Anti-NMDAR encephalitis across the lifespan: Clinical, electrophysiological, and prognostic insights from a Latin American cohort

Abstract

Background and objectives: Anti-N-Methyl-d-aspartate receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis, primarily affecting young females. Its clinical heterogeneity, particularly in underrepresented populations, poses diagnostic and therapeutic challenges. Epidemiological data from Latin America remain limited. This study aimed to characterise the demographic, clinical, and neuroimaging features of NMDARE in Latin American tertiary centres, with a focus on age-related differences.

Methods: A retrospective cohort study included NMDARE cases between January 2016 and December 2024. Inclusion criteria required anti-NMDAR antibody positivity in CSF and/or serum. Demographic, clinical, and paraclinical data were systematically collected. Comparisons between paediatric (<18 years) and adult (≥18 years) patients were conducted using appropriate statistical tests.

Results: Of 1026 screened patients, 58 tested positive for anti-NMDAR antibodies, and 49 met inclusion criteria. Female predominance was higher among adults (61.5 % vs. 30.4 %; p = 0.03). Adults more frequently presented with confusion (57.7 % vs. 13 %; p = 0.003), mood disturbances (61.5 % vs. 26.1 %; p = 0.03), cognitive impairment (76.9 % vs. 36.1 %; p = 0.001), and dysautonomia (19.2 % vs. 0 %; p = 0.04). Speech disturbances (56.5 % vs. 34.6 %; p = 0.02), movement disorders (56.5 % vs 34.6 %, p = 0.06), and EEG abnormalities (69.6 % vs. 42.3 %; p = 0.01) were more frequent in paediatric patients. CSF pleocytosis was independently associated with ICU admission (OR = 11, p = 0.01). Relapse occurred in 10 % of cases.

Discussion: In this Latin American cohort, NMDARE presents distinct age-dependent clinical profiles. While existing diagnostic criteria are broadly applicable, awareness of age-specific features-particularly psychiatric symptoms in adults and EEG abnormalities in children-may improve diagnostic accuracy and guide tailored management strategies. Larger cohort studies in other populations have reported different findings, underscoring the importance of regional studies and the need for additional research to validate and generalize these results.