Influenza-Associated Neurological Complications in Pediatric Patients: Clinical Characteristics, Outcomes, and Risk Stratification Using the Neuroinfluenza Severity Score  from the Multicenter TURK-INF Study

  1. Sevgi Kuş
  2. Şilem Özdem Alataş
  3. Gülşen Akkoç
  4. Sevliya Öcal Demir
  5. Mustafa Gençeli
  6. Murat Sütçü
  7. Sema Yıldırım Arslan
  8. Esra Çiftci
  9. Selim Öncel
  10. Gül Arga
  11. Şefika Elmas Bozdemir
  12. Elif Kıymet
  13. Yıldız Ekemen Keleş
  14. Edanur Yeşil
  15. Manolya Kara
  16. Nazan Dalgıç
  17. Ümit Çelik
  18. Canan Özlü
  19. Ayşe Tekin Yılmaz
  20. Esra Çakmak Taşkın
  21. Semra Bayturan
  22. Özlem Özgür Gündeşlioğlu
  23. Mavera Uşaklıoğlu Erol
  24. Tuğçe Tural Kara
  25. Zeynep Özel
  26. Selin Taşar Karabulut
  27. Ümit Aslan Sarıtaş
  28. Selin Koçar
  29. Nihal Olgaç Dündar
  30. Fatih Durak
  31. İsmail Hakkı Akbeyaz
  32. Feyza İnceköy Girgin
  33. Özge Metin Akcan
  34. Büşra Kaygusuz Aydemir
  35. Hamit Acer
  36. Solmaz Çelebi
  37. Rabia Tütüncü Toker
  38. Muhittin Bodur
  39. Hatice Sınav Ütkü
  40. Halil Özdemir
  41. Tanıl Kendirli
  42. Elif Somuncu
  43. Deniz Camcı Erten
  44. Müjgan Arslan
  45. Muhammet Furkan Korkmaz
  46. Hande Gazeteci Tekin
  47. Fatma Kuşgöz
  48. Güldane Dikme
  49. Burçin Gönüllü Polat
  50. Çiğdem Yanar Ayanoğlu
  51. Leyla Bulut Özen
  52. Ulaş Özdemir
  53. Esra Sarıgeçili
  54. Pakize Cennetoğlu
  55. Ali Korulmaz
  56. Ömer Karaca
  57. Meryem Baysal
  58. Filiz Kibar
  59. Edibe Pembegül Yıldız
  60. Demet Demirkol
  61. Ayşe Kübra Açık
  62. Mustafa Agah Tekindal
  63. Ayper Somer
  64. Ergin Çiftçi
  65. Hasan Tezer
  66. Ateş Kara
  67. Dilek Yılmaz
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Abstract

Background Influenza-associated neurological complications (IANC) encompass a broad spectrum ranging from febrile seizures to severe encephalopathy with substantial morbidity and mortality. We aimed to describe the clinical characteristics and outcomes of pediatric IANC and evaluate the prognostic utility of the Neuroinfluenza Severity Score (NISS). Methods 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 six-month follow-up data were analyzed. NISS was developed using variables reflecting disease severity, and outcome analysis was performed. Results Among 5,093 hospitalized children with influenza, 397 (7.8%) developed neurological complications. The median age was 45.6 months, and 70.8% were younger than five years. Seizures were the most frequent manifestation (70.8%), followed by encephalopathy (10.9%) and meningoencephalitis (5.0%). Complete neurological recovery occurred in 90.2% of patients, whereas 5.0% developed long-term neurological sequelae, and overall mortality was 1.3%. ROC analysis demonstrated excellent predictive performance of NISS for unfavorable neurological outcomes, with an optimal cutoff ≥ 2 yielding 82.1% sensitivity and 91.9% specificity (AUC 0.913, 95% CI 0.856–0.969; p < 0.001). Patients with severe neuroinfluenza were associated with delayed oseltamivir initiation, prolonged hospitalization, elevated inflammatory markers, and more frequent high-risk neuroimaging abnormalities and had significantly long-term neurological sequelae (29.5% vs. 0.6%), and mortality (8.2% vs. 0%). Conclusions IANC should be considered in children presenting with acute neurological manifestations, even in the absence of respiratory symptoms. The NISS demonstrated excellent ability to identify patients at increased risk of poor neurological outcomes, long-term sequelae, and mortality, providing a practical tool for early risk stratification and timely escalation of care.

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