Progressive MS: A Deep Mystery Beginning To Reveal Its Secrets?

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The words "progressive multiple sclerosis" carry with them a sense of dread and panic for most MS patients. When I was newly diagnosed, I of course immediately hit the Internet, and discovered that there were four primary types of multiple sclerosis: Relapsing Remitting MS (RRMS), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS), and Progressive Relapsing MS (PRMS). It only took an hour or so of reading for me to realize that the progressive forms of the disease (SPMS, PPMS, and PRMS) were very scary indeed. Not that RRMS is any picnic, but patients with progressive MS have few if any treatment options, and generally suffer much more aggressive disease and a quicker rate of disability. My mind immediately rejected the notion that I might have one of these forms of MS, but as time played out and the course of my disease became clear, I was given the diagnosis I had come to suspect but refused to accept: PPMS. Now, after eight years, that diagnosis itself has come into question (click here), but still, the clinical course my disease most resembles is PPMS.

A spin around the Internet MS forums quickly reveals that there is much confusion about progressive MS among much of the MS population, especially the newly diagnosed. It's extremely important for patients to understand the differences between the MS subtypes, as treatment and symptom management options vary widely, and informed decisions can only be made if a patient has a good grasp on just what they're dealing with. There are several good sites that explain the differences between the MS subtypes (click here for one), so I won't go into an in-depth discussion of their differences here. In a nutshell, RRMS (which represents about 85% of the MS population) is marked by the disease course that features distinct relapses and remissions. During a relapse, an RRMS patient experiences an acute worsening of symptoms, often to a very debilitating degree. This is followed by a period of remission, when the patient reverts more or less back to normal, sometimes suffering from residual effects that remain from their previous relapses. After a period of years, a majority of RRMS patients transition to SPMS (click here for more info), when they stop experiencing relapses and remissions and instead start suffering from a steady increase in disability, with none of the distinct "ups and downs" of RRMS. In addition to a lack of relapses and remissions, SPMS patients also experience a severe reduction in the amount of inflammation seen in their central nervous systems, despite the ongoing nature of their disease.

PPMS patients (about 10% of the MS population) never experience periods of relapses and remissions, but instead suffer a steady decline in functionality from the onset of their disease. PPMS is distinct in many ways from the other forms of MS, so much so that some doctors and researchers think that it may in fact be a completely different disease. Unlike RRMS, PPMS attacks men and women in equal numbers. MRIs reveal that PPMS patients generally have less lesions than RRMS patients but usually exhibit more spinal lesions, and even though their lesion load is less, quite often their disease is much more aggressive and debilitating. Additionally, spinal fluid analysis is usually less definitive for PPMS patients, as they sometimes don't exhibit the telltale O-bands seen in about 95% of RRMS patients. Additionally, PPMS patients don't exhibit the widespread central nervous system inflammation that is one of the hallmarks of RRMS.

PRMS (about 5% of the MS population) is the rarest common form of MS, and patients afflicted with it experience a steady decline punctuated by acute exacerbations, which are not followed by remissions. This is generally the most aggressive form of the disease.

In my 8+ years of haunting various MS Internet forums, I've seen many patients confused about the differences between SPMS and PPMS, often wondering which variant of the disease they are suffering from. The difference is actually quite clear; if a patient has ever experienced a period of relapses and remissions, then they by definition cannot have PPMS. Anybody who has previously received a definite diagnosis of RRMS, and has experienced exacerbations followed by periods of relief, but now finds that they are now facing a decrease in relapses but a steady increase in symptoms, is likely transitioning to SPMS.

Almost all of the approved MS drug therapies are meant for RRMS patients and are effective to varying degrees in reducing the amount of relapses suffered by the patients taking them, benefits which are accomplished by modulating or suppressing the systemic immune system. At the present time, there is only one drug approved for SPMS patients, the chemotherapy agent Novantrone, and there are no proven effective treatments for PPMS. Often, MS Neuros will try some of the approved therapies on their progressive patients (usually their SPMS patients), in the hopes of positively impacting the disease, but these attempts generally prove to be unsuccessful.

Because of the aggressive nature of progressive multiple sclerosis, and the extreme difficulties in treating it, progressive MS remains a frightening proposition for patients and a confounding problem for the physicians trying to treat them. Often, treatment is limited to symptom management because none of the approved MS treatments, most of which work in one way or another to reduce inflammation in the central nervous system, have any positive effect on progressive MS patients who typically exhibit little or no CNS inflammation. One of the prevailing mysteries of MS is why, in the face of this lack of inflammation, the disease continues to progress without hesitation.

Research conducted over the past few years has started to shed light on some of the mechanisms at play in progressive MS. It appears that, at least in some of progressive MS patients (and especially in SPMS patients), a kind of rogue immune system develops within the patients’ central nervous system, which operates independently from the greater systemic immune system (click here, here, and here). This "immune system within an immune system" is comprised of lymphatic tissue (the kind that produces immune system cells) which develops within the CNS, safe behind the blood brain barrier. These lymphatic tissues produce immune cells (primarily B cells), which it is believed drive the continuing disease process seen in progressive MS. Because this process occurs behind the blood brain barrier, which functions to sequester the CNS from toxins and pathogens that might attack the rest of the body, it is protected from the drugs effective in treating RRMS, which work by down regulating the systemic immune system but have no effect within the central nervous system itself. This explains why drugs like Tysabri, which despite its known potential problems is very effective in treating RRMS (click here), have little or no efficacy in treating the progressive forms of the disease. The drugs simply have no access to the self-contained immune process that appears to be taking place within the central nervous system in some progressive MS patients.

