Patient-Reported Experiences of Long-Term Recovery and Persistent Psychosocial Burden in NMDAR Encephalitis

BACKGROUND AND OBJECTIVES: N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune disorder with severe neuropsychiatric symptoms. Although neurologic recovery is often favorable, emerging evidence shows high prevalence of long-term sequelae affecting quality of life. Most studies rely on standardized assessments, leaving patient-reported experiences underexplored. We examined long-term psychosocial outcomes using a mixed-methods approach integrating patient-reported outcome measures (PROMs), neuropsychological testing, and semistructured interviews informed by qualitative findings from SAPIENCE Level 1. METHODS: Sixty-five patients with NMDAR encephalitis were recruited across 3 centers (Berlin, Barcelona, and Lyon) at a median of 7.3 years postonset. Remote assessment included semistructured interviews, validated PROMs (sleep quality, fatigue, depression, anxiety, and quality of life), and neuropsychological testing. Multiple regression models were used to identify factors associated with health-related quality of life (HRQoL). RESULTS: Although 76.9% of patients returned to predisease occupations, substantial long-term burden persisted. Memory deficits dominated the postacute phase (68.8%) and remained most commonly reported at follow-up (29.7%). High rates of fatigue (54.4%), sleep disturbances (49.2%), and anxiety (77%) were observed with strong intercorrelations among symptom domains. Sleep disturbances showed the strongest association with reduced quality of life. Initial misdiagnosis occurred in two-thirds of patients. Despite generally positive health care experiences, 54% reported negative social relationship impacts and 46.2% found return to normalcy challenging. DISCUSSION: NMDAR encephalitis is associated with persistent multidimensional burden despite favorable global recovery. Sleep disturbance emerges as a central and potentially modifiable determinant of HRQoL, while persistent cognitive and psychosocial challenges underscore the need for integrated long-term care. These findings also highlight the importance of patient-reported and qualitative assessments.