Vascular multiple sclerosis: addressing the pathogenesis, genetics, pro-angiogenic factors, and vascular abnormalities, along with the role of vascular intervention

Abstract

Dysfunction in the epithelium, breakdown of the blood-brain barrier, and consequent leukocyte and T-cell infiltration into the central nervous system define Vascular Multiple Sclerosis. Multiple sclerosis (MS) affects around 2.5 million individuals worldwide, is the leading cause of neurological impairment in young adults, and can have a variety of progressions and consequences. Despite significant discoveries in immunology and molecular biology, the root cause of MS is still not fully understood, as do the immunological triggers and causative pathways. Recent research into vascular anomalies associated with MS suggests that a vascular component may be pivotal to the etiology of MS, and there can be actually a completely new entity in the already available classification of MS, which can be called 'vascular multiple sclerosis'. Unlike the usual other causes of MS, vascular MS is not dependent on autoimmune pathophysiologic mechanisms, instead, it is caused due to the blood vessels pathology. This review aims to thoroughly analyze existing information and updates about the scattered available findings of genetics, pro-angiogenetic factors, and vascular abnormalities in this important spectrum, the vascular facets of MS.

Keywords: cerebral venous insufficiency; endothelial dysfunction; inflammation; vascular multiple sclerosis.

Figure 1

A summary of the mechanisms of the autoreactive T-cell response and the resultant autoimmune disease of multiple sclerosis in the central nervous system. APCs, antigen-presenting cells.

Figure 2

The positive feedback loop between hypoxia and inflammation (original figure, created from Biorender, modified from Figure by Yang et al.). PHD, prolyl hydroxylase.