Preliminary follow-up data of an Italian multicenter cohort of paediatric anti-N-methyl-D-aspartate receptor encephalitis

Objective: To provide data on long-term follow-up of a cohort of children with anti-NMDAR encephalitis, focusing on disease course and outcome, with respect to treatment received. Methods: Data were collected through a questionnaire sent to the main Italian paediatric neurology centres, including both follow-up data of patients reported in the first Italian multicenter series of paediatric anti-NMDAR encephalitis in 2015, and new cases. Results: 35 children with anti-NMDAR encephalitis, from 14 Italian centres, were included (22 females; median age at onset 9.1 years, range 1.2-17.7). Prodromal symptoms occurred in 32.3% cases, behavioural/psychiatric disturbances in 100%, movement disorder in 100%, language disturbances in 97.1%, hyporeactivity/vigilance disturbances/catatonia in 91.4%, epileptic seizures in 85.7%, sleep disturbances in 78.8%, dysautonomias in 71.4%. Dysautonomias were more frequent in patients 12 years old than in younger children (90.9% vs. 62.5%, respectively). In the acute phase, median mRS in the whole cohort was 5 (range 3-5). All patients had positive anti-NMDAR antibodies in serum and/or CSF; tumour was detected in 1. All patients received first-line immune therapy, whereas second-line treatments were used in 45.7% at first event. 22.8% patients relapsed. Median mRS at follow-up was 1 (range 0-5) (length of follow-up: median 22 months, range 4-137). In the patients previously reported in 2015, there was a slight improvement in outcome with longer follow-up (mRS 0: 55.5% vs. 77.8%, respectively). Patients who received second- line immune therapy at the first episode of anti-NMDAR encephalitis were less likely to relapse than those who only received first-line treatments (6.2% vs. 36.8%, respectively). Conclusions: In our cohort, dysautonomias are more frequent in older children, and outcome tends to improve with time. Our data suggests that the use of second-line immune therapy reduces the rate of relapse in paediatric anti-NMDAR encephalitis. This represents to date the largest Italian series on paediatric anti-NMDAR encephalitis.