Debunking the latest study ‘debunking’ CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Re: Debunking the latest study ‘debunking’ CCSVI

Postby brocktoon » Mon Sep 23, 2013 1:35 pm

I should clarify that stenotic group does not just include those with narrow caliber, or where the measured area of signal is below a certain threshold. It also includes those who may have missing jugular(s), or even abnormally closed jugular(s) in which no signal is generated on contrast-enhanced venography, or time-of-flight venography. Those cases would be considered stenotic. Using MR we have shown ~70% stenotic/anomalous in two sets of data of MS patients in papers. And 55-60% with another paper using similar criteria. Granted, we have our own criteria for stenosis classification, but we have consistent results and there is striking similarity between the normals flow and non-stenotic group flow. It would be very interesting to take stenotic cases classified with catheter venography and compute flow using MR with them to see if the results are similar! And I wonder what explanation can be given to the non-stenotic MS subset with similar total flow and normalized flow to our healthy controls.

Are you going to be at the Sherbrooke conference this weekend? I am eager to present and discuss our latest findings with you. I will have to read up on the Trabbaloussee research in the meanwhile.
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby Cece » Tue Sep 24, 2013 2:23 pm

brocktoon wrote:Are you going to be at the Sherbrooke conference this weekend? I am eager to present and discuss our latest findings with you. I will have to read up on the Trabbaloussee research in the meanwhile.

Now there is one more reason to regret that I won't be able to make it to Sherbrooke.
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby Cece » Tue Feb 11, 2014 6:53 pm

brocktoon wrote:Another big problem with this study is that the MS group is not separated in any way, which hinders the ability to analyze the data properly. Our group has already replicated the bar graph with our recent MRI flow findings and we have observed similar findings to the Rodger paper, but when the MS group is separated into stenotic and non-stenotic subgroups, we see lower IJV flow in the stenotic group compared to the controls and non-stenotic MS groups. We still have to work on the statistics for the data set though and hope to have a paper on it within a few months.

Is this your group's work?
From ISNVD 2014 http://www.isnvdconference.org/program/ ... -book.html
Classification of Venous Outflow in the Extracranial Vessels in a Large Cohort of MS Patients

Sean Sethi, MS, David Utriainen, Robert Loman, MD, Imran Saqib, E. Mark Haacke, Ph.D. – MR Innovations, Inc., Wayne State University

Background: MRI is a viable modality for evaluating structure and function of the extracranial vessels.

Objectives:To re-evaluate extracranial vessel blood flow using in-house software SPIN (Detroit, MI), and to classify venous collateral flow in MS and normal control populations using MS data from four different imaging sites using MRI.

Methods: A group of 67 healthy control (HC) subjects as well as 761 multiple sclerosis (MS) subjects from four different imaging sites were imaged with 3T MRI scanners using a comprehensive CCSVI protocol. Phase contrast flow quantification (PC-FQ) and MR Venography imaging were exclusively used to quantify blood flow of the extracranial vessels and to anatomically characterize subjects into stenotic (ST) and non-stenotic groups. Venous vessel flows were normalized to arterial flow at the C2/C3 and C5/C6 vertebral level. Data were analyzed and subjects were classified into different venous collateral groups based on four different pathways. Determination of delay between IJV peak flow and carotid systolic peak flow was analyzed to determine whether there were differences in time delay for each group.

Results: In the MS cohort, more than 50% of the subjects were ST. Normalized IJV flow for the ST-MS group was similar for each site, and lower than the NST group and the HC groups—which were found to have similar normalized IJV flow. The ST group also showed higher flow in Type 3 and Type 4 venous collaterals, indicating a longer transit time for extracranial venous blood to drain back to the heart.

Conclusion: This shows further evidence for abnormal flow in the MS cohort not only in the IJVs, but non-primary venous pathways as well.

The flow time in the stenotic group was not just higher in the IJVs, but also in the collateral veins. I do not understand why that would be, unless there are blockages in the vertebral veins or vertebral plexus or there is congestion that slows it down?
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby Cece » Tue Feb 11, 2014 7:00 pm

Quantitative Flow Differences between Multiple Sclerosis and Healthy Control Subjects

Sean Sethi, MS, David Utriainen, BS, Wei Feng, PhD, Ana M. Daugherty, MA, Naftali Raz, Ph.D., J. Joseph, Hewett, MD, E. Mark Haacke, Ph.D.

Background: MRI is a reliable method for quantifying blood flow and visualizing head and neck vasculature in 3D.

Objectives: To provide a retrospective, statistical analysis on a group of healthy control (HC), stenotic MS (ST), and non-stenotic MS (NST) subjects to determine the optimum flow thresholds to differentiate HC from MS.

