By Heidi Splete

Reports of children in the United States with influenza-associated encephalopathy or encephalitis (IAE) increased from none during the 2020-2021 flu season to a preliminary 14% for the 2024-2025 season, based on a new analysis from the Centers for Disease Control and Prevention (CDC).

IAE involves a range of neurologic syndromes triggered by flu infection of the respiratory tract, with diagnosis based on brain lesions detectable on imaging, wrote Amara Fazal, MD, and colleagues at the CDC’s National Center for Immunization and Respiratory Diseases.

A series of anecdotal reports of pediatric cases with IAE in January 2025 prompted the CDC’s investigation; the findings were published in the Morbidity and Mortality Weekly Report (MMWR).

IAE is potentially fatal but rare, and no national surveillance exists for the condition specifically. The researchers reviewed data from the Influenza-Associated Pediatric Mortality Surveillance System for flu seasons from 2010-2011 to preliminary data from 2024-2025.

No pediatric influenza deaths with IAE were identified during 2020-2021, but the median proportion was 9% across the study period. Preliminary data through February 8, 2025, showed that nine of 68 pediatric flu deaths (13%) involved IAE, including four with acute necrotizing encephalopathy (ANE).

The findings were limited by several factors including the potential over- or underestimation of cases, incomplete data for the current season, and lack of data on the prevalence of IAE overall, such as less severe cases, and the inability to compare ranges of illness over time because of the absence of established surveillance, the researchers wrote.

However, the results suggest that clinicians consider IAE in children with febrile illness and neurologic symptoms compatible with IAE, the researchers noted. These symptoms include “seizures, altered mental status, delirium, decreased level of consciousness, lethargy, hallucinations, or personality changes lasting more than 24 hours,” they wrote. Influenza-associated ANE should be considered in children with IAE symptoms accompanied by rapid neurological decline and lesions on imaging, they added.

“CDC has posted a national call for possible pediatric IAE cases identified during this influenza season on EPI-X and can be contacted at severeflu@cdc.gov,” the researchers wrote.

View From the Clinic

“Currently, influenza related death is reported to Centers for Disease Control and Prevention, but severe manifestations of influenza such as IAE that may significantly harm people without causing death are not tracked,” said Lori Handy, MD, MSCE, associate director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, and assistant professor of clinical pediatrics at the Perelman School of Medicine, Philadelphia, in an interview.

“Understanding the epidemiology of circulating infectious diseases and sharing that with the healthcare community helps clinicians better identify what might be impacting a given patient they are seeing,” Handy said. “When that infectious disease is vaccine preventable, it is critical that both healthcare providers and the public understand the whole spectrum of the disease to better appreciate the value and importance of getting vaccinated,” she added.

Although IAE is a known complication of flu infection, it is rare, and many healthcare providers may be unfamiliar with it, Handy said. “The MMWR publication alerts providers during this flu season to help them make this diagnosis more rapidly and be able to provide the best evaluation and treatment for their patients,” she noted.

Stay Vigilant to Potential for IAE

“During influenza season, consider IAE in children with febrile illnesses and neurologic signs or symptoms as outlined in the MMWR: Seizure, change in mental status, delirium, decreased level of consciousness, lethargy, hallucinations, or personality changes lasting > 24 hours,” said Handy. “Consider ANE if there are also compatible changes on neuroimaging, and when these diagnoses are being considered, begin antiviral therapy,” she said.

“We need to best understand the full spectrum of disease, not just those cases that result in death,” said Handy. “Providers can help by identifying and reporting cases so that we can have a better understanding of how often this is occurring, and then studies to identify optimal strategies for prevention and treatment can occur,” she said.