Headache and Trigeminal Neuralgia in Multiple Sclerosis

headache migraine
headache migraine
Researchers found that abnormal magnetic resonance imaging suggests that in patients with multiple sclerosis, headaches often precede diagnoses.

Even though migraines and trigeminal neuralgia (TN) frequently occur in patients with multiple sclerosis (MS), researchers are still attempting to untangle the relationship between pain and MS. Some theories about the headache-MS connection include:

  • pathology that includes B-cell follicles in the gyri and meninges
  • inflammation-influenced cortical demyelination that promotes cortical spreading depression
  • lesions in the midbrain1

Another potential cause of migraines that occur in patients with MS may be interferon therapy. Patients with relapsing-remitting MS tend to experience more headaches than do patients with other types of MS. Women are 3 times as likely to have migraines with MS as men. Of the migraine types, chronic migraines occur with greater severity and impair quality of life more than episodic migraines in patients with MS.1

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Targeting the Pain of MS

Patients with MS and pain are challenging to treat because so few receive adequate analgesia for their pain. One of the emerging theories is that resident glial cells and infiltrating immune cells prompt the chronic pain associated with MS.2

“New pharmacologic entities targeting multiple pathways which are recruited not only during disease progression but that are also likely involved in the generation of untreatable painful syndromes could represent a significant advance in the parallel management of MS disabilities and of the concurring pain symptoms,” said Stefania Ceruti, PhD, associate professor of pharmacology from the University of Milan, Italy in the journal Pain Management. “To this aim, glial cells appear as one of the most promising targets for the development of new therapies that would lead to a significant improvement in the quality of life of MS patients.”2

Patients With MS Who Have Headaches

To better characterize the association between headaches and MS, neurologists Yeşim Beckmann, MD, and Sabiha Türe, MD, from Izmir Katip Celebi University, Izmir, Turkey, surveyed 754 patients (median age, 36 years; 61% women) with MS and headaches, which occurred in 68% of all participants. By far, the most common type of headache in patients with MS were migraines (39%), closely followed by medication overuse headaches (38%), and tension headaches (20%).3

Although other studies demonstrated that more women with MS are likelier than men with MS to have migraines, the men in this study were slightly more likely than women to have migraines, at 40% and 38%, respectively.3 Most of the patients with headache were treated with interferon beta (73.8%), fingolimod (14.8%), teriflunomide (7.2%), and natalizumab (4.3%).3

“We believe that as a consequence of our methodology the headache prevalence reported in this paper reflects the frequency of headaches in MS patients more accurately,” wrote Dr Beckmann and Dr Türe. “Despite its high prevalence and proven disability for sufferers, headaches can be neglected during patient physician visit since physicians focus on the symptoms related to MS. Taken together, headaches should be evaluated in all MS patients because of their high prevalence, impact, and negative effect on MS prognosis and treatment.”3

Trigeminal Neuralgia May Precede MS

Pain is often a symptom of MS and TN is one of the most common pain syndromes associated with MS.4 Patients with MS have a 20-fold chance of developing TN, regardless of the type of MS.5

MRI is the usual diagnostic for MS and for TN secondary to MS.5 Depending on the location of the nerve damage, MRI can help neurosurgeons identify the root cause of TN and can use the imaging for surgical microvascular decompression to treat the pain.5

Often, TN precedes an MS diagnosis.4 That was the premise behind a survey by neurologist Ahmad Fallata, MD, from the University of Manitoba, Winnipeg, Manitoba, Canada, and colleagues who queried 8590 patients in the North America Research Committee on Multiple Sclerosis Registry.4 The prevalence of TN in this population was 9.7%, with 15.0% reporting that their facial pain preceded their MS diagnosis.4 Patients most likely to report TN were women and those with longer TN duration and pain.4 The mean age at TN presentation was 45.3 years.4

“TN can be primary (idiopathic) or secondary—that is due to some other underlying condition, such as a tumor or multiple sclerosis,” said coauthor and neurologist Ruth Ann Marrie, MD, PhD, FRCPC, associate professor from the University of Manitoba in Winnipeg, Canada in an interview with Neurology Advisor. “There are several features that should prompt a clinician to think about secondary TN including age of onset <50 years, abnormalities on the neurologic examination, or other associated symptoms.”

Pharmacologic treatments were overwhelmingly more common than invasive procedures, with most patients taking anticonvulsant medications.4 Although most of the registry patients did not undergo procedures, 10% of those who did chose gamma-knife radiotherapy.4

“There has been little or no evaluation of the role of lifestyle factors on TN in MS, but some studies suggest that smoking may be associated with worse pain in general; so quitting smoking may be helpful,” Dr Marrie said.

Summary and Clinical Applicability

Headaches, and migraines in particular, frequently occur in patients with multiple sclerosis. Emerging evidence suggests that targeted therapies that address the cause of the pain may provide adequate analgesia.


1. Husain F, Pardo G, Rabadi M. Headache and its management in patients with multiple sclerosis. Curr Treat Options Neurol. 2018;20(4):10.

2. Ceruti S. What role does multiple sclerosis play in the development of untreatable painful conditions? Pain Manag. 2018;8(1):37-44.

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

4. Fallata A, Salter A, Tyry T, Cutter GR, Marrie RA. Trigeminal neuralgia commonly precedes the diagnosis of multiple sclerosis. Int J MS Care. 2017;19(5):240-246.

5. Di Stefano G, Maarbjerg S, Truini A. Trigeminal neuralgia secondary to multiple sclerosis: from the clinical picture to the treatment options. J Headache Pain. 2019;20(1):20.