Longitudinal Disability, Cognitive Impairment, and Mood Symptoms in Patients With Anti-NMDA Receptor Encephalitis

Abstract

Background and Objectives Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures. Methods This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores. Results Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1–75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1–9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3–5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6–17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51–174), median/mean mRS and CASE were 2 (IQR = 1–3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02–30.9, p = 0.047). Despite both mRS and CASE improving from baseline (p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric). Discussion Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.