July 2015: Dr. Fox’s team publishes final results of the clinical study to investigate differences in venous flow between people with MS and people without MS. The team studied 61 people with MS (4 with CIS; 28 with relapsing-remitting MS; 19 with secondary-progressive MS; 10 with primary progressive MS) and 20 people without MS (15 healthy and 5 with other neurological conditions). Ultrasounds were performed by trained technicians who were “blinded” as to whether the participants had MS or not. Using strict interpretations of CCSVI, the team found that 21% of the MS group met two or more criteria and 20% of the non-MS group met the criteria. This difference between groups was not statistically significant.
Using more broad interpretations of CCSVI, the team found that 36% of the MS group met CCSVI criteria and 40% of the non-MS group met the criteria. The difference between the groups was not statistically significant. The team concludes that its observations do not support an increased prevalence of CCSVI in MS and do not support a role of CCSVI in the MS disease process. They also suggest that differences in published findings likely relate to how ultrasound assessments are conducted and interpreted. ("No Association of Chronic Cerebrospinal Venous Insufficiency with Multiple Sclerosis" Robert J Fox, Claudiu Diaconu, Leasa Baus, Alia Grattan, Irene Katzan, Jar-Chi Lee, Larry Raber, Alexander Rae-Grant, Sneha Ramesh, Mei Lu, Esther SH Kim. Can J Neurol Sci. 2015; published in Early View on July 21, 2015.) Read the open-access paper.
October 2013: Team publishes results from a small study related to hydration levels and CCSVI assessments.
June 2013: Dr. Fox requested an extension to this grant to finish analyzing scans and prepare results for publication in scientific journals. He has presented preliminary results at several medical conferences.
September 2012: Researchers continue with their progress in the seven Society-funded CCSVI studies in MS. Read about the most recent progress.
January 2012: Dr. Fox’s team continues to use MR venography, ultrasound, MRI and clinical measures in people with MS or who are at risk for MS (CIS) and comparison groups to evaluate vein drainage. The ultrasound team, which underwent training in the technique originally used by Dr. Zamboni, found several aspects of the published methodology ambiguous, and they have standardized the protocol and analysis to achieve consistent results.
Early on they identified physiological and technical factors that can complicate screening for vein blockages using ultrasound, including that heartbeat irregularities, stages of breathing, head position and pressure applied by the operator could alter results; and that the state of hydration of the subject (whether they drank adequate amounts of fluids) might impact results of several of the criteria used to determine CCSVI.
The team reported at the international ECTRIMS/ACTRIMS congress in October 2011 preliminary results of ultrasound assessments. Pooling the results of the ongoing, blinded study of CCSVI in MS and non-MS controls, they reported results from the first 20 subjects, finding that 6 (30%) met criteria for CCSVI, four subjects met no criteria, and none met criteria for reverted postural control of cerebral venous outflow. Nine subjects (45%) had a flap and/or septum/abnormal valve. Identifi¬cation of deep cerebral vein reflux depended upon the ultrasound technique. They noted that this finding highlights the importance of ultrasound methodology in performing and interpreting deep cerebral vein assessments. (P1104 – “Ultrasound assessment of chronic cerebrospinal venous insufficiency.” R. Fox, L. Baus, C. Diaconu, A. Grattan, I. Katzan, S. Kim, M. Lu, L. Raber, A. Rae-Grant)
At the same ECTRIMS/ACTRIMS meeting, the team shared preliminary results from an ongoing study of vein structure in autopsy specimens from seven people who had MS in their lifetimes, compared to six people who did not have MS. In this unblinded study, they identified abnormalities inside the vein tubes (lumen) that drain the brain and found a variety of structural abnormalities and anatomic variations in both groups. However, they reported higher frequency of abnormalities in those who had MS (2 abnormalities in 2 out of 6 controls versus 9 abnormalities in 6 out of 7 MS patients). They noted that MR venography may be less effective than ultrasound for identifying these venous abnormalities, and that ultrasound that examines only vein wall circumference may miss some intraluminal abnormalities. (Abstract 134 – “Anatomical and histological analysis of venous structures associated with chronic cerebro-spinal venous insufficiency.” C. Diaconu, S. Staugaitis, J. McBride, C. Schwanger, A. Rae-Grant, R. Fox)