Clinical, Biochemical, Lifestyle, and Sleep Characteristics Associated With Chronic Primary Headache in Children and Adolescents: A Cross-Sectional Comparative Study

Öz

Chronic primary headache in childhood causes substantial functional impairment and may involve interacting clinical, familial, biochemical, lifestyle, and sleep-related factors. This cross-sectional comparative study evaluated factors independently associated with chronic headache status in 300 participants aged 6–18 years, including 200 with chronic and 100 with episodic primary headache. Headache characteristics, family history of migraine, serum 25-hydroxyvitamin D, vitamin B12 and ferritin levels, Pittsburgh Sleep Quality Index scores, and actigraphy-derived sleep and physical activity parameters were assessed. Binary logistic regression was performed, while EEG findings were descriptively evaluated in a clinically selected subgroup. Compared with the episodic group, participants with chronic headache had poorer subjective and objective sleep characteristics, lower vitamin D, vitamin B12 and ferritin levels, and less daily physical activity (all p<0.01). Subjective sleep duration <7 hours/night (adjusted OR [aOR]=3.24), PSQI score >8 (aOR=2.91), vitamin D <20 ng/mL (aOR=2.17), physical activity <30 minutes/day (aOR=1.98), and family history of migraine (aOR=2.83) were independently associated with chronic headache status. In the objective sleep model, sleep efficiency <85% (aOR=3.07), wake after sleep onset >40 minutes/night (aOR=2.48), and total sleep time <7 hours/night (aOR=2.91) remained independently associated with chronic headache, alongside low vitamin D status and physical activity. EEG abnormalities were unrelated to headache intensity (p>0.05). These findings support multidimensional assessment of pediatric chronic headache, although causality cannot be inferred from the cross-sectional design.

Anahtar Kelimeler

• pediatric headache
• sleep
• actigraphy
• vitamin D
• physical activity

Etik Beyan

The study protocol was reviewed and approved by the Recep Tayyip Erdoğan University Non-Interventional Clinical Research Ethics Committee (Decision No: 2025/464). Written informed consent was obtained from parents of all participants, and verbal or written assent was obtained from children, in accordance with age and level of understanding. The study was conducted in accordance with the Declaration of Helsinki and national ethical regulations.

Çocuk ve Ergenlerde Kronik Primer Baş Ağrısıyla İlişkili Klinik, Biyokimyasal, Yaşam Tarzı ve Uyku Özellikleri: Kesitsel Karşılaştırmalı Çalışma

Öz

Çocukluk çağındaki kronik primer baş ağrısı, önemli düzeyde işlevsel yetersizliğe yol açmakta ve klinik, ailesel, biyokimyasal, yaşam tarzı ve uyku ile ilişkili faktörlerin etkileşimini içerebilmektedir. Bu kesitsel karşılaştırmalı çalışmada, 6–18 yaş aralığında kronik primer baş ağrısı olan 200 ve epizodik primer baş ağrısı olan 100 olmak üzere toplam 300 katılımcı değerlendirildi. Baş ağrısı özellikleri, ailede migren öyküsü, serum 25-hidroksivitamin D, vitamin B12 ve ferritin düzeyleri, Pittsburgh Uyku Kalitesi İndeksi puanları ile aktigrafiyle ölçülen uyku ve fiziksel aktivite parametreleri incelendi. Kronik baş ağrısı durumuyla bağımsız olarak ilişkili faktörleri belirlemek amacıyla ikili lojistik regresyon analizi uygulandı. EEG bulguları ise klinik olarak seçilmiş bir alt grupta betimsel olarak değerlendirildi. Epizodik gruba kıyasla kronik baş ağrısı olan katılımcılarda öznel ve nesnel uyku özellikleri daha kötü, vitamin D, vitamin B12 ve ferritin düzeyleri daha düşük ve günlük fiziksel aktivite daha azdı (tümü p<0,01). Gecelik öznel uyku süresinin <7 saat olması (düzeltilmiş OR [dOR]=3,24), PSQI puanının >8 olması (dOR=2,91), vitamin D düzeyinin <20 ng/mL olması (dOR=2,17), fiziksel aktivitenin <30 dakika/gün olması (dOR=1,98) ve ailede migren öyküsü (dOR=2,83) kronik baş ağrısı durumuyla bağımsız olarak ilişkiliydi. Nesnel uyku modelinde uyku etkinliğinin <%85, uyku başlangıcı sonrası uyanıklığın >40 dakika/gece ve toplam uyku süresinin <7 saat/gece olması bağımsız ilişkisini korudu. EEG anormallikleri baş ağrısı şiddetiyle ilişkili değildi (p>0,05). Bulgular, pediatrik kronik baş ağrısında çok boyutlu değerlendirmeyi desteklemektedir; ancak kesitsel tasarım nedensellik çıkarımına izin vermemektedir.

