No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study

Wattjes, Mike P.; Oosten, Bob W. van; Graaf, Wolter L. de; Seewann, Alexandra; Bot, Joseph C.J.; Berg, René van den; Uitdehaag, Bernard M. J.; Polman, Chris H.; Barkhof, Frederik

doi:10.1136/jnnp.2010.223479

Cited by 122 publications

(122 citation statements)

References 18 publications

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“…Patients with MS were autonomously seeking treatment at the department of cardiovascular and thoracic surgery of Onze-Lieve-Vrouw Ziekenhuis Aalst for so-called chronic cerebrospinal venous insufficiency syndrome, which is presumed to be caused by stenoses or obstructions of the internal jugular and/or azygos veins (12). However, jugular vein stenoses can also be found in healthy individuals (13). Patients with MS with internal jugular vein stenosis detected by CT venography were scheduled at their own explicit request for angioplasty.…”

Section: Resultsmentioning

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.

108

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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Section: Resultsmentioning

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.

108

104

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“…Similar prevalence rates of CCSVI in this MR imaging substudy were found, as in the previous study. 13 A number of recent reports have presented evidence against the CCSVI hypothesis in MS. [18][19][20][21][22][23][24][25][26][27][28][29] The possible reasons for the discrepancies in findings between different studies are numerous. 30 Veins have a tendency to collapse and change their morphology and size.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] Some recent studies were able to partially reproduce original findings [2][3][4] with substantially lower sensitivity and specificity for MS, 9-17 while others were not able to support these findings using various imaging techniques. [18][19][20][21][22][23][24][25][26][27][28][29] In the CTEVD study, 13 the largest case-control study, to date, to investigate the prevalence of CCSVI in patients with MS, CIS, and other neurologic diseases, and HCs using specific proposed Doppler sonography criteria, 3 increased prevalence of CCSVI in MS was shown but with modest sensitivity and specificity. Despite the currently ongoing debate about whether CCSVI is associated with MS or not, 30 its significance in relation to MR imaging parameters also needs to be determined, both in patients with MS and HCs.…”

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confidence: 99%

No Association Between Conventional Brain MR Imaging and Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis

Zivadinov

Cutter

Marr

et al. 2012

AJNR Am J Neuroradiol

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“…Doepp and colleagues found no evidence of CCSVI in patients with MS using Doppler criteria [Doepp et al 2010]. Using magnetic resonance venography (MRV) and flowquantification study, Wattjes and colleagues found no evdience of venous back flow in patients with MS, and no difference between patients with MS and controls in terms of outflow abnormalities [Wattjes et al 2010]. Lastly, in a case control study, Sundströ m and colleagues found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux in patients with MS [Sundstrom et al 2010].…”

Section: Subsequent Studiesmentioning

confidence: 99%

Multiple sclerosis and chronic cerebrospinal venous insufficiency: a critical review

Awad

Marder

Milo

et al. 2011

Ther Adv Neurol Disord

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Chronic cerebrospinal venous insufficiency (CCSVI) was recently proposed as a contributing factor in the pathology of multiple sclerosis. This concept has gained remarkable attention, partly because endovascular neurointervention has been suggested as a treatment strategy. This review summarizes available evidence and provides a critical analysis of the published data. Currently, there is inconclusive evidence to support CCSVI as an etiological factor in patients with multiple sclerosis. Endovascular procedures should not be undertaken outside of controlled clinical trials. Keywords: chronic cerebrospinal venous insufficiency, multiple sclerosisThe origin of the hypothesis Chronic cerebrospinal venous insufficiency (CCSVI) as a potential etiopathogenic entity in multiple sclerosis (MS) has recently been suggested and gained significant attention.Over the past few years, Zamboni and colleagues were the first to propose and explore this novel and controversial idea [Zamboni et al. 2009b,c,d]. The theory of CCSVI suggests that MS may be causally related to an inflammatory or immune reaction to iron that accumulates in the central nervous system (CNS) secondary to insufficiency of cervical and cerebral venous blood vessels [Zamboni, 2006]. The same investigators detected venous insufficiency by ultrasound and transcranial Doppler. These patterns of venous insufficiency in cranial and cervical blood vessels were seen in patients with MS and absent in control cohorts.In 2010, Zivadinov and colleagues studied 16 patients with relapsing remitting MS (RRMS) and eight matched, healthy controls by 3 T scanner using susceptibility-weighted imaging sequence [Zivadinov et al. 2010]. According to the authors, all 16 patients with MS fulfilled the diagnosis of CCSVI compared with none of the healthy controls. In patients with MS higher iron concentrations were found in the thalamus, globus pallidus, and hippocampus. Iron concentration measures were related to longer disease duration and increased disability, and increased MRI lesion burden and brain atrophy. Similar results were reported by Haacke and colleagues in the same year . Subsequent studiesAs mentioned above, the proposal of CCSVI as an etiological factor or disease modifier in MS is controversial. Subsequent to the initial observations, other investigators conducted their own studies to determine the existence and prevalence of CCSVI in patients with MS and control cohorts.One positive study by Al-Omari and Rousan showed that in 25 patients with MS there was evidence of CCSVI in 84%, whereas none of the 25 controls displayed evidence of cerebral or cervical venous abnormalities [Al-Omari and Rousan, 2010]. There was no blinding of the investigators in this study.All other published studies, however, could not reproduce the findings published by Zamboni and coworkers [Doepp et al. 2010;Krogias et al. 2010;Sundstrom et al. 2010;Wattjes et al. 2010;Yamout et al. 2010]. Doepp and colleagues found no evidence of CCSVI in patients with MS using Doppler criteria [...

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No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study

Cited by 122 publications

References 18 publications

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

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

No Association Between Conventional Brain MR Imaging and Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis

Multiple sclerosis and chronic cerebrospinal venous insufficiency: a critical review

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