Tuesday, January 19, 2010
Friday, May 8, 2009
A recent news article raises some questions that are of utmost importance to any patient dealing with serious/chronic illness. Although the article is more an opinion piece then straight up journalism, the issues it talks about are vitally important.
In a nutshell, the piece is concerned with the fact that the FDA is currently in the process of deciding whether to classify adult stem cells as prescription medicines, which would thereby give the FDA the right to regulate the way such medicine will be administered. Please keep in mind, we're not talking about embryonic stem cells here, so there are no moral politics involved in this matter. At issue is adult stem cell therapy, which comes with none of the complicated moral questions surrounding embryonic cells. Instead, it's money, scads and scads of dollars, that are at the heart of the issue.
The drug companies (Big Pharma) are lobbying hard to get the FDA to declare stem cells "prescription drugs", thereby giving the drug companies considerable control over this revolutionary medical technology. Stem cells hold the promise of completely changing the face of modern medicine. They are the key to unlocking the human body's own ability to heal and regenerate itself. Stem cells could make the way medicine is currently practiced, with all of its invasive surgeries and use of potentially toxic pharmaceuticals, as obsolete as the medical practices of the 1700s are today.
This all presents a great threat to the pharmaceutical industry. Over the last 50 years, the marketing of pharmaceuticals has become an industry that generates hundreds of billions of dollars each year. Much of this money is generated by drugs used to treat "chronic" illnesses, such as diabetes and multiple sclerosis. Diseases such as these are cash cows for the industry, because patients stricken with them are forced to be consumers of the industry's products for life. Medicine is well on the way to transforming previously fatal diseases, such as some forms of cancer and AIDS, into chronic illnesses, creating yet more lifelong consumers of expensive pharmaceutical therapies.
The success of stem cells would mean that many of the medicines used to treat chronic illnesses would be rendered instantly obsolete. Big Pharma stands to lose billions and billions of dollars if the promise of stem cells turns out to be even only partially fulfilled.
It's important to remember that all of the companies that make up "Big Pharma" are public companies, and as such are by law beholden to their stockholders, not to the patients that take their products. Their primary mandate as public companies is not to benefit mankind through the creation of medical miracles, but to earn ever increasing amounts of money.
While on the face of it this would seem to be all well and good, as the best way for pharmaceutical companies to make money is to create effective drugs, there is actually a basic conflict to this equation. Turning potentially fatal or disabling diseases into manageable chronic illnesses generates huge amounts of wealth, but curing those same illnesses puts an end to the cash flow. Thus, we see great amounts of effort and capital going into researching drugs that treat illnesses, but not much going into research that might actually cure them.
I'm not suggesting that there is some evil conspiracy afoot, or that there is a cabal of miserly old men sitting in an opulent conference room somewhere, casually devouring infants as they plot to make untold billions of dollars by ensuring that illnesses are never cured. If that were the case, the solution would be easy, simply eradicate that opulent conference room and the baby eaters in it, and proceed on to the cures. Instead, the problem is much more insidious.
Over 70% of medical research in the United States is funded by the pharmaceutical companies. As stated before, the primary mandate of these companies is to make money, which they do best by discovering "blockbuster" drugs that will generate billions of dollars. Therefore, pharmaceutical research money is funneled towards projects that hold the promise of just such discoveries.
Research scientists, as well-meaning as they might be, still must rely on grants from pharmaceutical companies to fund their research (and therefore pay their rent, feed their families, and advance their careers), and thus are naturally inclined to conduct research that will attract pharmaceutical company dollars. In a way, it's a vicious cycle; pharmaceutical companies tend to fund only those projects which they think have the biggest profit potential, thereby influencing researchers and scientists, who, after all, need to make a living, to embark upon research that is likely to have the profit-making potential that the drug companies are looking for.
Stem cells threaten to throw this whole system on its ear. The process of extracting stem cells from a patient (usually from bone marrow or fat tissue) can be done in a doctor's office, and the processing of such cells can take place in laboratories outside the purview of the pharmaceutical companies. These procedures are not so complicated that the industrial might of the pharmaceutical industry is needed to make them a reality. They are more on the scale of fertility treatments, which are administered in local clinics by local doctors without the "help" of Big Pharma.
If the pharmaceutical industry is successful in its lobbying efforts to get the FDA to declare stem cells "prescription drugs", the power of stem cells will be ripped from the hands of physicians and placed in the hands of public companies whose profit-making mandate could actually lead to the suppression of potentially revolutionary stem cell therapies. This would have tragic consequences for the millions of patients that could potentially benefit from stem cell treatments.
