Influenza can look like a run-of-the-mill childhood illness, but in an occasional patient it can cause a life-threatening illness known as acute necrotizing encephalopathy (ANE). This isn't a normal fever or headache—it's a catastrophic neurologic emergency characterized by out-of-control brain swelling and an incessant immune attack.A new JAMA review illuminates 41 pediatric cases of ANE in the U.S. from late 2023 through spring 2025. In nearly all cases, the patients had previously been healthy before developing acute and severe flu-like symptoms. Of these cases, 27% ended in death, and 63% of survivors had moderate to severe neurologic disability three months after the illness.What Is Acute Necrotizing Encephalopathy (ANE)?ANE occurs when the body’s immune system goes into overdrive during an influenza infection. Dr. Thomas LaRocca, co-senior author of the study and pediatric critical care specialist at Stanford, describes it as “similar to the sepsis response” in which the immune system causes damage to the brain instead of fighting infection.Typically, after a few days of flu symptoms—fever, congestion, vomiting—kids suddenly develop neurologic signs like seizures, altered mental status, or coma. In all 41 cases, children suffered significant brain swelling. 95% had fevers, while 68% experienced seizures.ANE resembles the worst-case scenario of flu complications—fast, deadly, and difficult to treat once it spreads.Pandemic-Level Numbers During Two Severe Flu SeasonsWhile ANE is rare historically, researchers identified 41 confirmed cases across 23 U.S. pediatric hospitals over two flu seasons, an unusually high incidence tied to aggressive influenza activity in 2023–2025.The majority of children were 5 years old, previously healthy, and almost all infections were associated with influenza A (39 of 41), with only two cases attributed to influenza B. Disturbingly, only six children had been vaccinated against the flu that year—fewer than 16%, versus about 55% national pediatric vaccination coverage.This stark gap raises a critical warning: even though ANE is rare, it’s heavily preventable through vaccination.Why Timing and Early Treatment Is Important?ANE progresses quickly. Nearly half of the fatal cases occurred within eight days of hospitalization; survivors spent an average of 22 days in hospital, with 11 days in ICU.Treatment must start fast. As Dr. Keith Van Haren, pediatric neurologist at Stanford and co-author, stresses: early intensive care—combining steroids to calm the immune system and plasma exchange (replacement of a child’s plasma with donor plasma)—can significantly improve chances.Despite ANE’s reputation as nearly always fatal, about 70% of survivors regained some mobility: 19 could sit, 16 could stand, and 13 could walk independently within three months—even after severe brain swelling.Dr. LaRocca and Van Haren also point out that intensive neurocritical care, careful immunotherapy, and early support increase recovery odds even when the diagnosis appears grim.ANE represents just one extreme of flu’s neurological impact. During the 2024–25 season, 13% of pediatric flu deaths involved encephalopathy or encephalitis (IAE), with ANE being the most severe subtype. Historically, the average rate has been around 9% of child flu deaths—ranging from 0% in the mild 2020–21 season to 14% in 2011–12.These statistics remind us that while ANE is rare, brain complications from flu are not negligible—and they disproportionately affect young children under 5.Why Vaccination Is The Best Prevention For Kids?Both experts and study authors emphatically agree: prevention is better than cure.“Vaccinate,” Van Haren said plainly. Not only does the flu shot reduce typical risks like respiratory failure—but it also prevents extreme complications like ANE. For children who survive one episode of ANE, vaccination becomes even more critical to avoid recurrence.Given that only a small fraction of affected children had been vaccinated, these deaths and disabilities were arguably avoidable.What Parents Should Watch For?Here’s what families and healthcare providers should know:Monitor flu symptoms closely—especially in kids who develop neurological signs like confusion or seizures.Act early, don’t wait for symptoms to escalate. Ensure transfer to hospitals equipped for neurocritical care and plasma exchange.Remember that ANE progresses fast—every hour counts.If your child survives, rehabilitation is possible. Many children regain functional abilities despite initial severe outcomes.Don't let hope fade early; survival is real when aggressive care is delivered promptly.The unusual spike in ANE during the 2023–2025 flu seasons serves as a wake-up call to both the medical community and families: even previously healthy children are vulnerable. While ANE remains a rare complication, early recognition and intervention can dramatically alter its course.More broadly, this work underscores the hidden dangers of influenza—and why simple preventive steps matter so much.Flu-Linked brain swelling in children is rare but when it does strike, it can be fatal or leave lifelong disability. Vaccination, vigilant symptom awareness, and rapid access to advanced care are key to prevention and survival. In cases where the immune system spirals out of control, timely and aggressive treatments like steroids and plasma exchange can make the difference between recovery and tragedy.