Influenza-Associated Acute Necrotizing Encephalopathy in US Children

Question  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?

Findings  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.

Meaning  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.

Importance  Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective  To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.