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. 

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.

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.

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.