Migraine white matter hyperintensities and cerebral microinfarcts are silent cryptogenic strokes and relate to dementia
Introduction
The presence of multiple silent or sub-clinical lacunar strokes is known to correlate with dementia [1], [2]. A silent stroke is generally defined in terms of MRI (magnetic resonance imaging): it is hyperintense on T2-weighted images and hypointense on T1-weighted images. A lesion which fulfills only the first criterion is a “white matter hyperintensity”. Large cortical strokes and strategic hit infarcts are also recognized to cause dementia. However, there are more subtle MRI-imaging abnormalities, namely migraine white matter hyperintensities and leukoaraoisis, which can be passed over as incidental findings but which are being increasingly recognized as components of vascular dementia. There also exist microinfarcts which, as will be discussed below, cannot be imaged on conventional MRI. Less common causes of cerebral small vessel disease not associated with vascular risk factors will not be discussed in this paper.
Section snippets
Hypothesis
Migraine white matter hyperintensities and cerebral microinfarcts (CMI) are silent cryptogenic strokes and relate to dementia. They are to be distinguished from leukoaraiosis, which is an area of low-flow ischemia in watershed and end-zone capillary beds caused by the vascular remodeling of arterioles that occurs in prolonged inadequately treated hypertension.
Blood supply of the cerebrum
Blood supply to the cerebral cortex is supplied by the anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) [3]. The basic pattern is the same for all three arteries. The MCA is the largest: it gives off deep ganglionic branches, the lenticulostriate arteries, at its stem or M1 segment; these arteries enter the brain in the perforated substance (hence the alternate name of “perforators”). When the middle cerebral artery enters the Sylvian fissure, it starts to divide into the
Migraine white matter hyperintensities
Migraine white matter hyperintensities are seen on T2-weighted and FLAIR imaging sequences. Although particularly common in migraine patients, similar abnormalities can be seen in patients with vascular risk factors such as hypertension, hypercholesterolemia, or diabetes mellitus, all of which are known to cause white matter changes, the odds ratio being 4.14 (migraine vs. normal control) [7]. Igarashi et al. studied the phenomenon in 91 migraineurs; the incidence of hyperintensities was 29.4%
Evidence that migraine white matter hyperintensities are strokes
There is no pathology available on migraine white matter hyperintensities. Aradi et al. performed a quantitative MRI study of migraine white matter hyperintensities which included, in addition to routine MRI sequences, quantitative single voxel spectroscopy [9]. Compared to contralateral normal-appearing white matter in the same subject, the lesions were characterized by increased apparent diffusion coefficient and decreased N-acetylaspartate and creatine/phosphocreatine concentrations. The
Cerebral microinfarcts
There does exist pathology on what appear to be even smaller embolic strokes, which are the CMI which have been reported in elderly subjects, as reviewed by Brundel et al. [11]. These microinfarcts, which range in size from 50 µm to a few mm and occur in both grey matter and white matter, are too small to image with conventional clinical MRI and require a 7.0 tesla (T) machine (which would not be of general clinical use because it cannot image the temporal lobes due to a low signal-to-noise ratio
Migraine and cryptogenic stroke
Migraine is statistically associated with cryptogenic strokes, which are embolism-like strokes for which an embolic source cannot be found. Among 1810 patients with ischemic stroke or transient ischemic attack included in the Oxford Vascular study, 36.9% had cryptogenic events and 28% of the 36.9% said that they had been diagnosed with migraine at some point in the past [15]. The association was greater for women than for men, for patients over the age of 65, and for patients with no vascular
Leukoaraiosis: the other kind of white matter hyperintensity
Silent cryptogenic strokes must be distinguished from leukoaraiosis, which is a different clinical and pathological entity. Leukoaraiosis refers to diffuse white matter hyperintensities (bright on T2, not hypodense on T1) which are also seen in the four capillary beds described above, although, for unknown reasons, the internal watershed zone is not typically involved early on. Silent cryptogenic strokes and leukoaraiosis are two different pathological processes affecting the same capillary
Therapeutic implications
- 1.
Are migraine white matter hyperintensities an indication for starting an anti-platelet drug? This has not been formally tested, but it seems logical.
- 2.
Care should be exercised in treating hypertension in patients with leukoaraiosis. The blood pressure goals are unknown for this patient population. Hydralazine might be a drug of choice because it directly paralyzes arteriolar smooth muscle cells, which is a kind of partial compensation for failed auto-regulation; however, there is no evidence that
Conflicts of interest
There are no conflicts of interest.
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