CCSVI: Three Years On, Some Thoughts and Observations

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It seems almost incredible, but it's been nearly 3 years since I wrote my first Wheelchair Kamikaze post on CCSVI (click here). At the time of that first post, CCSVI had hardly been heard of outside of some researchers in Italy and a few dozen patients debating the merits of the hypothesis on an Internet forum. Today, CCSVI has become a patient driven social media medical phenomenon. An estimated 25,000-30,000 patients have already undergone CCSVI treatment, researchers from around the world are investigating the hypothesis, and the surgical treatment of CCSVI has become a thriving industry. CCSVI has certainly come a long way, but in many ways we've only taken the first steps on what could be an epic journey.

Last week, the International Society for Neurovascular Disease (ISNVD) held its second annual scientific meeting, which lasted five full days, in Orlando, Florida. A tremendous amount of information about the nature and treatment of CCSVI was exchanged by researchers and physicians, a compendium of which can be found in a 106 page online PDF publication put out by the Society (click here).

Of most interest to patients are undoubtedly the treatment outcomes reported by several CCSVI treatment practitioners (which can be found on pages 62, 79, 83, 84, 86, and 87 of the PDF), which displayed a wide variety of treatment outcomes, but do seem to suggest several identifiable trends. It appears that quality of life issues (fatigue, cognitive issues, heat sensitivity) saw more benefit post treatment than mobility related issues, and that RRMS patients fared better than patients suffering from SPMS or PPMS. None of these studies was double blinded, all being observational and most relying on self-reported information, which can lead to inaccuracies. Still, the findings generally fall in line with some of the few double blinded studies that have been done, such as a recently completed study done in Italy (click here). CORRECTION:an anonymous reader points out that this Italian study was in fact not double blinded, and just used an independent physician to evaluate EDSS scores. Thanks for the heads up.

The meeting did bring into focus the fact that the CCSVI treatment protocol is far from standardized, with physicians varying in opinion on issues ranging from which veins to treat, whether treatment should concentrate on valves rather than the veins themselves, the use of intravascular ultrasound, and other important issues, a list of which can be found on pages 104-106 of the PDF document linked to above. There were quite a few presentations on the use of noninvasive imaging techniques (Doppler Ultrasound and MRV technology) to diagnose CCSVI, with the consensus appearing to be that neither method was especially accurate, except for extremely specialized MRV protocols that are practiced at only a few facilities. One leading CCSVI practitioner went so far as to state that he no longer requires his patients to undergo Doppler Ultrasound investigations before venoplasty, since the ultrasound results were found to be so prone to error (page 63 of the PDF).

In addition to presentations involving CCSVI treatment techniques, some important observations about the nature of the condition were also presented. The effects of reduced blood flow through the brain were discussed, as was the possible connection between bloodflow disruptions and a breakdown of the blood brain barrier, and the role of iron deposition in the MS disease process. In all, my impression (keeping in mind that I did not attend the meeting) is that the findings presented at this year's ISNVD scientific meeting were more evolutionary than revolutionary, which I suppose is something to be expected. The explosion of interest in CCSVI amongst interventional radiologists and research physicians must logically lead to attempts to fill in the many gaps of knowledge that remain in regards to CCSVI, before more dramatic leaps in understanding can be accomplished.

This eruption of interest in CCSVI within the interventional radiology community is in some ways a double-sided sword. On the plus side, it has given patients access to treatment, which in the early days was extremely hard to come by. Today, patients have their choice of treating physicians, and must do their due diligence when choosing which physician in whose hands to place themselves. As noted above, treatment techniques and philosophies vary widely from physician to physician, and patients exploring the possibility of CCSVI treatment should not be shy about asking questions in an effort to find a doctor whose treatment modality best fits their comfort level.

On the potentially negative side, CCSVI has become big business. With CCSVI treatment procedures costing about $10,000, and somewhere between 25,000-30,000 patients already treated, a little math reveals that treating CCSVI has already generated hundreds of millions of dollars in gross revenue for treating physicians. Yes, those procedures covered by medical insurance probably don't get reimbursed at the full rate charged, but this is likely made up for by patients who have undergone multiple procedures because of CCSVI's ongoing problems with restenosis. Given the fact that the number of treated patients represents only a tiny percentage of the worldwide MS population, it's easy to see that CCSVI treatment could quickly develop into a multibillion-dollar a year enterprise.

The David vs. Goliath narrative that has driven the CCSVI story thus far may soon become obsolete. To be sure, the neurology community still remains incomprehensibly steadfast in its negativity regarding CCSVI, but this is becoming counterbalanced by the enthusiasm of the interventional radiology community, and, I suspect, by the interests of the medical device manufacturers, who also stand to profit greatly should CCSVI become an accepted treatment option for MS patients. Despite the fact that very legitimate issues remain regarding the efficacy of CCSVI treatment and the lack of a consensus as to optimal interventional techniques, CCSVI treatment is being aggressively marketed by several US and international treatment facilities, which should raise some ethical questions.

Until issues with effectiveness and technique are satisfactorily answered, the CCSVI treatment procedure must be considered an experimental one, a fact that should not be lost on patients who are understandably desperate to address their illness but are faced with a dizzying array of statistics, patient testimonials, and marketing efforts by for-profit ventures. In a very real way patients who choose to undergo CCSVI treatment at the current time are guinea pigs, a fact that I understood explicitly when I underwent my venoplasty back in the dark ages of CCSVI, almost two years ago. Although we've come a long way since then, in some ways the procedure remains as experimental as ever, as physicians treat a much wider array of veins much more aggressively than they did back when I underwent the procedure. Though the treatment is a minimally invasive one, it is not without risks, as is evidenced by the contingent of patients who have experienced clotting issues and vein thrombosis in the aftermath of their procedures. Indeed, one of the presentations at ISNVD highlighted a patient whose condition worsened after treatment (page 89 of the PDF), a rare occurrence to be sure, but a possibility that must factor into the decision-making process of patients considering venoplasty.

One of the most volatile controversies raging on CCSVI forums and social media sites is whether or not the condition is a cause or effect of multiple sclerosis, with those arguing for CCSVI as cause often citing the fact that the venous abnormalities being found appear to be congenital (developed in the womb) in nature. I am unsure as to the question of cause vs. effect, although I do believe that if CCSVI is a cause of MS, it is only one of many factors involved in the initiation of the disease. Even if the vascular defects being found in the veins of MS patients are congenital, this does not necessarily mean they are a cause of multiple sclerosis. There are many congenital defects that cause no adverse effect whatsoever, and I'd venture to say that many of us have some physical trait somewhere in our bodies that is outside of normal variance.

We've all heard stories of world-class athletes suddenly collapsing during or directly after extreme physical exertion. Quite often, the follow-up story is that the unfortunate athlete was a victim of a congenital heart defect, which would never have been noticed had that person not pushed his body to physical extremes. Had they not been athletes, they very well could have lived a normal life span. Likewise, a person born with congenitally abnormal ligaments in their knees might never know of their condition unless they encounter an environmental element (such as a hit to their knees) that brings their abnormality to the fore, in the form of a knee injury more severe than that which might have been suffered by a person with "normal" ligaments. Given the varied elements that have been linked to MS (infectious agents, exposure to toxins, vitamin deficiencies, genetic markers, etc.), a likely scenario is that vascular abnormalities play a part in predisposing an individual to developing MS when exposed to an unfortunate storm of other factors.

To my mind, it is becoming increasingly clear that, despite our greatest hopes, CCSVI is only a part of a much bigger and more complex MS picture. Precisely how big a part it plays is still open to question. Although CCSVI treatment does appear to benefit many patients, it has also been shown to be of little or no value to many others. CCSVI does not explain some of the factors that have previously been established about MS, such as the geographic distribution of the disease (click here), the male-female ratio that is well known to exist in MS (click here), the existence of "multiple sclerosis clusters" (which would seem to point to an infectious cause-click here), or the unmistakable link between MS and Epstein-Barr virus (click here). Nevertheless, CCSVI offers the promise of opening up whole new areas of research into the causes of, and treatments for, multiple sclerosis. Certainly, interested MS patients should investigate the possibility of CCSVI treatment, and make a sober assessment as to whether now is the proper time for them to jump in.

There are several ongoing research projects that should further illuminate the CCSVI picture scheduled to publish results later this year, but further robust and expeditious research is desperately needed. It is essential that we ascertain just how prevalent CCSVI is in the healthy population, gain a better understanding of the role, if any, of vascular abnormalities in the MS disease process, determine which MS patients respond best to CCSVI venoplasty, refine the techniques used to treat CCSVI, reduce the number of patients who experience restenosis, and see the development of surgical implements specifically designed to treat venous abnormalities. Neurologists need to get on board to provide interdisciplinary expertise to CCSVI studies. After all, whatever the results of the research, positive or negative, answering these questions can only be in the best interest of their patients.

CCSVI has come a long way, but there is still a long way to go. Thankfully, the pace of CCSVI research is gaining momentum, and hopefully we will see answers to many of our questions sooner rather than later. In the meantime, my best advice is to educate yourself to the best of your ability, be your own most powerful advocate, and make treatment decisions based more on reason than emotion.

