Mar 05, 2013
Researchers at the University of Texas Health Science Center at Houston have published their first results from a National MS Society-supported study investigating CCSVI (chronic cerebrospinal venous insufficiency) using several different imaging techniques to examine blood outflow from the brain. For the first portion of the study, the team, purposefully unaware of any participant’s diagnosis, used Doppler ultrasound to investigate venous drainage in 276 people with and without MS. They report much less prevalence than previously reported by other groups and no statistical difference between those with MS and those without MS. The study, by Andrew D. Barreto, MD, Jerry S. Wolinsky, MD, and colleagues, was published early online in the Annals of Neurology.
Background: 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 in MS, a postulated abnormality of blood drainage from the brain and spinal cord in MS originally reported by Paolo Zamboni, MD (University of Ferrara, Italy). In the interim since the Society-funded studies began, there have been conflicting results reported on the prevalence of CCSVI in MS, and the emergence of reports of CCSVI in people who do not have MS. There has also been variability in the methods used to study this phenomenon, including by Dr. Zamboni.
The Society-supported projects examine 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 objective results.
One of the seven teams has now published first results from a portion of its comprehensive study at the University of Texas Health Science Center at Houston. Dr. Wolinsky assembled an expert team with diverse specialties to increase understanding of CCSVI. They tested several imaging methods including ultrasound, the relatively noninvasive imaging techniques using an MRI machine and intravenous contrast agent, and direct radiologic investigation of the major veins by direct injection of veins with radio-opaque contrast. The goal was to validate a reliable diagnostic approach and to demonstrate that CCSVI is specific to MS and contributes to disease activity.
The collaborators in this project, all from University of Texas Health Science Center at Houston, include the Chief of Vascular Interventional Radiology (Alan M. Cohen, MD) the director of the neurosonography laboratory (Dr. Barreto), the Chief of Cardiovascular MRI (Larry A. Kramer, MD), and expert MS neurologists (Drs. Wolinsky, Staley A. Brod, John W. Lindsey and Flavia Nelson).
The study: This was a single-center study that enrolled MS and non-MS volunteers at the University of Texas Health Science Center at Houston. MS participants were 18 to 65 years. Of 206 recruited, 128 had relapsing-remitting MS, 48 had secondary-progressive MS, 15 had primary-progressive MS, 12 had clinically isolated syndrome, and 3 had progressive relapsing MS. There were 70 non-MS volunteers, including 37 with other neurological diseases, 22 with cerebrovascular diseases, and 11 healthy controls.
For the first portion of this comprehensive study, the team focused on using Doppler ultrasound to evaluate venous drainage in a blinded fashion (meaning neither the technician performing the scan, nor the professional reading the scan, knew the disease status of the participant). The team utilized a standard Doppler ultrasound machine rather than purchasing the specific machine used by Dr. Zamboni’s team. The protocol used to evaluate extracranial and intracranial vessels using criteria consistent with those originally published by Dr. Zamboni (J Neurol Sci 2009;282:21-27) is described in detail in the published paper.
They report that 82 out of 276 (29.7%) participants fulfilled at least one of five criteria for anomalous venous outflow proposed by Dr. Zamboni; 13/276 (4.7%) fulfilled two criteria consistent with CCSVI; none fulfilled more than 2 criteria. CCSVI was found in 7.14% of non-MS participants and in 3.88% of MS participants, a difference that was not statistically different. There was no significant difference between MS subgroups, and also no significant differences between MS and non-MS subjects for measures of cross-sectional areas of the internal jugular veins or for venous flow rates.
The team concludes that they find less CCSVI than previously reported by other groups, and that their findings do not support the idea that CCSVI is causally related to MS. They are now focusing on whether ultrasound can be complemented or supplanted by MRV and/or transluminal venography. UPDATE: Additional imaging results have now been published - Read more
The authors describe some of this study’s limitations. First, it is from a single center, and they did not use multiple trained sonographers and image interpreters. However, they point out that they also obtained alternative neuroimaging results which were blinded to the results reported from ultrasound, and these results will be published in a future paper. The team did not test whether the neurosonologist remained blinded to the diagnostic status of participants, but note that all subjects were instructed not to discuss medical history. They also did not assess venous anomalies such as dysfunctional valves, which were not described in the original CCSVI articles but were added to consensus protocols after this study began. Finally, they did not have participants repeat testing, so it is not known whether abnormal findings would be reproduced at a later point.
Comment: This thorough study adds to a growing body of evidence exploring the phenomenon of CCSVI. Additional results expected from this and other teams in coming months should shed further light on CCSVI and its implications for people who live with MS and for advocacy organizations such as the National MS Society, whose research focuses on speeding research toward stopping MS, restoring function, and ending MS forever.