Autoimmune encephalitis in older adults: Atypical presentation, therapeutic approaches and implication for diagnostic criteria.

INTRODUCTION: Autoimmune encephalitis (AE) is a complex neurological disorder characterized by inflammation of the brain triggered by the immune system. Emerging evidence suggests that age may influence disease presentation, antibody profiles, treatment responses, and outcomes in AE. This study investigates age-related differences in AE by analyzing clinical features, diagnosis, treatment patterns, and outcomes between cohorts of younger and older adults. METHODS: A retrospective observational study was conducted on AE patients diagnosed between January 2005 and December 2022 at two academic medical centers. Patients were categorized into younger adults (<65 years) and older adults (≥65 years). Clinical characteristics, antibody profiles, treatment modalities, and outcomes were compared between the two groups. RESULTS: In our retrospective cohort of 183 AE patients, 23% (n = 42) were older adults. In comparison to younger adults, they were more likely to be non-Hispanic White (80.9% vs. 52.8%, p < 0.001) and have a Charlson comorbidity index (CCI) >2 (p < 0.001), but less likely to present with headache (6.9% vs. 42.4% p < 0.001), sleep disturbances (p = 0.034), and in subacute fashion (14.6% vs 32.1%, p = 0.029). Older adults had a lower prevalence of CSF pleocytosis (p < 0.001). Younger adults had a higher proportion of anti-NMDAR encephalitis, while older adults were more likely to have anti-LGI1, and anti-CASPR2 antibody encephalitis. Older adults with a positive antibody status were less likely to meet probable antibody-negative AE clinical consensus criteria (9.5% vs 34.2% p = 0.027). In terms of treatment and outcome, older adults were less likely to receive second-line immunotherapy (7.1% vs 32.8%, p < 0.001), and have a longer median length of stay (19 vs 10 days p = 0.042). After eliminating antibody status in a secondary analysis, older adults were less likely to present with headache (OR 10.9, p = 0.002), meet probable antibody-negative clinical consensus criteria (OR 9, 0.014), and receive second-line immunotherapy (OR 4, p = 0.038). CONCLUSION: Older adults with autoimmune encephalitis are less likely to have headaches and CSF pleocytosis, even though they have similar outcomes to younger adults. Diagnostic criteria may need to be modified for older adults, and future research should explore treatment options specific to their age group.