Influenza is associated with a variety of respiratory and non-respiratory complications. In addition to pneumonia and myocarditis, neurological manifestations are also part of the spectrum of the disease. The acute necrotizing encephalopathy (ANE), which has been described in Japan since the late 1970s and has been sporadically worldwide, has been particularly serious. Acute neurological deterioration with radiological evidence of bilateral thalamic lesions are characteristic.
National survey on influenza-associated ane in the USA
Table of Contents
- National survey on influenza-associated ane in the USA
- High proportion of healthy children with severe neurological findings
- Mostly influenza A, vaccination protection only documented in a few children
- High mortality despite intensive immunomodulatory therapy
- Demand for consistent vaccination and early intensive therapy
- Conclusion: early detection, intensive therapy and prevention
Based on clinical reports on an increase in pediatric ane cases in the influenza seasons 2023/2024 and 2024/2025, a US working group initiated a multicenter examination, the results of which were published in ‘Jama’. The study included children and adolescents up to 21 years with acute encephalopathy, laboratory -confirmed influenza and thalamic lesions in imaging.
High proportion of healthy children with severe neurological findings
Between October 2023 and May 2025, a total of 58 cases from 23 clinics were recorded through specialist societies, health authorities and direct inquiries at 76 academic centers, 41 of which met the inclusion criteria. The median age was five years. 76 % of the children were previously healthy, 12 % had complex previous illnesses.
Common symptoms were fever (93 %), encephalopathy (100 %) and seizures (68 %). Laboratory chemical were increased liver enzymes (78 %), thrombocytopenia (63 %) and increased liquor protein mirror (63 %). There was a genetic test in 32 patients, with 47 % risk variants identified. Among them were 34 % mutations in the Ranbp2 gene, which is encoded by a core pore protein and has long been described with a genetic predisposition for ane.
Mostly influenza A, vaccination protection only documented in a few children
Influenza A was detected in 95 % of children, most often the H1N1PDM09 variant. Influenza B occurred in two cases. Of 38 patients with documented vaccination status, only 16 % had received age -appropriate seasonal flu vaccination.
High mortality despite intensive immunomodulatory therapy
Most patients received combined immunomodulatory treatments, in particular methylprednisolone (95 %), intravenous immunoglobulins (66 %), tocilizumab (51 %), plasma apheresis (32 %), anaKinra (5 %) and intrathecal methylprednisolone (5 %).
The median length of stay was eleven days in the intensive care unit and 22 days in the hospital. Eleven children (27 %) died in the median three days after the start of symptoms, mostly as a result of a brain annex. Of the survivors, 63 % showed a moderate to severe disability after 90 days.
Demand for consistent vaccination and early intensive therapy
In an accompanying editorial, Timothy M. Uyeki, Chief Medical Officer of the Influenza Division at the National Center for Immunization and Respiratory Diseases of the US Center for Disease Control and Prevention (CDC) in Atlanta, emphasized the extraordinary severity of the illness and raised the urgent need for clinical standards for diagnostics and therapy national surveillance. He also recalled the recommendation for annual influenza vaccination for all children from six months in the United States.
In contrast, the permanent vaccination commission (STIKO) at the Robert Koch Institute (RKI) recommends that the seasonal influenza vaccination in Germany are not for healthy children, but only for children from six months with increased risk due to certain previous illnesses-such as chronic respiratory diseases such as asthma or cystic fibrosis as well as other serious basic diseases.
The high mortality and the frequent permanent disabilities underline the need for preventive measures, in particular consistent influenza vaccination, as well as early, intensive medical therapy.
Conclusion: early detection, intensive therapy and prevention
In the case of predominantly healthy children, the case series shows a high mortality and morbidity of the influenza-associated Ane. The authors emphasize prevention, early detection, intensive treatment and standardized management protocols as central requirements; The editorial also underlines the need for epidemiological monitoring and guidelines. A specific protective effect of influenza vaccination against ANE is not proven; However, their benefits to prevent influenza is secured.
