Rare flu complication causing brain swelling on the rise in kids, study finds

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LOS ANGELES - A rare but deadly flu complication in children—one that causes severe brain swelling and dangerous immune system overreactions—may be survivable with fast, targeted hospital care, according to a Stanford Medicine-led study published July 30 in JAMA.

The condition, known as influenza-associated acute necrotizing encephalopathy (ANE), affected 41 children across 23 U.S. hospitals between 2023 and 2025. ANE is extremely rare but often fatal. More than one in four of the children in the study died, and most survivors faced moderate to severe neurological disability in the months that followed.

Doctors say flu vaccination is critical for preventing such complications.

What is influenza-associated acute necrotizing encephalopathy?

The backstory:

ANE is one of the most severe, known complications of influenza infection. It causes brain swelling and a runaway immune response that can lead to rapid neurological decline and death. The report found that many of the affected children were previously healthy.

• Median age of patients: 5 years
• Virus type: 39 had influenza A, 2 had influenza B
• Vaccination status: Only 6 of 38 with known records had received a flu shot that season

All patients developed brain swelling; 95% had fevers and 68% experienced seizures at onset.

What treatments helped children survive?

What we know:

Of the 41 children studied, 11 (27%) died, most within a week of hospital admission. The rest experienced varying degrees of recovery:

• 63% of survivors had moderate to severe disability at 3 months
• 13 children regained the ability to walk independently
• 16 children could stand unaided
• 19 could sit without assistance

Doctors said aggressive treatment in pediatric intensive care units—particularly at hospitals with neurocritical care teams—was associated with better outcomes.

FILE - A healthcare worker prepares a flu vaccine. A new Stanford-led study urges annual flu vaccination for children to help prevent rare but deadly complications like acute necrotizing encephalopathy.  (Tess Crowley/Chicago Tribune/Tribune News Service via Getty Images)

Therapies included:

• Plasma exchange, to remove inflammatory compounds from blood
• IV immunoglobulin, to modulate the immune response
• Steroids, to reduce brain inflammation

"The number of kids who had pretty good outcomes surprised me; it was better than I thought it would be," said Dr. Keith Van Haren, co-senior author and pediatric neurologist at Stanford. "Don’t give up."

Why is flu so dangerous for children?

Why you should care:

"Flu is notoriously dangerous for kids; it always has been," Van Haren said, especially for children under 5. He stressed that while ANE is rare, flu can also lead to other life-threatening complications, including pneumonia, respiratory failure, and other types of encephalopathy.

Most children in the study had no preexisting health conditions.

What they're saying:

Dr. Thomas LaRocca, co-senior author and pediatric critical care specialist at Stanford, emphasized the importance of doctors recognizing the signs of ANE early. "It is essential that doctors promptly identify patients with ANE to ensure they receive rapid, intensive care," he said.

Following the rise in ANE cases during the severe 2024–25 flu season, researchers launched a nationwide effort to track and study the condition. They hope further research will uncover more about the underlying mechanisms of ANE and improve treatment protocols.

The study included contributions from more than 50 children’s hospitals and academic institutions across the U.S. No external funding supported the study.

Doctors say the most important step for parents is to make sure their children receive annual flu vaccines, which offer strong protection against ANE and other serious complications.

"We want to protect them from the deadly stuff," Van Haren said. "That’s what the vaccine can do."