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Migraine and MS – new insights

By Priscilla Lynch - 23rd Jun 2024

Migraine and MS

Interferon seems to raise migraine risk in people with MS, while rituximab may lower it

 A significant proportion of people with multiple sclerosis (MS) experience headaches as a result of their condition, and treatment with interferon-based therapies seems to increase the risk of worsening headaches or developing new ones, a new study has found.

In contrast, people with MS who took the CD20 antibody rituximab had a significantly lower risk of migraine, found the study published in the journal Multiple Sclerosis and Related Disorders.

A common symptom of MS is primary headaches, likely a result of MS-related damage to certain brain structures or the impact of disease-modifying therapies.

“Headaches can have a significant impact on the MS population, but the relationship between headaches and the course of MS, as well as the impact of MS on primary headaches, is still not fully understood,” the team of researchers from Cairo University, Egypt wrote.

The study researchers analysed 281 MS patients with headache complaints who were seen at neurology units at Cairo University Hospitals from October 2020 to April 2022.

The median age of patients was 33 years old, with a range of 22-to-55 years. The majority were women (74.7 per cent) and the majority had relapsing-remitting MS (RRMS; 73.3 per cent). About one-quarter (25.6 per cent) had secondary-progressive MS. Only a small proportion had primary-progressive MS (PPMS; 1.1 per cent).

Migraine prevalence

After reviewing medical records and interviewing patients about their headache characteristics and patterns, the researchers found that two-thirds of the patients (66.5 per cent) were diagnosed with migraine, and almost one-third (31 per cent) with tension-type headache. Another 2.5  per cent were diagnosed with other types of primary headache.

Almost half of the patients (47.7 per cent) experienced headaches after their MS diagnosis. For half of those, headache symptoms only began after they started a disease-modifying therapy.

The team found tension-type headaches were significantly more common in men, in patients with progressive forms of MS, and in those with a more severe MS-related disability.

Migraines, on the other hand, more commonly occurred in women, patients with RRMS, those with milder disability, and those treated with interferon-based medications or fingolimod.

Migraines were also more frequent in patients with MS lesions in the periaqueductal gray, a cell-dense brain region involved in the control of pain and analgesia.

Lesions in sensorimotor regions, which are involved in processing tactile stimuli and sensory information from the skin, were significantly correlated with headache severity and were present in more than half of patients (53.4 per cent) with severe headaches.

Drug therapy impact

Many patients included in the study were treated with interferon-based therapies (44.1 per cent), followed by fingolimod (27.4 per cent), rituximab (18.1 per cent), and the anti-inflammatory cyclophosphamide (7.5 per cent).

The team found treatment with interferon-based therapies was linked to an increased risk of worsening pre-existing headaches and the appearance of new headaches. Patients taking these medications had a 63 per cent higher risk of experiencing worsened headaches and twice the risk of developing new-onset headaches, compared with other treatments.

On the other hand, patients on rituximab had an 89 per cent lower risk of worsened headaches and an 82 per cent lower risk of new-onset headaches. “Interferon can exacerbate pre-existing headaches and even cause new ones,” the researchers wrote. “Additionally, the location of MS plaques may play a role in the frequency and severity of headaches.”


Abdel Naseer M, Shehata HS, Khalil S, Fouad AM, Abdelghany H. Prevalence of primary headaches in multiple sclerosis patients. Mult Scler Relat Disord. 2024 Jun;86:105602

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