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Rapid Treatment Needed to Reduce Mortality From Flu-Linked Acute Necrotizing Encephalopathy in Children

76 percent of the children in the study had no significant medical history; 27 percent of patients died

By Elana Gotkine HealthDay Reporter

MONDAY, Aug. 4, 2025 (HealthDay News) — Influenza-associated acute necrotizing encephalopathy (ANE) in children is associated with high morbidity and mortality, according to a study published online July 30 in the Journal of the American Medical Association.

In a multicenter case series, Andrew Silverman, M.D., from Stanford University in Palo Alto, California, and colleagues examined the clinical presentation, interventions, and outcomes among U.S. children diagnosed with influenza-associated ANE.

Overall, 41 of 58 submitted cases from 23 U.S. hospitals met the inclusion criteria. The researchers found that 31 cases (76 percent) had no significant medical history and five (12 percent) were medically complex. Clinical presentation included fever, encephalopathy, and seizures (93, 100, and 68 percent, respectively). Fifteen (47 percent) of the 32 patients with genetic testing had genetic risk alleles potentially related to the risk for ANE, including 11 (34 percent) with RANBP2 variants. Only six (16 percent) of 38 patients with available vaccination history had received age-appropriate seasonal influenza vaccination. Most patients received multiple immunomodulatory treatments, including methylprednisolone, intravenous immunoglobulin, tocilizumab, plasmapheresis, anakinra, and intrathecal methylprednisolone (95, 66, 51, 32, 5, and 5 percent, respectively). The median intensive care unit stay was 11 days and median hospital length of stay was 22 days. Eleven patients died (27 percent) at a median of three days from symptom onset, including 91 percent from cerebral herniation. Sixty-three percent of the 27 survivors with 90-day follow-up had at least moderate disability.

“We saw that critical-care management of brain swelling, along with immune modulating therapies such as plasma exchange and intravenous immunoglobin, appeared helpful for patients who recovered,” co-senior author Thomas LaRocca, M.D., Ph.D., also from Stanford University, said in a statement.

Several authors disclosed ties to the pharmaceutical industry.

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