With the eagerly anticipated research studies on the role of CCSVI in Multiple Sclerosis, and clinical trials evaluating balloon angioplasty as a treatment for CCSVI and Multiple Sclerosis underway,.............
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The Breakthrough Treatment for MS | View it in your browser. |
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Effectiveness of CCSVI Treatment CCSVI is undoubtedly one of the major discoveries in medicine this century. To actually define a new medical condition with anatomical abnormalities is a breathtaking development.  It is no surprise that it has created considerable controversy in the medical world. How could we have missed something so important and indeed there are some published papers which cast doubt on the very existence of CCSVI? Having observed the lesions on Doppler ultrasound, venogram and with intravascular ultrasound, it is clear that this is a real condition and in time all doubts will be cast aside.The area where there is still some doubt however is whether treating these lesions produces a worthwhile clinical benefit. CCSVI is a great discovery but is it a breakthrough in treatment for patients with MS and other neurovascular conditions? The Bologna conference in March 2011, from the International Society of Neurovascular Disease (ISNVD), was a great platform for the presentation of new research into CCSVI. It was also a good forum for introducing the next generation of studies which are aimed at investigating the effectiveness of CCSVI treatment.  The current president of ISNVD is Professor Robert Zivadinov; a consultant neurologist from Buffalo University in New York. His background is in Multiple Sclerosis research mainly into pharmaceutical treatments for the disease. It was very clear from his conference presentations, and in conversation, that he is an academic heavyweight who has concluded that CCSVI is a very important area requiring clinical investigation. He is involved in one of the three randomised controlled trials into CCSVI treatment and has a strong association with Paulo Zamboni and the University of Ferrara.This combined team from these two Universities, Buffalo and Ferrara, have published an early trial on the effectiveness of treatment in the European Journal of Vascular and Endovascular Surgery (1). Although the number of patients was small, fifteen in total, the results are suggestive of a positive effect from CCSVI treatment. There was no control group in the study but the angioplasty treatment was staggered with a group of eight patients treated initially and the other seven treated after a six month delay. One of the traditional study endpoints in MS is the frequency of relapses which was reduced in the early treatment group. Two of the initial group had a relapse in the next six months as opposed to five from the seven who were in the delayed group (had not been treated at that point). Of even greater significance was the fact that the brain volume of the treated group was reduced compared to the untreated group. This would suggest that treatment of the venous outflow from the brain, reduces swelling and inflammation. As Prof Zivadinov suggests, the numbers are too small to make any firm conclusions but the positive outcomes give great encouragement for future research. As part of our ongoing investigative approach to CCSVI treatment in Scotland, we are collecting a large amount of data including an independent assessment of neurological function. Early indications are that our results are very similar to those being published and presented at International conferences. It will be some time before we have the data fully analysed but we are very encouraged by the objective improvements reported both here in the UK and abroad, The largest randomised controlled trial is due to start in Italy , BRAVE DREAMS, is looking at several hundred patients and will hopefully be of a size that can allow more concrete conclusions to be drawn.  Another New York based study at Albany University, under the direction of Dr Manish Mehta, is a prospective randomised double blind trial which aims to recruit 600 patients. Initial results were presented at the Second CCSVI Conference in New York in July 2011. 48 patients who had undergone angioplasty treatment were assessed after 4.5 months using the Expanded Disability Severity Score (EDSS). The EDSS is a very difficult score to improve but in these patients there was a statistical improvement in those with relapsing remitting MS and secondary progressive MS. The patients with primary progressive did not improve on EDSS. 79 patients were evaluated with a timed 25 foot walk which showed significant improvements. He also reported that there were improvements in fatigue and quality of life indices for those who had undergone treatment.While these results are far from conclusive, in combination with the excellent safety data which has recently been published, they are very encouraging and suggest that CCSVI is not just a major discovery but may also have opened the way for improved treatments for MS.  References :
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he Breakthrough Treatment for MS | View it in your browser. |
