Investigating the relationship between vasovagal syncope and migraine: a case-control study among Lebanese patients

Background: This study investigates the association between migraines and vasovagal syncope (VVS), focusing on shared autonomic dysfunction mechanisms in a Middle Eastern population. Methods: Using a case-control design, 163 participants (57 with migraines and 106 controls) were assessed through validated tools, including the Migraine Disability Assessment (MIDAS) and Patient Health Questionnaire-4 (PHQ-4). Results: Multivariable analyses results demonstrated a significant association between migraines and VVS, with migraine patients exhibiting nearly threefold higher odds of VVS. Gender differences were pronounced, with females displaying higher susceptibility. Additional drug use and comorbid conditions were also significant factors. Interestingly, the MIDAS score was not found to be significantly correlated with VVS, highlighting the intricacy of autonomic dysfunction. Conclusions: These findings underline that screening for autonomic dysfunction must be conducted in migraine patients and that gender-specific approaches should be adopted in their clinical management. Further research is needed to study the causative pathways and to validate these findings in a large and varied population.

Migraine; Vasovagal syncope; Autonomic dysfunction

[1] Li XY, Yang CH, Lv JJ, Liu H, Zhang LY, Yin MY, et al. Global, regional, and national epidemiology of migraine and tension-type headache in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019. The Journal of Headache and Pain. 2023; 24: 126.

[2] Headache Classification Committee of the international headache society (IHS) the international classification of headache disorders, 3rd edition. Cephalalgia. 2018; 38: 1–211.

[3] Pavelić AR, Zebenholzer K, Wöber C. Reconceptualizing autonomic function testing in migraine: a systematic review and meta-analysis. The Journal of Headache and Pain. 2024; 25: 54.

[4] Moulton EA, Becerra L, Johnson A, Burstein R, Borsook D. Altered hypothalamic functional connectivity with autonomic circuits and the locus coeruleus in migraine. PLOS ONE. 2014; 9: e95508.

[5] Choi I, Jeon SR. Neuralgias of the head: occipital neuralgia. Journal of Korean Medical Science. 2016; 31: 479–488.

[6] Hatoum T, Raj S, Sheldon RS. Current approach to the treatment of vasovagal syncope in adults. Internal and Emergency Medicine. 2023; 18: 23–30.

[7] Tajdini M, Tavolinejad H, Aminorroaya A, Aryan Z, Jalali A, Alaeddini F, et al. Clinical associations of injuries caused by vasovagal syncope: a cohort study from a tertiary syncope unit. Journal of the American Heart Association. 2023; 12: e027272.

[8] Cho BH. The pathophysiology of syncope and the role of transcranial Doppler in its diagnostic evaluation. Journal of Neurosonology and Neuroimaging. 2024; 16: 51–62.

[9] Stewart JM. Common syndromes of orthostatic intolerance. Pediatrics. 2013; 131: 968–980.

[10] Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the population-based CAMERA study. Neurology. 2006; 66: 1034–1037.

[11] Kossaify A, Kallab K. Neurocardiogenic syncope and associated conditions: insight into autonomic nervous system dysfunction. Archives of the Turkish Society of Cardiology. 2013; 41: 75–83.

[12] Paisley RD, Arora HS, Nazeri A, Massumi A, Razavi M. Migraine and vasodepressor syncope in a large family. Texas Heart Institute Journal. 2009; 36: 468–469

[13] Stewart WF, Lipton RB, Kolodner K. Migraine Disability Assessment (MIDAS) score: relation to headache frequency, pain intensity, and headache symptoms. Headache. 2003; 43: 258–265.

[14] Al Jumah M, Al Khathaami AM, Kojan S, Hussein M, Thomas H, Steiner TJ. The prevalence of primary headache disorders in Saudi Arabia: a cross-sectional population-based study. The journal of headache and pain. 2020; 21: 11.

[15] Caro-Fuentes S, Sanabria-Mazo JP. A systematic review of the psychometric properties of the Patient Health Questionnaire‑4 (PHQ‑4) in different populations. Journal of the Academy of Consultation-Liaison Psychiatry. 2024; 65:178–194.

[16] Löwe B, Wahl I, Rose M, Spitzer C, Glaesmer H, Wingenfeld K, et al. A 4-item measure of depression and anxiety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. Journal of Affective Disorders. 2010; 122: 86–95.

[17] Shankhwar V, Urvec J, Steuber B, Schmid Zalaudek K, Saloň A, Hawliczek A, et al. Effects of menstrual cycle on hemodynamic and autonomic responses to central hypovolemia. Frontiers in Cardiovascular Medicine. 2024; 11: 1290703.

[18] Lin W, Liu Y, Liang CS, Yeh PK, Tsai CK, Hung KS, et al. Syncope in migraine: a genome-wide association study revealing distinct genetic susceptibility variants across subtypes. Journal of Clinical Neurology. 2024; 20: 599–609.