The Chalk and Cheese of CCSVI

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#MSResearch #MS Blog CCSVI debunked

Rodger IW et al. Evidence against the Involvement of Chronic Cerebrospinal Venous Abnormalities in Multiple Sclerosis. A Case-Control Study.PLoS ONE 8(8): e72495. doi:10.1371/journal.pone.0072495






Objective.Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI.



Methods. A case-control study was conducted in which 100 MS patients aged between 18–65 y meeting the revised McDonald criteria were randomly selected and stratified into one of four MS subtypes: relapsing/remitting, secondary progressive, primary progressive and benign. Control subjects (16–70 y) with no known history of MS or other neurological condition were matched with the MS cases. All cases and controls underwent ultrasound imaging of the veins of the neck plus the deep cerebral veins, and magnetic resonance imaging of the neck veins and brain. These procedures were performed on each participant on the same day.



Results. On ultrasound we found no evidence of reflux, stenosis or blockage in the internal jugular veins (IJV) or vertebral veins (VV) in any study participant. Similarly, there was no evidence of either reflux or cessation of flow in the deep cerebral veins in any subject. Flow was detected in the IJV and VV in all study participants. Amongst 199 participants there was one MS subject who fulfilled the minimum two ultrasound criteria for CCSVI. Using MRI we found no significant differences in either the intra- or extra-cranial venous flow velocity or venous architecture between cases and controls.



Conclusion. This case-control study provides compelling evidence against the involvement of CCSVI in multiple sclerosis.




So there you have it CCVI is debunked…or is it?
Normally I wait until the end of the month for these posts, but as it is the August holidays….I thought I would take a break and rather than turn the comments off, I would leave them on…..until some idiot starts posting the insults….So I say reframe from this and have your say. If the idiots arrive then unfortunately it stops and the comments stay off on future posts too.
So we go from 100% problems in the original Zamboni study to 0.5% in this study. 0% is almost as unusual as 100%.

The Bard of CCSVI (Prof Z) moans “it was not valid” and tweets that “Patients maintain confidence in our work despite negative studies”
Must admit the “is not valid” rings bells with the last time we had a debate on the negative findings (Click here).
Our friend Joan had a lot to say so if you want that opinion click here and get find out how the character of a person is assassinated such that they are the evil drug baron that did the negative study.
Em……rings bells of the circular sent round about that Nasty ProfG, who may have said something like “where is the evidence” or “Don’t do it unless part of a trial..you shouldn’t be paying for something of unproven benefit”. I think this approach tends to weaken the stance taken.
However, The Bard posted
We read with interest the article published by Rodger and Co-Authors “Evidence against the Involvement of Chronic Cerebrospinal Venous Abnormalities in Multiple Sclerosis. A Case-Control Study” (Plos One August 2013, Volume 8, Issue 8, e72495). 
As correctly reported, in 2009 we described the presence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS), proven by color Doppler ultrasonography (CDUS) and confirmed by catheter venography. 
1 The results obtained by the Canadian researchers are exactly the antipodes of what we found, since they were unable to demonstrate any venous flow abnormalities in the MS patients investigated both with CDUS and MRV. We briefly discuss below, why the methodology adopted by the Authors may lead to a so strong discrepancy in comparing results. 
i) Regarding CDUS methodology, we were very surprised that the Authors failed to use the updated methodology recently recommended by an international consensus in order to improve the reproducibility of the CDUS protocol.  (non-updated methods showed 100% concordance with CCSVI did they not?)
2 The only meta analysis of all reports from 2005 till June 2011 demonstrated a strong prevalence of CCSVI in MS, but with marked heterogenicity among studies. 
3 To avoid this and to make the studies more comparable after June 2011, seven international scientific societies developed a technically detailed protocol, not cited yet. 
ii) Contrary to the recommended protocol, we were impressed in the Rodger study by the absence of any M-mode analysis for investigating the criterion #3.2 CDUS M-mode is indispensable to detect intraluminal obstacles and fixed valve leaflets, which represents the majority of CCSVI venous abnormalities. In figure 1 the valve motility of a normal subject is well apparent as compared by a patient with CCSVI and MS (VV do you agree as our resident value expert). 
This represents an intraluminal obstacle leading to flow blockages and/or bidirectional flow depicted in the figure 2, and seen by several Authors, but, unfortunately, never detected in the survey reported by the Authors. 
iii) Regarding MRV methodology we were again surprised by the focus of the investigation in the upper and mid region of the neck, where significant differences in jugular flow rate where never detected in CCSVI condition. To the contrary, several reports measured significant restriction of the jugular flow rate, increased flow through the collaterals, and extraluminal stenosis in the lower portion of the neck, exactly where Rodger et al. omitted to perform any assessment.
Maybe we will have a reply 
However the debate rages on and on

