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.     

Platelet dysfunction and stroke in the female migraineur

Some studies suggest that platelet activation and aggregation are associated with migraine, likely secondary to changes occurring during the acute attack. Evidence also suggests that platelet clots can lodge in small cerebral vessels, and that the resultant is chemia and inflammation can induce cortical spreading depression with aura-like symptoms and pulsatile headache. Endothelial dysfunction, a result of numerous vascular, genetic, and environmental risk factors, is more common in women with migraine and leads to altered hemostasis. When associated with other factors, such as oral contraceptive use, there may be an increased tendency for thrombus formation, secondary migraine with aura, transient ischemic attacks, and stroke. Identifying those migraineurs at highest risk of developing endothelial dysfunction and platelet disorders may allow for preventive strategies to avoid the cerebral consequences.     

Spinal cord infarction during use of zolmitriptan: a case report

A 50-year-old woman with a history of migraine without aura, predominantly occurring around her menstrual periods, developed a spinal cord lesion following the use of zolmitriptan. The partial lesion of the cord at T7 predominantly involved the spinothalamic pathways on the left side. Clinical features suggested that the lesion was an ischemic infarct, and this was confirmed by an MRI scan. There were no other known risk factors for vascular disease. There has been mild improvement of her symptoms, but most of the symptoms did not resolve. There are isolated case reports of stroke secondary to the use of triptans, however, this is the first case of spinal cord infarction reported following the use of this group of drugs. The temporal relationship suggests that the spinal cord infarction may be related to the use of zolmitriptan.     

Migraine and cerebrovascular disease

Migraine and cerebrovascular disease are linked in different ways: migraine may be a potential cause of stroke as in migrainous infarction, headache may be a symptom of cerebrovascular disease and also a risk factor for stroke, the association of migraine and stroke may constitute specific syndromes such as CADASIL and MELAS. The new IHS 2003 criteria, though preserving their main structure, have changed the terminology regarding secondary headaches, now described as “attributed to” another disease rather than “associated with” it. The more detailed knowledge of causal links between the underlying disorder and headache, has allowed to strengthen the terminology. Many cerebrovascular disorders as cerebral haemorrhage, venous sinus thrombosis, carotid or vertebral dissections and ischaemic stroke may present with a headache or be followed by it. In subarachnoid haemorrhage (SAH) headache may constitute an important warning sign before the bleeding. An interesting issue is the hypothesis that migraine may be a potential risk factor for stroke. Recent studies have underlined the increased relative risk of ischemic stroke in female migraineurs. Many potential mechanisms have been hypothesized: (1) alterations of vasoreactivity due to vessel wall dysfunction, (2) release of vasoactive substances during migraine, (3) platelet hyperactivity as expression of serotoninergic dysfunction in migraineurs, (4) intriguing studies have described a high prevalence of migraine with aura in stroke patients with patent foramen ovale (PFO). Differential diagnosis between migraine and stroke remains fundamental: some types of migraine can mimic cerebrovascular disease such as familial hemiplegic migraine, and basilar migraine. Migraine and stroke may be part of syndromic complexes as in CADASIL and MELAS. In conclusion migraine is a risk factor for cerebrovascular disease, it may be the cause of stroke as in migrainous infarctions, stroke may induce headache which may be a relevant symptom of cerebrovascular disease, yet migraine remains an essentially benign condition.     

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.     

Newest aspects on the association between migraine and cardiovascular disease: The role of modifying factors

Migraine has been established as a risk factor for ischemic stroke. Further evidence suggests that migraine is also associated with other ischemic vascular events, including myocardial infarction and cardiovascular death. However, these associations appear to be limited to the subgroup of patients with migraine with aura (MA). Moreover, there is increasing evidence that among patients with MA, additional subgroups exist that carry particular increased risk. The association with ischemic stroke is, for example, particularly strong for younger women with MA who smoke and/or use oral contraceptives. Results from recent studies support an even more complex interrelationship characterized by additional modifying effects of other factors on the association between MA and ischemic vascular events. These include vascular risk factors, migraine attack frequency, and genetic variants. In addition, there appear to be differential effects with regard to ischemic stroke and myocardial infarction. These new findings await confirmation in independent patient populations and are currently not sufficient to argue for a change in diagnostic testing or treatment.     

