Neurological and cognitive outcomes after antibody-negative autoimmune encephalitis in children

Aim: To characterize the neurological and cognitive outcomes in children with antibody-negative autoimmune encephalitis (Ab-negative AE).

Method: A cohort of children presenting to our institution over a 10-year period with autoimmune encephalitis was identified by structured retrospective review of medical records. Clinical features at presentation and final follow-up were recorded. Neuropsychological testing was performed in a subset of patients. Outcomes after Ab-negative AE were compared with outcomes after N-methyl-D-aspartate receptor antibody encephalitis (NMDARE).

Results: Forty-four patients (26 females, 18 males, median age 9y 2mo [interquartile range 4y 5mo-11y 8mo], 23 with NMDARE) with a diagnosis of autoimmune encephalitis were included. Postencephalitic epilepsy was more frequent after Ab-negative AE compared to NMDARE (61% vs 14%, p=0.002). Cognitive testing was performed in a subset of patients (n=21; Ab-negative AE=11, NMDARE=10). Full-scale IQ was lower after Ab-negative AE than NMDARE (mean IQ 75 vs 92, p=0.02), primarily because of reduced verbal comprehension index (80 vs 98, p=0.01) and working memory index (77 vs 95, p=0.09). The cognitive function most commonly impaired was executive function (80% [8/10] vs 22% [2/9]).

Interpretation: Ab-negative AE was associated with poorer cognitive outcomes than NMDARE at 1-year follow-up. Further studies are required to evaluate if immunotherapy can be optimized to improve outcome.