Elsevier

The Lancet Neurology

Volume 17, Issue 2, February 2018, Pages 174-182
The Lancet Neurology

Series
The pathophysiology of migraine: implications for clinical management

https://doi.org/10.1016/S1474-4422(17)30435-0Get rights and content

Summary

The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients.

Introduction

The ongoing Global Burden of Diseases, Injuries, and Risk Factors Study continues to identify migraine as a leading cause of disability worldwide,1, 2 particularly in individuals younger than 50 years.3 Notably, disorders that are commonly comorbid with migraine, including neck pain, depression, and anxiety, are also among the top ten causes of disability worldwide, placing migraine in a central position among the world's most disabling disorders.1, 2 Furthermore, medication overuse headache is now one of the top causes of disability worldwide.1 The overlap between migraine and several other commonly disabling disorders indicates that they might have common mechanisms; improved understanding of these shared mechanisms could inform the clinical management of the diseases that cause a substantial proportion of the world's leading disability.

Much progress has been made in the understanding of migraine, which has created new opportunities for more effective management of patients. In this Series paper, I describe the most recent advances in genetics and pathophysiology, and their implications in the management of patients with migraine.

Section snippets

Classification and diagnosis

The International Classification of Headache Disorders (ICHD) remains an invaluable resource for criteria for the diagnosis of migraine. The evolution of this classification system reflects a growing understanding of the heterogeneity of headache disorders and their variable clinical presentations. Several important revisions regarding migraine diagnosis have been made in the most recent iteration of the ICHD (ICHD-3 beta4). For example, using the ICHD-2 criteria, patients needed to have 15

Genetics

Although migraine is commonly familial, genome-wide association studies have not yet identified any genetic alterations with large effect sizes.11 Single gene mutations have been found in rare migraine syndromes, including familial hemiplegic migraine and monogenic vasculopathies,4, 12, 13, 14 as well as in individual families. Two genetic mutations associated with migraine identified in two families are in the gene encoding the enzyme casein kinase 1δ (CK1δ). These mutations are also

Phases of a migraine attack

A migraine attack can be divided into phases on the basis of its temporal relationship to headache: the premonitory phase (precedes headache), the aura phase (immediately precedes or accompanies headache), the headache phase, and the postdrome phase (after resolution of headache).18 Although this description of a migraine attack is practical, the phases of an attack can be overlapping and variable. Some symptoms of a migraine attack (sensory sensitivity and neck pain) might be present

Management

Effective clinical management of migraine requires recognition and elimination of specific exacerbating factors, and personalisation of acute and preventive treatment approaches.

Conclusions and future directions

The pace of progress in the understanding of migraine is accelerating rapidly, and the direct translation of the results of basic migraine research into new treatments that specifically target migraine mechanisms is particularly gratifying. Improved understanding of genetic factors underlying migraine has the potential to tailor therapies to individuals with different genetic backgrounds. Characterisation of the premonitory phase of a migraine attack and its underlying mechanisms provides an

Search strategy and selection criteria

References were identified by searches of PubMed between Jan 1, 2012, and Aug 31, 2017, and references from relevant articles. The search terms “migraine”, “diagnosis”, “disability”, “genetics”, “pathophysiology”, “PET”, “MRI”, “electrophysiology”, “pharmacology”, “premonitory”, “aura”, “postdrome”, “therapy”, “treatment”, “CGRP”, and “PACAP” were used. I did not apply any language restrictions. The final reference list was generated on the basis of relevance to the topics covered in this

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