Dr Traboulsee's venography imaging study

[Cece]

Dr. Traboulsee is running the Canadian clinical trial of CCSVI, and if his imaging study results are any indicator, he is not an optimal choice to be running the big trial. The imaging study came out Tuesday (Oct 8 ).
http://www.medpagetoday.com/Neurology/M ... id=5517461

More than 50% venous narrowing according to venography was found in 74% of MS patients, 66% of siblings, and 70% of controls. When identified by reductions in venous blood flow, narrowing was present in 51% of patients, 45% of siblings, and 54% of controls.

This was using catheter venography, but not intravascular ultrasound. While not the gold standard when used without ivus, catheter venography should have been enough to capture a difference if the IR was experienced and if there is a difference there.

Remember the Fox study looking at cadavers? Dr. Fox of the Cleveland Clinic found equal amounts of vein wall stenosis in both MS patients and controls, but he found intraluminal abnormalities in much greater prevalence among the MS patients. These intraluminal abnormalities are the problem; for me personally, both my jugulars had bad valves within the veins that were seen on MRI, ultrasound, venogram and ivus. One possibility with Dr. Traboulousee's nonresults is that he is counting that vein wall stenosis, as Dr. Fox also observed, that is equally prevalent in both groups.

Dr. Traboulousee did take this into consideration when he looked with the external ultrasound:

Ultrasound studies disclosed no abnormalities in half the MS patients as well as in half of the non-MS participants. Rates of absent valves, asynchronous valves, immobile valves, and valves that did not close fully were also nearly identical in patients versus controls.

But it is inside-the-vein intravascular ultrasound (ivus) that is needed, and in the hands of someone who has learned to see with it.

We can't ignore evidence. We also need to make sure we are interpreting evidence correctly, and that the evidence is gathered by someone who can recognize a valvular stenosis if one is there. The talk of death knells is over-done. We just had the Sherbourne National CCSVI Society meeting with positive research from Dr. Beggs and from Dr. Haacke's lab. CCSVI remains controversial but we have yet to have had the right studies done.

[DougL]

From Toronto Star...

Still, others report lasting improvements and for that reason Traboulsee is continuing to pursue another study to determine if there are benefits to liberation therapy.

...

Still, Traboulsee, who is the MS Society of Canada Research Chair, argues that more research must be done to determine what effect, if any, venous dilation has.

[Cece]

Bad ccsvi news always gets lots of press.
Dr. Traboulousee has to justify why he's not shutting down his own clinical trial in light of the bad McMasters results and now his own results.

here's the global post
http://www.globalpost.com/dispatch/news ... le-and-wit

"Sometimes these things can become separated, and what we've found is that although CCSVI as defined by Zamboni doesn't really exist ... we still have the situation where thousands of Canadians have gone abroad and have had a treatment ... (and many have) reported significant improvement."

Other underlying theories in medicine have been proven wrong but have still led to benefit for patients, he said. "I think it justifies going forward.

"But I'll be honest — I don't fully understand how they're feeling better," admitted Traboulsee, suggesting that opening up veins may set off a process in the nerves or cause the release of substances that reduce symptoms like fatigue and brain fog.

When has a theory in medicine been proven wrong but still led to benefits? If we replace 'insufficiency' in CCSVI with 'hypertension', then the same treatment (angioplasty) is treating the hypertension not an insufficicency. The benefit would be there but not for the originally expected reason.

The part about opening up veins setting off a process in the nerves sounds a bit like the theory that angioplasty impacts the vagus nerve leading to improvements. Have we talked at all about the possibility that opening veins could cause the release of substances that reduce symptoms? I don't know what substances those would be.

[PointsNorth]

MaClean's article

http://www2.macleans.ca/2013/10/08/ccsv ... csvi-rare/

[Cece]

MaClean's article

http://www2.macleans.ca/2013/10/08/ccsv ... csvi-rare/

Great find. Anne Kingstom rocks it out again.

For one, the UBC study departs from Zamboni’s work in that it focuses on venous architecture, not blood flow. Zamboni uses catheter venography to enter and scan the vein only after doppler ultrasound reveals measurable problems with flow or reflux. The UBC study, on the other hand, used CV on everyone. Also unclear is how the UBC researchers measured stenosis since veins are such irregular vessels. Another question is the role valve malformation plays in causing stenosis, something that can’t be detected on venography. Then there’s an interesting inconsistency across centres: UBC found jugular stenosis in almost all subjects; the University of Saskatchewan detected as many as one-third less in its subjects.

