CCSVI Study by the CostelloTeam - National Multiple Sclerosis Society

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CCSVI Study by the CostelloTeam


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Study on CCSVI in MS at Hotchkiss Brain Institute, University of Calgary

In June 2010, the National MS Society (USA) and the MS Society of Canada committed over $2.4 million to support seven new research projects on the role of CCSVI (chronic cerebrospinal venous insufficiency) in MS, an abnormality of blood drainage from the brain and spinal cord in MS originally reported by Dr. Paolo Zamboni. The new projects take a comprehensive look at the structure and function of veins draining the brain and spinal cord in people representing a spectrum of MS types, severities and durations, and compare them to structure and function of veins in people with other diseases and healthy volunteers. The studies incorporate high standards of experimental blinding and controls designed to provide unbiased results. Following is a description of one of the seven projects.

Title: Determining the relationship between CCSVI and MS

Fiona Evanne Costello, MD, FRCP
Hotchkiss Brain Institute
Faculty of Medicine, University of Calgary
Calgary, Alberta
Timing: 7/1/10-6/30/12
Amount: C$199,994.18 for 2 years
  • A series of recent publications have suggested that some people with MS have obstructions in the veins that drain blood in the brain and spinal cord that may contribute to nervous system damage in MS.
  • Dr. Costello’s team examined a cross-section of 120 people with MS compared to 60 healthy controls, seeking linkages between vein abnormalities and different aspects of MS activity and tissue damage.
  • Their results should provide insight into the significance of differences in vein drainage and the implications for the future treatment of MS.
About the Investigator: Fiona Costello is a member of the Hotchkiss Brain Institute at the University of Calgary’s Faculty of Medicine, as well as an MS treating neurologist and neuro-ophthalmologist at Foothills Medical Centre. She is also Director of the NeuroProtection and Repair Evaluation Unit of the Hotchkiss Brain Institute’s Arresting MS Program. She trained at Memorial University of Newfoundland, where she completed her medical degree and residency training in neurology. In 2000, Dr. Costello did a clinical fellowship in neuro - ophthalmology at the University of Iowa Hospitals and Clinics before taking her first faculty position as Assistant Professor at the University of Ottawa. She moved to the University of Calgary in 2007, where is currently Associate Professor in the Departments of Clinical Neurosciences and Surgery. She has authored numerous relevant publications in the areas of MS and the use of optic neuritis as a system model of MS. She has received many honors including the North American Neuro-Ophthalmology Society Young Investigator Award; and was recently named one of Caldwell Partners Canada’s “Top 40 Under 40” for advances in MS research.

Dr. Costello, with co-investigator Dr. Michael Hill, Associate Dean of Clinical Research and a member of the Hotchkiss Brain Institute at the University of Calgary who has expertise in clinical epidemiology; has assembled a highly experienced team of collaborators including radiologists specializing in imaging of the blood vessels, interventional radiologists, and magnetic resonance imaging experts.

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 were recruited from the Calgary MS Clinic at Foothills Medical Centre. Recruitment number is approximate and is subject to change.

Additional Personnel:
  • Dr. Mayank Goyal, Hotchkiss Brain Institute, University of Calgary
  • Dr. Richard Frayne, Hotchkiss Brain Institute, University of Calgary
  • Dr. Jean K. Mah, Hotchkiss Brain Institute, University of Calgary
  • Dr. Jeptha Davenport, Hotchkiss Brain Institute, University of Calgary
  • Dr. James Scott, University of Calgary
  • Dr. Deepak Bhanyana, University of Calgary
  • Dr. David Lautner, University of Calgary

Progress updates

September 2012: Researchers continue with their progress in the seven Society-funded CCSVI studies in MS. Read about the most recent progress.

January 2012: The University of Calgary team has initiated a prospective cross-sectional study to determine the association between ultrasonography (US) and magnetic resonance venography (MRV) measures of venous outflow in MS patients. This study will evaluate 120 people with MS (including 65 with relapsing-remitting MS, 20 with secondary-progressive MS, 10 with primary-progressive MS, 10 with neuromyelitis optica, and 15 with pediatric MS) and 60 age- and sex-matched healthy control subjects. To date, 98 participants have been recruited. The main outcome measure will be the proportion of cases and controls with US and MRV evidence of extracranial venous outflow obstruction. Secondary outcomes will include MRI measures of brain inflammation, Expanded Disability Status Scale (EDSS) scores, and extracranial US measures of venous wall thickening and jugular valve competence.

The team published a paper based on the cases of five people who had experienced medical complications after undergoing procedures focused on treatment of venous abnormalities: “Complications in MS Patients after CCSVI Procedures Abroad.” Burton JM, Alikhani K, Goyal M, Costello F, White C, Patry D, Bell R, Hill M. (Calgary, AB) Can J Neurol Sci 2011 Sep;38(5):741-6.

June 2014: In another publication, the team detected no differences in the proportion of venous outflow abnormalities -- as measured by ultrasonography or gadolinium-enhanced magnetic resonance venography -- between 120 people with MS and 60 controls without MS. This study also revealed significant methodologic concerns in the proposed diagnostic criteria for CCSVI. CMAJ Epub ahead of print, 2014 Jun 2

Quotes from Dr. Fiona Costello

  • “Dr. Zamboni’s findings have raised intriguing questions about the role of CCSVI in MS. At this point, our goal is to determine the prevalence of venous outflow insufficiency in a sizeable MS population, with validated and reliable measures of venous anatomy. Furthermore, we aim to study the concordance between the extent of venous obstruction and other established measures of disease activity.”
  • “The data we obtain from our study will enhance our understanding about the role of venous insufficiency and possible consequences of myelin loss, axonal damage, and neuronal degeneration in MS.”