Headaches and MS linked, and therapies may affect them: Study

Interferon seems to raise risk, while rituximab may lower it

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A person grimaces and holds his head while red lines are shown radiating from the forehead.

A large 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 study found. In contrast, the CD20 antibody rituximab that’s used off-label in MS significantly reduced the risk.

MS occurs when the immune system launches an inflammatory attack on the myelin sheath — a protective coating around nerve fibers that’s critical for the efficient transmission of nerve signals — leading to a wide range of symptoms. A common symptom of MS is primary headaches, or those caused by problems in the brain’s pain-sensitive structures. They are likely a result of MS-related damage to certain brain structures or the impact of disease-modifying therapies.

Not much is known about the characteristics of primary headaches in people with MS, or about the factors that may make them more or less likely to occur in patients. “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 Egypt wrote.

Their study, “Prevalence of primary headaches in multiple sclerosis patients,” was published in the journal Multiple Sclerosis and Related Disorders.

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Migraines, tension headaches common

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

The patients, with a median age of 33, were mostly women (74.7%) and the majority had relapsing-remitting MS (RRMS; 73.3%). About one quarter (25.6%) had secondary progressive MS (SPMS). Only a small proportion had primary progressive MS (PPMS; 1.1%).

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

Migraines are characterized by severe pain, usually on one side of the head, often accompanied by nausea, vomiting, and extreme sensitivity to light and sound. In some cases, a migraine can be preceded by an aura, with changes in vision or tingling in the hands or face.

Tension-type headaches affect both sides of the head and come on slowly, usually without causing nausea, vomiting, or light sensitivity.

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Headaches after diagnosis for many

Almost half of the patients (47.7%) 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 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 (sold as Gilenya, among others).

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%) with severe headaches.

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

The team found treatment with interferon-based therapies was linked to an increased risk of worsening preexisting headaches and the appearance of new headaches. Patients taking these medications had a 63% 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% lower risk of worsened headaches and an 82% lower risk of new-onset headaches.

“Interferon can exacerbate preexisting 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.”