Rare flu-linked brain inflammation on the rise in U.S. children, study warns

• New Stanford-led research identifies spike in cases of influenza-linked acute necrotizing encephalopathy (ANE)

• Nearly one-third of affected children died, with most fatalities occurring within 72 hours

• Flu vaccination remains critically low among those afflicted, with prevention key to survival

A devastating but rare complication of influenza is on the rise among children in the U.S., prompting warnings from Stanford Medicine scientists and a call for urgent clinical awareness.

The conditioninfluenza-associated acute necrotizing encephalopathy (ANE)is a swift and often fatal inflammation of the brain triggered by viral infection. A new nationwide study publishedin JAMA reveals a troubling uptick in pediatric ANE cases and underscores the diseases rapid progression and poor outcomes.

The investigation, led by Stanford researchers Molly Wilson-Murphy and Rachel Walsh, along with collaborators at 23 pediatric hospitals, began after an alarming number of children developed ANE during the 20242025 flu season. Their analysis included 41 cases across the U.S., revealing a grim picture: 27% of children diagnosed with ANE died, most within three days of symptom onset due to brain herniationa catastrophic shift of brain tissue.

This disease progresses incredibly fast. You can go from drowsy to life-threatening in just a few hours, said Dr. Keith Van Haren, pediatric neurologist at Stanfords Lucille Packard Childrens Hospital and study co-author.

Lingering neurological damage

Even among the 30 children who survived, the prognosis was often bleak. Just 43% had regained the ability to walk unaided after three months, and many continued to struggle with long-term neurological disorders such as epilepsy. Van Haren likened the recovery process to that of a traumatic brain injury.

Survival, researchers found, hinged on making it through the first seven days post-infection. That first week is really perilous, Van Haren said. Getting kids through it gives them a shot at meaningful recovery.

ANE symptoms often mimic the flu at first, but can quickly escalate. Parents are urged to monitor for sudden drowsiness, behavioral changes, or unresponsivenessall early signs of a potentially deadly neurological shift.

Wilson-Murphy emphasized the importance of fast action. Rapid treatment may save lives and minimize long-term difficulties, she said in a statement. She urged caregivers to seek emergency medical attention if their child seems off during a flu episode.

Flu vaccine shows preventive potential

Though the root cause of ANE remains unknown, the study highlighted one strong correlation: lack of vaccination. Of the 41 children studied, only six had received their seasonal flu shot. Among those who died, just one had been vaccinated.

The authors stress that flu vaccination remains the most effective step in preventing this rare but deadly complication. Theres still so much we need to learn about ANE, Wilson-Murphy said, but awareness, early detection, and prevention through vaccination are our best tools right now.