Image by kairin via Flickr
After months of anticipation by the worldwide MS community, the results of the University at Buffalo's CCSVI imaging study were disclosed today (click here for report). While they may not be quite as dramatic as some patients had hoped, the results do show an unambiguous link between the vascular abnormalities known as CCSVI and Multiple Sclerosis. (For those readers unfamiliar with CCSVI, click here)
The Buffalo study of 500 subjects showed that 56.4% of the MS patients imaged suffered from a narrowing of their extracranial veins (CCSVI), while 22.4% of healthy test subjects also exhibited such narrowing. This contrasts markedly with the over 95% to 100% correlation found in the smaller unblinded studies previously reported on by the founder of the CCSVI theory, Dr. Paolo Zamboni, who also found no evidence of such abnormalities in healthy control subjects. There were several additional small studies done elsewhere that also had reported a CCSVI-MS correlation of over 90%.
All participants in the Buffalo study underwent ultrasound (Doppler) scans of the head and neck, with some also being imaged with MR venograms. Of the subjects studied, 10.2% were borderline for CCSVI, which allows for some variance in the interpretation of the final numbers.
Upon first look, the much lower correlation between MS and CCSVI shown in the Buffalo study when compared to previous studies may seem disappointing, but in my opinion the less dramatic numbers may actually give the CCSVI theory greater scientific credibility.
MS is an extremely heterogeneous disease, meaning that the symptoms and clinical presentations exhibited can vary widely from patient to patient. This has led some researchers to conjecture that what we now call Multiple Sclerosis may in fact be a collection of different maladies that share common symptoms and markers. This could explain the wide variance in effectiveness seen in the current arsenal of MS treatments.
Furthermore, the diagnosis of MS is an inexact science, and in any large population of MS patients, as many as 10% to 15% could be misdiagnosed. The list of diseases that can be mistaken for MS is quite extensive, and some can be almost indistinguishable from Multiple Sclerosis. For a must read, comprehensive discussion of the many diseases that can be misdiagnosed as MS, click here.
Given the tremendous variance seen in MS patients, and the high level of misdiagnosis, the chances of finding any single trait common in upwards of 95% of MS patients is very unlikely. In fact, I participated in a "Natural History of MS" study at the National Institutes of Health, conducted specifically to identify clinically definite MS patients for use in future NIH studies, precisely because the institution was finding that the high percentage of misdiagnosed patients were skewing the results of the MS studies they were undertaking.
Moreover, unlike the anatomy of arteries associated with the CNS, which is well-known and displays uniformity from patient to patient, the CNS venous system is much less understood. Venous anatomy can differ markedly from patient to patient, making it difficult to define exactly what "normal" looks like.
For these reasons, the initial claims of an almost universal correlation between MS and CCSVI raised red flags for researchers when first presented with the CCSVI theory of MS. While these claims sparked tremendous fires of hope in community of MS patients around the world, they simultaneously cast doubt on the validity of the theory among many serious medical investigators.
The trial results released today by the University at Buffalo fall more in line with what would be expected of an MS breakthrough given science's current body of knowledge regarding the disease. While not the eye-popping numbers reported in the previous studies, the 2:1 ratio of CCSVI found in MS patients when compared to healthy subjects is still dramatic and exciting, and should give curious researchers much reason for continued and vigorous investigation of the theory.
If these early trial results findings hold up, the fact that over 50% of MS patients appear to display signs of a striking vascular abnormality raises a host of intriguing questions. Is the abnormality itself directly responsible for the neurologic symptoms and the damage being experienced by these patients, or does it work in concert with other factors to injure the CNS? Conversely, does the mechanism that is wreaking havoc on a patient's CNS also do damage to their vascular system? How does CCSVI fit with other mysteries associated with MS, such as the existence of "MS clusters", and the geographic distribution of MS? How does CCSVI relate to the signs of autoimmunity that are displayed even in MS patients with CCSVI, and what do we make of those patients who don't display signs of CCSVI? Are they suffering from a completely different disease, and is CCSVI simply a component in a much more complex totality?
Furthermore, we can't discount the anecdotal reports of the dozens of MS patients that have already undergone surgery to correct CCSVI, the majority of whom have reported notable improvements in their disease states. The patients who underwent Dr. Zamboni's Liberation Procedure, a type of balloon angioplasty, showed a significant decrease in relapse rates and a general overall improvement in their health status. The same can be said for the majority of patients treated by Dr. Michael Dake at Stanford University, and Dr. Marian Simka in Poland. While anecdotal reports are subjective rather than objective, and therefore not typically suitable for scientific scrutiny, they certainly can't be dismissed offhand, either.
Over the coming months, much intense research will be underway attempting to answer the many questions surrounding CCSVI. This report out of the University of Buffalo is only the first of many to come, and it would be a mistake to draw anything but preliminary conclusions from it. That said, CCSVI continues to intrigue and tantalize us with the possibility that it could reshape our fundamental understanding of Multiple Sclerosis. Unfortunately, patience will be necessary as we wait for further research results, and patience is a commodity in very short supply among people suffering from progressive, debilitating disease.
