Abstract
The relationship between multiple sclerosis (MS) and the vasculature has been discussed in many facets: lesions centered by a small blood vessel are characteristically present in MS, as noted initially by Charcot 1 on histologic analyses, and confirmed in vivo by very recent ultrahigh-field magnetic resonance imaging (MRI) studies. The disruption of small-vessel blood–brain barrier is a hallmark during the development of MS plaques. As an early event during the autoimmune cascade, autoreactive T lymphocytes migrate into the central nervous system and initiate a focal immune response. 3 This inflammatory process can result in microvascular damage by different mechanisms: cytotoxic T cells may recognize antigens on endothelial cells and activate a clotting cascade which, in turn, leads to thrombosis. Likewise, antibodies may recognize their antigens at the vessel wall and induce vascular damage by complement activation. Furthermore, inflammatory edema may impair microcirculation through focal tissue swelling, whereas exudation of inflammatory cells and intravascular fibrin deposition may induce acute and chronic venous obliterations. Finally, inflammation is able to modulate the vascular tone as well as the mircocirculation and, as a consequence, to trigger local changes in the blood flow, as shown by experimental studies that showed a complex and dynamic relationship between vasodilator and vasoconstriction factors in MS. 4
Perfusion measurements in MS using radioactive 133Xe, positron emissoin tomography, or single-photon emission computed tomography techniques reported decreased perfusion in both gray and white matter in MS compared with healthy individuals. Wuerfel et al demonstrated that the initial prominent increase in cerebral blood volume CBV and cerebral blood flow (CBF) weeks before lesion detection by other MRI modalities was followed by a gradual decline. Cerebral blood flow and CBV remained below baseline in those lesions that developed persistent T1w hypointensity. 5 It seems that in the acute phase, inflammation-related vasodilatation could explain the changes, whereas in later stages, hypometabolic gliotic scars develop. Several perfusion MRI studies reported decreased normal-appearing white matter as well as gray matter perfusion in MS.
In 2006, Zamboni et al published a hypothesis that, in analogy to chronic perivenous inflammation of the legs, cerebrocervical venous failure caused MS. 6 Although the concept has unsolved methodological weaknesses and cannot sufficiently explain the underlying pathophysiology, it raised enormous public and patient interest. So far, other groups could not unanimously and convincingly replicate the data originally presented. 7
The present study by ElSankari et al 8 applied a very recently developed method—measuring simultaneously arterial, venous, and cerebrospinal fluid flows cervically and intracranially applying retrospectively gated 2D-phase contrast MRI to avoid a varying gap between trigger signal and sequence start—to a small cohort of clinically isolated syndrome (pre MS) and MS patients in comparison to healthy controls. Applying this advanced technique, the authors were able to address different aspects of the hypothesized rheological alterations in MS in one experiment.
DISCLOSURE/CONFLICT OF INTEREST
The author declares no conflict of interest.