In November 2009, Italian researcher Dr. Paolo Zamboni, made headlines worldwide with his study of CCSVI or chronic cerebro-spinal venous insufficiency. The MS community responded – with great hope, excitement and a call for immediate action. The MS Society shares this optimism and recognizes that this concept has already opened up new avenues of research and may lead to potential therapies.
As with any new hypothesis, there are a number of questions still to be answered. To ensure we realize the full potential of any new discovery, early results need to be replicated and validated in multiple, large, and well-designed studies. While the pace of this process may seem frustratingly slow, it is critical to producing the very best answer for people living with MS around the world. Dr. Zamboni has opened a door for the community, and now we need to proceed with a balance of hopefulness and scientific rigour.
People with MS and the medical community alike still have many questions. The MS Society is committed to helping the MS community find those answers. In November 2009, the MS Society issued a request for research operating grants to study the relationship between CCSVI and MS. The call for specific research proposals is unique and unprecedented in the MS Society’s 60-year history.
By funding research into MS and CCSVI, the MS Society hopes to clarify the relationship between CCSVI and MS and to identify what treatment potential it may offer to people living with MS.
Chronic cerebrospinal venous insufficiency (CCSVI) is a term used to describe a situation in which the venous system is not able to efficiently remove blood from the central nervous system. It is stated that this is related to narrowing of small venous structures in the neck, chest and spine. The suggested mechanism involves the development of ‘substitute circles’ of venous blood vessels in an attempt to facilitate drainage from central nervous system pathways. The hypothesis goes on to suggest that because these compensatory blood vessels don’t have the same wall integrity as larger veins, they tend to leak blood into the adjacent tissue, depositing iron there which triggers an immune response.
Watch this series of videos on CCSVI hosted by the MS Clinic at Health Sciences Centre in Winnipeg on December 14, 2009.
The MS Society hosted a webcast on CCSVI on April 7 and 14, 2010.
Why is there a sudden interest in CCSVI and MS?Learn more...
Much of the interest in this idea relates to research coming from cardiovascular literature. Current information about CCSVI derives from three studies:
In late 2009, the work of Dr. Paolo Zamboni and colleagues was published; titled Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Researchers report on observations involving 65 people with different types of MS compared with 235 people who were healthy or who had other neurological disorders. Authors report an association between having MS and signs of venous insufficiency – suggesting that blood drainage by veins may be impaired, contributing to nerve tissue damage.
In December A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiencywas published. Dr. Zamboni and colleagues report on 65 people who underwent a surgical procedure to relieve the venous narrowing. Authors report that all participants were on disease modifying treatments. People with relapsing MS showed improvement in some study parameters at 18 months, but there was no improvement documented for those with progressive MS.
In February of 2010, researchers from the University of Buffalo shared some preliminary observations from the work of Dr. Robert Zivadinov and colleagues. Using a sophisticated ultrasound technique to screen 500 study participants, Dr. Zivadinov noted evidence of CCSVI in 56.4% of people with MS, but also in 22.4% of healthy controls. An update on Dr. Zivadinov’s work was presented at the American Academy of Neurology Meeting in April 0f 2010.
What is the MS Society’s position on CCSVI?Learn more...
The MS Society of Canada believes that this topic opens up new avenues of research in MS including the possibility of new treatments. Although the early data are of great interest, it is important to acknowledge that the concept of CCSVI as a cause of MS and the use of stents or balloons to widen veins as treatments are ideas that need to be replicated and validated in much larger well-designed studies. First, it will be necessary to understand the relationship between CCSVI and MS. If such a relationship is established, it will then be important to determine if and what intervention is needed. This work would include a clear understanding of possible benefits and risks as they apply to people living with MS who are planning to undergo treatment of CCSVI.
The MS Society of Canada is closely monitoring all ongoing research related to CCSVI and will post new information on www.mssociety.ca/ccsvi as it becomes available. On June 11, 2010 the research funded by the MS Society on CCSVI and its relationship to MS was announced.
Do these reports of a possible association between insufficient vein drainage and MS mean that MS is caused by venous insufficiency? Learn more...
Not necessarily. Based on what has been published so far, it can only be said that MS may occur in association with impaired venous drainage of the central nervous system. This impairment, if truly present, could cause MS but it is also possible that it is incidental to the disease, given Dr. Zivadinov’s observation (see Why is there a sudden interest in CCSVI and MS?) of CCSVI in 22.4% of healthy controls, it is not possible to confirm a causal relationship between CCSVI and MS at this time and more study is needed.
*What guidance does the MS Society provide on CCSVI?Learn more...
The decision to seek treatment of any kind is a personal one. The MS Society of Canada respects the right of people living with MS to make their own treatment decisions including the choice to seek treatments which may be considered experimental. The role of the MS Society is to provide guidance to people to make informed decisions by providing the best information and evidence available to assist those we serve in their decision-making.
