2025 American Academy of Neurology Abstract Website

Mar Guasp¹, Juliette Brenner², Pauline Dumez³, Patrice LaLive⁴, Katharina Wurdack⁵, Stefan Macher⁶, Kang Wang⁷, Gemma Olivé⁸, Jonas Yeung⁹, Giovanni Di Liberto¹⁰, Klaus-Peter Wandinger¹¹, Dominik Zieglgänsberger¹², Mamoru Shibata¹³, Eri Fukao¹⁴, Takayasu Mishima¹⁵, Hiroto Nakagawa¹⁶, Tsubasa Takizawa¹⁷, Sho Shimohama¹⁷, Yoshikane Izawa¹⁷, Eric Lancaster¹⁸, Wolfram Sühs¹⁹, Jose Maria Cabrera Maqueda²⁰, Elianet Fonseca⁸, Eugenia Martinez-Hernandez²¹, Marianna Spatola²², Renaud Du Pasquier²³, Frank Leypoldt²⁴, Romana Hoeftberger⁶, Carsten Finke²⁵, Thais Armangue²², Maarten Titulaer²⁶, Mateus Simabukuro²⁷, Jerome Honnorat²⁸, Takahiro Iizuka²⁹, Josep Dalmau²²
¹Hospital Clínic Barcelona - IDIBAPS/CaixaResearch Institute, ²Erasmus University Medical Center, ³Université Claude Bernard Lyon, ⁴Hôpitaux universitaires de Genève, ⁵Charité Medical University Hospital, Berlin, ⁶Medical University of Vienna, ⁷School of Medicine, Zhejiang University, Hangzhou, ⁸IDIBAPS, ⁹Alice Ho Miu Ling Nethersole Hospital, ¹⁰Lausanne University Hospital (CHUV) and University of Lausanne, ¹¹University Hospital Schleswig-Holstein Lübeck, ¹²Kantonsspital St. Gallen, ¹³Tokyo Dental College Ichikawa General Hospital, ¹⁴Show General Hospital, ¹⁵Sakura Medical Center, Toho University, ¹⁶Kagoshima Medical Association Hospital, ¹⁷Keio University Hospital, ¹⁸The University of Pennsylvania, Dept. of Neurology, ¹⁹Hannover Medical School, ²⁰Hospital Clínic Barcelona - IDIBAPS, ²¹Hospital Clinic Barcelona, ²²IDIBAPS/CaixaResearch Institute, ²³Service of neurology, CHUV, ²⁴University Hospital Schleswig-Holstein, Campus Kiel Department of Neurology, ²⁵Charité Berlin, ²⁶Erasmus Medical Center, ²⁷Hospital Das Clinicas, Sao Paulo U Scho of Med, ²⁸Hospices Civils de Lyon, ²⁹Department of Neurology, Kitasato University School of Medicine

Objective:

To investigate patients with prolonged (≥9 months) super-refractory anti-NMDAR encephalitis (NMDARe).

Background:

In NMDARe patients who fail first-line (steroids, IVIg, plasma exchange) and second-line (rituximab and cyclophosphamide) immunotherapies, the role of third-line therapies is unclear due to late effects of previous treatments and reporting bias.

Design/Methods:

International retrospective observational study of NMDARe patients who remained in a minimally conscious state for ≥9 months. Data were obtained by chart review and structured questionnaires.

Results:

We identified 43 NMDARe patients, median age 23 (IQR 20-32) years; 38 (88%) women. All were admitted to ICU (median stay 298 [247-379] days) due to motor agitation (37%), dyskinesias (44%), seizures (67%), hypoventilation (79%) or dysautonomia (90%). All had abnormal EEG, 28/43 (65%) brain MRI abnormalities, 37/38 (97%) pleocytosis (median 65 [27-150] WBC/µL), and 22/43 (51%) ovarian teratomas (4 bilateral). Common ICU complications included sepsis and thrombotic events; 6 patients were resuscitated from cardiac arrest. Treatment included first-line immunotherapy (42/43, 98%), second-line immunotherapy (39/43, 91%), and third-line immunotherapy (19/43, 44%) such as bortezomib (17), methotrexate (8); tocilizumab (4); daratumumab (2), and other (3). Yet, all patients remained in a state of minimal consciousness/unresponsiveness for 360 (299-780) days. After a median follow-up of 3.4 (2-6) years, 9 (21%) died, 5 (12%) remained unresponsive (mRS 5), 5 (12%) moderately-severely impaired (mRS 3-4), and 24 (56%) improved (mRS 0-2; 20 returning to premorbid activities). Among all patients who improved (n=24), only 8 received third line immunotherapy. Conversely, among all patients who did not improve (n=19), 12 received third line immunotherapies. Three patients had complete recovery after being in coma 2-4 years and without immunotherapy 13-33 months.

Conclusions:

NMDARe can associate with extremely prolonged states of minimal consciousness, but with potential for recovery. This study shows the difficulty in assessing third line therapies in a disease as complex as NMDARe.