Prolonged Vegetative State in Anti-NMDA Receptor Encephalitis: Complications, Outcomes, and Implications
Mar Guasp1, Mateus Simabukuro2, Guillermo Muñoz-Sánchez3, Juliette Brenner4, Katharina Wurdack5, Kang Wang6, Patrice LaLive7, Gemma Olivé8, Jonas Yeung9, Klaus Peter Wandinger10, Stefan Macher11, Giovanni Di Liberto12, Eric Lancaster13, Teresa Casadevall14, María Jesús Martínez-González15, Juan Pablo Fernández-Carrasco16, Mamoru Shibata17, Eri Fukao18, Takayasu Mishima19, Hiroto Nakagawa20, Tsubasa Takizawa21, Sho Shimohama21, Yoshikane Izawa21, Shuichiro Neshige22, Roger Borràs23, Esther Aguilar8, Laura Marmolejo Alcaide8, Jesus Planaguma8, Ariel Heller24, Maya Tojima25, Akio Ikeda25, Yolanda Blanco Morgado3, Renaud Du Pasquier26, Wolfram Sühs27, Frank Leypoldt28, Romana Hoeftberger11, Carsten Finke29, Maarten Titulaer30, Thais Armangue31, Francesc Graus23, Takahiro Iizuka32, Josep Dalmau8
1Hospital Clínic Barcelona - IDIBAPS, 2Hospital Das Clinicas, Sao Paulo U Scho of Med, 3Hospital Clínic Barcelona, 4Erasmus University Medical Center, 5Department of Neurology, Charité Universitätsmedizin Berlin, 6Department of Neurology, the First Affiliated Hospital, School of Medicine, Zhejiang University, 7University Hospital of Geneva, 8Neuroimmunology Program, IDIBAPS, 9Alice Ho Miu Ling Nethersole Hospital, 10Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Lübeck, 11Medical University of Vienna, 12Lausanne University Hospital (CHUV) and University of Lausanne, 13The University of Pennsylvania, Dept. of Neurology, 14Hospital Comarcal Sant Jaume de Calella, 15Cruces University Hospital, Biobizkaia Health Research Institute, 16Hospital Carlos Van Buren de Valparaíso, Universidad de Valparaíso, 17Tokyo Dental College Ichikawa General Hospital, 18Showa General Hospital, 19Sakura Medical Center, Toho University, 20Kagoshima City Medical Association Hospital, 21Keio University School of Medicine, 22Hiroshima University Graduate School of Biomedical and Health Sciences, 23IDIBAPS, 24Children's Hospital of Pittsburgh/University of Pittsburgh Medical Center, 25Kyoto University Hospital, 26Service of neurology, CHUV, 27Hannover Medical School, 28University Hospital Schleswig-Holstein, Campus Kiel Department of Neurology, 29Charité Berlin, 30Erasmus Medical Center, 31IDIBAPS-HClinic, 32Department of Neurology, Kitasato University School of Medicine
Objective:
To investigate long-term outcomes and treatment response in patients with anti-NMDAR encephalitis (NMDARe) with prolonged impaired consciousness.
Background:
As recovery in NMDARe is typically delayed and slow, prolonged unconscious states raise key questions involving in-hospital complications, the choice and duration of immunotherapy, long-term outcomes, and the point at which deficits may be considered irreversible.
Design/Methods:
Multicenter retrospective study included NMDARe patients with a vegetative state (unresponsive wakefulness) lasting ≥9 months. Outcomes were: death; and achieving command-following, a modified Rankin Scale score (mRS)=2, or recovery (mRS=0 with return to premorbid activities). Competing risks analysis assessed survival, and predictors of death, mRS=2, and recovery.
Results:
Forty-five patients were identified (38 female; median age 22 [IQR 19–31]). All had impaired consciousness a median of 9 days after symptom onset (5–16). All received first-line immunotherapy; 41 (91%) second-line, and 18 (40%) third-line. Twenty-one (47%) had ovarian teratomas, removed in 20. Median durations were: vegetative state 399 days (307–698), ICU stay 275 days (189–354), mechanical ventilation 270 days (195–394), and hospitalization 474 days (349-715). Thirteen (28%) patients were resuscitated from cardiac arrest. After 5 years (IQR 2.5–6.8), 28 (62%) improved (mRS≤2; 15 recovered), 11 (24%) had mRS=3-5, and 6 (13%) died. Five began command-following 11 months (1.5–21) after last immunotherapy. Estimated cumulative incidences at 5 and 10 years were 66% and 76% for achieving mRS=2, and 32% and 54%, respectively, for recovery. Teratomas were associated with lower probability of good outcome (sHR=0.39, 95%CI:0.18–0.84, p=0.016); older age (sHR=1.10/year, 95%CI:1.04–1.23, p=0.0052) and higher NMDARe One-Year Functional Status (NEOS)2 score (sHR=1.51, 95% CI:1.12-2.04, p=0.0072) predicted death.
Conclusions:
In NMDARe, recovery from prolonged impaired consciousness is more common than expected. In these patients, assessment of treatment effects and refractoriness may underestimate delayed responses, extended therapy needs, or spontaneous recoveries. Futility decisions should therefore be individualized with multidisciplinary input, and made after prolonged follow-up.
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