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 headaches^1,2.  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 relapse	Migraine with Aura‡
Triggers	Infections, stress	Sleep deprivation, some foods*, weather changes, menstruations, fluorescent lights
Presenting symptoms	Unilateral painful optic neuritis, focal supratentorial syndrome, focal brainstem or cerebellar syndrome, or partial myelopathy	Visual scotoma, migratory paresthesia and dysphasic speech associated or followed with migraine type headache
Duration	1-30 days	5 minutes – 60 minutes
Neurological examination	Neurological deficits	Normal

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 interactions^9,10. 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. 

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

References

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