For most children, influenza (flu) usually means unpleasant symptoms like a fever, sore throat, and achy muscles. But for a small subset of kids, the flu can trigger a rare but serious complication called influenza-associated acute necrotizing encephalopathy (ANE). This form of brain inflammation typically occurs in response to a virus — such as those that cause the flu — and can lead to lasting neurological problems and brain damage. Now, findings of a multicenter study, published today in JAMA, led by Molly Wilson-Murphy, MD , and Rachel Walsh, MD, in Boston Children's Neuroimmunology Center suggest that ANE is often fatal in these children — despite intensive treatment.
Revealing the risks of influenza-associated ANE
During the 2024-5 U.S. flu season, clinicians at large pediatric centers reported an increased number of children with influenza-associated ANE. This anecdotal rise in cases prompted Wilson-Murphy and her colleagues at Stanford University and elsewhere to collect data on pediatric patients who had been diagnosed with ANE between 2023 and 2025.
After analyzing data on 41 patients from 23 U.S. pediatric hospitals, the team found that influenza-associated ANE carried a high risk of morbidity and mortality . Although most children were previously healthy and didn't have a significant medical history prior to diagnosis, Wilson-Murphy and her colleagues found that influenza-associated ANE had a 27 percent mortality rate. Those patients died within an average of just three days of exhibiting symptoms, typically from brain herniation.
Of the 30 children who survived influenza-associated ANE, several still experienced neurological difficulties such as epilepsy three months later. Likewise, just 43 percent had regained the ability to walk unassisted.
"While rare, ANE is potentially devastating and can progress very quickly. It is incredibly important for providers to be able to recognize ANE and to act immediately, as rapid treatment may save lives and minimize long-term difficulties," says Wilson-Murphy. "Vaccination may be important in helping to prevent ANE."
Vaccination remains key
In addition to shedding light on the severity of influenza-associated ANE, the study highlights the importance of vaccinating children against the flu. Of the 41 patients included in the review, only six had received an age-appropriate flu vaccine for the season during which they developed influenza-associated ANE. Only one of the 11 children who died had received a flu shot. These findings support those from previous research, including a large Japanese epidemiologic study, which showed that mass vaccination of school-aged children significantly reduced death from influenza-associated encephalopathy, likely through decreased community transmission.
Along with the role of flu vaccination in prevention, Wilson-Murphy and her colleagues point to the importance of prompt diagnosis and treatment of influenza-associated ANE. Because death occurred quickly in fatal cases, rapid, intense management of the condition — including neuroprotective critical care and immunotherapy — is key.
"There is still so much we have yet to learn about ANE, but we hope this study has helped raise awareness and pave the way for more surveillance and recognition and, ultimately, to advances in treatment," says Wilson-Murphy.
