Rare but Severe Flu Complication Affects 27% of Children Despite Intensive Care: Understanding Acute Necrotizing Encephalopathy and Prevention Strategies for the Upcoming Flu Season

Influenza, a common yet serious viral infection, is set to return during the upcoming flu season, typically commencing in October. Last year, an estimated 47 million to 82 million flu cases were reported in the United States between October 2024 and May 2025, resulting in approximately 610,000 to 1.3 million hospitalizations, according to preliminary data from the US Centers for Disease Control and Prevention (CDC).

The elderly are more susceptible to fatalities from flu, but children can also succumb to the illness. The CDC has reported that an average of 37 to 199 child deaths occur per flu season due to complications related to the flu.

Recently, a study published in JAMA focused on a severe complication associated with influenza in children called acute necrotizing encephalopathy (ANE). This condition carries a mortality rate of 27% despite intensive care and treatment, according to the new research.

I sought insights into complications linked to flu, specifically ANE, its implications for children, prevention methods, and key information parents should be aware of as we approach the next flu season. To help address these questions, I spoke with Dr. Leana Wen, a wellness expert at CNN and clinical associate professor at George Washington University.

CNN: What complications can arise from the flu, and who is at higher risk?

Dr. Leana Wen: Most people will recover from the flu without encountering any complications. However, some individuals may develop severe health issues or even die due to complications such as pneumonia, sinus and ear infections, neurological disorders, and worsening of existing medical conditions like heart and kidney diseases.

Individuals over 65 years old, children under 2, and pregnant women are more susceptible to flu complications. Additionally, people with chronic lung disease, diabetes, heart disease, liver disorders, kidney dysfunction, and immune system deficiencies face an increased risk.

CNN: What is ANE, and how common is it?

Wen: Acute necrotizing encephalopathy (ANE) is a rare but severe condition that arises from influenza infection. It causes inflammation in the brain, potentially leading to seizures, impaired consciousness, coma, long-term brain damage, and death.

The exact prevalence of ANE or its recent trends remains unknown. However, it has been most closely linked with influenza, particularly in children.

CNN: What did researchers learn about children with ANE?

Wen: Researchers gathered information from US pediatric hospitals and public health agencies concerning cases of pediatric ANE treated between October 2023 and May 2025. In total, they included 41 children with influenza-related ANE.

The median age of these children was 5, and approximately three out of four were previously healthy. It’s worth noting that only 16% of those for whom vaccination history was available had received the flu vaccine that season.

All patients in this study became severely ill and developed encephalopathy or altered brain function. Sixty-eight percent experienced seizures, and most exhibited abnormalities in their platelet count, liver enzymes, and spinal fluid composition.

Most patients received a combination of treatments, including steroids and immunoglobulins. Out of 41 patients in the analysis, 11 died. The median period between symptom onset and death was just three days; most children who died had severe brain swelling that compressed vital areas responsible for breathing and heart function. All but one of the deceased children had not received the latest flu vaccine. Among the survivors included in the analysis, 63% exhibited at least moderate disability.

The main takeaways are that ANE, although rare, is extremely serious with a high mortality rate and long-term disability risk. Prompt diagnosis and treatment are crucial due to its rapid progression. Second, most children diagnosed with ANE were previously healthy. Third, while some vaccinated children still became ill, the majority of those with ANE and almost all fatalities occurred in unvaccinated individuals.

CNN: How can ANE be prevented?

Wen: The exact cause of ANE remains unknown, nor is it clear whether there are any measures to prevent the condition once someone contracts the flu. However, getting the flu vaccine decreases the risk of contracting the flu and developing severe complications. This JAMA study also suggests that vaccination reduces the likelihood of developing ANE and dying from it. Both the article and its accompanying editorial emphasize the importance of keeping up-to-date with the flu vaccine.

CNN: What else should parents and families know ahead of the next flu season?

Wen: Influenza is a common illness that can lead to serious complications, even in previously healthy individuals. The flu vaccine reduces the risk of contracting the virus and developing complications. The CDC recommends the flu vaccine for virtually everyone aged 6 months and older. Parents should ensure their children receive the flu vaccine annually and encourage other family members to do so as well.

Of course, flu is not the only contagious respiratory illness that can spread during fall and winter months. People with fever and active respiratory symptoms should avoid contact with others, particularly those at higher risk for severe illness. Good hand hygiene and wearing masks in crowded indoor settings can help reduce the spread of contagious diseases.