CCSVI: Recent research findings
22nd June, 2012
Italian clinician and researcher, Dr Zamboni first proposed the possibility that chronic cerebrospinal venous insufficiency (CCSVI) could be related to the development of MS in 2009. Since then there has been a considerable effort by the international research community to replicate his findings, with mixed results.
Dr Zamboni has now published results of a clinical trial to test the safety and efficacy of a surgical procedure to widen blocked veins draining the brain and spinal cord as a treatment for MS.
This latest research by Dr Zamboni and his colleagues was conducted in a small group of 29 people with MS. They were observed for two years before and two years after the percutaneous transluminal angioplasty procedure. Expanded Disability Status Score and relapse rates were recorded at regular intervals before and after the treatment. All patients received the surgical procedure and the medical assessors were aware of the patients’ treatment status (i.e. unblinded). 45% of the patients received more than one procedure due to restenosis. The results indicate a statistically significant overall improvement in EDSS in the two years following the procedure, although four patients had a worsening EDSS. Relapse rates were also lower in the period after the procedure.
Dr Zamboni and his colleagues conclude that the results support the design and execution of a randomised controlled trial that would also include MRI imaging. However, they acknowledge the limitations of the current results due to the small study size and lack of a placebo control and blinding. The authors do not endorse the use of the treatment outside of clinical trials at this stage.
At the same time the European Society of Neurosonology and Cerebral Hemodynamics has published a statement in the Journal of Neurology. The authors reviewed the five ultrasonographic criteria for CCSVI. They conclude that the criteria are questionable due to a combination of methodological and technical errors as well as the inappropriate application of scientific data to differing situations. They strongly discourage the use of interventional treatment. Read the abstract here
This comes after the American Food and Drug Administration (FDA) issued a medical devices safety communication in early May 2012. The Communication warned of the potential dangers of balloon angioplasty devices and stents and emphasised the lack of clear evidence on the existence of CCSVI or its link to MS. Read the communication here
Meanwhile, further data on the prevalence of CCSVI in people with MS continues to appear in the peer reviewed medical literature. For example, Zivadinov and his colleagues in the USA compared CCSVI results with MRI data in people with MS and healthy controls. They found that the presence of CCSVI was not associated with more severe lesion burden or brain atrophy. In another paper, Zivadinov and colleagues also looked at the association of CCSVI with clinical features of MS such as disability and MS type. They found that CCSVI was more common in progressive forms of MS (secondary and primary), but did not correlated with disability levels in any form of MS.
Blinkenberg and colleagues in Denmark, used ultrasound and magnetic resonance (MR) venography in a small study to investigate CCSVI. They found that there was no evidence for an increased prevalence of CCSVI in people with MS compared to healthy controls. Scientists in Italy found no association between paediatric onset MS and CCSVI. McTaggart and colleagues used sonography and MR venography to assess CCSVI in people with MS and healthy controls. The investigators were blinded to the medical status of the participants. They found an increased presence of flattening of the internal jugular vein in people with MS compared to healthy controls. They suggest this finding warrants further investigation to determine whether this plays any role in the development or progression of MS.
In Australia, Dr Brian Chambers has submitted his progress report on the MSRA-funded study to investigate the presence of cerebral venous drainage abnormalities in people with MS and healthy controls. His findings are yet to be published in the peer-reviewed literature, but the preliminary conclusions can be read here.
The Alfred Hospital in Melbourne has a clinical trial planned details available here which has received ethical approval from the Hospital’s Ethics Committee. Earlier this year, MSRA received a grant application from the investigators for this trial. The application is currently undergoing an expedited peer review process ahead of the usual MSRA grant rounds timeline. This involves an independent review of the application by three international assessors, which will be followed by consideration by the MSRA Research Management Council. Should the application be approved through this process the funds raised by CCSVI Australia and currently held by MSA – NSW/ACT/VIC, will be passed to the Alfred Hospital accordingly.
MS Australia and MSRA are committed to minimising the impact of multiple sclerosis on the lives of Australians and we keep an open mind to possible new treatments. However, we can only support the introduction of new treatments following rigorous scientific testing and evidence. MS Australia and MS Research Australia will continue to update people with MS on the latest research and developments in CCSVI.