The implications of these discoveries are tremendous. They suggest that therapies delivered directly into the central nervous system may be effective in treating progressive MS, and indeed, one study has demonstrated that intrathecal (spinal) injections of methotrexate do seem to be effective in treating progressive MS (click here [full disclosure, this study was conducted by my neuro, Dr. Saud Sadiq]). The NIH is currently conducting a study testing the effectiveness of intrathecal Rituxan in SPMS patients (click here). This also illustrates the importance of research done very recently that has demonstrated a possible method for temporarily opening up the blood brain barrier, allowing for delivery of drugs into the CNS (click here).

Furthermore, the development of immune cell producing tissues within the central nervous system means that addressing many of the suspected MS triggers (viruses, toxins, possibly CCSVI) would have little or no effect on the disease once this rogue immune system is in place. Indeed, we do have anecdotal reports that CCSVI treatment appears to be less effective in patients suffering from the progressive forms of multiple sclerosis, and none of the approved RRMS drug therapies has been shown to be of any benefit for progressive patients.

It took me quite some time to grasp the implications of this "rogue immune system" theory, but I've developed the following analogy that I think illustrates the problem fairly well. Imagine a lit match being held to a sheet of paper. The lit match represents whatever it is that triggers MS and the early RRMS stage of the disease, and the sheet of paper represents progressive MS. Once the match touches the paper and ignites it, extinguishing that match will have no effect whatsoever on the burning sheet of paper. Likewise, once a compartmentalized immune system develops within the CNS (the burning sheet of paper), extinguishing the conditions which allowed for it to develop (the lit match) will be ineffective in curtailing the disease. Indeed, this is exactly what we do see with current accepted MS treatment modalities, and, anecdotally at least, in the treatment of CCSVI.

Therefore, the possibility exists that there is a window of opportunity before these lymphatic tissues develop and the disease goes progressive during which the treatment of MS has its best chance of curtailing the advance of the disease.

Clearly, research priorities must be shifted to definitively identifying the underlying causes that initiate the aberrant immune response seen in MS, rather than simply finding new and more profitable ways of suppressing the immune system, many of which are of questionable effectiveness in stopping RRMS from transitioning to progressive disease (click here). Plainly, there are processes driving the disease even in its earliest stages that are not directly related to the systemic immune system. We must also learn if progressive disease is in fact driven in large part by a self perpetuating immune reaction developing within the CNS, and if so identify which progressive patients are suffering from this development, and of course also find safe and effective methods to fight it.

Science is finally beginning to tease apart the intricate puzzle of multiple sclerosis, but vigorous and innovative research is urgently required, as is a shift away from much of the current thinking about the disease, which has proven hugely profitable to Big Pharma, but of little value when it comes to eradicating MS. Real hope is on the horizon, but new maps must be drawn to finally deliver MS patients to the promised land.

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 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.

Situation Normal, All Fracked Up…

Image by Mathieu Struck via Flickr

When I started this blog, I was determined that it wouldn't be a treatment diary, so I haven't detailed the daily, weekly, and monthly ins and outs of my medical meanderings. Still, I've recently written about the fact that my diagnosis has been called into question, and I've received several inquiries in that regard. I thought it might be helpful if I gave a few more details about my mystery diagnoses, and how it's affected some of the treatment choices I've made and continue to make.

After my diagnosis of MS in March 2003, I quickly became uneasy with my doctor's conclusion. Like most other newly diagnosed patients, I immediately hit the Internet, reading all I could about the disease and interacting with dozens of patients on MS forums. The more I investigated, the less convinced I became that I actually had multiple sclerosis. Yes, two lesions did show up on my MRI, one tiny spot in my brain, and a much larger and more troublesome lesion at the base of my brainstem. Tests on my cerebral spinal fluid, though, revealed no Oligoclonal-bands (click here), telltale signs of CNS immune activity that show up in a majority of MS patients. O-bands are a bit less common in patients with progressive MS, the flavor of the disease I was suspected of having, but still, their lack fueled my reason to doubt.

Additionally, I had a variety of peculiar physical symptoms and some health history that just didn't seem to mesh with a diagnosis of Multiple Sclerosis. About six years before my first MS symptom struck (a slight limp in my right leg, which has since progressed to severe weakness and spasticity in my entire right side, and progressing weakness on the left), I was suspected of having Discoid Lupus (click here), a form of Lupus that attacks the skin. Although that diagnosis was never quite nailed down, my doctors at the time were confident that I did have something very strange going on in my immune system. After approximately 3 years, my Discoid Lupus type symptoms (small skin blemishes that left tiny crater shaped scars, hence the word "Discoid") burned out, to my considerable relief. Soon after, though, I was diagnosed with Hashimoto's Thyroiditis, an autoimmune disease that destroys the thyroid gland. I started showing signs of other types of endocrine dysfunction as well, indicating a cascading failure of my pituitary gland. Although Hashimoto's Thyroiditis is often seen in patients with MS, pituitary problems are not. About three years after these endocrine problems surfaced, my telltale limp showed up, and I was soon given the MS label.

About a year into my MS saga, I switched MS doctors and started seeing my current neurologist. He immediately suspected that I might be suffering from some other disease (he suspected Neurosarcoidosis-click here), and ordered an extensive battery of tests. When none came back positive, he deduced that Primary Progressive Multiple Sclerosis was the most likely diagnosis, and so the initial determination stood.

Since there is no actual test for MS, determining whether a patient suffers from it is a diagnosis by exclusion. The physician explores other possibilities that might explain the patient's symptoms, and if none pans out, the diagnosis of MS is assumed. In many patients, multiple sclerosis makes itself readily apparent. A relapsing remitting course of disease, the occurrence of enhancing CNS lesions on MRI images, and the presence of O-bands in the cerebrospinal fluid are all highly indicative of a multiple sclerosis diagnosis. Cases of the disease that are progressive from the outset are harder to diagnose, as there are quite a few maladies that can mimic progressive MS (click here).

