Influenza-associated neurological complications in pediatric patients: clinical characteristics, outcomes, and the neuroinfluenza severity score in the multicenter TURK-INF study.

UNLABELLED: Influenza-associated neurological complications (IANC) encompass a broad clinical spectrum, ranging from febrile seizures to severe encephalopathy associated with neurological morbidity and mortality. We aimed to describe the clinical characteristics and outcomes of pediatric IANC and to explore the Neuroinfluenza Severity Score (NISS) as a retrospective measure of disease severity. This retrospective multicenter study included children aged 1 month to 18 years hospitalized with laboratory-confirmed influenza and neurological manifestations at 21 tertiary centers in Türkiye during the 2023-2025 influenza seasons. Clinical, laboratory, neuroimaging, treatment, and available 6-month follow-up data were analyzed. NISS was constructed post hoc as an exploratory retrospective severity index incorporating clinical course, management, and neuroimaging variables. Neurological outcomes were assessed using available 6-month follow-up data. Among 5093 hospitalized children with laboratory-confirmed influenza, 397 (7.8%) had neurological complications. The mean age was 45.6 months, and 70.8% were younger than 5 years. Only 5 children (1.3%) had received seasonal influenza vaccination, and respiratory symptoms were absent in approximately one-quarter of patients. Seizures were the most frequent neurological manifestation, occurring in 306 patients (77.1%), while acute encephalopathy occurred in 72 (18.1%). Most patients achieved complete neurological recovery; however, persistent neurological sequelae occurred in 5.0% and mortality was 1.3%. In exploratory ROC analysis, higher NISS values were associated with poor neurological outcomes (AUC 0.890, 95% CI 0.819-0.960; p < 0.001). A NISS threshold of ≥ 2 yielded a sensitivity of 79.5% and specificity of 90.8% within this retrospective cohort. Patients with NISS ≥ 2 had longer hospitalization and higher rates of persistent neurological sequelae and mortality.

CONCLUSION: IANC should be considered in children presenting with acute neurological manifestations, including those without prominent respiratory symptoms. Although most affected children recover completely, a subset experience persistent neurological morbidity or death. NISS may provide a standardized retrospective summary of neurological disease severity; however, its post hoc construction and inclusion of variables arising during the clinical course preclude its use as an early prediction or risk-stratification tool. Prospective validation using baseline variables is required before clinical application.

WHAT IS KNOWN: • Influenza is a common cause of hospitalization in children and may be associated with neurological complications ranging from febrile seizures to acute necrotizing encephalopathy. • Despite increasing recognition of influenza-associated neurological complications, important uncertainties remain regarding their underlying pathophysiology, determinants of disease severity, optimal management, and long-term neurological outcomes.

WHAT IS NEW: • Children aged ≥5 years were more likely to present with acute encephalopathy compared with seizures after simple febrile seizures were excluded. • The NeuroInfluenza Severity Score (NISS) was evaluated as an exploratory post hoc severity index for classifying neurological disease severity during hospitalization.