Abstract
Objective
Recent studies have shown a pathophysiologic link between headache and multiple sclerosis (MS), but the prevalence of primary headaches among patients with MS differs substantially across studies. This meta‐analysis aimed to comprehensively gather available evidence to estimate the prevalence of primary headaches among patients with MS.
Method
We systematically searched the electronic databases including PubMed, Embase, and Scopus for cohort, case–control, cross‐sectional studies that measured the prevalence of headache among patients with MS. Two reviewers independently screened titles and abstracts to identify the eligible studies and the full texts of the included studies were reviewed. Newcastle‐Ottawa Scale (NOS) was used to assess the risk of bias of the included literatures. We then conducted a meta‐analysis using Stata Software 15.0 to calculate the pooled prevalence of headaches among patients with MS and assess the source of heterogeneity.
Results
We identified 16 eligible studies covering a total of 3,560 patients with MS. The pooled estimated prevalence of primary headaches among patients with MS was 56%. The statistical heterogeneity was moderate with I2 of 82.1% (p < .001). Both a visual inspection of the funnel plot and Egger’ regression tests revealed no significant publication bias (p = .44). The pooled estimated prevalence of migraine (55%) was higher in comparison with that of tension‐type headache (20%). The prevalence of migraine subtype was 16% and 10% for migraine without aura and migraine with aura, respectively. The pooled prevalence of primary headache in case–control group (57%) was approximately in line with the cross‐sectional group (56%).
Conclusion
The overall prevalence of primary headaches among patients with MS was considerably high. Clinical screening of headache among patients with MS will be helpful to formulate an individualized treatment plans and alleviate the physical and mental impact of the disease.
1 INTRODUCTION
Multiple sclerosis (MS) is a chronic and progressive demyelinating disease of the central nervous system (CNS), which is characterized by spatially and temporally multiple lesions of unknown etiology (Hauser & Cree, 2020). Epidemiological studies have shown an increasing prevalence of MS in overall in Europe, Latin America, Middle East, and the Mediterranean Basin (Benito‐León & Bermejo‐Pareja, 2010; Cristiano et al., 2016). On the other hand, recent studies have shown that comorbid diseases such as stroke, epilepsy, and headache can adversely affect the quality of life, treatment outcome, and life expectancies in MS patients (Moisset et al., 2013).
Headache is a common neurological comorbidity in MS. The prevalence of primary headaches among patients with MS has been reported to be high, ranging from 35.5% to 70%, with migraine and tension‐type headache being the most frequent types (Busillo et al., 2014; Foley et al., 2013; Moisset et al., 2013). An autopsy of MS patient demonstrated a lymphatic follicular structure proliferation leading to an inflammatory response of the brain meninges (Koshihara et al., 2014). T‐cell and B‐cell activation in meningitis has been presumed to contribute to the high prevalence of headache, especially migraine headache, in patients with MS (Levy, 2009; Moreno et al., 2018). On the other hand, both headache and MS are associated with the functional or structural alterations of brainstem and cortex (Bourgeais‐Rambur, Beynac, & Villanueva, 2019; Tortorella et al., 2006), suggesting a shared anatomical basis for the comorbid relationship between headache and MS.
The prevalence of both migraine and MS is highest in white race, followed by black race, and finally yellow race (Applebee, 2012). However, epidemiologic evidence from current studies showed low consistence in primary headache prevalence among patients with MS. Therefore, we systematically reviewed and meta‐analyzed the available studies to investigate the overall prevalence of primary headaches among patients with MS and provide guidance for screening and diagnosing the primary headaches comorbid with MS in clinical practice.