• Posted July 31, 2025

Flu-Linked Brain Swelling Is Rare in Kids, But It Can Be Fatal

A life-threatening condition involving out-of-control brain swelling can occur in kids who are battling the flu, but it’s extremely rare. 

A review of recent cases highlights the importance of quick diagnosis and aggressive treatment to saving the lives of kids with the condition, called influenza-associated acute necrotizing encephalopathy (ANE).

“It is essential that doctors promptly identify patients with ANE to ensure that these children can receive rapid, intensive care at hospitals that offer advanced neurocritical care and have experts familiar with immunomodulating medications,” explained co-senior author Dr. Thomas LaRocca. 

He’s a clinical assistant professor and a pediatric critical care medicine specialist at Stanford Medicine and Packard Children’s Health Alliance in Alameda, Calif. 

The research was published July 30 in the Journal of the American Medical Association.

ANE can occur suddenly. 

“It’s similar to the sepsis response, this massive burst of inflammation that becomes its own problem,” LaRocca explained in a Stanford news release.  “It’s like the immune system is going into a panic attack.”

Two main treatments are used to help ease the condition: Steroid therapy to calm the immune system, and a treatment akin to dialysis, in which the child’s blood plasma is removed and replaced with plasma from a healthy donor. 

Between 2023 and 2025, 41 cases of ANE were detected across the United States — an unusually high number that seemed linked to severe flu seasons, the research team said.

In 27% of those cases, the child died, and almost two-thirds of those who survived were still dealing with moderate to severe disability three months later, the researchers found. 

Children hit by ANE averaged 5 years of age and were generally healthy before they became sick with flu. Most (39 of 41) had contracted the influenza A virus, the other two had influenza B.

It’s possible that vaccination might have prevented many of these tragedies: Only six of the 41 patients had gotten that season’s flu vaccine, the researchers noted. 

As ANE set in, all 41 patients experienced brain swelling, most (95%) had fevers and 68% had seizures, their case histories showed. 

The average hospital stay was 22 days, with an median 11 of those days spent in an ICU. (Median means half had longer ICU stays, half shorter.)

ANE claimed the lives of 11 patients, and eight of those fatalities occurred with just eight days of hospitalization.

Of the 30 who survived, 19 patients were able to sit up again three months after they'd fallen sick,16 patients could stand independently and 13 could walk independently.

Only proper diagnosis and care can give families the hope of these recoveries, said study co-senior author Dr. Keith Van Haren.

“For clinicians, the takeaway from our report is that early, intensive management of brain swelling and the immune response really seemed to help children with this condition recover,” he said. Van Haren is a pediatric neurologist at Lucile Packard Children’s Hospital Stanford.

“The number of kids who had pretty good outcomes surprised me; it was better than I thought it would be,” he added. Van Haren noted that ANE is generally regarded by doctors as likely to be fatal.

“We identified ANE patients with a wide range of outcomes, from no residual neurological deficits to, unfortunately, fatal complications,” LaRocca added. “We saw that critical-care management of brain swelling, along with immune modulating therapies such as plasma exchange and intravenous immunoglobin, appeared helpful for patients who recovered.”

Adding in immune-based therapies could be crucial, since the underlying problem in ANE is a runaway immune response, the doctors said.

Of course, prevention is always the best option, and in this scenario that means getting a flu shot.

“For doctors, our message is that these kids can recover remarkably well, even if they appear gravely ill early in their course. Don’t give up. And for parents, it’s: Vaccinate!” Van Haren said.

“Acute necrotizing encephalopathy is the most severe flu complication, but it’s only the tip of the iceberg for what flu can do,” he added. “Flu causes all kinds of complications, including other forms of brain swelling, as well as pneumonia and respiratory failure. Vaccines really do help protect wonderfully against all those complications.”

More information

Learn more about acute necrotizing encephalopathy at Boston Children’s Hospital.

SOURCE: Stanford Children’s, news release, July 30, 2025