Pediatric autoimmune encephalitis in Denmark during 2011-17: A nationwide multicenter population-based cohort study

BACKGROUND: The incidence of pediatric autoimmune encephalitis (AIE) is unknown. Our aim was to assess the incidence of pediatric AIE in Denmark 2011-17.

METHODS: In a nationwide population-based setting, we retrieved data on all children tested for AIE before age 18 years. We reviewed medical records in a) children with AIE antibodies (n = 18) to assess whether children fulfilled the AIE consensus criteria, b) children tested negative for AIE antibodies who were registered with an AIE diagnostic code to estimate the incidence of "antibody negative but probable AIE", and c) a reference cohort (n = 596) to determine the positive predictive value of International Classification of Diseases (ICD) codes used for anti-NMDAR encephalitis.

RESULTS: 375 children were tested for AIE 2011-17 (median age 11.1 years; 54% girls); 18 children (5%) had AIE antibodies (percentage tested positive): CSF GAD65-IgG (3.1%), plasma NMDAR-IgG (2.8%), CSF NMDAR-IgG (1.8%), plasma GAD65-IgG (1.0%), and plasma CASPR2-IgG (0.4%). Five children fulfilled the criteria for probably/definite anti-NMDAR encephalitis (incidence: 0.07/100,000 person-years; 95% CI = 0.03-0.17), and 4 children with anti-GAD65 associated AIE (incidence = 0.055/100,000 person-years, 95% CI = 0.021-0.15). The incidence of "antibody negative but probable AIE" was 0.055/100,000 person-years (95% CI = 0.021-0.15). The positive predictive value of ICD diagnostic codes used for anti-NMDAR encephalitis was 8%.

CONCLUSIONS: We diagnosed only children with anti-NMDAR, anti-GAD65, and "antibody negative but probable AIE". Before examining AIE antibodies, clinical presentation, paraclinical studies (CSF, EEG, and MRI), and incidence of pediatric AIEs should be considered. Updating the ICD to include AIE codes is warranted.