PRESS RELEASE
Bologna, Tuesday Sept. 8, 2009
FONDAZIONE HILARESCERE
Venous Function And Multiple Sclerosis
International Coterie

Four main points concerning the relationship between CCSVI and MULTIPLE SCLEROSIS were covered by several experts at a Meeting in Bologna. All the investigations that gave an answer to these 4 fundamental points were coordinated by Prof Paolo Zamboni who discovered CCSVI and its association with Multiple Sclerosis; in some other cases, research was carried out in cooperation between Prof Zamboni and major foreign Universities.
1) What is the origin of the extracranial cerebral vein stenoses which characterize CCSVI?
2) Are there advanced diagnostic systems capable of identifying which changes are caused by CCSVI in the central nervous system?
3) Can CCSVI be treated and how?
4) Can CCSVI therapy improve the clinical outcomes of MS and affect its prognosis?


Venous Function And Multiple Sclerosis is an international coterie of experts who met in Bologna on September 8 to discuss these issues from the perspective of neurologists – who have developed the scientific body of knowledge on MS – and the vascular and neurological surgeons who have further investigated these topics following the discovery of CCSVI. All investigations were coordinated by Professor Paolo Zamboni who discovered CCSVI and its association with multiple sclerosis.
This first study was conducted by an Italian research team composed of the vascular surgeons’ group headed by Professor Paolo Zamboni from the University of Ferrara and the neurologists’ group from the Department of Neurosciences of the Bellaria Hospital in Bologna headed by Dr. Fabrizio Salvi.
Fondazione Hilarescere is a foundation specially set up to provide adequate means and resources for research into medical and scientific insights aimed at fully understanding and curing diseases which are still partly unknown.
Fondazione HILARESCERE, chaired by Professor Fabio Roversi-Monaco, was set up on an initiative of Fondazione Cassa di Risparmio in Bologna.


THE MOST IMPORTANT ANSWER OF ALL:
endovascular therapy has led to a decrease in the number of disease relapses, a marked reduction in the number of active brain and spinal lesions and also a clear-cut improvement in the patients’ quality of life.
Prof. Paolo Zamboni headed a study where, together with Dr. Fabrizio Salvi, he was able to show that in patients with the clinical form of Relapsing-Remitting MS – which is the most common – there is a drop in the number of active lesions which persists up to 18 months after surgery. The percentage of active lesions falls from 50% to 12%, thus showing that the additional treatment of CCSVI reduces the aggressiveness of the disease. This finding is further confirmed by the number of patients who showed no relapses after endovascular surgery. In the 2 years before surgery, acute multiple sclerosis attacks were found in 50% of the recruited patients, while in the 2 years following surgery 73% of the patients had no more attacks, with a change in the clinical course of the disease. In all these patients also cognitive and motor activities – assessed by means of an outcome measure called MSFC - are significantly and persistently improved while the same is not true for patients with the progressive forms of the disease. In the latter, however, progression was stopped and the patients’ quality of life improved.
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The experts discussed, provided data and gave an answer to all 4 fundamental questions:
1) What is the origin of the extracranial cerebral vein stenoses which characterize CCSVI?
3 scientists answered this question from different perspectives: Professor Byung B. Lee, Georgetown University School of Medicine di Washington DC, showed that the malformations found in CCSVI are congenital truncular malformations which therefore certainly precede the development of Multiple Sclerosis. For this reason they cannot be regarded as a consequence of Multiple Sclerosis. Prof. Lee showed in which phases of the venous system development the malformations observed in CCSVI may appear. Byung B. Lee is the Chairman of the World Consensus Conference which gathers vascular experts from 47 countries and recently approved a scientific update on venous malformations in Montecarlo. (1)
Professor Giulio Gabbiani, Centre Médical Universitaire di Ginevra, demonstrated that there are no auto-immune phenomena in diseased veins thus excluding that the malformations found in CCSVI result from Multiple Sclerosis. He showed the results of a study which provides a histologic comparison between the walls of the veins affected by CCSVI-MS and those of normal subjects. Furthermore, at molecular level, CCSVI veins are structurally different from those of the control subjects, thus confirming the approach of the Montecarlo Consensus Conference. Prof. Gabbiani is one of the most important world experts in microscopic vessel wall morphology. (2)





The third presentation was about whether – genetically speaking – these malformations have any correlation with the findings so far obtained from the genetic study of MS. Prof. Alessandra Ferlini, Director of the Institute of Genetics at the University of Ferrara, discussed this point by presenting the promising results of a pilot study. (3)

2) Are there advanced diagnostic systems capable of identifying which changes are caused by CCSVI in the central nervous system?
This is the second question addressed at the Meeting. Professor Mark Haacke, Director of the MRI Istitute for Biomedical Research in Detroit (4,5,6) and Professor Bianca Weinstock-Guttman, Neurologist at the Jacobs Neurological Institute (7) showed new magnetic resonance (MRI) parameters linked to CCSVI which might in the future bring about a true revolution in the way of diagnosing MS. These new parameters include: quantification of iron deposits and volume assessment of intracranial veins and CSF.