Migraine and Raynaud phenomenon: possible late complications of Kawasaki disease

Migraine and Raynaud phenomenon often coexist and may reflect similar vascular reactions. Both have been associated with vascular endothelial cell dysfunction. Kawasaki disease is a systemic vasculitis of unknown etiology that affects children and may lead to the formation of coronary artery aneurysms. Endothelial cell dysfunction has been demonstrated late in Kawasaki disease and is not restricted to coronary vessels. We report the case of a patient who developed typical migraine with aura and Raynaud phenomenon at the age of 14, 12 years after onset of Kawasaki disease. His migraine responded well to pizotifen, and both migraine and Raynaud phenomenon improved after initiation of treatment with valproic acid. We postulate that both migraine and Raynaud phenomenon in this case represent late consequences of Kawasaki disease and result from extracoronary endothelial dysfunction.     

Risque vasculaire et migraine : données acquises et nouveautés

It is well established that migraine is associated with an increased relative risk of ischemic stroke. This relative risk is dramatically increased when migraine with aura is associated with tobacco consumption or contraceptive pill with oestrogen. Migraine is also associated with an increased relative risk of subcortical white matter hypersignals and with patent foramen ovale. Recent Dutch population survey has suggested an increased relative risk of silent infarcts in migraine, especially in cerebellum. Migrainous infarct could not explain these facts: this diagnosis is extremely rare and required a complete and totally negative diagnostic work-up. Recent US epidemiological data suggests an increased risk of coronary artery diseases in migraine with aura in women older than 45. The increased risk of ischemic events is probably multifactorial with more traditional vascular risk factors in migrainers, endothelial dysfunction, decreased level of circulating progenitor cells, prothrombotic circulating factors, and venous thromboembolic disease. Up to now, it is not established that prophylactic treatment of migraine could modify the vascular risk associated with migraine.     

Migraine and genetic and acquired vasculopathies

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.     

Migraine and cerebrovascular diseases: Epidemiology,pathophysiological, and clinical considerations

Migraine and cerebrovascular diseases are disabling disorders, which are possibly closely interrelated. Heterogeneous and scattered evidence in literature remains a challenge. We searched for systematic reviews including diverse cerebrovascular events in migraineurs and reported relevant original studies to update the evidence when necessary. The studies show that migraine is associated with increased risk of transient ischemic attacks, any stroke, and possibly hemorrhagic stroke. In addition, migraine with aura increases the risk of ischemic stroke and white matter abnormalities. Migraine without aura increases the risk of cervical artery dissection as a cause of ischemic stroke. Groups with specific risk profiles are women, young people, smokers, and oral contraceptive users. The pathophysiology of the association remains uncertain. However, genetic and environmental factors may be involved in intricate mechanisms responsible for oxidative stress, vascular dysfunction and, ultimately, vascular events. In conclusion, migraine is a potential risk factor for cerebrovascular diseases. Migraineurs should be carefully evaluated considering their vascular risk assessment based on current evidence, so that healthcare professionals can provide appropriate and individualized management of other cardiovascular risk factors, notably quitting smoking and restricting use of oral contraceptives.     

