Finally, there has long been discussion of an association between migraine and patent foramen ovale. A few physicians in the past favored a causal role and advocated closure of the foramen in an attempt to alleviate migraine but several trials have failed to sustain this concept. Migraine with aura has been especially associated with an open foramen. However, large cross-sectional (Rundek et al) and case-control (Garg et al) studies have not affirmed these associations and the issue, while still under discussion, has been of waning interest.
Imaging changes in migraine There are cerebral imaging changes in migraineurs that are suggestive of small ischemic lesions. A number of cross-sectional population studies, such as the ones by Kurth and colleagues, Scher et al, and Kruit and coworkers, have indicated that MRI changes in both the deep and subcortical white matter are more frequent in women migraine patients who experienced auras than in those without auras and in the general population. A high frequency of migraine headaches is also associated in some studies with an increased number of white matter lesions including, according to some observers, lesions in the cerebellar white matter.
The implications of these frequently encountered small white matter lesions in migraineurs that are familiar to neurologists are unclear. The findings are a cause for neurological consultation, sometimes with the question of multiple sclerosis. Several studies indicate that migraineurs with these changes have no greater cognitive decline over time than those in the general population. In discussion with patients, we tend to underemphasize these lesions and the risk of stroke but point out that the importance of the usual stroke risk factors: smoking, hypertension, hyperlipidemia, and cardiac rhythm abnormalities.
Pathogenesis of Migraine
So far, it has not been possible to determine from the many clinical observations and investigations, a unifying theory as to the cause of migraine. Tension and other emotional states, which are claimed by some migraineurs to precede their attacks, are so inconsistent as to be no more than potential aggravating factors. Clearly, an underlying genetic factor is implicated, although it is expressed in a recognizable mendelian pattern in only a small number of families (see above). How this genetic predisposition is translated periodically into a regional neurologic deficit, unilateral headache, or both is unknown. For many years, our thinking about the pathogenesis of migraine was dominated by the views of Harold Wolff and others—that the headache was caused by the distention and excessive pulsation of branches of the external carotid artery. Certainly, the throbbing, pulsating quality of the headache and its relief by compression of the common carotid artery supported this view, as did the early observation of Graham and Wolff that the headache and amplitude of pulsation of the extracranial arteries diminished after the intravenous administration of ergotamine.
The importance of vascular factors continues to be emphasized by more recent findings, but not in the way envisaged by Wolff. For example, in a group of 11 patients with classic migraine, Olsen and colleagues, using the xenon inhalation method, noted a regional reduction in cerebral circulation spreading forward from the occipital region during the period when neurologic symptoms appear. They concluded that the reduction in blood flow was consistent with the cortical spreading depression syndrome described below. In a subsequent study, Woods and colleagues described a patient who, during positron emission tomography (PET), fortuitously had an attack of common migraine with blurred vision. Sophisticated measurements showed a reduction in blood flow that started in the occipital cortex and spread slowly forward on both sides, in a manner much like spreading cortical depression (see below) and Cutrer and colleagues, using perfusion-weighted MRI, corroborated the finding of diminished occipital cerebral blood flow during the aura. However, a study using single-photon emission computed tomography (SPECT) in 20 patients during and after attacks of migraine without aura disclosed no focal changes of cerebral blood flow; also, no changes occurred after treatment of the attacks with 6 mg of subcutaneous sumatriptan (Ferrari et al, 1995).