AAN 2019 Annual Meeting Coverage

Migraine continues to be identified as the one of the leading causes of morbidity worldwide.1-3

As part of the Hot Topics in Headaches and Related Disorders II: Migraine Pathophysiology, Brain Imaging and Therapeutic Advances at the AAN 2019 Annual Meeting in Philadelphia, Prof. Andrew Charles (UCLA Goldberg Migraine Program) gave a lecture titled Update on Migraine Pathophysiology. Prof. Charles started by discussing migraine genetics, and noted that despite migraine being a common condition, genome-wide association studies have not yet identified any genetic alterations with large effect sizes. While migraine-associated gene polymorphisms exist, a wide range of factors typically contribute to the onset of a migraine attack, including genetic, environmental, and metabolic factors.3,1,4 Despite these findings, Prof. Charles pointed out that there is a long way to go towards fully understanding migraine genetics.-

Prof. Charles proceded to explain that several anatomical brain regions are involved in migraine attacks, including the trigeminocervical complex, the cortex, thalamus, hypothalamus, and the brainstem. In his opinion, each of these areas could potentially be responsible for the typical migraine symptoms, via a variety of pathophysiological mechanisms. Prof. Charles described the calcitonin gene-related peptide (CGRP) as integral to our current understanding of migraine pathophysiology. However, he raised questions relating to the nature of the triggers of CGRP release, as well as whether the location of its effect lies within the central or peripheral nervous system. Prof. Charles also cited a recent study showing that neurons in the parabrachial nucleus expressing CGRP are activated by noxious stimuli—e.g. shock, heat, or itch—suggesting that factors distinct from vascular events are involved in CGRP release.5

He further stressed that while the pathophysiology of migraine remains incompletely elucidated, it likely involves a crosstalk between central and peripheral nervous systems, as well as the contribution of different brain areas.

Prof. Charles concluded that metabolic, hormonal, environmental, and genetic factors all play a role in migraine, and reminded the audience of the ongoing challenge of fully understanding the interplay of these various elements.

“There is a long way to go to understand migraine genetics”

– Professor Andrew Charles

References

  1. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries,1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet.2016;388:1545-1602.
  2. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390:1211-1259.
  3. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17:174-182.
  4. Royal P, et al. Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK. Neuron. 2019;101:232-245.e236.
  5. Campos CA, et al. Encoding of danger by parabrachial CGRP neurons. Nature. 2018;555:617-622.