Migraine as a systemic vasculopathy

Epidemiological studies suggests that migraine is associated with disorders of the cerebral, coronary, retinal, dermal and peripheral vasculature. There is evidence that migraine is associated with endothelial dysfunction, both as a cause and a consequence. Endothelial dysfunction, a vascular risk factor, is characterized by endothelial activation and impaired vascular reactivity. Plasma and genetic biomarkers for these conditions have been identified. The clinical significance lies in the potential for the rapid identification of migraineurs at increased risk of ischaemic stroke and vascular disease through ascertainment of endothelial dysfunction biomarkers. It is uncertain whether stroke, myocardial infarction and other vasculopathies can be prevented by migraine prophylaxis, endothelial repair, platelet inhibition or a combination of these strategies.     

Spreading Depolarization May Link Migraine and Stroke

Migraine increases the risk of stroke, particularly in young and otherwise healthy adults. Being the most frequent neurological condition, migraine prevalence is on a par with that of other common stroke risk factors, such as diabetes or hypertension. Several patterns of association have emerged: (1) migraine and stroke share a common association (eg, vasculopathies, patent foramen ovale, or pulmonary A‐V malformations); (2) injury to the arterial wall such as acute arterial dissections can present as migraine aura attacks or stroke; (3) strokes rarely develop during a migraine attack, as described for “migrainous stroke.” Increasing experimental evidence suggests that cerebral hyperexcitability and enhanced susceptibility to spreading depolarization, the electrophysiologic event underlying migraine, may serve as a mechanism underlying the migraine‐stroke association. Mice carrying human vascular or neuronal migraine mutations exhibit an enhanced susceptibility to spreading depolarization while being particularly vulnerable to cerebral ischemia. The severe stroke phenotype in migraine mutant mice can be prevented by suppressing spreading depolarization. If confirmed in the clinical setting, inhibiting spreading depolarization might protect migraineurs at stroke risk as well as decrease attacks of migraine.     

PET and Doppler sonography in headaches

Whether the primary mechanisms of migraine are vascular or neurogenic is, as yet unresolved. Early studies using Doppler sonography prompted heterogeneous results, mainly due to methodological differences. However, blood flow measurements using single photon emission tomography (SPECT) or positron emission tomography (PET) have not revealed any differences in cerebral blood flow in migraine without aura. Moreover, specific migraine compounds do not alter cortical blood flow. During attacks, increased blood flow is found in the cerebral hemispheres in cingulate, auditory and visual association cortices and the brain stem. Altogether, these findings suggest that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control, rather than in primary vessel diameter changes.     

Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.     

Migraine and ischaemic vascular events

An association between migraine and ischaemic vascular events, particularly ischaemic stroke, has been debated for many years. The pathophysiology of migraine has been explored in detail, and it is known that a dysfunction of brain cells and arteries is a major component of this disorder. The involvement of cerebral arteries during the migraine attack as well as the high prevalence of migraine among young individuals with ischaemic stroke has led to the hypothesis that migraine may be a risk factor for ischaemic stroke. Furthermore, there is evidence that the vascular nature of migraine is not limited to meningeal blood vessels and that migraine and overall cardiovascular disease may share aetiological pathways. The aim of this review is to summarize the epidemiological evidence that links migraine with ischaemic stroke and ischaemic heart disease and to discuss potential biological mechanisms.     

Retinal vascular caliber and migraine: the Blue Mountains Eye Study

OBJECTIVE: To assess whether migraine is associated with retinal microvascular caliber. BACKGROUND: Migraine is believed to be associated with vascular disease, but few studies have investigated the relationship between structural microvascular changes and migraine. DESIGN: Population-based cross-sectional study. METHODS: Participants in the Blue Mountains Eye Study follow-up (1997 to 1999, n = 2,335, aged 54+) had retinal photographs taken. A computer-assisted method was used to measure average retinal arteriolar and venular diameters and calculate the arteriole-to-venule ratio. History of migraine was recorded by interview using International Headache Society criteria (1988). RESULTS: Subjects giving a history of migraine without aura (n = 128) had narrower retinal arterioles than subjects giving a history of migraine with aura (n = 182) or subjects with no migraine history (n = 1619). After multivariate adjustment, mean retinal arteriolar diameter was 4.3 microm (95% confidence interval 0.5, 8.1) narrower in subjects reporting migraine without aura as compared to subjects with no migraine. CONCLUSIONS: Individuals with a history of migraine without aura were more likely to have slightly narrower retinal arteriolar caliber than individuals without migraine. This relationship was not present for migraine with aura. These data support the hypothesis that microvascular disease may be associated with certain types of migraine.     

