CCSVI (the Vascular Theory of MS): Separating Fact from Fiction

Since the airing of a Canadian television newsmagazine piece on CCSVI, there has been a veritable frenzy on Internet chat rooms and bulletin boards regarding this radical new theory. Unfortunately, the tsunami of information that is being bandied about is often misleading and sometimes just plain wrong. Based on scant knowledge, many are making extraordinary claims regarding the theory and the treatment options it presents, most of them based on little actual fact.

For those unfamiliar with CCSVI (chronic cerebrospinal venous insufficiency), I've made two previous posts about it, which you can find here and here. I've been fastidiously following the development of the theory and the treatments being used as a result of it for at least ten months now. Though I'm far from the be-all and end-all of CCSVI information, I do feel qualified to make some intelligent observations about it.

For readers unacquainted with CCSVI, the theory basically states that narrowing in the veins that drain the central nervous system (CNS) leads to an abnormal flow of blood through the CNS, which damages nerve tissue via several different mechanisms, and leads to the lesions and immune responses that are the hallmarks of Multiple Sclerosis. First proposed by an Italian doctor, Dr. Paolo Zamboni, whose wife was stricken with MS, the theory has won over several fervent supporters. Dr. Zamboni is treating MS patients with a modified balloon angioplasty procedure he calls "The Liberation Procedure", and another physician at Stanford University, Dr. Michael Dake, is opening up the blocked veins of MS patients using stents. There is also a doctor in Poland, Dr. Marian Simka, who appears to be using a combination of these two methodologies. As knowledge of the theory has spread, many harsh critics have quite expectantly begun to ring in. I'll attempt here to cut through the noise, and present the facts as I know them, along with some commentary.

To begin with, let me state that although I remain somewhat skeptical, I'm a cautious believer in the concepts put forth by the CCSVI theory. It is certainly my hope that the theory bears fruit, as it will offer MS patients a myriad of new options to treat the disease, and will lead research scientists in entirely new directions as they investigate the many aspects of Multiple Sclerosis. Hopefully, it will help bring about a rethinking of the autoimmune theory of MS, which states that, for reasons unknown, the immune system goes bonkers and starts attacking the body's own cells. Quite frankly, we've been fed that line of bullshit for far too long. If the CCSVI theory starts gaining significant traction, expect a withering storm of criticism to come from some mainstream neurologic circles, as well as from the pharmaceutical industry, which stands to lose untold billions in the sales of drugs designed to suppress the immune system.

Dr. Zamboni's research began with his imaging the vascular systems of MS patients, sufferers of other neurologic diseases, and healthy subjects. He reports that he found signs of vascular abnormalities in almost 100% of the MS patients he studied, but none in either the patients with other neurologic diseases, or the healthy subjects. On its face, this would seem to be very compelling evidence. However, as my doctors at the National Institutes of Health (NIH) have pointedly explained, this claim throws up some big red flags. Because MS is a notoriously hard disease to diagnose, and there are many diseases that mimic MS, in any large population of diagnosed MS patients, there will be a significant segment that have in fact been misdiagnosed. Therefore, finding 100% of any trait among a large population of MS patients is practically impossible. As a matter of fact, the way I first became involved with the NIH was as part of a study being used to identify patients that the National Institutes of Health could be certain actually suffer from MS, because misdiagnosed patients were skewing the results of many of the MS studies they had undertaken. The NIH is trying to identify a pool of patients they can be confident actually have MS, for use in future studies. This is how the NIH ascertained that it's very likely I do not have MS.

Still, the Zamboni findings appear to be compelling. Before they can be accepted as scientific fact, though, they must be replicated by independent researchers, and so far, no such evidence has been presented. There are several different research groups currently putting together studies of CCSVI, and a large imaging study is already ongoing at the University of Buffalo, so we should have either independent verification or refutation of the theory sometime within the next 6 to 12 months. Before we get these independent reports, however, it is extremely premature to state anything with certainty about the theory.

In my mind, CCSVI could explain several of the mysteries surrounding MS, but fails to explain many others. It's one of the first theories to adequately explain the formation of lesions and the immune response that are the calling cards of MS. It also explains findings such as those that tie cigarette smoking to an increased incidence of MS and a quicker progression of the disease. Since smoking is known to exacerbate vascular issues, if MS is in fact a vascular disease, it stands to reason that smoking would have a considerable negative effect on it.

