This Is MS Multiple Sclerosis Community: Knowledge & Support

This the new finding they hinted at in their newsletter, IMO:

"In this large MS cohort, the presence of CCSVI did suggest an association with disease progression, a finding that was not shown in Zamboni's smaller cohort, Zivadinov notes."

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National CCSVI Society: <strong><br /><a href="http://tinyurl.com/44znbct">http://tinyurl.com/44znbct</a> ~Website<br /><a href="http://tinyurl.com/3wzmkmg">http://tinyurl.com/3wzmkmg</a> ~Facebook</strong><br />

This just came into my mail:

EMBARGOED FOR RELEASE: February 9, 2010
Story available at http://www.buffalo.edu/news

First Blinded Study of Venous Insufficiency Prevalence in MS Shows Promising Results
BUFFALO, N.Y. – More than 55 percent of multiple sclerosis patients entered in the initial phase of the first randomized clinical study to determine if persons with MS exhibit narrowing of the extracranial veins causing restriction of normal outflow of blood from the brain were found to have the abnormality, neurology researchers at the University at Buffalo have found.
When the 10.2 percent of subjects in which results were border line were excluded, the percentage of affected MS patients rose to 62.5 percent, preliminary results show, compared to 25.9 percent of healthy controls.
These preliminary results are based on the first 500 participants in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study, which began at UB in April 2009. Investigators are planning to examine 500 additional subjects, who will be assessed in the second phase of the study with more advanced diagnostic tools. Complete data on the first 500 will be presented at the American Academy of Neurology meeting in April.
Robert Zivandinov, MD, PhD, UB associate professor of neurology and principal investigator on the study, says he is “cautiously optimistic and excited” about the preliminary data. Zivadinov directs the Buffalo Neuroimaging Analysis Center (BNAC) located in Buffalo General Hospital of Kaleida Health, where the study is being conducted.
“The data encourage us to continue on the same course,” he says. “They show that narrowing of the extracranial veins, at the very least, is an important association in multiple sclerosis. We will know more when the MRI and other data collected in the CTEVD study are available.” The analyses are being conducted by an independent statistician.
The investigation is the first step in determining if a condition called chronic cerebrospinal venous insufficiency (CCSVI) is a major risk factor for MS. CCSVI is a complex vascular condition discovered and described by Paolo Zamboni, MD, from Italy's University of Ferrara. Zamboni’s original investigation in a group of 65 patients and 235 controls showed CCSVI to be associated strongly with MS, increasing the risk of having MS by 43 fold.
Zamboni and Zivadinov hypothesize that this narrowing restricts the normal outflow of blood from the brain, resulting in alterations in the blood flow patterns within the brain that eventually cause injury to brain tissue and degeneration of neurons.
The first 500 patients, both adults and children, were grouped based on their diagnosis: MS, clinically isolated syndrome (CIS) and “other neurologic diseases” (OND), in addition to healthy controls.
All participants in the first phase underwent ultrasound (Doppler) scans of the head and neck in different body postures to view the direction of venous blood flow. MS subjects also underwent MRI scans of the brain to measure iron deposits in lesions and surrounding areas of the brain, using a method called susceptibility-weighted imaging. Iron findings on these images will be related to subjects’ disability and neuropsychological symptoms.
Of the total participants, 97.2 percent were adults, with the 280 MS patients comprising the largest disease cohort examined in the study to date. The majority of MS subjects were diagnosed with the relapsing-remitting form of MS. There were 161 healthy controls. Doppler scan results were reported on five specific criteria that affect venous blood flow. Patients who met at least two of the criteria were considered to have CCSVI. More detailed analysis of specific Doppler criteria and their association to disease status is underway.
When the 10.2 percent borderline subjects were included in the “normal” category (no venous insufficiency), the CCSVI prevalence was 56.4 percent in MS subjects and 22.4 percent in healthy controls.
In this large MS cohort, the presence of CCSVI did suggest an association with disease progression, a finding that was not shown in Zamboni’s smaller cohort, Zivadinov notes.
The finding that 22.4 percent of healthy controls also met two CCSVI criteria requires continuing investigation, he says.
Bianca Weinstock-Guttman, MD, UB associate professor of neurology in the UB School of Medicine and Biomedical Sciences and a co-principal investigator on the study, notes that the results of the CTEVD research will pose new and provocative questions about the CCSVI theory.
Murali Ramanathan, PhD, associate professor in the Department of Pharmaceutical Sciences, UB School of Pharmacy and Pharmaceutical Sciences, and Ralph Benedict, PhD, UB professor of neurology and psychiatry, also are major contributors to the study.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

These results are significant enough for everybody to get screened for CCSVI when
- MS is suspected
- MS is confirmed
- MS has been around a long, long time

It should now be part of everyone's MS check up.

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National CCSVI Society: <strong><br /><a href="http://tinyurl.com/44znbct">http://tinyurl.com/44znbct</a> ~Website<br /><a href="http://tinyurl.com/3wzmkmg">http://tinyurl.com/3wzmkmg</a> ~Facebook</strong><br />

I disagree, and in fact I think these results lead to the opposite conclusion: people should not rush to get screened for CCSVI, and it certainly shouldn't be routine (yet).

Based on these numbers, current CCSVI testing has little diagnostic value for MS. Whether you have MS or not, tests may or may not show CCSVI. The Buffalo stats suggest false positive and false negative results are both fairly common, at roughly 25% and 45%, respectively.

