Multiple Sclerosis and Migraine


By Dr Saloua Mrabet, Tunis, currently Fellow with BartsMS

“Doctor!! Am I having a relapse? Do I need a new MRI? Do I need steroids?”

These are some basic questions when your patient with Multiple Sclerosis (PwMS) calls you very anxious after a typical migraine attack.

And even more perplexed when you answer “No!! it’s not a relapse”.

She adds “But Doctor!! I am really struggling, I’m unable to live normally. I feel a throbbing pain or a pulsing sensation in one side of my head which sometimes moves to the other side. It’s associated with nausea and vomiting and extreme sensitivity to light and sound and can last for hours even days. The pain can sometimes be so severe that it interferes with my daily activities, I can’t cook, I can’t take care of my 2-year-old baby and I can’t even talk to my husband and friends. All I can do is lie in my bed in a dark and quiet room”.

For decades, headache was considered as an atypical symptom of MS or a « red flag » leading to other differential diagnoses. Meanwhile, several studies confirmed that primary headaches are common in PwMS with a pooled prevalence estimated at 57% and with predominance of migraine without aura and tension-type headaches1,2.  Recently, a systematic review of MS morbidities examined the period before clinical MS onset and identified that migraine is part of the MS prodrome3.

First of all, how to differentiate between an MS relapse and an episode of a migraine (especially with aura)

In PwMS, a relapse is defined as an acute or subacute monophasic clinical episode lasting at least 24 hours, with patient-reported symptoms and objective findings typical of MS in the absence of fever or infection.

 Multiple Sclerosis relapseMigraine with Aura‡
TriggersInfections, stressSleep deprivation, some foods*, weather changes, menstruations, fluorescent lights
Presenting symptomsUnilateral painful optic neuritis, focal supratentorial syndrome, focal brainstem or cerebellar syndrome, or partial myelopathyVisual scotoma, migratory paresthesia and dysphasic speech associated or followed with migraine type headache
Duration1-30 days5 minutes – 60 minutes
Neurological examinationNeurological deficitsNormal
* List of migraine potential dietary triggers5: Chocolate, citrus fruits, nuts, ice cream, tomatoes, onions, dairy products, alcoholic beverages, monosodium glutamate, histamine, tyramine, phenylethylamine, nitrites, aspartame, sucralose, and gluten

A special mention to hemiplegic migraine which is a rare form of migraine with aura (atypical migraine with aura) including motor aura 6. The aura consists of fully reversible motor weakness or fully reversible visual, sensory and or speech/language symptoms. The most frequent are sensory symptoms. Motor weakness varies from mild clumsiness to complete paralysis in the areas affected by sensory symptoms. The different aura symptoms slowly progress over 20–30 min in the order of visual, sensory, motor, aphasic, and basilar disturbances6.

Coexistence of neurological symptoms with white matter abnormalities could be tricky when the diagnosis of MS is not yet established. Typically, MS lesions are ovoid with a suggestive topography (periventricular, cortical or juxtacortical) with gadolinium enhancement.  Whereas, in patients with migraine lesions are smaller, punctuate and mainly subcortical without evidence of gadolinium enhancement at any stage4.

Disease-modifying treatments (DMTs) for MS and Migraine

Studies performed before the era of disease-modifying treatments (DMTs) for MS confirmed the possible coexistence between MS and Migraine. Therefore, results were not influenced by the possible effect of DMTs such as interferons which have been associated with an increased risk of headache in clinical trials and post-marketing reports. Fingolimod was also reported to be associated with daily persistent headache in some PwMS5. In Alemtuzumab-treated patients, headache was reported mainly as an infusion reaction7.   

In the 2-year CLARITY Extension study, headache was the third most frequent reported adverse event in MS patients treated with Cladribine (14,9% of all included patients)8. For other DMTs (glatiramer acetate, teriflunomide, dimethyl fumarate, Natalizumab, Ocrelizumab and Daclizumab), they have not been reported to have major associated headaches5.

Practical points

The management of migraine in people with MS follows the same principles as in the general population. It’s based on an accurate diagnosis followed by the treatment with pharmacological and non-pharmacological modalities. Moreover, pharmacological treatment includes acute symptomatic treatment when the patient experiences a headache attack and daily preventive medications if migraine episodes are frequent and debilitating9.

Headaches should be evaluated regularly in all PwMS because of the well-demonstrated high prevalence and the negative effect on patient’s quality of life.

For the diagnosis of migraine in PwMS, clinicians should consider the possible secondary causes of headaches in a young patient especially if it persists despite appropriate treatment. 

The possible diagnosis of medication overuse headache is also to be considered because PwMS can use pain killers for many reasons.

Moreover, evaluation of the relationship between current DMT and the headache is mandatory because some of them such as interferons may cause or exacerbate headaches.

Furthermore, screening of frequent comorbidities to both conditions like depression and anxiety is recommended because of the possibility to worsen and increase migraine attacks.

When considering preventive therapies, caution is needed because of the increased risk of adverse events with the multiple medication interactions9,10. Although considered one of the most prescribed treatment options for migraine in adults, tricyclic antidepressants should be avoided in PwMS as they could worsen a previous cognitive impairment. Non-pharmacological interventions should also be encouraged. 