Zamboni has yet to respond to the UBC study. When he does, it will be in a a scientific journal, he said in an email, adding: ”But if narrowing is the outcome measure of this study, it does not correspond to luminal defects, and thus ultimately to CCSVI.”

Dr. Trabalousee's study appears to have been measuring vein wall stenosis narrowing, not intraluminal defects.

[Trabalousee] admitted he didn’t know how CCSVI treatment might help, suggesting it might have to do with stimulation of vagus nerve or cytokine released from the veins.

Ok what's cytokine and what does it do if it's released from the veins?

Five hundred patients have volunteered for 100 spots at four centres in B.C., Manitoba and Quebec.

Unlike Dr. Siskin's study, Dr. Trabalousee's study has no shortage of patient volunteers. Why the difference? Did it cost a patient money to be in Dr. Siskin's trial, or was the demand for the procedure in the Albany area already satiated after three years of availability of the procedure?

“Now social media determines research priorities,” he says.

Woohoo! If this is true, then we will be getting a large-scale multicenter randomized controlled trial using experienced IRs who have done no fewer than 200 CCSVI procedures using IVUS and using CCSVI-related symptoms not MS as the outcome measures.
I will wait patiently for this.

Sorry for the very long post, I hope others will discuss too....

[cheerleader]

Thank goodness we have Anne Kingston doing her due diligence as a reporter!! She looks beyond death knell headlines. Her exceptional understanding of the science is so appreciated!!

Yes--it's flow, not architecture.

It's a shame that Traboulsee doesn't seem to know about the improvements in CSF flow after venoplasty, as cited by BNAC;
http://www.ncbi.nlm.nih.gov/pubmed/23523158
This is certainly a tangible change.

Not sure how venoplasty would release "helpful" cytokines (protein messenger cells that affect the immune system). Cytokines are known to be inflammatory and injurious after angioplasty, and are a part of endothelial dysfunction and restenosis.
http://www.ncbi.nlm.nih.gov/pubmed/11281299

Geesh....Traboulsee could really benefit from going to a CCSVI conference and talking to the doctors...he really should go to ISNVD.
I think he has so many volunteers because Canadians don't have any other covered/insured or local options. Siskin's trial suffered from lack of US volunteers, who could be treated in the states via self-pay or insurance.
cheer

[Leonard]

consider this scenario:

people with MS and people without MS have the same narrowings in the neck (which I did not believe for one moment and is contrary to the findings of Zivadinov, Zamboni and many others).
but assume that, so ccsvi explains nothing, it is an illusion and neurologists rejoice (mind you, the game is not played, he who laughs last, laughs best..).

but now you get over 40 and the lining of intestine becomes more permeable.
in people with poor circulation and outflow through the IJVs (of more than just the blood!), the perfusion of the cartilage of the sinuses is poor causing inflammation of the sinus, similar to poorly perfused cartilage in a joint which then causes arthritis.
there is a common cause, that is the gut.

and then you get MS (see last page of http://www.thisisms.com/forum/general-d ... 8-450.html sorry to push my own story up again, but I really believe in it....)
and that MS has most certainly to do with the poor flow.
in other words, they need to check a few things at the same time, ccsvi in isolation may be nothing but in combination with a broken gut, ho whow ....
or in combination with a broken BBB due to blood back-up: when Cpn or EBV get hold of the receptors, ho whow...

all in all, I find Dr. Trabalousee's study very tendentious, biased, coloured, one-sided...

[brocktoon]

With such variability in the venous system size, it is no wonder there are so many false positives in the MS and normal groups when stenosis is determined as a percentage. We are looking at some of our MRI data right now to see if we can use their method to show the same results.

[1eye]

Traboulsee could really benefit from going to a CCSVI conference and talking to the doctors...he really should go to ISNVD.
I think he has so many volunteers because Canadians don't have any other covered/insured or local options. Siskin's trial suffered from lack of US volunteers, who could be treated in the states via self-pay or insurance.