I urge all MS patients, and those who love them, to continue advocating strongly for further research into CCSVI, and to reach out to healthcare providers and let it be known that the status quo is unacceptable. Research into CCSVI and other "outside the box" theories must be dynamically pursued. Fixation on the autoimmune theory has yielded imperfect treatments but no cures, and in the unlikely event that CCSVI turns out to be nothing but a promising dead end, the time and effort spent researching it may yet yield discoveries that could finally unlock the mystery of MS. We must make our voices heard, and fight as if our lives depend on it. The excitement over CCSVI reveals the widespread discontent with current MS treatment strategies. We must channel that discontent into a force that will not be denied.
Thanks for the great post. At first I was disappointed at the low rate of pwMS who showed stenosis in the Buffalo study, but I realized that there is so much misdiagnosis (I was just recently rediagnosed with lyme, chlamydia pneumonia, and mycoplasm pneumonia) that nothing to do with MS will ever approach anything close to 100%. Also, once the results are in for the brain/iron study, the numbers may go up. Still and all, the big question remains: Do those with MS who show stenosis and undergo the liberation procedure see a halt to their disease? That, in the end, is what counts.ReplyDelete
From your mouth to God's ear.ReplyDelete
I pray that the VA will undertake a study that will being CCSVI treatment to the many veterans who suffer from MS!
I am lucky to have people looking out for my wife in areas where I can't. I am a strong voice for my wife in marching for a cure. These results, though not as optimistic as once though, are a beam of light into an unresearched area. Why stop at the neck... The problem may lie lower... It is apparent that iron is the cause of MS symptoms... lets look at this from a whole new angle, and stop fixating on autoimmuneReplyDelete
Like others who have commented, I am very curious about the deposition of iron and how it relates to the degree of disability. This may change the standard MS MRI protocol. As it is well documented, the number of lesions and whether or not those lesions enhance often has no correlation to a patients presenting disability.ReplyDelete
500 is still a small study and it was limited to investigation of the internal jugulars. What will the numbers be if we add the azygous vein into the picture? Will the %age of CCSVI increase or decrease as compared to healthy controls. Spinal lesions are least responsive to any of the MS therapies. I wish the studies under way were including the azygous vein.
I'm impatient for personal reasons but I can see that this is the tip of the iceberg for studies and protocols of CCSVI. The thing is, this is the first time such a major development has happened in the cyber-age. Patients are educating and advocating for themselves in numbers unseen. Gone are the days when a patient has to wait for their annual neuro visit to hear about a new treatment. There has been a shift in power. I know I was the first to inform my neuro and MS Clinic about CCSVI last September. I'm not looking so crazy now!
Great blog. Thanks for keeping the masses in the loop.
I am certainly excited by these developments, but I can't help but wonder why the research team lumped CIS patients in with CDMS? Surely they were aware that it takes up to 15 years for these patients to convert and about 20% never do, so this was something that was sure to skew the results in a negative direction? I'm confused as to why they would include this group knowing that we (yes I am one) may not be definitive....just a thought I wanted to put out there...ReplyDelete
Great blog. I mentioned this last post in my blog http://tecnologiaesalute.it ... sorry but it's in italian only :-) It's exactly what I support myself.ReplyDelete
well stated, thanks.ReplyDelete
Good review of the results, good explanation of hidden variables. Thank you.ReplyDelete
keep writing also to facebook ccvis, otherwise i was missing your wise and enlighting comment..........ReplyDelete
shoshi - israel
Absolutely great to follow your blogg. Here in Sweden it is dead quiet on CCSIV. No press and the profession says nothing. Could be they are chocked or confused - who knows?ReplyDelete
You write; "as if our life depends on it". I know you really mean that our life depends on it.
A question - have you written a book or more. You definitely have the talent.
Thank you :)ReplyDelete
Thank you, Marc. I'm also following the news as they appear, and trying to make my own non-self-biased interpretations. I found that you're quite sucessful at doing this.ReplyDelete
Since there was a post from Sweden earlier, this one comes from FINLAND. Can anyone in this very MS-affected country tell me if they've encountered any professionals talking about it? Is there anything moving here in the CCSVI direction?
Best wishes to all
Great stuff Mark, as usual.ReplyDelete
Another very useful and informative post!
I think we need to keep in mind several caveats stated by Dr. Zivadinov, the prinicipal investigator:
The first is crucial: "Our findings indicate this is the real thing, and it's important to let patients and physicians know that. Based on our numbers, we believe diagnostic testing should be offered to MS patients."
Then, in terms of the limitations of the data:
The preliminary results are based only on ultrasound tests of the first 500 participants in the study. Dr. Zivadinov has said that "We will know more when the MRI and other data collected in this study are available."