Laboratory models and animal testing have shown that these treatments are extremely viable, and many could likely be ready to treat human patients within the next five years, if left in the hands of physicians and researchers. If, instead, stem cells are declared "prescription drugs", these therapies might not see the light of day for decades.
If you or a loved one suffers from a chronic illness, it is time for your voice to be heard. Call your senators, call your congressman, write letters to your newspapers. Demand that your friends and family do the same. Climb up on soapboxes and scream from mountaintops. Bang drums, put on face paint, and go on the warpath. Treat this issue as if your very life depends on it, because it does...
CCSVI Presented in an Elegant and Thoughtful Way
As many of you know, I have been working on some articles around the theory, data and progress around CCSVI (chronic cerebrospinal insufficiency) and multiple sclerosis (MS).
I thought I would bring to you a lovely overview and personal perspective on CCSVI and MS that was written by someone who is able to sum things up in a tidy, yet thought-provoking way. I bring you CCSVI (the Vascular Theory of MS): Separating Fact from Fiction. The author, Marc, is also known as The Wheelchair Kamikaze, and he has been keeping up with the news on this developing theory since it was just a fairly obscure entry in the medical literature.
I was so impressed with the way that Marc was able to convey the basics on CCSVI and his opinion around this theory, that I have frequently found myself wondering how I could say the same thing as well as he did - until right now, when I realized that I could just bring the article to you to read for yourself (blame the delay on my MS-related cognitive dysfunction).
So, without further ado, go read this fresh opinion on CCSVI. While you are at it, check out some of the rest of the site, especially the photographs, which were taken from the perspective of a wheelchair.
Read what The Wheelchair Kamikaze has to say about CCSVI:
Read more about CCSVI and MS:
Monday, January 18, 2010
This is what I did for my husband, and this is my best advice. Not everyone can get on a plane to fly to Poland. Most will need to find local help. You can do it.
Get a "team" together. This can be healthy spouses, siblings, children, friends. Assign them your case. You will work together to find a doctor to treat you.
Print out Dr, Zamboni's research papers.
Get together Dr. Mark Haacke's protocol for MRV testing-
Look for local "interventional radiologists". Search for these doctors on the internet. They often practice in groups or at universities. If you cannot find any of these doctors in your area, search for vascular surgeons. IR docs use magnetic resonance venography and venography to find venous abnormalities. They do it every day. Vascular surgeons understand the importance of venous return.
Call these doctors, email these doctors, tell them you would like to be tested for internal jugular vein and azygos vein stenosis, and send them the Zamboni research. Tell them you have headache and swelling as sign of blocked veins. Mention that interventional radiologist Dr. Michael Dake at Stanford University is conducting a clinical trial on this, and he believes that Dr. Zamboni is right.
Do not stop. We have a group of patients on the east coast of the US that spent months contacting hundreds of interventional radiologists. They found one willing to look at this, and now there are finally more coming on board. Once these doctors see the glaring evidence of venous malformation in MS patients, they are convinced it is real. Then they talk with their IR doc colleagues, and the word spreads.
When I went to Stanford last year, no one was talking about CCSVI. But slowly, the interventional radiology doctors are learning about this condition. Go to them with your team. Convince them to test you, to be a part of medical history. (You may have to offer to pay for your initial testing...but insurance will cover it once stenosis is proven. This is what we did.) Do it today.
CCSVI – Some More ThoughtsLast modified: 16.01.2010 - 18:35 CET Created: 16.01.2010 - adm
Written by Ashton Embry PhD. New Pathways Magazine. Nº 58. November/December 2009
Last month I described the basics of the concept of chronic cerebrospinal venous insufficiency (CCSVI) which undoubtedly marks the start of a new era in understanding and treating MS. In this issue, Ian Cook has followed up on CCSVI and has focused on currently-available treatments for relieving CCSVI as well as a major research project which will be done at the University of Buffalo over the next few years. In this column I want to address a few issues that have arisen with the advent of the CCSVI concept. These include the role of CCSVI in MS, the historical roots of the concept, the current response of the main elements of the MS community to CCSVI, and what might be done to get treatment of CCSVI available as soon as possible.
The idea that CCSVI is the cause of MS is already being bantered about. I can certainly understand this but to me such a way of thinking is not productive. What need to be answered in this regard are questions such as “Does CCSVI play a major role in the MS disease process?” and “Does CCSVI come before or after the onset of CNS autoimmunity?” To me I think we can answer the first question with, “Given the current data it is almost a certainty that CCSVI is a key part of the MS story”. I say this because 1) almost everyone with MS tested at four different research centres in three different countries exhibited CCSVI, 2) CCSVI explains a number of previously puzzling characteristics of MS lesions such the association of iron and the venocentricity, and 3) CCSVI is theoretically compatible with all we know about MS. Notably, inclusion of CCSVI as an important part of the MS disease process provides a much improved explanation of all the features of MS.
