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.

Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study

“…These changes seem to have a different origin from perfusion changes observed in the occipital cortex. They are also different to those observed in MS patients (reviewed in [47] and [48]) and could be associated to the complex and not yet fully understood pathophysiology of NMO [1].…”

Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

“…Accordingly, this provokes the lysis of erythrocytes and the formation of ''iron sludge,'' which activates inflammation, thus contributing to MS pathology (487). However, a number of established research groups found strong evidence against CCSVI (456). For example, Doepp et al found that only a small population of MS patients has CCSVI according to Zamboni's criteria, and that a large majority of those with CCSVI show no measurable hemodynamic alterations (117).…”

“…In a nutshell, CCSVI is not a plausible cause of MS. However, CCSVI should not be confused with anomalies in cerebral blood flow and small veins and venules inside CNS tissue, as accumulating data foster further concepts, which involve vascular changes and obstructed circulation in MS initiation (106,456). Varga et al reported that cerebral blood flow is decreased in the normally appearing white matter (NAWM) of patients with CIS compared with control subjects (449).…”

Iron in the brain: Heavy metal mismanagement

“…In the process of demyelination, the myelin sheath is stripped off neurons in a pattern that follows the venous system [13]. The loss of myelin insulation and plaque formation not only interferes with the transmission of the nerve impulse, but also means loss of support for the neuron, potentially leading to cell death [14]. Eventually the neurodegeneration spreads, encompassing the entire CNS [15].…”

“…The oxidative stress due to venous haemorrhage and iron deposits can have real implications on the process in demyelination. Aside from MS, iron deposition has been observed in other demyelinating diseases, such as in Hurst acute haemorrhagic leukoencephalitis [14].…”