Pathogenesis of Migraine

Posted by Carla Rothaus

Are effective therapies available to prevent migraine? 

Although the pathogenesis of migraine is incompletely understood, it is considered to involve the trigeminal nerve and its axonal projections to the intracranial vasculature (termed the trigeminovascular system). Read the NEJM Review Article here.

Clinical Pearls

Q: What are some of the typical features of migraine?

A: A diagnosis of migraine should be considered if a typical attack of head pain is unilateral, pulsating, and aggravated by physical activity. Common accompanying symptoms are nausea, vomiting, photophobia, and phonophobia. Some persons report that the migraine is preceded by an aura, which is characterized by reversible focal neurologic symptoms, typically comprising visual or hemisensory disturbances.

Q: What is the epidemiology of migraine?

A: Migraine is the second most prevalent neurologic disorder, with a female-to-male ratio of 3:1 and an estimated 1-year prevalence of approximately 15% in the general population. The prevalence peaks between the ages of 35 and 39 years, and about 75% of affected persons report the onset of migraine before the age of 35 years. Migraine also affects a considerable proportion of children, with one population-based study showing a 1-year prevalence of about 7% among school-age children. Since the disorder tends to remit with older age, an onset of migraine after the age of 50 years should arouse suspicion of a secondary headache disorder.

Morning Report Questions

Q: What medications are used to treat migraine?

A: The most widely used initial medications for migraine are nonsteroidal antiinflammatory drugs (NSAIDS), which are low-cost, over-the-counter analgesic agents. Effectiveness has been best documented for acetylsalicylic acid, ibuprofen, and diclofenac. Triptans are considered second-line medications, and in patients for whom one oral triptan is ineffective, others in the drug class may provide adequate pain relief. Patients are advised to switch from one oral triptan to another if three migraine attacks have been treated without success. There has been cautious enthusiasm for the small-molecule calcitonin gene–related peptide (CGRP) receptor antagonists, called gepants, and the 5-hydroxytryptamine type 1F (5-HT1F) receptor agonists, called ditans, in the treatment of acute migraine. The Food and Drug Administration has approved the following oral gepants and ditans for the treatment of acute migraine: ubrogepant, rimegepant, and lasmiditan. At present, the high costs and restricted availability of gepants and ditans probably limit their use to patients for whom NSAIDs and triptans are ineffective, have unacceptable side-effect profiles, or are contraindicated.

Q: Are effective therapies available to prevent migraine?

A: Advice regarding when preventive treatment should be initiated in the course of an individual patient’s migraine trajectory varies among countries, but such treatment is generally recommended for patients who have at least two migraine days per month and whose lives are adversely affected despite therapy. Off-label use of therapies has become common because of the limited number of approved preventive medications. New mechanism-based preventive therapies have recently been introduced. These include four injectable monoclonal antibodies targeting CGRP or its receptor (eptinezumab, erenumab, fremanezumab, and galcanezumab), which all have documented effectiveness in randomized trials for the preventive treatment of episodic and chronic migraine. These drugs have a rapid onset of effect and result in few adverse events, the most common being injection-site reactions, such as erythema and pain.

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