Methods: A group of 138 MS and 67 HC subjects were imaged on 3T Siemens scanners between two sites. Both 2D TOF MRV and 3D time resolved CE MRAV were used to determine if IJV stenosis was present, subdividing the MS group into ST and NST. The 2D PC was used to quantify flow through the major arteries and IJVs at both C2 and C6 levels. The ratio between the larger IJV flow (dJ) versus the smaller IJV flow (sdJ) was calculated as sdJ/dJ. IJV flow was then normalized to the total arterial flow (tA), providing two major criteria for both levels, the tIJV/tA, where tIJV is the sum of both IJV flows, and sdJ/tA. MANOVA and ROC curve analysis were done. Significance was determined at p=0.05.

Results: In the MS sample, 66 (48%) were NST and 72 (52%) were ST. When comparing the ST and HC groups, optimum thresholds were determined to be: 0.62 for C6tIJV/tA, 0.66 for C2tIJV/tA, 0.16 for C6sdJ/tA, 0.10 for C2sdJ/tA, 0.31 for C6sdJ/dJ, and 0.14 for C2sdJ/dJ. The subjects that meet both: tIJV/tA criteria are 9% HC, 11% NST, and 61% of ST; sdJ/tA criteria are 13% HC, 6% NST, and 60% ST;and sdJ/dJ criteria are 13% HC, 7% NST, and 44% ST.

Conclusion: The current sample of MS patients and HC indicates that there is a statistically significant difference in venous outflow through the IJV between the two groups. These criteria may provide the means of assessing vascular abnormalities in MS subjects quickly using MRI

After all the controversy over whether CCSVI even exists, let alone is associated with MS, it feels good to have progress on that front.
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby brocktoon » Thu Feb 13, 2014 7:37 am

Yes, that is our work. I should mention that only the second abstract (138 vs 67) was literally submitted to American Journal of Neuroradiology last week. It is a very robust paper so I am excited and hopeful to hear back from them.

The first abstract "Classification..." paper is not done yet, but we finally have the data for about 650 MS and 67 HC, so I would be cautious in quoting it.

It was a great conference (and city!) and we hope to establish some new collaborations from it.
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby Cece » Thu Feb 13, 2014 8:05 am

brocktoon wrote:Yes, that is our work. I should mention that only the second abstract (138 vs 67) was literally submitted to American Journal of Neuroradiology last week. It is a very robust paper so I am excited and hopeful to hear back from them.

Congrats on finishing and submitting. Exciting indeed!
The first abstract "Classification..." paper is not done yet, but we finally have the data for about 650 MS and 67 HC, so I would be cautious in quoting it.

Let me know if you want it removed or shortened. There is a difference between a conference abstract and an abstract from a paper that has been peer-reviewed and published, that's very true.
I compare this to the early days when all we had to go on was Dr. Zamboni's initial papers and I think what a difference five years has made.
Thank you for your contributions and may all future collaborations and contributions be just as strong!
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby brocktoon » Fri Feb 14, 2014 11:05 am

Thank you so much. It was a laborious effort and a culmination about about 4 years of processing and reviewing about 2000 MS cases from many different sites. I am really crossing my fingers for its acceptance. You can leave it up as I don't mind it being there so people can see what we are doing, I am very grateful that people have picked up on it and are talking.
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby 1eye » Sat Feb 15, 2014 8:25 pm

Is MRI capable of distinguishing host from parasite? I am concerned so many people have these altered and misshaped veins. Anybody know why? I didn't have much trouble till middle age.\
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Re: Debunking the latest study ‘debunking’ CCSVI

Postby cheerleader » Sun Feb 16, 2014 12:49 pm

Thanks to Brocktoon's team for scientifically elucidating the real difference between the stenosis seen in healthy controls and pwMS....it's not OK to deem "CCSVI positive" as jugular stenosis as >50% in one location and thereby see it in healthy controls and pwMS (as the recent negative Canadian study headed up by Dr. Machan, to be published in the Lancet, ugh)---

There is much more subtlety in this analysis, and I'm trusting it will be published. This research is real science based on statistics, not just some irrelevent percentage which becomes the cut-off for CCSVI positive and negative, and then everyone gets tossed in one bin or another. When we see the real analysis presented in this specific manner, the difference between HCs and pwMS is striking.

This was a ton of work for the analysts involved--and I was really, really happy to see this presentation at the ISNVD. PwMS who have stenotic veins have a serious situation. As to 1eye's question---MRI can show us much, but it was only upon venography that Dr. Dake commented to Jeff that he had never seen such malformed veins before, and that the lining of Jeff's veins were unusually "sticky." There is much more to learn--about endothelial dysfunction, collagen remodeling and venous malformations. We're at the beginning.

I'm just happy we have such great minds and scientists, like the members of the ISNVD, looking at this problem--
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