Hypermobility Spectrum Disorders and Active Migraine in Israeli Adolescents: A Nationwide Study

Objective: To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel.Background: The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations.Methods: This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 +/- 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined.Results: Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses.Conclusions: We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.