Over the last 2 years, most interventionists have become familiar with the term CCSVI (chronic cerebrospinal venous insufficiency). They share in common a passing exposure to the postulated concept of an association between venous obstruction to drainage of the brain and spinal cord and multiple sclerosis (MS), but most lack firsthand experience evaluating or treating CCSVI. Many are aware of the frequently contentious and inflamed public discussions among groups of interested parties, including neurologists, MS patients and their families, interventionists, federal officials, etc., and thus have decided to observe the drama rather than join the heated fray.

In discussions around the world in cath labs, angio suites, operating rooms, neurology departments, and MS clinics on patient social networks; in feature pages of prominent newspapers and magazines and programming of mainstream media outlets; and at local, national, and international medical meetings, the proposed relationship between MS and extracranial venous obstruction is examined, questioned, but always debated. Everyone wants to learn more.

Everyone wants to understand: What do we know and what don't we know about CCSVI?


As all involved focus on these two unknowns, it may prove pragmatically more relevant at this early stage of our fundamental knowledge to consider: What do we need to know? Or posed in another way: What is necessary to establish before it is reasonable to embark on large-scale controlled, multi-institution, randomized trials of CCSVI treatment capable of demonstrating or disproving a link between MS and venous obstruction?

When considering the inability over the last 150 years to definitively grasp the underlying cause of MS, the conceptual difficulties that persistently challenge our understanding of the interplay between anatomical and physiological factors that contribute to symptomatic venous obstruction of other vascular territories, and the difficult-to-comprehend roles of a variety of conditions that apparently portend a predisposition to developing MS, it is unlikely that the CCSVI theory will lend itself to easy pathophysiological examination. Paradoxically, it may prove easier to move forward with CCSVI treatment studies that incorporate established objective endpoints accepted by MS neurologists rather than pursue unproven evaluations of specific but possibly irrelevant physiological consequences of venous flow disturbances.


It is understandable that the vast majority of neurologists who deal with MS patients are highly skeptical of CCSVI. Most neurologists have lived through a series of unproven and even dangerous pseudotherapies that prey on the vulnerability and hope-seeking nature of patients with an incurable, progressively disabling disease. From snake venom, to bee stings, and hyperbaric oxygen, etc., neurologists are especially sensitive to potential scams that have plagued the MS landscape, while at the same time consciously aware that many patients are marginally satisfied by their response to the “effective” approved pharmacological therapies.

Despite the current criticism of CCSVI and the recognition that most conversations on the subject between neurologists and interventionists don't always go well, there is experience that is providing data and evidence to support future randomized controlled treatment trials. Undoubtedly, one of the foremost issues to be addressed is the risk to patients of any CCSVI treatment procedure. Fortunately, the safety of currently practiced endovascular therapy—predominantly percutaneous balloon angioplasty (PTA), is the one area where a substantial fund of data is available from the estimated 13,000 to 15,000 patients treated to date worldwide.

Multiple large patient series published in the medical literature document that any serious complications from PTA of jugular and azygous veins are exceedingly rare.1-5 Untoward effects that are encountered are not dissimilar from adverse events known to accompany balloon dilation of lesions in other venous territories. Establishment of a safety profile for endovascular treatment of CCSVI that is consistent in these reports is a very important step forward and the demonstration of only mild side effects in a minority of patients is critical to advancing further study.


So, as we are poised at this snapshot in time, ready to advance to the next chapter of the CCSVI story—one that will hopefully include genuinely collaborative, multidisciplinary controlled treatment trials with randomized designs and meaningful objective efficacy endpoints—it is important to think about the future and what we would like to know. From this perspective, we can focus on the long list of questions that we hope future trials will bring us closer to answering. In terms of CCSVI diagnosis, treatment, and follow- up, some of the interesting unresolved issues are noted in the Questions Concerning Diagnosis and Treatment and Questions Concerning Posttreatment and Follow-Up sidebars.

In addition to this abridged list of questions are three of the most fundamental issues yet to be understood: What is the endovascular treatment of venous obstruction really affecting—is it flow or something else? Is there any evidence that the trajectory of disease progression is altered after CCSVI treatment? Finally, how can interventionists engage MS neurologists in a nonthreatening, meaningful collaboration to study a concept they regard as total lunacy?

Addressing these and other concerns will sternly test the resolve, patience, and willingness of all concerned individuals to engage in multidisciplinary collaborations to better understand the nature of CCSVI and potentially benefit the lives of MS patients.

Michael D. Dake, MD, is Thelma and Henry Doelger Professor (III), Department of Cardiothoracic Surgery, Stanford University School of Medicine and Falk Cardiovascular Research Center in Stanford, California. He has disclosed that he holds no financial interest related to this article. Dr. Dake may be reached at mddake@stanford.edu.