AIE is a rapidly progressive encephalopathy caused by antibody-mediated neuroinflammation. It is increasingly recognized in children but diagnosis is challenging before age 18 years owing to a) numerous differential diagnoses, b) low incidence, and c) changes of mood, behavior, and personality, possibly coinciding with puberty. Anti-NMDA receptor (NMDAR) encephalitis is the most frequent AIE in children. Knowledge of incidence of pediatric autoimmune encephalitis is a key component of the pre-test probability of autoimmune encephalitis in children.

To assess the incidence of pediatric autoimmune encephalitis (AIE) in Denmark 2011–17. 

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 with negative AIE antibodies with an AIE code to estimate the incidence of “antibody negative but probable AIE”, and c) a reference cohort (n=578) to determine the PPV of ICD codes for AIE.

 375 children were tested for AIE 2011–17 (median age 11.1 years; 54% girls); 18 children (5%) were AIE antibody positive (proportion of positive tests): 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 antibodies fulfilled the criteria for 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 for anti-NMDAR encephalitis was poor. 

 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.