Neurol India Home 

Year : 2020  |  Volume : 68  |  Issue : 6  |  Page : 1338--1339

Association between Multiple Sclerosis and Headache: An Unresolved Conundrum

Debashish Chowdhury 
 Professor of Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India

Correspondence Address:
Dr. Debashish Chowdhury
Professor of Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi

How to cite this article:
Chowdhury D. Association between Multiple Sclerosis and Headache: An Unresolved Conundrum.Neurol India 2020;68:1338-1339

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Chowdhury D. Association between Multiple Sclerosis and Headache: An Unresolved Conundrum. Neurol India [serial online] 2020 [cited 2021 Mar 6 ];68:1338-1339
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In the current issue, in a paper titled “Investigation of the association between headache type, frequency, and clinical and radiological findings in patients with multiple sclerosis”,[1] the authors assessed 320 patients of multiple sclerosis (MS) and found that primary headache was present in 54.4% of the patients [migraine in 30.6% and tension-type headache (TTH) in 23.8%)] at the time of admission. They also found that patients with TTH had higher disability scores than those with migraine (4.7 versus 1.8; P < 0.001). This is possibly due to the fact that the patients with TTH had greater mean disease duration than those with migraine (9.9 versus 4.9; P < 0.001). There were also more juxta-cortical lesions in migraine patients. Being a retrospective study, the implications of these findings are difficult to interpret although broadly speaking this frequency of occurrence of headache in MS is consistent with previously reported studies.[2],[3] The authors however, did not segregate the results in terms of MS subtypes.

During the last two decades, the association between headache and MS has received much attention from researchers. The frequency of headache in MS has been reported to vary widely from 4 to 69%.[4] Recent clinic-based studies have also shown a high frequency of migraine, TTH, and medication overuse headache in MS patients.[2],[3]A metanalysis also reported that MS patients do have a high frequency of pain syndromes (67%), the commonest of which is a headache (43%).[5] However, there is still uncertainty as to whether MS patients have a greater prevalence of headaches than the general population because the case-control studies have produced conflicting results. While some studies showed an increased prevalence of headache in MS patients as compared to controls, others did not.[4],[6] Since headache is a very common complaint in the general population, further larger cross-sectional case-control and longitudinal cohort studies will be needed to answer this question.

The understanding of this association is not merely academic. Indeed, it has important pathophysiological, diagnostic, and therapeutic implications. The high prevalence of headache in MS patients makes us ponder whether this is just a comorbid association or is a primary symptom of MS. It has been suggested that MS can trigger migraine and vice versa. Pathological studies have shown that the meninges of MS patients had lymphoid follicle-like structures and an increased number of macrophages, T, and B-cells. It has been postulated that these may be responsible for meningeal inflammation and can trigger headaches, particularly migraine in MS patients.[4] Locations of the MS plaques in the brain may also be important. MS patients with migraine-like headaches have a greater frequency of lesions within the midbrain/periaqueductal grey matter area which has been recognized as important areas involved in central pain regulation.[4] Contrast enhancing (CE) lesions on MRI has been found in asymptomatic MS patients with migraine thereby raising the possibility that migraine might have triggered MS. Migraine patients are known to have changed in the serotonin levels in their brain which in turn can disrupt the blood-brain barrier (BBB). Due to the breach in BBB together with neurogenic inflammation and release of potent neuropeptides during recurrent bouts of headache, an immune mechanism may set up which can facilitate the development of MS. However, these hypotheses remain speculative as both the diseases can occur alone and therefore, a cause-and-effect relationship is difficult to establish.

Diagnostically, the clinical significance of recurrent headaches in a patient who is later diagnosed as clinically or radiologically isolated syndrome (CIS/RIS) remains unclear. This assumes importance in view of a recent study that reported migraine or probable migraine in 78% of MS or CIS patients at the time of presentation.[7] This study also showed that the headaches decreased significantly after six months following treatment with immunomodulators. Therefore, the question arises should the young patients with typical or atypical headache phenotypes undergo MRI to diagnose early MS? Headache disorders being so common and a lack of a distinctive headache phenotype in MS makes it difficult to argue for such an approach. MS therapy can also lead to headaches. A recent study involving 515 MS patients with headache found that in 80%, the headaches occurred after the initiation of therapy.[3] Hence the relative contributions of the disease and the therapy in causing headache need to be looked into greater detail.


1Demetgul O, Duman T, Guntel M. Investigation of the association between headache type, frequency, and clinical and radiological findings in patients with multiple sclerosis. Neurol India 2020;68:1333-7.
2Fragoso YD, Adoni T, Alves-Leon SV. Migraine in 746 patients with multiple sclerosis. Arquivos de Neuro-psiquiatria 2019;77:617-21. DOI: 10.1590/0004-282x20190100.
3Beckmann Y, Türe S. Headache characteristics in multiple sclerosis, Multiple Sclerosis and Related Disorders. 2019;27:112-116. 2018.09.022.
4La Mantia L, Prone V. Headache in multiple sclerosis and autoimmune disorders. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2015;36(Suppl 1):75-78. DOI: 10.1007/s10072-015-2146-9.
5Foley PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, et al. Prevalence and natural history of pain in adults with multiple sclerosis: Systematic review and meta-analysis. Pain 2013;154:632-42.
6Gustavsen M, Celius E, Winsvold B, Moen S, Nygaard G, Berg- Hansen P, et al. Migraine and frequent tension-type headache are not associated with multiple sclerosis in a Norwegian case-control study. Mult Scler J Exp Transl Clin 2016;2:1-4.
7Gebhardt M, Kropp P, Jürgens TP, Hoffmann F, Zettl UK. Headache in the first manifestation of Multiple Sclerosis - Prospective, multicenter study. Brain and Behavior 2017;7:e00852. DOI: 10.1002/brb3.852.