Despite the fact that progressive MS is notoriously hard to treat, and there are currently no approved treatments for PPMS, I am not the type to sit around and do nothing while some insidious enemy hacks away at my body, and my neurologist is known for his aggressiveness in fighting the disease. We embarked on a comprehensive battle to attack my disease, which has included a wide variety of treatments, some quite outside the box, which are literally almost too long to list. Suffice it to say, none has had any effect whatsoever on the course of my disease.

Along the way, my illness has shown itself time and again to be extremely atypical, most notably in the fact that my MRI images have never changed. The two lesions that showed up in 2003 are still there today, and have never altered in size or appearance, or been joined by any others. MRI images of my CNS taken eight years ago are indistinguishable from those taken six months ago. Because of all of the atypical features of my illness, I eventually decided to seek another expert opinion, and was seen at the Johns Hopkins MS center in the winter of 2006. After undergoing a rigorous series of tests, Johns Hopkins also concluded that although my disease was certainly strange, they could find no indication that it was anything other than atypical PPMS. During the following few years, I kept in contact with the doctors at Johns Hopkins, and in 2008, after I sent them some recent MRI images (which remained unchanged) and explained that my disease had progressed significantly, it was requested that I come back down to Baltimore for another examination. This time, the doctors concluded that I very likely did not have MS, but they could not come up with a suitable alternate diagnosis. Several were suggested (Sjogren's disease and mitochondrial disease among them), but further testing ruled out these other illnesses.

At this time, I was accepted into a study being conducted at the National Institute of Health's main campus in Bethesda, Maryland, which was seeking to identify patients with clinically definite multiple sclerosis for use in further MS research. The NIH was finding that many of the subjects they were using in their multiple sclerosis research studies were actually misdiagnosed, and these misdiagnosed patients were polluting their research data. Over the next 18 months, I made four visits to the NIH's tremendously impressive facility outside of Washington, DC, during which every conceivable test was conducted. At the end of the process, the NIH declared that my test results and disease presentation did not fit the definition of multiple sclerosis by any known diagnostic criteria, but they too could not come up with a reasonable alternative. Needless to say, the situation was, is, and I'm sure will continue to be incredibly frustrating.

My primary neurologist here in New York, who runs a state-of-the-art research laboratory in addition to his clinical practice, recently did an extensive analysis of my spinal fluid, which turned out to be so strange that he had the analysis, which took several weeks to complete, repeated to confirm the results. Unlike many other MS patients, my neurologist and I have a very comfortable and frank relationship, and he told me just how bizarre my spinal fluid scans were in very colloquial and colorful language (I'll let you use your imagination to fill in the blanks).

Since it now seems likely that I'm suffering from either a) one of the strangest cases of MS on record, or b) some other autoimmune process that is attacking my central nervous system in addition to various other bits of my anatomy, my neuro suggested that I try IVIG (click here), a treatment that has been shown to be effective in some cases of MS, and perhaps more importantly for me, a variety of other autoimmune conditions that can attack the CNS. IVIG is a blood product made up of the antibodies of over 1,000 blood donors, which has been shown to attenuate the aberrant immune response seen in a variety of diseases, and is typically given monthly. Since I have a history of experiencing unexpected and sometimes frightening side effects from new medications, we started out by doing half a dose of IVIG about a month ago (the treatment is usually given in two infusions over two days, but I only did one infusion the first time around). I didn't suffer any negative side effects, so later this week, on Tuesday and Thursday, I'll be doing my first full dose of IVIG.

Many of you are probably asking yourselves where CCSVI fits into my treatment picture. I had my first venoplasty about 13 months ago, which did reveal a blockage caused by a muscle pressing on my right internal jugular vein, but no other readily apparent venous abnormalities. Unfortunately, the muscle bundle is currently impossible to treat using the available treatment modalities, as ballooning would have no effect on the pressure being put on the vein by the muscle, and a stent would likely be bent out of shape, and possibly fracture, due to that same pressure. It is also uncertain as to whether the muscle bundle is causing significant disruption to the perfusion of blood through my central nervous system (Dr. Zamboni himself had a look at my images, and cast doubt as to the significance of the blockage). I had been planning to undergo another CCSVI treatment procedure sometime soon, because of the advances that have been made in the treatment protocol in the 13 months since my first attempt, but I've decided to put this off for at least a few months in order to properly ascertain whether or not the IVIG is having the desired effect. Doing a CCSVI treatment now would only muddy the waters, and the blood thinning regimen given after the procedure could interact with and/or interfere with the action of the IVIG.

I recently underwent a Doppler sonogram done to the Zamboni protocol, which did reveal signs of CCSVI (confusing, since my initial venoplasty did not reveal these abnormalities). This further blurs the issue, as it's become quite clear that I likely do not have MS, and CCSVI has been shown to have a high correlation with multiple sclerosis. However, recent studies also seem to indicate that the venous abnormalities known as CCSVI may also be prevalent in other neurologic diseases, so I very well could have both CCSVI and a disease other than multiple sclerosis. If the IVIG doesn't do it's stuff, I will definitely revisit CCSVI, very likely sooner rather than later. Even if I do experience benefit from IVIG, I'm inclined to undergo another venoplasty sometime in the not-too-distant future, to investigate the blood flow abnormalities indicated by the Doppler ultrasound. As I've written before in this space, waiting on getting a CCSVI venoplasty done is not a terrible option, as knowledge regarding CCSVI is constantly growing, and the treatments used to address it are evolving by the day.

