Influenza-associated acute necrotizing encephalopathy carries a high morbidity and mortality rate among children but flu vaccination, early detection, and a standardized treatment approach may prevent the condition.
RT’s Three Key Takeaways:
- Severe Outcomes in Children — Influenza-associated acute necrotizing encephalopathy (ANE) carried a 27% mortality rate and left most survivors with moderate to severe disability, even with aggressive treatment.
- Low Vaccination Rates — Only 16% of affected children had received a flu shot, highlighting influenza vaccination as a key preventive measure against the most severe ANE cases.
- Opportunities for Prevention — Researchers stress that early recognition, timely intervention, and standardized treatment approaches, combined with higher flu vaccination rates, are critical to reducing ANE’s devastating impact.
Researchers found that even with aggressive treatment strategies, influenza-associated acute necrotizing encephalopathy carries a high morbidity and mortality rate among children, according to a new study published in JAMA.
Findings also pointed to influenza vaccination, early detection of illness, and a standardized approach to treatment as potential opportunities to prevent this condition.
A newly published multisite research study involving Jonathan D. Santoro, MD, Director of the Neuroimmunology Program within the Neurological Institute at Children’s Hospital Los Angeles, investigates the severity and treatment effectiveness for influenza-associated acute necrotizing encephalopathy, a devastating neurologic condition that can follow an influenza infection in rare cases. Dr. Santoro leads the Strategic Therapies for Overcoming Reactive iMmunology (STORM) Lab at CHLA. He and his team participated in this study, along with CHLA’s Neurocritical Care specialists.
Influenza-associated encephalopathy comprises a variety of neurologic syndromes, which can include cognitive disfunction (encephalopathy), inflammation in the brain, and the death of cells in the brain, also known as necrosis. Acute necrotizing encephalopathy (ANE) is the most severe type of influenza-associated encephalopathy and has been known to disproportionately impact children.
“Although anyone can be affected by influenza-associated ANE, children seem to be more commonly affected and often have more severe outcomes,” Dr. Santoro explains. “Studying rare diseases is very complicated and requires many different centers, and that was why collaboration was key in this project.”
While influenza is the most common virus known to trigger ANE, others include SARS CoV-2 and human herpesvirus 6. Certain genetic variants are associated with ANE, but the condition’s underlying mechanisms are not fully understood and optimal treatment strategies have not been developed. The study involving Dr. Santana and his team explored data from cases of influenza-associated ANE among U.S. children during the past two flu seasons to better understand outcomes and effective interventions.
Specifically, this new study gathered data from 23 different hospitals across the U.S. on 41 children between 0 and 18 years of age who developed influenza-associated ANE. These data included influenza test results, neuroimaging findings, inflammatory genetic markers, and particular clinical symptoms. Researchers also analyzed each patient’s vaccination history, genetic and laboratory findings, treatment interventions, length of hospital stay, and clinical and functional outcomes.
Among these patients, scientists determined that influenza-associated ANE had a 27% mortality rate, even with aggressive treatment strategies utilizing multiple therapeutic methods. Most of the patients were treated with several immunomodulatory treatments, such as methylprednisolone and intravenous immunoglobulin, which are designed to modify the body’s immune response to infection.
The researchers established that most of the patients did not have a notable medical history involving other infections or conditions. However, genetic testing revealed that patients had a high rate of ANE risk alleles, or genetic variations known to increase the risk of ANE.
Also, a majority of these patients had the H1/2009 influenza A strain, and only 16% of them had previously received seasonal flu vaccination. This was much lower than the national pediatric flu vaccination rates during this period.
Additionally, the researchers examined outcomes for the patients at several points following the onset of their symptoms. Of the 41 patients observed in the study, 11 died due to their illness. And of the survivors, 63% were seen to have moderate to severe disability 90 days after symptom onset.
The data showed that even with the implementation of aggressive therapeutic approaches, influenza-associated ANE had a high morbidity and mortality rate in a group of previously healthy children. The low influenza vaccination rate among these children pointed to a potential area of opportunity, as did the speed with which the condition progressed after the onset of symptoms. While ANE is not itself vaccine-preventable, there was a clear trend toward negative outcomes for patients who were not vaccinated against influenza.
Based on these findings, the researchers identified increased flu vaccination rates, early recognition of symptoms, aggressive and timely treatment, and a standardized approach to managing the condition as steps that could help prevent influenza-associated ANE.
“The public health implications of a vaccine-preventable disease like this one are profound,” Dr. Santoro says. “The data that has come out of this study will hopefully inform public health monitoring and spur interventional trials to prevent morbidity and mortality in this dreadful disease.”