偏头痛相关性脑卒中发病中抗磷脂抗体的作用

目的研究和探讨偏头痛与缺血性卒中的相关性以及抗磷脂抗体在偏头痛相关性卒中发病中的作用. 方法运用问卷调查方式统计普通人群及脑梗死患者偏头痛的患病率,将脑梗死患者按有否偏头痛病史分为两组,用 ELISA方法分别测定其血清抗心磷脂抗体( anticardiolipin antibodies , ACA)水平. 结果①脑梗死患者偏头痛的患病率与普通人群偏头痛的患病率分别为 20.0 %和 6.0%,二者之间差异有显著性意义(χ2=13.2671,P< 0.01).②脑梗死伴有偏头痛史者和无偏头痛史者,其 ACA阳性率分别为 41.7 %和 19.5 %,二者差异具有显著性意义(χ 2=5.0133,P< 0.05). 结论偏头痛病史与脑梗死具有明显相关性.抗磷脂抗体可能参与偏头痛所相关的脑梗死的发病机制.     

Role of dopaminergic system in migraine

The theory that hypersensitivity of dopamine (DA) system is involved in the pathogenesis of migraine has been supported by various authors on the basis of clinical, pharmacological and, recently, genetic evidence. Apomorphine, a selective and specific DA agonist, has a cerebral vasodilatatory effect and increases blood flow significantly in the middle cerebral artery in migraineurs. Processes from central DA neurons terminate in close contact with penetrating arterioles and cerebral capillaries in the cerebral cortex. This finding reaffirms the role of central neurogenic mechanisms in the regulation of the cerebral circulation and, we believe, further supports the major role of dopamine in the neurogenic mechanisms of migraine. Various studies have been carried out to verify the involvement of DA in migraine pathogenesis using molecular genetics as a tool. A positive association between the “dopaminergic” phenotype of migraine without aura and the D2 receptor gene has been found. To explain dopaminergic hypersensitivity in migraine without aura, we will study the genes encoding proteins involved in the signal transduction system.     

Brain hypoxia: the turning-point in the genesis of the migraine attack?

The hypothesis postulates that a brief episode of focal cerebral hypoxia occurs in every attack of migraine. Clinical, biochemical and technical (EEG and CT scans) evidence is summarized suggesting that cerebral hypoxia may indeed occur in the course of a migraine attack. Focal hypoxia is seen as the turning-point in the pathogenesis of the attack. It may be provoked by different mechanisms in different patients; the potential role of decreased oxygen supply and of increased oxygen need are reviewed and excess sympathetic drive is considered a potential key mechanism in a majority of patients. Whether or not focal hypoxia leads to a genuine migraine attack, depends largely upon the quality of the whirlpool of biochemical, vascular and hematological changes that follow the hypoxic episode. These changes are discussed and it is concluded that those which have been reported to occur during migraine attacks could be due to a preceding hypoxic event. Finally, the hypoxia viewpoint is confronted with some popular theories about the pathogenesis of migraine. It is found that the other points of view are compatible with the hypoxia hypothesis.     

How Imaging Can Help Us Better Understand the Migraine-Stroke Connection

Migraine and stroke are among the most prevalent and disabling neurological diseases. Epidemiologic studies showed that there is an association between migraine and stroke. Migraineurs, especially those with aura, are more likely to develop subclinical infarct-like lesions in the brain and are at risk for cryptogenic or cardioembolic stroke. Migrainous headache can be found at the onset of acute ischemic stroke in some patients, and in rare instances, an infarction can be directly attributed to a prolonged migraine aura, ie, migrainous infarction. Importantly, recent studies suggest that in the event of cerebral artery occlusion, even a history of migraine is sufficient to accelerate infarct progression and worsen outcomes. The mechanisms underlying the migraine-stroke connection are multifactorial, with genetic predisposition, aura-related electrophysiological mechanisms (cortical spreading depolarization), and cerebral microembolism being the most convincing ones at this point. Here, we provide a comprehensive overview on recent imaging studies that have helped us better understand the complex association between migraine and stroke.