As I'm sure you can imagine, this has all been extremely hard to sort out, but I'm now comfortable with my treatment decisions going forward. Despite the questions surrounding my diagnosis, I still consider myself an MS patient (since no other label really applies), and the experience of my disability progression is identical to that of a patient suffering from aggressive PPMS. In spite of the confusion and distress caused by all of this uncertainty, in a way not having a diagnosis gives me some reason for optimism, as it could turn out that whatever I have is more treatable than PPMS. I continue to hope that some brilliant doctor, upon examining me and going over my voluminous record of test results, will suddenly exclaim, "Eureka! You're suffering from the most advanced case of Cooties I've ever seen! Simply eat 10 red M&Ms a day for the next two weeks, and you'll soon be running marathons…"

Hey, if you don't have dreams, you have nightmares…

Live Webcast, "Repairing the Nervous System in MS: Progress and Next Steps": Tuesday, 01/11/11, 2 PM ET

The National Multiple Sclerosis Society is holding a live webcast on Tuesday, January 11, at 2 PM, focusing on the latest research efforts in neurorepair and neuroregeneration, two of the holy grails of MS investigation. (Click here for more info and to register)

This topic should be of extreme interest to all MS patients, regardless of your feelings about the NMSS, mainstream neurology, and CCSVI. Even in a CCSVI best case scenario, in which the hypothesis does turn out to be the primary cause of MS, damage done to the central nervous system will still need to be repaired to restore functionality to the patient once disease progression has been stopped. Damaged nerve cells rarely if ever repair themselves, so strategies for stimulating such repair are vital.

This webcast will feature the following panel of world-class MS researchers:

Dr. Peter Calabresi, Professor of Neurology and Director, Johns Hopkins MS Center, Baltimore, MD;
Protecting the nervous system from MS damage, novel ways to track repair

Dr. Ian D. Duncan, Professor of Medical Sciences at the University of Wisconsin, Madison;
Novel imaging technologies, transplanting cells to promote repair

Dr. Charles ffrench-Constant, Chair of Medical Neurology, University of Edinburgh, UK;
Transplanting repair cells and stimulating natural nervous system repair

Dr. Gavin Giovannoni, Chair of Neurology at Barts and The London School of Medicine and Dentistry,
Screening molecules for their protective properties and conducting clinical trials

As is noted above, some very interesting topics will be discussed, including the use of stem cells to stimulate nervous system repair.

(Click here) to find out what time the webcast will be held in your time zone. Choose "America/New York" in the "From Time Zone" window.

Bits and Pieces: From Sublime to Ridiculous

Image via Wikipedia

Faithful readers of this blog know that I like to regularly share various news items that I find interesting or otherwise tickle my fancy, most of which have at least some peripheral relationship to Multiple Sclerosis. Here's another such collection, along with some commentary. This compilation includes items that range from the extremely serious to the extremely silly, which more or less reflects the real life balance needed to maintain one's sanity. Even though we're dealing with a serious illness, we don't need to be serious about it all the time. In any event, I'll try to put these in some semblance of order, in descending rank from serious to silly…

• "Multiple Sclerosis Will Become a Controlled Disease like AIDS" screams the headline of this article (click here), which talks about some of the breakthroughs that geneticists have made in identifying genes associated with MS. While these discoveries are both encouraging and fascinating, transforming MS into a controlled disease falls far short of the expectations and wishes of those afflicted with the illness. While controlling MS is certainly preferable to just letting the disease run rampant through our brains and spines, it sure would be nice to see the scientific bar raised a bit, to include at least a cursory mention of the possibility of a cure.

  As anybody knows who lived through the scourge of AIDS in the 1980s and 90s, a time when people were being buried at a tragic and distressing rate, the fact that AIDS is now for the most part controllable by means of a cocktail of strong antiviral medications is definitely a huge relief. Certainly, the hunt for a cure for the disease hasn't been abandoned, but you can't help but think that the fact that the disease is now considered controllable has lowered the urgency of that endeavor. I'd hate to see the same situation arise for MS, but in reality, I suppose it already has.

  The advent of disease modifying drugs that do nothing to address the still mysterious root cause of MS, but which have been a tremendous financial boon to the pharmaceutical industry, has almost certainly dampened research efforts to hunt for the genesis of the disease. The fact that these drugs are tremendously expensive and must be taken for the life of the patient has turned MS into a multibillion dollar a year windfall for pharmaceutical companies. Since these companies fund over 70% of the medical research done in this country, and they are public companies whose mission is to constantly increase profits, their money flows towards research that shows the potential for tremendous financial return, which most often takes the form of blockbuster immunosuppressive or immunomodulating drugs.

  Many neurologists have expressed genuine shock over the tremendous emotional embrace given by the MS patient population to the CCSVI hypothesis and the Liberation Procedure used to address it. This surprise on the part of the physicians exposes a serious disconnect between MS Neuros and their patients. MS sufferers innately know that the sometimes extremely toxic drugs they are being given will in no way free them from their disease. They may improve a patient's quality of life by cutting down on MS relapses, but they do nothing to slay the enemy within. Since CCSVI apparently offers at least the hope of a cure, patients have latched onto the theory like shipwreck survivors grasping at life preservers. Regardless of the ultimate outcome of the CCSVI debate, hopefully the patient-doctor dynamic has forever been altered, and even if CCSVI turns out to be less than we now hope it will be, patient driven initiatives will help jumpstart the search for a cure.

• Speaking of disease modifying drugs, the FDA has approved the first oral treatment for RRMS. Developed by the pharmaceutical company Novartis, the drug is called Gilenya, formerly known as Fingolimod or FTY 720. This is the first MS Disease Modifying Drug that doesn't require injections or intravenous infusions (click here for info).

  Hooray, right? No more sticking yourself with needles, or spending several hours a month in an infusion suite, what could be bad about that? Well, unfortunately, potentially quite a bit.

  During trials, Gilenya was found to increase the chances of developing severe, sometimes fatal infections, as well as an increased propensity for melanoma, a deadly skin cancer. In addition, there was some association of the drug with adverse vascular events, macular degeneration, and the possibility of lymphoma.

  On the plus side, Gilenya does dramatically decrease the relapse rates of patients taking it, and also dramatically cuts down on the number of enhancing lesions seen during MRI imaging. There is also some evidence that the drug may be neuroprotective, one of the holy grails of MS research, and for that reason it's currently being trialed on PPMS patients, for whom there are no approved, or even unapproved, treatments. Gilenya may also slow disease progression, another holy grail of MS research.