Bits and Pieces: CCSVI, Stem Cells, Big Pharma, Boobs, and A Sad Goodbye

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( For those readers who receive Wheelchair Kamikaze via email, this post contains videos, which can only be viewed on the WK website.)

As you may have noticed, I've changed the look of Wheelchair Kamikaze, more out of necessity than preference. Google's Blogger service, which hosts this blog, has been introducing new blog templates over the last year or so. Along with these new templates, some new functionalities have been added, many of which don't work with the templates originally provided by the Blogger. One of these new functionalities provides an easy way to reply to individual comments left by blog readers, which I thought would be an elegant and useful tool to utilize. Unfortunately, this new function doesn't work with the old blog template that I had been using, so, after holding out for several months, I've finally switched to one of Blogger's new designs. Not so sure that I am all that thrilled with its look and feel, so I'll probably be doing some tinkering over the next several weeks. Feel free to leave your input and or suggestions on the new design in the comments section of this post if you're so inclined.

As for this edition of Bits and Pieces, I've collected some interesting links related to CCSVI, stem cell research, and a very important new law that will finally rip away the veil of secrecy that now shields the financial monkeyshines that go on between pharmaceutical companies and the physicians that they constantly court to get them to prescribe their products.

Included in the mix is a video of Suzanne Somers talking about her boobs, so let me never be accused of not providing culturally redeeming materials…

♦ On the CCSVI front, The International Symposium on Endovascular Therapy was held this past week in Miami, Florida (click here). The symposium featured several presentations on CCSVI, including data from what I believe is the first large-scale study looking at CCSVI treatment outcomes since Dr. Zamboni first published his initial findings. This study (click here), conducted in Sicily, tracked 170 patients who underwent CCSVI angioplasty. Patients were assessed by physicians prior to treatment using the standard scale to measure MS disability (EDSS), and were asked to assess their own quality of life using a 16 item questionnaire. At the three-month point post treatment, it was found that median EDSS scores fell from 4.5 to 4.0, with patients who suffered from less disability benefiting more than patients with more severe disability. Quality of life scores followed a similar pattern, indicating that patients relatively less impacted by the disease reported greater improvements than those experiencing a more advanced disease state. Since the symptoms most often cited as being improved by CCSVI treatment are fatigue, cognitive functioning, and heat intolerance, these findings do make some sense. Patients with less advanced disease (as defined by mobility issues) often find these symptoms to be their most debilitating, whereas more severely disabled patients might not find the relief of the symptoms quite so impactful. The authors of the study note that a longer observation time and a control group are needed to confirm these findings.

♦ An interesting theory out of Australia links chlamydia pneumonia infection with CCSVI (click here). According to this theory, the venous defects and anomalies found in the veins of MS patients might not be congenital (developed in the womb), but instead may be caused by chronic inflammation due to infection with the chlamydia pneumonia bacteria. According to this hypothesis, when inflammation within the vein walls subsides, it may leave behind the webs, septums, and valvular abnormalities now being found by doctors performing CCSVI angioplasty. There has long been a small but adamant group of researchers (led by a research team at Vanderbilt University) and patients who believe that MS is caused by chlamydia pneumonia, and some of these patients have successfully treated their disease using a long-term course of combination antibiotic therapy. More info on the link between MS and CPN can be found that CPNhelp.org (click here).

The proposed link between CPN and CCSVI certainly opens the door to new areas of investigation, and highlights just how much there is left to be learned about CCSVI and its relation to multiple sclerosis. What initially seemed to be a relatively simple hypothesis with a fairly straightforward minimally invasive surgical solution is now slowly being understood to be more complex than we had originally anticipated. The treatment protocol used to alleviate CCSVI is still a work in progress, with the techniques used varying greatly from physician to physician, and the results experienced by patients who undergo the procedure varying widely as well. Unfortunately, very little scientifically valid tracking of patient results has thus far been done, so most of our evidence remains anecdotal. The discovery of the vascular abnormalities associated with MS, now called CCSVI, is, I think, an extremely important one, but it's becoming increasingly clear that CCSVI is a part of a bigger MS puzzle, one that includes not only vascular issues but also genetic predisposition, infectious exposures, and environmental factors as well.

♦ The coming 6-12 months should bring important research data from ongoing CCSVI studies, information that very well could raise as many questions as it answers, as is so often the case with scientific investigation. The upcoming second annual International Society for Neurovascular Disease (ISNVD) meetings will be held in Orlando, Florida from February 18-22nd, and should bring with it a veritable smorgasbord of CCSVI findings (click here). For those readers in the Central Florida area, a patient information program is being held on February 18 at the Orlando Hilton, and registration is now open for the event (click here). Please note, for those not in the Florida area, registration for a live webcast is also available, at the link previously provided.

♦ Here's a chance for you to get involved in CCSVI activism. Activist Karen Golden Oronte has started a letter writing campaign to members of the US Congressional MS Caucus. A list of Congress members to write to, as well as tips on what points to make in your letter, can be found on the always informative CCSVI in MS Facebook page (click here). Compared to coverage in other countries, CCSVI has received very little attention here in the US (strangely so, actually), and this letter writing campaign is a great idea for raising awareness of the issue amongst our elected representatives. So write a letter and use the tools of democracy to make our voices heard. Power to the people, right on!

♦ It seems there has recently been a palpable uptick in the number and pace of advancements being made in the field of stem cell research. One early stage study was recently completed on patients suffering from SPMS, using autologous (taken from the patients themselves) mesenchymal stem cells infused into the patient intravenously (click here). Although the study was small (10 patients) and primarily aimed at assessing the safety of this kind of stem cell treatment, it also assessed the impact of the treatment on some of the visual deficits experienced by the patients involved. After 10 months researchers were able to document several physiological improvements in the treated patients.

♦ An interesting study done on mice demonstrated that exposing older mice with MS like nervous system damage to blood taken from younger mice activated stem cells resident in the central nervous systems of the older mice, resulting in nervous system repair (click here). Although this research is in its earliest stages, this may point the way to therapies that allow the stem cells that are resident in all patients to someday be stimulated to regenerate nervous system damage done by diseases like MS. In early MS, stem cells that are already a part of the nervous system can effectively repair damage done to myelin, but this ability decreases with age and time afflicted with the disease. In this study, exposure to youthful blood increased myelin regeneration in older subjects.

♦ Another group of researchers were for the first time able to convert umbilical cord stem cells into oligodendrocytes, the central nervous system cells that produce myelin (click here). This is a very important advance, as stem cells specifically targeted at central nervous system damage would, in theory, be more effective at repairing this damage than generic stem cells when transplanted into a patient. The use of umbilical cord cells circumvents all of the moral and ethical controversies surrounding the use of embryonic stem cells, and research on these cells, as well as on adult stem cells, offers the greatest promise for rapid deployment into a clinical setting.

♦ As an American male who was a teenager in the 1970s, I can attest to the incredibly powerful effect that the jiggling Suzanne Somers, star of the sitcom Threes Company, had on the raging hormones of red-blooded American males of the era. I'm not too proud to admit that I watched the show not for the deadpan humor of Norman Fell or the comedic timing of John Ritter, but for the substantial endowments of the young Ms. Somers, which the producers of the show put to prodigious use by packing each half-hour with as many scenes of the actress dressed in tube tops or cut off T-shirts as possible. I've been aware for the last several years that Ms. Somers has been battling breast cancer, and was extremely heartened to come across this video clip, in which she explains that she appears to be winning the battle, and that an experimental stem cell treatment helped regrow one of her breasts after breast cancer surgery. Breast cancer is serious business, as is the disfigurement its treatment can leave behind, so this was all very welcomed news. Here's Suzanne Somers, happily explaining how stem cells helped her grow a boob:




♦ Under the United States' new healthcare law, sometimes derisively referred to as Obamacare, pharmaceutical companies will soon be forced to disclose the payments they make to doctors in an attempt to increase the sales of the drugs and medical devices the companies produce (click here). Physicians are routinely paid tens of thousands of dollars in "consulting fees", are treated to all expenses paid "educational symposiums" that are most often held at luxury resorts in exotic locations (where more time is spent on the golf course than in educational conferences), and are treated to expensive dinners, all in the name of "educating" them as to the merits of a particular pharmaceutical product. Analysts have found that at least one quarter of doctors routinely taking cash payments from drug or device makers, and that two thirds accept gifts of food, including lunch for staff members and dinners for themselves.

The New York Times reports that it "has found that doctors who take money from drug makers often practice medicine differently from those who do not and that they are more willing to prescribe drugs in risky and unapproved ways, such as prescribing powerful antipsychotic medicines for children." How nice.