The fate of Dr. Siskin's trial makes it glaringly obvious that "MS" sufferers in Canada are being held as political hostages. In the US government is at a stand-still, and the rightist party threatens to force the nation, not just individuals who happen to be civil servants, into bankruptcy. Obama-care (as it's cutely called) is under attack for being too fair and equitable and not favouring enough rich businessmen. But a government agency has declared its allegiance to lobbyists of the drug-vending kind, by overtly moving to block a study that has no government support, into a treatment that does not involve drugs, ostensibly for "MS". Drug manufacturers stand to profit tens of billions of dollars if they can maintain monopoly over it. Competition will succeed where 150 years of medicine and research have failed.

By insisting that Dr. Siskin's study have "enough" US volunteers, who will have to either pay the bills themselves, or be able to convince insurance companies to go against "medical advice", the FDA is showing that its advice comes from a higher power, with enough money to back up its opinions. It's not about nationalism. It's about the fact that people from Saskatchewan were instrumental in building the Canadian health-care system. This all happened a long time ago but it's still considered "socialist" because its creation was not motivated by greed. Gary Siskin is being protected from the iron fist of "socialism", which would "force" the taxpayer to support the study. It's about the drug lobby, and the "socialist" president, Barak Obama.

Dr. Sclafani, the world's foremost expert on treatment and diagnosis of the venous anomalies of CCSVI, using the best tool available, intravascular ultrasound (putting the ultrasound probe inside the vein, at the business end of the catheter), or IVUS, offered his assistance to this trial. It would have made an important difference. It was refused.

Dr. Traboulsee is aware of the redundancy veins provide. He seems not to admit the real possibility that it is this very redundancy that makes the characteristic remissions of "MS" possible. That is consistent with a preconceived belief that "MS" has nothing to do with veins, which his study goes on to conclude.

[AMcG]

I have just received a copy of this paper and it is very poor research even poorer than I expected. There are a lot of basic mistakes in it and I will try and write a longer analysis tomorrow. But I could not resist quick note about the venography results.

Venography results for BC and Sask are the reverse of each other! BC has more normals fitting Zamboni criteria than Msers . Sask has the reverse ! Yet they are both supposedly assessing samples from the same population by the same instrument! How can this be ?

Let me try and put this in a simpler way. If I had a voltmeter and put it on a mains socket on one side of my room and it read 230volts and I then did the same on a socket on the other wall and it read 110volts. I would assume there was something wrong either with my wiring or with my voltmeter or with my sockets. The voltages should be the same. I would look for the fault and until I found it I would not trust my voltmeter as it could be faulty. Traboulsee just accepts this situation. A 'careful' scientist would not. To stretch the analogy a bit further what if I fixed the fault and both sockets then read 230volts. So the 110v should have been 230volts. If I do that to Traboulsees results then either the BC results would then agree with sask in which case Traboulsee's overall results would support CCSVI! Or the Sask results would change in line with BC and the opposite really would be proven. How can Traboulsee not even comment on this? A 'careful' scientist would be forced to suspect a confounding variable affecting his measurements. Until he could account for it he would probably not publish. Not resolving that inconsistency completely undermines Traboulsee's conclusion.

And it gets worse! In the fullness of time I expect this paper to be universally ridiculed it is that bad. Anyway I must to bed. I think CCSVI has nothing to fear from this paper.

[cheerleader]

With such variability in the venous system size, it is no wonder there are so many false positives in the MS and normal groups when stenosis is determined as a percentage. We are looking at some of our MRI data right now to see if we can use their method to show the same results.

Great! That would be an interesting paper -- And then you could add your flow quantifications, and show how percentage of stenosis is not the measure, but hemodynamics are the crux of CCSVI diagnostics.
cheer

[Cece]

With such variability in the venous system size, it is no wonder there are so many false positives in the MS and normal groups when stenosis is determined as a percentage. We are looking at some of our MRI data right now to see if we can use their method to show the same results.

Okay, so veins can be larger or smaller. Is a 66% stenosis in an 18 mm diameter vein equal to no stenosis at all in a 6 mm diameter vein (in terms of the available CSA)? But the former would be considered stenotic and the latter wouldn't, in Trabalousee's study?

AmCG, that is terrible news if the research is poor, because he is conducting the CCSVI treatment study too.