Other testing centers are showing fairly different results, which is another argument for waiting until the best testing procedures are understood.

I think the bottom line is that the Buffalo results demonstrate how much we still have to learn about this, while providing enough positive evidence of something going on to encourage the research needed to figure it out.

Right now, given the state of CCSVI testing, I think getting screened is only of much practical use if you're planning to have surgical intervention if the test results are positive. But just knowing you have (or don't have) CCSVI isn't of much practical value on its own. It's interesting, and I admit I'd love to know my own CCSVI status, but given the state of testing and the fact that I'm not ready to do anything surgical based on the results, it just doesn't make sense to pay for this testing.

In engineering, people often propose interesting tests to run on our designs. But we have to step back and ask, "what will I do differently based on the results?" If the answer is "nothing" or "not much", then the test has no value beyond the fun of knowing, and is rarely worth spending time and effort on.

/Scut

Scut,

You gave me something to think about, but I then thought about all the neurologial tests I had when I was being diagnosed: evoked potentials, MRI, neurological exmas, etc. etc. Was any one test definitive? No. Do they, as a composite, lead to an diagnosis? Yes.

Some of these tests were negative. And I was still diagnosed.

Also, what about establishing a baseline? If my veins look lik X today and are scanned in two years, how have they changed? Given that Buffalo linked CCSVI progression to MS progression, the veins could be an indicator or a result of progression, but they certainly seem to accompany it. I think that's also important to monitor, even if treatment is not effective, available, or possible in my case.

Cheers,
Sandra

_________________
National CCSVI Society: <strong><br /><a href="http://tinyurl.com/44znbct">http://tinyurl.com/44znbct</a> ~Website<br /><a href="http://tinyurl.com/3wzmkmg">http://tinyurl.com/3wzmkmg</a> ~Facebook</strong><br />

My questions would be:
What was the criteria for normal, healthy control participants?
Why did they not do an MRI for the 26% normal, healthy that showed stensois? It sounds to me like we do not know if those healthy control people who have a stenosis have lesions on their brain!

I am speaking about this from a personal perspective. Dake tested my normal, healthy daughters. One was okay, the other had a stenosis and she had lesions on her brain.

Sharon

WOW, Sharon, you are so sharp. Excellent point. No pun intended, LOL!

Pam

Sharon is very sharp, and speaks from experience. Dr. Zivadinov told a story in Bologna, similar to that of Sharon's daughter. A young woman, one of the "normal" controls, showed CCSVI. She later came back with what appeared to be an MS attack, and then they gave her an MRI, which showed lesions. But I have to say, 26% in normal controls is mighty high. More research needs to be done.
cheer

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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

Just plain speculation, but where did they get the normal, healthy controls from? They will have looked at students, staff, things like that. But I think there will have been also quite a number of relatives of MS sufferers, as this is a very sensible reason to take part in an MS study as a healthy control. And if CCSVI really is congenital, there might be a genetic cause. And well, relatives are strongly linked genetically...

I wonder if they have considered this.

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"There is only one good, knowledge, and one evil, ignorance." Socrates

I suspect part of the reason is cost. MRI scans aren't cheap, since they tie up a very expensive piece of medical equipment for a long time for each scan.

Also, remember that this is just a preliminary report on the first stage of the research. The press release indicates they have more data to process for the full analysis, and I'd bet money they're trying to figure out an explanation for that 26%, too. They may well schedule follow-up MRIs or other tests for the 26%, if they don't have them already.


Exactly. My understanding is that the rate of MS in the population is well below 1%, in fact closer to 0.1%, so that still leaves more than 25% unexplained CCSVI.

/Scut

Cah ... I was thinking the exact same thing ... that a lot of MS people probably brought relatives with them who may have volunteered to be tested - which could elevate that number.

Most people who don't know someone with MS wouldn't volunteer for an MS study ... I wouldn't think (and wouldn't travel for one that doesn't pay) ... you're probably right that some of those people have a little relation to someone with MS and whatever that amounts to in relation (may not be much ... but it's something).

It's prob that the 25% will develop MS, if they haven't already, if no MRI was done of the 25% then who knows...

This was one of my first thoughts as well. When I participated, my father (no MS) came along and participated as well as a control. If there is a genetic component to MS this would most likely skew the control group as they are not truly a random sampling of healthy controls from the general population.

What I am also curious about is CCSVI something that can have an onset later in life? In this case it may not cause problems because of a delay in onset and symptoms appearing due to the slow cumulative nature of the damage. In essence, something else gets you naturally before the damage can show. This would go against the thought of CCSVI being purely congenital and might suggest that rather it is something you could be at risk for developing through another external factor or factors (think heart disease).

Also, I am technically CIS for purposes of this study because I have had only had one attack that I am aware of and it resolved itself. Based on my MRIs and the multiple brain and spinal lesions and being positive for O-bands the neuro I see assures me that I am CDMS as far as he is concerned.

As far as I am concerned these early preliminary results do not cast dought and do open up new avenues for thinking about all of the relationship possibilities. From an academic point of view, this is interesting and should be pursued. Looking at it from a real world point of view, let's move forward with the treatments when it is found and start collecting some real quality of life data.

So, if they took out all the relatives of pwms, then what would the numbers be?
Anyhow, I was just told by a doctor, that they had seen 2 other advanced MS patients and those patients had anomalies of the main cervical and thoracic veins. The problem may be, that different pwMS, just have the problems elsewhere than where the researchers are looking. I think Buffalo knows that, too, which is why they want to continue.
Why