The MS Society of Canada believes that this topic opens up new avenues of research in MS including the possibility of new treatments. Although the early data are of great interest, it is important to acknowledge that the concept of CCSVI as a cause of MS and the use of stents or balloons to widen veins as treatments are ideas that need to be replicated and validated in much larger well-designed studies. First, it will be necessary to understand the relationship between CCSVI and MS. If such a relationship is established, it will then be important to determine if and what intervention is needed. This work would include a clear understanding of possible benefits and risks as they apply to people living with MS who are planning to undergo treatment of CCSVI.
The MS Society of Canada is closely monitoring all ongoing research related to CCSVI and will post new information on www.mssociety.ca/ccsvi as it becomes available. On June 11, 2010 the research funded by the MS Society on CCSVI and its relationship to MS was announced.
What are the potential complications for this procedure?Learn more...
Endovascular intervention for CCSVI is an invasive procedure and as such, does carry a risk for significant complication. Two cases have been described in the January Issue of the Annals of Neurology. In August of 2009, a 51 year old woman died from a cerebral hemorrhage attributed to the blood thinner she was taking to minimize the risk of clot formation post endovascular intervention for CCSVI. In November a second event was documented when a stent, inserted in the jugular vein to maintain vein flow, dislodged itself and travelled to the heart. Open heart surgery was needed to retrieve the stent. Other possible complications of this endovascular intervention may include, but are not limited to:
Bleeding and/or bruising at the at the insertion site.
Perforation and/or hemorrhage along the path of the vascular catheter as it is advanced.
Dislodgement of blood clots along the path of catheter, resulting in heart attack or stroke.
Formation and dislodgement of clots from the tip of the catheter leading to heart attack or stroke.
Infection.
*Can I be tested or treated for CCSVI right now?Learn more...
The decision to seek treatment of any kind is a personal one. The MS Society of Canada respects the right of people living with MS to make their own treatment decisions including the choice to seek treatments which may be considered experimental. The role of the MS Society is to provide guidance to people to make informed decisions by providing the best information and evidence available to assist those we serve in their decision-making.
The treatment is currently unavailable in Canada. As well, specialized equipment and training is needed to test for the condition. For these reasons, CCSVI cannot be easily tested for or treated in Canada at this time.
Additionally, for safety reasons, the MS Society recommends that people with MS be examined or treated for CCSVI only within an established research protocol where suitable safety and outcome monitoring is assured.
Between the MS Society of Canada and the U.S. National MS Society, seven studies have been funded to research CCSVI's relationship to MS. Please note enrollment is limited and these studies are aimed at achieving better understanding of the relationship between CCSVI and are not designated to treat CCSVI.
Will the treatment of CCSVI be useful for the various forms of MS?Learn more...
Whether this type of treatment will be useful in any form of MS is currently unknown as research on this question is at a very early stage. Much more work needs to be done.
What are the next steps to study the CCSVI hypothesis?Learn more...
With any research, it is important to validate and replicate known results and answer questions that test the reliability of the stated theory. One can look at the next steps in two parts:
Part 1: Determine the relationship between CCSVI and MS.
Researchers agree generally that information must be gathered on frequency and prevalence of the condition before moving on to testing the treatment of blocked veins. A sample of questions that need to be answered in this first step:
Does it occur in all people with MS and in all types of MS?
Does CCSVI occur in people who do not have MS?
Does CCSVI occur in children?
Is CCSVI caused by MS or vice-versa?
What are the implications of the blocked veins? Poor blood flow? Iron deposits?
Answering the above questions involves the use of imaging technologies and not treatment of the condition itself.
Part 2: Determine the effects of treating venous insufficiency.
If part 1 is successfully completed and the results demonstrate that people with MS do have blocked veins, researchers might then look at how treatment of the condition could benefit care of people with MS. Questions that will need to be answered include:
Do the effects of the treatment work in all types of MS?
How long do the treatment effects last?
Can the results be replicated in a ‘blinded’ study where neither participants nor researchers are aware of the treatment they are receiving?
What are the reliability, risks and benefits of the treatment?
How does this treatment compare in effectiveness and safety to existing therapies?
Researchers around the world, including Canada, are in the midst of developing research protocols to understand CCSVI as it relates to MS.
Is it true as some people have suggested that the MS Society's dependence on money from the pharmaceutical industry is impeding its support of Dr. Zamboni's research?Learn more...
No. The MS Society's total grant revenue is less than 7%, including less than 2% received from pharmaceutical companies. Funding received from pharmaceutical companies is in alignment with the Rx&D Code of Conduct and strictly adheres to the MS Society of Canada's policy on industry partnerships. These funds enable the Society to better meet the needs of people with MS in direct support of our mission and are essential to ensure current funding dedicated to core operations is not compromised. The funding that supports our research and client programs come from fundraising events and the donations of donors committed to ending MS.
What is happening in Canada and the U.S. to further the understanding of CCSVI and MS? Learn more...