Further, the Buffalo News story notes that these are "preliminary" results based only on ultrasound and that the follow on study will use more advanced diagnostic tools. It notes that Dr. Zivadinov says that the difference between the Buffalo and Ferrara data might be explained by the use of different devices to diagnose the blockages.
more blog posts like this will help highlight the need for urgency, in this matter. If they have uncovered new technology which shows an abnormality, why don't they just carry out the operation anyway?
Private health clinics will be on this first, but why is our health care system not already converted to this way of thinking. The implications to the initial findings could be dramatic, if CCSVI is connected to MS or not.
there is already a huge demand for the screening for CCSVI. Surgical procedures have already taken place safely.
If this is a safe procedure, why can't many patients, go for the scan,to see if they have CCSVI. This will only help from an informational point of view. If it help ward off MS symptoms, great. We can take it from there.
They can argue about the safety of the procedure but there is no valid argument for not insisting that, all MS patients go for screening immediately, just in case.
OK, Since we've heard from both Sweden and Finland, I thought I would give you all the CCSVI status from another Nordic country, Norway.ReplyDelete
Back in November, I contacted our MS Association about CCSVI (after reading about it in one of Marc's posts). The association posted a news article online several days later. After the article was posted, the local MS discussion boards took up the topic. However, there has not been one word in the media here.
Two days ago, I sent a detailed letter on CCSVI to NRK, the Norwegian national public broadcasting company. My letter contained an appeal that they should cover this very important news story via their media network. So far I haven't heard back, but I am still hopeful. Norway also has a very high incidence of MS and it is very important that we get the word out.
Thanks for adding a rational voice to the discussion. Too many of us were too caught up with irrational exuberance. Based on the INITIAL assessment to the Bufalo data, one could surmise we have NOT found a definitive cause, but we DO have and extremely significant contibuting and/or associated factor. We need to press on for more research in CCSVI.ReplyDelete
Really good read! A great perspective on what is going on.....you have an excellent way of viewing thingsReplyDelete
Leave it to you Marc to issue a level headed perspective on all of this. Good Job!ReplyDelete
Thank you for posting this very valuable information! We learn something new every day.ReplyDelete
God Bless you Marc. I hope that they find a way to help you, either with CCSVI or some other way. You have a wonderful spirit and am glad that you share your life so much with us. You inspire me to not lose hope.ReplyDelete
hey marc. this is a great summation and interpretation of what's happening right now with CCSVI. very informative. thank you!ReplyDelete
I agree, very exciting data.ReplyDelete
Just today I saw your blog for the first time.My most sincere compliments to you! I particularly laughed at "our" view of people from a wheelchair. One not in a wheelchair could never fully comprehend the closeness we feel to all the "upstanding" folks around us. Butt you, as I, are madder than hell about sidewalk curb cuts. 90% of those (few) existent are too high to handle.Question: Why bother at all? See you soon, loriReplyDelete
Thank you for posting this informative piece and adding your distinctive insight. I'm wondering why can't physicians do a simple blood test such as a D-Dimer which is used to determine veneous insufficiency in heart disease prior to the more expensive CT scans. It may be an question born of ignorance but being a natural cynic, I always question why the least expenisve option is not tried first. Has anyone heard about blood testing to determine CCSVI?ReplyDelete
Brilliant post. Wish I had the patience to write something as good as that. Will spread the word on my Facebook page and on Twitter.ReplyDelete
Thank you for a considered, informed, up-to-date and well written article. Your website makes for one the most enjoyable reads on the net.
Keep up the good work..
..AndyCapped from Melbourne Australia
Doing a D-dimer test would indicate a venous stenosis, but *only* if the stenosis were due to a blood clot (thrombus). If the venous stenosis were due to some other cause (plaque, or other defects of the vein walls, causing a narrowing), then D-Dimer wouldn't work.
In cases where a venous stenosis is caused by non-blood-clot causes, there wouldn't be any detectable blood byproducts to look for.
Thanks for the great blogReplyDelete
This comment has been removed by a blog administrator.ReplyDelete
Sorry, I did not mean to be annonymous, and left some typing errors in my previous post, but I don't know how to eliminate it. Could you do it, please ?ReplyDelete
A number of the "healthy" control patients were relatives of MS people. No way to know how many. But one cannot exclude that CCSVI might be a family unherited condition, that precedes MS, and that MS will develop in only some of the CCSVI+ people. You may find more CCSVI in relatives than in non relative "healthy" people. We need to know the exact number of family members that were included in the "healthy" cohort. This could explain the high prevalence of CCSVI+ people among the "healthy" controls.
Dr.Dana Spence at MSU in Michigan,has tested blood samples and found MS blood has 3 times the level of ATP as compared to nonMS subjects.ReplyDelete
ATP is produced by Red Blood Cells when they are stressed passing thru restricted veins. ATP levels signal the body as to what amount of NO2 is needed in the blood .NO2 regulates the amount the veins dialate (open) for passage.
Testing blood for ATP levels could indicate restrictions of any type (CCSVI for example).
I'm an MSer that is a proud participant in this study..ongoing.. i have another one on Thursday! :)ReplyDelete