Jul 18, 2013
Researchers at the University of Texas Health Science Center at Houston have published additional results from a National MS Society-supported study investigating CCSVI (chronic cerebrospinal venous insufficiency) using imaging techniques to examine blood outflow from the brain. Results of the first part of this study using Doppler ultrasound were previously published. This part of the study was conducted to learn to what extent ultrasound findings were supported by other imaging techniques. The team used magnetic resonance venography (MRV) and transluminal venography (TLV) in a subgroup of people with MS who had already undergone ultrasound vein scanning. They reported poor agreement between ultrasound and MRV, and that TLV detected no pressure readings that would indicate functional vein blockages. The study, by Staley A. Brod, MD, Jerry S. Wolinsky, MD, and colleagues, was recently published early online in the Multiple Sclerosis Journal.
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 further results from a 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 (Andrew D. Barreto, MD), Director of Magnetic Resonance Research (Ponnada Narayana, PhD) the Chief of Cardiovascular MRI (Larry A. Kramer, MD), and expert MS neurologists (Drs. Wolinsky, Staley A. Brod, John W. Lindsey and Flavia Nelson).
This was a single-center study that enrolled MS and non-MS volunteers at the University of Texas Health Science Center at Houston. For the previously reported 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 reported much less prevalence than previously reported by other groups and no statistical difference between those with MS and those without MS.
For the next portion of the study reported here, the team studied a subset of those with MS who had completed the first part of the study, to compare ultrasound imaging results with two other approaches – magnetic resonance venography (MRV) and transluminal venography (TLV) to image the venous drainage system.
MRV study: Of 206 people with MS who completed the ultrasound scans for the first part of the study previously reported, 98 also underwent MRV for the next part of the study. They averaged 47.6 years of age and had had MS an average of 9.9 years. Sixty-two had relapsing-remitting MS, 23 had secondary-progressive MS, 5 had primary-progressive MS, 6 had clinically isolated syndrome, and 2 had progressive relapsing MS.
The participants were examined while lying down in a 3T scanner. The novel MRV procedure involved scanning before and after the injection of a contrasting agent (gadofosveset trisodium) to permit enhanced images of the veins in the head and neck regions. (Full technical details of the study are explained in the paper.)
The investigators compared ultrasound findings of stenosis (narrowing of veins) meeting CCSVI criteria with those using MRV. In 71 people out of 98, neither technique detected CCSVI. In 26 people, ultrasound and MRV findings did not agree in terms of whether or not CCSVI was present. The investigators reported that MRV may have advantages for imaging certain regions of the venous system that are poorly detected by ultrasound, such as the azygous system and regions of venous outflow from the brain obscured by dense bones at the skull base.
TLV study: Of the 98 people with MS who underwent both ultrasound and MRV scanning, 40 were also examined using transluminal venography (which involves obtaining pictures of the anatomy by surgically inserting a catheter into the vein). These included 29 with relapsing-remitting MS, 8 with secondary-progressive MS, and 3 with clinically isolated syndrome.
One out of 39 people with accessible azygous veins showed minimal narrowing. Internal jugular veins showed degrees of stenosis in 55%, and valves were detected in nearly all of the internal jugular veins. Despite these findings, TLV detected no pressure readings that would indicate functional vein blockages in any of the veins.
The authors note that their findings do not indicate altered vein flow in people with MS, and do not support a significant role for CCSVI in MS.
Comment: This study adds to a growing body of evidence exploring the phenomenon of CCSVI and imaging technologies to study it. Additional results expected from 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.