I wrote a 'Point of View' for the Annals of Neurolgy and submitted it. Unsurprisingly it was rejected. AoN did not even ask for comments from my reviewers (Profs Zamboni, Sclafani and Pillinger). The article is posted below. Please note that it was submitted to AoN on 2-Nov-10, some of the information is already out of date. For instance I did not use the term CCSVI syndrome. I submitted similar articles to other medical journals but was rejected each time. I will tell you about this in latter posts.
I have a letter awaiting publication in the Multiple Sclerosis Journal, hopefully it will be published soon.
ANA 10-1462 (warning it is 3500 words)
2000 Multiple Sclerosis Patients Have Already Chosen A Novel Therapy
People with Multiple Sclerosis discuss Chronic CerebroSpinal Venous Insufficiency avidly, using the worldwide web. Over 2000 People with Multiple Sclerosis have already received therapy for Chronic CerebroSpinal Venous Insufficiency.
This point of view addresses:
a) Knowledge and understanding of many Multiple Sclerosis patients concerning Chronic CerebroSpinal Venous Insufficiency.
b) Brief review of many neurologists’ position, and of recent ‘Chronic CerebroSpinal Venous Insufficiency’ investigations lead by Multiple Sclerosis neurologists.
c) Personal reflections on Multiple Sclerosis and this symptomatic therapy.
d) Pointers to views of a group of vocal and politically aware patients.
21st century communication facilities mean that patients can be as informed about Chronic CerebroSpinal Venous Insufficiency as most neurologists. People with Multiple Sclerosis are patients exercising informed choice when undergoing Venoplasty for Venous Insufficiency, not blindly accepting the latest snake oil.
Venoplasty for Venous Insufficiency is available for people with Multiple Sclerosis, with the financial means to procure it, in a rapidly expanding number of centres around the world. I predict that the number of People with Multiple Sclerosis having had Venoplasty for Venous Insufficiency will exceed 5000 cases in 2012. If MS experts do not start to consider the patients’ view, the divide between MS neurologists and many of their patients could well become a chasm.
MS is an unpredictable and poorly understood disease and it is the right of everyone with this life long and progressive disease, to select a safe symptomatic therapy, without interference.
People with Multiple Sclerosis (pwMS) discuss Chronic CerebroSpinal Venous Insufficiency (CCSVI) avidly, using the worldwide web. Globally, over 2000 pwMS have already received testing and therapy for CCSVI, Hubbard web interview (1). These actions are in direct opposition to leading MS neurologists and MS Societies in UK, USA, Canada, Germany, among others, who are siding with MS experts.
My point of view addresses:
a) Knowledge and understanding of many MS patients concerning CCSVI.
b) Brief review of many neurologists’ position, and of recent ‘CCSVI’ investigations by MS neurologists.
c) Personal reflections on MS and this symptomatic therapy.
d) Pointers to views of a group of vocal and politically aware patients.
Knowledge of CCSVI is moving rapidly for web literate people with MS. A number of patients have read research initiating from a theory by Professor Paolo Zamboni, University of Ferrara, Italy (2, 3). Their next step was to read pilot studies from vascular specialists, in countries as diverse as Jordan (4) and Poland (5). Added to this is the real life clinical experience of over 2000 pwMS, who have undergone balloon venoplasty to de-stenose major veins. This data makes it difficult for most rational pwMS to say that restrictions in major veins are definitely absent from their bodies. Next they need to decide to obtain a diagnosis now or await more research.
It is noted that many pwMS use the term CCSVI for restrictions in major veins, which is the symptom found by vascular specialists. CCSVI is the term Zamboni uses for his hypothesis (2). Sclafani (6) describes the pathology of vein restrictions as fused, reversed, thickened, and other abnormally located and developed valves, with atresias, hypoplasias, duplications, webs, septums, and kinks also occurring. These abnormalities are mostly located centrally near the confluens, Sclafani also reports. Web discussion pwMS report that vein restrictions have been found and treated in left and right internal jugular, azygos, hemi azygos, left and right brachiocephalic veins. Diversity of vein restrictions may relate to the type or severity of MS but there is no conclusive evidence concerning this.
