Clinical Features and Biomarkers Associated With Intensive Care–Dependent Refractory NMDAR Encephalitis

BACKGROUND AND OBJECTIVES: A subset of patients with NMDAR encephalitis is resistant to first-line and second-line immunotherapy and requires prolonged intensive care. The clinical definition of refractory, intensive care-dependent NMDARE (RI-NMDARE) is lacking, and its frequency, risk factors, and outcomes are unknown. The aim of this study was to define RI-NMDARE and compare its clinical and biomarker characteristics with those of severe NMDARE. METHODS: This was a retrospective cohort study including patients with nonherpetic NMDARE admitted to intensive care units (ICUs) and diagnosed at the French National Reference Center, from 2005 to 2023. Favorable outcome was defined as a modified Rankin Scale (mRS) score < 2 at 24 months from onset. RESULTS: = 0.046) compared with non-RI-NMDARE patients. DISCUSSION: RI-NMDARE represents a distinct, high-risk subgroup with a severe clinical profile marked by rapid disease progression; the triad of seizures, movement disorders, and dysautonomia; and elevated biomarkers. RI-NMDARE is associated with poorer outcomes, underscoring the need for early recognition and tailored therapeutic strategies.