JAMA

Rare flu-linked brain disorder associated with high mortality in U.S. children

August 4, 2025

Study details: A multicenter case series identified 41 pediatric patients with influenza-associated acute necrotizing encephalopathy (ANE) across 23 U.S. hospitals during the 2023–2024 and 2024–2025 influenza seasons. Inclusion required acute encephalopathy or seizures, positive influenza testing, and characteristic neuroimaging (notably thalamic lesions). Data were collected via medical record review and clinician documentation, with follow-up to 90 days post-illness.

Results: Most affected children were previously healthy and unvaccinated. Clinical features included rapid onset of severe encephalopathy, seizures, elevated liver enzymes, thrombocytopenia, and elevated CSF protein. Neuroimaging consistently showed multifocal lesions with prominent thalamic and frequent brainstem involvement. Mortality was high, with deaths typically occurring within three days of onset due to cerebral herniation. Among survivors, significant neurologic sequelae were common at short-term follow-up. Genetic variants (e.g., RANBP2) were identified in a subset, suggesting host susceptibility.

• Clinical presentation: 93% had fever, 100% had encephalopathy, 68% experienced seizures, and 76% had no significant medical history
• Vaccination status: Only 16% had received age-appropriate seasonal influenza vaccination
• Outcomes: 27% died (median 3 days from onset); 63% of survivors had moderate to severe disability at 90 days

Clinical impact: Influenza-associated ANE is a rare but catastrophic complication, often affecting previously healthy, unvaccinated children. Early recognition, prompt neuroimaging, and intensive management are critical, though optimal treatment protocols remain undefined.

Source:

Influenza-Associated Acute Necrotizing Encephalopathy (IA-ANE) Working Group; Silverman A, et al. (2025, July 30). JAMA. Influenza-Associated Acute Necrotizing Encephalopathy in US Children. https://pubmed.ncbi.nlm.nih.gov/40736730/