Anahtar Kelimeler

• pediatrik baş ağrısı
• uyku
• aktigrafi
• D vitamini
• fiziksel aktivite

Kaynakça

1. 1. Abu-Arafeh I, Razak S, Sivaraman B, Graham C. Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies. Dev Med Child Neurol 2010;52(12):1088-97.
2. 2. Onofri A, Pensato U, Rosignoli C, et al. Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis. J Headache Pain 2023;24(1):8.
3. 3. Wöber-Bingöl C. Epidemiology of migraine and headache in children and adolescents. Curr Pain Headache Rep 2013;17(6):341.
4. 4. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38(1):1-211.
5. 5. Powers SW, Patton SR, Hommel KA, Hershey AD. Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses. Pediatrics 2003;112(1 Pt 1):e1-5.
6. 6. Kernick D, Reinhold D, Campbell JL. Impact of headache on young people in a school population. Br J Gen Pract 2009;59(566):678-81.
7. 7. Blaauw BA, Dyb G, Hagen K, et al. Anxiety, depression and behavioral problems among adolescents with recurrent headache: the Young-HUNT study. J Headache Pain 2014;15(1):38.
8. 8. Hsu TW, Chen MH, Chu CS, et al. Attention deficit hyperactivity disorder and risk of migraine: a nationwide longitudinal study. Headache 2022;62(5):634-41.

