Migraine and multiple sclerosis: The final answer?

It is generally accepted that migraine is more common in people with multiple sclerosis (PwMS; Mrabet et al., 2022 Mrabet S Wafa M Giovannoni G. Multiple sclerosis and migraine: Links, management and implications. Multiple Sclerosis Related Disorders. 2022; 104152 Abstract Full Text Full Text PDF Scopus (3) Google Scholar ), but is this simply the chance association of two common disorders? Two large meta-analyses estimated the prevalence of migraine in PwMS at about 31% ( Mirmosayyeb et al., 2020 Mirmosayyeb O Barzegar M Nehzat N Shaygannejad V Sahraian MA Ghajarzadeh M. The prevalence of migraine in multiple sclerosis (MS): A systematic review and meta-analysis. J. Clin. Neurosci. 2020; 79: 33-38 Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar ; Wang et al., 2021 Wang L Zhang J Deng ZR Zu MD Wang Y. The epidemiology of primary headaches in patients with multiple sclerosis. Brain Behavior. 2021; 11: e01830 Crossref PubMed Scopus (8) Google Scholar ). Shared features include being White, female, and having a diagnosis in early adult life. It has been proposed that migraine might be a causal risk factor for MS ( Kister et al., 2012 Kister I Munger KL Herbert J Ascherio A. Increased risk of multiple sclerosis among women with migraine in the Nurses’ Health Study II. Multiple Sclerosis J. 2012; 18: 90-97 Crossref PubMed Scopus (32) Google Scholar ), who documented a small but significant increased risk of MS (29%) in females at baseline, compared to those without migraine. The authors ( Kister et al., 2012 Kister I Munger KL Herbert J Ascherio A. Increased risk of multiple sclerosis among women with migraine in the Nurses’ Health Study II. Multiple Sclerosis J. 2012; 18: 90-97 Crossref PubMed Scopus (32) Google Scholar ) debate whether the higher rate of migraine in PwMS is due to errors in diagnosis of MS in migraine sufferers. Thus, women with migraine are more likely to be seen by a neurologist who arranges a brain scan that suggests MS based on non-specific white matter changes that are common in migraine. Alternatively, migraine-like headache may be a presenting symptom of MS or part of the MS prodrome ( Tremlett et al., 2022 Tremlett H Munger KL Makhani N. The multiple sclerosis prodrome: Evidence to action. Front. Neurol. 2022; 12761408 Crossref PubMed Scopus (5) Google Scholar ). Both explanations were considered unlikely, and it is concluded that because migraine generally predates MS by many years, and migraine at MS onset is rare, suggests that migraine is more likely a pre-existing diagnosis.