To characterize neuropsychological profiles and within-patient change in pediatric autoimmune encephalitis (AE), with longitudinal comparison between anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and seronegative cases.

While functional outcomes in pediatric AE are often favorable, prior studies report impairment across cognitive domains inclusive of attention, processing speed, visuospatial skills, and executive functioning. Post-herpes simplex virus (HSV) anti-NMDAR encephalitis cases represent a distinct subgroup with poorer outcomes and more global cognitive impairment. However, comparative longitudinal data across autoantibody subtypes remains limited.

We conducted a retrospective review of pediatric AE cases who underwent standardized neuropsychological testing at a single center. Demographics, clinical, and neuropsychological data were extracted from medical records. Domain-level performance was summarized descriptively.

Of the six patients included, four had anti-NMDAR encephalitis (one post-HSV), and two met the Graus et al. 2016 criteria for possible seronegative AE. Longitudinal comparisons were available for one anti-NMDAR encephalitis case and one seronegative case. Five had pre-existing neurodevelopmental conditions, and three received special education services. Among the three non-post-HSV anti-NMDAR encephalitis cases (ages 5-17; n=3), functional outcomes were generally favorable, but impairments existed in attention, visuospatial, fine motor, and executive functions. The two possible seronegative cases demonstrated favorable functional outcomes with milder cognitive impacts, although one patient exhibited fluctuating performance with disease flare. Available longitudinal data showed partial recovery with domain-level performance reflecting evolving strengths and weaknesses over time. The post-HSV anti-NMDAR encephalitis case with onset at 13 months of resulted in severe, persistent neurodevelopmental impairment and limited functional recovery.

Neuropsychological sequelae after pediatric AE are heterogenous; however, recognizable patterns of deficiencies in attention, processing, visuospatial and executive functioning are prevalent across variable AE subtypes. Longitudinal assessment reveals that cognitive outcomes evolve over time, often with partial yet incomplete recovery. These findings underscore the utility of standardized neuropsychological assessments to guide individualized rehabilitation and educational planning.