On the other hand, the theory does not address what we know about the geographic distribution of MS, the male-female ratio that is well known to exist in MS, the existence of "MS clusters" (which would seem to point to an infectious cause), or the unmistakable link between MS and Epstein-Barr virus (100% of MS patients are infected with EBV. I know, many of you reading this have never had Mono, but the vast majority of people infected with EBV have no idea that they carry the virus. It can often be asymptomatic, or present as a bad cold or flu).

Having said that, MS is an extremely heterogeneous disease, and it may be that CCSVI is THE answer for a subset of MS patients, but may play only a partial role, or no role whatsoever in others diagnosed with the Multiple Sclerosis.

As for the surgical interventions now being used on patients whose imaging (via MRV and/or Doppler imaging studies) indicates that they have venous abnormalities related to the CNS, there are controversies surrounding these, as well. The problems stem from the fact that the procedures being used were all developed for use in clearing out the obstructed arteries of cardiac patients. Remember, CCSVI is concerned exclusively with veins.

There are major differences between arteries and veins, both in form and function. Arteries are designed to facilitate the outflow of blood from the heart to the various organs and regions of the body. They must be able to withstand the tremendous internal blood flow pressures generated by the beating heart, and thus their walls are stiff and resistant to tears and breaks. Veins, on the other hand, function to return deoxygenated blood to the lungs and heart. They are designed to be flexible and pliant, and their walls are much thinner and more prone to tearing than the walls of arteries. Arteries grow narrower in the direction of blood flow, while the opposite is true of veins, which grow wider as they return blood to the cardiopulmonary system. Therefore, a stent that gets loose in an artery is typically only pushed deeper into that artery. A stent that gets loose in a vein generally has a clear path to the heart.

In self-reported results, Dr. Zamboni's balloon angioplasty Liberation Procedure appears to be quite effective in reducing relapse rates and disease severity. Unfortunately, as many as 50% of the patients treated suffer restenosis of the veins opened by the Liberation Procedure, and thus require multiple interventions. As with any surgery, there is risk involved, and that risk is multiplied each time the intervention must be repeated. Furthermore, stenosis that is found in problematic areas, such as high in the jugulars, is not treatable by balloon angioplasty.

The surgery being attempted at Stanford University is much more aggressive, and places stents at the stenosed areas of blockage. Stenting has very rarely been tried in veins, and much less so in veins associated with the brain and spinal cord; the stents used have been almost exclusively designed for use in arteries. So far, slightly over 60 patients have been treated with this procedure, and there have been some serious complications reported. Despite the fact that I have a significant stenosis in my left upper internal jugular, both the doctors at the National Institutes of Health and my primary neurologist have repeatedly and adamantly warned me against undergoing this procedure, citing the possibilities of brainstem hemorrhages, stent migration (which would almost inevitably lead to stents finding their way into the heart), and the ever present danger of bleeding and blood clots. Although the majority of the patients that have undergone this procedure report positive results, a minority have had a difficult time recovering from surgery, and have reported nerve pain and nerve damage. There has been one near calamity associated with the surgery, as one patient required emergency open-heart surgery to retrieve a stent that had become dislodged in his jugular and migrated to his heart. (Update: as of 12/08/09, CCSVI surgical procedures at Stanford have been halted, pending the start of a clinical trial, scheduled to begin in the first quarter of 2010.)

In short, the research surrounding CCSVI appears to be very promising. Until this research is replicated by independent organizations, no real conclusions can be drawn. There have been many other promising leads in the history of MS research that have eventually led to dead ends. I'm hopeful that CCSVI will not be one of them, and instead will lead to a seismic shift in our understanding of not only MS, but other so-called autoimmune diseases as well. I cannot make any such statement, however, until the research is verified by multiple sources. As for the surgical procedures now being offered to treat stenosed veins, they must be characterized as experimental, and as such, carry with them a sizable degree of risk, more so with the stenting procedure than with balloon angioplasty. If CCSVI theory turns in to CCSVI fact, these surgical procedures will in time be refined, and the risk in undergoing them will be diminished.

As exciting as Dr. Zamboni's research is, I think it's important that the MS community as a whole steps back and takes a breath, and waits to see what further research bears out. I understand how hard this can be with a progressive neurologic disorder breathing down your neck. Believe me, I'm nearing the point of desperation myself, but in situations like these, we cannot let hope and emotion cloud our actions and understanding of the issues. These are potentially life and death matters, and need to be approached with clarity of mind and a complete grasp of the complicated issues being presented.