Vascular pathology in multiple sclerosis: mind boosting or myth busting?

Abstract

The investigation of central nervous system vascular changes in the pathophysiology of multiple sclerosis (MS) is a time-honored concept. Yet, recent reports on changes in venous cerebrospinal outflow, the advent of new magnetic resonance imaging techniques and the investigation of immunomodulatory properties of several vascular mediators on the molecular level have added new excitement to hypotheses centering around vascular pathology as determining factor in the pathophysiology of MS. Here we critically review the concept of chronic cerebrospinal venous insufficiency in MS patients and describe new imaging techniques including perfusion weighted imaging, susceptibility weighted imaging and diffusion weighted imaging which reveal central nervous system hypoperfusion, perivascular iron deposition and diffuse structural changes in the MS brain. On a molecular basis, vascular mediators represent interesting targets connecting vascular pathology with immunomodulation. In summary, the relation of venous changes to the pathophysiology of MS may not be as simple as initially described and it certainly seems awkward to think of the complex disease MS solely as result of a simple venous outflow obstruction. Yet, the investigation of new vascular concepts as one variable in the pathophysiology of the autoimmune attack seems very worthwhile and may add to a better understanding of this devastating disorder.

Figure 1

Scheme depicting the possible interplay between vascular mediators and changes in microcirculation during autoimmune inflammation of the CNS. Altered microcirculation may lead to iron deposition and increased leukocyte infiltration. In turn, pleiotropic factors such as vascular mediators released by immune cells and the activated endothelium can cause neovascularization and lead to the recruitment of further effector cells. This mechanism may be part of a feed-forward loop that perpetuates the inflammatory process in MS.