Although the 2024–25 influenza season officially wound down in late spring 2025, warning signs of its impact on children emerged much earlier. In late January 2025, clinicians around the country began reporting unusually severe neurologic complications—including fatal cases of acute necrotizing encephalopathy (ANE)—in children hospitalized with influenza. These early alerts prompted the U.S. Centers for Disease Control and Prevention (CDC) to conduct a rapid assessment, summarized in a February 2025 Morbidity and Mortality Weekly Report (MMWR), which flagged a rising share of influenza-associated pediatric deaths that involved encephalopathy.
By the time the full flu season concluded in spring, a more comprehensive national analysis—published in September 2025—confirmed just how severe the burden had been. The retrospective CDC report documented 109 pediatric cases of influenza-associated encephalopathy (IAE), including 37 cases of ANE, and underscored that the 2024–25 season recorded the highest number of influenza-associated pediatric deaths since national tracking began in 2004.
Because no dedicated national surveillance system yet exists for these neurologic complications, CDC had to combine ongoing pediatric mortality data with outreach to state and local health departments and hospitals to capture cases. Analyses such as these typically take months after a season ends to allow time for case reporting, data validation, and review of hospital and laboratory records—explaining why the full picture of this crisis has only recently come into focus.
This retrospective analysis underscores both the heavy toll of the 2024–25 flu season and the longstanding gaps in pediatric influenza vaccination and neurologic surveillance. While influenza’s respiratory complications are well known, its potential to trigger sudden, life-threatening brain inflammation often remains underrecognized by both clinicians and families.
Understanding IAE and ANE
For non-clinicians, influenza-associated encephalopathy (IAE) refers to a spectrum of brain dysfunction that occurs when an influenza infection—typically confined to the respiratory tract—triggers an intense immune response that affects the brain. Children with IAE may develop sudden confusion, seizures, hallucinations, or loss of consciousness, sometimes only a day or two after the onset of typical flu symptoms like fever or cough.
A particularly severe form, acute necrotizing encephalopathy (ANE), involves widespread inflammation and damage—sometimes including hemorrhage—in deep brain structures such as the thalami. ANE often progresses rapidly, leading to critical illness, prolonged hospitalization, long-term neurologic impairment, or death. Although ANE is rare, it is disproportionately seen in children and carries a high fatality rate.
These conditions are not caused by direct invasion of the brain by the flu virus but by the body’s dysregulated inflammatory response. This distinction is important because it underscores that even children without underlying health problems can be affected.
A Season of Historic Pediatric Losses
The 2024–25 influenza season was notable not only for its high overall severity but also for the highest number of influenza-associated pediatric deaths recorded during any seasonal flu epidemic since tracking began, apart from the 2009 H1N1 pandemic. IAE, though relatively rare, emerged as a key driver of critical illness and mortality.
Of the 109 pediatric IAE cases identified nationwide:
- 74% required intensive care,
- 54% needed invasive mechanical ventilation, and
- 19% of all IAE patients died.
Children with acute necrotizing encephalopathy (ANE) faced even graver outcomes: 41% succumbed to their illness, and among survivors, nearly all experienced persistent neurologic deficits at hospital discharge.
Who Was Affected — And How
IAE disproportionately affected young children: the median age was just 5 years, and more than half of those affected were previously healthy. Neurologic symptoms—primarily altered mental status, seizures, and hallucinations—typically appeared within two days of initial flu symptoms, often signaling rapid disease progression.
For ANE patients, the median age was 4 years. Seizures were observed in 87% of these cases, compared to 45% in children with other forms of IAE. ICU admission was universal for ANE patients, and nearly 90% required mechanical ventilation. The median hospital stay among survivors stretched to 30 days, underscoring the intensive and prolonged care needs for these critically ill children.
Vaccination Gap Leaves Children Vulnerable
Perhaps the most striking finding was the low uptake of seasonal influenza vaccination: among vaccine-eligible children with IAE, only 16% had been vaccinated against flu that season. For those with ANE, the figure was slightly lower, at 13%.
Annual flu vaccination has been shown to reduce both the risk and severity of influenza illness, including life-threatening complications in children. However, vaccination rates among U.S. children have declined in recent years, leaving many at risk for preventable outcomes. This gap highlights an urgent need for renewed vaccination outreach, especially ahead of severe flu seasons.
Treatment and Supportive Care
While most hospitalized children (84%) received influenza antivirals—typically initiated a median of 3 days after symptom onset—only 10% began treatment prior to hospitalization. Among ANE patients, the majority also received corticosteroids (88%), intravenous immunoglobulin (67%), or other immunomodulators, reflecting the complexity of managing this aggressive neurologic syndrome.
Early antiviral initiation remains critical for reducing complications in children at high risk, though its role in preventing or mitigating IAE specifically remains unclear. The CDC report notes the need for more research into whether early treatment influences neurologic outcomes.
Public Health Implications: Surveillance and Clinical Awareness
The CDC’s investigation revealed another critical gap: the absence of standardized national surveillance for influenza-associated neurologic complications. Without a dedicated system, cases of IAE often go underrecognized and underreported.
For frontline clinicians, heightened vigilance is essential during influenza season. Children presenting with fever, altered mental status, or seizures should prompt consideration of IAE, rapid initiation of antivirals, and early escalation to intensive care when warranted.
Parents and caregivers should be aware that influenza can present with sudden neurologic signs—an urgent warning that demands immediate medical evaluation.
Looking Forward: Bridging the Gaps
CDC has announced plans to integrate IAE and ANE surveillance into existing influenza tracking systems for the upcoming 2025–26 season—a significant step toward understanding the true burden of these complications and refining prevention strategies.
For policymakers and healthcare systems, the findings underscore the importance of robust vaccination campaigns, rapid antiviral access, and greater investment in pediatric neurocritical care capacity during peak flu seasons.
The 2024–25 season’s toll on children and families offers a sobering reminder: influenza remains far from a routine illness, and protecting children will require a combination of vigilant clinical recognition, improved vaccination coverage, and enhanced national surveillance.
The study’s authors represent a wide-ranging collaboration across U.S. federal, state, and academic institutions. Lead investigators came from the CDC’s Influenza Division within the National Center for Immunization and Respiratory Diseases, alongside colleagues from the Epidemic Intelligence Service and the Career Epidemiology Field Officer Program. Additional contributors included teams from more than 25 state and territorial health departments, major pediatric and academic medical centers such as Children’s Hospital Colorado, Riley Hospital for Children at Indiana University Health, Cincinnati Children’s Hospital Medical Center, Boston Children’s Hospital, Vanderbilt University Medical Center, Washington University School of Medicine, Stanford University, and others, reflecting a nationwide effort to capture and analyze cases of pediatric influenza-associated encephalopathy and acute necrotizing encephalopathy.
Read the full paper.
Disclaimer: This article is for informational purposes only and is not intended to provide medical advice, diagnosis, or treatment. Readers should consult a qualified healthcare professional for medical concerns.