Children may be more likely to survive a rare, potentially fatal influenza complication if they receive rapid treatment for brain swelling and extreme immune responses, a Stanford Medicine-led report found.
The researchers hope to raise awareness about the condition, called influenza-associated acute necrotizing encephalopathy, and to inform parents and physicians about its prevention and treatment. Flu vaccines are a key protective strategy for ANE and other severe flu complications in kids, according to the report, which is published in JAMA.
“Acute necrotizing encephalopathy is the most severe flu complication, but it’s only the tip of the iceberg for what flu can do,” said co-senior author Keith Van Haren, MD, associate professor of neurology and neurological sciences and of pediatrics. Van Haren is also a pediatric neurologist at Lucile Packard Children’s Hospital Stanford.
“Flu causes all kinds of complications, including other forms of brain swelling, as well as pneumonia and respiratory failure. Vaccines really do help protect wonderfully against all those complications.”
Influenza-associated acute necrotizing encephalopathy causes brain swelling and a runaway immune response, a combination that can be fatal. As outlined in the report, the researchers analyzed 41 cases of ANE that occurred across the country from 2023 to 2025, an unusually high number tied to severe flu seasons.
Among the cases in the report, 27% of affected children died. Of the survivors, 63% still had moderate to severe disability three months after they became sick. Receiving rapid, targeted care in a pediatric intensive care unit was associated with a greater chance of recovery.
“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,” said co-senior author Thomas LaRocca, MD, Ph.D., a clinical assistant professor and a pediatric critical care medicine specialist at Packard Children’s.
The threat of flu
“Flu is notoriously dangerous for kids; it always has been,” Van Haren said, noting that children younger than five years face the highest risk of serious illness or death.
The study’s lead authors are Andrew Silverman, MD, and Rachel Walsh, MD, both of whom were residents in pediatric neurology at Stanford Medicine when the project began.
Silverman is now a medical fellow at Weill Cornell Medical School, and Walsh is now a fellow at Boston Children’s Hospital and Harvard Medical School. Van Haren and LaRocca share senior authorship of the study with Molly Wilson-Murphy, MD, of Boston Children’s Hospital and Harvard Medical School.
“For clinicians, the takeaway from our report is that early, intensive management of brain swelling and the immune response really seemed to help children with this condition recover,” Van Haren said.
The most important thing that parents can do is ensure that children receive their annual flu vaccines, he said, noting that the vaccines greatly reduce a child’s chance of becoming seriously ill with flu.
More cases in a bad flu season
Van Haren, LaRocca and their colleagues began investigating ANE in 2024 because they noticed the condition was on the increase. Typically, they see one case every year or two at Packard Children’s.
During the severe 2024–25 flu season, in which the predominant circulating strain of influenza A hit kids especially hard, they treated four children with ANE and heard reports from colleagues of cases elsewhere in Northern California.
The team initiated a national inquiry to academic societies, state and federal public health agencies, and pediatric specialists across the country to ask if other institutions were experiencing a similar uptick—the answer was yes—and to request cases to analyze. In total, 41 cases from 23 hospitals across the United States met the criteria for inclusion in the report.
The median age of the children with ANE was five years. Thirty-nine children were infected with influenza A; two had influenza B. Most children had been healthy, with no significant medical history, before contracting the flu. Among the 38 ANE cases for which the child’s vaccination history was known, only six had received flu vaccines during the season they became ill. At the onset of their illness, all patients had brain swelling, 95% had fevers and 68% had seizures.
Eleven patients (27%) died of ANE, eight within a week of admission to the hospital. Patients died due to swelling and herniation of the brain. Only one of the patients who died had received a flu vaccine.
Patients’ median stay in the intensive care unit was 11 days, and their median total hospital stay was 22 days. The 30 children who survived experienced varying degrees of long-term effects; some made full recoveries, while others did not.
Using reports collected for up to 90 days after the children became sick, the researchers saw that of the 30 survivors, 19 patients regained the ability to sit, 16 patients could stand independently and 13 could walk independently.
Better-than-expected outcomes
“The number of kids who had pretty good outcomes surprised me; it was better than I thought it would be,” Van Haren said, noting that ANE is regarded by physicians as likely to be fatal.
“We identified ANE patients with a wide range of outcomes, from no residual neurological deficits to, unfortunately, fatal complications,” LaRocca said.
“We saw that critical-care management of brain swelling, along with immune-modulating therapies such as plasma exchange and intravenous immunoglobulin, appeared helpful for patients who recovered.”
The immune therapies are important because the underlying problem in ANE includes an out-of-control immune response, Van Haren said.
“It’s similar to the sepsis response, this massive burst of inflammation that becomes its own problem,” he said. “It’s like the immune system is going into a panic attack.”
Giving steroids can help calm the immune system, as can plasma exchange, which involves removing the patient’s blood plasma in a process similar to kidney dialysis and replacing it with plasma from a healthy donor.
Further research to better understand the pathophysiology of ANE and learn more about effective treatments is warranted, LaRocca said.
“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,” Van Haren said. “And for parents, it’s: Vaccinate!”
Flu is more than fever, aches and pains, he added.
“We want to protect them from the deadly stuff,” Van Haren said. “That’s what the vaccine can do.”
More information:
Influenza-Associated Acute Necrotizing Encephalopathy in U.S. Children, JAMA (2025). jamanetwork.com/journals/jama/ … 1001/jama.2025.11534
Citation:
Rare, serious flu complication in kids needs rapid treatment, study finds (2025, July 30)
retrieved 30 July 2025
from https://medicalxpress.com/news/2025-07-rare-flu-complication-kids-rapid.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
Children may be more likely to survive a rare, potentially fatal influenza complication if they receive rapid treatment for brain swelling and extreme immune responses, a Stanford Medicine-led report found.
