Patient-Reported Outcome Measures in NMDA Receptor Encephalitis

Abstract

Background and objectives: 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.

Methods: 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).

Results: 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.

Discussion: 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.

Figure 1. Self-Reported complaints and Their Perceived Burden on Day-to-Day Life During the Postacute Phase of NMDAR Encephalitis

Point size is scaled by severity (frequency * median symptom burden). Cognitive complaints (apricot/orange) are the most frequently mentioned symptoms. While most psychiatric symptoms (red) and all problems with sleep and fatigue (green) are reported by more than 50% of the patients, most problems with sleep and fatigue also have a high symptom burden (median ≥50). Note that seizures were perceived to have the highest burden on day-to-day life (median 60) despite a relatively low prevalence after the acute phase. Single patients reported compulsive behavior, mania, headache, loss of appetite, and increased dreaming (each N = 1, not shown).

Figure 2. Correlation Plot of Health-Related Quality of Life (HRQoL) With (A) Long-Term Symptoms and (B) Disease Coping Behaviors in Patients With Anti-NMDAR Encephalitis

(*p < 0.05, **p < 0.01, ***p < 0.001). In Panel A, significant negative correlations are observed between HRQoL and long-term symptoms, particularly cognitive fatigue, sleep problems, and memory satisfaction, as well as depressive and anxiety symptoms. By contrast, the physical domain of HRQoL presents a more complex picture, displaying variable degrees of correlation with a variety of symptoms. Panel B reveals that positive coping behaviors, notably self-efficacy and self-encouragement, are positively associated with HRQoL, whereas negative coping behaviors, such as resignation, are strongly negatively associated with HRQoL, indicating that a tendency to give up or feel helpless is linked with poorer patient-reported outcomes in quality of life.

Figure 3. Neuropsychiatric Scales With Cutoffs for Symptom Severity of Affective Changes, Sleep Quality, and Fatigue in Postacute Patients With Anti-NMDAR Encephalitis

Figure 4. Decreased Satisfaction With Memory and Perceived Everyday Memory Ability in Patients With Anti-NMDAR Encephalitis

Raincloud plots illustrating the distribution of patient scores of the MMQ subscales. Gray vertical lines denote the mean and SD of the German normative data while black vertical lines indicate the mean and SD of the patient cohort. MMQ = Multifactorial Memory Questionnaire.

Figure 5. Association Between Fatigue Scale for Motor and Cognitive Functions (FSMC) Scores and Health-Related Quality of Life (HRQoL)

Scatterplot illustrating the negative correlation between FSMC scores and HRQoL, indicating that higher levels of fatigue as measured by the FSMC are associated with lower perceived quality of life. Each point represents an individual participant's scores. The green line represents the best-fit linear regression line (y = −0.01x + 3.63), with the shaded area depicting the 95% CI for the regression estimate.