  I find the mechanism of the drug somewhat troubling, though. Like Tysabri, Gilenya inhibits the ability of immune system T cells to gain entrance to the Central Nervous System, where they significantly contribute to the CNS damage seen in MS patients. While Tysabri accomplishes this by blocking T cells from crossing through the blood brain barrier that separates the Central Nervous System from the rest of the body, Gilenya keeps T cells trapped in the lymphatic system, not only restricting their access the CNS, but to the rest of the body as well. In effect, Tysabri keeps the cops out of one specific neighborhood, but Gilenya keeps them trapped in the police station. Since the compound was only trialed for two years, no one can say for sure what the long-term effects of so profoundly altering our delicately balanced immune systems might be. Sounds like many doctors are going to be cautious about this drug, at least at first (click here for info).

  On an interesting side note, Gilenya is derived from an ancient Chinese herbal remedy called Cordyceps, which is a fungus that grows on the back of caterpillars, and is purported to have many medicinal properties, including those of an aphrodisiac. It's also supposed to increase blood flow and oxygen supplies throughout the body (possible CCSVI implications?) (click here for info). Cordyceps is available through online vitamin and herbal supplement retailers (click here), but I'm not sure what alterations were made to the compound when Novartis synthesized and patented it. Strangely enough, Cordyceps in its raw form is known to increase the activity of the immune system, but some MS patients do report it helps their MS fatigue.

• In yet more drug news, the FDA has approved Nuedexta (click here for info), the first drug designed to combat "emotional incontinence", otherwise known as the pseudo-bulbar affect (click here for info). Some MS and ALS patients suffer from a very strange symptom: the inability to control their emotions, which often leads to inappropriate fits of laughing and crying. I must admit, I do get awfully weepy at some movies, and have even been known to cry at commercials, but these reactions predate the onset of my MS. Throw "Casablanca" in the DVD player, and I'm apt to start crying from beginning to end. What can I say? I'm hopelessly smitten with Ingrid Bergman, and when Humphrey Bogart makes the ultimate sacrifice, letting the love of his life, once lost but then found, fly off with another man in the name of a greater cause, well, pass me the tissues, and they'd better be two ply…

• It appears that a slightly bonkers British chap has eclipsed me as a real Wheelchair Kamikaze. Seems this bloke has attached a gasoline engine to a standard mobility scooter, and reached speeds approaching 70 mph (click here). Hey, my hats off to him, and I heartily applaud his efforts. Wait a second, since he's using a scooter, I guess I can still hold onto my Internet moniker. He's the Scooter Kamikaze. And, in keeping with mobility device kamikaze tradition, he made a pretty cool video of his exploits…

• And in news that has nothing at all to do with MS, it seems that a time traveler has been caught in a 1928 film starring Charlie Chaplin. In the background of a scene in the Chaplin film "The Circus", it appears that a woman walks by apparently talking into a cell phone. Of course, cell phones weren't invented back in 1928, so her actions are quite mysterious. I love the idea of time travel, and if one day I seem to simply disappear, look for me back in 1935, dancing a mean jitterbug at The Savoy Ballroom in Harlem, burning my shoe leather to some big band version of Fats Waller's "This Joint Is Jumping". I'm assuming, of course, that traveling back in time would cure my MS. Anyway, here's a piece from the Chaplin film, showing the alleged time traveler…

Related articles

• From Cicada Fungus To MS Drug: How Big Will Novartis' New Pill Be? (blogs.forbes.com)
• Gilenya priced at $4000/month, 30-50% higher than MS self-injections (brassandivory.org)

Some Revised Thoughts on the Current State of CCSVI

Last week, I published a post on my thoughts regarding the current state of CCSVI research and treatment (click here). The post elicited much response, and many well thought out comments were left by readers who both agreed and disagreed with my points of view. As I've stated before, I welcome all readers to post their opinions, as a healthy exchange of ideas is the only way to draw informed conclusions, especially on subjects as new and controversial as CCSVI.

After reading and considering many of the responses arguing that research into whether or not venous blockages correlate with MS, and, if so, whether these abnormalities are cause or effect, were basically a waste of time and that treatment studies should take the forefront, I've changed my original point of view. While I still do think that academic research into the venous abnormalities we've come to call CCSVI is important, I now believe that treatment studies should be given the highest priority possible.

I've come to this conclusion for a variety of reasons. First, treatment studies themselves will show whether or not CCSVI abnormalities are indeed related to MS, and if they play a role in causing or exacerbating the disease. If, under rigorous trial conditions which include pre-and post-procedure neurologic evaluations, patients are found to respond favorably to the liberation procedure, then obviously CCSVI is not only related to MS, but plays an important role in the disease process. If patients fail to respond, then the opposite conclusions can be drawn.

Second, the noninvasive imaging techniques used to detect CCSVI have been shown to be less than reliable, and catheter venography has thus far proven to be the gold standard in finding blockages in the veins associated with the central nervous system. Based on the accounts of both the physicians who have performed the procedures, and patients themselves, Doppler sonography, MRV's, and CT venograms have all been shown to be prone to both false positives and false negatives when compared to the findings of catheter procedures, for a variety of reasons (technological limitations, operator deficiencies, etc.). Thus, any studies based strictly on noninvasive imaging will always have a cloud of doubt hovering over them. Better to cut to the chase, and perform catheter venography on test subjects. If that venography detects abnormalities, these abnormalities should be addressed by balloon angioplasty, which has been shown to be an extremely safe procedure when done by experienced physicians. Again, whether or not patients respond to angioplasty would answer questions of correlation and causation.