[1eye]

…large-scale multicenter randomized controlled trial using experienced IRs who have done no fewer than 200 CCSVI procedures using IVUS and using CCSVI-related symptoms not MS as the outcome measures.
I will wait patiently for this.

Is 200 the number? The large Italian study said they had to reach 400 before the complications went to a low enough rate.

Say it is 400. Now also accept the figure I have heard, that some 60,000 CCSVI procedures have been done. If they could only do one per patient, and physicians had shared this work evenly, and they all followed the same procedure, for everybody to have reached the end of the learning curve, there would have to have been 150 physicians doing it. At $6,000 each, say, that's 2.4 million dollars each. Not in Canada, you say? Pity.

…percentage of stenosis is not the measure…

I have heard/read the term 50% stenosis. That would mean a minimum 16-fold reduction in blood flow rate, if it were judged by the vein's radius, without a corresponding blood pressure rise. I don’t have the heart muscle strength anymore (since mitoxantrone), to raise my veins’ blood pressure much, so my brain ends up working mighty slowly…

[brocktoon]

With such variability in the venous system size, it is no wonder there are so many false positives in the MS and normal groups when stenosis is determined as a percentage. We are looking at some of our MRI data right now to see if we can use their method to show the same results.

Okay, so veins can be larger or smaller. Is a 66% stenosis in an 18 mm diameter vein equal to no stenosis at all in a 6 mm diameter vein (in terms of the available CSA)? But the former would be considered stenotic and the latter wouldn't, in Trabalousee's study?
(

Good question, it depends on where that stenosis takes place. But let's consider that a vein's largest area below the mandible is 18mm^2, and the smallest would be 6mm^2. So therefore, by Traboulsee's reading, the calculation would be 6mm^2/18mm^2 which is 33%, or ~66% stenosed, and therefore categorized as stenosis. Let's consider someone, who may have a closed vessel, or maybe a hypoplastic jugular vein and his maximum diameter is 8mm^2, and now let's say his smallest caliber size is 7 mm^2. The calculation comes out to 88%, or 12% stenotic, which would not be categorized as stenosis, even though this area size is very small and most likely has very reduced flow out of that vessel. What if the values were 2mm^2 and 3mm^2 (non-stenotic)? or 40mm^2 and 100 mm^2 (stenotic).

Using a fixed value may be a safer bet because it may only take a certain area size to guarantee XYZ ml/s amount of flow. And we have 4 papers using an approach where stenosis is defined as IJV calibier <= 12.5 mm^2 above the C3 neck level, and <= 25mm^2 below the C3 neck level, with consistent results.

[1eye]

Resistances in series are always greater than highest value. So in that sense the smallest narrowness (however you define it, radius, diameter, CSA, or caliber); these produce at most a two-dimensional value. Add time and you get linear flow rate. But volumetric flow rate is 3 space dimensions plus time. Because the length of the stenosis determines the flow resistance, calculating resistance and measuring pressure drop across the length of a stenosis will give you the volumetric flow rate per second. So will Doppler ultrasound and area of the vein, more or less.

All other things being equal, we are interested in the effect of stenosis, or blockage, or malformation, on the individual vein flow rates in the neck. Assuming there are no more changes in flow resistance or local pressure before and after the stenosis, you can gauge neck flow rate reduction by measuring it in two places, for instance at neck arteries and neck veins, much as Dr. Zamboni has done.

Is there a relationship between type of vein and function, or impairment of it.?

Overall flow rate can't change from in to out. But over an individual vein or few veins it can, if volumetric flow rates are different at top and bottom of the neck in that vein, and they are among the largest vessels of that type in the neck, affecting the flow rates through specific parts of the brain served by those veins more than others. The same situation could be affecting arteries if, for example one carotid has a stenosis. That might affect blood supply in a unilateral fashion. Could that affect the bilateral symmetry of symptoms? Individual symptoms, such as affect only one eye?

A stenosis in one vein means either the overall flow volume decreases, or the slack must be taken up somewhere else. New collaterals will bring it back to normal. Until and unless they grow, either you have an overall slowdown, or increased upstream pressure. I expect the gradual progression may be due to increased upstream diameters (compliance) from higher pressure when angiogenesis is no longer able to increase overall capacity of the neck. That, like increased ventricle pressure, may compact the brain's tissue.

Will local pressure increase cause BBB leaks? Lesions?