Flu and the Brain: Influenza-Associated Encephalopathy in U.S. Children, 2024–25

The 2024–25 flu season was historically severe, with more reported flu deaths in children than in any seasonal epidemic since tracking began in 2004 (excluding the 2009–10 pandemic). In January 2025, CDC heard of several children who had died of a rare, devastating brain complication of flu. A CDC team led by Amara Fazal, working with dozens of state and hospital collaborators, described the cases.

What IAE and ANE are

Influenza-associated encephalopathy (IAE) covers neurologic syndromes triggered by flu infection of the airways: the body's inflammatory response goes awry and impairs the brain to varying degrees. Its most severe form, acute necrotizing encephalopathy (ANE), strikes children disproportionately. It brings rapid neurologic decline, with brain scans showing tissue death or bleeding in the thalami, and often ends in lasting disability or death.

No national surveillance for flu's neurologic complications exists, so on February 28, 2025, CDC asked clinicians and health departments to report cases in children under 18.

The cases

Of 192 reports, 109 met the criteria for IAE — the largest U.S. series of children with IAE reported to date.

Source: CDC, MMWR.

Who was affected. About half the children were girls (46%) and half non-Hispanic White (52%). Most (89%) had influenza A; among those with a known subtype, 63% had A(H1N1)pdm09 and 37% A(H3N2), roughly matching what was circulating nationally.

How it began. The most common signs at first assessment were altered mental status (88%), respiratory symptoms (87%) and fever (85%). Neurologic symptoms began a median of 2 days after the flu started. Nearly all (94%) had brain imaging: abnormal in 97% of ANE cases and 49% of other IAE cases.

Treatment. 84% received flu antivirals, but a median of 3 days after illness began, and 90% only on or after hospital admission. Children with ANE also received corticosteroids (88%), intravenous immunoglobulin (67%), other immune-modulating drugs such as tocilizumab, baricitinib or anakinra (56%), and plasma exchange (44%).

Outcomes. Of 70 IAE survivors with information at discharge, 47% had not returned to their previous neurologic state. Among ANE survivors, only one of 13 had. ANE survivors spent a median of 30 days in the hospital; children who died of ANE did so a median of 4 days after admission.

Pediatric IAE cases reported to CDC, 2024–25. Credit: CDC, MMWR.

What it means

• Any child can be affected. More than half these children had no underlying conditions.
• Clinicians should think of IAE in children with encephalopathy or reduced consciousness and a recent or current fever while flu is circulating.
• Vaccination. Since 2010, CDC and its Advisory Committee on Immunization Practices have recommended a flu vaccine every year for everyone 6 months and older. Vaccination prevents flu, lessens its severity — including critical, life-threatening illness — and cuts children's flu hospitalizations and emergency visits. Yet children's flu vaccination rates have declined in recent years, and only 16% of eligible children in this series had been vaccinated.
• Early antivirals. Few children got oseltamivir before admission. Antivirals are recommended as soon as possible for outpatients at high risk of complications, and may be considered for others. Whether they affect IAE is unknown, but in one study, oseltamivir for outpatients aged 5–17 was linked to fewer hospitalizations for serious neuropsychiatric events, including seizures, altered mental status and encephalitis.

A separate U.S. case series of 41 children with flu-associated ANE over the 2023–24 and 2024–25 seasons found similar patterns: 16% vaccinated, 76% with no significant medical history and 27% dying within days of symptom onset. The two studies may overlap, by an amount that cannot be measured.

Limitations

The cases were a convenience sample and may not represent all U.S. cases; with no standard diagnostic criteria, IAE is likely underdiagnosed and undercounted; and data came from medical records abstracted onto report forms.

Sources

Based on Fazal A, Harker EJ, Neelam V, et al., "Pediatric Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy — United States, 2024–25 Influenza Season," MMWR, Centers for Disease Control and Prevention; a work of the United States government in the public domain.