The possibility of reducing disability progression is a dream of most pwMS. Patients have been informed that vascular comorbidity is associated with a substantially increased risk of disability progression in MS, even though this study did not investigate restrictions in veins, Marrie et al (7). An inquiring pwMS then asks, “Is there are a correlation between MS and restrictions in major veins?” Large-scale research is being conducted at the Buffalo Neuroimaging Analysis Center (BNAC) Buffalo, New York, USA, with 1700 subjects and controls (8). Zivadinov et al presented preliminary results from BNAC at the Annual Meeting of the American Academy of Neurology, in Toronto, Canada in April 2010 (9). This research clearly shows that a correlation exists between vein restrictions and MS in more than 50% of pwMS, but BNAC’s use of relatives of pwMS as controls complicates any interpretation of the control group data. Demands, from pwMS, for testing for possible vascular problems, like restrictions in major veins, naturally followed such results.
Vascular researchers have used a non-invasive screening for vein restrictions in the neck, using Colour Doppler Senography, Simka et al (5). The gold standard for diagnosis uses selective venography. This method and the defects of others are described Hojnacki et al (11). Patients appreciate that the only definitive test for restrictions in major veins uses an invasive selective venogram. Sclafani (6) reiterates that without the selective venography procedure no confirmed or negative diagnosis may be given. Vascular specialists, who undertake selective venography daily, inform pwMS that it and balloon venoplasty are low risk procedures. This makes their choice of invasive venoplasty simpler. Plus the fact that no death has been reported following balloon venoplasty is the unequivocal web message circulating among pwMS. It is noted that one pwMS with a family history of stroke died of a brain haemorrhage while on the anticoagulant warfarin, following stenting for CCSVI (web information). Patients susceptible to brain haemorrhage from clot reduction medication should be prescribed low risk drugs, for example, low molecular weight heparins, instead of oral anticoagulants.
Patients, who understand the risks of ballooning veins, will not wait for proof of a link between MS and restricted major veins. They challenge the need to wait for 5 to 10 years for detailed and expensive research programmes, demanded by some MS neurologists (10). PwMS do not understand why MS neurologists believe they have the right to control symptomatic treatment for pwMS in an area, which is outside their expertise. Consider the use (in the UK) of botulinum toxin (botox) by urologists for pwMS with bladder issues (11). The UK MS Society and many neurologists support this procedure after a trial with 43 patients. Why was this totally different standard used, compared to the extensive double blind, multi-centre clinical trials being demanded for CCSVI? Balloon venoplasty is an available procedure, which simply adapts methods in everyday use (1, 6). This information assists early adopters in their decision to choose venoplasty for venous insufficiency (VVI) treatment.
Brief review of neurologists’ concerns and their ‘CCSVI’ investigations.
The first academic salvo over CCSVI emanated from MS neurologists at Wayne State University in March 2010 (10), followed by a Lancet Neurology editorial reporting opinions of UK ‘leading experts’ to attempt to justify halting any treatment of CCSVI symptoms in pwMS. “Poor judgment in medicine can lead to interventions with fatal consequences. Lives should not be lost before these interventions are halted”, commented Jane Qiu, (12), in May 2010. Some MS neurologists have marshalled additional opposition to Zamboni’s hypothesis, with papers from Germany and Sweden. Doepp et al (13) report that no cerebrocervical venous congestion was found in an extended extra- and transcranial color-coded sonography study in a small sample of 56 MS patients and concluded that Zamboni’s hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS is challenged. Sundström et al (14) studied 21 relapsing-remitting multiple sclerosis cases and 20 healthy controls with phase-contrast magnetic resonance imaging. In addition, in pwMS, contrast-enhanced magnetic resonance angiography was performed. The study concluded that no evidence confirming the suggested vascular multiple sclerosis hypothesis was found.
