June 25, 2014
CCSVI Case-Control Neurosonography Results Announced
Background: Determining the link between CCSVI and multiple sclerosis
Chronic cerebrospinal venous insufficiency (CCSVI) has been a topic of active discussion over recent years. The association between CCSVI and MS, originally reported by Dr. Paolo Zamboni, MD from the University of Ferrara in Italy, has challenged the widely accepted theory that MS is an immune-mediated inflammatory disease. Dr. Zamboni describes CCSVI as the disruption of blood flow in which the venous system is not able to efficiently remove blood from the central nervous system, resulting in increased pressure in the veins of the brain and spinal cord and subsequent damage to these areas.
In June 2010, the National MS Society (USA) and the MS Society of Canada committed over $2.4 million to support of seven new research projects that would gain further insight into the relationship between CCSVI and MS. Using advanced imaging techniques and experimental design, the Society-supported studies observe the structure and function of veins draining the brain and spinal cord in people with MS, and compare them to structure and function of veins in healthy volunteers as well as people with other neurological diseases.
At the two-year milepost, researchers leading this work reported significant progress in their study goals. Although research continues for several of the teams, some are already presenting preliminary results at medical meetings, and have been active in sharing technical advice so that the projects can move forward quickly and consistently.
One of the seven teams has now published the first results from its comprehensive study in Annals of Neurology. Dr. Jerry S. Wolinsky, MD from the University of Texas Health Science Centre in Houston assembled a group of experts with diverse specialties to examine the role of CCSVI in MS, and validate a reliable technique for CCSVI screening.
The collaborators in this project, all from University of Texas Health Science Center at Houston, include the Chief of Vascular Interventional Radiology (Dr. Alan M. Cohen, MD) the director of the neurosonography laboratory (Dr. Barreto, MD), the Chief of Cardiovascular MRI (Dr. Larry A. Kramer, MD), and expert MS neurologists (Drs. Wolinsky, Staley A. Brod, John W. Lindsey and Flavia Nelson).
This was a single-center, prospective case–control study involving MS and non-MS volunteers at the University of Texas Health Science Center in Houston. Altogether, 276 subjects were studied: 206 with MS and 70 non-MS. The purpose of the first portion of the study was to compare the prevalence of CCSVI as defined by neurosonography (NS) in MS and non-MS subjects. To achieve this, Dr. Wolinsky and his team used Doppler ultrasound to observe venous drainage in a blinded fashion. This means that the technician performing the scan, known as the neurosonologist, as well as the professional reading the scan were not aware of the disease status of the participants.
The team utilized a standard Doppler ultrasound machine rather than purchasing the specific machine used by Dr. Zamboni’s team. When looking at the structures in the brain, the researchers followed protocol and used criteria consistent with those originally published by Dr. Zamboni (J Neurol Sci 2009;282:21-27), which is described in detail in the published paper.
What they found:
The results of the study showed 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. In addition, the number of participants that exhibited 0, 1, or 2 Zamboni criteria did not differ significantly between people with MS and non-MS controls, or amongst MS subgroups (i.e. relapsing-remitting MS, clinically isolated syndrome, and progressive MS)
Dr. Wolinsky and his team are now comparing data from ultrasound to abnormalities seen through other imaging techniques such as magnetic resonance venography (MRV) or transluminal venography (TLV). This work will determine the veracity of the conclusions based on ultrasound alone and will be featured in future publications.
Overall, the results of this study show that CCSVI is much less prevalent in study participants than previously reported and did not distinguish people with MS from the non-MS group. The researchers conclude that their findings do not support a causal association between CCSVI and MS pathology.
The authors reported a number of study limitations, the first being that it is a single-centre study. They note that results from larger multi-centre studies, such as the one conducted in Italy may be useful to consider. They also noted that although neurosonography expertise in this study is robust, the researchers did not employ multiple trained sonographers and image interpreters.
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 their medical history. They also did not examine other venous irregularities such as dysfunctional valves, which were recently added to the consensus protocol. Finally, they did not have participants repeat testing, so it is not known whether abnormal findings would be observed again in the future.
The release of the first MS Society of Canada/National MS Society joint funded CCSVI study demonstrates an effort to better understand CCSVI in the context of MS. The work of Dr. Wolinsky adds to the growing line of evidence exploring CCSVI, and his work in comparing a variety of imaging methods to accurately identify CCSVI will provide a deeper understanding of this phenomenon. His team points out that discrepancy in results are due to many factors, which are outlined in detail in the paper. With this in mind, the MS Society and the MS community as a whole can appreciate that further research is required to see a clearer picture.
Source: Barreto, AD et al. Chronic Cerebrospinal Venous Insufficiency: Case–Control
Neurosonography Results. Annals of Neurology 2013;DOI: 10.1002/ana.23839. Online First