Symptom evolution, persistence, and pharmacological management in paediatric NMDA receptor antibody encephalitis

To characterise symptom onset, progression, and persistence in paediatric N-methyl-D-aspartate receptor antibody encephalitis (NMDARE) using the Paediatric Autoimmune encephalitis Severity Scale (PASS), and to describe real-world symptomatic pharmacological management.

We performed a retrospective study of children (<18 years) with confirmed NMDARE admitted to two tertiary centres (2012-2024). Disease severity was assessed using the modified Rankin Scale (mRS) and PASS at nadir, discharge, one year, and last follow-up. Symptomatic treatments and their timings, clinician-rated benefits and adverse events were recorded, with adverse event:benefit ratios calculated.

Thirty-five patients were included (median age 8 years [IQR 4-13]; 71% female). Median peak severity was mRS 5 and PASS 22/30. Seizures and psychiatric manifestations were the most frequent presenting symptoms, whereas movement disorders, motor deficits, and autonomic dysfunction typically appeared later. Younger children (<12 years) presented with a more florid neurological picture, whereas older patients more often presented with psychiatric features; both groups progressed to similar multisystem severity at nadir. At one year, 68% achieved mRS 0-1 (median PASS 3/30), increasing to 87% at last follow-up (median 5 years). PASS identified persistent impairments in activities of daily living (26%), speech/communication (17%), and sleep (14%) at last follow-up. Symptom-directed treatments showed high perceived benefit across drug classes; second-generation antipsychotics were generally well tolerated, except risperidone, which showed higher adverse event rates.

Persistent neurocognitive and functional deficits are common following NMDARE, captured better by PASS than mRS. Symptom-directed treatments showed overall favourable tolerability, with second-generation antipsychotics except risperidone demonstrating good safety.