Jovanovic, Milan

Background: Influenza-associated encephalopathy, encephalitis, and acute necrotizing encephalopathy (ANE) are rare but potentially life-threatening neurological complications of influenza. Adult cases remain poorly characterized because the available literature is largely limited to isolated case reports and small case series. Methods: A PRISMA-guided scoping review of the MEDLINE database was conducted through 31 May 2026. Published adult cases of influenza-associated encephalopathy, encephalitis, and ANE were identified and analyzed for demographic characteristics, clinical presentation, neuroimaging findings, treatment, and outcomes. Results: Eighty-three adult cases reported between 1958 and 2026 were included. The mean age was 45.6 ± 17.8 years, and 57.8% were male. Two-thirds did not have any underlying comorbidities. Neurological symptoms developed a mean of 4.6 days after influenza onset, with influenza A accounting for 80.7% of infections. Fever (91.6%), altered mental status (86.7%), and seizures (36.1%) were the most common manifestations. Encephalitis was the predominant presentation (44.5%), followed by encephalopathy (31.3%) and ANE (24.1%). MRI most frequently demonstrated cerebral hemispheric lesions (53.0%) and bilateral thalamic involvement (36.4%), while EEG abnormalities were reported in 69.6% of patients. Overall mortality was 22.9%, highest among patients with ANE (45.0%). Among survivors, 28.9% experienced persistent neurological sequelae. Conclusions: Influenza-associated encephalopathy, encephalitis, and ANE are rare in adults but are associated with substantial morbidity and mortality. This review represents the largest adult cohort reported to date and provides important insights into the clinical spectrum, neurodiagnostic findings, and outcomes of these uncommon complications. This review highlights significant gaps in knowledge and the need for collaborative multicenter studies to improve the diagnosis, treatment, and outcome of these severe complications of influenza infection.