CCSVI - Chronic cerebro-spinal venous insufficiency

This page is intended for information only about CCSVI and the research that is happening in BC. We DO NOT perform any
investigations or treatments at our clinic. I (Dr. Crippen) find the

idea of venous disease causing MS symptoms fascinating. There are

ongoing studies at only one facility in British columbia. More

information can be found below here.

THE UNIVERSITY OF BRITISH COLUMBIA HOSPITAL MS CLINIC

June 11th, 2010 Update on CCSVI.

On June 11, 2010, the MS Society of Canada selected the BC/SASK collaborative CCSVI research proposal for funding.

This pivotal study will seek to verify Dr. Zamboni’s earlier findings on chronic cerebrospinal venous
insufficiency (CCSVI), a hypothisis of a condition he found only in

patients with MS and which he did not seen in healthy controls. Dr.

Zamboni’s belief is that CCSVI may play an important role in the

symptoms that affect many MS patients and that treatment of CCSVI could

improve their lives.

The goal of the BC/SASK CCSVI study is to verify the condition itself, and the usefulness of non-invasive
techniques to screen for CCSVI. This information will be much needed if

results from this study, and other research projects being undertaken,

confirm that future therapeutic trials are warranted. This study is the

only funded project that will use three diagnostic tests to investigate

how to image CCSVI. Specifically, we are investigating the use of

catheter venography as the “gold standard” to detect CCSVI. This is more

comprehensive than ultrasound alone. Both ultrasound and Magnetic

Resonance Imaging of the veins (MRV) will be compared to catheter

venography to determine which of these tests are adequate and reliable

for detecting CCSVI in the near future.

This initial study will recruit 100 MS and 100 non-MS subjects from existing patient rosters at the MS
Clinic at UBC Hospital and the Saskatoon MS Clinic. Letters of

invitation will be sent to all potentially eligible subjects identified

from these rosters by the research team. This will include subjects with

twins or family members with confirmed MS. This group of subjects will

allow us to verify the condition of CCSVI and to determine if there is a

genetic (inherited) link to this condition. While many other patients

will want to volunteer, and we thank them for their support, our initial

numbers will be limited. We will continue to apply for more funding so

that we can better understand CCSVI and MS.

We believe that the BC/SASK CCSVI study will only be the beginning of more research that will benefit
people with MS in Canada. Both our teams in Vancouver and in

Saskatchewan have applied for grant funding from the Canadian Institutes

of Health Research, and fundraisers at VGH & UBC Hospital

Foundation and UBC Faculty of Medicine Development Office are working

with donors to fund this valuable research.
For more information, please check the following websites:

www.mssociety.ca
www.mriresearch.ubc.ca/
www.nationalmssociety.org
www.cnmsc.org/

Sincerely,
Anthony Traboulsee, MD
Assistant Professor (UBC Faculty of Medicine/Neurology)
Medical Director, UBC Hospital MS Clinic and Clinical Trials Group
ccsvi@brain.ubc.ca

CCSVI and MS – Background Information

Multiple Sclerosis is the leading cause of disability in Canada. Over 60,000 Canadians are affected by
this disease. The cause of MS is unknown but likely the interaction

between genes and the environment play an important role. It is a

disease that randomly attacks the myelin coating of nerves in the brain,

optic nerves and spinal cord.

Chronic cerebrospinal venous insufficiency (CCSVI) is a proposed hypothesis that is detected through
an ultrasound and catheter venography in patients with MS where large

veins that drain the blood from the brain and spinal cord appear to be

narrowed compared to people without MS. The belief is this may cause

congestion of blood in the brain and trigger attacks of inflammation,

possibly by causing iron deposits.

Liberation treatment is the term coined by Dr. Zamboni for the dilation or repair of these narrowed
veins. A catheter with a balloon is inserted into the narrowed vein and

then the balloon is inflated to correct the narrowing. Some surgeons

have placed stents (metal tubes) in the narrowing to prevent blockages

from recurring. Stents have worked well for problems with narrowed

arteries. However, unlike arteries which are quite stable, veins tend to

fluctuate in size. Veins change in size and shape with breathing and

with a transition from lying to standing. This normal and regular

fluctuation may increase the potential for a venous stent to dislodge.

