Migraine is generally considered a common condition in people living with multiple sclerosis (MS) [1]. Back in 1952, D. McAlpine and N. Compston intended to describe “some aspects of the natural history of disseminated sclerosis” [2, p. 135]. They investigated a group of 250 individuals with MS and reported that five of them had experienced migraine in the three months before the onset of the disease. All five patients had a previous history of migraine [2, 3]. More recently, F.L.A. Yusuf and co-authors reviewed 29 studies and found that people with MS commonly experience migraine before the onset of the disease [4]. The prevalence of migraine in patients with MS varies across different countries – higher in American and African countries (43%), lower in European and Asian countries (25% and 24%, respectively) [5]. Researchers are investigating why migraine and MS can occur together.
What is the relationship between migraine and MS?
Ruth Ann Marrie, the Past Chair of the Medical Advisory Committee for the MS Society in Canada and a professor at the University of Manitoba, says, “Migraine is what we call episodic headache. Typically, people with migraine experience periods of throbbing headache, which can concern one half of the head or the entire head. In these periods, people can be sensitive to bright lights, sounds or strong smells. Therefore, people with migraine prefer to quietly lie down in the dark. The headache, which is sometimes accompanied by nausea or vomiting, can last on average a couple of hours or shorter if one takes medications. However, for some people, headaches can be longer lasting.” The episodes of headache are interspersed with periods of complete freedom from symptoms [6].
Disentangling the nature of the possible co-occurrence of migraine and MS poses a significant challenge. Recently, M.K. Horton and co-authors found no evidence indicating that migraine is a causal risk factor for MS. However, they identified several genetic variants shared between MS and migraine. This can partially explain the overlap between the two conditions [7]. Moreover, among the Northern California MS cohort, people with MS who experienced migraine – 38.9% – were more likely to be female, have ever smoked, and have a history of depression compared to people with MS who did not have migraine [7].
The timing of the diagnosis of migraine in people with MS can also vary. Professor Marrie added, “Some people can have migraine long before any symptom of MS, whereas others may develop or be diagnosed with migraine after the diagnosis of MS. One aspect to consider is that people with MS see neurologists more often, compared to the general population. Therefore, there is a possibility that some of the differences that we see in the timing of labelling of migraine in people with MS is related to the fact that most of them regularly see a neurologist. I saw many people who clearly had a history of migraine, but only got a label during neurological visits for MS. This is one factor that can influence the timing of when these diagnoses appear.”
Migraine and MS in clinical trials and healthcare
The International Headache Society (IHS) defines the migraine as a primary headache disorder – a condition by itself, not caused by any other disorders [8]. The British Association for the Study of Headache (BASH) provides guidelines to help clinicians identify signs of secondary headache disorders due to other underlying problems [9]. After an accurate diagnosis, migraines in adults and children with MS are managed according to standard recommendations, with special consideration for issues relevant to MS patients [10]. For example, some pharmacological treatments, such as interferon-β, may contribute to worsen migraine in some people with MS [11].
It is crucial to represent individuals with common comorbidities in clinical trials to reliably predict the benefits and risks of the drug in people who will use it in the real world [12]. In this regard, Professor Marrie adds, “If we do not describe people in clinical trials with respect to the comorbidities they have, we do not really know how they compare to the patients we see in clinical practice. We need to know how well the information from clinical trials applies to clinical practice. Furthermore, comorbidities can have an impact on outcomes, on relapses, and disability progression, and this is often what we are trying to address in clinical trials. So, the differences and the characteristics of people in the trials related to their comorbidities may influence the rate of events in clinical trials. We need to start describing who is in the trial and to investigate the efficacy and safety of disease-modifying therapies in people with comorbidities.”
A meta-analysis of phase-III clinical trials investigated the prevalence of comorbidities in nearly 18,000 people with MS enrolled in 17 clinical trials. It revealed that 46.5% of participants had one or more comorbid conditions. Migraine was one of the most prevalent comorbidities, especially in female participants and younger age groups [12].
Lifestyle modifications can help managing migraine
Ann Yeh, professor at the Department of Paediatrics (Neurology) of the Hospital for Sick Children – University of Toronto – told us, “When managing migraine in children as in the adult population, we start from lifestyle modifications. A headache can be managed in a conservative manner, meaning by changing sleep habits, getting enough sleep, eating breakfast, and ensuring adequate fluid intake in the morning. In the paediatric population, we found that headaches can be brought up by stressors. Therefore, self-examination of the nature of these stressors that trigger migraine is part of our counseling with children. Furthermore, we are looking at physical activity as an intervention to mitigate depression and fatigue. If headache is associated with depression and fatigue, perhaps physical activity can also improve those symptoms. We are strong proponent of physical activity for many reasons. Beyond that, we do have therapeutic options for frequent headaches that are not responsive to lifestyle modifications.”
S. Mrabet and co-authors highlighted another interesting point: considering its benefits for both MS and for migraine, physical exercise can be recommended to people who have both conditions [10, 13, 14].
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Written by Stefania de Vito
Special thanks to Professor Ruth Ann Marrie (University of Manitoba), and Professor Ann Yeh (University of Toronto), for their insights.
References
[1] Hawkes CH et al. Mult. Scler. Relat. Disord. 2023; 74: 104769.
[2] McAlpine D & Compston N. Q. J. Med. 1952; 21: 135-167.
[3] Kister I et al. Mult. Scler. J. 2012; 18(1): 90-97.
[4] Yusuf FLA et al. Expert Rev. Neurother. 2020; 20(8): 799-819.
[5] Mirmosayyeb O et al. J. Clin. Neurosci. 2020; 79: 33-38.
[6] Ahmed F. Br. J. Pain 2012; 6(3): 124-132.
[7] Horton MK et al. Neurol. 2023; 100(13): e1353-e1362.
[8] https://ichd-3.org
[9] https://bash.org.uk/guidelines/
[10] Mrabet S, Wafa M, & Giovannoni G. Mult. Scler. Relat. Disord. 2022; 68: 104152.
[11] Patti F et al. Acta Neurol. Scand. 2012; 125(2): 91-95.
[12] Salter A et al. Neurol. 2024; 102(5): e209135.
[13] Barber M & Pace A. Curr. Pain Headache Rep. 2020; 24 (8): 39.
[14] Kalb R et al. Mult. Scler. J. 2020; 26(12): 1459-1469.