Under the new regulations, a website will be set up on which patients can research exactly how much pharmaceutical largess their physicians have received, and thus be able to make better informed medical decisions for themselves. All I can say is, it's about freaking time…

♦ On a very sad note, one of my favorite recording artists, the incomparable Etta James, has died. Although beset with drug abuse problems for much of her life, Ms. James had an incomparable voice, one that conveyed the deepest of emotions with a simple inflection or a throaty growl. Having spent much of my career working for a major label music company, I can attest to the fact that many of today's most lauded singing stars sound no better than you or I do when warbling in the shower (you would be shocked, believe me), their careers kept aloft by the prodigious use of electronic wizardry and slick production. Not so with Etta James, who built a career in an era when actual talent and the soul of an artist were required to achieve stardom. Sleep well Etta, your powerful essence will live forever in the hearts of many, in the form of your magnificent music.

Related articles

• Hurry up and wait for a CCSVI strategy (macleans.ca)
• Blood Vessel Condition Tied to MS, with Caveats (nlm.nih.gov)
• Risk factors for CCSVI are similar to risk factors for developing MS, UB study shows (eurekalert.org)
• Welcome (thinkccsvi.com)

Research Roundup: CCSVI, New Drugs, and Other Items of MS Interest

The last two months have brought a deluge of MS research data, much of it coming out of October's ECTRIMS (European Council on Treatment and Research in Multiple Sclerosis) conference, this year held in Amsterdam. While the meeting was dominated by the release of drug study data (naturally), there was also tantalizing research data revealed regarding CCSVI as well as a number of other MS related matters. I'll attempt to provide a broad overview of the recent research goings-on, and will try my best to not put readers to sleep with too much scientific mumbo-jumbo. Just in case, better grab a blanket and a pillow, because I have a feeling this is going to be long…

♦ CCSVI - On the CCSVI front, ECTRIMS appears to have been the latest venue for the ongoing pissing war that's being waged between CCSVI supporters and detractors, featuring dueling research reports, most of which are entirely based on imaging studies finding greater or lesser degrees of venous abnormalities in MS patients. To my mind, the problem with all of these studies, both pro and con, is that the imaging techniques used (MRVs and Doppler sonography) are prone to technical and/or operator error, so the wide disparity in findings may more reflect the failings of the technology then the hypothesis being explored. MRVs are highly subject to artifacting, and sonography is extremely operator dependent. While time and experience has brought more accuracy to both technologies in regards to revealing CCSVI, the fact remains that the only way to assess the state of a patient's veins with a high degree of accuracy is to actually go in and explore those vessels with an invasive (minimally) catheter venography, which so far has proved impractical for large-scale study purposes, especially when it comes to subjecting healthy subjects to a potentially (again, minimally) risky procedure.

While quite a few studies were presented that refute the theory that multiple sclerosis has a vascular component (click here), some others provided intriguing finds that support the CCSVI hypothesis. The most striking of these was a small study out of the esteemed Cleveland Clinic that compared jugular and azygos veins taken postmortem from the cadavers of MS patients and healthy control subjects. This of course begs the question, can a cadaver truly be a healthy control subject? Certainly, healthy though they might once have been, at the very least they'd be terrible guests at dinner parties. But I digress… The unique aspect of this study is that investigators were actually able to hold and examine the veins in question, the only imaging technology utilized being the ever trusty human eye (presumably aided by some type of optical magnification).

Although quite small, limited to only 13 subjects, the study hints at some rather dramatic trends (click here). The researchers looked at the veins of 7 MS and 6 non-MS subjects, and found a variety of structural abnormalities and anatomic variations. Interestingly, vein wall stenosis (narrowing) occurred in equal numbers among the MS and non-MS samples. More prevalent in the MS veins, though, were abnormalities involving malformed valves and anomalous membranes (structures such as webs and septums that shouldn't be there) which could lead to disrupted blood flow. These types of abnormalities would be difficult to spot using noninvasive imaging methods, casting further doubt on studies reliant strictly on traditional MRV in particular, and also Doppler sonography unless the operators were well-versed in protocols specifically designed reveal such anatomic irregularities.

The findings of this study, if borne out by future, larger investigations, could shed light on the wide disparity in benefit (or, often, lack of benefit) experienced by those who have undergone CCSVI venoplasty (click here for a terrific discussion of this, written by Julie Stachowiak of about.com). Many CCSVI treatment procedures, especially those done within the first year or so after knowledge of CCSVI hit the mainstream MS population, concentrated primarily on areas of venous narrowing, which the Cleveland Clinic findings suggest are not as abnormal as first thought. Since these narrowings were seen in equal numbers among MS and non-MS subjects, they may fall within the parameters of normal anatomic variation, and have little actual significance.

The high prevalence of malformed or misplaced valves and other anatomic structures within the veins of MS patients, on the other hand, could very well prove to have considerable import. Although the goal of CCSVI treatment has in large part shifted away from simply expanding narrowed veins and moved more towards clearing malformed or otherwise broken valves, aberrant membranes  would in many cases be difficult to treat using the balloon venoplasty techniques currently employed to address CCSVI. In theory, some of these treatments may have coincidentally alleviated the effects of such abnormal membranes by disrupting them and compressing them against the vein walls of treated patients. If this were the case, and these membranes eventually returned to their original form, this might explain the far too common phenomenon of restenosis experienced by patients treated for CCSVI. The failure to properly treat malformed valves and abnormal and misplaced membranes within the veins might also explain the failure of CCSVI treatment to significantly benefit many of those who have undergone treatment. This of course assumes that the MS-CCSVI link exists, which despite a growing body of anecdotal evidence, still needs to be confirmed by scientifically robust studies.

The Cleveland Clinic cadaver study certainly illustrates how little we still actually know about CCSVI and the proper way to treat it, and that some of the initial assumptions upon which treatment methodologies were based might have been misguided. Certainly, should CCSVI prove to be a vital piece of the MS puzzle, CCSVI venoplasty techniques must be refined, and very likely equipment and devices specifically designed to treat the condition effectively need to be developed and put on the market. As I've mentioned in previous posts, the study and treatment of CCSVI is still in its infancy, and patients and physicians alike need to be careful not to put the cart before the horse, despite the tremendous amount of hope and excitement that CCSVI has generated.

Another interesting CCSVI research project, conducted by the Buffalo Neuroimaging Analysis Center (BNAC) looked at the phenomenon of CCSVI in healthy patients, and attempted to identify risk factors that might be involved in the development of the condition (click here). BNAC has imaged hundreds of MS patients and healthy controls, and found that CCSVI is present in roughly 25% of non-MS subjects. By pinpointing the factors that might lead to the development of CCSVI in otherwise healthy people and cross-referencing these with known risk factors for MS, the relationship between CCSVI and MS might better be assessed.

Since a picture is said to be worth a thousand words, I suppose a video made up of moving pictures would be worth several million words, so, in the interest of saving you pages and pages of reading, here is the head researcher at BNAC, Dr. Robert Zivadinov, discussing the results of this study:






Indeed, the findings of this study are fascinating, in that many of the known risk factors of MS (particularly infection with the Epstein-Barr virus) also seem to be prevalent in healthy subjects who exhibit CCSVI when subjected to noninvasive imaging techniques. As Dr. Zivadinov stated, study findings such as these only emphasize the need for continued, multidisciplinary research into the CCSVI-MS connection. My e-mail inbox sees a steady flow of notes from patients who have benefited from CCSVI treatment, but also a disturbingly high number of reports from patients disappointed in the lack of results they've experienced. The CCSVI story has only started to be written, and with more research results set to be released in the coming months, our knowledge of the condition should expand exponentially.

Perhaps the most well-known MS sufferer to undergo CCSVI treatment is Montel Williams, who recently discussed his experience in this video with the celebrity physician Dr. Oz. Unfortunately, Dr. Oz gets some of the particulars about CCSVI treatment wrong, but there certainly is value in Montel's testimony. Here is Montel's story, in his own words:





♦ Pharmaceuticals -some late stage MS drug trial results have been released recently, most describing extremely positive results. Disparaging Big Pharma is a favorite pastime of mine, and I think the pharmaceutical companies deserve all the disparaging they can get, due to their sometimes devious and deceitful ways of doing business, and their iron grip on most of the medical research that takes place in the USA. Unlike some other MS advocates, though, who disparage all Big Pharma MS products as snake oil, I've come to realize the value of the ever-expanding arsenal of disease modifying drugs. Though none of them offers anything close to a cure, for those patients who find them effective, they do increase quality of life, sometimes dramatically so. Of course, many of them do come with a laundry list of frightening potential side effects, but by reducing relapse rates and in some cases alleviating the burdens of disability, the current crop of disease modifying drugs has been a godsend to the patients on whom they are effective. Hopefully some of the newer compounds on the horizon will be all the more effective while at the same time limiting deleterious side effects.

One of the most promising new compounds is BG 12, an oral MS drug being developed by Biogen. Also known as oral fumarate, BG 12 has been shown in late stage phase 3 trials to not only dramatically decrease relapse rates and the number of lesions seen in the MRIs of treated patients, but also appears to significantly delay the progression of the disease in some patients (click here). Research results showed that BG 12 reduced relapse rates by 50% when compared to placebo, and also reduced the risk of disease progression by 38% over placebo. The drug works in a way very different than any existing MS medication, by suppressing pro-inflammatory factors called cytokines, and possibly providing some protection against nerve cell death. Encouragingly, the drug also appears to have a very benign side effect profile, with the most common side effects being gastric disturbances and diarrhea. The drug does not appear to open patients up to opportunistic infections or cancers, as do some of the other available MS pharmaceutical therapies. Given that BG 12 is an oral drug that seems to be very effective, and carries with it a relatively benign side effect profile, I expect this drug may prove to be very popular with patients and the doctors who treat them.