Third, if CCSVI does indeed prove to be a major piece of the MS puzzle, we need to refine the techniques and technology of the liberation procedure. Currently, many patients experience improvements soon after undergoing the procedure, only to see those improvements dissipate when their newly opened veins close up again. This phenomenon itself would suggest that CCSVI at least plays a role in the MS disease process, and also indicates that much learning needs to be done about the best practices, procedures, and equipment to be used when undertaking the liberation procedure. Virtually all of the medical equipment currently used in the treatment of CCSVI was developed primarily for use in arteries, which are vastly different in an anatomical sense to veins. Vein specific equipment, especially stents, needs to be developed if the liberation procedure does prove to be a major player in the treatment of Multiple Sclerosis.

Several other concerns have recently come to my attention. It seems to be becoming clearer that CCSVI is likely not just confined to the jugular and azygous veins, as has been thus far thought; the picture appears to be more complex. Dr. Zamboni has recently suggested that abnormalities in the lumbar veins could very well play a major role in progressive illness, and many venograms are finding abnormalities in the vertebral veins as well. The vertebrals are the vessels that return blood to the heart and lungs from the brain when patients are in an upright position. The jugulars take over this function when patients are lying flat. Thus, problems in the vertebrals could theoretically play just as important a role as jugular abnormalities. In my particular case, the catheter venogram done during my unsuccessful liberation procedure turned up blockages not only in my right internal jugular, but also abnormalities in my vertebral veins as well. Unfortunately, there is currently no accepted method for addressing stenosis in either the vertebral or lumbar vessels. Clearly, research into these concerns is necessary.

We must see collaboration between neurologists and vascular specialists if the myriad questions surrounding CCSVI are to be answered in any definitive fashion. I'm aware of several treatment studies that are currently awaiting approval, and of several doctors who are chomping on the bit waiting to get started conducting these trials. They'll have no problem finding patients willing to participate in these studies, but funding may be a dilemma. The MS patient population must get behind the studies, not only in body and spirit, but with their wallets too. When these studies are finally approved and announced, CCSVI advocates the world over, and those who love them, will need to step up to the plate and donate either directly to the institutions conducting the studies, or to nonprofit CCSVI advocacy groups that are currently readying to launch. Patient advocacy has pushed CCSVI out of the shadows and into the spotlight that currently shines on it, and that same advocacy will likely be necessary to take CCSVI from hypothesis to either positive or negative conclusion.

The CCSVI studies recently approved by the MS Societies of the United States and Canada will provide valuable data in assessing many of the questions that CCSVI theory has posed. I'm particularly intrigued by the study that will look at sets of twins in which one has has developed MS but the other has not. In fact, all of the approved studies will add greatly to the CCSVI knowledge base. But for a patient population desperate for answers, suffering with a disease in which time itself is an enemy, answering academic questions simply isn't enough. We must find out, as quickly and definitively as possible, whether or not the liberation procedure is as beneficial to some MS patients as anecdotal reports make it appear to be. Desperate times call for desperate measures, and for many MS patients, myself included, these are indeed desperate times...

Some Thoughts on the Current State of CCSVI

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Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.

-Sir Winston Churchill, November 1942

It's now been almost 13 months since I first posted information on CCSVI, in a piece titled "Is MS Actually a Vascular Disease?" (click here). At that time, CCSVI was hardly a blip on the MS radar screen, knowledge of it confined mostly to a few dozen patients fervently researching and discussing Dr. Zamboni's findings on the patient forums at ThisisMS.com. A small handful of MS patients had been treated by Dr. Michael Dake, at Stanford University, having stents placed in the narrowings (stenosis) found in the veins associated with their central nervous systems.

Well, what a difference a year has made. CCSVI has created a firestorm in the MS community, as desperate patients have embraced the theory as their best hope to beat back this horrifying beast we call Multiple Sclerosis. Canadian television has aired numerous news pieces detailing the theory and the "liberation procedure" used to treat it (click here), hundreds of patients have been treated for the condition at locations scattered around the world, and the Internet is full of seemingly miraculous before and after videos portraying patients whose MS symptoms have dramatically declined after undergoing endovascular procedures to address their vascular abnormalities (click here). Just this past Thursday, the US and Canadian MS societies announced $2.4 million in grants to fund seven trials designed to test the validity of the CCSVI theory (click here).

Still, there is widespread disgruntlement among the MS patient population, many of whom are dismayed at the almost complete lack of treatment options available locally in the US and Canada, feel that research is moving much too slowly, and in fact believe that a conspiratorial cabal of pharmaceutical companies, mainstream neurologists, and MS societies is intent on suppressing and killing the CCSVI theory in order to protect huge profits and rapaciously defended spheres of influence.

I understand the desperation and anger these patients feel, which speaks loudly not only of the promise of CCSVI, but also of the failure of mainstream neurology to come up with any options better than simply suppressing or modifying our immune systems, often with drugs that carry with them the possibility of terrifying side effects. We are told that our immune systems have somehow gone bonkers and decided to attack our own tissues, but we've never been told why, and with the tremendous profits being generated by drugs companies marketing drugs targeted at the immune system, that why has been left to dangle in the air, twisting in the breeze. CCSVI appears to answer that vital why, in a fairly elegant and easy to understand manner, and thus has been embraced by a patient population frantic for answers.

It's important, though, to take a step back and calmly assess the situation as it now stands. We must guard against hope eclipsing reason, which is difficult to do when, as MS patients are fond of saying, time equals brain. With the omnipresent escort of progressing disability haunting us, we all want solutions, and we want them as quickly as possible.

Still, it's important to discern the realities of where the state of CCSVI research now stands. Many patients insist that the theory has been proven, and that a simple and minimally invasive procedure can halt or reverse the ravages of their illness. It's quite possible that they are correct about the procedure, but the fact is, as has been stated by Dr. Zamboni (click here) and some of the other leading CCSVI researchers and physicians themselves (click here and here), that research is desperately needed to prove or disprove the association between MS and CCSVI, that the procedures used to treat the venous abnormalities that have come to be called CCSVI need to be refined and perfected, and that new medical devices (stents) must be developed specifically for use within the CNS venous system.