It is much harder to answer the second question. Currently, there is no evidence or theoretical reasoning that supports a model that has CCSVI following the onset of autoimmunity. It is much more reasonable to assume CCSVI precedes autoimmunity because such a model is theoretically sensible and has been sporadically postulated by MS researchers over the past 150 years. In regards to CCSVI coming first, some researchers have suggested that the venous blockages are congenital and are in place at birth. This is doubtful given that adequate vitamin D can prevent MS but right now our ignorance of how and when CCSVI is generated is profound.
The concept that MS is primarily a vascular disease can be traced back to 1863 when a researcher named Eduard Rindfleisch proposed that “the primary cause of MS is an alteration of individual blood vessels”. He based this interpretation on his consistent observations that a vein was present in the centre of each lesion. Over the next 100 years, the vascular basis for MS resurfaced every so often based on the close association of lesions with veins but never really took off due to a lack of any convincing evidence. The last main champion of the concept was Dr Roy Swank who thought venous blockages and resultant breeches in the blood-brain barrier were due to fat globules. This led him to advocate for his well known dietary therapy for relieving the fat-induced, vascular problems.
Over the last 60 years, the vascular hypothesis was completely overshadowed by the autoimmune theory for MS which came into vogue in the 1930s and which has become steadily more popular since that time. It must be emphasized that the vascular hypothesis has never been disproved; it has been simply ignored because of the complete focus on immunological aspects of MS.
Of course, with the discovery of CCSVI in virtually every person with MS, we finally have that elusive, convincing evidence that vascular problems are indeed a major part of MS. CCSVI marries all the vascular-related data gleaned from detailed studies of MS lesions with the huge immunological data base which has accumulated over the past 50 years. The two different data sets now fit very well together in a model in which impaired venous drainage causes breeches in the blood-brain barrier (vascular hypothesis) which then leads to autoimmune reactions (autoimmune hypothesis).
With the recognition of CCSVI and the resultant much better understanding of the MS disease process, one might expect that MS researchers and clinicians would be falling over themselves to redirect their efforts to take into account this major discovery. Unfortunately this is not the case and the main reaction from the clinicians is, at best, one of wait and see or, at worst, total rejection. One person with MS I know recently asked their neurologist about CCSVI and how they might get it treated. The neurologist became agitated and stated that CCSVI was nonsense and there was no evidence for it. I expect such an uninformed reaction is commonplace. MS clinicians are content to simply prescribe an MS drug and they don’t want to think about a completely new way of treating MS until they have to.
The MS research community has exhibited a similar, highly skeptical reaction to CCSVI and I expect they will not even consider incorporating CCSVI into their research plans until the data become so overwhelming they will have little choice but to do so. So where will this overwhelming evidence come from? The good news is that there are a few far-sighted researchers who have seen the obvious “paradigm shift” nature of CCSVI and are starting to undertake significant CCSVI studies. The most progressive of these are Drs Bianca Weinstock-Guttman and Robert Zivadinov of the University of Buffalo whose planned research is discussed by Ian Cook in this issue. I believe once the results of the Buffalo study are announced (2012?), CCSVI will experience a tipping point and everyone from researchers, to clinicians, to the main MS charities, will get on the CCSVI bandwagon.
Given the data we have, it is not a stretch to say that all persons with MS have impaired venous drainage which is actively, or potentially, contributing to their MS disease progression. Given this, it is not surprising that every person with MS who understands the implications of CCSVI wants to have their venous problems resolved by vascular surgery as soon as possible. Unfortunately very few medical centres are doing vascular procedures to relieve CCSVI and thus it is basically impossible for almost all persons with MS to get the important vascular treatments they need.
It is hard to know how the MS patient community can improve this appalling situation and get relief for both CCSVI and the great frustration many are feeling. It seems to me a patient revolt is needed and it is also essential that this unacceptable situation be widely exposed through the media. Perhaps persons with MS should follow the advice given in the 1976 movie, Network, and go to the window and shout “I am as mad as hell and I am not going to take this anymore” (http://www.youtube.com/watch?v=WINDtlPXmmE&feature=related).
Finally, another obvious question which needs to be answered is what nutritional strategies can be adopted to offset the effects of CCSVI. I will address this in my next column.
