To understand clinical presentation, interventions, and outcomes among US children diagnosed with acute encephalopathy with biphasic seizures and late restricted diffusion (AESD).

AESD is a rare but severe neurologic condition for which epidemiologic and management data remain limited. Here we report the largest US case series to date.

We conducted a retrospective multicenter case series of children diagnosed with AESD with longitudinal follow-up. Inclusion/diagnostic criteria included diffusion restriction in subcortical white matter, fever, and encephalopathy (Sakuma et al 2024).

Twenty-five cases (14 female; median age 21 months, range 2-153) from 9 US hospitals are presented. Seventeen (68%) had no significant past medical history; 8 (32%) had a history of seizure or developmental delay. Of the 16 patients with imaging available from day 1-2 of fever onset, 6 (37.5%) did not show emergence of diffusion restriction until after day 3. Seizures were seen in all but one patient, with status epilepticus in 18 (72%) and a biphasic course of seizures in 18 (72%). The median AESD severity score (Tada et al 2015) was 5 (1-7). A triggering infection was identified in 19 patients (76%), with all but one being viral. Seventeen (68%) patients had systemic complications including transaminitis, respiratory failure, shock, acidosis, thrombocytopenia, and coagulopathy. Twenty-three patients (92%) received acute phase immunomodulatory treatments, with methylprednisolone in 22 patients (88%) and intravenous immunoglobulin (IVIg) in 18 (72%). Eight patients (32%) received escalating immunotherapy including anakinra, tocilizumab, and plasmapheresis. At discharge 17 of 23 patients with available data (73.9%) had moderate disability (mRS ≥3).

MRS obtained at discharge, 6 month follow up, and most recent follow up was not predicted by age at presentation, AESD risk score, or immunotherapy regimen.

Despite aggressive multimodal therapy, AESD carried a high morbidity rate in this cohort of predominantly young and previously healthy children.