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Press Release: There is no correlation between CCSVi and MS

12/10/2012

 

Lyon. 12th October, 2012. The CoSMo study, recently concluded, highlights that 97 % of people suffering from MS does not have the CCSVI (Chronic Cerebrospinal Venous Insufficiency). In the remaining 3 %, the CCSVI can be verified with a percentage which is totally equivalent observed both in healthy controls, in patients suffering from MS and in patients suffering from other neurological diseases. No difference is encountered between the CIS (Clinically Isolated Sindrome) with respect to relapsing-remitting, either secondary or primary progressive MS forms. In the CCSVI diagnosis no risk factors, like age and gender, were highlighted. These, in summary, are the results of the CoSMo study, promoted and financed by AISM (Italian Multiple Sclerosis Society) and presented to ECTRIMS, (European Committee for Treatment and Research in Multiple Sclerosis).

 

CoSMo “Observational Study of the prevalence of CCSVI in Multiple Sclerosis in Other Neurodegenerative Diseases (OND)” is the largest observational and multicentric study, with double-blind reading performed to date, with an investment of 1.5 million euros: 1767 case analysed, 35 neurological centres involved and 26 trained sonologists covering the whole country, 3 international expert for the centralised reading of the exams. A 2-year lasting work to achieve the completion of the study. The final evaluation of the CoSMo study has been performed on 1165 patients affected by MS, compared with 376 healthy controls and with 226 patients affected by other neurological diseases.

 

The mechanism of centralised blinded reading, competent and free from any biased judgement connected to the interaction with the person examined, combined with the wide multicentricity, the numbers of samples analysed and with the widest database of examined subjects (which remains at the complete disposal of the whole scientific community) are the strengthpoints and unicity of this study, and ensure its scientific reliability.

 

CoSMo. Study, data analysis
Upon a total of 1165 people with MS examined, the CCSVI was observed in only 38 subjects, that is, in only 3.26% of patients with MS. The CCSVI is evident in 12 healthy subjects on 376 examined, equivalent to 2.13% of cases; besides, it has been detected in 3,10% of the cases of patients affected by other neurological pathologies: only 6 on 226.

 

Such low frequency, combined with the small presence of CCSVI in all the three different groups of people analysed, removes any possible doubt and eliminates the possibility of association between MS and CCSVI – explains professor Mario Alberto Battaglia, chairman of the Italian Foundation Multiple Sclerosis (FISM) – To treat MS and defeat it, it is necessary to address research trends towards other directions”.

 

 

THE OPINION OF THE MAIN INVESTIGATORS OF COSMO STUDY
Giancarlo Comi –. Director of the Department of Neurology and the Institute of Experimental Neurology, University ‘Vita-Salute’ – San Raffaele, Milan: The data show that the CCSVI is not a pathology linked to multiple sclerosis. In fact, it is encountered in similar percentage also in healthy subjects. For some time, for numerous reasons, widely supported  by evidence-based literature, the scientific community, had already excluded the idea that the CCSVI could be the cause of MS. However, many among us, the researchers in MS fields, had considered they it could not be excluded a priori that this condition might play a role, even secondary, among the different and multiple factors involved in influencing the evolution of multiple sclerosis. The CoSMo results highlight that there is no possibility, not even for a minimal role of CCSVI in MS. There is no reason that could lead to treat CCSVI in order to cure multiple sclerosis”.

 

Gianluigi Mancardi – Chairman of AISM Scientific Committee, and Director of Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy.Different studies on CCSVI and SM were carried out on small numbers; for this reason, the Italian MS Society (AISM) selected a so wide sample: the more subjects are included in the study the most reliable the results will. Besides, a study which is reliable has to be multicentric, that is to say, carried out by many different Centres. Many studies on CCSVI are single-centred and, hence, could lack of scientific validity. In order to establish the possible association of a condition with a disease, it is necessary to see it anywhere, in any diagnostic center, so that’s why we involved so many participants. An fundamental value of CoSMo is its mechanism of blind-reading, both by the local examiner, as well as by the central reader, because this ensures that the judgement is not biased by the knowledge of the person examined”.