Wednesday, January 13, 2010
There are interventional radiologists around the world looking at CCSVI. If you are unable, ask family members and friends to be your advocates. Find local groups of MS patients and caregivers to work with you. Come to ThisIsMS.com to meet others. Join local Facebook pages. But DO NOT send money to people who solicit funds on the internet....EVER! Joan
Best Answer - Chosen by Voters
I've had the liberation procedure, I'd do it again in a heartbeat, I've had no relapses since experiencing it, and don't really care what the National Pharmaceutical Society has to say about it, since they have no problem with pushing unproven toxic drugs in my veins at 30k a year. While I appreciate the absolute LACK of answers in the post below for what it is, "just repeating the byline", the fact remains that there is ample scientific study so far to conclude that we should be looking at this very closely. Angioplasty is a relatively safe procedure, with NO adverse effects experienced by the participants. Considering that the ONLY people who relapsed, were the once experiencing re-stenosis of the treated veins, which were then brought OUT of relapse and into remission by being retreated, well why not ask them if they think "there's no evidence"? By the way, even though the NMSS chickens have no interest at the moment of weaning from the pharmaceutical teat, the MS Association had no problem with presenting the current state of research, which is improving and moving along rapidly. The previous poster would do well to check it out a bit more thoroughly than a very old, scripted, dry and "safe" statement the NMSS issued months ago.
Nobody but the patient him/herself can answer the question about risks, it's the doctors job to present the pros/cons and the patient decides what their risk tolerance is. I weighed a life of progressing disabilty, augmented by bankrupting drug avenues that provide little hope, or a relatively benign and simple procedure, not without risks, but neither is liposuction, and made my choice. Since the NMSS invested their entire $ budget into pharmaceuticals to combat your immune system, and no one is getting any better, well perhaps they were looking in the wrong place.
I weighed, I took the risk, I now reap the benefits 24 hours a day 7 days a week and have NO regrets. My life improves daily. Put that in an official press release.
Tuesday, January 12, 2010
"In the early 1930s, Thomas Rivers and colleagues provided the first evidence that immune cells can attack the brain. Their simple experiments established what is now the most well-studied model of autoimmunity—the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
Studies had shown that injection of foreign brain tissues into the brains of rabbits could cause paralysis (2). Intrigued, Rivers—then a virologist at The Rockefeller Institute—set out to duplicate these studies in monkeys. Rivers and his colleagues injected Rhesus macaques with normal brain extracts from rabbits and showed that most of the monkeys developed acute CNS disease with immune cell infiltration and demyelinating lesions. No infectious agent could be cultured from the animals, putting to rest suspicions of an infectious etiology. Rivers' group also noted that the disease-inducing capacity of the brain extracts paralleled their myelin content, providing the first hint that myelin was involved in disease induction. Thus, the experimental allergic (now “autoimmune”) encephalomyelitis (EAE) model was born. The group published these observations in three articles in the Journal of Experimental Medicine (3–5)."
EAE continues to be the medical model neurologists and immunologists study today, even though this model for MS is deeply flawed. Researchers continue to give mice EAE by injecting them with antigen, and then try to "cure" them with a variety of immune blocking or modulating medicines.
Here's a paper from 2005
"Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate
EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certai n approaches. The reasons underlying such failures are discussed here.
Many scientists interested in developing new therapies for MS criticize the EAE model for its poor record of predicting outcomes in the clinic, especially for those instances when promising therapies indicate that they are beneﬁcial in models of EAE, yet then fail in subsequent clinical trials.
Nevertheless, the EAE models are rapid, and can quickly give indications of whether a particular mechanism of action of a speciﬁc drug has merit when taken into an in vivo model that recapitulates many aspects of the human disease, MS"
So, the reason we still use the EAE model for MS is because it is a RAPID proof of DRUGS? Because these drugs can cure mice of EAE????
MS researchers continue to use this disease model, to the exclusion of other research, even in light of the fact that these treatments appear to cure mice of EAE...but FAIL IN CLINICAL TRIALS OF HUMANS WITH MS.
Insanity is repeating the same actions over and over again and expecting different results. We have had seventy five years of EAE research, and we are not closer to understanding MS.
Perhaps we need to find a new model?
It's a fascinating theory for sure and I hope the world wide attention it is getting will give it a chance to be explored and researched. Whether it's cause or symptom, it needs investigating. But isn't it typical that the people/organisations who are most supposed to have an interest in finding a cure for MS are the ones putting a stopper on it straight away? It's just like with LDN (low dose naltrexone) the minute something looks like a safe way of a treatment or cure the people whose main interest is their profit come out to dash people's hopes.
Well, I will stick with my LDN for the time being as this treatment I've already secured for myself. It's such a shame though that less lucky people (especially those without the internet) don't know about LDN or CCSVI as doctors won't even tell them about it.