3) The third question that was answered at the Meeting was: Can CCSVI be treated and how? Innovative minimally-invasive endovascular repair techniques were discussed on account of the findings obtained by Dr. Roberto Galeotti (8), Head of the Interventional Radiology Section at the University Hospital of Ferrara who was the first in the world to perform this type of surgery, and Dr. Michael Dake, Chief of Cardiovascular and Interventional Radiology at Stanford University School of Medicine (California), who was the first to treat CCSVI outside Italy.
The most important finding is safety. At 2-year follow-up no major complications were observed. All surgical procedures were performed on a day hospital basis. Statistically, this treatment decreases pressure in the cerebral veins in a highly significant way, thus showing its enormous anti-inflammatory potential. (8)
The risk of re-stenosis is 16 times higher in the jugular veins than in the azygos vein, thus pointing to the need for more sophisticated and efficient tools to approach the former. Research will make such tools available during 2010.

4) The fourth and fundamental point is whether CCSVI therapy can improve the clinical conditions of MS and affect its prognosis.
Dr. Fabrizio Salvi from the Bellaria Hospital in Bologna was the first Neurologist who studied the clinical correlations of CCSVI treatment in MS patients together with Prof. Paolo Zamboni. The patients enrolled in this study were 120 from all clinical classes, but only the results of the 65 subjects who are over 18 months from surgery will be reported in order to describe the outcome with the greatest possible accuracy. Generally speaking, patients treated with endovascular therapy showed a decrease in the number of disease relapses, a marked reduction in the number of active brain and spinal lesions and also a clear-cut improvement in the patients’ quality of life. The findings of this investigations will soon be published in detail on the Journal of Vascular Surgery (8).



Finally, Dr. Robert Zivadinov, Jacobs Neurogical Institute di Buffalo, discussed the results of a revolutionary pilot study performed last year where both American and Italian patients were blindly assessed in the USA by means of advanced MRI technology, then submitted to vascular surgery in Italy and followed up during the following year (9). This study was defined by the patients who volunteered to participate as the study of the 50,000 miles for treatment, because of the many trips they had to take overseas. This study was sponsored by Fondazione Hilarescere.

References
World Consensus Conference on Venous Malformations, Montecarlo September 4th 2009. This document was approved by experts from 47 different countries and will be published on all most important vascular surgery journals.
G. Gabbiani, M. Coen, F. Mascoli, P. Zamboni. Manuscript in preparation.
A. Ferlini, M. Bovolenta, M. Neri, F. Gualandi, A.Yuryev, F. Salvi, A. Liboni and P. Zamboni. Manuscript in preparation.
Haacke EM, Makki M, Ge Y, Maheshwari M, Sehgal V, Hu J, Selvan M, Wu Z, Latif Z, Xuan Y, Khan O, Garbern J, Grossman RI. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging. 2009;29:537-44.
A. V. Singh and P. Zamboni Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab. 2009 Sep 2. [Epub ahead of print]
P. Zamboni, E. Menegatti, B. Weinstock-Guttman, C. Schirda, J. L. Cox, A. M. Malagoni, D. Hojnacki, C. Kennedy, E. Carl, M. G. Dwyer, N. Bergsland, R. Galeotti, Sara Hussein, I. Bartolomei, F. Salvi, R. Zivadinov. The severity of altered venous haemodynamics is related to CSF dynamics in chronic cerebrospinal venous insufficiency Submitted To Current Neurovascular Research
P. Zamboni, E. Menegatti, B. Weinstock-Guttman, C. Schirda, J. L. Cox, A. M Malagoni, D. Hojnacki, C. Kennedy, M. G. Dwyer, N. Bergsland, R. Galeotti, I. Bartolomei, F. Salvi, M. Ramanathan, R. Zivadinov. Csf flow and brain volume in multiple sclerosis are associated with altered cerebral venous doppler haemodynamics. Study presented at the European Multiple Sclerosis Congress ECTRIMS Düsseldorf, 9-12 September 2009
P. Zamboni, R. Galeotti; E. Menegatti; A. M. Malagoni, S. Gianesini, I. Bartolomei, F. Mascoli, F. Salvi Endovascular treatment of chronic cerebrospinal venous insufficency. A prospective opern-label study. Journal of Vascular Surgery, 2009, in press.
P. Zamboni, R. Galeotti, B. Weinstock-Guttman, G. Cutter, E. Menegatti, A. M. Malagoni, D. Hojnacki, J. L. Cox, C. Kennedy, I. Bartolomei, F. Salvi, R. Zivadinov Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis . A longitudinal pilot study. Study presented at the European Multiple Sclerosis Congress ECTRIMS Düsseldorf, 9-12 September 2009


Bologna, 8 September 2009
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