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

Authors

Sevgi Kuş, Şilem Özdem Alataş, Gülşen Akkoç, Sevliya Öcal Demir, Mustafa Gençeli, Murat Sütçü, Sema Yıldırım Arslan, Esra Çiftci, Selim Öncel, Gül Arga, Şefika Elmas Bozdemir, Elif Kıymet, Yıldız Ekemen Keleş, Edanur Yeşil, Manolya Kara, Nazan Dalgıç, Ümit Çelik, Canan Özlü, Ayşe Tekin Yılmaz, Esra Çakmak Taşkın, Semra Bayturan, Özlem Özgür Gündeşlioğlu, Mavera Uşaklıoğlu Erol, Tuğçe Tural Kara, Zeynep Özel, Selin Taşar Karabulut, Ümit Aslan Sarıtaş, Selin Koçar, Nihal Olgaç Dündar, Fatih Durak, İsmail Hakkı Akbeyaz, Feyza İnceköy Girgin, Özge Metin Akcan, Büşra Kaygusuz Aydemir, Hamit Solmaz Acer, Solmaz Çelebi, Rabia Tütüncü Toker, Muhittin Bodur, Hatice Sınav Ütkü, Halil Özdemir, Tanıl Kendirli, Elif Somuncu, Deniz Camcı Erten, Müjgan Arslan, Muhammet Furkan Korkmaz, Hande Gazeteci Tekin, Fatma Kuşgöz, Güldane Dikme, Burçin Gönüllü Polat, Çiğdem Yanar Ayanoğlu, Leyla Bulut Özen, Ulaş Özdemir, Esra Sarıgeçili, Pakize Cennetoğlu, Ali Korulmaz, Ömer Karaca, Meryem Baysal, Filiz Kibar, Edibe Pembegül Yıldız, Demet Demirkol, Ayşe Kübra Açık, Mustafa Agah Tekindal, Ayper Somer, Ergin Çiftçi, Hasan Tezer, Ateş Kara, Dilek Yılmaz

Published in

European journal of pediatrics. Volume 185. Issue 10. Sep 15, 2026. Epub Sep 15, 2026.

Abstract

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.
 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.
• 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.
• 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.

PMID:
42745076
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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