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How do we account for this stark contrast? While the populations of MS patients and healthy subjects appear to be reasonably similar in all the studies, at least two major differences in methodology could account for the negative findings in the German/British study:

# As opposed to the other studies, it only examined the jugular veins high up, near the angle of the jaw, where additional veins, called collaterals, often branch off the jugulars to maintain blood flow even if there is a blockage. Moreover, as the exam was limited to the top of the neck, it would not have picked up decreased blood flow due to severe jugular narrowing lower down, especially at the base of the neck, near the head of the collar bone, where vein anomalies often occur and there is little or no collateral circulation to maintain blood flow.

# It assessed jugular vein narrowing in the “sagittal” plane (the ultrasound probe is placed parallel to the length of the vessel). The Zamboni technique uses the “transverse” plane ( the probe is placed at a 90 degree angle to the length of the vessel) to look for narrowing, webs, or abnormal valves that Dr. Zamboni believes are often missed in the sagittal plane examination.

There is an article on CTV's website about why studies find conflicting results. The article which is by Doctor Lorne Brandes and uses CCSVI as an example! The article is titled:

<< When studies disagree: cancer treatment and CCSVI as examples

June 21, 2010 11:17 by Dr. Lorne Brandes >>

Here's the link to the article:

http://healthblog.ctv.ca/post/When-stud ... mples.aspx

Scroll down to the second part of the article to read Dr. Brandes' two bullet points on possible reasons why the 2 small studies from Germany and Britain didn't find CCSVI. Here is a quote from the article:



The whole article is well worth reading. How I missed it when it first came out I don't know. My apolgies if this has already been posted on ThisisMS.

It is regretful that Drs. Doepp and co-authors’ attempt to reproduce Professor Zamboni’s discovery of a link between multiple sclerosis and disturbance of the outflow veins of the brain and spine has been unsuccessful. It is particularly unfortunate that the authors’ misunderstanding of Dr. Zamboni’s publications about this subject have led to their conclusions that “No cerebrocervical venous congestion in patients with multiple sclerosis" exists

The authors mis-state several of the criteria for a positive ultrasound examination. They state that reflux must be present in both internal jugular veins or both vertebral veins. This is not accurate. Reflux in any one of these veins was considered a positive criteria by Zamboni.

It appears to me that Dr Doepp and colleagues have tried to elicit reflux by testing for incompetent valves in the lower jugular vein. Incompetent valves result in reversal of blood flow from the heart back up into the jugular veins. They used the Valsalva maneurer, a technique to increase pressure in the chest that reverses blood flow. However, Zamboni explicitly states that one should assess flow “never in (by) a forced condition such as the Valsalva manoeuvre.”

That the authors’ attempts were unsuccessful is not surprising. The ultrasound examination used by Zamboni is a simple one but the description of the technique has not been fully elaborated in his papers. Thus performance of the ultrasound by some investigators is often at variance and this may lead to differences of results. At my own institution, we were surprised that non-invasive testing by ultrasound did not correlate with the very obvious obstructive phenomena seen on catheter venography, which remains the Gold Standard of assessing veins. We also had difficulty identifying CCSVI on ultrasound, initially using the Valsalva maneuver during out testing. In fact we were able to find an obstruction in only one patient of twenty. It was only after being shown how to correctly perform this simple screening test by the Zamboni team during a visit to Ferrara, that we have become facile in detecting these abnormalities. It is clear that there is a learning curve to the use of this technique.

Nor does this paper refute the concept of CCSVI. Doppler ultrasound is only a screening test for CCSVI. When Doppler shows signs of CCSVI, the gold standard test of catheter venography is indicated to detect the sites of potential obstruction. Doppler is not the definitive test of CCSVI because it cannot assess the azygous vein, an important contributor to cerebrspinal venous outflow resistance. Catheter venographies routinely show evidence of outflow obstructions. Sluggish flow, reversal of flow, extensive collateral veins, strictures, duplications, reversed valves, thickened incompletely opening valves and misplaced valves are among the many abnormalities seen in MS patients that we never see in patients without MS.

The paper by Sundstrom and coauthors similarly rejected the CCSVI hypothesis by performing MR venograms and flow quantification in the neck. MR venography is suboptimal as a screening test because it underestimates and overestimates stenoses quite regularly. One can see from their illustrations two MRV images. It is noteworthy that neither image shows the portion of the jugular vein where lesions causing flow resistance are usually found: behind the clavicle as the vessel enters the chest. Both images show considerable collateral vasculature suggestive of CCSVI. Moreover the image on the right on page 258 purports to show a stenosis with an arrow. It is well known that most of the narrowings referred to by the white arrow are a common transient, non-stenotic narrowing caused by a true narrowing below the clavicle. Catheter venography shows abnormalities that cannot be detected by MRV.

I was struck by the rapidity of publication of both articles. Surprising! Both papers were accepted within six weeks. I have never had such rapid decision, editing and publication of any of my more than 120 publications.

This debate is going to be a challenging one. One side wants randomized prospective trials to prove efficacy. However while many proceduralists have noted sometimes impressive gains for patients, these proceduralists need to evaluate nuances of techniques before consensus can be built regarding the best approach to therapy. Only then can intelligent, carefully designed randomized prospective trials begin. Some who commonly perform randomized trials will try to reduce the work of those who will try to develop the best practices because they are not randomized. However, in my view this is a necessary initial step toward the final trials.

angioplasty.
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