Influenza-Associated Acute Necrotizing Encephalopathy in US Children

What were the clinical characteristics, management approaches, and outcomes among children with influenza-associated acute necrotizing encephalopathy (ANE) in the US during the 2023-2024 and 2024-2025 influenza seasons?In this multicenter case series of 41 children from 23 US hospitals, influenza-associated ANE carried a 27% mortality rate despite multimodal therapy. Most patients (76%) had no significant medical history, despite 15 of 32 tested (47%) having genetic risk alleles potentially related to risk of ANE identified during diagnostic evaluation. The H1 2009 influenza A strain predominated (34% of cases), and only 16% had received seasonal influenza vaccination. Among survivors, 63% had moderate to severe disability at 90-day follow-up.Influenza-associated ANE represents a rare but devastating neurologic complication primarily affecting previously healthy children. The high morbidity and mortality emphasize the need for prevention, early recognition, intensive treatment, and standardized management protocols.

Corresponding Author: Andrew Silverman, MD, MHS, Pediatric Neurology, Stanford University, 730 Welch Rd, Second Floor, Palo Alto, CA 94304 (Aesilver@stanford.edu).

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