Genzyme announced the results of phase 3 trials of the drug Alemtuzumab, which was previously known as Campath and will be marketed under the name Lemtrada (click here). This very powerful drug is given intravenously, with infusions once a day for 5 consecutive days for the first treatment and then, a year later, 3 infusions during 3 consecutive days. Lemtrada severely depletes the human immune system, acting on both lymphocytes and monocytes, which are then reconstituted by the body, resulting in permanent changes in the immune systems of patients treated with the drug. In effect, Lemtrada "reboots" the immune system, in the hopes that the reconstituted immune system will no longer attack a patient's own nerve cells. Trial results showed Lemtrada to reduce relapse rates by 49% when compared to patients taking Rebif, along with a 42 percent reduction in the risk of sustained accumulation (worsening) of disability as measured by the Expanded Disability Status Scale (EDSS). Previous trials have shown that the effects of Lemtrada are very long-lasting, with patients showing significant benefit five years after initial treatment ended (click here). However, while these results are very impressive, Lemtrada does carry with it the risk of some serious side effects. About 16 % of treated patients develop autoimmune thyroid disease, and 1% develop a potentially lethal autoimmune blood disorder known as ITP. Because of this, patients using the drug must be carefully monitored, and use of Lemtrada may be limited to patients with highly active disease. Research is currently underway to develop ways to identify patients most at risk for the autoimmune side effects of Lemtrada, to more easily identify patients who should be excluded from this treatment option (click here).

The potential MS vaccine Tovaxin has been granted fast-track status for the treatment of SPMS by the FDA (click here). Fast-track status can cut in half the time it takes a drug to be approved, and if Tovaxin does eventually get such an approval, it will only be the second drug specifically approved for the treatment of secondary progressive multiple sclerosis in the United States. Tovaxin is a compound individualized for each patient, which desensitizes a treated patients immune system T cells to their own nerve cells, thereby stopping the autoimmune reaction (click here). Several years ago, Tovaxin failed to meet the goals of its phase 2 trials (click here), and although it had shown great promise, was left for dead. The company developing it, Opexa, later re-examined the failed trial data and determined that Tovaxin had indeed demonstrated positive effect, and now Tovaxin has risen like Lazarus, giving it (and Opexa's stockholders) new life…

A study done to assess the risk of stopping Tysabri for "drug holidays" showed that this practice significantly increases the risk of patients suffering MS relapses within six months after stoppage (click here). The idea of drug holidays came about because Tysabri is linked with PML, a potentially fatal brain infection, the risk of which increases with the amount of time a patient is on Tysabri. It was thought that taking occasional breaks from Tysabri might allow the immune system to reconstitute itself enough to combat the emergence of PML, but this study suggests that temporarily switching to another MS therapy unfortunately carries with it an increased risk of patients suffering an MS relapse. Kind of a "damned if you do, damned if you don't" scenario…

♦ Miscellaneous Studies - A variety of other MS related research results have also recently been announced. The active ingredient in the spice saffron may prove to be effective in combating MS (click here). In experiments, this ingredient was shown to combat inflammation and cell stress, at least in petri dishes and test tubes. Interestingly, saffron is often used in Asian cuisines, and the incidence of MS is much lower in Asian countries than it is here in the West. The spice tumeric (cumin) has also been shown to have strong anti-inflammatory properties, and this spice too is used heavily in some Asian cuisines. So go out and have some Indian food, it's good for you. Chicken Tikka Masala, yum…

Researchers in Sweden have discovered that young people between the ages of 16 and 20 who work overnight shifts or odd hours are twice as likely to develop multiple sclerosis as those who never worked such hours (click here). The researchers explained the sleep restriction associated with working the night shift has already been shown to increase the risk for certain health problems, including heart disease, thyroid disorders and cancer, likely by interfering with melatonin secretion and increasing inflammatory responses. Kind of an odd finding, but upsetting circadian rhythms has been shown to have an adverse effect on health, so these Swedish meatballs might be on to something…

German researchers have linked gut bacteria to multiple sclerosis (click here). We all have millions of microbes living in our guts, normally to no ill effect. However, more and more research links these bacteria to some autoimmune diseases. The researchers who did this study used mice genetically engineered to develop a Multiple Sclerosis like disease, and allowed some to develop gut bacteria, and others to remain gut microbe free. About 80% of the mice with gut bacteria went on to develop MS like symptoms, while none of the sterile mice did. While it's a far cry to go from mice to humans, this study does demonstrate that intestinal microbes do interact with the immune system, something that has long been suspected. Of course, most of the bacteria are in our guts is harmless, and some even serve a beneficial effect, but these research results certainly warrant further investigation.

Well, let's call it a wrap. There's an astounding amount of MS research being conducted, much of it driven by the huge profits to be made treating MS patients with hyper expensive drugs that tamper with the little understood human immune system. Still, as is evidenced by the last few investigations I mentioned, the breadth of MS research is quite wide, and each bit of knowledge uncovered may hold the key that finally unlocks the puzzle that is MS. Certainly, research into CCSVI has the potential to upend much of the conventional wisdom regarding the disease, and it's of the utmost importance that MS patients themselves drive such research forward, by educating themselves, advocating for energetic and innovative research into the disease, and agitating against those who stand in the way. Power to the people, y'all…

Related articles

• Risk Factors For CCSVI Are Similar To Risk Factors For Developing MS (medicalnewstoday.com)

A Few Bits, a Couple of Pieces, and a Happy Thanksgiving to All…

With Thanksgiving week upon us, I'm going to keep this one relatively short. Stay tuned, though, as next week I plan on posting a review of the latest in MS research, as there's been lots of important info released over the past six weeks or so. I'll cover the latest news on CCSVI, disease modifying drugs, and other MS research findings, along with the usual few dollops of opinion tossed in.

Please, don't let the inevitable tremendous anticipation of next week's post distract you from enjoying the holiday festivities. As difficult as it may be, try to stay focused on the turkey.

For those readers outside of the United States, who don't celebrate Thanksgiving this week, you'll just have to find something else to occupy your time. My European friends can busy themselves with happy thoughts about figuring out how to survive the impending collapse of the continent's economic system. Actually, we all can probably occupy our minds with such thoughts, as things aren't so hot in the US or Asia either.

WK readers in Canada, whose relatively sane economic policies have spared that country much of the turmoil roiling the rest of the world, will have to find some other distraction. Since Canadian Thanksgiving was last month, perhaps thoughts of hockey will have to suffice, or finding new and entertaining uses for maple syrup. It'll be hard to beat Sortilege (click here), though, which for the uninitiated is some pretty strong hooch made with maple syrup. BTW, kudos on the Canadian national anthem. As far as national anthems go, "Oh Canada" kicks major booty…

Okay, I said I was going to keep this short, and it's already getting long, so on with the show…

♦ A neuroimmunology researcher from the Scripps Institute sent me a note alerting me to an online petition she has started (click here), urging the US government to devote more funds to basic biomedical research at the National Institutes of Health.
 
I agree with her sentiments wholeheartedly, as the NIH is a precious resource that can't be left to wither on the vine, and is one of the last bastions of unbiased large-scale medical research left in the USA. The vast majority of our medical research is funded by for-profit pharmaceutical and medical device companies, who naturally devote their hard-earned bucks to research that stands a chance of turning them a huge profit. Don't get me wrong, I'm a big fan of capitalism, but money and medicine often make for terrible bedfellows. Even in this time of looming budget deficits, squeezing the NIH of funds will do nothing to solve our economic problems. Consider the following numbers:

For 2011 budget, U.S. spending on:
Social security was $2564 per citizen (20.8% of the budget)
Defense was $2203 per citizen (18% of the budget)
Medicare was $1569 per citizen (12.8% of the budget)
Medicaid was $1172 per citizen (7.8% of the budget)
NIH was $99 per citizen (0.8% of the budget)

Certainly, the funding of medical research is one of the last places we should be looking for savings. Finding newer and more effective treatments and even cures for dread diseases would pay huge dividends in the long run, both in human capital and reduced health care costs. I would think this issue is something that rational citizens across the political spectrum should be able to agree on. So please sign the petition…

♦ I recently came across an interesting new medical information website, called Medify.com (click here). The site offers links to lots of research abstracts and papers, along with patient to patient communities. A wonderful source of medical info, some of it otherwise hard-to-find, well worth checking out.

♦ Saving the best bit of medical info for last, here's some extremely exciting news: one of the nation's first multiple sclerosis stem cell therapy trials has been given the green light (click here), and should be soon underway. The Multiple Sclerosis Resource Center of New York (MSRCNY), in conjunction with the International Cellular Medicine Society (ICMS), will be conducting a 20 subject trial on patients with a definitive diagnosis of progressive MS, using mesenchymal stem cell derived neural progenitor cells, harvested from the patients' bone marrow, in an attempt to regenerate damaged nervous system tissues.

