CCSVI Research Round-up March 2013
4th March, 2013
In 2009, Italian clinician and researcher, Dr Zamboni, first proposed the possibility that chronic cerebrospinal venous insufficiency (CCSVI) - two or more abnormalities in the veins or blood flow that drains the brain - could be related to the development of MS. There has been a considerable effort by the international research community to replicate Zamboni’s findings, with mixed results (see earlier MSRA news articles on CCSVI).
The early part of 2013 has brought a new study by West Australian researchers and publication of a number of international prevalence and treatment studies - summaries can be found below. The current weight of evidence suggests that CCSVI is not causally related to MS, and is frequently also found in people who do not have MS. There is also evidence to suggest that changes to the veins draining the brain and spinal cord may occur as a result of ageing in MS.
No randomised controlled trial of endovascular treatment (to widen blocked veins) for CCSVI in people with MS has been completed. Trials are either underway or in planning in Canada, Italy and Australia with results some way off.
Further understanding of the relationship between CCSVI and MS will come from several large studies funded by the USA and Canadian MS societies into the prevalence of CCSVI in MS. These studies are in the final stages and the USA National MS Society plans a webcast in the northern hemisphere spring this year to provide an update on progress (visit the NMSS website for further information). A very large prevalence study is also planned in Italy.
An interesting commentary, documenting the Canadian experience of the CCSVI debate from the perspective of media, science policy and politics has been published in the open access journal Bio Med Central Medical Ethics. The full article can be accessed here.
Recent research - Prevalence studies
A new study led by neurologist Prof Allan Kermode, at the Australian Neuromuscular Research Institute and Sir Charles Gairdner Hospital, Perth studied 30 people with MS and 10 healthy controls using both ultrasound and magnetic resonance venography, considered to be the most accurate way to assess CCSVI. No participants had the two positive sonographic findings required for a CCSVI diagnosis. Two control individuals and one MS patient had single abnormal findings. As such no follow-up venography procedures were undertaken on MS patients. However, the team did assess venography images in nine consecutive non-MS patients who were undergoing venography for other reasons and six of the nine individuals showed venous narrowing. The authors concluded that narrowings of the internal jugular veins are found commonly in healthy individuals and are not more prevalent in MS.
Researchers in Naples conducted a sonographic assessment of CCSVI in 146 people with all forms of MS and 38 healthy individuals. Results were analysed by three neuroradiologists who were blinded to participant status. CCSVI was significantly more common in MS. CCSVI did not correlate with the clinical course but did associate with increasing patient age. The authors do not support a causal role for CCSVI in MS, and suggest that it is more likely to be a consequence of disease.
Another Italian study included 68 MS patients and 68 healthy people. They found no significant difference in the prevalence of CCSVI as defined by the Zamboni criteria in the MS group. CCSVI was associated with increasing age in people with MS, but not controls, and there was no difference according to MS clinical characteristics. The researchers noted that the blinding of sonographers to disease status was incomplete and discussed the role that this may play in their own and other studies. The authors rule out a role for CCSVI in causing MS or its severity and cannot discount that CCSVI is a consequence of MS and/or ageing.
American researchers have assessed CCSVI prevalence in 206 MS patients and 70 non-MS individuals using ultrasound. Care was taken to blind sonographers and the clinician who assessed the neuroimaging results. The team found no difference in the prevalence of CCSVI in people with MS and controls. They also found no differences in extra-cranial or intra-cranial flow rates. The authors conclude that CCSVI is not causally associated with MS.
The American Journal of Neuroradiology has also just published a collection of articles on CCSVI in MS with accompanying editorial commentary in their March News Digest. These articles predominantly rule out a causative role for CCSVI in MS, but also discuss some anatomical changes which may be more common in the veins of people with MS. Some authors describe their work to improve the tools used to assess and diagnose vascular changes.
Recent Research - Treatment studies
The MS Study Group of the Italian Society of Neurology, conducted a clinical follow-up of people with MS undergoing endovascular treatment for CCSVI. Detailed data was collected from 462 people with MS before and after the procedure, with an average of 31 weeks follow-up. Despite reports of a perceived benefit by people undergoing the procedure, there was no difference in Expanded Disability Status Score measured before and after the procedure. The number of relapses in people who discontinued MS treatments following endovascular treatment and those who continued with medications were not significantly different.
In a separate publication the authors documented the adverse events experienced by participants in the study. Serious adverse events were recorded in 3% of patients and included jugular blood clot in seven patients, expansion of the fluid filled cavities in the brain, stroke, changes to heart rhythm, seizures, aspiration pneumonia, high blood pressure with increased heart rate, or bleeding of bedsore. One patient died as a result of a heart attack 10 weeks after the treatment. While these may not all be related to the procedure, the authors stress the need for caution in light of these adverse events. Due to the risk of adverse events and lack of objective clinical benefits, the authors conclude that endovascular treatment should not be recommended for treatment of MS.
Canadian researchers have conducted a follow-up study of 30 people with MS who underwent endovascular treatment for CCSVI. Three methods were used to assess the outcomes: one subjective, one semi-objective and one objective. According to the subjective criteria patients reported significant improvements at 3 months follow-up, but this effect was reduced by the 12 months follow-up. The subjective and semi-subjective tests did not show any improvements over the 12 months follow-up. Venography conducted at the end of the study showed seven patients with occlusions in at least one vein, however, the clinical status of these patients did not deteriorate in comparison to those who did not show venous abnormalities.