CIRSE Commentary on the Treatment of Chronic Cerebro-Spinal Venous Insufficiency (CCSVI)
Chronic Cerebro-Spinal Venous Insufficiency or CCSVI is a putative new theory, which is suggested by some to have a direct causative relationship with the symptomatology associated with multiple sclerosis (1). The core foundation of this theory is that there is abnormal venous drainage from the brain, due to outflow obstruction in the draining jugular vein and/or azygous veins. This abnormal venous drainage, characterised by special ultrasound criteria called the Venous Hemodynamic Insufficiency Severity Score (VHISS), is said to cause intra-cerebral flow disturbance or outflow problems, leading to peri-ventricular deposits (2). In the CCSVI theory, these deposits have a great similarity to the iron-deposits seen around the veins in the legs in patients with chronic DVT.
Dr. Zamboni who first described this new theory has promoted balloon dilatation to treat the outflow problems, thereby curing CCSVI and, by the same token, alleviating MS complaints. However, this theory does not fit into the existing bulk of scientific data concerning the pathophysiology of MS. Nevertheless, there is an increasing acceptance of CCSVI and the associated balloon dilatation treatment worldwide, disregarding the fact that there is only low grade scientific evidence, mainly coming from one source. The treatment is called the “Liberation Treatment”, and the results from the treatment can also be watched on YouTube. There are well-documented testimonies by MS patients who have gained improvement in their personal quality of life after the treatment. There are however no data available from patients who underwent unsuccessful treatments.
There are currently several centres actively promoting and performing balloon dilatation, with or without stenting, for CCSVI. However, it must be stated that no randomised trial data are available to back the theory behind the treatment or to support its use. There are also no RCTs currently in progress. Therefore, the basis for this treatment rests on anecdotal evidence and successful testimonies by patients. It is for these reasons that CIRSE feels that this is not a sound basis to currently offer this new treatment, which has not yet been part of a RCT.
The core of this new theory is the CCSVI syndrome, or the abnormal venous drainage from the brain. However, venous drainage from the head has an impressive anatomic variation, which is not very well catalogued in most textbooks. Also valves can be present at a variety of sites in the head and neck veins. Interventional Radiologists who practise para-thyroid sampling are well aware of the huge variety in venous anatomy. Besides the huge variation in normal venous anatomy the jugular veins have some natural narrowing at two sites and the azygous vein, prominent in the CCSVI theory, does not drain the brain at all. The azygous can clearly drain the spinal cord but not solely, as there are many intercostal venous collaterals which fulfil the same function.
In addition, the fact that this imaging is done in the supine position will have a great influence on blood flow and image interpretation. There have recently been randomised studies comparing socalled venous stenoses in patients with and without MS (3-4). Both studies show that there is no difference in the prevalence of venous stenoses between the two groups. This seems to be a very strong argument against the existence of CCSVI. However, physicians performing CCSVI treatment point out that these studies were not performed according to the specific Venous Hemodynamic Insufficiency Severity Score (VHISS) criteria. The other part of the theory is that the venous outflow obstruction needs to be treated. However, if there is a real haemodynamic venous outflow obstruction, there should also be a pressure gradient and this gradient should disappear after successful balloon dilatation. It has been shown, and confirmed by those who perform balloon dilatation for CCSVI, that over the so-called stenosis there is never a measurable pressure gradient. Those who perform this treatment argue that it is not the pressure gradient but the change in outflow pattern, caused by this stenosis, that is the pathological entity.
What remains is the issue of anecdotal successful treatments. Undoubtedly there are some patients who obtain symptom relief after treatment for CCSVI, but this could be just a placebo effect. In itself, there is nothing wrong with the placebo effect, as long as we recognise it. Indeed, many treatment successes in medicine are based on or helped by a placebo effect. It is also known that the more invasive the treatment is and the more the treating physician believes in the treatment, the stronger the placebo effect is. Furthermore, MS can affect emotional and labile responses and is characterised by spontaneous relapses and remissions. This makes the gathering of scientific evidence to support CCSVI theory difficult in anything other than a RCT.
What we now have is the dilemma of a new treatment being promoted and carried out by some early pioneers with the popular press trumpeting its success, and thus decreasing the chances of performing a properly conducted trial because it is considered un-ethical not to offer patients this new and promising treatment. The primary task of physicians is “Primum non nocere” or not doing harm. We believe that one way harm can be caused is by offering treatments without any scientific proof of efficacy as well as the more usual forms of medical harm. Arguments such as; “there is nothing else”, or “Do you know how much they pay for medication that does not work?” are not valid or scientific to support the use of this treatment.
Confronted with these contradictions and lack of evidence for CCSVI treatment, some pioneers have taken to calling their work on MS patients a phase 1 study. However, a phase 1 study without a protocol, approval by medical ethical committee, informed consent or safety committee oversight does not qualify. CIRSE believes that only properly conducted trials with significant scientific rigor can solve this dilemma. We believe that a small prospective randomised trial, with a sham arm, is required. A trial monitored by an independent society, such as the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and/or the European Society of Neurology would be ideal.
As doctors and interventional radiologists, we certainly hope that all of the anecdotal reports detailing improvements in QOL will prove to be true, and that patients will benefit from this new treatment. We, as IR’s, have a long history of introducing pioneering treatments that have proved to be of enormous benefit to patients over the last 30 years. Recently, new treatments such as fibroid embolisation, vertebroplasty and carotid stenting have all been tested in randomised trials. We believe that CCSVI treatment should be evaluated in the same manner. Furthermore, we believe that until real scientific data is available for CCSVI and balloon dilatation, this treatment should not be offered to MS patients outside of a well designed clinical trial.
References:
1: Zamboni P. The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med. 2006;99:589-93. 2: Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, et al. The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol. 2009;24:133-8.
3: Krogias C, Schröder A, Wiendl H, Hohlfeld R, Gold R. Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients. Nervenarzt. 2010;81:740-6. 4: Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol. 2010;68:173-83.
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