- Silvia Lane, Woodcote, Oxfordshire
Read more: http://www.dailymail.co.uk/health/article-1242441/Could-multiple-sclerosis-caused-blocked-veins.html#ixzz0cQtuVMPY
Radical MS Theory Stirs Interest
Wedge-shaped medullary lesions in multiple sclerosis.
Qiu W, Raven S, Wu JS, Carroll WM, Mastaglia FL, Kermode AG.
Centre for Neuromuscular and Neurological disorders, University of Western Australia, Australia;
Department of Neurology, Sir Charles Gairdner Hospital, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia;
Department of Neurology, the Third Affiliated Hospital of Sun yat-sen University, Guangzhou, China.
Multiple sclerosis (MS) is a heterogeneous disease with variable clinical features and magnetic resonance imaging (MRI) findings. We report four MS cases with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata demonstrated on MRI. The clinical features and MRI characteristics of the medullary lesions suggest an impairment of venous drainage.
We propose that the formation of these wedge-shaped lesions may be related to the pattern of venous drainage in the ventral medulla and raised venous pressure due to chronic cerebrospinal venous insufficiency which has recently been described in MS. Copyright © 2010 Elsevier B.V. All rights reserved.
Thursday, January 7, 2010
Jan 07, 2010
UPDATE: Research into Blood Flow in the Brain and Venous Insufficiency, or CCSVI, in MS – Letters of Intent Received from Request for Research Applications Released Worldwide
Updated January 7, 2010
Summary: Recent reports are calling attention to the idea that a phenomenon called CCSVI, a reported abnormality in blood drainage from the brain and spinal cord, may contribute to nervous system damage in MS. This hypothesis has been put forth by Dr. Paulo Zamboni from the University of Ferrara in Italy. Based on the results of his initial preliminary findings, Dr. Zamboni states that this pilot study warrants a subsequent larger and better controlled study to definitively evaluate the possible impact of CCSVI on the disease process in MS.
It has been proposed by Dr. Zamboni, but not yet proven, that CCSVI may be corrected through endovascular surgery, which involves inserting a tiny balloon or stent into blocked veins in order to permit the flow of blood out of the brain and spinal cord, a procedure that has been called “liberation therapy” in some reports.
UPDATE: The National MS Society is undertaking the funding of new research on CCSVI in MS and has invited investigators worldwide to apply for grants that would explore this lead. In response to a January 6 deadline, the National MS Society and the MS Society of Canada received numerous letters of intent from investigators from seven countries. These letters of intent, which briefly describe the proposed research, will be reviewed and those that meet grant guidelines will be invited to submit full research proposals.
CCSVI Research Funding Timeline
January 12, 2010 – Investigators whose letter of intent meet guidelines are invited to submit full research proposals with a deadline of February 9, 2010.
May 2010 – International panel of experts conducts an expedited review of all applications received through this special request for applications.
June 2010 – Funding decisions announced.
July 1, 2010 – Anticipated start date for funding of any successful research applications.
The applications will undergo an accelerated review process by an international panel being convened in cooperation with other MS Societies to ensure an expedited, coordinated response. If this hypothesis is confirmed, it may open up new research avenues into the underlying pathology of MS and new treatment approaches to therapy.
Background: In a recent study by Dr. Zamboni and colleagues, the team evaluated abnormalities of blood outflow in major veins draining from the brain and spinal cord to the heart in 65 people with different types of MS, compared with 235 people who were either healthy or who had other neurological disorders. They used sophisticated sonography techniques to detect abnormalities of venous drainage. The investigators reported evidence of slowed and obstructed drainage in the veins draining the brain and spinal cord in many of those with MS. They also found evidence of the opening of “substitute circles” – where the flow is deviated to smaller vessels to bypass obstructions, and these were often found to have reverse flow (reflux) of blood back into the brain.
The investigators call this venous obstruction “chronic cerebrospinal venous insufficiency,” or CCSVI. The treatment status of the people with MS (i.e., whether or not they were on an MS disease modifying drug) did not appear to influence whether they showed signs of CCSVI. The authors speculated that the reverse flow of blood back into the brain might set off the inflammation and immune-mediated damage that has been well described in MS. This study was published in June 2009 (J Neurol Neurosurg Psychiatry 2009; 80:392-399).
It is proposed, but not yet proven, that CCSVI may be corrected through endovascular surgery. This surgery is being called “liberation therapy” in some reports. One study getting underway was described at the 2009 ECTRIMS meeting in September. It involves a collaboration between researchers in Italy, Buffalo (NY) and Birmingham (AL) who are attempting to treat venous obstruction in 16 individuals using balloon dilation such as has been used for many years to treat blocked arteries.
