An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis.

E. Mark Haacke,Paolo Zamboni,Yulin Ge,Sean K. Sethi,Sagar Buch

doi:10.3389/fneur.2021.561458

E. Mark Haacke, Paolo Zamboni + Show 3 more

Open Access

https://doi.org/10.3389/fneur.2021.561458

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Abstract

The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.

Highlights

Multiple sclerosis (MS) is usually described as an inflammatory, demyelinating, autoimmune disease [1]
All this evidence of venous vascular abnormalities in MS leads to a critical hypothesis as to one potential cause of MS: “Local disrupted venous flow leads to remodeling of the medullary veins followed by a breakdown of the endothelium with the subsequent escape of glial cells, cytokines, etc. that in turn lead to the autoimmune demyelinating process and subsequent tissue death and atrophy.”
Whether or not venous flow disruption occurs first, the pathological course of MS is consistent with the continual feedback loop of constantly reducing blood flow over time

Summary

Introduction

Multiple sclerosis (MS) is usually described as an inflammatory, demyelinating, autoimmune disease [1]. It is thought that the autoimmune processes may lead to a breakdown of the capillary and venous wall with increased perivascular inflammatory cells and other detrimental factors which attack the myelin sheath and lead to neurodegeneration [2]. In this overview, we will review the literature focusing on the changes in the venous vasculature and inflammation, which are likely to be the earliest processes in the development of the disease. For this review, the PubMed (www.ncbi.nlm.nih.gov/pubmed/) database was used and the search terms were (venous pathology) AND (MS OR multiple sclerosis) with a date range of 1940—present, which resulted in 900+ papers. For an in-depth discussion of the topics covered, the readers should refer to the original publications

Objectives

Conclusion