Thus far, the only positive peer-reviewed research that has been published regarding the association between CCSVI and MS comes from Dr. Zamboni, and from the research team at the Buffalo Neuroimaging Analysis Center (BNAC), whose initial trial results involving 500 patients were released in April. All other reports are strictly anecdotal, and as such have little credence in the eyes of science. It's vital for completely independent researchers to confirm the initial groundbreaking work done by Dr. Zamboni, to firmly establish that CCSVI is significantly more prevalent in MS patients than in the general population, and, once confirmed, that CCSVI is a cause rather than an effect of the disease. Despite many patients’ belief otherwise, neither of these two propositions has yet been established in any scientifically valid manner. Only once CCSVI is determined to be a causative factor of MS will the MS societies fund studies on treatment.

In the meantime, privately funded studies looking at treatment options have already been proposed, and some should be getting underway sometime this summer.

The studies recently funded by the US and Canadian MS societies are targeted at precisely the two primary goals of proving the CCSVI/MS connection and showing that CCSVI is a cause rather than an effect of the disease. Much has been made of the fact that $2.4 million is hardly an overwhelming amount of money to be spent on CCSVI research, especially when placed in the context of the tens of millions of dollars being spent researching other aspects of MS, but at least it's a start. Without the groundswell of patient activism and advocacy, there most assuredly would have been no funding given to CCSVI research whatsoever, and I urge patients to continue to agitate for more, and more timely, research to be done.

The genie of patient activism is out of the bottle, and wielded wisely, can exert great influence on the powers that be. We must be careful, though, to guard against hysteria and extremism, to keep the CCSVI movement from being branded the lunatic fringe of the MS patient community. Discretion is often the better part of valor, and the movement would do well to heed Teddy Roosevelt's advice to speak softly and carry a big stick. That big stick is money, as the MS societies rely heavily on donations from the population at large (contrary to popular belief, only 5% of their contributions come from the pharmaceutical companies). I would expect that a smart and well-organized campaign that impacted the societies’ bottom line would quickly get their attention. Efforts can be made, too, to get CCSVI sympathetic members placed on the boards of the societies, as was recently tried unsuccessfully in Canada (click here). There will soon be CCSVI specific nonprofit organizations moving to the forefront, and support for these organizations should rank high on the list of those patients seeking to further the cause of CCSVI.

Switching to the question of diagnosis and treatment, I'm getting more and more concerned about people flying all over the world to get treatment that is quite possibly temporary (angioplasty) or carries with it unknown but very possibly real and troublesome risks (stents). Again, I completely understand the desperation of those willing to spend tens of thousands of dollars, and travel thousands of miles, to get treatment. I myself was lucky enough to get treatment locally, although my liberation procedure was unsuccessful (click here). But as the pool of treated patients grows, some obvious trends are emerging.

Even when initially successful, patients treated with balloon angioplasty are too often experiencing restenosis within weeks or months of the initial procedure. This means that they must either spend more time and money traveling across continents to be treated once again, or swallow their losses. Patients treated with stents are also experiencing problems with restenosis and clotting, and the very use of the currently available stents (which were designed primarily for use in arteries located within the chest cavity, vessels that differ dramatically in their anatomy from the veins associated with the CNS venous system), presents a host of potentially dire unknowns.

Dr. Zamboni has repeatedly stated that he's very wary of stents being used in the jugular or azygos veins, and when the doctor who treated me first presented my difficult case to Dr. Zamboni, Zamboni recommended traditional open neck surgery (as in, slicing and dicing) rather than stenting. Many patients have been stented for CCSVI successfully, but once those stents go in, they're in there for life, and nobody knows what affect the stresses of bending, stretching, and torque that the stents will experience in the neck will have as time passes. Stents specifically designed for use in the veins associated with the CNS are a must if CCSVI does indeed prove to be fact rather than merely theory.

Patients considering the liberation procedure must also keep in mind that not all patients treated see benefit, and some have even reported getting worse after treatment. We've all seen the miracle videos on the Internet, but people on whom the treatment had no or negative impact generally don't make videos for YouTube or show up on the various patient forums. Therefore, what we see and read on the Internet is extremely skewed towards the positive. Between patients who have contacted me through this blog and others that I know personally, I'm aware of quite a few people who have received absolutely no benefit from the procedure. Of course, given the heterogeneous nature of MS (the disease is very different in different patients), this shouldn't come as a surprise, but patients need to be keenly aware that the liberation procedure in its current form is not always the panacea that its most fervent advocates often assert it to be.

Another important consideration for those patients who do decide to pursue CCSVI treatment is the experience of the doctor doing their procedure. Most Interventional Radiologists (the specialists who do endovascular procedures) have far more experience treating arteries than veins. In fact, the CNS venous anatomy has been so little studied that no definition of "normal" has been agreed upon, and this anatomy can and does vary widely from patient to patient.

Furthermore, CCSVI is not limited to only one type of abnormality; a multitude of abnormal findings have been discovered in the jugular and azygos veins of MS patients. These abnormalities include vein narrowing, abnormal and dysfunctional valves, anomalous membranes, and even septums that divide the blood vessel in two. Many doctors just starting to do liberation procedures will have little experience dealing with this variety of abnormality. The physician who did my procedure, Dr. Salvatore Sclafani, has publicly stated that, despite 30 years experience doing catheter procedures, it wasn't until he had done the procedure on about 20 patients that he started to feel comfortable with the "art" of liberation, and that he was learning copious amounts with each patient he treated.

Undoubtedly, as more and more patients undergo the procedure, the methods and equipment used will be altered and refined, and procedures done a year from now will likely be much more sophisticated than those that have been done to this point. Although the idea of waiting for treatment is abhorrent to many patients, it may actually be in their best interests to allow doctors to gain the experience necessary to perform the liberation procedure effectively, safely, and with long-lasting results. We are in an age of discovery, and the book on CCSVI and the best ways to treat it has only started to be written.

