Migraine and Tension-Type Headache Are Associated with Multiple Sclerosis: A Case–Control Study

<b>Background/Objectives</b>: Over the past few decades, there has been increased scientific interest in the prevalence of headache disorders among people with MS (pwMS). Although the latest data suggest an association between migraine and multiple sclerosis, studies have been providing inconsistent results largely due to methodological differences, including small sample sizes, lack of control groups, absence of structured headache diaries, and variability in diagnostic criteria. This study aims to address the question of whether pwMS have a higher prevalence of primary headache disorders than healthy controls (HCs) and whether MS is associated with an increased risk of headaches. <b>Methods</b>: In this cross-sectional, case-control study, consecutive pwMS from Eginition University Hospital, Athens, Greece, along with matched HCs, were recruited. Both groups were assessed for headache disorders, over the past 3 months from the day of recruitment, using a semi-structured questionnaire and diagnosed according to the International Classification for Headache Disorders 3 (ICHD-3) criteria. A multivariable logistic regression model adjusted for age and sex evaluated the association between MS and headache disorders. <b>Results</b>: Ninety-six pwMS and ninety-six matched HCs met the inclusion criteria and were enrolled in the study. A higher prevalence of primary headache disorders in pwMS (71.9%) compared to HCs (43.8%) was observed. Specifically, 28.1% of pwMS had migraine, and 38.5% had tension-type headache (TTH). PwMS were significantly more likely to be diagnosed with any primary headache disorder (OR = 4.54; 95% CI: 2.28 to 9.04; <i>p</i> = 1.7), migraine (OR = 2.21 95% CI: 1.05 to 4.62; <i>p</i> < 0.05), and TTH (OR = 2.16 95% CI: 1.16 to 4; <i>p</i> < 0.05) compared to HCs. <b>Conclusions</b>: Our study suggests that primary headache disorders are more prevalent in pwMS in a cohort recruited from the MS outpatient clinic at Eginition University Hospital in Athens, Greece, compared to the general population and highlights the need for targeted headache management within this group. Prospective longitudinal studies are needed to draw more robust conclusions on a potential association and its underlying mechanisms.