Reflections on the first
CCSVI International Conferences
March 2011 will be remembered as the month when CCSVI really took to the world stage. The First International Venous Endoplastic Forum in Poland and the First meeting of the International Society of Neurovascular Disease in Italy brought together most of the world’s experts on this condition, to share their experience and present vital new research in this area.
The meeting in Katowice Poland attracted delegates from as far away as Argentina and including a wide range of specialties, neurology, cardiology, vascular surgery, intervention radiology and general practitioners. It underlined the fact that the treatment of MS is now truly multidisciplinary. The presentations included an excellent paper by Dr Ivo Petrov from Bulgaria showing significant improvements in oxygen saturation following the procedure. He postulated that this was a possible reason for the immediate improvement that patients describe after angioplasty.
We heard news of a 500 patient study from Poland submitted for publication which showed CCSVI on venography, the gold standard, in 94% of cases. This paper will be of immense importance as it bypasses the controversy over the negative Doppler studies, very dependent of operator bias. Prof Miro Denislic, a neurologist from Solvenia, presented their findings which, in keeping with several other papers, showed that improvements in fatigue were the most persistent benefits in patients after angioplasty. I (Dr Tom Gilhooly) presented our early findings from structured telephone questionnaires on 45 patients at one month post procedure. This shows 60% of patients reporting an improvement in quality of life and a similar percentage reporting an improvement in fatigue.
Another Polish paper showed no change in the EDSS score at 6 months but an improvement in fatigue. The EDSS ( Expanded Disability Status Score) relies very heavily on measuring motor function and does not appear to be sensitive enough to pick up improvements in many other areas such as sensation, bladder function and fatigue. It is doubtful if this tool will be useful in future studies as there are other validated research tools which are more sensitive.
My abiding memory of this conference will be the valuable time I had with Dr Franz Schelling, an Austrian doctor who has been proposing the vascular theory of MS for over 40 years. He showed me from first principles the importance of venous hypertension on the brain and told me he spent several years discussing this with Paulo Zamboni before the seminal CCSVI papers appeared. I left Poland with a strong sense that by improving venous hypertension we have for the first time, a possible way to really make a difference in this disease. Combining this approach with immune modulation could produce the most effective treatments yet for MS.
The first meeting of the International Society of NeuroVascular Disease (ISNVD) in Bologna was a first rate scientific meeting. It consisted of two days of intense activity with 50 presentations ranging from animal research to presentations of the science on flow dynamics. There were so many highlights it would be difficult to describe them all. The mouse model for CCSVI was produced by ligating the jugular vein and showed a significant disturbance of gait.
An understanding of flow dynamics in the brain is vital and Prof Clive Beggs from Bradford University gave an excellent overview of this. His conclusion was that extracranial blockages in venous drainage will produce increased back pressure on the small veins in the brain. This is more likely to happen in the deep veins and would explain the appearance of perivenular lesions in white matter. One of the most impressive studies presented was by American Neurologist David Hubbard an expert of functional MRI scanning. This advanced type of imaging shows clear differences in blood flow between healthy normal patients and those with CCSVI.
The differences in flow are improved following angioplasty providing an objective measure of improvement which is difficult to achieve with other methods.
Prof Robert Zivadinov, the next President of ISNVD after Paulo Zamboni, presented an excellent paper soon to be published which showed the severity of CCSVI was directly related to reduced cerebral blood flow in both white and gray matter. It was another fine example of the scientific papers which validate the vascular hypothesis in MS. This is a compelling theory where back pressure in the veins leads to breakdown of the blood brain barrier tight junctions. This allows the movement of iron and other blood products into the brain tissue. It was postulated that iron is a good candidate for activation of the immune system and destruction of the brain cells and myelin sheath. In this model, the T cells enter the brain tissue to mop up the damage caused by this inflammation rather than being activated in an autoimmune process.
I had the opportunity to speak with all of the speakers including Paulo Zamboni who was very supportive of our work in the UK.
Prof Andrew Nicolaides chaired the session on consensus white paper from the society which outlines very carefully the current situation with respect to the scientific research on CCSVI. I was fortunate to spend some time with him and he was very clear that our approach in the UK was the correct one. It is vital to get experience of the condition and the angioplasty procedure before embarking on a randomised trial. He will be a valuable mentor in the future to make sure our study design is correct and has enough statistical power to demonstrate the proper outcomes. A large prospective blinded study is planned in Italy which has been funded partly by the government. It is planning to treat 650 patients over 20 centres in Italy and should help to establish the value of this treatment. There were some concerns at the conference over the design of the study and particularly that it is very difficult to blind patients to a treatment which can be painful.
Dr Mike Dake from Stanford is also involved in a blinded study where the patients will be anaesthetised to mask any pain during the procedure. Listening to these discussions was very helpful in planning our three country randomised trial on CCSVI. It is clear we need to take advice from several quarters to get this right but this was a great start to the process.
The next ISNVD meeting is in Orlando Florida next year by which time I hope to have at least one completed paper to contribute. Both Paulo Zamboni and Prof Mark Haake asked if I would be involved in the committees of the society and it will be a great honour to do so. The overwhelming feeling at the conference was one of great excitement.
We are at the beginning of a process which is going to change the lives of millions of people. I think this is why I became a doctor in the first place and despite all the opposition that this new idea has had, the feeling from both Katowice and Bologna is that this is now unstoppable.