LETTER TO THE EDITOR

We read with great interest the recent article by Mohan et al which showed an extensive meshwork of perivascular fibrosis in multiple sclerosis (MS) lesions (6). The perivascular fibrosis in MS appears to be very similar to the extensive collagen deposition around veins and venules we have shown to occur in leukoaraiosis (LA) lesions 1, 2, 7 (Fig. 1). LA is an age‐related white matter degeneration characterized by spongiosis, gliosis, demyelination and capillary degeneration (8), as well as endothelial dysfunction (5), increased blood‐brain barrier permeability (4) and cognitive impairment (9). We found an increase in the thickness of the walls of veins and venules in the periventricular white matter with normal aging, but in LA lesions, there was a much greater degree of venous wall thickening, which resulted in narrowed lumina and even occlusion. Using routine stains, these thick‐walled veins can be easily mistaken for hyalinized arterioles, but with alkaline phosphatase histochemistry, which preferentially stains afferent brain blood vessels, we showed that the affected vessels were exclusively venous. We demonstrated staining for collagens type I, III and IV by immunohistochemistry (other collagens antibodies were not tested). This collagen deposition is similar to that which occurs in arteriolar hyalinization and in the vascular fibrosis in MS lesions shown by Mohan et al (6). In addition, similar vascular fibrosis has been reported by Farkas and colleagues to occur in rat brain capillaries in aging and hypertension (3).

Figure 1.

Venous collagenosis in leukoaraiosis. Collagen is stained green. The arrow indicates an unaffected arteriole.

Mohan et al have suggested that the perivascular collagen meshwork might have anti‐inflammatory properties that may contribute to limiting the enlargement of MS lesions. In contrast to MS lesions, LA lesions have not been thought to involve a significant inflammatory component. The focus has instead been on ischemia in LA lesions. For example, inhibition of blood flow by venous fibrosis and stenosis might induce chronic ischemia and/or edema in the deep white matter, leading to LA 1, 2, 7. It is unknown why the veins become thickened in the deep white matter in LA. Similarly, the cause of vascular fibrosis in MS lesions is unknown. Perhaps, an understanding of the mechanism in one of these pathological processes could lead to insight into the pathogenesis of the other.