The director of the MSRCNY, Dr. Saud Sadiq, is my personal neurologist, and I know firsthand that his research facility, staffed with world-class scientists from around the world, has been hard at work for many years doing groundbreaking research in preparation for this trial. Stem cell therapy offers tremendous hope for MS patients, as it holds the promise of actually repairing the damage done by MS and restoring function lost to the disease. Let's all hope this first trial is a resounding success, one from which we all may reap tremendous benefit in the years to come. The trial is set to run for three years.

♦ I leave you with the following piece of eye candy (it's not hard on the ears, either), which is simply breathtaking. It takes 30 seconds or so to really get going, but be patient, and you'll be amazed by a stunning natural phenomenon, created by nothing more exotic than a flock of starlings…



Murmuration from Sophie Windsor Clive on Vimeo.


 

Happy Thanksgiving! Gobble, gobble…

Related articles

• NIH Seeks Advice on Budget Crunch (news.sciencemag.org)

Bits and Pieces: End of Summer Edition

Image by Claudio.Ar via Flickr

Well, here's another collection of various items of interest (well, at least of my interest), most of which have something to do with MS, and none of which have anything to do with the end of summer. Just thought I'd note that the seasons have changed once again, and we are now officially in autumn, my favorite time of year.

Time just whizzes by, doesn't it? I've noticed that the older you get, the faster time seems to pass, so much so that it becomes increasingly difficult to get your arms around the quickly passing days, and events unfold at breakneck speed. Remember when the two-month summer vacation from grade school seemed like an eternity, filled with innumerable dramas and intricate subplots? Now two months seem to pass in the time it takes me to let out a good yawn.

Just goes to show how subjective is our existence. I suppose this ever increasing sense that time is speeding up has something to do with the fact that as we get older, each increment of time becomes a lesser part of our lives. For example, a two-day-old infant experiences a single day as 1/2 their lives, whereas, at 48 years old, a single day represents 1/17520 of my existence. All the more reason to try to make the most of your remaining time on earth, and here I've gone and completely wasted about a minute of your precious, ever dwindling allotment of life. Please forgive me.

With that, my latest collection of flotsam and jetsam…

♦ Researchers have discovered that the brains of MS patients show a marked deficiency in substances known as Neuro-Steroids (click here). Neuro-Steroids help build brain cells and maintain their function, thus increasing their levels in patients deficient in them might not only stop MS in its tracks, but also actually repair some of the damage that the disease does to the central nervous system. Better still, drugs designed to increase the level of Neuro-Steroids are already being trialed for use in combating epilepsy and depression, meaning that, if successful, Neuro-Steroid drugs could be on the market much quicker than a newly discovered compound that has yet to hit the trial pipeline. Of course, this research is still in its early stages, but it does seem quite promising.

♦ In other drug-related news, researchers have figured out a way to deliver drugs across the blood brain barrier, an obstacle that has inhibited the treatment of many central nervous system diseases throughout the history of medicine (click here). The blood brain barrier functions to keep the brain and spinal cord out of harm’s way by carefully selecting just what substances can cross from the bloodstream into the CNS, much like the doorman at an exclusive nightclub picks and chooses amongst the riffraff clamoring to get in, only allowing entry to the anointed few deemed worthy of such a privilege, a practice that made me want to vomit even back in the glory days when I was "fortunate" enough to be one of those deemed worthy. Anyway, researchers have now figured out a way to open a temporary window in the blood brain barrier, potentially paving the way for a new level of efficiency in treatments designed specifically for central nervous system disorders.

♦ Researchers in Japan have discovered a high-tech method of analyzing cerebral spinal fluid (CSF), allowing for the differentiation between MS and other neurologic diseases (click here). This could be hugely important, as currently there is no test specific for MS, making it a diagnosis by exclusion. In other words, doctors diagnose MS primarily by eliminating other possible causes of a patient's symptoms and diagnostic test results, a process which results in a fairly wide margin of error and a misdiagnosis rate of about 5%-10% . That's right, for every 10 people reading these words, there's a good chance that one of you has been misdiagnosed. So put that in your pipe and smoke it.

♦ A bit of bad news, as simvastatin (otherwise known as Zocor) has been found to be ineffective as a treatment for MS (click here). Four or five years ago there was much buzz about the statin drugs (commonly used to treat high cholesterol) possibly being of use in the treatment of MS, potentially as an add-on to be used in addition to other therapies, but recent research results have been disappointing.

♦ In CCSVI related news, the Buffalo Neuroimaging Analysis Center (BNAC) published a comprehensive overview of all of the CCSVI research that has been done to date. The BNAC Patient Advisory Council, of which I am part, put together an easy-to-read digest distilled from the much longer piece, written specifically with patient education in mind (click here). It's done in a question-and-answer format, and should provide a nice overview of the current state of CCSVI knowledge.

♦ The Canadian province of Saskatchewan this week announced that it will be sending MS patients to Albany, New York to participate in a CCSVI treatment clinical trial (click here). Although CCSVI research is not moving along as fast as many of us wish it would, in actuality the pace of research is quickening and gaining momentum, and hopefully we will soon start to reap the benefits of that research.There is still far more about CCSVI that we don't know than we do, and getting those questions answered, dither pro or con, in the quickest possible fashion is in the best interests of all, regardless of their stance on the hypothesis.

♦ For those interested in a comprehensive and extremely well researched and well-written account of the history of the CCSVI hypothesis and the science behind it, a terrific resource is the book "CCSVI As the Cause of Multiple Sclerosis" (click here), written by Marie Rhodes, a nurse and MS patient who was at the forefront of the CCSVI movement when it was in its early infancy. The book offers a wealth of knowledge, and is even available in a Kindle version.

♦ The Multiple Sclerosis Association of America (MSAA), a terrific organization that does much to aid MS patients, is offering a couple of interesting programs that caught my eye. The first is a webinar series designed to instruct patients on taking care of their financial well-being (click here), an incredibly important topic given the fact that so many of us are either already on disability or are contemplating a potentially financially treacherous future out of the workplace. The first webinar, "Being Money Smart", is scheduled for October 6, so sign up now!

The second program is the MSAA's Annual Art Showcase, which is now accepting submissions (click here). This year's theme is "Change", and artists are encouraged to interpret this theme as creatively and broadly as they wish. The showcase is limited to two dimensional art, and doesn't include photography (boo!).

♦ For those interested in the alternative treatment Low Dose Naltrexone (LDN), Julie Stachowiak, who writes About.com's invaluable weekly column on MS, has been keeping a diary of her recent foray into the world of LDN (click here). Naltrexone is an old drug that is used to treat various addictions, but in very low doses it has been purported to alleviate the symptoms of MS and a variety of other diseases. Anecdotal accounts seem very encouraging, with many patients reporting significant improvements while taking LDN. I tried LDN early on in my MS adventures, but found it didn't do anything for me. Of course, I'm not the best example to go by, since my diagnosis is quite uncertain (click here).

Unfortunately, because Naltrexone is an off patent drug it's cheap and there's not much money to be made from it, so very few if any scientifically valid clinical trials have been done to test its efficacy on MS patients. Just another of the many travesties visited upon chronically ill patients worldwide by a medical research system driven more by the quest for profit than by the desire to alleviate the misery of millions. Harrumph.

♦ Researchers in Scotland have found that marriage between cousins is not to blame for the high rate of MS found in that region (click here). Scotland has one of the highest rates of MS in the world, approximately 1 in 500, and the islands in which the study was conducted, Orkney and Shetland, have rates higher still. Far be it for me to cast judgment, so all I'll say to those contemplating marrying a close relative is that you can put any fears about your future children being predisposed to developing MS to rest. As for fears about extra limbs, or eyeballs in the middle of their foreheads, well, that's another story…

♦ In a sad bit of news, a lion suffering from Multiple Sclerosis like symptoms in Brazil died this past July (click here). Apparently, the plight of Ariel the lion touched the hearts of many, and his story was chronicled on his own website and Facebook page. Since I believe in a just universe, I'd like to think that Ariel is now in lion heaven, where he is using his fully functional claws, paws, and powerful legs to viciously maul and tear to pieces all of the naughty wildebeests and zebras who were sent to wildebeest and zebra hell. For everything, there is a season…

As Porky the Pig might say, th-th-th-that's all folks…

A Patient's Perspective on CCSVI, in Words and Pictures (Part Four)

On July 15, 2011 it was my honor to give a presentation at the Patient Information Day of the Second Annual CCSVI Update Symposium, held at the Crowne Plaza Hotel in Times Sq., New York City. The organizer of the symposium, Dr. Salvatore Sclafani, asked me to write an essay for oral presentation on "A Patient's Perspective on CCSVI", using some of the photographs I've taken from my wheelchair mounted camera to illustrate my talk. I've posted the resulting essay here in four parts, spaced a few days apart. Here's the finale, part four (click here for part one, part two, or part three):

This is one of my favorite photos that I've taken from my wheelchair. It was taken in Central Park, in an especially beautiful section called The Conservatory Gardens. The gardens are truly spectacular, and I'd urge anyone who has the chance to visit them to do so, especially in spring or autumn, when they are bursting with color.