In a small, open-label study by Dr. Zamboni and colleagues published in December, the team evaluated the safety and preliminary outcomes of vascular surgery (percutaneous transluminal angioplasty) in 35 individuals with relapsing-remitting MS, 20 with secondary-progressive MS, and 10 with primary-progressive MS. (J Vasc Surg 2009; 50:1348-1358) They reported some positive impacts and suggested that controlled trials were necessary to better determine potential safety and benefits of this procedure.
Next Steps: The National MS Society has prompted communications between MS Societies worldwide and leveraged resources to ensure an open exchange of information and a coordinated and expedited approach to conducting and evaluating additional research on CCSVI. On December 16, 2009, the Society released a worldwide Request for Applications to the scientific community to explore CCSVI, and is collaborating with the MS Society of Canada and possibly other societies to convene an international panel of experts to conduct an accelerated review of proposals. We are also working with our sister MS Societies around the world to assure that our research strategies are coordinated. Through an internationally coordinated and expedited review process, new CCSVI research projects are expected to begin July 1, 2010. (See Research Funding Timeline above for more details.)
According to the Buffalo Neuroimaging Analysis Center, although 500 subjects have already been selected for their initial combined transcranial and extracranial venous doppler evaluation study, they are still seeking participants for a larger-scale clinical study with the aim of evaluating the prevalence of venous obstruction in people with MS. This study does not involve treatment of obstructions.
To get the quickest answers and most reliable results about benefits and risks of any surgical procedure that might attempt to address blood flow in or out of the brain, it is crucial that such surgery be performed only as part of controlled trials, especially since there have been anecdotal reports of surgical attempts to treat CCSVI in people with MS resulting in adverse events, including one reported death.
Many questions remain about how and when this phenomenon might play a role in nervous system damage seen in MS, and at the present time there is insufficient evidence to prove that this phenomenon is the cause of MS.
Frequently Asked Questions About CCSVI and MS
Q: What is the National MS Society’s view of CCSVI?
A: In trying to find the cause and more effective treatments for a disease as complex and unpredictable as multiple sclerosis, the Society is steadfast in its commitment to pursue all promising avenues of research that can lead to improved treatments and ultimately, a cure. It is important for researchers to think outside the box and we believe Dr. Zamboni has done this. His hypothesis is a path that must be more fully explored and Dr. Zamboni himself has stated that additional research is essential to evaluate it.
Q: Will the National MS Society fund research into CCSVI in MS?
A: The National MS Society is pursuing follow-up research in how CCSVI might be involved in the MS process and we have invited investigators from around the world whose research is relevant to MS to submit proposals to apply for grants that would explore this lead. These applications will undergo an accelerated review process.
Q: Do the reports of a possible association between insufficient vein drainage and MS mean that MS is caused by venous insufficiency?
A: No. Based on results published about these findings to date, there is not enough evidence to say that obstruction of veins causes MS, or to determine when this obstruction may occur in the course of disease.
Q: If CCSVI turns out to be important in MS, can it be treated?
A: No one knows yet. Surgical procedures for CCSVI in MS are still experimental and should be undertaken only as part of formal clinical trials that include all of the standard safeguards that are followed in such trials.
Q: How can I get involved in research on CCSVI in MS?
A: A larger-scale clinical study is getting underway in Buffalo, New York and is now recruiting participants nationwide with the aim of evaluating the prevalence of venous obstruction in people with MS. This study does not involve treatment of venous obstructions.
Q: I have MS. Should I be tested for signs of CCSVI?
A: We do not recommend testing for signs of CCSVI unless you are involved in a research study exploring this phenomenon, since at this time there is no proven therapy to resolve any abnormalities that might be observed, and it is still not clear whether relieving venous obstructions would be beneficial.
Q: Does CCSVI make the standard treatments of MS meaningless?
A: No. There is ample evidence proving that the FDA-approved therapies for MS provide benefit for people with most forms of MS.
A: As new information becomes available about CCSVI, it will be posted on the National MS Society’s Web site, www.nationalMSsociety.org
The origins of multiple sclerosis (MS) have long remained elusive and older theories, including that of autoimmunity, have been widely questioned. In recent years, researchers have consistently demonstrated that the immune changes in MS developed after the presence of brain lesions. In addition, in first describing MS, Marie Charcot noted vascular changes in the brain that she couldn’t explain. Other scientists have made similar observations.
Viral infections, particularly Epstein-Barr virus and cytomegalovirus have been implicated as potential immune triggers. Other suspected causes included industrial chemicals and toxins, low vitamin D levels, and brain injuries.