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CCSVI Update A clear understanding of Multiple sclerosis has proved elusive for generations of doctors and scientists.The first suggestion that there could be a vascular component to the disease dates back 180 years to Sir Robert Carswell from Glasgow. He was drawing an image of a post mortem sample of brain tissue from an MS patient and commented that "there appears to be vascular lesions here". Dr Franz Schelling from Austria has been a lone voice for many years in promoting this theory and I spent an intriguing half hour with Franz as he drew the various venous sinuses on napkins at the CCSVI conference in Poland this year. It was Franz who convinced Paulo Zamboni to explore this field and the results of that collaboration has changed the world of medicine. The recent discovery of the importance of CCSVI has filled in many of the gaps in our understanding of the disease.  At the International Society of Neurovascular Diseasemeeting in Bologna in March this year, Dr David Hubbard, a consultant neurologist from San Diego, gave the clearest description of MS that I have ever heard. He described how leakage of blood products across the blood brain barrier caused the initial damage in the brain tissue. The immune system became aware of this damage and was triggered to respond as a secondary event. I sought him out later to congratulate him on his presentation and particularly the clarity of his description of how the vascular and immune parts of the disease interact. This made sense on many levels and explained why most current treatments are only partially effective as they are aimed at the secondary and not the primary driver of the disease. This new paradigm does not exclude the immune system and immune modulating drugs as part of a treatment regime but this new understanding gives new possibilities for treatment with the possibility of improved outcomes.Treating venous pressure by means of angioplasty could be a relatively safe and easy way of improving outcomes in MS if this theory is proven to be correct. A recent study by Ivo Petrov from Bulgaria, presented a series of over 461 CCSVI procedures carried out in Sofia, showed no major complications which confirmed the safety of angioplasty in MS (1). A new paper published in the Journal 'Brain' in June 2011 appears to support this new paradigm (2). A research team from Vienna examined post mortem samples of 30 MS patients and 25 controls who died of other causes. For the first time, they have shown that the most recent MS lesions were associated with oxidative stress damage consistent with leakage across the blood brain barrier. Older lesions showed the T lymphocyte infiltration typical of an immune response.  A good demonstration of the damage that blood products can produce is in cellulitis in legs associated with varicose veins. As the veins enlarge, the increased pressure in the vessel causes the junction between endothelial cells lining the vein to widen allowing blood products to leak into the leg tissues. This causes inflammation in the tissues with the classic inflammatory signs of redness, heat, swelling and pain as seen in this image.The brain has the relative protection of the blood brain barrier but this is simply a tighter connection between endothelial cells, thirty proteins joining the cells as opposed to the usual ten. Increased venous pressure in the deep veins of the brain will eventually loosen even these tight junctions and when the blood products leak into brain tissue the damage will be similar to that seen in leg cellulitis. The secondary immune response is triggered to try in an attempt to limit this damage but in itself, this response can increase inflammation. After seven years of successfully using LDN in the management of MS, I knew that the immune system was an important factor in all types of the disease. Paulo Zamboni, Franz Schnelling, David Hubbard and others are helping us to understand the complex interplay between the immune system and the venous system in MS. A combined approach to the management of the disease is a logical way forward. Like any new paradigm, this will take some time to be accepted by all of those involved in treating and raising the awareness of this condition but as the research stacks up, it will become clear that a major step towards understanding and successfully treating MS has taken place. There is still much to learn and many unanswered questions but CCSVI has taken us a long way towards better understanding and treatment of this complex condition. References :
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It has become clear that one of the main issues with CCSVI is venous hypertension; raised pressure within the venous system of the brain. This increased pressure is transmitted to the deep veins in the white matter of the brain and in time affects the integrity of the tight junctions of the blood brain barrier.
Dr Salvatore Sclafani from New York pointed out that the veins are totally dependent on the venous blood for their nutrients and therefore this flow should not be disrupted for any significant period of time. Overenthusiastic and aggressive use of balloon catheters to disrupt valves could be damaging to the veins in the long term if the oxygen supply is reduced by the very procedure which is aimed at restoring normal flow. Current practice in the UK is similar to other centres where the valves and other intraluminal obstructions are treated with a combination of balloons, cutting wires, cutting balloons and particularly double balloons.
Professor Paulo Zamboni has obviously given this area much thought and has filed a patent for a device called a valvulotome. He feels this will be the most effective way of dealing with abnormal valves without damaging the vessel wall but on further questioning it became clear that there is no suitable valvulotomes available at present which are the right size for use in the jugular veins. This type of device is designed to permanently damage the valves without damaging the surrounding veins. It has been used in cardiology to remove the valves of the saphenous veins used in cardiac grafting.