The association between migraine and juvenile stroke: a case-control study

BACKGROUND: Several studies suggest an association between migraine and juvenile stroke. Because of some shortcomings, we designed another case-control study of a homogenous group of patients with juvenile cerebral ischemia. This study is part of a larger German epidemiological research project on the association of migraine with cerebrovascular disease. METHODS: We enrolled 160 consecutive patients under the age of 46 years with first-ever ischemic stroke or transient ischemic attack and 160 strictly sex- and age-matched controls. Patients suffering from arterial dissection, brain hemorrhage, cranial sinus thrombosis, lacunar stroke, or from migrainous infarction were excluded. Migraine was diagnosed according to the criteria of the International Headache Society by the same 2 independent interviewers. For analyzing the data, nonparametric statistical methods including odds ratio and 95% confidence interval were used. RESULTS: Migraine was a significant risk factor for juvenile stroke for the total sample with an odds ratio of 2.11 (confidence interval, 1.16 to 3.82). The odds ratio was even higher in the subgroup under the age of 35 (3.26) and in the female subgroup (2.68). We found migraine to be independent from other vascular risk factors, from etiology, and from the territory of stroke. CONCLUSION: We can confirm the findings of previous studies showing a significant association between migraine and juvenile stroke in women. Furthermore, our data suggest migraine to be an even more significant risk factor for patients under the age of 35 and to be independent from other vascular risk factors.     

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives.     

Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI, diffusion and perfusion MRI and MRS

Prolonged hemiparetic migraine aura can cause diagnostic confusion and be mistaken for ischaemic stroke occurring during the course of a migraine--'migrainous infarction'. We report a case of prolonged hemiparesis occurring during the course of a migraine attack. Though initially confused with migrainous infarction, we suggest with sequential magnetic resonance imaging, magnetic resonance angiography, diffusion, perfusion images and magnetic resonance spectroscopy that the hemiplegia was not of vascular origin and that the patient had sporadic hemiplegic migraine. We hypothesize that the mechanisms of sporadic hemiplegic migraine probably lie at a cellular level, similiar to familial hemiplegic migraine.     

A history of migraine is not a risk factor to develop an ischemic stroke in the elderly

OBJECTIVE: To assess the prevalence of migraine in elderly patients hospitalized with ischemic stroke compared with vascular and nonvascular control groups. BACKGROUND: Migraine is a disease with a presumed vascular mechanism. While migraine is a common complaint of young victims of ischemic stroke, it is unclear whether a current or past history of migraine constitutes a risk factor for developing an ischemic stroke in the elderly. METHODS: We obtained current and past headache history from 100 consecutive patients hospitalized with ischemic stroke (aged 60 years or older) and compared the results with 100 patients hospitalized due to acute myocardial infarction and 100 hospitalized patients with no vascular disease. RESULTS: The sex and the age of the patients did not differ among the groups. The lifetime prevalence of migraine (8% of the patients with ischemic stroke, 8% of the nonvascular controls, and 15% of the patients with acute myocardial infarction) or of all types of headaches (27%, 30%, and 15%, respectively), did not differ significantly between the groups. CONCLUSIONS: Based on the reported history, elderly migraineurs are not at increased risk to develop ischemic stroke.     

Cardiovascular diseases and erectile dysfunction

Until recently, erectile dysfunction (ED) has been considered to be psychogenic in nature in most cases. Advances in our knowledge about the physiology of erection and the pathophysiology of ED have clarified that it is due to organic causes in most cases. Atherosclerosis-associated intraorgan lesion is most frequently encountered. ED is closely related to common cardiovascular risk factors, such as diabetes mellitus, arterial hypertension, dyslipidemia, smoking, physical inactivity. Endothelial dysfunction is of great and universal importance for the genesis of cardiovascular diseases (CVD) and ED. As a manifestation of endothelial dysfunction, ED is an independent risk factor for CVD since vascular endothelial damage is one of the first stages of atherosclerotic plaque formation. ED is an early symptom that is suggestive of atherosclerotic lesion of arterial vessels, coronary arteries in particular. The first manifestation of atherosclerosis in the large arteries is frequently the life-threatening complications myocardial infarction or stroke, which underlines the importance of timely detection of early-stage vascular system lesions. Understanding ED of arteriogenic origin as an early sign of vascular lesion gives a clinician the unique chance to take preventive measures that can prevent complications of CVD.     

Methamphetamine-related stroke: four cases.

