Overview:

CCVSI or chronic cerebrospinal venous insufficiency is an abnormality in blood drainage from the brain and spinal cord.  Back in 2009 a hypothesis put forwawrd by Dr. Paolo Zamboni from the University of Ferrara in Italy that CCVSI may be related to multiple sclerosis.

The results of initial preliminary findings by Dr. Zamboni set off a flurry of activity and research into CCVSI to evaluate what impacts it might have on the diseases processes associated with MS. Many studies have since taken place many of which conflict with Dr. Zamboni’s initial findings.  The debate over CCVSI continues to this day and some levels of research are still underway.

Exacerbating the debate are people with MS who have had medical procedures done to remove restrictive brain flow and stated improvements.  Many people report positive results in symptoms relief such as cognitive improvement, memory improvement, feeling better, reduced depression, less stress with heat and more.  However clinical studies of CCVSI have shown to be inconclusive while some appear to show benefits.

CCVSI Explained:

CCSVI is a narrowing of veins in the neck and chest that carry blood away from the brain and spinal cord.  The theory put forward is when blood flow is slowed it backs up into the brain and spinal cord just like if you constrict a garden hose.  This leads to oxygen loss and deposits of iron in the brain.  Back in 2009 Dr. Zamboni stated that when he used ultrasound technology and compared blood vessels of people with and without multiple sclerosis he found abnormal blood flow in all patients studied with MS and none in those without hence setting off a flurry of news reports, research and people seeking a CCVSI treatment course.

CCSVI Example DiagramThe connection to CCVSI remains highly controversial with some researchers stating treatment can relieve MS Symptoms while others say CCVSI is not even real comparing it to snake venom, bee stings and other mechanisms people have attempted to mitigate MS symptoms and flare-up’s.

In 2010 Dr. Zamboni in speaking with the US National Multiple Sclerosis Society suggested that if further evidence supports the link between MS and CCSVI, that its treatment may ultimately add to the arsenal of therapies available for MS. He emphasized the need for more research on his hypothesis, and noted that people with MS should remain on their immunomodulatory therapies as has his wife after her endovascular surgical procedure.

The MS Society of Canada has continued research on CCVSI and is still exploring the conditions possible effects on multiple sclerosis.  Canada has per capita more incidence of MS than any other nation in the world it has been said.

Studies:

With MS affecting millions of people globally it is essential that research continues to take place in respect to CCSVI and MS.  Health care providers and systems need research data that confirms the linkage between CCSVI that is valid and concrete which currently does not exist even though at least seven significant studies have been done with conflicting results.

In June 2010, the MS Society of Canada and the USA National MS Society jointly contributed over $2.4 million to support 7 research projects focused on the relationship between CCSVI and MS. All applications were reviewed by an international panel that included experts in interventional radiology, vascular surgery and neurology. The MS Society of Canada worked collaboratively with their American counterparts to assemble the reviewers, who assessed the scientific merit and feasibility of the proposed research, as well as the experience of the applicant teams.

Using advanced imaging techniques and experimental design, those studies which were approved for funding evaluated the structure and function of veins draining the brain and spinal cord in people living with MS, and compared them to the structure and function of veins in healthy volunteers as well as people affected by other neurological diseases.

At the three-year milepost, researchers leading this work are reporting data at major scientific conferences and in various peer-reviewed journals:

2011 Study:

A study in 2011 of 710 MS patients attending six centers (five Italian and one Canadian)  were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni. CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centers. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni . Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. They concluded that the methods for diagnosing CCSVI need to be refined, as the differences between the results at the participating centers, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favor a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

2013 Study:

On October 8th 2013 A research group from the University of British Columbia, Vancouver Coastal Health, and University of Saskatchewan published a study in the U.K. medical journal The Lancet, reporting on the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in people with MS, their unaffected siblings and healthy volunteers. The MS Society of Canada/National MS Society (USA) joint funded study enrolled 177 participants across three centres in Canada, broken down as follows:

67 people with relapsing-remitting MS, 12 people with progressive MS, 55 siblings unaffected by MS, 43 healthy people who were controls.

Dr. Anthony Traboulsee and his team evaluated each group to look for indications of narrowing of the internal jugular and azygous veins. According to Italian vascular surgeon Dr. Paolo Zamboni, who in 2009 identified CCSVI as a potential cause of MS, the internal jugular and azygous veins are affected in MS, resulting in decreased blood flow from the brain resulting in inflammation. Dr. Zamboni created a list of venous structural and functional abnormalities that define CCSVI that can be identified using various imagine techniques, particularly ultrasound. His ultrasound criteria are now used in other CCSVI studies to determine if similar results can be replicated in other people with MS.