For me, this photo embodies two key elements, freedom and patience. While the element of freedom may be easy to discern, the patience involved in taking the photo is probably harder to detect. When I first discovered this fountain, adorned with sculpted sparrows, I also saw real-life sparrows utilizing it as a birdbath, just as the artist intended. I found the juxtaposition of the inanimate and live birds striking, and hoped to capture a moment that would illustrate the coming together of nature and such a graceful example of the power of the human imagination. In order to capture the fleeting moment caught in this frame, I sat in one spot for about an hour and a half, taking literally hundreds of photos, systematically shooting pictures in rapid-fire mode every time a bird took off or landed. Luckily for me, one of those hundreds of photos turned out to be this one. Patience does have its rewards.

When it comes to the pace of CCSVI research and treatment, I completely understand how difficult it can be to be patient. Those of us suffering from chronic, progressively disabling disease know all too well that the clock is ticking. Any youthful notions of immortality or indestructibility were demolished the moment we were shown MRI images depicting holes in our brains and spinal cords. Stripped of such illusions, a certain desperation can set in, and the desire to do something, anything, to stave off a calamitous future takes hold. This desire can manifest in many forms, from outright panic to steely determination, but every self-empowered MS patient has their radar set to scan the horizon for any new development that might save them from a dreadful end.

CCSVI certainly holds the promise of potential salvation. This radical new approach to looking at MS, offering fundamentally new ideas about how to treat the disease, gives the afflicted a life ring to grab onto, a ring plainly inscribed with the word Hope. But we are yet in the early stages of our understanding of CCSVI and how best to treat it. The treatment procedure I underwent a little bit over a year ago is far different than the procedures being done today, and procedures being done a year from now will likely be more different still. Therefore, while no one could argue with any patient choosing to pursue treatment now, for some the decision to be patient and wait cannot be viewed as a terrible choice. Sometimes, the race does go to the swift, but there are times too that discretion is the better part of valor.

As for the other element prominent in this photo, freedom, well, that is what I wish for every MS patient, everywhere. Freedom from the fear that we wear as a second skin, freedom from the cognitive deficits that threaten to steal our very essence, freedom from the braces, canes, scooters, and wheelchairs that that we use to compensate for our damaged bodies, freedom from the grip of a medical establishment that all too often seems more designed to seek profits than cures. Let us all someday soon alight like birds from a fountain, our sweetest dreams come true, and our fondest desires realized.

A Patient's Perspective on CCSVI, in Words and Pictures (Part Two)

On July 15, 2011 I was honored to give a presentation at the Patient Information Day of the Second Annual CCSVI Update Symposium, held at the Crowne Plaza Hotel in Times Sq., New York City. The organizer of the symposium, Dr. Salvatore Sclafani, asked me to write an essay for oral presentation on "A Patient's Perspective on CCSVI", using some of the photographs taken from my wheelchair mounted camera to illustrate my talk. I'll post the resulting essay here in four parts, spaced a few days apart. Here's part two (click here for part one):

I photographed this poor soul just a few blocks away from Roosevelt hospital, on Manhattan's West Side. Judging by the hospital bracelets on his wrist, he'd obviously been newly discharged. The bracelet warning of his being a fall risk resonates in any number of ways, coming to metaphorical fruition probably within hours of his leaving the hospital.

Patients dealing with multiple sclerosis, or any serious incurable illness, are far too well acquainted with the notion of risk. From the moment of our diagnosis we are bombarded by a befuddling array of new and frightening information and faced with making with grave choices, all of which entail varying degrees of risk. I vividly remember the day of my diagnosis, when, with my head spinning with fear and confusion, I was handed a pile of videotapes and told to go home, watch them, and choose my treatment option. I felt as if I'd been handed citizenship papers to a world in which I never wanted to be part of and for which I had no roadmap or experience to draw on.

My reaction to being confronted with this new path, riddled with pitfalls and landmines, was to intensely educate myself as best I could. I quickly learned that every choice confronting the MS patient is fraught with risk. Doing nothing is obviously risky. There is a reason they call MS a progressively disabling disease. It progresses. The existing mainstream treatment options all carry some degree of risk, ranging from relatively minor flulike symptoms all the way to ghastly and deadly brain infections, and many of these drugs are of questionable efficacy at best.

Now, CCSVI has entered the picture. What at first seemed like a relatively simple hypothesis, with a relatively simple solution, has turned out to be more complicated than most expected. Instead of arcane and impossible to understand ideas about autoimmunity, many of which sound like bullshit because they very likely are, CCSVI postulates that MS is the result of disrupted blood flow through the central nervous system, a relatively easy idea to wrap your brain around. Likewise, its treatment, the opening of blocked veins through a minimally invasive procedure also seems relatively simple when compared to traditional MS therapies, all of which ominously tinker with the workings of the infinitely complex human immune system.

Unfortunately, things are turning out to be not quite as simple as first hoped. As research into CCSVI has picked up, we've been confronted with a sea of sometimes contradictory findings. The CCSVI treatment procedure itself is a work in progress, with many treating physicians reporting a surprisingly steep learning curve required to master the procedure. The techniques being used are undergoing constant refinement, with no standard of practice fully agreed upon by all of the physicians currently involved in treating CCSVI.

Please don't misunderstand me, I fully believe that there is merit to CCSVI, and that its treatment has the potential to help a significant portion of the MS population, but once again, in considering whether to undergo CCSVI treatment, the MS patient is confronted with the weighing of risk. Not all patients are helped by treatment, and those that are helped often find the benefits they receive only temporary, requiring them to undergo multiple procedures to maintain their perceived gains. A small percentage of patients suffer potentially serious side effects, including blood clots and the formation of scar tissue in their veins. There's also the cost of the procedure to consider, which can be substantial if not covered by insurance, the expenditure of which brings no guarantee of success.

It's vital that every MS patient considering any new treatment to honestly tally their own unique risk/reward calculation, and the only way to properly do this is to self-educate with all blinders off. When it comes to making decisions as vital and controversial as to when and whether to undergo CCSVI treatment, I've often found more value in listening to and understanding the opinions of those you don't agree with than to those you do. A truly well-informed patient should be intimately familiar with both sides of every argument regarding their own care and treatment.

Click here for part three…

A Patient's Perspective on CCSVI, in Words and Pictures (Part One)

On July 15, 2011 I was honored to give a presentation at the Patient Information Day of the Second Annual CCSVI Update Symposium, held at the Crowne Plaza Hotel in Times Sq., New York City. The organizer of the symposium, Dr. Salvatore Sclafani, asked me to write an essay for oral presentation on "A Patient's Perspective on CCSVI", using some of the photographs taken from my wheelchair mounted camera to illustrate my talk. This was a challenging proposition, since none of my photos were taken with MS or CCSVI in mind, but the presentation turned out well, and I was not pelted with rotten vegetables or garbage, as I feared. I'll post the resulting essay here in four parts, spaced a few days apart. Here's part one:

This photo is of an abandoned structure on the Manhattan side of the Hudson River, known as the 69th St. Transfer Bridge. Built in 1911, during its heyday, when Manhattan's Riverfront was teeming with industrial activity, the structure was used to transfer railcars onto barges for trips to freight ships or across the Hudson to rail lines in New Jersey. It is now listed on the National Register of Historic Places.

I've long found this derelict structure to be captivating, and have often felt a sort of kinship towards it. Like me, the transfer bridge once stood tall and strong, hard-working, perfectly in sync with the beehive of action that surrounded it. Now wrought immobile by rust and decay, the transfer bridge is a stubborn old beast, still able to grab attention in spite of its diminished state.

Like many of my MS brothers and sisters, I too can no longer function as I once did. Instead of rust doing its insidious damage to the hard steel of the bridge, a mysterious disease process now does ongoing injury to the all too soft tissues of my central nervous system, creating neurologic deficits that in eight short years have left me spending much of my time sitting in a wheelchair. But, like this structure, I too refuse to go quietly into the night, and hope, through words and images, to at the very least give voice to the stresses, frustrations, and emotions that come part and parcel with having a progressively debilitating chronic illness. In my fellow patients, I've met countless individuals whose guts, courage, and spirit inspire me, and whose determination to live fulfilling lives in spite of the disease should serve as lessons to us all, sick and healthy alike.

Of course, this photo not only depicts the long abandoned transfer bridge, but also rays of sun light bursting through a threatening cloud bank, daggers of illumination cutting through a potential source of gloom. These rays of light are akin to Dr. Zamboni's CCSVI hypothesis, giving hope to a patient population searching so desperately for answers. Despite the incremental advances made in treating the disease over the last decade or so, MS has remained a maddeningly elusive target, its victims left to choose among an array of drugs which, in varying degrees, all carry with them the risk of serious downside, and none of which offers a cure.