In short, what we don't know still vastly outweighs what we do know about CCSVI and its role in MS. I personally believe that CCSVI will prove to be a major piece of the MS puzzle. I don't believe that it will be THE answer for all MS sufferers. The promise of CCSVI is tremendous, and in conjunction with advances being made in stem cell therapies, a new age in the understanding and treatment of MS could very well be dawning. But as tedious and frustrating as it might be, we must let the course of science wind its way towards definitive answers. Those who feel they cannot wait and choose to be pioneers in the treatment of CCSVI, would do well to remember the experiences of the pioneers who settled the American West. Some made it to California, struck gold, and became rich beyond their wildest dreams. Others, like the Donner Party (click here), became hopelessly stranded en route, and suffered disastrous consequences.

Due to the nature and speed of my disease progression, I decided to follow the trail blazed by the first and bravest pioneers, and underwent the liberation procedure, although I made it clear that I would only agree to balloon angioplasty, and would not consider the use of stents (my doctor was in agreement). I may revisit that decision as my disease marches onward. Each patient must decide for themselves their tolerance for risk, but hopefully, as the saga of CCSVI continues to unfold, those risks will be considerably diminished. At the very least, the issue of CCSVI has pushed researchers to look beyond the autoimmune theory, and that alone is a very good thing.

Amazing Pre and Post CCSVI Liberation Procedure Videos (Updated)

The following videos were posted to YouTube by MS patient named Denise. I don't have much information about her, and I don't know where her procedure was done, or if balloon angioplasty or stents were used. Upon watching these videos, though, the results speak for themselves. If you are unfamiliar with CCSVI or the Liberation Procedure, please click here.

Here's the video taken a few days before the patient underwent the Liberation Procedure:

And here's the video taken less than 24 hours after her procedure:

Obviously, the improvements depicted are startling. I've been in touch with many patients who have undergone the procedure, both on the Internet and in person, and although many have reported improvements in their condition, this is one of the most dramatic cases I've seen/heard of.

It's hard to know what to make of these results. I don't think the patient in the videos above was "faking". Of course, I've no proof of that, but it would be a hell of an acting job if she was playing make-believe.

Naturally, it's thrilling to see such improvement, and I certainly wish that my procedure had gone as well (click here for info on my Liberation Procedure). From a scientific and medical standpoint, though, it's difficult to understand the mechanism behind the improvements depicted in the videos.

Certainly, less than 24 hours after the procedure, the reversal of nerve damage could not account for such a fast turnaround of symptoms. Nerve cells simply don't heal that quickly, and if damaged enough, they do not heal at all. I think it's safe to rule out nerve regeneration as being responsible for the improvements seen above.

The only other explanation I can come up with is that the opening of the patient's jugular vein had a remarkable anti-inflammatory effect on her CNS, which would mean that most of her problems were caused by inflammation, rather than actual nerve damage. Steroids are given to MS patients because of their powerful anti-inflammatory properties, and in some patients the beneficial action of steroids can be quite rapid, but not nearly as fast or as powerful as those that we see in the above videos. It generally takes cells at least a few days to recover from inflammation, so this solution too is problematic.

Dr. Sclafani, who did my procedure, reports that some of his other Liberation Procedure patients displayed surprising improvements soon after the procedure, but that in many cases these improvements were short-lived. Dr. Sclafani's sample size is small, though, so not much can really be read into them.

Whatever the reasons for the startling results seen in Denise's videos, I certainly hope she has lasting benefits, and continued improvement in her condition. As more and more research gets done on CCSVI, answers to the many questions surrounding the theory should start coming in.

Full-scale trials of the Liberation Procedure will be getting started this summer, and recently the government of Kuwait announced that all Kuwaiti MS patients will undergo the procedure, paid for by the state-funded medical system (click here for info). Kuwait has some 5000 MS patients, and it's expected that 10 patients per week will be getting "liberated".

Within several months, we should start getting some hard data regarding the effectiveness of treatment and the validity of CCSVI. For hundreds of thousands of MS patients, this data cannot come too soon...

IMPORTANT UPDATE: Wheelchair Kamikaze reader (and good friend) Bestadmom posted an alarming update on Denise's condition, which deteriorated about a week after her procedure. I'll include a brief summary of what happened here, and you can read a full account of the problems Denise encountered (in her own words) by clicking on the comments link, below, and reading Bestadmom's very informative post.

In a nutshell, Denise's condition reverted back to her "pre-liberation" days, with a sudden onset of her old symptoms. A return trip to the hospital where she had her liberation done showed that the stents that had originally been implanted during her procedure had restenosed and had to be removed (I was not previously aware that stents could be removed). A new set of stents was put in place (based on her account, it seems that four new stents in total were implanted), and the situation must have been dicey, since a neurosurgical team was put on standby.

The second procedure seems to have been pretty rough on Denise, but she is reporting that her symptoms do appear to be resolving once again.

Denise's experience is an enlightening example of both the promise and perils of the current CCSVI situation. Clearly, CCSVI offers the MS population real reason for hope, but the study of CCSVI, and its treatment, are still in their infancies. Techniques and materials need to be refined and developed specifically for the purpose of intervening in the array of venous blockages that have come to be known as CCSVI. This can only happen under the auspices of scientifically valid trials, whose progress can seem agonizingly slow for a patient suffering from progressive and debilitating neurologic disease.

Discretion is often the better part of valor, and it's very easy to allow hope to eclipse reason when one is staring at the dark at the end of the tunnel. Each of us needs to make their own determination of their tolerance for risk, but as more and more is learned about CCSVI, and its treatment, the risk profile associated with CCSVI should decline considerably. As previously stated, the next 6 to 12 months should be very telling.