For some balance we also have had another paper published recently
Karmon Y, Zivadinov R, Weinstock-Guttman B, Marr K, Valnarov V, Dolic K, Kennedy CL, Hojnacki D, Carl EM, Hagemeier J, Hopkins LN, Levy EI, Siddiqui AH. Comparison of Intravascular Ultrasound with Conventional Venography for Detection of Extracranial Venous Abnormalities Indicative of Chronic Cerebrospinal Venous Insufficiency. J Vasc Interv Radiol. 2013 doi:pii: S1051-0443(13)01106-8. 10.1016/j.jvir.2013.06.012. [Epub ahead of print] 
PURPOSE:To investigate prevalence of extracranial abnormalities in azygos and internal jugular (IJ) veins using conventional venography and intravascular ultrasound (IVUS) in patients with multiple sclerosis (MS) being evaluated for chronic cerebrospinal venous insufficiency, a condition of vascular hemodynamic dysfunction. 
MATERIALS AND METHODS: PREMiSe (Prospective Randomized Endovascular therapy in Multiple Sclerosis) is a venous angioplasty study that enrolled 30 patients with relapsing MS. The patients fulfilled two or more venous hemodynamic extracranial Doppler sonography screening criteria. Phase I of the study included 10 patients and was planned to assess safety and standardize venography, IVUS, and angioplasty and blinding procedures; phase II enrolled 20 patients and further validated diagnostic assessments using the two invasive techniques. Venography was considered abnormal when ≥ 50% lumen-diameter restriction was detected. IVUS was considered abnormal when ≥ 50% lumen-diameter restriction, intraluminal defects, or reduced pulsatility was detected. 
RESULTS: No venography-related or IVUS-related complications, including vessel rupture, thrombosis, or side effects of contrast media were recorded among the 30 study patients. IVUS-detected venous abnormalities, including chronic, organized, thrombus-like inclusions were observed in 85% of azygos, 50% of right IJ, and 83.3% of left IJ veins, whereas venography demonstrated stenosis of ≥ 50% in 50% of azygos, 55% of right IJ, and 72% of left IJ veins. Sensitivity of venography for detecting IVUS abnormalities was 52.9%, 73.3%, and 80% for the azygos, left IJ, and right IJ veins, respectively.
CONCLUSIONS: IVUS assessment of azygos and IJ veins showed a higher rate of venous abnormalities than venography. IVUS provides a diagnostic advantage over conventional venography in detecting extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency.
Not 100% but then it is no-where near 0.5%, surely enough pages inches (cm) have been spent on this subject. 

There clearly is not a 100% link with MS and it is not causal based on loads and loads of studies, maybe you disagree but the weight of evidence just keeps piling up. 

Did they use the right protocols?

I suppose some of the people showing such high rates do sometimes get their character assassinated also. That may be equally unfair however sometimes…maybe rightly so as some of them are blaggards.
However this study relates to PREMise trial and the results of this were leaked, so we know where that went (click here) a big thumbs down.
Lets see the results of the clinical studies and put it to bed one way or the other, surely they must come sometime soon. I wonder what ECTRIM 2013 will bring? I do know it will bring MS Question Time so don’t forget to ask some questions for the panel of Neuros. The more contentious the better? 
Thank you for reading this far. Please do not post insulting or malicious posts as you stop the enjoyment of many others……
They serve no purpose except to insult 

About the author

MouseDoctor

3 comments

  • Dear Andy Clarke
    Sorry but MD2 decided to delete their comments and that removed yours too..that was not intended.

    Slow day?….Not really I have plenty of things to do.

    Regards as always. However the above post is topical

  • So there you have it!

    3 hours and thirty minutes and Americians have not even woken up,

    I have been called Billie Buckshitter and a troll

    I think Johnny Fartpants is better description..my Dad always used to say Give you a**e a chance when I would ask too many questions

    You have been warned and it is time to follow through with the threat.
    I was personally looking forward to VVs take on this, or maybe Joans, but just goes to show how one rotten egg can spoil the basket so Ta Ta for Now

    The experiment is over and I dpn't even do Facebook

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