A US Case Series of Acute Encephalopathy with Biphasic Seizures and Restricted Diffusion (AESD)

ObjectiveTo understand clinical presentation, interventions, and outcomes among US children diagnosed with acute encephalopathy with biphasic seizures and late restricted diffusion (AESD). BackgroundAESD 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. Design/MethodsWe 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). ResultsTwenty-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. ConclusionsDespite aggressive multimodal therapy, AESD carried a high morbidity rate in this cohort of predominantly young and previously healthy children.