UTHealth Study Finds CCSVI Rare in Both People With and Without Multiple Sclerosis

Researchers at The University of Texas Health Science Center at Houston (UTHealth) used multiple imaging techniques and found that chronic cerebrospinal venous insufficiency (CCSVI) is uncommon and occurs at similar low rates in people with multiple sclerosis (MS) and in volunteers without MS.

The interdisciplinary team published these findings in the Annals of Neurology after conducting a blinded, methodical evaluation of venous drainage using several established imaging approaches. The study aimed to validate reliable diagnostic methods for CCSVI, determine whether CCSVI is specific to MS, and assess whether CCSVI contributes to MS disease activity or progression.

“Our results in this phase of the study suggest that findings in the major veins that drain the brain consistent with CCSVI are uncommon in individuals with MS and quite similar to those found in our non-MS volunteers,” said Jerry Wolinsky, M.D., principal investigator and the Bartels Family and Opal C. Rankin Professor of Neurology at The UTHealth Medical School. “This makes it very unlikely that CCSVI could be the cause of MS, or contribute in an important manner to how the disease can worsen over time.” Wolinsky also serves on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston and directs the UTHealth MS Research Group.

CCSVI was first described by Italian neurosurgeon Paolo Zamboni, M.D., as a condition in which veins that drain the central nervous system appear abnormal. Zamboni’s work suggested a possible link between CCSVI and MS, but not all research teams have been able to reproduce those results. The UTHealth study was designed to examine this question rigorously by comparing people with MS to a control group of volunteers without MS while using multiple imaging modalities.

Diagram of veins in the neck affected by CCSVI — Neuroscientist Paolo Zamboni described CCSVI as a disorder in which veins draining the central nervous system are abnormal. The image shows veins of the neck; the internal jugular vein (V. jugularis interna) may be stenosed or have a malformed valve that can be associated with CCSVI. Collateral veins may be visible on MR venography. Image credited to Gray’s Anatomy.

UTHealth was one of three U.S. institutions to receive an initial grant to study CCSVI in the context of multiple sclerosis. The funding was part of a joint $2.3 million commitment from the National MS Society and the MS Society of Canada to support investigations into the potential vascular contributors to MS.

The research team employed several imaging strategies to evaluate the major venous pathways that drain the brain. These included Doppler ultrasound to study venous flow dynamics, magnetic resonance imaging (MRI) performed with an intravenous contrast agent to visualize venous anatomy, and direct radiologic venography—using injection of radio-opaque contrast—to assess the structure of the major veins. By combining these approaches, the investigators sought to identify a consistent, reproducible diagnostic method for CCSVI and to compare its prevalence between groups.

Throughout the study the team was blinded to each participant’s clinical diagnosis to prevent bias. Doppler ultrasound assessments were performed in a cohort of 276 participants that included both people with MS and non-MS volunteers. Applying the diagnostic criteria for CCSVI originally described by Zamboni, the UTHealth investigators observed a lower prevalence of CCSVI than had been reported in some earlier studies, and importantly, they found no statistically significant difference in CCSVI frequency between those with MS and those without MS. Analyses of MRI and direct venography data are being finalized and prepared for publication to provide a fuller account of the imaging results.

Multiple sclerosis is an unpredictable and often disabling disease of the central nervous system that disrupts communication within the brain and between the brain and the rest of the body. MS affects more than 400,000 people in the United States and approximately 2.1 million people worldwide.

Study Team and Notes

Co-investigators from the UTHealth Medical School and Mischer Neuroscience Institute who contributed to this study include:

Alan M. Cohen, M.D., Professor and Chief of Vascular Interventional Radiology
Andrew Barreto, M.D., Assistant Professor of Neurology and Director of the Neurosonography Laboratory
Larry Kramer, M.D., Professor of Diagnostic and Interventional Imaging and Chief of Cardiovascular MRI
Ponnada Narayana, Ph.D., Professor of Diagnostic and Interventional Imaging and Director of the MR Research Group
Staley A. Brod, M.D., Professor of Neurology
John W. Lindsey, Professor of Neurology
Flavia Nelson, Associate Professor of Neurology

Contact: Deborah Mann Lake – UT Health

Source: UT Health press release

Image Source: The CCSVI illustration is credited to Gray’s Anatomy and is in the public domain.

Original Research: The full open-access article “Chronic cerebrospinal venous insufficiency” by Andrew D. Barreto, M.D.; Staley A. Brod, M.D.; Thanh-Tung Bui, M.D., RVT; James R. Jemelka, M.A.; Larry A. Kramer, M.D.; Kelly Ton, B.S.; Alan M. Cohen, M.D.; John W. Lindsey, M.D.; Flavia Nelson, M.D.; Ponnada A. Narayana, Ph.D.; and Jerry S. Wolinsky, M.D., was published in Annals of Neurology (published online February 26, 2013). DOI: 10.1002/ana.23839.

In summary, this blinded, multi-modality imaging study from UTHealth reports that CCSVI is an uncommon finding and that its occurrence does not differ significantly between people with multiple sclerosis and people without MS. These findings argue against CCSVI being a primary cause of MS or a major contributor to MS progression, and they emphasize the importance of rigorous, reproducible imaging methods when evaluating vascular hypotheses related to neurological disease.