The researchers hope to raise awareness about the condition, called influenza-associated acute necrotizing encephalopathy, and to inform parents and physicians about its prevention and treatment. Flu vaccines are a key protective strategy for ANE and other severe flu complications in kids, according to the report, which is published in JAMA.
“Acute necrotizing encephalopathy is the most severe flu complication, but it’s only the tip of the iceberg for what flu can do,” said co-senior author Keith Van Haren, MD, associate professor of neurology and neurological sciences and of pediatrics. Van Haren is also a pediatric neurologist at Lucile Packard Children’s Hospital Stanford.
“Flu causes all kinds of complications, including other forms of brain swelling, as well as pneumonia and respiratory failure. Vaccines really do help protect wonderfully against all those complications.”
Influenza-associated acute necrotizing encephalopathy causes brain swelling and a runaway immune response, a combination that can be fatal. As outlined in the report, the researchers analyzed 41 cases of ANE that occurred across the country from 2023 to 2025, an unusually high number tied to severe flu seasons.
Among the cases in the report, 27% of affected children died. Of the survivors, 63% still had moderate to severe disability three months after they became sick. Receiving rapid, targeted care in a pediatric intensive care unit was associated with a greater chance of recovery.
“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,” said co-senior author Thomas LaRocca, MD, Ph.D., a clinical assistant professor and a pediatric critical care medicine specialist at Packard Children’s.
The threat of flu
“Flu is notoriously dangerous for kids; it always has been,” Van Haren said, noting that children younger than five years face the highest risk of serious illness or death.
The study’s lead authors are Andrew Silverman, MD, and Rachel Walsh, MD, both of whom were residents in pediatric neurology at Stanford Medicine when the project began.
Silverman is now a medical fellow at Weill Cornell Medical School, and Walsh is now a fellow at Boston Children’s Hospital and Harvard Medical School. Van Haren and LaRocca share senior authorship of the study with Molly Wilson-Murphy, MD, of Boston Children’s Hospital and Harvard Medical School.
“For clinicians, the takeaway from our report is that early, intensive management of brain swelling and the immune response really seemed to help children with this condition recover,” Van Haren said.
The most important thing that parents can do is ensure that children receive their annual flu vaccines, he said, noting that the vaccines greatly reduce a child’s chance of becoming seriously ill with flu.
More cases in a bad flu season
Van Haren, LaRocca and their colleagues began investigating ANE in 2024 because they noticed the condition was on the increase. Typically, they see one case every year or two at Packard Children’s.
During the severe 2024–25 flu season, in which the predominant circulating strain of influenza A hit kids especially hard, they treated four children with ANE and heard reports from colleagues of cases elsewhere in Northern California.
The team initiated a national inquiry to academic societies, state and federal public health agencies, and pediatric specialists across the country to ask if other institutions were experiencing a similar uptick—the answer was yes—and to request cases to analyze. In total, 41 cases from 23 hospitals across the United States met the criteria for inclusion in the report.
The median age of the children with ANE was five years. Thirty-nine children were infected with influenza A; two had influenza B. Most children had been healthy, with no significant medical history, before contracting the flu. Among the 38 ANE cases for which the child’s vaccination history was known, only six had received flu vaccines during the season they became ill. At the onset of their illness, all patients had brain swelling, 95% had fevers and 68% had seizures.
Eleven patients (27%) died of ANE, eight within a week of admission to the hospital. Patients died due to swelling and herniation of the brain. Only one of the patients who died had received a flu vaccine.
Patients’ median stay in the intensive care unit was 11 days, and their median total hospital stay was 22 days. The 30 children who survived experienced varying degrees of long-term effects; some made full recoveries, while others did not.
Using reports collected for up to 90 days after the children became sick, the researchers saw that of the 30 survivors, 19 patients regained the ability to sit, 16 patients could stand independently and 13 could walk independently.
Better-than-expected outcomes
“The number of kids who had pretty good outcomes surprised me; it was better than I thought it would be,” Van Haren said, noting that ANE is regarded by physicians as likely to be fatal.
“We identified ANE patients with a wide range of outcomes, from no residual neurological deficits to, unfortunately, fatal complications,” LaRocca said.
“We saw that critical-care management of brain swelling, along with immune-modulating therapies such as plasma exchange and intravenous immunoglobulin, appeared helpful for patients who recovered.”
The immune therapies are important because the underlying problem in ANE includes an out-of-control immune response, Van Haren said.
“It’s similar to the sepsis response, this massive burst of inflammation that becomes its own problem,” he said. “It’s like the immune system is going into a panic attack.”
Giving steroids can help calm the immune system, as can plasma exchange, which involves removing the patient’s blood plasma in a process similar to kidney dialysis and replacing it with plasma from a healthy donor.
Further research to better understand the pathophysiology of ANE and learn more about effective treatments is warranted, LaRocca said.
“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,” Van Haren said. “And for parents, it’s: Vaccinate!”
Flu is more than fever, aches and pains, he added.
“We want to protect them from the deadly stuff,” Van Haren said. “That’s what the vaccine can do.”
More information:
Influenza-Associated Acute Necrotizing Encephalopathy in U.S. Children, JAMA (2025). jamanetwork.com/journals/jama/ … 1001/jama.2025.11534
Citation:
Rare, serious flu complication in kids needs rapid treatment, study finds (2025, July 30)
retrieved 30 July 2025
from https://medicalxpress.com/news/2025-07-rare-flu-complication-kids-rapid.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
