Venous Multiple Sclerosis Hypothesis | CCSVI

replicating the ultrasound methods used by Dr. Zamboni to investigate the association of CCSVI with major clinical types of MS and in non-MS control groups. The team is also testing whether other imaging methods can confirm the ultrasound findings, while identifying the most reliable technique to screen for CCSVI.

Term/Amount: 7/1/10-6/30/12; $574,958

Project Details: Recent preliminary studies have suggested that a phenomenon called Chronic Cerebrospinal Venous Insufficiency (CCSVI), a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paolo Zamboni from the University of Ferrara in Italy. This pilot study warrants a subsequent larger and better controlled study to definitively evaluate the possible impact of CCSVI on the disease process in MS.
Dr. Wolinsky has assembled an expert team to increase our understanding of CCSVI. Using a comprehensive approach, this team will first attempt to replicate the ultrasound methods used by Dr. Zamboni in 100 people with all major clinical types of MS, compared with 175 people in various non-MS control groups. Then, they are seeking to determine whether the findings are validated by noninvasive imaging techniques, such as an MRI machine using a powerful magnet. The team includes experts in MS, as well as experts from other fields such as vascular disease and venous imaging.
Validating a reliable diagnostic approach and demonstrating that CCSVI is specific to MS and contributes to disease activity would be necessary first steps before controlled therapeutic trials may be attempted.

studying the prevalence of CCSVI in people with MS and controls without MS, using catheter venography, ultrasound, and magnetic resonance venography. Unique to this study is the inclusion of family members, such as identical twins of MS patients who have not developed MS, in control groups. They also hope to verify the usefulness of techniques that would make it easier to screen for CCSVI.

Timing: 7/1/10/-6/30/12 Amount: C$200,000 over two years

Project Details: This team is taking a comprehensive approach to study the prevalence of venous insufficiency in 200 people with MS and controls without MS, using catheter venography, Doppler ultrasound such as what was originally used to identify CCSVI, and magnetic resonance studies of the veins (MR venography). A unique aspect of this program is that they are including family members – including identical twins of MS patients who have not developed MS -- as control groups to gain further insight into CCSVI. The team hopes to verify the usefulness of non-invasive techniques that would make it easier to detect venous insufficiency, should this and other research suggest that future therapeutic trials are warranted.
Recruitment: A total of 200 participants including eligible persons with MS and their family members who are registered with the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). Recruitment number is approximate and is subject to change.

employing powerful MRI technology to explore vein anatomy and assessing for iron deposits in the brains of people with MS and in age-matched healthy volunteers. These studies work towards mapping out normal variations in brain vein anatomy and providing insight into CCSVI in MS.

Timing: 7/1/10-6/30/12 Amount: C$102,866 over 2 years

Project Details: This team is employing “3 Tesla” MRI technology that is twice as powerful as a standard MRI magnet to explore differences in the anatomy of veins in the neck, chest and spine and to assess for iron deposits in the brain. They are comparing findings in 50 people who have MS with those in 50 age-matched healthy volunteers. They are also using Doppler ultrasound techniques that were used by originators of the CCSVI hypothesis, and seeking verification that there is a relationship between blocked veins and areas of iron deposition in the brain by measuring levels of iron in the brain in those with and without vein blockages. The questions the team is focused on include: How frequent are the vein blockages and abnormalities in people who do not have MS? How frequently do they occur in people with MS? Can the team detect brain iron pooling in patients with blocked veins?
These studies should lead to a better understanding of normal variations in the anatomy of the veins that drain the brain, and the potential role of venous insufficiency in MS.
Recruitment: A total of 100 participants including participants with MS and healthy individuals. Participants will be recruited through The Ottawa Hospital MS Clinic Research Unit. Recruitment number is approximate and is subject to change.

studying people with MS or who are at risk for MS (CIS) and comparison groups including healthy volunteers and people with brain atrophy (shrinkage) from Alzheimer’s disease. This team is using the ultrasound techniques originally used by Dr. Zamboni, as well as magnetic resonance studies of the veins (MR venography), MRI scans of the brain, and clinical measures to determine MS activity and atrophy. They are also examining neck and spinal cord tissue from MS patients at autopsy to provide a tissue-based evaluation of CCSVI and its possible relationship to MS.

