CDC Reports Largest Pediatric Influenza-Associated Encephalopathy Case Series in 2024-2025 Season

The 2024-2025 US influenza season saw the largest reported case series of children with influenza-associated encephalopathy (IAE) to date, with 109 cases, including 37 with acute necrotizing encephalopathy (ANE), according to a study published in the CDC’s Morbidity and Mortality Weekly Report.1

The 2024-2025 season was historically severe, recording the highest cumulative influenza-associated hospitalization rate since 2010-2011 and the greatest number of pediatric influenza-associated deaths since surveillance began in 2004.2,1 Although no US surveillance system currently exists for neurologic complications of influenza, patients may have been affected by IAE.

IAE refers to neurologic syndromes triggered by influenza virus infection of the respiratory tract, leading to a dysregulated host inflammatory response and varying degrees of brain dysfunction. ANE represents one of the most severe forms of IAE, characterized by rapid neurologic decline and neuroimaging evidence of necrosis or hemorrhage involving the thalami. ANE disproportionately affects children and has a poor prognosis, with a high risk of lasting neurologic sequelae or death.

US pediatric influenza-associated encephalopathy (IAE) cases surged during the 2024-2025 season, highlighting severe health risks and the need for better surveillance. | Image Credit: Dr_Microbe - stock.adobe.com

In January 2025, the CDC was alerted to several deaths among children with influenza-associated ANE.3 Due to the lack of formal surveillance, the agency requested that clinicians and health departments report possible cases of pediatric IAE, including influenza-associated ANE, to better characterize the condition nationwide during the 2024-2025 influenza season.1

The neuroimaging findings and discharge diagnoses for each reported case underwent review by a physician to categorize them as IAE or influenza-associated neurologic disease. IAE cases were further subcategorized as ANE or other IAE.

The CDC received 192 reports that met surveillance criteria. Of these, 109 were classified as IAE, with 37 (34%) subcategorized as ANE and 72 (66%) as other IAE. An additional 82 reports did not meet the IAE criteria and were categorized as other influenza-associated neurologic disease.

Among the 109 IAE cases, the median patient age was 5 years (IQR, 3-10). About half of the patients were female (46%), were non-Hispanic White (52%), and were previously healthy with no underlying medical conditions (55%). At initial assessment, the most common signs and symptoms were altered mental status (88%), respiratory symptoms (87%), and fever (85%).

Additionally, neurologic symptoms commenced a median of 2 days (IQR, 1-3) after illness onset. Neuroimaging was performed in 94% of patients with IAE, with abnormal findings reported in 97% of ANE cases and 49% of other IAE cases.

Influenza antiviral treatment was administered to 84% of patients with IAE, beginning a median of 3 days after illness onset. Among 90% of all patients with IAE, antiviral treatment started on or after the date of hospital admission. Of the 93 patients with available vaccination information, 15 (16%) had received at least 1 dose of the 2024-2025 seasonal influenza vaccine 14 or more days before illness onset.

Regarding hospital care, 74% of all patients with IAE were admitted to an intensive care unit (ICU), 54% received invasive mechanical ventilation, and 19% died. Of the 70 survivors with available discharge data, 47% had not returned to their neurologic baseline.

All 37 patients with ANE were admitted to an ICU, 89% received invasive mechanical ventilation, and 15 (41%) died. Of the 13 survivors with available discharge data, only 1 returned to neurologic baseline at discharge.

The researchers acknowledged several of the report's limitations, including that the cases represented a convenience sample that may not reflect all US IAE cases during the 2024-2025 influenza season. Additionally, the absence of standardized diagnostic criteria for IAE may have led to underdiagnosis, potentially underestimating its true incidence. In response, the CDC is strengthening its surveillance efforts to better understand the nationwide impact of IAE.

“Additional measures are needed to develop and implement surveillance to improve understanding of the incidence, potential risk factors, severity, and public health impact of IAE in the United States,” the authors concluded. “CDC is integrating surveillance for IAE and ANE into existing CDC-sponsored surveillance systems for the 2025-26 influenza season to better understand these serious and potentially preventable complications of influenza.”

References

1. Fazal A, Harker EJ, Neelam V, et al. Pediatric influenza-associated encephalopathy and acute necrotizing encephalopathy — United States, 2024–25 influenza season. MMWR Morb Mortal Wkly Rep. 2025;74(36):556-564. doi:10.15585/mmwr.mm7436a1
2. McCormick B. US flu hospitalizations reach highest levels in over a decade. AJMC®. September 15, 2025. Accessed October 8, 2025. https://www.ajmc.com/view/us-flu-hospitalizations-reach-highest-levels-in-over-a-decade
3. Fazal A, Reinhart K, Huang S, et al. Reports of encephalopathy among children with influenza-associated mortality — United States, 2010-11 through 2024-25 influenza seasons. MMWR Morb Mortal Wkly Rep. 2025;74(6):91-95. doi:10.15585/mmwr.mm7406a3