Tejal Somvanshi
Children with a rare but deadly flu complication now have a better chance of survival if they receive rapid treatment, according to a new Stanford Medicine-led study. The condition, called influenza-associated acute necrotizing encephalopathy (ANE), causes brain swelling and a runaway immune response that can be fatal if not treated quickly.
Frequently Asked Questions
Acute necrotizing encephalopathy (ANE) is a rare but serious complication that can occur following influenza infection. It causes severe brain swelling and a runaway immune response that can be fatal if not treated quickly. This condition primarily affects children and can develop rapidly after initial flu symptoms appear. ANE is characterized by symmetrical lesions in the brain, particularly in the thalamus region, and often leads to seizures, altered consciousness, and in severe cases, coma or death.
ANE is considered rare, but recent research has identified an uptick in cases. A Stanford Medicine-led study identified 41 cases across 23 U.S. hospitals during the 2023-2025 flu seasons, which represents an unusual increase. Typically, medical centers might see only one case every year or two. The condition has a high mortality rate (27% in the study) and significant disability rate among survivors (63% had moderate to severe disability three months later).
Parents should seek immediate medical attention if their child with flu develops any neurological symptoms, including:
- Seizures or convulsions
- Extreme drowsiness or difficulty waking
- Confusion or disorientation
- Severe headache
- Abnormal movements or posturing
- Loss of consciousness
These symptoms may develop rapidly, sometimes within days of initial flu symptoms like fever, cough, and congestion. Early intervention is critical for improved outcomes.
Yes, flu vaccination appears to be highly protective against ANE. The Stanford study revealed that only 16% of children who developed ANE had received their flu vaccine, which is significantly lower than the national pediatric vaccination rate of approximately 50%. Medical experts strongly emphasize that annual flu vaccination is the most effective way to prevent this severe complication. The research shows that vaccination not only reduces the risk of contracting influenza but also helps prevent the development of severe complications like ANE if infection does occur.
Yes, genetic factors appear to play a significant role in susceptibility to ANE. The Stanford study found that nearly half of the tested patients harbored mutations in specific genes (including RANBP2, UNC93B1, and TLR3) that are associated with ANE susceptibility. This suggests that some children may have a genetic predisposition to developing this severe complication when infected with influenza. However, it’s important to note that most children who developed ANE in the study had been previously healthy with no significant medical history, indicating that this complication can affect children without known risk factors.
Treatment for ANE requires immediate intensive care intervention. The study showed that prompt, targeted care in pediatric intensive care units significantly improved outcomes. Treatment approaches typically include:
- High-dose steroids (used in 95% of patients in the study)
- Intravenous immunoglobulin therapy (used in 66% of cases)
- Plasma exchange to remove inflammatory proteins (32% of cases)
- Targeted immunomodulatory drugs like tocilizumab (51% of cases)
- Advanced neurocritical care to manage brain swelling
- Antiviral medications to treat the underlying influenza infection
Early identification and rapid treatment are crucial for improving survival chances and reducing long-term neurological damage.
Researchers analyzed 41 cases of ANE across 23 U.S. hospitals during the 2023–2025 flu seasons, finding the condition more common than previously thought. The study revealed sobering statistics: 27% of affected children died, while 63% of survivors still had moderate to severe disability three months later.
“Acute necrotizing encephalopathy is the most severe flu complication, but it’s only the tip of the iceberg for what flu can do,” said Dr. Keith Van Haren, associate professor at Stanford Medicine and pediatric neurologist. “Flu causes all kinds of complications, including other forms of brain swelling, as well as pneumonia and respiratory failure.
The study found that children receiving rapid care in pediatric intensive care units had better outcomes. Most children developed ANE after experiencing typical flu symptoms like fever, which was present in 95% of cases. Within days, they developed serious neurological problems, including seizures in 68% of patients, followed by brain swelling.
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Doctors used multiple treatments to fight the dangerous brain inflammation, including high-dose steroids (given to 95% of patients), intravenous immunoglobulin (66%), plasma exchange (32%), and medications that target specific inflammatory pathways like tocilizumab (51%).
Genetic testing revealed a significant finding: nearly half of the tested patients carried mutations in genes associated with ANE susceptibility, including RANBP2, UNC93B1, and TLR3. This suggests some children may have a genetic predisposition to this severe complication.
Perhaps most striking was the vaccination gap—only 16% of children who developed ANE had received their flu shot, far below the approximately 50% national vaccination rate for children. This highlights vaccination as a critical preventive measure.
“For doctors, our message is that these kids can recover remarkably well, even if they appear gravely ill early in their course. Don’t give up,” said Dr. Van Haren. “And for parents, it’s: Vaccinate!”
The study’s co-senior author, Dr. Thomas LaRocca, emphasized the importance of specialized care: “It is essential that doctors promptly identify patients with ANE to ensure that these children can receive rapid, intensive care at hospitals that offer advanced neurocritical care and have experts familiar with immunomodulating medications.”
Experts from multiple institutions, including the CDC, are now calling for enhanced prevention, early recognition, standardized treatment protocols, and improved guidelines to address current gaps in care for this serious condition.Parents should be aware of warning signs—a child with flu who develops neurological symptoms like seizures, disorientation, or extreme drowsiness requires immediate medical attention. The researchers hope raising awareness about ANE will help more children receive the rapid intervention they need to survive this dangerous complication.