Term/Amount: 7/1/10-6/30/12; $571,261

Project Details: Recent preliminary studies have suggested that a phenomenon called Chronic Cerebrospinal Venous Insufficiency (CCSVI), a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paolo Zamboni from the University of Ferrara in Italy. This pilot study warrants a subsequent larger and better controlled studies to definitively evaluate the possible impact of CCSVI on the disease process in MS.
Dr. Fox and his team are seeking to reproduce these findings in 90 people with different forms of MS and 80 controls without MS. His team is conducting the same tests that were done in the original studies (ultrasound tests of the veins in the neck), an MRI test that looks specifically at veins, and neurological examinations. Most of these MS patients have been followed for the past 10 years in a longitudinal study using quantitative clinical and imaging measures, which will provide an opportunity to compare CCSVI findings to MS disease evolution. To distinguish whether vein abnormalities are from atrophy (brain tissue volume loss) and not specifically MS, they also are comparing the MS group to people with atrophy from Alzheimer's disease. Finally, they are examining the neck and spinal cord veins obtained via autopsy from people with MS and non-MS controls.
Data from these studies will shed light on the meaning of Dr. Zamboni’s original reports and how CCSVI relates to disease activity in MS.

using magnetic resonance (MRI) scans to generate detailed images of the head and neck veins in people with early and later MS, healthy volunteers, and controls with other neurological conditions. This team is also using the ultrasound techniques originally used by Dr. Zamboni. If they obtain similar results as those published by Dr. Zamboni, it would represent a powerful confirmation of the CCSVI hypothesis and help lead the way toward trials of appropriate treatment.

Term/Amount: 7/1/10-6/30/12; $593,261

Project Details: Recent preliminary studies have suggested that a phenomenon called Chronic Cerebrospinal Venous Insufficiency (CCSVI), a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paolo Zamboni from the University of Ferrara in Italy. This pilot study warrants a subsequent larger and better controlled study to definitively evaluate the possible impact of CCSVI on the disease process in MS.
Dr. Field’s team is using alternative imaging methods, in addition to the ultrasound method used in Dr. Zamboni’s original reports, to conduct a controlled study of the CCSVI hypothesis in people with MS. This study uses an MRI scanner to generate highly detailed images of the head and neck veins in 112 people with early and later MS, 56 controls without MS, and 56 people with other neurological conditions. The team is also measuring the rate at which blood flows in the veins. Dr. Field’s collaborates have years of experience in bioengineering, radiology, and medical physics.
If this technique obtains similar results as the ultrasound method originally used, it would represent a powerful confirmation of the CCSVI hypothesis and help lead the way toward trials of appropriate treatment targeting abnormal veins.

examining a cross-section of people with MS compared to other neurological diseases and healthy volunteers. The team is seeking linkages between vein abnormalities and different aspects of MS activity and tissue damage to gain insight into the significance of differences in vein drainage and their implications for the future treatment of MS.

Timing: 7/1/10-6/30/12 Amount: C$199,994.18 for 2 years

Details: This controlled study will carefully compare vein drainage between a cross-section of 120 people with MS with that seen in 60 healthy controls. In those MS patients who exhibit signs of abnormalities of vein drainage, the investigators will explore whether the sites and severity of vein abnormalities correlate with common markers of MS disease activity, seeking linkages between any venous abnormalities observed and many different aspects and measures of MS activity and tissue damage.
The team is using ultrasound as originally used by Dr. Zamboni, and magnetic resonance studies of the veins (MR venography) to further explore the prevalence of venous insufficiency. The technologists and radiologists who interpret all scans will be blinded as to the clinical status of the participants.
This study should help quickly determine whether there are significant differences in venous drainage in people with MS, and their implications for the future treatment of MS.
Recruitment: A total of 180 participants including adults and children with MS and healthy participants. Participants with MS will be recruited from the Calgary MS Clinic at Foothills Medical Centre. Recruitment number is approximate and is subject to change.

studying vein abnormalities in children and teenagers who have MS, and healthy controls of the same age. The team is seeking to determine whether the veins are abnormal at an early age among pediatric MS patients. These findings will add additional depth to studies of CCSVI in adult MS.

Timing: 7/1/10/-6/30/12 Amount: C$196,579.14 for 2 years

Project Details: Recent preliminary studies have suggested that a phenomenon called Chronic Cerebrospinal Venous Insufficiency (CCSVI), a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paolo Zamboni from the University of Ferrara in Italy. This pilot study warrants a subsequent larger and better controlled studies to definitively evaluate the possible impact of CCSVI on the disease process in MS.
Dr. Banwell, a noted expert in pediatric MS, has assembled a team to study CCSVI in pediatric MS patients – a population where the disease process is at a very early stage, and where advanced age and other health conditions that might affect blood flow do not exist. They are determining whether CCSVI occurs in children with MS using non-invasive MRI measures of vein anatomy and novel measures of venous flow and are comparing the results to children without MS. The team also is using “hemodynamic” (blood flow) tests to investigate a hypothesis that might explain how blood flow problems could lead to myelin damage, through the accumulation of excess iron.
Determining whether the veins and vein flow are abnormal very early in the MS process in pediatric MS will add additional depth to studies of CCSVI in adult MS.
Recruitment: A total of 60 participants that includes healthy children and adolescents and pediatric MS participants. Participants with MS will be within 5 years of their first MS attack and recruited from the Pediatric MS Clinic atSickKids . Recruitment number is approximate and is subject to change.