Recent studies on the Nipah virus, H5N1-related encephalitis, influenza-associated encephalopathy (IAE), and the acute necrotizing encephalopathy (ANE) outbreak in India, especially in Kerala state. All these studies are highlighted in the World Federation of Neurology (WFN) neuroinfectious disease update. ANE is the most severe type of IAE, which is a spectrum of neurological symptoms that follow an influenza infection. ANE usually starts with a viral prodrome and quickly develops unconsciousness, focal deficits, and seizures. Imaging frequently shows profound grey matter lesions and symmetric thalamic lesions together with diffuse cerebral inflammation. A multicenter analysis was prompted by the apparent increase in pediatric ANE cases over the recent flu season in the United States, even though these cases are uncommon.
The Influenza-Associated ANE (IA-ANE) working group recently published a report in JAMA describing 41 pediatric cases of ANE from 23 hospitals in the U.S. from October 2023 to May 2025. Approximately 78% of children had not received an influenza vaccination, and 76% had no prior history of any medical conditions. Rapid neurological deterioration and viral prodrome were reported in 68% of cases with a median Glasgow Coma Scale score of 6. About 95% had positive influenza A (H3 or H1 2009) tests. Genetic testing (n = 32 children) showed that 15 had a possible propensity with Ran Binding Protein 2 (RANBP2) mutations being the most common.
Magnetic resonance imaging (MRI) consistently demonstrated bilateral thalamic T2 hyperintensities, often extending to the subcortical white matter, basal ganglia, and brainstem. Restricted diffusion was observed in 97%, susceptibility-weighted imaging in 73%, and nearly half reported trilaminar necrosis of the thalami. High-dose methylprednisolone (95%), oseltamivir (76%), and the remaining drugs, like anakinra, tocilizumab, plasmapheresis, and IVIG, were used in combination with antivirals and immunotherapy. Despite intensive treatment, approximately 27% of patients died within the first 3 days of admission, mostly from herniation and cerebral oedema. At 90-day follow-up, 63% of survivors had moderate to severe disabilities, which included dystonia (30%), spasticity (60%), and epilepsy (20%). The potential preventive role of vaccination is highlighted by the fact that just one youngster who died had received the seasonal influenza vaccine.
Globally, H5N1-related encephalitis is still emerging in addition to seasonal influenza. A 3-year-old Mexican child died in April 2025 from an H5N1 illness, which was traced to the D1.1 strain that was circulating among North American wild birds. The same strain has affected poultry workers in the U.S., a Canadian teen, and caused deadly sickness in Louisiana. Cambodia is responsible for half of the 22 cases and eight deaths reported worldwide in 2025.
Animal studies verify neurotropism in mammals, including marine animals and cats, even though encephalitis has been infrequently linked to H5N1 infections. There was no sustained person-to-person transmission of human illness, which mostly affects poultry and dairy workers. The World Health Organization’s risk assessment for the impact on public health is still low.
Nipah virus caused four confirmed cases in Kerala (May-July 2025), marking the 9th outbreak since 2018. Transmitted from fruit bats via contaminated sap or fruit, it carries a 40-100% fatality rate and presents pneumonic or encephalitic illness. Human transmission occurs, but no treatment or vaccine exists. This report underscores the need for early detection, vigilance, vaccination, and surveillance against neurotropic viruses.
Reference: Billioux BJ, Nath A. WFN Neuroinfectious Disease Update [August ’25]. World Federation of Neurology. Published August 15, 2025. Accessed August 20, 2025. https://wfneurology.org/activities/spotlight-on-current-global-neuro-infections/neuro-covid-updates/neuro-id-update-august-25
