CCSVI March 2013

Valdueza JM, Doepp F, Schreiber SJ, van Oosten BW, Schmierer K, Paul F, Wattjes MP. What went wrong? The flawed concept of cerebrospinal venous insufficiency. J Cereb Blood Flow Metab. 2013 Feb 27. doi: 10.1038/jcbfm.2013.31. [Epub ahead of print]

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis(MS), coining the term of chronic cerebrospinal venous insufficiency ('CCSVI'). The diagnosis of 'CCSVI' is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS. Many investigators tried to replicate Zamboni's results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the 'CCSVI' concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat 'CCSVI' in the care of MS patients, outside of the setting of scientific research.

This is open access so you can read and debate it yourself  but this study indicates that the concept of CCSVI may be based on thin ice
and this paper calls for a "complete halt to therapy".
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"With the ‘old’ ‘CCSVI’ criteria being refuted, the ‘new’ criteria seem to call for new confirmatory studies to confirm or refuse the new results. However, the scientific quality appears unaltered low, as the core statements of our critical discussion also apply to the new modified criteria"

I see the hate campaign will be on its way again however coupled with hints of the blinded trial not being positive then it is going to be increasingly difficult to argue against this view.

CoI: One of the authors works at the Blizard Institute (Neuroscience) & Barts Health


But if a group were going to try to refuse it it may be this next group

Zivadinov R, Magnano C, Galeotti R, Schirda C, Menegatti E, Weinstock-Guttman B, Marr K, Bartolomei I, Hagemeier J, Maria Malagoni A, Hojnacki D, Kennedy C, Carl E, Beggs C, Salvi F, Zamboni P. Changes of Cine Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis Treated with Percutaneous Transluminal Angioplasty: Case-control Study. J Vasc Interv Radiol. 2013 Mar 20. doi:pii: S1051-0443(13)00531-9. 10.1016/j.jvir.2013.01.490. [Epub ahead of print
PURPOSE:To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA).
MATERIALS AND METHODS: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis.
RESULTS: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group.
CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.
If you have angioplasty on stenosed veins then you get increased blood flow. 

Mistry N, Dixon J, Tallantyre E, Tench C, Abdel-Fahim R, Jaspan T, Morgan PS, Morris P, Evangelou N.Central Veins in Brain Lesions Visualized With High-Field Magnetic Resonance Imaging: A Pathologically Specific Diagnostic Biomarker for Inflammatory Demyelination in the Brain. JAMA Neurol. 2013 Mar:1-6. doi: 10.1001/jamaneurol.2013.1405. [Epub ahead of print]

IMPORTANCE There is no single test that is diagnostic for multiple sclerosis (MS), and existing diagnostic criteria are imperfect. This can lead to diagnostic delay. Some patients require multiple (sometimes invasive) investigations, and extensive clinical follow-up to confirm or exclude a diagnosis of MS. A diagnostic biomarker that is pathologically specific for the inflammatory demyelination in MS could overhaul current diagnostic algorithms. OBJECTIVE To prospectively assess the diagnostic value of visualizing central veins in brain lesions with magnetic resonance imaging (MRI) for patients with possible MS for whom the diagnosis is uncertain. DESIGN Prospective longitudinal cohort study. The reference standard is a clinical diagnosis that is arrived at (after a mean follow-up of 26 months) by the treating neurologist with a specialist interest in MS. The 7-T MRI scans were analyzed at baseline, by physicians blinded to the clinical data, for the presence of visible central veins. 
PARTICIPANTS A consecutive sample of 29 patients referred with possible MS who had brain lesions detected on clinical MRI scans but whose condition remained undiagnosed despite expert clinical and radiological assessments. 
EXPOSURE Seven-Tesla MRI using a T2*-weighted sequence. MAIN OUTCOMES AND MEASURES The proportion of patients whose condition was correctly diagnosed as MS or as not MS, using 7-T MRI at study onset, compared with the eventual diagnosis reached by treating physicians blinded to the result of the MRI scan. 
RESULTS Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions. 
CONCLUSIONS AND RELEVANCE In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms.

This is not really CCSVI, but it just says that veins are at the centre of lesions in those that get diagnosed with MS.

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