Amphetamine use in certain parts of the United States has risen dramatically. Methamphetamine, the most-common illicitly abused type of amphetamine, can be inhaled, injected intravenously, or smoked. It is a potent sympathomimetic that may lead to vascular events including myocardial infarction and stroke. Because of the demographics of drug use, these potentially devastating events usually occur in relatively young patients. The pathophysiology of stroke related to amphetamine use is multifactorial. Elevation in blood pressure, vasculitis, or other vascular toxicity are postulated as major mechanisms. Four cases of stroke associated with the use of methamphetamine, all occurring in patients ranging in age from 29-45 years, are described. Methamphetamine use appears to be a risk factor for the development of stroke. The rise in methamphetamine use will undoubtedly result in increased Emergency Department admissions with clinical presentations very similar to those of cocaine intoxication.     

Are vascular disorders more prevalent in the relatives of children and adolescents with migraine?

The objective of the study was to assess whether a family history of vascular disorders is more common in children and adolescents with migraine than in the general population. Family history of stroke, arterial hypertension, myocardial infarction and diabetes was investigated by history taking in relatives of ambulatory children and young adults with migraine and in a control group. The odds ratios (ORs) with 95% confidence intervals (95% CI) were used as a risk measure. Using univariate and multivariate (logistic regression) analysis, family history was assessed in the whole sample and in subgroups by sex and age, degree of relationship (parents and grandparents vs. relatives), disease type (migraine with and without aura), and type of vascular disorder. The sample included 143 cases (migraine with aura 35, migraine without aura 108) and 164 controls aged 3-24 years (mean 12 +/- 3.8 years). Patients with migraine were at increased risk of vascular disorders in parents and grandparents but not in all relatives. Multivariate analysis indicated family history of stroke as most common only in boys. In conclusion, our study provides some clues to the assumption that migraine and vascular disorders have common pathogenic mechanisms and that genetic susceptibility plays a role in increasing the risk of migraine in the offspring of families with one or more cerebrovascular or cardiovascular conditions.     

Microalbuminuria and cardiovascular risk

The term 'microalbuminuria' has been introduced to describe a measurable increase in urine albumin excretion, which is still within normal total urine protein excretion levels. Many data suggest that microalbuminuria is of value as an index of vascular damage, especially in hypertension and diabetes, and there is increasing information on its associations with traditional cardiovascular risk factors and its prognostic value. The association between microalbuminuria and peripheral markers of endothelial damage or dysfunction, such as von Willebrand factor, suggests the possibility that microalbuminuria may be a simple, cheap and easy index of endothelial abnormalities in cardiovascular disease. Nevertheless, further information on the value of microalbuminuria in other atherosclerotic vascular complications, such as ischaemic heart disease, stroke and peripheral artery disease is still needed.      

Mechanisms of homocysteine-induced atherothrombosis

Elevation of plasma homocysteine level is a risk factor for cardiovascular disease, stroke, and venous thromboembolism. It is still uncertain, however, whether hyperhomocysteinemia is a causative factor or a marker of vascular disease. The strongest evidence that homocysteine plays a causal role in atherothrombosis has been provided by studies using animal models. In the past decade, considerable progress in defining the vascular effects of hyperhomocysteinemia was achieved through the use of genetic and dietary approaches to induce hyperhomocysteinemia in experimental animals. A key vascular phenotype observed in hyperhomocysteinemic animals is endothelial dysfunction, manifested by decreased bioavailability of endothelium-derived nitric oxide. Impairment of endothelial function may be mediated by either accelerated oxidative inactivation of nitric oxide or inhibition of nitric oxide production caused by the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Hyperhomocysteinemia also increases susceptibility to arterial thrombosis and accelerates the development of atherosclerosis in susceptible models such as the apolipoprotein E-deficient mouse. Mechanisms of atherothrombosis may include homocysteine-induced thiolation or acylation of plasma or endothelial proteins and endoplasmic reticulum stress, which activates signal transduction pathways leading to inflammation and apoptosis.