tetano
Editor, Senior Moderator
Eur J Pediatr
. 2026 Sep 15;185(10):752.
doi: 10.1007/s00431-026-07411-6.
Sevgi Kuş 1 , Şilem Özdem Alataş 2 , Gülşen Akkoç 3 , Sevliya Öcal Demir 3 , Mustafa Gençeli 4 , Murat Sütçü 5 , Sema Yıldırım Arslan 6 , Esra Çiftci 7 , Selim Öncel 8 , Gül Arga 9 , Şefika Elmas Bozdemir 10 , Elif Kıymet 11 , Yıldız Ekemen Keleş 11 , Edanur Yeşil 12 , Manolya Kara 13 , Nazan Dalgıç 14 , Ümit Çelik 15 , Canan Özlü 16 , Ayşe Tekin Yılmaz 17 , Esra Çakmak Taşkın 18 , Semra Bayturan 19 , Özlem Özgür Gündeşlioğlu 20 , Mavera Uşaklıoğlu Erol 21 , Tuğçe Tural Kara 22 , Zeynep Özel 23 , Selin Taşar Karabulut 2 , Ümit Aslan Sarıtaş 2 , Selin Koçar 2 , Nihal Olgaç Dündar 24 25 , Fatih Durak 26 , İsmail Hakkı Akbeyaz 27 , Feyza İnceköy Girgin 28 , Özge Metin Akcan 29 , Büşra Kaygusuz Aydemir 29 , Hamit Solmaz Acer 30 , Solmaz Çelebi 7 , Rabia Tütüncü Toker 31 , Muhittin Bodur 31 , Hatice Sınav Ütkü 8 , Halil Özdemir 9 , Tanıl Kendirli 32 , Elif Somuncu 9 , Deniz Camcı Erten 10 , Müjgan Arslan 33 , Muhammet Furkan Korkmaz 34 , Hande Gazeteci Tekin 35 , Fatma Kuşgöz 36 , Güldane Dikme 12 , Burçin Gönüllü Polat 37 , Çiğdem Yanar Ayanoğlu 38 , Leyla Bulut Özen 14 , Ulaş Özdemir 15 , Esra Sarıgeçili 39 , Pakize Cennetoğlu 40 , Ali Korulmaz 41 , Ömer Karaca 42 , Meryem Baysal 19 , Filiz Kibar 43 , Edibe Pembegül Yıldız 44 , Demet Demirkol 45 , Ayşe Kübra Açık 22 , Mustafa Agah Tekindal 46 , Ayper Somer 21 , Ergin Çiftçi 9 , Hasan Tezer 47 , Ateş Kara 48 , Dilek Yılmaz 2 49
Affiliations
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.
Keywords: Acute encephalopathy; Children; Influenza seasons; Influenza-associated neurological complications; Seizures.
. 2026 Sep 15;185(10):752.
doi: 10.1007/s00431-026-07411-6.
Influenza-associated neurological complications in pediatric patients: clinical characteristics, outcomes, and the neuroinfluenza severity score in the multicenter TURK-INF study
Sevgi Kuş 1 , Şilem Özdem Alataş 2 , Gülşen Akkoç 3 , Sevliya Öcal Demir 3 , Mustafa Gençeli 4 , Murat Sütçü 5 , Sema Yıldırım Arslan 6 , Esra Çiftci 7 , Selim Öncel 8 , Gül Arga 9 , Şefika Elmas Bozdemir 10 , Elif Kıymet 11 , Yıldız Ekemen Keleş 11 , Edanur Yeşil 12 , Manolya Kara 13 , Nazan Dalgıç 14 , Ümit Çelik 15 , Canan Özlü 16 , Ayşe Tekin Yılmaz 17 , Esra Çakmak Taşkın 18 , Semra Bayturan 19 , Özlem Özgür Gündeşlioğlu 20 , Mavera Uşaklıoğlu Erol 21 , Tuğçe Tural Kara 22 , Zeynep Özel 23 , Selin Taşar Karabulut 2 , Ümit Aslan Sarıtaş 2 , Selin Koçar 2 , Nihal Olgaç Dündar 24 25 , Fatih Durak 26 , İsmail Hakkı Akbeyaz 27 , Feyza İnceköy Girgin 28 , Özge Metin Akcan 29 , Büşra Kaygusuz Aydemir 29 , Hamit Solmaz Acer 30 , Solmaz Çelebi 7 , Rabia Tütüncü Toker 31 , Muhittin Bodur 31 , Hatice Sınav Ütkü 8 , Halil Özdemir 9 , Tanıl Kendirli 32 , Elif Somuncu 9 , Deniz Camcı Erten 10 , Müjgan Arslan 33 , Muhammet Furkan Korkmaz 34 , Hande Gazeteci Tekin 35 , Fatma Kuşgöz 36 , Güldane Dikme 12 , Burçin Gönüllü Polat 37 , Çiğdem Yanar Ayanoğlu 38 , Leyla Bulut Özen 14 , Ulaş Özdemir 15 , Esra Sarıgeçili 39 , Pakize Cennetoğlu 40 , Ali Korulmaz 41 , Ömer Karaca 42 , Meryem Baysal 19 , Filiz Kibar 43 , Edibe Pembegül Yıldız 44 , Demet Demirkol 45 , Ayşe Kübra Açık 22 , Mustafa Agah Tekindal 46 , Ayper Somer 21 , Ergin Çiftçi 9 , Hasan Tezer 47 , Ateş Kara 48 , Dilek Yılmaz 2 49
Affiliations
- PMID: 42745076
- DOI: 10.1007/s00431-026-07411-6
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.
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.
Keywords: Acute encephalopathy; Children; Influenza seasons; Influenza-associated neurological complications; Seizures.