Reflections on MS and this symptomatic therapy
A cursory analysis of these neurologist lead studies questions why none used published diagnosis methods described by vascular practitioners (5, 6, 8, 11), and why the etiopathogenesis of MS has a “prevailing view” (14) after over 150 years of diverse opinions on MS. The web has generated conspiracy theories as to the reasons behind the purpose and funding of such research. Many rational pwMS feel cast adrift by many MS neurological researchers, who have failed to attempt to address the fundamental questions on vein restrictions and MS, which are:
1 – What proportion of pwMS have restrictions in major veins, when investigated using invasive selective venoplasty?
2 – What happens to the physical health, mental health and general well being of pwMS, if all occurrences of restrictions in major veins are de-stenosed, using balloon venoplasty?
In near future, I hope that some MS researchers appreciate that the definitive diagnosis and therapy, uses venography, an invasive procedure, to conscious patients. Blinding of studies is highly problematic and ethical approval of an invasive procedure to non-MS controls could be difficult. Trial subjects are likely to read web reports saying that balloon venoplasty may be felt, as the subject is conscious throughout the procedure. I am curious to know if real blinding is possible in such trials. Proper studies will require designs, which are markedly different from the placebo-controlled double blind ones used for new MS drugs. These studies should test de-stenosis in combination with the best available MS drug therapy and alone in drug naïve pwMS.
Currently, vascular and MS researchers cannot agree if restrictions in major veins are present in pwMS, let alone how to find this symptom, or what to call it. PwMS will be best served by joint research on the fundamental questions, rather than a turf war, which is occurring currently.
In my personal attempt to gain an overview of MS, over the past 8 years, I have studied many MS papers. With this overview, I suspect that MS will be found to be a disease initiated by genetic traits combining with gestational, immunological, environmental, vascular and other factors. These factors, in non-unique permutations and combinations, provoke some people with genetic susceptibility to develop MS, but not others, even with homozygotic twins (15). This makes Multiple Sclerosis a truly complex multi-factorial disease, and years more research will be needed before the genetics and interactions between relevant factors are fully explained. However, why is this safe symptomatic therapy not permissible in the intervening period?
From anecdotal reports following venoplasty for venous insufficiency (VVI), I suggest that two separate groups of symptom changes may require investigation in future research:
- Early, possibly vascular driven symptom changes.
- Later, possibly neurologically driven symptom changes.
The early improvements described by early MS adopters of VVI include reduced cognitive/brain fog, eased muscle spasm/tone, warmer feet and/or hands and the return of rapid eye movement (REM) sleep. These changes are reported as starting only hours or days after the de-stenosis procedure. I suspect that these changes will be attributed to improved CNS perfusion, gained from better blood flow. The resultant reduced levels of waste products in the cerebrospinal fluid and then in CNS cells is likely to be the more significant factor in the improvement in cell performance, rather than improved oxygen levels. My judgment comes from considering hyperbaric oxygen therapy, which certainly increases oxygen in the CNS and has been used for 25 years in pwMS. Oxygen therapy has had limited success, when compared with the anecdotal reports following VVI. Lack of oxygen could lead to cell damage and death, which are irreversible. Whereas, elevated waste product levels could simply slow performance of CNS cells and is in theory reversible. Further research is needed to determine the mechanism bringing the positive effects but the anecdotal evidence from the large majority of 2000 pwMS, in multi-centres, does not suggest there are sufficient risks to justify waiting for more research. The low risk procedure of VVI appears to alleviate CCSVI in most pwMS. Unfortunately, it is only available for people with sufficient money or insurance to pay for it.
Later and gradual improvements described following VVI include anecdotal reports of changes to most symptoms of MS. These changes are often reported as occurring more than 90 days after de-stenosis therapy. Remarkable changes include a patient who was wheelchair bound but became able to walk again after de-stenosis therapy and an intensive programme of physical therapy. I suspect that remylination is a factor in this type of case but brain plasticity also needs to be investigated, as either or both may occur. Remylination is a slow and usually incomplete process in pwMS; therefore any similarities or differences in the CNS following VVI need to be fully investigated, using the latest scanning techniques.