CCSVI Ultrasound TestingIn this study, Dr. Traboulsee and colleagues used ultrasound and catheter venography, the latter technique involving insertion of a plastic tube. The tube allows entry of dyes that would enhance x-ray visualization of the veins in the head and neck. CCSVI as described by Dr. Zamboni was detected in 2% of people with MS, 2% of unaffected siblings of people with MS, and 3% of the healthy control group. Catheter venography was also used to detect narrowing of the veins. Vein narrowing was seen in 74% of people with MS, 66% of siblings, and 70% of healthy controls.

Using ultrasound, CCSVI as described by Dr. Zamboni was detected in 44% of participants with MS, 31% of unaffected siblings of people with MS, and 45% of healthy controls. Ultrasound also showed that 41 out of 79 people with MS (52%) displayed no structural abnormalities in their head and neck veins.

Overall, results from the study display no association between CCSVI and MS, and that the significance of venous narrowing in MS symptoms is still in question.

According to Dr. Traboulsee, only a few studies have employed catheter venography to evaluate the prevalence of CCSVI in people with MS. In the article he stated that this technique is a “gold standard procedure that has been proposed as a guide for decision making in endovascular treatment”. As research on CCSVI ensues and data surfaces, standardizing protocols which accurately observe and measure vein blockage and impeded blood flow becomes increasingly important.

It is apparent from the data that the prevalence of CCSVI is higher when looking at ultrasound data in comparison to venography. This is likely due to differences in the sensitivities and specificities of the techniques, which means that one would detect alterations in the veins that the other could not. What is most important here is that the percentage of people with CCSVI is the same for all groups (people with MS, their unaffected siblings and healthy individuals), which confers no association between the condition and MS.

Interestingly, researchers found a high rate of vein narrowing in the healthy control group, which according to Dr. Traboulsee has not been previously reported.

“Our results confirm that venous narrowing is a frequent finding in the general population, and is not a unique anatomical feature associated with multiple sclerosis. This is the first study to find high rates of venous narrowing in a healthy control group, as well as the first to show that the ultrasound criteria usually used to ‘diagnose’ CCSVI are unreliable, so if there is a connection between venous narrowing and MS, it remains unknown, and it would certainly appear to be much more complicated than current theories suggest.”

The recent research findings from the study led by Dr. Anthony Traboulsee indicate there is no connection between CCSVI and MS. The pan-Canadian Clinical Trial that is already underway will continue to investigate whether venous dilation procedures could be beneficial for treatment of MS symptoms. Dr. Traboulsee remains committed to evaluating CCSVI procedures with robust methods and utilizing patient-focused outcomes. We respect and honour the personal health care decisions of those who live with MS and remain committed to funding research that will answer the questions of those who live with the disease.

January 2015

CCSVI Pathogensis DiagramA comprehensive literature search was conducted to identify available published, peer-reviewed, clinical studies evaluating the association of CCSVI with MS, the reproducibility of proposed ultrasound criteria for CCSVI detection, the safety and efficacy of “Liberation treatment surgery” in open-label and randomized-controlled trial (RCT) settings.

There is substantial heterogeneity between ultrasound case-control studies investigating the association of CCSVI and MS. The majority of independent investigators failed to reproduce the initially reported high prevalence rates of CCSVI in MS. The prevalence of extracranial venous stenoses evaluated by other neuroimaging modalities (contrast or MR venography) is similarly low in MS patients and healthy individuals. One small RCT failed to document any benefit in MS patients with CCSVI receiving “Liberation treatment”, while an exacerbation of disease activity was observed. “Liberation treatment” has been complicated by serious adverse events (SAEs) in open-label studies (e.g., stroke, internal jugular vein thrombosis, stent migration, hydrocephalus).

CCSVI appears to be a poorly reproducible and clinically irrelevant sonographic construct. “Liberation treatment” has no proven efficacy, may exacerbate underlying disease activity and has been complicated with SAEs. “Liberation treatment” should stop being offered to MS patients even in the settings of RCTs.

2015 Study

Another recent study in Italy  utilizing C1-C2 X-Ray’s showed looked for compression of the internal jugular veins, in front position, shows a prevalence of 48% and it is equally distributed in the various segments of these veins in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and Multiple Sclerosis (MS).

We investigated 386 patients suffering from CCSVI and Multiple Sclerosis and a control group of 156 patients without MS.  Data analysis of C1-C2 X-Ray parameters shows statistical significance of severe anterior intrusion and right laterality misalignment in the people with CCSVI and MS, that are two to three times more frequent as compared to controls. Considering the novelty of this work and the total absence of scientific similar works able to confirm this data, it is necessary to continue these studies in order to improve the clinical management of these patients and to perform therapeutic strategies based on venous decompressive treatments both surgical that manipulatives.

