Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study
TL;DR: Migraine pain was not accompanied by extracranial arterial dilatation, and by only slight intracranial dilated arteries, and future migraine research should focus on the peripheral and central pain pathways rather than simple arterial Dilatation.
Abstract: Summary Background Extracranial arterial dilatation has been hypothesised to be the cause of pain in patients who have migraine without aura. To test that hypothesis, we aimed to measure extracranial and intracranial arteries during attacks of migraine without aura. Methods In this cross-sectional study, we recruited patients aged 18–60 years from the Danish Headache Centre and via announcements on a Danish website. We did magnetic resonance angiography during spontaneous unilateral migraine attacks. Primary endpoints were difference in circumference of extracranial and intracranial arterial segments comparing attack and attack-free days and the pain and the non-pain side. The extracranial arterial segments measured were the external carotid (ECA), the superficial temporal (STA), the middle meningeal (MMA), and the cervical part of the internal carotid (ICA cervical ) arteries. The intracranial arterial segments were the cavernous (ICA cavernous ) and cerebral (ICA cerebral ) parts of the internal carotid, the middle cerebral (MCA), and the basilar (BA) arteries. This study is registered at Clinicaltrials.gov, number NCT01471314. Findings Between Oct 12, 2010, and Feb 8, 2012, we recruited 78 patients, of whom 19 women had a scan during migraine and were included in the final analysis. On migraine compared with non-migraine days, we detected no statistically significant dilatation of the extracranial arteries on the pain side (ECA, mean difference 1·2% [95% CI −5·7 to 8·2] p=0·985, STA 3·6% [–3·7 to 11·0] p=0·532, MMA 1·7% [–1·7 to 5·2] p=0·341, and ICA cervical 2·3% [–0·3 to 4·9] p=0·093); the intracranial arteries were more dilated during attacks (MCA, 13·0% [6·4 to 19·6] p=0·001, ICA cerebral 11·5% [5·6 to 17·3] p=0·0004, and ICA cavernous 11·4% [5·3 to 17·5] p=0·001), except for the BA (1·6% [–2·7 to 5·9] p=0·621). Compared with the non-pain side, during attacks we detected dilatation on the pain side of the intracranial arteries (MCA, mean difference 10·5% [0·7–20·3] p=0·044, ICA cerebral (14·4% [4·6–24·1] p=0·013), and ICA cavernous (9·1% [3·9–14·4] p=0·003) but not of the extracranial arteries (ECA, 2·1% [–3·8 to 9·2] p=0·238, STA, 3·6% [–3·7 to 10·8] p=0·525, MMA, 2·7% [–1·3 to 5·6] p=0·531, and ICA cervical , 5·0% [–0·5 to 10·4] p=0·119). Interpretation Migraine pain was not accompanied by extracranial arterial dilatation, and by only slight intracranial dilatation. Future migraine research should focus on the peripheral and central pain pathways rather than simple arterial dilatation. Funding University of Copenhagen, the Lundbeck Foundation, the Research Foundation of the Capital Region of Denmark, Danish Council for Independent Research-Medical Sciences, and the Novo Nordisk Foundation.
Citations
More filters
TL;DR: Investment in understanding migraine leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.
Abstract: 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.
1,036 citations
Cites background from "Magnetic resonance angiography of i..."
...In addition, Amin and colleagues (40) demonstrated in a study using...
[...]
...Human studies show no meaningful change in external carotid branches (40, 58, 713),...
[...]
...spontaneous migraine attacks (40), something which has been previously demonstrated during experimentally triggered migraine (713)....
[...]
...The results further indicate that intracranial vessels show only a slight dilation that is not affected by sumatriptan, making the vascular theory obsolete (40)....
[...]
TL;DR: Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals.
Abstract: Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.
645 citations
Cites background from "Magnetic resonance angiography of i..."
