Significance and Prevalence of Headache in Multiple Sclerosis

Research study results showed that treatments for multiple sclerosis precipitated headaches and migraines.

Migraine is at least 3 times more common in patients with multiple sclerosis (MS) than in the normal population, the significance of which is not well understood. Recent studies have indicated a preponderance of headache complaints in patients with MS that could be due to multiple etiologies.

The majority of headaches reported in studies were migraine, although tension-type headache (TTH) is also commonly observed.1,2 “Headache is common among people with MS,” explained Ruth Ann Marrie, MD, director, Multiple Sclerosis Clinic, Health Sciences Centre in Winnipeg, Manitoba, Canada. “This is not entirely surprising given that a large proportion of people with MS are women—and women are at greater risk of migraine, for example.” Dr Marrie reported that in her practice she sees many headache types, including but not limited to tension type headache, migraine, cluster headache, and occipital neuralgia.

Migraine and MS

Kister and colleagues1 reported a 64% headache prevalence rate in a cross-sectional study of patients at the New York University MS center, of which 72% were diagnosed as migraine. They found that migraine headache was specifically associated with a higher incidence of new or worsening symptoms of MS compared with other types of headache. Although the mechanisms of this correlation were unknown, several theories were suggested. The first was that migraine could initiate an inflammatory response in the brain that would be associated with greater numbers of T1- and T2-enhancing MS lesions. However, the white matter lesions sometimes associated with migraine are smaller and do not enhance on contrast imaging as with MS.

A second explanation was that altered pain perception and a decreased pain threshold associated with migraine may cause patients with MS to experience greater distress from the same symptoms as patients without migraine. Patients with migraine were also likely to experience more frequent episodic neurologic dysfunction (ENDs), especially in cases of migraine with aura. Other pain syndromes such as trigeminal and occipital neuralgia, facial pain, L’hermitte’s sign, temporomandibular joint pain, and non-headache pain, as well as a history of depression were likely to be comorbid with migraine.1

Yet another theory suggested that spreading of cortical depression in migraine with aura enhances previously undetected symptoms of MS, although the study investigators dismissed this notion. According to co-investigator, Teshamae Monteith, MD, a neurologist in Miami, Florida and headache medicine fellowship director and chief, Headache Division, Department of Neurology, University of Miami, Miller School of Medicine, “typically, MS lesions appear in the deep white matter although cortical involvement including cerebral atrophy is described. MS lesions in the brainstem or pons have been associated with migraine like headache. The pons is an important area for migraine.”

Headache as an Early Sign of MS

The prevalence of headache in early MS at first occurrence of neurologic symptoms is even higher than at other times, reported by Gebhardt, et al at a rate of 78% in a study of 50 patients with MS with clinically isolated syndrome.2 Because these patients tended to be younger than other patients with MS, the study pointed to headache as an important early symptom of undetected MS and suggested the need for magnetic resonance imaging (MRI) of the head to improve a common latency in MS diagnosis.

The rate of headaches then decreased to 61% at 6 months — in contrast with a study by Beckman, et al4 in which medications overuse was found to be the cause of headaches — which Gebhardt and colleagues attributed to likely improvement as a result of immunotherapeutic treatment for MS, including beta interferon and intravenous immunoglobulin therapy.2,3

Identification of migraine at the time of clinically isolated syndrome was predictive of a more symptomatic MS course and was more likely to be associated with the relapsing remitting form of the disease (RRMS) than other forms of headache.1-3 Kister and colleagues also reported a higher incidence of symptoms involving other systems, including visual, psychiatric, and cognitive symptoms and brainstem involvement.1 Scores on scales measuring anxiety, depression, fatigue, and sleepiness were all higher in patients  with migraine, although this did not translate into greater disability.1

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Treating Migraine in MS

Because the underlying mechanisms are unknown, specific treatment strategies for migraine and other headache types in MS have yet to be explored, and tend to be treated separately. “MS and migraine are separate entities,” Dr Montieth explained, adding that “MS patients respond well to migraine treatments in most cases.”

Treatment of headache in MS should also take into account the high potential of disease modifying drugs (DMDs), particularly interferons used to treat MS, to induce headache symptoms. The Beckman study4 found that 80% of patients with MS reported headache following the initiation of any kind of MS therapy.

Dr Marrie pointed out that, “MS management involves addressing acute relapses, preventing relapses and disability progression and chronic symptom management. Each of these are components of therapy. Since neurologists often manage headache disorders, this can be incorporated into the care of the person with MS, although headache management may require a different approach — that is, if none of the symptom management therapies can be dually used to manage headache. If headache management is particularly difficult, a neurologist with subspecialty expertise in headache might need to be involved.”


1. Kister I, Caminero AB, Monteith TS, et al. Migraine is comorbid with multiple sclerosis and associated with a more symptomatic MS course. J Headache Pain 2010;11:417-425.

2. Gebhardt M, Kropp P, Hoffmann F, Zettl UK. Headache in the course of multiple sclerosis: a prospective study. J Neural Transm (Vienna). 2019;126:131-139.

3. Gebhardt M, Kropp P, Hoffmann F, Zettl UK. Headache at the time of first symptom manifestation of multiple sclerosis: a prospective, longitudinal study. Abstract. Eur Neurol. 2018;80:115-120.

4. Beckmann Y, Türe S. Headache characteristics in multiple sclerosis. Mult Scler Relat Disord 2019;27:112-116.