Frequently Asked Questions about the BC/SASK CCSVI Study

Q. When will the BC/SASK CCSVI study start?
A. The funding period begins July 1st, 2010. Applications have already
been submitted to research ethics boards at each institution. The

research ethics board is a group of individuals (scientists, physicians,

ethicists, lawyers, and members of the community) that provide an

independent review of human research studies. Ethics approval can take

weeks or months depending on the nature of the study. We are targeting

to start the study in July or August 2010.

Q. How can I participate?
A. This initial study will recruit 100 MS and 100 non-MS subjects from existing
patient rosters at the MS Clinic at UBC Hospital and the Saskatoon MS

Clinic. Letters of invitation will be sent to all potentially eligible

subjects identified from these rosters by the research team. This will

include subjects with twins or family members with confirmed MS. This

group of subjects will allow us to verify the condition of CCSVI and to

determine if there is a genetic (inherited) link to this condition.

Q. I am not a patient at the MS Clinic at UBC Hospital. Am I eligible to enrol in the study?
A. This initial study will be limited to subjects from existing patient
rosters at the centers. Some subjects in BC who are followed at another

MS clinic in BC (e.g. Victoria, Prince George, Kelowna, Burnaby) could

be eligible if they have participated in the Canadian Collaborative

Genetics Study in MS at some point over the last 10 years and otherwise

meet enrolment criteria. Letters of invitation will go out to eligible

participants.

Q. What can I do if I am not selected?
A. Your continued support of our research efforts in CCSVI, even if you
are not a subject for this specific study, will help us to understand

CCSVI and this will benefit all those affected by MS. We believe that

this will be only the beginning. Future studies will depend on the

results of this research that must be done with the utmost care and

integrity.

Q. How long will the diagnostic study take to complete and until we see results?
A. We expect to have all subjects recruited, and all diagnostic studies analyzed before the end of the two year funding period.

Q. CCSVI is being screened/diagnosed at many global centres already. How can this be happening without the
proper studies and do we really need a study to look at diagnostic

validation?
A. A goal of our study is to verify Dr. Zamboni’s
findings on the hypothesis of CCSVI and to determine if ultrasound or

MRI venography are accurate enough to detect this proposed condition. It

is well known to the medical community that findings such as Dr.

Zamboni’s need careful replication and verification before being

accepted as a clinical procedure. The medical literature is full of

examples where a claim has been made (e.g. non approved cancer

treatments), people travel to less regulated regions (e.g. Mexico,

China) and undergo treatment which later has been shown to be

ineffective or dangerous. For the well-being of our patients, it is

imperative that we proceed with any treatment based on evidence-based

data.

Q. Will participants have the Liberation treatment?
A. This particular study is only focused on imaging and the best method to
detect this proposed condition. However, we are actively fundraising

for and will be applying for further funding to undertake a treatment

study if our initial findings support this approach.

Q. Who will be eligible for future studies?
A. We do not know at this time. We will not know until we have a better understanding about CCSVI and MS.

Q. Would having testing done at a private facility increase my chances of participating?
A. No.

Q. Why are more centers not involved besides BC and Saskatchewan?
A. In 2009, the MS programs in BC and Saskatchewan joined together as the
Western Pacific Regional Research and Training Committee (WPRRTC) to

undertake collaborative research and training projects. This initiative

was supported by the MS Society of Canada’s endMS campaign that

identified centers of excellence in MS across Canada. Future studies

could include more interested centers. Increasing the number of centers

at this time would cause additional delays.
What other projects related to CCSVI are planned by the BC/SASK CCSVI Research Team?
A.
The majority of MS research in Canada is funded by the MS Society of

Canada which is completely supported by donations. The Canadian

Institutes of Health Research (CIHR) is another major funding agency for

research in Canada. The team from Vancouver Coastal Health
and UBC
submitted a grant application to CIHR on March 1st, 2010. If successful,

the team will be able to investigate the role of iron in the brain in

CCSVI and MS and develop new MRI techniques for the imaging of MS. The

SASK research team has also submitted a grant to CIHR investigate

imaging of iron in the MS brain using a highly specialized and unique

Synchrotron technology (www.lightsource.ca). The next round of grant

applications for the MS Society and CIHR is in September and October of

2010. Those grants would not start until the spring of 2011. Many grants

are rejected the first time and need to be rewritten and resubmitted

which could delay them by 6 to 12 months. Studies looking at the

benefits of treatment could begin after the results of the current

diagnostic study are known, depending on available future funding.
Frequently Asked Questions about CCSVI and MS

Q. What are the results of the liberation treatment so far?
A. Dr. Zamboni’s study treated 65 MS subjects with different types of MS
(35 RRMS, 20 SPMS, 10 PPMS). There was no control group and all patients

knew they had the procedure performed (“unblinded”). The doctor

assessing them was also aware of the treatment (“unblinded”). 47% had

re-stenosis of the vein that was dilated. While this was an important

“pilot” study, Dr. Zamboni believes this requires further testing to

validate his findings. Since then, several patients have paid for

treatment outside of research studies. There is no careful or systematic

follow-up of these patients to know how many benefit, how they benefit,

what predicts who will benefit and how sustainable the benefit is.

