Dong H, Ding H, Young K, Blaivas M, Christensen PJ, Wang MM. Advanced Intimal Hyperplasia Without Luminal Narrowing of Leptomeningeal Arteries in CADASIL. Stroke. 2013
CADASIL is the most common form of heritable stroke and vascular dementia. The clinical presentation is very well known, although less is known about the pathophysiology of the disease. In this issue, Dong et al. investigated leptomeningeal arteries of 6 patients with genetically diagnosed CADASIL, 6 controls within the age range that those with CADASIL and 6 aged controls. The authors obtained morphometric and immunological arterial characteristics in cases and controls. The authors found that in arteries from patients with CADASIL, the intima was 5 fold thicker, the media was thinner and the sclerotic index was greater than in those without CADASIL. Surprisingly, the lumen was not significantly smaller despite the intima hyperplasia. The hyperplastic intima expressed muscle-like proteins.
If the intima was 5 times thicker and the lumen remained the same, why do patients ultimately develop strokes? How could an intact lumen be associated with cortical dysfunction that eventually leads to dementia as the authors suggested? Several explanations come to mind. We don’t know based on the published data if all leptomeningeal arteries had the same size across groups. This is important, because the proportion of the intima and the media vary according to arterial size. Also, these specimens might represent a very early form of intima hyperplasia. According to the classic model of atherosclerosis by Glagov et al. we know that coronary arteries enlarge to compensate for up to 40% of intima thickening before the lumen becomes compromised. Although this is less well-established in brain arteries, it could be an explanation. If these findings are confirmed in larger datasets, one might think of potential ways treat this disease. Antiproliferative measures could be imagined to arrest the intima thickening and preserve the lumen. If we could identify the process even earlier, more aggressive controls of concomitant vascular risk factor might be warranted to avoid further intima thickening. The work by Dong et al. broadens the horizons to imagine new treatments of this and other arteriopathies that cause stroke and vascular dementia.