In November 2009, the MS Society issued a request for research proposals to study the relationship between CCSVI and MS. The call for specific research proposals is unique and unprecedented in the MS Society’s 60-year history. Our sister organization, the National MS Society in the U.S. held a similar call.
The two organizations received numerous letters of intent from investigators. These letters of intent, which briefly describe the proposed research, were reviewed and a number of applicants were invited to submit full research proposals. These proposals underwent a rigorous review process to insure the funding went to the projects which evidenced a solid scientific methodology, offering the best opportunities for findings which would advance our knowledge about CCSVI and how it may impact MS care.
The timeline for review and funding of CCSVI proposals was as follows:
January 12, 2010 – Investigators whose letter of intent meets guidelines invited to submit full research proposals.
February 9, 2010 – Deadline for proposals.
May 2010 – International panel of experts conducts expedited review of all applications received through this special request for applications.
June 11, 2010 – Funding decisions announced.
July 1, 2010 – Anticipated start date for funding of successful research applications.
This process was open to proposals from qualified investigators based in Canadian institutions. Peer review was conducted by an international panel of experts from relevant fields and in collaboration with our sister organization in the U.S.
The MS Society of Canada did not place a limit on the number of proposals to be funded. Individual project grants will be funded to a maximum of $200,000 ($100,000 per year for two years). It is important to clarify that there was no pre-determined limit to the number of projects that could be funded. A commitment to fund all projects approved by the review committee was assured from the outset.
In addition to this special competition, the ongoing annual research funding program is open to researchers for further study of CCSVI.
What is the selection process to receive operating grants related to CCSVI and MS and how will approved grants receive funding from the MS Society? Learn more...
The MS Society of Canada's MS research program invests only in research that is of the highest level of scientific excellence and relevance to MS. The CCSVI and MS research grants are adjudicated through a rigorous peer-review process by an international review committee. This process is precisely designed to identify research that will most ably investigate the hypothesis of CCSVI and its relation to MS. The international review panel will make their recommendation to the non conflicted* medical advisory committee (MAC) which in turn makes recommendations to the Society’s Board of Directors for funding through the MS research program and based on available resources generated through donations, grants are awarded.
*non conflicted MAC – members have not submitted a grant and are not from the same institution as a researcher who has submitted a grant
How much time and funding are needed to study the CCSVI hypothesis?Learn more...
The amount of time and funding required to investigate CCSVI will be significant. It is impossible to predict an exact timeline or budget needed to move any theory from hypothesis to reliable therapy.
However, researchers agree that the first stage in advancing research is to focus in on understanding the relationship between CCSVI and MS. This will involve determining the best use of imaging technologies to study CCSVI.
The MS Society continues to fund some of the world’s most promising research guided by Canadian researchers who have dedicated their careers to ending MS. Monies committed to CCSVI will not take away from current funding commitments or from the much-needed services that the MS Society delivers from coast-to-coast.
What is the MS Society’s role in CCSVI research? Learn more...
The MS Society’s primary role in research is to fund the avenues of greatest potential and scientific excellence. It is with this role in mind that the MS Society opened up its research grant application process specifically to study CCSVI and MS.
By funding research into MS and CCSVI, the MS Society hopes that clarity will emerge as to the relationship between the two. If the treatment of CCSVI is proven to be a valid therapeutic treatment option for MS, then the MS Society would have a role in lobbying to make it widely accessible.
What is the MS Society of Canada doing to bring pressure on the Government of Canada and provincial governments to make CCSVI screening and treatment available for people with MS? Learn more...
The responsibility for the administration of health services is vested with the provincial governments. As we have seen, the cost of drugs prescribed to treat MS is a barrier to access in the absence of provincial government funding support. To overcome this, the MS Society has advocated regularly for inclusion of scientifically proven drug therapies on provincial drug funding plans, once Health Canada approval for marketing has been secured.
Access to diagnostic testing and surgical intervention such as suggested in the CCSVI hypothesis falls under a somewhat different process. In this case, ultrasound, the test needed to image CCSVI, as well as the venoplasty procedure proposed to widen vein strictures, would in theory, be covered by provincial plans. The barrier to access in this situation is a lack of data supporting the hypothesis for both diagnosis and intervention. Consequently, MS specialist practitioners do not refer patients for investigation of CCSVI and are awaiting results of research currently underway. Toward that end, the MS Society of Canada has invited research proposals for a closer look at CCSVI and its relationship to Multiple Sclerosis. See What is happening in Canada and the U.S. to further the understanding of CCSVI and MS? for more information about this process.
"As President and CEO of the MS Society, I am aware of the tremendous interest across Canada and around the world caused by the recent news coverage of the CCSVI study. Indeed I share your excitement and hope in the preliminary findings of this study. I also celebrate and respect the integrity of our research funding programs which will continue to ensure that the very best projects are selected and supported."
Yves Savoie
President and chief executive officer
President, Ontario Division
