Long-Term Outcomes in Autoimmune Encephalitis

Abstract

Background and Objectives Autoimmune encephalitis is a rare disease associated with considerable morbidity in the acute phase of the disease. Nationwide cohort studies investigating long-term cognitive outcomes are rare. Furthermore, although bedside cognitive assessments are frequently used in clinical practice to evaluate patients with AE, there is currently no consensus on the optimal test for this purpose. Using the unique Danish centralized antibody testing setup, we identified an unselected, nationwide AE cohort. We then performed a comprehensive evaluation of long-term cognitive outcomes. Methods All adult patients with seropositive AE diagnosed in Denmark from 2009 to 2022 were identified and invited to participate in the study. Participants underwent neuropsychological testing and bedside cognitive testing (Montreal Cognitive Assessment [MoCA], Mini-Mental State Examination [MMSE], Addenbrooke’s Cognitive Examination [ACE], and Frontal Assessment Battery [FAB]). Fatigue, depression, anxiety, life satisfaction, and quality of life were assessed using questionnaires. Results We included 86 of 108 eligible patients. The median time from symptom onset to participation was 77 months (interquartile range 35/125). All patients with anti-N-methyl-D-Aspartate receptor (NMDAR) encephalitis (NMDARE) (n = 33) and 86% of patients with limbic encephalitis (n = 37) obtained modified Rankin Scale (mRS) 0–2 at the time of testing, while 45% of patients with NMDARE and 43% of limbic encephalitis had multidomain cognitive deficits on formal neuropsychological testing. Memory, visuoconstruction, and executive function were the most affected cognitive domains. Postencephalitic dementia was present in 15% of the cohort, affecting primarily patients with limbic encephalitis, and was associated with higher mRS at peak disease, older age at disease onset, and relapsing disease. The MoCA had the strongest correlation with mean neuropsychological z-score and had the highest sensitivity and specificity for detecting cognitive impairment among patients with NMDARE and limbic encephalitis, when compared with the other bedside cognitive screening tools. There was a high prevalence of fatigue (38% NMDARE and 29% limbic encephalitis), and overall life satisfaction correlated strongly with both fatigue and depression scores in both groups. Discussion Long-term cognitive impairment and fatigue were prevalent in AE, despite good functional outcomes as measured by the mRS. The MoCA correlated well with neuropsychological performance and could be the bedside test of choice if a neuropsychologist is not readily available.