Dr. Zamboni’s Work
Dr. Paolo Zamboni is a professor of vascular medicine at the University of Ferrara as well as the Director of their Vascular Center. When his wife was diagnosed with MS in 1995 he began to rigorously study this disorder. Poring over brain imaging studies, he too noted vascular changes. With his expertise, he realized that the changes he was seeing in the cerebrosinal vasculature of MS patients paralleled the changes observed in the legs of patients with peripheral artery disease.
Dr. Zamboni concluded that in MS the veins that drain the brain and spinal cord are blocked or damaged. Consequently, surrounding tissue is damaged. Dr. Zamboni calls the disease process in MS one of chronic cerebrospinal venous insufficiency (CCSVI).
Vascular Changes in MS
Specifically, Dr. Zamboni noted that the lesions seen in MS all occur adjacent to veins and expand in the direction opposite normal blood flow. This suggested that there was venous involvement and that a countercurrent, chaotic blood flow was likely eliciting damage similar to that seen in his chronic vascular disease (CVD) research.
In vascular disease, veins become stretched or varicose. This occurs because veins have very thin weak walls with little muscle supporting them. Veins can be compared as strings relative to the thick ropy arteries. When blood becomes backed up in veins, veins need to expand and widen.
This, in turn, affects valves. The valve flaps become so far apart that they don’t function properly. This impairs venous return. The blood has nothing to hold it back so it slips back down the vein through the poorly functioning valves.
The resulting congestion causes a backup of fluid. The fluid migrates through the vein wall and out into the tissue. In peripheral artery disease affecting the legs, this is seen as a swollen, edematous ankle. Wherever it occurs, if this disease process persists, fluid from the circulation migrates out leaking red blood cells as well.
Iron deposits resulting from red blood cell protein (hemoglobin) accumulations trigger an immune response. Excess iron deposits and the presence of iron pigment (hemosiderin) granules are the hallmark of chronic vascular disease (CVD). Hemosiderin is present in the brain lesions of MS.
The immune system changes, such as an influx of cytokines, are characteristic of both chronic vascular disease and MS. The tissue changes seen in biopsies of lesions collected by Dr. Zamboni support these findings.
The immune process that occurs in response to these lesions is a true immunological defect but lacks the characteristic changes that occur in autoimmune diseases. For instance, serum from patients with MS will not cause MS in other species.
Dr. Zamboni has placed stents, to widen the jugular veins affected by stenosis in the brains of patients with MS. The results have been impressive and it is thought that this surgery will halt the disease process. To date, patients who have surgery in Italy and at Stanford University have shown good improvement.
However, the surgical program implemented by Dr. Dake at Stanford University has been halted until sufficient evidence from clinical trials is available. Studies to date have supported Dr. Zamboni’s findings, and the results of a large study being conducted in Buffalo, New York will be available in February 2010.
What This Means
Although MS has been a disease primarily treated by neurologists and by a number of medications used to slow the inflammatory process, a consultation with a vascular specialist may be the next step in the history of treatment for MS. Drugs like low dose naltrexone (LDN) still play an important role in restoring homeostasis and enhancing the healing process. And until Dr. Zamboni’s surgical results have been confirmed by clinical trials, MS patients must wait for the next chapter in this story.
Monday, January 4, 2010
Radical MS Theory Stirs Interest
Can multiple sclerosis be treated with a simple surgical procedure?
That question -- raised by the research of an Italian physician -- is causing a stir among those who study the condition, which has long been regarded as an autoimmune disease.
Instead, according to Paolo Zamboni, MD, of the University of Ferrara, in Ferrara, Italy, MS may result from poor vascular circulation in the brain.
The theory is this: Abnormal flow through the azygous and jugular venous systems results in a build-up of iron in the brain. The excess iron damages blood vessels and allows the metal, as well as other substances, to cross the blood-brain barrier.
The hypothesis has immediate clinical implications. First, if narrowed or obstructed veins are the cause of the condition, people might easily be screened for MS long before symptoms appear.
And second, a simple surgical procedure -- a percutaneous transluminal angioplasty -- could open the veins and perhaps halt or reverse the course of the disease.
The case is not proved, and experts caution that more study is needed to overthrow the reigning paradigm. In particular, they warn patients against seeking vascular surgery before the issue is settled -- one way or another -- by a full-scale, randomized blinded controlled trial.
"Most experts regard it as a long shot" that needs to be studied, said John Richert, MD, executive vice president for research and clinical programs at the National Multiple Sclerosis Society.
But Zamboni told a Canadian newspaper recently, "I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis."