...[2] found evidence for slight intracranial vasodilatation that was not affected by sumatriptan, and no evidence for extracranial vasodilatation in patients undergoing spontaneous attacks, suggesting that vascular changes might not have a primary role in migraine....
[...]
TL;DR: Treatments that target calcitonin gene-related peptide (CGRP) and its receptor are proving effective for migraine treatment, and the hypothesis that CGRP has a major role in migraine pathophysiology is strongly supported.
Abstract: Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.
536 citations
TL;DR: The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy.
Abstract: 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.
318 citations
TL;DR: Current concepts of CSD and its potential roles in migraine are summarized, and ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon are addressed.
Abstract: Cortical spreading depression (CSD), a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the 1940s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. Substantial evidence from animal models provides indirect support for this hypothesis, and studies showing that CSD is common in humans with brain injury clearly demonstrate that the phenomenon can occur in the human brain. Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon.
314 citations
References
More filters
5,847 citations
TL;DR: The epidemiologic profile of migraine has remained stable in the United States during the past 15 years and more than one in four migraineurs are candidates for preventive therapy, and a substantial proportion of those who might benefit from prevention do not receive it.
Abstract: Objectives: 1) To reassess the prevalence of migraine in the United States; 2) to assess patterns of migraine treatment in the population; and 3) to contrast current patterns of preventive treatment use with recommendations for use from an expert headache panel. Methods: A validated self-administered headache questionnaire was mailed to 120,000 US households, representative of the US population. Migraineurs were identified according to the criteria of the second edition of the International Classification of Headache Disorders. Guidelines for preventive medication use were developed by a panel of headache experts. Criteria for consider or offer prevention were based on headache frequency and impair- ment. Results: We assessed 162,576 individuals aged 12 years or older. The 1-year period prevalence for migraine was 11.7% (17.1% in women and 5.6% in men). Prevalence peaked in middle life and was lower in adolescents and those older than age 60 years. Of all migraineurs, 31.3% had an attack frequency of three or more per month, and 53.7% reported severe impairment or the need for bed rest. In total, 25.7% met criteria for "offer prevention," and in an additional 13.1%, prevention should be considered. Just 13.0% reported current use of daily preventive migraine medication. Conclusions: Compared with previous studies, the epidemiologic profile of migraine has remained stable in the United States during the past 15 years. More than one in four migraineurs are candidates for preventive therapy, and a substantial proportion of those who might benefit from prevention do not receive it.
1,932 citations
Karlstad University1, Dresden University of Technology2, Karolinska University Hospital3, Mental Health Services4, Phillips University5, University of Florence6, Karolinska Institutet7, John Radcliffe Hospital8, King's College London9, London School of Economics and Political Science10, Lund University11, Harvard University12, University of Basel13, Norwegian University of Science and Technology14, University of Zurich15, Umeå University16, University of Cambridge17, University of Lausanne18, University of Sassari19, European Monitoring Centre for Drugs and Drug Addiction20, Aalborg University21, Cliniques Universitaires Saint-Luc22, Maastricht University Medical Centre23, Radboud University Nijmegen24, Stockholm School of Economics25
TL;DR: The present report presents much improved cost estimates for the total cost of disorders of the brain in Europe in 2010, covering 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items.
1,325 citations
TL;DR: This new report presents updated, more accurate, and comprehensive 2010 estimates of annual costs for brain disorders in Europe for 30 European countries.
Abstract: BACKGROUND AND PURPOSE: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, ...
1,297 citations
TL;DR: Findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control.
Abstract: Evidence from animal experiments shows that the brain stem is involved in the pathophysiology of migraine. To investigate human migraine, we used positron emission tomography to examine the changes in regional cerebral blood flow as an index of neuronal activity in the human brain during spontaneous migraine attacks. During the attacks, increased blood flow was found in the cerebral hemispheres in cingulate, auditory and visual association cortices and in the brain stem. However, only the brain stem activation persisted after the injection of sumatriptan had induced complete relief from headache and phono- and photophobia. These findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control.
1,291 citations