Q. Is the liberation treatment safe?
A. Theoretically, venous dilation alone should be relatively safe.
However, in February 2010, it was reported that two patients had serious

complications from stents (metal tubes) used in their veins. One

patient suffered a fatal blood clot in the brain, while another had to

undergo open heart surgery after a jugular vein stent dislodged into her

right ventricle. These stents were inserted by one of the top

interventional radiologists in the world. The risk with less experienced

physicians is unknown.

Q. Could the liberation treatment make MS worse?
A. In Dr. Zamboni’s pilot study, based on reviewing his paper, it appears
as though some patients had an increase in their MS relapse rate.

Q. What are the results of other research studies?
A. Preliminary results from Dr. Zivadinov at the Jacobs Center in Buffalo
demonstrated that approximately 56% of MS patients had abnormalities on

ultrasound suspicious for CCSVI but so did 22% of healthy volunteers.

This is somewhat different from the 100% rate of abnormality Dr. Zamboni

reported in MS patients and 0% in healthy volunteers. It could suggest

that CCSVI is less common or less distinct than previously thought.

Conversely it could suggest that ultrasound is not accurate enough to

detect CCSVI. It does clearly show the importance of independent

research in any new medical claim.

Q: My ultrasound said I have CCSVI. What can I do?
A: While this may be accurate, it is also possible that the test is
providing a “false positive” result due to lack of standardization and

lack of experience. Furthermore, detecting CCSVI would not necessarily

lead to immediate treatment until that treatment is proven to be safe

and effective.

Q: I want my MRI checked for CCSVI.
A: Most MRI’s for the routine monitoring of MS do not include pictures of
the veins and would not be suitable for checking for CCSVI. A

specialized MRI examination, known as MR venography (MRV) is needed. The

BC/SASK CCSVI research project will determine if MRV and ultrasound are

sensitive and accurate enough to detect CCSVI.

Q: Can I get tested for CCSVI?
A: The best test for detecting CCSVI is not yet known. We continue to speak
with physicians around the world interested in CCSVI, and have come to

the conclusion that there remains a lack of standardization on the best

way to diagnose CCSVI. The BC/Saskatchewan CCSVI study will answer this

question.

Q: Where can CCSVI be treated?
A: Several private and mostly for profit groups are advertising surgical
procedures for CCSVI. This treatment in MS is still experimental and we

recommend that treatment only occur as part of a clinical trial that

includes all of the standard safeguards that are followed in such

trials.

Q: How do I know if treatment of CCSVI is part of a research study?
A: You should be given an informed consent form that has been reviewed and
approved by an ethics board. The ethics board should be clearly

identified on the consent form. In general, there should be no cost or

payment for participation in a research study.

Q: Why does more research need to be done?
A: Many of us in the MS clinical and research community watched this story
with great interest, but also with some natural skepticism as we have

seen similar claims of potential causes and cures in the past. Dr.

Zamboni’s results are preliminary or “pilot” data that require

independent validation. This process of independent validation has been

one of the greatest advancements in modern medicine and is crucial for

confirming important results and preventing potentially dangerous or

useless but costly treatments from being undertaken. Dr. Zamboni agrees

that this is an important step that must be undertaken. The many

advances in care for MS patients today exist because of this process and

the sacrifice made by many volunteers.

Q: How can I support this work?
A: Funding to support this important research will be critical. Donations
can be made through the MS Society of Canada (www.mssociety.ca), the VGH

and UBC Hospital Foundation (www.worldclasshealthcare.ca) or the UBC

faculty of Medicine (www.med.ubc.ca).

Q: Where can I get updates?

www.vchri.ca
www.mssociety.ca
www.mriresearch.ubc.ca/
www.nationalmssociety.org
www.cnmsc.org/