Vascular aspects of multiple sclerosis

D’haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; Keyser, Jacques De

doi:10.1016/s1474-4422(11)70105-3

Cited by 215 publications

(194 citation statements)

References 93 publications

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“…In addition, the astrocytes produce and release high levels of endothelin-1 that may reach the intracerebral arterioles and induce long-lasting vasoconstriction. 36 …”

Section: Venous Flowsmentioning

confidence: 99%

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

ElSankari

Balédent

Pesch

et al. 2013

J Cereb Blood Flow Metab

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Venous dysfunction has recently been hypothesized to contribute to the pathophysiology of multiple sclerosis (MS). 2D phasecontrast (PC) magnetic resonance imaging (MRI) is a non-invasive and innocuous technique enabling reliable quantification of cerebrospinal fluid (CSF) and blood flows in the same imaging session. We compared PC-MRI measurements of CSF, arterial and venous flows in MS patients to those from a normative cohort of healthy controls (HC). Nineteen MS patients underwent a standardized MR protocol for cerebral examination on a 3T system including Fast cine PC-MRI sequences with peripheral gating in four acquisition planes. Quantitative data were processed using a homemade software to extract CSF and blood flow regions of interest, animate flows, and calculate cervical and intracranial vascular flow curves during the cardiac cycle (CC). Results were compared with values obtained in 21 HC using multivariate analysis. Venous flow patterns were comparable in both groups without signs of reflux. Arterial flows (P ¼ 0.02) and cervical CSF dynamic oscillations (P ¼ 0.01) were decreased in MS patients. No significant differences in venous cerebral and cervical outflows were observed between groups, thereby contradicting the recently proposed theory of venous insufficiency. Unexpected decrease in arterial perfusion in MS patients warrants further correlation to volumetric measurements of the brain.

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“…In addition, the astrocytes produce and release high levels of endothelin-1 that may reach the intracerebral arterioles and induce long-lasting vasoconstriction. 36 …”

Section: Venous Flowsmentioning

confidence: 99%

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

ElSankari

Balédent

Pesch

et al. 2013

J Cereb Blood Flow Metab

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“…A number of studies found that cerebral blood flow (CBF) is globally impaired in early diagnosed relapsing-remitting MS and primary progressive MS, indicating that it is an integral part of the disease that is already present at the time of diagnosis (3)(4)(5). Animal studies have shown that chronic hypoperfusion of the brain can lead to neurodegenerative changes, including axonal degeneration (6).…”

mentioning

confidence: 99%

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

D’haeseleer

Beelen

Fierens³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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111

104

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Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown. We investigated whether the potent vasoconstrictor endothelin-1 (ET-1) is involved. We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein. The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on postmortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to noninvasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.M ultiple sclerosis (MS) is a poorly understood chronic disorder of the CNS, characterized by focal inflammatory demyelinating lesions and degenerative processes (1). Immune responses play a crucial role in the pathogenesis of focal lesions that constitute the pathological substrate for relapses. However, the underlying mechanism of the progressive degeneration of axons, which is the primary determinant of long-term disability in MS, is not clear (2), and treatment is lacking.A number of studies found that cerebral blood flow (CBF) is globally impaired in early diagnosed relapsing-remitting MS and primary progressive MS, indicating that it is an integral part of the disease that is already present at the time of diagnosis (3-5). Animal studies have shown that chronic hypoperfusion of the brain can lead to neurodegenerative changes, including axonal degeneration (6).The underlying mechanism of reduced CBF in MS is unknown. Plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) (7) were found to be elevated in patients with MS (8), and this was associated with alterations of extraocular blood flow (9). The reason for the increase in ET-1 levels in MS was unclear, and the findings have not received much attention. We hypothesized that ET-1 might play a role in reducing CBF in MS. ResultsInternal Jugular Vein ET-1 Levels. Individuals with critical illness and systemic conditions known to be associated with increased levels of ET-1 were excluded (10). Ten subjects with MS according to the revised McDonald criteria (11) and 10 matched control subjects were included. Patients with MS were autonomously seeking treatment at the department of cardiovascular and thoracic surgery of Onze-Lieve-Vrouw Ziekenhuis Aalst for so-c...

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“…The above studies for the first time linked brain perfusion to the venous outflow. This is particularly intriguing in MS because chronic hypoperfusion is a well-known aspect not attributable to autoimmunity [61]. For instance hypoperfusion precedes plaques formation [62].…”

Section: The Pathogenic Hypothesis Linking Ccsvi To Msmentioning

confidence: 99%

The Pathology of the Internal Jugular Vein Wall in Multiple Sclerosis

Pedriali¹,

Zamboni²

2015

J Mult Scler

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In the last years it has been described a condition named Chronic Cerebrospinal Venous Insufficiency (CCSVI), frequently but not exclusively associated to Multiple Sclerosis (MS), which generated a strong scientific controversy about the epidemiological prevalence and the possible role in the complex, multi-factorial MS ethio-pathogenesis.However, CCSVI description also stimulated a considerable research activity on the extracranial veins. Among the fields of interest, the pathology of the Internal Jugular Veins (IJVs) was deeply investigated by some groups, so improving our knowledge in an underestimated field of MS research. Currently, the available papers clearly show the presence of abnormalities in the IJV wall of MS patient's respect to control tissue. In the tunica intima a significant derangement and loss of the endothelial cells have been described. Interestingly scanning electronic microscopy showed absence of endothelium in the defective jugular valves. In the adventitia it has been described an inverted ratio between type I and type III collagen, with prevalence of the latter. Finally, in the adventitia layer it has been found the presence of calcifications arranged around the vena venarum. Assessment of immune cells in the three IJV layers did not demonstrate increased infiltration. Current studies do not clarify the origin of the pathology of the IJV in patients with MS. Congenital, infectious, or even post thrombotic ethiology have been advocated. Finally, the review summarizes studies which link the CCSVI pathophysiology to the complex MS pathogenesis, and particularly to the impact of restricted brain outflow on the cerebral spinal fluid dynamics and cerebral perfusion.

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Vascular aspects of multiple sclerosis

Cited by 215 publications

References 93 publications

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

Concomitant Analysis of Arterial, Venous, and CSF Flows using Phase-Contrast MRI: A Quantitative Comparison Between MS Patients and Healthy Controls

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

The Pathology of the Internal Jugular Vein Wall in Multiple Sclerosis

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