Amongst the anecdotal reports are instances where improvements to MS symptoms only last for a few days. MS symptoms vary greatly over time, so such short-lived benefits could be due to a post procedure boost or placebo effect. Future studies need to be sufficiently long term in order to reduce any criticism of the reporting of such effects and also need to monitor possible re-stenosis in trial subjects.
Research and anecdotal evidence is far from proving a cause or effect relationship between major vein restrictions and MS. However, patients are not concerned if the correlation coefficient between MS and vein restrictions is 0.55 (8), 0.84 (3), 0.9 (4) or 0.9 (2), and they are indifferent if their vein restrictions are a cause or a product of MS. They simply ask:
Do I have the symptom, restricted major veins, or not?
Some PwMS consider that a diagnosis of MS is sufficient for them to demand an invasive catheter venogram in order to identify any venous abnormalities worthy of venoplasty for venous insufficiency (VVI).
MS experts would be prudent to remember that treating symptoms with available therapies, before understanding the whole disease process has been a successful medical and pharmaceutical practice for many decades. PwMS do not intend to deviate from this custom now and are not prepared to wait for an explanation of the science behind the correlation between restrictions in major veins and MS, before correcting any symptoms identified. MS neurologists should step aside and stop obstructing pwMS from obtaining this low risk diagnosis and therapy, or face the anger of politically active pwMS
Vocal and politically aware patients
In the absence of collaboration from most neurological MS experts, pwMS, their families and carers have created a website, www.ccsvialliance.org
, to supply balanced information, primarily to United States residents. Additionally, http://csvi-ms.net/en
provides background on CCSVI and a comprehensive reference list. In the UK on 12 July 2010, the Daily Telegraph, page 23, titled an article ’It’s a turf war, and we are the losers’. The main article text is available online (16).
21st century communication facilities mean that patients can be as informed about CCSVI as most MS neurologists. The web is brimming with the latest research papers in this area, plus seminars from vascular experts who have performed VVI are available online. No longer is a knowledgeable pwMS forced to wait for pronouncements from their MS neurologist. PwMS are patients exercising informed choice when undergoing VVI, not blindly accepting the latest snake oil on offer.
Professor Zamboni recommends that balloon venoplasty be used alongside disease modifying drug therapy for MS, in monitored situations. Hardly a radical suggestion, while more research is conducted, for patients coping with this life long and disabling disease. Balancing the risks against possible benefits must be entrusted to informed MS patients. People with MS, like me, should be permitted to choose for themselves. In our global village, the de-stenosis procedure or venoplasty for venous insufficiency (VVI) is available for pwMS with the financial means to procure it, in a rapidly expanding number of centres around the world. This gives some pwMS the choice they deserve and I predict that the number of pwMS having had VVI will exceed 5000 cases in 2012, such numbers will make the current position taken by many MS experts untenable. I advise MS experts to start to consider their patients’ view, otherwise the divide between MS neurologists and many of their patients could well become a chasm.
My personal conclusion to my research was to make a trip from Oxford, England to Athens, Greece for a diagnosis. There I was told that I had restrictions in four major veins and I asked to have them de-stenosed, using balloon venoplasty. The diagnosis and procedure was performed successfully by pioneering, consultant vascular surgeon, Mr C Kartkaletsis and team in June 2010.
I fully appreciate that it is too soon to conclude anything about the long-term impact of VVI on my MS. Above all, MS is an unpredictable and poorly understood disease. However, it is my right, and that of all others with this life long and progressive disease, to select a safe symptomatic therapy, without interference or obstruction from experts.
Mark A Walker, Oxford, England.
Author’s names, degrees and affiliations;
Mark A Walker, BPharm, MIPharmM, MRPharmS.
Chair, Oxford Multiple Sclerosis Therapy Centre. www.omstc.org
Charity Number 900278
I have no conflicts of interest and I have received no financial support for this article.
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Chronic Cerebrospinal Venous Insufficiency
Venoplasty for Venous Insufficiency