Multiple sclerosis (MS) is a chronic inflammatory disease leading to multifocal neuronal demyelination and axonal damage in the central nervous system (CNS). MS symptoms vary widely but typically do not include headaches. A large spectrum of headaches manifestations was reported as comorbidities in MS and results in additional disability. Migraine, tension-type headache and cluster headache are the most frequently reported primary headache syndromes in patients with MS (pwMS). Secondary causes of headache should be excluded (cerebral vein thrombosis, CNS or systemic infection, cervical and/or cranial trauma, headaches associated with psychiatric disorders, medication overuse headache, etc.) in this particular population. A careful medical history and general and neurological examinations and sometimes further investigations may be needed to rule out secondary headache syndromes. In pwMS, the headache could be an adverse effect of the disease-modifying therapies or a complication of pain medication overuse prescribed to relieve other causes of pain related to MS (neuropathic pain, mechanical pain, pain associated with spasticity, etc.). Migraine-type headache occurs in pwMS more frequently than in the general population. It can precede the disease onset, be associated with relapses, or appear during the MS course. A predominance of brainstem inflammatory lesions is described on magnetic resonance imaging (MRI) in MS patients with migraine. The relationship between both conditions remains unclear. Migraine and MS occur in the same demographic groups with similar background factors, including gender, hormonal status, and psychological features (anxiety, depression, stress). An early diagnosis and adequate treatment of migraine in MS patients are important to improve their quality of life. In this review, we focus on the relationship between MS and Migraine, discuss the differential diagnoses of migraine in pwMS, and describe its management in this particular context.
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