Dr Saloua Mrabet, Assistant Professor in Neurology, Department of Neurology, Clinical Investigation Center Neurosciences and Mental Health, Razi University Hospital La Manouba 2010-Tunis, Faculty of medicine of Tunis, University of Tunis El Manar

Disclaimer: The opinions expressed on this Blog are those of the author and nobody else.


  1. Wang L, Zhang J, Deng ZR, Zu MD, Wang Y. The epidemiology of primary headaches in patients with multiple sclerosis. Brain Behav. 2021;11(1):e01830. doi:10.1002/brb3.1830
  2. La Mantia L, Prone V. Headache in multiple sclerosis and autoimmune disorders. Neurol Sci. 2015;36 Suppl 1:75-78. doi:10.1007/s10072-015-2146-9
  3. Yusuf FLA, Ng BC, Wijnands JMA, Kingwell E, Marrie RA, Tremlett H. A systematic review of morbidities suggestive of the multiple sclerosis prodrome. Expert Rev Neurother. 2020;20(8):799-819. doi:10.1080/14737175.2020.1746645
  4. Applebee A. The clinical overlap of multiple sclerosis and headache. Headache. 2012;52 Suppl 2:111-116. doi:10.1111/j.1526-4610.2012.02243.
  5. Fragoso YD, Adoni T, Gomes S, et al. Persistent headache in patients with multiple sclerosis starting treatment with fingolimod. Headache. 2015;55(4):578-579. doi:10.1111/head.12526
  6. Russell MB, Ducros A. Sporadic and familial hemiplegic migraine: pathophysiological mechanisms, clinical characteristics, diagnosis, and management. Lancet Neurol. 2011;10(5):457-470. doi:10.1016/S1474-4422(11)70048-5
  7. CAMMS223 Trial Investigators, Coles AJ, Compston DA, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786-1801. doi:10.1056/NEJMoa0802670
  8. Giovannoni G, Soelberg Sorensen P, Cook S, et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018;24(12):1594-1604. doi:10.1177/1352458517727603
  9. Chisari CG, Sgarlata E, Arena S, D’Amico E, Toscano S, Patti F. An update on the pharmacological management of pain in patients with multiple sclerosis. Expert Opin Pharmacother. 2020;21(18):2249-2263. doi:10.1080/14656566.2020.1757649
  10. Husain F, Pardo G, Rabadi M. Headache and Its Management in Patients with Multiple Sclerosis. Curr Treat Options Neurol. 2018;20(4):10. Published 2018 Mar 24. doi:10.1007/s11940-018-0495-4

About the author

The MS Bloggger


  • Migraines are not rare in the general public. Two of my closest friends and my cousin suffer from frequent migraines. They don’t have MS.

    I have MS and rarely get migraines or headaches.

    • Yes, Migraine is a frequent condition in the general population. Patients with MS don’t necessarily have migraine or other headache types. However, the association is more and more reported. In this situation, the management of both diseases becomes tricky.

  • A migraine that lasts 1 hour – I WISH!!! I assume in your table that you mean the aura lasts 5-60 mins. My migraines last 3 disabling days from start of prodrome to end of postdrome. The intense pain lasts around 24hours. Please clarify the duration of the migraine in your article.

    • Thanks for your question. Yes, the duration of 5 to 60 minutes refers to the symptoms of the aura by analogy to the symptoms of the relapse. The headache can last from 4 to 72 hours.

  • Is it possible for migrainous activity to be constant (I mean migraine pain and/or sensory symptoms that are always present)?

    • Migraine typically presents with attacks of headache limited in time (4-72 hours). Exceptionally, it could last more. Sensory symptoms which are part of the aura didn’t exceed 1 hour and are followed by a headache.

  • I found this article very enriching as it disringuishes clearly between a relapse and a migraine attacke especially that both diseases coexist frequently. Sheding the light on the impact of MS treatment on migraine is crucial as it has been hilighted in this article in a very clear way.

  • Valuable and interesting post.
    I had frequent headaches and also less frequent migraines for many years.

    However it was a couple of years or so before diagnosis that the migraines stopped happening. I put this down to the attention I had from a friend training to be a osteopath. To help his own professional development he provided such time and attention into my treatment of head, neck and shoulders.

    On the basis of my own personal experience I would definite endorse use of non pharmacological interventions. However, the nhs unfortunately offers PwMS little or nothing in the way of interventions beyond prescribing DMTs and other meds and a degree of on going monitoring. Consequently any intervention is for those who can pay.

    What I now find is that I experience what I describe as being ‘headachy’ when experiencing stronger fatigue and the stronger the ‘headachy’ pain is, combined with brain fog, then it means I’m on the sofa having a ‘MS day’ of feeling rough and incapable of doing anything.

  • Many thanks, Dr. Mrabet, for posting this. This is a great and very necessary article! I will share it with an international group of several thousand people with ms, users of one of the dmts, that I moderate. I am one of them myself and have had two or three episodes of migraine with aura but, in my case, without headache. Several times, posts from group members made me think that although they have ms what they might be reporting in certain moments might be more related to migraines. May I suggest that you consider writing a short text in more common (rather than scientific) terminology and provide it to different national ms societies for their websites? I believe this would be very helpful for people with ms! Keep up the good work and post again! 🙂



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