ArticlesMagnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study
Introduction
Migraine is the most prevalent neurological disorder, affecting more than 100 million people in Europe1 and the USA.2 It ranks in the top 20 of the most disabling medical illnesses globally, and has substantial effects on the quality of life of patients and their families and on health costs.3 However, the pathophysiological mechanisms of migraine are not fully understood.4 For decades, the throbbing pain during migraine headache was thought to originate from dilated cranial arteries. Tunis and Wolff5 reported increased pulsation of the superficial temporal artery (STA) during attacks. Unilateral stimulation of extracranial and intracranial arteries was associated with ipsilateral head pain.6
During the past two decades, however, the focus on this vascular hypothesis has diminished, and neuronal mechanisms have been suggested to generate migraine headache without abnormal activation of perivascular sensory fibres.7 Findings from studies using novel brain imaging methods during migraine attacks lent support to this view.8, 9 The vascular hypothesis was further challenged by the advent of non-vasoconstrictor anti-migraine treatments, such as ditans10 and calcitonin-gene-related peptide (CGRP)-receptor antagonists,11 which questioned the role of vasoconstriction in the antimigraine action of triptans. Findings from studies using high-resolution magnetic resonance angiography (MRA) suggested that vasodilatation might be involved, but also provided conflicting results.12, 13 These MRA studies can be criticised because they used pharmacological triggers—glyceryl trinitrate12 and CGRP13—to provoke migraine attacks.
Large-scale studies of spontaneous migraine attacks with MRA are challenging for logistical reasons and have not been done. During attacks, patients are nauseated and afraid of vomiting, and their pain is aggravated by physical activity. For these reasons, they do not want to travel and are therefore not easily recruited. Furthermore, the attacks occur unpredictably and, when the attack occurs, immediate access to an MRI scanner is necessary. Consequently, to the best of our knowledge, MRI-based direct measurement studies of cerebral or extracerebral arteries during spontaneous migraine attacks have not been done.
We set up to test the hypothesis that intracranial and extracranial arteries would be dilated on the headache side during a migraine attack. We also hypothesised that therapeutic use of the selective antimigraine drug sumatriptan, a 5-hydroxytryptamine (5-HT1B/1D) agonist, would cause vasoconstriction as well as pain relief.
Section snippets
Study design and participants
We recruited participants via an announcement on a Danish website for recruitment of volunteers to health research and from the outpatient clinic at the Danish Headache Center (Glostrup Hospital, Copenhagen, Denmark). We approached only the patients who lived within 50 km of Glostrup Hospital. Patients were eligible for inclusion if they were aged 18–60 years and had a verified diagnosis of migraine without aura in accordance with the International Headache Society criteria.14 Exclusion
Results
We recruited 78 patients, of whom 19 completed the scan during a migraine attack and were included in the final analysis (figure 2). Eight of these 19 patients were recruited through the Danish recruitment website and 11 were recruited at the Danish Headache Center. All patients recruited were women. Median age was 33 years (range 19–52), median duration of disease was 16 years (5–34), and median attack frequency was 3 per month (1–8) for the whole group. 15 (79%) of the 19 patients had
Discussion
In our study, extracranial dilatation of arteries did not occur during spontaneous migraine attacks. These findings are in contrast with the classic hypothesis suggested by Harold G Wolff and still seen in many textbooks: that dilatation of extracranial arteries might be the cause of migraine pain.12, 13 Another major finding from our study was that sumatriptan relieved migraine pain in parallel with constriction of normal calibre extracerebral arteries, but that it had no effect on dilated
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