The source of hope called CCSVI has burst through this haze of confusion and energized MS patients worldwide, like starved seedlings suddenly exposed to a sunny day. Although still early in the game, the very promise of CCSVI has beckoned patients to organize and educate themselves, and to ask questions that were in dire need of asking.

By shaking up the status quo, CCSVI has already won a tremendous victory, and the hope it has given to many is nothing short of a blessing. But in assessing the full impact of CCSVI, we must also be careful not to be blinded by these same bright rays of hope, as investigations into CCSVI, and the methods to treat it are still in their infancy, and the full impact of the hypothesis has yet to be determined. Certainly, we have seen the CCSVI treatment procedure help many patients, sometimes dramatically, but we have also seen it be less than effective for a substantial number of those who have undergone it. In fervently desiring CCSVI to provide answers for all, we must guard against hope eclipsing reason, and understand that there is still much to be learned.

Click here for part two

Finally! Canadian Government Decides to Fund CCSVI Treatment Trials…

Image via Wikipedia

In a surprise move, the Canadian federal government has reversed its previous decision, and decided to fund CCSVI treatment trials on MS patients (click here). Just last year, government officials decided against funding such trials, citing a lack of evidence that a clear link existed between CCSVI and MS. Now, a working group of scientific advisors, after reviewing already published research in addition to the preliminary data from the seven ongoing studies funded by the MS societies of Canada and the USA, has concluded that there is enough evidence of a relationship between the vascular abnormalities collectively known as CCSVI and Multiple Sclerosis to warrant federally funded treatment trials (click here).

This is extremely welcome news to MS patients worldwide. Although treatment trials won't answer many of the scientific and medical questions surrounding the CCSVI hypothesis, such trials will determine whether catheter venoplasty, when used to open blocked veins and improve impeded bloodflow through the central nervous system of MS patients, results in an improvement of symptoms and/or a slowed progression of the disease. While academic questions such as cause and effect ultimately must and will be answered, the most pressing issue for MS patients themselves is whether or not getting treatment for CCSVI will improve their symptoms and lessen the long-term impact their potentially crippling disease.

What's of primary importance now that a mandate has been given to commence treatment trials is the design of those trials and exactly which treatment protocols will be used on the patients enrolled in them. Over the last 18 months we've learned that treating CCSVI is far less simple than was originally thought, and the physicians most experienced in the treatment of CCSVI are in unanimous agreement that the learning curve involved with perfecting the technique is steep, and the methodologies used are still a work in progress. The fact is that many of the treating physicians use quite disparate treatment protocols, and there is no clear consensus on best practices and a standardization of treatment methodology.

As CCSVI treatment has thus far been unavailable in Canada, there is an absence of Canadian physicians experienced in the treatment procedure. I trust that the scientists involved in the Canadian trials are fully aware of such issues, and that the physicians who will be performing the treatment procedures will undergo training at the hands of the experienced physicians outside of Canada who have been blazing the trail in performing what is still an experimental procedure. It's vital that these trial procedures be done using the latest and most effective techniques, as sub-optimal procedures will lead to sub-optimal results, which would be disastrous for the advancement of the science, and could easily lead to false conclusions about the effectiveness of treatment.

I would expect that the Canadian trials will not only demonstrate whether CCSVI treatment is effective, but, if it is, which symptoms are most impacted by improving venous blood flow, and which patient populations stand to most benefit from CCSVI treatment. MS is an extremely heterogeneous disease, with no two patients experiencing the malady quite the same way. A recent study (click here) by a CCSVI treatment practice in Poland found that patients most likely to benefit from CCSVI treatment are younger females (under the age of 30) with Relapsing Remitting Multiple Sclerosis, who have had the disease for relatively short amount of time and have not yet experienced severe mobility issues. Keeping in mind that the study was based on a relatively small sample size (47 patients), and the long-term effects of successful CCSVI treatment are still unknown, such data does make some sense in the context of what is known about MS pathophysiology, especially once the disease moves from its relapsing remitting form into its progressive stages.

Recent evidence has provided tantalizing clues that suggest that the progressive stages of the disease may be driven by an abnormal immune response contained entirely within the central nervous system, in a sense approximating a rogue immune system that operates separate and apart from the systemic immune system at work in the rest of the body (I'll blog about this in the near future). The implications of these findings, if correct, are profound, and would suggest that once the disease enters its progressive stages, treatments that are effective in RRMS, even CCSVI, may be rendered useless, as they do nothing to address an aberrant immune response that is contained entirely behind the blood brain barrier, operating independently and completely unto itself.

Be that as it may, the MS community on the whole should loudly applaud the Canadian government for taking the bold if belated step of federally funding vitally important CCSVI treatment trials. At the very least, such trials will pry scientific attention away from its current togmatic insistence that MS is strictly an autoimmune disease confined only to the central nervous system, and see it as a systemic problem with physical implications reaching beyond the brain and spinal cord. For far too long the autoimmune model of the disease has ruled the day, generating billions of dollars of profit as it turned the treatment of Multiple Sclerosis a hugely lucrative business, while at the same time generating tangible but limited benefits to patients suffering from the disease. Let these Canadian trials be a huge step towards a new understanding of the MS, one that will lead to its final eradication and an end to the suffering of millions of patients worldwide.

CCSVI and MS: Cause, Effect, or Neither?

Image by Getty Images via @daylife

It's now been over 18 months since the news of Dr. Zamboni's vascular theory of MS, the CCSVI hypothesis, first made its way into the consciousness of the greater Multiple Sclerosis patient population. Touched off by news reports on Canadian television channel CTV, an inferno of hope raced through MS patients worldwide, and a firestorm of controversy regarding almost every aspect of the hypothesis was ignited, a conflagration that seems to only burn more intensely with each passing week. The relatively simple CCSVI hypothesis (which postulates that blockages in the veins draining the central nervous system lead to or contribute to the MS disease process) has managed to pit physician against physician, physician against patient, and patient against patient. While the various factions duke it out, an estimated 15,000-20,000 MS sufferers have undergone CCSVI venoplasty, with a wide variety of resulting outcomes, ranging from dramatic benefit to no benefit whatsoever to, in rare cases, a worsening of disease symptoms.

Several key questions have emerged regarding CCSVI during the last year and a half, primary among them whether or not CCSVI and MS have any link whatsoever, and if so, whether the venous anomalies collectively known as CCSVI are the cause or an effect of the disease. We've seen a steadily increasing flow of CCSVI research results, providing enough conflicting data to fuel all sides of the argument. As with all things Multiple Sclerosis, CCSVI presents a complex picture, and despite evangelical believers/nonbelievers on all sides of the squabble, at present the ultimate outcome of the CCSVI conundrum is as clear as mud. Here then is a brief look at some of the issues currently being batted about, with some small attempt on my part to make some sense of it all.

My personal belief is that CCSVI and MS do indeed have a relationship, at least in some MS patients. However, I acknowledge that my opinion is based primarily on anecdotal evidence, and anecdotal evidence alone is not enough to state anything with scientific certainty. Despite the insistence of many in the CCSVI advocacy community, the link between CCSVI and MS has not yet been established with evidence that measures up to the scientific standard. On its face, the basic premise of CCSVI, that restricted blood flow through the central nervous system, caused by vascular abnormalities that are very likely congenital, slowly cause damage to the CNS over the course of decades, eventually becoming significant enough to result in a clinical diagnosis of Multiple Sclerosis, seems simple and makes perfect sense. Yet upon closer inspection, the picture is not quite so clear-cut.

There have been several very convincing studies demonstrating that venous abnormalities now known as CCSVI occur more often in MS patients, and even in patients with other neurologic diseases, than in healthy control subjects. Conversely, there have also been quite a few studies disputing this. Almost all of these studies, pro and con, have relied on noninvasive imaging techniques (Doppler ultrasound or MRV) to ascertain the presence of these abnormalities. Unfortunately, neither of these noninvasive imaging techniques has proven to be entirely accurate, though Doppler ultrasound, in the hands of a skilled and well trained technician, does appear to be the more reliable of the two techniques. Still, we have research groups reporting widely divergent findings, and some of that divergence could possibly be attributed to the relative inaccuracy of the diagnostic methods being utilized.

Complicating matters further is the fact that human venous anatomy, with a few exceptions, has been very little studied. So little, in fact, that no clear-cut definition of "normal" exists when it comes to the anatomy of the veins that drain the central nervous system. It had previously been assumed that since the veins in question had so many built-in redundancies, any blockages encountered would be easily compensated for. While the Interventional Radiologists performing the CCSVI treatment procedure are reporting that the overwhelming majority of MS patients are indeed displaying a large number of venous abnormalities, we cannot state with any certainty that a significant portion of the healthy population does not also present with such abnormalities.

What are desperately needed are trials using catheter venography to ascertain the prevalence of CNS venous abnormalities in healthy control subjects. However, there are some ethical questions involved in performing this minimally invasive procedure simply for research purposes. Although the risk is low, catheter venography, like any invasive procedure, does carry with it the potential for dangerous complications, and the prospect of exposing healthy subjects to these risks has inhibited such studies from taking place. Until it can be established beyond dispute that vascular abnormalities in the jugulars, azygos, and other veins that drain the CNS are more prevalent in MS patients than in the general population, the question of the CCSVI/MS relationship will not be put to bed.

