Patient-Reported Outcome Measures in NMDA Receptor Encephalitis

The characteristics of persistent long-term symptoms and their contribution to subjective quality of life remain unclear in patients with NMDAR encephalitis. In this study, we aimed to evaluate postacute neuropsychiatric symptoms, subjective cognitive complaints, and disease coping mechanisms and identify predictors of health-related quality of life (HRQoL) after N-methyl-D-aspartate receptor (NMDAR) encephalitis.

This cross-sectional observational study investigated patients with NMDAR encephalitis in the postacute phase. Psychometric scales included assessment of neuropsychiatric symptoms (i.e., fatigue, sleep, anxiety, and depressive symptoms), HRQoL, everyday independence, metamemory (i.e., self-rated ability, satisfaction, and use of strategies), and coping strategies (i.e., self-efficacy, disease-related coping, and stress management).

A total of 50 patients (mean age 26.0 ± 10.1 years, 86% female) participated at a median of 4.15 (range 0.3-30.3) years after symptom onset. Patients reported significantly increased levels of anxiety (Beck Anxiety Inventory: 10.5 ± 7.7 [mean ± SD], 95% CI [8.32-12.71], p < 0.001) and depressive (Beck Depression Inventory-II: 11.4 ± 7.7 [9.22-13.62], p = 0.001) symptoms compared with the normative population. Both sleep problems (Pittsburgh Sleep Quality Index: 5.8 ± 3.0 [4.98-6.66], p < 0.001) and motor and cognitive fatigue (Fatigue Scale for Motor and Cognitive Function: 50.5 ± 23.1 [42.5-58.4], p < 0.001) were significantly more prevalent. Moreover, lower self-rated memory ability (Multifactorial Memory Questionnaire score: 54.6 ± 8.5 [52.1-57.1], p = 0.004) was associated with greater reliance on compensatory strategies and memory aids (r = -0.41, p = 0.004). Patients used significantly fewer cognitive coping strategies, such as relativization (11.7 ± 4.7 [10.3-13.1], p = 0.001), while depressive coping prevailed (49.1 ± 15.5 [44.5-53.8], p < 0.001). It is important to note that HRQoL was predicted by self-reported affective symptoms, self-efficacy, and coping behaviors in multivariable regression analyses, but not by acute disease severity or postacute physical disability.

Our findings show that persistent neuropsychiatric and subjective cognitive concerns explain a large part of the reduced quality of life in patients with NMDAR encephalitis. These findings have important implications for a patient-centered postacute care and the role of disease coping strategies in the neurorehabilitation of autoimmune encephalitis.