2017 Study

The clinical trial was launched in 2012 when Dr. Traboulsee received a grant from the MS Society and CIHR. Recruitment of MS participants occurred over two years, and those who displayed signs of CCSVI as determined by ultrasound and venography were randomized to receive either venoplasty or a sham procedure (placebo). A total of 104 participants from Vancouver, Winnipeg, Montreal and Quebec City were randomized: 49 participants received venoplasty and 55 received the sham procedure. Participants crossed over to the treatment or placebo arm at 48 weeks, for an additional 48-week treatment period. Preliminary results at 48 weeks were presented by interventional radiologist Dr. Lindsay Machan from UBC. They showed no statistical difference in outcomes between the two study groups in terms of MRI measures, clinical assessments of MS symptoms and patient self-assessments. The research team concluded that venoplasty is ineffective as a treatment for people living with multiple sclerosis.

And the debate continues….

View The List of CCSVI Studies and Documents And PubMed.gov by Clicking Here…

Does CCSVI Really Exist?

“The way the ultrasound is conducted is not yet standardized,” says Robert Fox, MD, staff neurologist and medical director at the Cleveland Clinic Mellen Center for MS. “It’s not like getting a blood count.” He found when people are examined with varied types of scans, the number of CCSVI cases changed.

Differences in scans could easily be attributed to water intake for example before the scans.

“If you don’t have a lot of volume in the veins they’re going to collapse down,” Fox says. When he had study participants drink Gatorade before their ultrasound, many of them no longer had signs of CCSVI. “Once you fill up the veins, you have much more blood flowing through them, and they’re much more plump.”

Surgeries Commence Without Confirming Data

ccsvi-infographic
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CCVSI treatment is called “liberation therapy” and is an endovascular surgery. Like Angioplasty  it involves placing a tiny balloon called a stent inside a blocked vein to open it up more and restore blood flow. When Zamboni studied this surgery in a group of MS patients, he claimed to have found that it did reduce relapses and the number of new brain lesions. However other studies have not found the same improvement. Some people with MS who’ve had the endovascular procedure claimed they felt better afterward, but researchers say this may be due to people’s high hopes about the surgery outcome.

And Even More…

In May 2012, the USA Federal Drug Administration (FDA) released a statement warning people with MS about the risks of surgery used to treat CCSVI. The statement cautions that these procedures have not been FDA-approved or proven safe and effective for treating MS.

CCSVI is treated with surgery, and any type of surgery can have risks.

“There have been some patients who have been seriously injured or have died as a result of this surgery,” Fox says. “I think in many people’s minds the issue has been sorted out,” He says his team is in the process of completing its studies, “but there does not seem like there is evidence in support of CCSVI. I think for many people this hypothesis of MS is winding down.”

Risks involved with endovascular surgery include:

  • Movement of the stent
  • Infection
  • Damage to the blood vessel, which could lead to clots
  • Bleeding from the blood thinners prescribed after surgery
  • Re-closing of the vein after surgery–called restenosis
  • Death

CCSVI Balloon StentThe FDA warning includes: The experimental procedure uses balloon angioplasty devices or stents to widen narrowed veins in the chest and neck. However, the FDA has learned of death, stroke, detachment and migration of the stents, damage to the treated vein, blood clots, cranial nerve damage and abdominal bleeding associated with the experimental procedure. Balloon angioplasty devices and stents have not been approved by the FDA for use in treating CCSVI.

Read The USA Federal Drug Administration Statement About CCVSI By Clicking Here Read The Entire FDA Warning By Clicking Here

“We need to stop this use of treatment when we don’t know if it’s useful or not,” says Robert Zivadinov, MD, PhD, professor of neurology at the University at Buffalo. He says endovascular surgery needs to be proven in carefully controlled studies before it can safely be used on people with MS.

But Zivadinov says researchers who claim CCSVI doesn’t exist are not interpreting the diagnostic criteria correctly. “Our studies are demonstrating that clearly there is this condition, and it’s present in about 30% to 50% of the subjects,” he says.

“Although this is a very controversial field, I am very certain that research should proceed,” Zivadinov adds. He says it’s important to keep studying CCSVI, to understand what it means for people with MS and other nervous system conditions.

The Vote is Still Out!

Research continues on CCSVI and we encourage you to stay tuned!

2014 VEITHsymposium: CCSVI Updates, Trials and Controversies: More Data Is Needed!