9. 9. Amiri P, Kazeminasab S, Nejadghaderi SA, et al. Migraine: a review on its history, global epidemiology, risk factors, and comorbidities. Front Neurol 2022;12:800605.
10. 10. Mungoven TJ, Henderson LA, Meylakh N. Chronic migraine pathophysiology and treatment: a review of current perspectives. Front Pain Res (Lausanne) 2021;2:705276.
11. 11. Grangeon L, Lange KS, Waliszewska-Prosół M, et al. Genetics of migraine: where are we now? J Headache Pain 2023;24(1):12.
12. 12. Altamura C, Corbelli I, de Tommaso M, et al. Pathophysiological bases of comorbidity in migraine. Front Hum Neurosci 2021;15:640574.
13. 13. Ashina M, Terwindt GM, Al-Karagholi MA, et al. Migraine: disease characterisation, biomarkers, and precision medicine. Lancet 2021;397(10283):1496-504.
14. 14. Olofsson IA. Migraine heritability and beyond: a scoping review of twin studies. Headache 2024;64(8):1049-58.
15. 15. Raucci U, Boni A, Evangelisti M, et al. Lifestyle modifications to help prevent headache at a developmental age. Front Neurol 2021;11:618375.
16. 16. Ioannidou E, Tsakiris C, Goulis DG, Christoforidis A, Zafeiriou D. The association of serum vitamin D concentrations in paediatric migraine. Eur J Paediatr Neurol 2023;47:60-6.
17. 17. Meng SH, Zhou HB, Li X, et al. Association between dietary iron intake and serum ferritin and severe headache or migraine. Front Nutr 2021;8:685564.
18. 18. Liampas I, Siokas V, Mentis AA, et al. Serum homocysteine, pyridoxine, folate, and vitamin B12 levels in migraine: systematic review and meta-analysis. Headache 2020;60(8):1508-34.
19. 19. de Tommaso M, Sciruicchio V, Delussi M, et al. Laser-evoked potential habituation and central sensitization symptoms in childhood migraine. Cephalalgia 2016;36(5):463-73.
20. 20. Coppola G, Di Lorenzo C, Schoenen J, Pierelli F. Habituation and sensitization in primary headaches. J Headache Pain 2013;14(1):65.
21. 21. Lewis DW, Ashwal S, Dahl G, et al. Practice parameter: evaluation of children and adolescents with recurrent headaches: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2002;59(4):490-8.
22. 22. Sandrini G, Friberg L, Coppola G, et al. Neurophysiological tests and neuroimaging procedures in non-acute headache: second edition. Eur J Neurol 2011;18(3):373-81.
23. 23. Eigenbrodt AK, Ashina H, Khan S, et al. Diagnosis and management of migraine in ten steps. Nat Rev Neurol 2021;17(8):501-14. doi:10.1038/s41582-021-00509-5.
24. 24. Guidetti V, Dosi C, Bruni O. The relationship between sleep and headache in children: implications for treatment. Cephalalgia 2014;34(10):767-76.
25. 25. Dosi C, Figura M, Ferri R, Bruni O. Sleep and headache. Semin Pediatr Neurol 2015;22(2):105-12.
26. 26. Isik U, Ersu RH, Ay P, et al. Prevalence of headache and its association with sleep disorders in children. Pediatr Neurol 2007;36(3):146-51.
27. 27. Meltzer LJ, Montgomery-Downs HE, Insana SP, Walsh CM. Use of actigraphy for assessment in pediatric sleep research. Sleep Med Rev 2012;16(5):463-75.
28. 28. Galland BC, Short MA, Terrill P, et al. Establishing normal values for pediatric nighttime sleep measured by actigraphy: a systematic review and meta-analysis. Sleep 2018;41(4):zsy017.
29. 29. Smith MT, McCrae CS, Cheung J, et al. Use of actigraphy for the evaluation of sleep disorders and circadian rhythm sleep-wake disorders: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2018;14(7):1231-7.
30. 30. Bruni O, Russo PM, Violani C, Guidetti V. Sleep and migraine: an actigraphic study. Cephalalgia 2004;24(2):134-9.
31. 31. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61(4):344-9.
32. 32. Huskisson EC. Measurement of pain. Lancet 1974;2(7889):1127-31.
33. 33. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28(2):193-213.
34. 34. Ağargün MY, Kara H, Anlar Ö. Pittsburgh Uyku Kalitesi İndeksi’nin geçerliği ve güvenirliği. Türk Psikiyatri Derg 1996;7(2):107-15.
35. 35. Sadeh A, Sharkey KM, Carskadon MA. Activity-based sleep-wake identification: an empirical test of methodological issues. Sleep 1994;17(3):201-7.
36. 36. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc 2008;40(1):181-8.
37. 37. Evenson KR, Catellier DJ, Gill K, Ondrak KS, McMurray RG. Calibration of two objective measures of physical activity for children. J Sports Sci 2008;26(14):1557-65.
38. 38. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96(7):1911-30.
39. 39. Kuratani J, Pearl PL, Sullivan L, et al. American Clinical Neurophysiology Society Guideline 5: minimum technical standards for pediatric electroencephalography. J Clin Neurophysiol 2016;33(4):320-3.
40. 40. Peltola ME, Leitinger M, Halford JJ, et al. Routine and sleep EEG: minimum recording standards of the International Federation of Clinical Neurophysiology and the International League Against Epilepsy. Epilepsia 2023;64(3):602-18.
41. 41. Selvanathan J, Tang NKY, Peng PWH, Chung F. Sleep and pain: relationship, mechanisms, and managing sleep disturbance in the chronic pain population. Int Anesthesiol Clin 2022;60(2):27-34.
42. 42. Araujo Gouhie F, Alves Silva D, Rizzo Parreira B, et al. Melatonin compared to other treatments for episodic migraine: a systematic review and network meta-analysis. Can J Neurol Sci 2025:1-7.
43. 43. Reina-Varona Á, Madroñero-Miguel B, Gaul C, et al. Therapeutic exercise parameters, considerations, and recommendations for migraine treatment: an international Delphi study. Phys Ther 2023;103(10):pzad080.
44. 44. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ 2015;350:g7594.
45. 45. Lund J, Berring-Uldum A, Colak M, Debes NMM. Headache in children and adolescents: the association between screen time and headache within a clinical headache population. Neuropediatrics 2022;53(4):221-6.