORSE is unknown. Design/Methods: Patients seen between January 1, 1999 and August 31, 2016, with criteria (Lancet Neurol 2016;15:391–404) for possible AE (n=98), were included. Clinical information was reviewed and antibody testing was performed. One autopsied case of NORSE not examined for NSA-abs was included. Outcome was compared between patients with features of NORSE and those with NSA-abs. Results: NSA-abs were identified in 38 of 98 (39%) patients with possible AE, including NMDA receptor (NMDAR)-abs (n=32), AMPAR-abs (n=3), LGI1-abs (n=2), GABAbR-abs (n=2), and antibodies not characterized yet (n=2); two patients had multiple NSA-abs. Twenty-seven of the 38 patients with NSA-abs responded to immunotherapies, and 28 (74%) ultimately recovered at the median follow-up (29 months; range, 1–179). Eleven of 98 (11%) patients had features of NORSE, and none had NSA-abs. Patients with NORSE presented with status epilepticus following fever, and were highly refractory to conventional antiepileptic treatment and first-line immunotherapies, but 3 of 5 patients treated responded to intravenous cyclophosphamide. Only 3 of 12 (25%) patients with NORSE recovered considerably but still had seizures frequently at the median follow-up (10 months; range, 3–84). Initial brain MRI in patients with NORSE was unremarkable, but follow-up MRIs in 9 of 11 patients showed symmetric T2/FLAIR hyperintensities in the hippocampus, amygdala, insula, claustrum, thalamus, and perisylvian operculum. In 10 of 12 (83%) patients brain atrophy developed. The autopsy of one case of NORSE showed nonspecific hippocampal pathology. Conclusions: NSA-abs were detected in 39% of patients with possible AE; 74% of these patients improved. In contrast, patients with NORSE did not have NSA-abs, were refractory to immunotherapies, and more frequently had poor outcome. Disclosure: Dr. Iizuka has received research support from Mitsubishi Tanabe Pharma Corporation. Dr. Kaneko has nothing to disclose. Dr. Tominaga has nothing to disclose. Dr. Kanazawa has nothing to disclose. Dr. Ugawa has received personal compensation for activities with CHUGAI-IGAKUSHA, Igaku-Shoin Ltd, Medical View Co. Ltd., and Blackwell Publishing K.K. Dr. Ugawa has received research support from Taiwan Movement Disorders Society, Chinese Neurology Society, Astellas Pharma Inc., Eisai Co., Ltd., FP Pharmaceutical Corporation, Otsuka Pharmaceutical Co., Ltd., Elsevier Japan K. K., KISSEI PHARMACEUTICAL CO., Ltd. Dr. Hara has nothing to disclose. Dr. Onozawa has nothing to disclose. Dr. Asari has nothing to disclose. Dr. Hata has nothing to disclose. Dr. Kaneko has nothing to disclose. Dr. Yoshida has nothing to disclose. Dr. Sugiura has nothing to disclose. Dr. Ugawa has received royalties from CHUGAI-IGAKUSHA, Igaku-Shoin Ltd, Medical View Co. Ltd., and Blackwell Publishing K.K. Dr Ugawa has received research support from Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labour and Welfare of Japan, and the Support Center for Advanced Telecommunications Technology Research. Dr. Watanabe has nothing to disclose. Dr. Tomita has nothing to disclose. Dr. Kosakai has nothing to disclose. Dr. Kaneko has nothing to disclose. Dr. Ishima has nothing to disclose. Dr. Kitamura has nothing to disclose. Dr. Dalmau receives royalties from the editorial board of Up-To-Date. Dr. Dalmau has received royalties from a patent from Memorial Sloan-Kettering Cancer Center and royalty payments and/or for technology and invention on NMDAR, GABA(B), GABAaR, DPPX, and IgLON5 antibody test. Dr. Dalmau has received research support from Euroimmun. Dr. Nishiyama has nothing to disclose.