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CDC Releases Reports of Encephalopathy in Children With Influenza-Associated Mortality
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Key Takeaways
- The 2024-2025 flu season has seen a significant rise in pediatric influenza-associated encephalopathy cases, including severe acute necrotizing encephalopathy.
- ANE is the most severe form of IAE, with high risks of long-term neurological complications and mortality.
The data were released in the CDC’s Morbidity and Mortality Weekly Report.
A report by the CDC highlights an increase in pediatric cases of influenza-associated encephalopathy (IAE), including several deaths from acute necrotizing encephalopathy (ANE), during the 2024–2025 influenza (flu) season. The findings, published in their Morbidity and Mortality Weekly Report (MMWR), contribute to growing concerns about the potential health consequences of severe flu infection as cases in pediatric patients soar across the United States.1
Encephalopathy spelling using wooden blocks | Image Credit: © H_Ko - stock.adobe.com
The 2024-2025 respiratory virus season has been one of the most significant seen in decades, with cases of flu, measles, norovirus, and other seasonal illnesses. As of the CDC’s MMWR ending the week of February 22, 2025, there have been a total of 98 influenza-associated pediatric deaths, and the agency estimates there have been at least 21,000 total deaths overall this season.2,3
Among the 3 primary IAE syndromes, ANE is the most severe and carries a high risk of long-term neurological complications and mortality. Next in severity is acute encephalopathy with biphasic seizures and late reduced diffusion, a condition marked by MRI-detected tissue damage. The mildest form, clinically mild encephalitis or encephalopathy with a reversible splenial lesion, generally has a more favorable prognosis.1
Less commonly, IAE can present as acute encephalopathy with refractory partial seizures or posterior reversible encephalopathy syndrome. The diagnostic criteria for ANE, including influenza-associated cases, are well defined and require a febrile illness preceding or occurring alongside neurological symptoms, rapid neurological decline, and neuroimaging findings showing symmetric lesions in the bilateral thalami and other brain regions.1
Following several anecdotal accounts, the CDC analyzed trends in the proportions of influenza-associated pediatric mortality with IAE from the 2010–2011 through 2024–2025 influenza seasons. Early data for the 2024–2025 season (through February 8, 2025) show that 13% of cases of influenza-associated pediatric mortality had IAE. Of the 1840 pediatric influenza-associated deaths during the 2010–2011 through 2024–2025 seasons, 9% had IAE, ranging from 0% (2020–2021) to 14% (2011–2012 season). The median age of patients with fatal IAE was 6 years, and only 20% had received influenza vaccination.1
The CDC reported that 54% of patients had no underlying medical issues, 20% had received greater than or equal to 1 dose of the current season influenza vaccine more than 2 weeks before illness onset, and 73% received influenza antiviral treatment.1
Timely recognition and intervention are crucial because progression to severe neurologic impairment and death from IAE can occur rapidly following the onset of flu symptoms. Fever and clinically compatible neurologic signs or symptoms, such as seizures, altered mental status, delirium, decreased consciousness, lethargy, hallucinations, or personality changes that last longer than 24 hours, can be indicative of IAE. Pediatric patients with signs of IAE, fast neurologic decline, and neuroimaging showing symmetric lesions affecting the bilateral thalami and other areas of the brain should be evaluated further for ANE.1
The CDC recommends early initiation of antiviral treatment for children at increased risk for influenza-associated complications; however, it is unknown whether antiviral treatment is beneficial for management of IAE.1
The rising incidence of influenza-associated encephalopathy, particularly the severe cases of ANE, underscores the critical need for heightened awareness and early intervention during the ongoing flu season. With pediatric influenza-related deaths already nearing 100 and a significant proportion involving IAE, timely diagnosis and management are essential to reducing morbidity and mortality.
