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      Symptoms related to the visual system in migraine

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          Abstract

          Migraine is a common headache disorder characterized by often-severe headaches that may be preceded or accompanied by a variety of visual symptoms. Although a typical migraine aura is not difficult to diagnose, patients with migraine may report several other visual symptoms, such as prolonged or otherwise atypical auras, “visual blurring”, “retinal migraine”, “ophthalmoplegic migraine”, photophobia, palinopsia, and “visual snow”. Here, we provide a short overview of these symptoms and what is known about the relationship with migraine pathophysiology. For some symptoms, the association with migraine is still debated; for other symptoms, recent studies indicate that migraine mechanisms play a role.

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          Pathophysiology of Migraine: A Disorder of Sensory Processing.

          Peter J Goadsby, Philip Holland, Margarida Martins-Oliveira … (2017)
          Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
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            Migraine pathophysiology: lessons from mouse models and human genetics.

            Michel D. Ferrari, Roselin Klever, Gisela Terwindt … (2015)
            Migraine is a common, disabling, and undertreated episodic brain disorder that is more common in women than in men. Unbiased genome-wide association studies have identified 13 migraine-associated variants pointing at genes that cluster in pathways for glutamatergic neurotransmission, synaptic function, pain sensing, metalloproteinases, and the vasculature. The individual pathogenetic contribution of each gene variant is difficult to assess because of small effect sizes and complex interactions. Six genes with large effect sizes were identified in patients with rare monogenic migraine syndromes, in which hemiplegic migraine and non-hemiplegic migraine with or without aura are part of a wider clinical spectrum. Transgenic mouse models with human monogenic-migraine-syndrome gene mutations showed migraine-like features, increased glutamatergic neurotransmission, cerebral hyperexcitability, and enhanced susceptibility to cortical spreading depression, which is the electrophysiological correlate of aura and a putative trigger for migraine. Enhanced susceptibility to cortical spreading depression increased sensitivity to focal cerebral ischaemia, and blocking of cortical spreading depression improved stroke outcome in these mice. Changes in female hormone levels in these mice modulated cortical spreading depression susceptibility in much the same way that hormonal fluctuations affect migraine activity in patients. These findings confirm the multifactorial basis of migraine and might allow new prophylactic options to be developed, not only for migraine but potentially also for migraine-comorbid disorders such as epilepsy, depression, and stroke.
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              The prevalence and characteristics of migraine in a population-based cohort: the GEM study.

              L J Launer, G Terwindt, M. Ferrari (1999)
              To describe the distribution of migraine and its subtypes in the general population. Previous population-based studies are limited by small samples or a narrow age range, do not provide prevalence estimates of migraine with and without aura, or underestimate prevalence by not accounting for patients missed as a result of using imperfect screening instruments. The participants in the Genetic Epidemiology of Migraine Study were comprised of 6,491 adults, age 20 to 65 years, selected randomly from two county population registries in the Netherlands to participate in a general health survey (52.7% response). Migraineurs were identified as follows: All participants were screened on headache history. Those meeting screen-positive criteria were given a detailed questionnaire on headache. A total of 1,292 randomly selected screen-positives (83% of screen-positives) and 197 randomly selected screen-negatives (5% of screen-negatives) were administered a semistructured clinical interview by telephone. Final diagnosis met 1988 International Headache Society criteria. Prevalence of migraine was estimated for sex and 5-year age strata. The lifetime prevalence of migraine in women was 33% and the 1-year prevalence of migraine in women was 25%. In men, the lifetime prevalence was 13.3% and the 1-year prevalence was 7.5%. Among patients with migraine in the past year, 63.9% had migraine without aura, 17.9% had migraine with aura, and 13.1% had migraine both with and without aura. The prevalence of migraine was significantly higher in women and not associated with socioeconomic status. Migraineurs suffered a median of 12 migraine attacks per year; 25% had at least two attacks per month. The prevalence of migraine is higher then previously reported. The coexistence of migraine with and without aura occurs frequently and has implications for future studies on the genetics of migraine.
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                Author and article information

                Contributors
                Robin M. van Dongen: Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                ORCID: https://orcid.org/0000-0002-7946-0485
                Joost Haan: Role: ConceptualizationRole: Writing – Review & Editing
                Journal
                Journal ID (nlm-ta): F1000Res
                Journal ID (iso-abbrev): F1000Res
                Journal ID (pmc): F1000Research
                Title: F1000Research
                Publisher: F1000 Research Limited (London, UK )
                ISSN (Electronic): 2046-1402
                Publication date (Electronic): 30 July 2019
                Publication date Collection: 2019
                Volume: 8
                Electronic Location Identifier: F1000 Faculty Rev-1219
                Affiliations
                [1 ]Department of Neurology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
                [2 ]Department of Neurology, Alrijne Ziekenhuis, Simon Smitweg 1, 2353 GA, Leiderdorp, The Netherlands
                Author notes

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-7946-0485
                Article
                DOI: 10.12688/f1000research.18768.1
                PMC ID: 6668047
                SO-VID: 9044264b-5e7b-480b-a876-76dc10d8b800
                Copyright © Copyright: © 2019 van Dongen RM and Haan J
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date accepted : 9 July 2019
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Subject: Review
                Subject: Articles

                Keywords: migraine aura,prolonged aura,persistent aura,retinal migraine,ophthalmoplegic migraine,photophobia,palinopsia,visual snow
                Data availability:
                Keywords: migraine aura, prolonged aura, persistent aura, retinal migraine, ophthalmoplegic migraine, photophobia, palinopsia, visual snow

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