Recent data from a national multicentre study have revealed a disturbing rise in influenza‑associated acute necrotizing encephalopathy (ANE) among previously healthy children in the U.S. between October 1, 2023 and May 30, 2025.
While ANE has historically been extremely rare—typically a handful of cases every few years—physicians began noticing an unusual cluster of cases in early 2024, prompting widespread collaboration among leading paediatric neurology centres.
Study Overview and Key Findings
A total of 41 confirmed cases were identified across 23 U.S. hospitals, with a median patient age of 5 years.
Most of the affected children had no prior medical conditions. Nearly all contracted influenza A, mostly subtypes H1N1 and H3N2; just two had influenza B.
Clinical presentation was rapid and alarming: all children developed encephalopathy (brain dysfunction), with 68% experiencing seizures and 93% presenting with high fever. Additional common laboratory abnormalities included elevated liver enzymes and thrombocytopenia.
Tragically, 27% (11 children) died, often within 3 days of symptom onset, largely due to brain herniation from swelling.
Among the survivors, 63% experienced moderate to severe disability three months later, affecting mobility, speech, and cognitive function.
Treatment & Prognosis
Due to the rarity of ANE, no standardized protocol exists, but early, aggressive neuro‑critical care combined with immunomodulating therapies showed better outcomes. Among the patients:
- 95% received methylprednisolone (steroids)
- 66% received intravenous immunoglobulin (IVIG)
- 51% received tocilizumab
- 32% underwent plasmapheresis (plasma exchange)
Some received anakinra or intrathecal steroids
Why the Surge? Surveillance and Vaccination Gaps
Health experts emphasize that low flu vaccination rates among children may have contributed to this increase. Only 6 of the 41 children (16%) had received an age‑appropriate seasonal flu vaccine—far below the national rate of approximately 50% during the 2023–25 seasons.
Among the 11 fatal cases, only one child had been vaccinated
Additionally, the U.S. did not have a national surveillance system specifically tracking ANE or influenza‑associated encephalopathies until February 2025, when the CDC began formal monitoring in response to these reports.
An expert editorial by CDC’s Dr. Timothy Uyeki accompanied the JAMA study, recommending sustained multi‑year surveillance to better understand incidence, risk factors, and recurrence risk.
Recognizing ANE: What Parents and Clinicians Should Watch
Early symptoms of ANE often mimic a typical flu: high fever, cough, sore throat, vomiting or diarrhoea. However, within 48 hours, neurological deterioration sets in:
- Unexplained lethargy, not relieved by antipyretics
- Sudden confusion or inability to focus
- Seizures or abnormal posturing
- Refusing to eat or interact meaningfully
Parents are advised: trust your instincts if your child seems neurologically unwell—especially with flu symptoms—and seek emergency care promptly.
Importance of Flu Vaccination
Study authors unanimously stress the critical role of annual flu shots for children aged 6 months and older, with young children receiving two doses one month apart if never previously vaccinated. Only about 55% of U.S. children were fully vaccinated during the 2023–24 season—the lowest rate in over a decade.
Since most severe flu complications, including ANE and death, have occurred in unvaccinated children, improving uptake is vital.
For children with a history of ANE, vaccination is especially crucial—because recurrence is possible with subsequent flu infections.
Moving Forward: What Needs to Change
Expanded surveillance across seasons to track incidence and risk factors
Consensus clinical protocols for early diagnosis and management
Public health campaigns to boost vaccination rates
Genetic research, as nearly half of tested children carried variants (e.g. RANBP2) associated with ANE susceptibility.
Final Thoughts
While ANE remains rare, the recent spike during consecutive severe flu seasons demonstrates that it can strike quickly and devastate even previously healthy children. The mortality and disability rates underline the urgency of vaccination, early recognition, and prompt, intensive treatment. Clinicians, parents, and public health authorities must work in concert to reduce risks and improve outcomes.
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