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
SeriesThe pathophysiology of migraine: implications for clinical management
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
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