Surge in Rare Pediatric Brain Disorder Linked to Flu Season

A surge in a rare but devastating neurological condition in children has been linked to the 2024-2025 flu season, according to a nationwide study published in JAMA.

Acute necrotizing encephalopathy (ANE), an autoimmune brain disorder triggered by viral infections, is characterized by rapid deterioration of brain function following an illness. The damage, which can involve brain swelling, bleeding, and tissue death (necrosis), is not from the viral invasion itself, but the body’s intense immune response.

During the 2024–2025 U.S. influenza season, pediatricians across the country reported a surge in ANE cases, which prompted the current study, said Kavita Thakkar, MD, assistant professor of Pediatrics in the Division of Neurology and Epilepsy, who was a co-author of the study.

In the study, 23 hospitals across the U.S. identified 41 confirmed cases in children, most of whom were previously healthy and under the age of 8.

“Acute necrotizing encephalopathy is a severe autoimmune neurological condition,” Thakkar said. “At our institution, we had a patient with this condition, and similarly, cases were observed at other institutions in the 2024–2025 influenza season. This prompted a national investigation.”

The study aimed to understand the clinical presentation, risk factors, treatment strategies and outcomes of children diagnosed with influenza-associated ANE. After analyzing the cases, investigators found that 93 percent of patients presented with fever, all experienced encephalopathy and 68 percent had seizures. Most were infected with influenza A, and only 16 percent of those with available records had received the seasonal flu vaccine.

“This study looked at 41 cases across multiple institutions across the U.S. over two influenza seasons,” Thakkar said. “The majority of affected children were between 2 and 5 years of age. One-third of them had a mutation in a gene called RANBP2, which makes them vulnerable to developing this condition.”

The outcomes were sobering. More than a quarter of the children died within days of symptom onset. Among survivors, nearly two-thirds were left with moderate to severe neurological disabilities, according to the findings.

The findings also underscore the importance of flu vaccination and rapid intervention, especially in young children, to prevent such catastrophic outcomes, Thakkar said.

“The study found a high mortality rate in this condition, and even the ones who survived had severe residual neurological disability,” Thakkar said. “One interesting finding was that amongst the cases observed, the majority had not received the seasonal influenza vaccine, so this may serve as a preventive strategy.”

Treatment approaches varied, with most patients receiving a combination of immunomodulatory therapies including steroids, IVIG and biologics.

The study highlights the need for greater awareness among clinicians and standardized treatment protocols, Thakkar said, which may serve as directions for future research.

“This study serves as a good background to recognize this condition as a severe complication of influenza,” Thakkar said. “Early recognition and prompt imaging and treatment should be performed in children who have Influenza-associated encephalopathy or brain dysfunction.”