Let's assume, though, based on the anecdotal reports, that there is a connection between CCSVI and MS. The big question then becomes whether CCSVI is the cause of the disease, or an effect of the Multiple Sclerosis disease process. Again, there is enough conflicting data to support both sides of the argument.

Those who support CCSVI as the cause of MS site several compelling reasons for their belief. One of these is that many of the abnormalities being seen in the veins of MS patients, such as anomalous membranes and fused valves, appear to be congenital in nature, that is, patients have had them since birth (click here). If these defects are congenital, and occur in greater preponderance in MS patients than the healthy population, it would seem reasonable to assume that they play a causative role in MS disease etiology. Another argument in favor of CCSVI as the cause of MS is the growing body of evidence that suggests that nervous system tissues in MS patients are damaged before the immune system comes into play (click here for one such study), findings that would seem to contradict the prevailing theory of MS, the "autoimmune theory". The autoimmune theory states that, for reasons unknown, the immune systems of MS patients go rogue and start attacking the patients' own central nervous system tissues. If some studies done within the last decade are correct, and CNS damage occurs before immune system involvement, this would apparently discredit many of the basic assumptions of the autoimmune theory, and CCSVI provides an explanation as to how this damage occurs.

While I've long held the autoimmune theory in contempt, and I'm convinced that the aberrant immune response seen in MS patients is a symptom of some larger underlying and as yet undiscovered cause, I'm not sure that cause is CCSVI. While the CCSVI hypothesis does in some ways elegantly account for some of the mysteries surrounding MS (the venocentric nature of MS lesions, the reduced volume of blood flow through MS brains, etc.), it does not account for several of the more confounding aspects of the disease. It's difficult for CCSVI to explain the geographical distribution of the MS population, which sees a far greater prevalence of MS the further away one gets from the equator (click here). Related to this geographic distribution, CCSVI also can't explain some of the migratory observations made in regard to disease prevalence (click here). When a person below the age of 15 migrates from an area of higher disease prevalence to one of lower prevalence, they take on the characteristics of their new home. When the migrant is over the age of 15, though, they retain the propensity for the disease of the area they migrated from. In other words, a person under the age of 15 migrating from Maine (high prevalence) to Florida (low prevalence) has the same low chance of getting the disease as a Florida native. However, older migrants retain the higher chance of getting the disease seen in Maine. Furthermore, children of these older migrants, born after the move south, take on the same lower chance of developing MS as children born to the native population.

Similarly, CCSVI cannot account for the existence of "MS clusters", which are small concentrations of population in which MS appears to be epidemic (click here). The most famous of these clusters is in the Faroe Islands, an island group situated between the Norwegian Sea and the North Atlantic Ocean. Prior to World War II, MS was virtually unknown among the native islanders. During World War II, the British, who have a high incidence of MS, occupied the island, and subsequent to this occupation, MS has become epidemic among the native population. Another such cluster was recently identified in a small town in Ohio, where over two dozen MS cases were discovered within a six block radius.

The geographic and migratory components of MS epidemeology, as well as the existence of MS clusters, are heavily suggestive of an environmental (infectious or toxic) element to the MS disease process, and indeed, recent studies have linked several viruses, most of them in the herpes family, to MS. Just within the last week or two, a study out of Taiwan, which looked at hundreds of thousands of subjects, found that people suffering an outbreak of shingles, a painful skin condition caused by the varicella zoster virus (which also causes chickenpox), are three times as likely to develop MS within the year as those who didn't suffer from shingles (click here). Likewise, the Epstein-Barr virus has also been cited as a possible infectious trigger of the disease, with some scientists stating that if a patient isn't infected with EBV, they won't get MS (click here).

Another potential problem with CCSVI as the cause of MS is the inflammatory patterns seen in patients afflicted with the disease. According to CCSVI theory, disrupted blood flow through the CNS creates damage and inflammation to the cells contained within, through a variety of possible mechanisms. This would lead one to expect that the longer the condition persisted, a patient's levels of inflammation would slowly increase over time, in a steady upward slope. However, in reality, RRMS patients see their greatest amount of inflammation early in the disease, during its relapsing remitting stage. Once the disease moves into the progressive stage, and RRMS turns into SPMS (normally within 10-15 years when left untreated) inflammation levels decrease dramatically. Patients with PPMS, who start out with progressive disease, very often show very little signs of CNS inflammation. As a matter of fact, this lack of inflammation, seen as enhancing lesions on MRI images, is a hallmark of progressive disease. This is why anti-inflammatory therapies such as steroids generally have little effect on patients with progressive illness.

Of course, none of this directly contradicts the idea that CCSVI may play some causative role in the disease of some MS patients, but it strongly argues against the idea that CCSVI is the primary cause of the disease.

Some compelling evidence that CCSVI may be an effect of MS has been presented by several researchers, most notably Dr. Robert Zivadinov and the researchers at the Buffalo Neuroimaging Analysis Center. Although Dr. Zivadinov's findings have been savaged by some of the most fervent "CCSVI as cause" proponents, the totality of the research done under his direction does point to the possibility that at least some of the venous abnormalities now called CCSVI are a result of the MS disease process. Although Dr. Zivadinov's opinions only recently made headlines (click here), he in fact implied them in research presented in October, 2010 at the annual ECTRIMS (European Committee on Treatment and Research in Multiple Sclerosis) conference. One paper presented at that time demonstrated that the severity of CCSVI increases with the severity of Multiple Sclerosis symptoms experienced by patients, and with a more advanced disease course (click here). These findings were backed up by papers presented by researchers from Beirut (click here) and Italy (click here). Another study presented by Dr. Zivadinov found that subjects who presented with CCSVI had significantly more lesions and brain atrophy as measured by MRI than those MS patients without vascular abnormalities (click here). Yet another investigation presented by Dr. Zivadinov looked at the correlation between a gene implicated with MS, and CCSVI, and found that the data supported an association between MS disease progression and CCSVI separate from the suspect gene. The implications of these findings are that CCSVI could be a risk factor in developing the disease, or a result of the progression of MS (click here).

Additionally, it would seem to me that the high rate of restenosis in patients who have undergone CCSVI treatment venoplasty could also hint that CCSVI is more an effect rather than the cause of MS. Despite the wide range of treatment methodologies being employed, patients are still experiencing a re-narrowing of their previously unblocked veins far too frequently. This has been seen even in patients who have had stents placed in their veins, only to see their veins stenosing in areas not stented. If CCSVI were an effect of the MS disease process, one would expect to see repeated restenosis of the veins as that disease process continued to impact a patient's vasculature.

So then, what conclusion can be drawn? Is CCSVI the cause of MS, an effect of the disease, or does it have no relation to Multiple Sclerosis at all? My honest belief is that the answer could be all three, depending on the individual patient.

Multiple Sclerosis is a remarkably heterogeneous disease, meaning that it impacts different patients in vastly different ways. Across the wide spectrum of MS patients, the primary symptom of the disease may be fatigue, cognitive dysfunction, muscle weakness, spasticity, eye trouble, nerve pain, or any combination thereof. Some patients can have the disease for decades and show very little physical disability, while others find themselves in a wheelchair (or worse) in less than 10 years (sometimes much less). Some patients have a great many lesions and very little disability, others have few lesions but devastating disability. Confounding the issue even more, MS comes in several different flavors, from Relapsing Remitting to Primary Progressive, and evidence suggests that the disease process at work in progressive disease may be quite different than that underlying Relapsing Remitting MS.

Given such a wide array of disease presentations, and thus the likelihood that a variety of mechanisms may be at play, it could very well turn out that CCSVI plays no role at all in the disease of some patients, a more causative role in the disease of others, and could be an effect of MS in yet another patient population. Very likely the line between cause and effect may be quite blurred, with CCSVI playing an exacerbating role in a disease that almost certainly has, in addition to a vascular component, very strong genetic and infectious components as well. The mix may be dramatically different from patient to patient, and indeed, CCSVI may be THE major factor in the disease of some patients, but play absolutely no role in the disease of others.

This may be reflected in the breakdown of outcomes reported by some of the Interventional Radiologists doing the CCSVI treatment procedure. The most widely quoted is Dr. Gary Siskin, of Albany New York, whose group has done over 700 procedures. Dr. Siskin has found that one third of his patients experience dramatic improvements, another one third experience mild improvements, and a final one third experience no improvement whatsoever. Further complicating this equation is the definition of just what constitutes a dramatic improvement. For somebody who's most disabling symptom is fatigue, a lifting of that fatigue would undoubtedly be called dramatic. For somebody more disabled, like I am, a lifting of fatigue, while certainly welcome, would hardly be defined as a dramatic improvement.

As I stated earlier, clear as mud…

Related articles

• The Rorschach test of CCSVI research (macleans.ca)
• Higher CCSVI rates with MS, but findings still unclear (ctv.ca)