The Relationship Between: Migraine, Deep White Matter Lesions and Posterior Circulation Ischemic Infarcts

Abstract

SUMMARY AND CONCLUSION M igraine is one of the head complaints arousing the most interest in the scientific community in recent years. There has been great interest in its relationship with ischemic event as a vascular risk factor or the presence of clinically silent stroke in patients with migraine or stroke as a direct complication of migraine with aura. This new approach in previously existing & known problems has reopened the debate in the role of blood vessels in pathophysiology of migraine. Migraine and stroke have an overlap of clinical features. Migraine is characterized by headache, and in a significant minority (20-40%) of cases, aura. Migraine aura (MA) is typically described as the gradual expansion of positive focal neurological symptoms (for example, scintillation, fortification, tingling) with a sequential progression when more than one symptom type is involved. Retinal migraine (monocular visual loss), hemiplegic migraine, basilar migraine, and migraine with prolonged aura prove particularly troublesome from the diagnostic standpoint. Similarly, when ischemia is associated with headache or with “positive” symptoms there may be a misdiagnosis of migraine, particularly if the ischemia is transient. Migraine and stroke are associated with a higher frequency than expected when observing the prevalence of both diseases among the general population. This relationship may be one of coincidence, similarity (migraine resembling stroke or stroke resembling migraine), origin (migraine and stroke as manifestations of the same underlying process) and causality (migraine may act as an additional risk factor for stroke or may be the direct cause of stroke). Migraine, particularly with aura and in women <45 years-old, is associated with an increased risk of cerebral infarction. This risk increases if the patient smokes or uses oral contraceptives. Migraine can also be a direct cause of a stroke, although it is an infrequent complication. Migraine with aura is associated with a risk factor of having subclinical infarctions in posterior fossa circulation. Migraine has associated with abnormalities of the vasculature (such as vasospasm, arterial dissection), and of the blood (including platelet-related hypercoagulability) which could result in ischemic stroke. Recent evidence suggests that endothelial activation, a process secondary to oxidative stress and resulting in hypercoagulability and inflammation, is more common in young migraineurs, particularly premenopausal women with aura. Up to 50% of patients who have migraine with aura have a patent foramen ovale (PFO) between the cardiac atria, which may allow shunting of vasoactive substances, such as serotonin, and emboli from the venous circulation. Migraine and stroke are also linked by at least two monogenic disorders: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL). CADASIL, a condition in which 30% report MA (often as the initial symptom), is one of the most common forms of hereditary stroke. It is characterized by progressive white matter degeneration and smooth muscle cell abnormalities. The most likely etiologic mechanism of posterior circulation territory infarcts in migraine patients, seems to be hypoperfusion and/or embolism, rather than atherosclerosis or small vessel disease. During and after migraine attacks, sluggish low cerebral flow below an ischemic threshold has been described. A decrease in brain perfusion pressure (e.g. during migraine) theoretically affects the clearance and destination of embolic particles; narrowing of the arterial lumen and endothelial abnormalities stimulate formation of thrombi; occlusive thrombi further reduce blood flow and brain perfusion. Because the deep cerebellar territories have a pattern of progressively tapering arteries with only few anastomoses present, they are likely to be particularly vulnerable to hypoperfusion related border zone infarct mechanisms. In migraine patients, white matter (WM) lesions of uncertain significance are a common finding in cranial MRI scans. Small-sized hyperintensities are observed (on T2-weighted sequences and FLAIR), especially in the periventricular and deep WM. The results on the prevalence of WM lesions in migraine patients differ according to their location (deep vs. periventricular). Furthermore, the risk of these lesions appears to be independent of age and the presence or absence of associated vascular risk factors. On the other hand, there is a significant association in women suffering >1 migraine/month. There have been no differences in the prevalence of these lesions in males. However, in periventricular WM lesions, no association with the presence of migraine attacks (with and without) or their frequency has been found in males or females.