Multiple sclerosis shrinks intralesional, and enlarges extralesional, brain parenchymal veins

Abstract

Objectives: Many multiple sclerosis (MS) lesions develop around small veins that are surrounded by perivenular inflammatory cells, but whether veins in the brains of people with MS are smaller or larger than similar veins in healthy volunteers or people with other neurologic diseases remains unknown. This question can be addressed by high-resolution, high-field-strength MRI.Methods: In a cross-sectional study performed on a standard 3 T clinical scanner, we acquired wholebrain T2*-weighted images with 0.55 mm isotropic voxels and reconstructed the courses of deep and superficial veins within the white matter. We compared the apparent diameters of intralesional and perilesional veins to those of extralesional MS veins, veins in healthy volunteers, and veins in individuals with other neurologic diseases.Results: We studied veins in 19 MS cases, 9 healthy volunteers, and 8 individuals with other neurologic diseases, analyzing a total of 349 veins. The mean diameter of intralesional veins (0.76 6 0.14 mm) was smaller than that of perilesional (1.18 6 0.13 mm; p , 0.001) and extralesional (1.13 6 0.14 mm; p , 0.001) veins, regardless of lesion size and location. Perilesional and extralesional MS veins were larger than non-MS veins (0.94 6 0.14 mm; p , 0.001), and intralesional MS veins were smaller (p , 0.001). Most multiple sclerosis (MS) lesions in the cerebral white matter expand outward from small, inflamed veins, 1,2 although demyelinated lesions not centered by small veins have been reported. Conclusions: 3The walls of veins in MS plaques are denser and heavily cellular, and perivenular fibrosis can be seen in the lesion center. 1 In chronic lesions, due to fibrosis and collagen deposition in the vein wall and perivascular space, venous caliber is significantly narrowed. 1,4 MRI venography at standard clinical field strength can demonstrate the perivenous distribution of MS lesions in vivo. 5 The ability to detect veins improves greatly as field strength increases, 6 because the degree to which deoxyhemoglobin in venous blood reduces signal intensity on T2*-weighted images becomes magnified.7 At 7 T, a central vessel can be identified in 87% of visible white matter lesions. 8An important open question is whether veins centering lesions are macroscopically different from veins outside lesions and from similar veins in healthy people and individuals with other neurologic diseases. One possibility is that the histopathologically observed perivenular cuffing and wall thickening induce macroscopic changes in intralesional veins. It is also possible, however, that such changes on MRI occur diffusely, affecting many if not all parenchymal veins in the MS brain; in this case, the changes would not be directly related to lesions, and their pathophysiologic significance would be less clear.

Slowly eroding lesions in multiple sclerosis

“…Spherical lesions were simulated as enlarging either as a result of inflammation at the lesion edge, which could increase LV in proportion to either the radius or the volume of the lesion, or alternatively at a fixed rate over time. Lesion shrinkage either could be most aggressive at the lesion center, where tissue damage is thought to be most severe (18), or alternatively could occur in a fixed amount per unit time over the entire extent of the lesion. The simulation was investigated in an attempt to understand the rate of decrease in lesion volume.…”

Advanced MRI and staging of multiple sclerosis lesions

“…Though recognized in pathological studies as early as the 19th century 10 , the perivenular topography of MS lesion development has only recently been directly visualized in vivo , using high-resolution susceptibility-sensitive imaging at a variety of magnetic field strengths (Supplementary information S1 (movie)) 11–18 . The reasons for the characteristic prominence of the central vein within MS demyelinated lesions in comparison to surrounding brain parenchyma are still open to debate, and include an elevated concentration of deoxyhaemoglobin (higher oxygen extraction at the site of inflammation) and changes in vessel diameter (slower venous flow, postinflammatory scarring processes of the vein wall) 19–21 .…”

Glucocorticosteroids: Risk-Benefit Appraisals in Multiple Sclerosis and MS-Associated Optic Neuritis

“…Smaller size veins surrounded by inflammatory cells are newly diagnosed pathological features in MS [69]. It is tempting to hypothesize that corticosteroids can induce atrophy/necrosis in neuro-vasculature structures in a manner consistent with their well known antiangiogenic properties [70].…”

“…GCs might then progressively accumulate new small lesionssustain or enlarge the lesion volume in a U-shape curve manner and deteriorate MS attacks in time. These concerns might be solvent by loosening the outcome measures, such as using non-conventional MRI scans [69,71] and tightening the analytical choices for effect estimates based on predetermined efficacy criteria. Our assessment insufficiently addresses issues pertaining to GC-mediated infections and/or reactivation of endogenous viruses and their impact on MS pathology.…”