Researchers in Buffalo, led by Robert Zivadinov, MD, PhD, of the Buffalo Neuroimaging Analysis Center, are currently trying to determine whether people with MS are more likely to have what has been dubbed "chronic cerebrospinal venous insufficiency."
They are enrolling 1,100 patients diagnosed with possible or definite MS, 300 age-and-sex-matched normal controls, and 300 patients with other autoimmune and neurodegenerative diseases.
"If we can prove our hypothesis, that cerebrospinal venous insufficiency is the underlying cause of MS," Zivadinov said in a statement, "it is going to change the face of how we understand MS."
The investigators are following up a small pilot study, as well as one conducted by Zamboni and colleagues and reported late last year in the Journal of Neurology, Neurosurgery & Psychiatry.
In that study, Zamboni and colleagues looked at venous outflow in 65 patients with clinically defined multiple sclerosis and 235 controls, using transcranial and extracranial Color-Doppler high-resolution examination.
The MS patients were 43 times more likely to have abnormalities than the controls, they reported (OR 43.0, 95% CI 29 to 65, P<0.0001).
Zivadinov and colleagues found a similar result in their small pilot study of 16 patients with relapsing-remitting MS and eight healthy controls: all the patients, but none of the controls, had chronic insufficient blood flow from the brain.
Also, in a report in press at the Journal of Vascular Surgery, Zamboni and colleagues offer results of a study in which they surgically treated 65 MS patients with abnormal cerebral venous outflow.
The effect of the surgery on MS symptoms was compared with rates of symptoms during the two years before the procedure.
According to published reports -- the final paper is not yet available -- during the 18 months following surgery, half of the patients with the remitting-relapsing form of the disease had no attacks. The corresponding rate before surgery was 27%.
As well, the proportion of patients with active gadolinium-enhanced lesions seen on MRI scanning fell from 50% to 12%.
While the results seem promising, they fall well short of proof, according to the MS society's Richert. "This is something that requires a well-controlled, blinded prospective study," he said.
One danger is that patients may jump the gun, Richert said. "There are a number of patients who may be expecting that they can just go to a vascular surgeon and get this done," he said.
"Our feeling is that this is an experimental procedure and that it should be undertaken by people with MS only as part of a formal clinical trial," Richert added.
Richert added that the results of Zamboni's surgical trial -- while good science -- aren't enough yet to overturn the existing paradigm.
Among other things, Richert said, it's possible that the apparent benefit was a long-lasting placebo effect.
In clinical trials with a placebo, he noted "reproducibly and consistently, the group on placebo does better on the trial than they did prior to entering the trial."
Zamboni and colleagues measured MS symptoms in patients before and after the procedure, rather than comparing surgical and control groups.
The changes that they saw, Richert said, are similar to those "that we tend to see in placebo groups in major drug trials."
He added that the MS society is "anticipating" proposals for a randomized trial of the surgery by its February grant deadline. The Canadian MS society said earlier this week that it will support such research if a proposal is made.
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20 Tips for a Positive New Year
1. Stay Positive. You can listen to the cynics and doubters and believe that success is impossible or you can know that with faith and an optimistic attitude all things are possible.
2. When you wake up in the morning complete the following statement: My purpose is_______________________.
3. Take a morning walk of gratitude. It will create a fertile mind ready for success.
4. Instead of being disappointed about where you are think optimistically about where you are going.
5. Eat breakfast like a king, lunch like a prince and dinner like a college kid with a maxed out charge card.
6. Transform adversity into success by deciding that change is not your enemy but your friend. In the challenge discover the opportunity.
7. Make a difference in the lives of others.
8. Believe that everything happens for a reason and expect good things to come out of challenging experiences.
9. Don't waste your precious energy on gossip, energy vampires, issues of the past, negative thoughts or things you cannot control. Instead invest your energy in the positive present moment.
10. Mentor someone and be mentored by someone.
11. Live with the 3 E's. Energy, Enthusiasm, Empathy.
12. Remember there’s no substitute for hard work.
13. Zoom Focus. Each day when you wake up in the morning ask: “What are the three most important things I need to do today that will help me create the success I desire?” Then tune out all the distractions and focus on these actions.
14. Instead of complaining focus on solutions. It’s the key to innovation.
15. Read more books than you did in 2009. I happen to know of a few good ones.
16. Learn from mistakes and let them teach you to make positive changes.
17. Focus on “Get to” vs “Have to.” Each day focus on what you get to do, not what you have to do. Life is a gift not an obligation.
18. Each night before you go to bed complete the following statements:
• I am thankful for __________.
• Today I accomplished____________.
19. Smile and laugh more. They are natural anti-depressants.
20. Enjoy the ride. You only have one ride through life so make the most of it and enjoy it.