 

  

 

The opinion of AISM, Italian MS Society
About 97% of patients suffering from MS is not affected by CCSVI. The percentage of chronic cerebrospinal venous insufficiency is similar in patients with MS (3%) as in patients affected by other neurological diseases (3%) and even in healthy controls (2%).

 

Therefore CCSVI is not a disease connected to multiple sclerosis. Based on the results obtained by the scientific research for people affected by MS, there is no need to carry out additional tests to diagnose CCSVI, nor is vein surgery required. To treat and defeat MS new approaches should be encouraged.

 

As promised the Italian MS Society (AISM) presents this scientific, reliable data available for all the patients with MS, to allow them to make decisions about their treatment, and to live their lives to the fullest.

 

AISM presents CoSMo results to national and international scientific research and clinical communities, so that the health of persons with MS may be protected and not put at risk without motivation.

 

AISM urges the Ministry of Health, the health Regional Authorities to take into account the CoSMo study results when defining clinical care pathways for multiple sclerosis, to provide people and health institutions with new recommendations.

 

As always has done in its history, AISM will continue to be at the forefront in encouraging the most promising and urgent research work in Italy and worldwide: investigating the causes of the disease, finding new treatments for the severe forms of MS (progressive MS), experimenting stem cell therapy in humans, making everyday care and rehabilitation more efficient, in order to promote autonomy and good quality of life that every person with MS wishes to have.

 

Antonella Moretti (CEO of AISM), Mario Alberto Battaglia (Chairman of FISM), Agostino D’Ercole (Chairman Italian MS Society)

 

 

 CoSMo STUDY
 

 

 

Identifying the prevalence of CCSVI in patients suffering from MS

The study started on December 30th, 2010 after a long period dedicated to work out an accurate scientific reference protocol, on the training, to obtain the authorization from Ethical Committees and Clinical Centers and recruit a large number of participants. It ends almost two years later, in September 2012.

 

The identikit. First multicentric epidemiological study, the largest performed to date. 35 clinical centers involved throughout the nation. It was conducted to study the prevalence of CCSVI in people with multiple sclerosis (compared to the prevalence in healthy volunteers and in other neurodegenerative diseases) making use of the Color Doppler ultrasound technique (ECD).

 

The study was entirely promoted and funded by the Italian Multiple Sclerosis Association through its Foundation FIMS, with a budget of about 1,5 million euros.

 

Training of certified sonologists
A total of 26 sonologists were trained and assigned to diagnostic examination, to ensure that the exam would be performed exactly as outlined in the basic and advanced protocol.

 

Training was conducted by sonologists with specific in venous ECD. Experience included at least 500 Doppler exams per year for two years, published articles in journals with documented impact factor during the last 5 years, consolidated experience as invited speakers at national and international Congress and training courses organized by scientific societies. Each recruited sonologist had to pass a practical test certified by the chairman of both Italian Neurosonology Societies (SINSEC and SINV).

 

Information accuracy and completeness.

The sample: the population survey is the largest so far analyzed in this field. 1767 patients examined, of which 1165 with MS, 376 healthy controls and 226 people with other neurodegenerative diseases.

Multicentricity is the fundamental characteristics. The association of a condition with a disease should be always observed, cannot depend on a single person or on a single machine. Many centers should take part in a study aimed at understanding with scientific evidence whether certain phenomena are related to a certain disease.

Another qualifying aspect of CoSMo is the use of a centralized, blind reading performed by international experts (see below).

In addition, all examinations were recorded and are available. This guarantees that data is checked and provides evidence of scientific rigor, and a potential for a subsequent confirming examination.

 

Test reading procedure: the value of central analysis

The local sonologist examines the patient sent to him by the neurologist not knowing if this patient is healthy, or is affected by multiple sclerosis or another neurological disease.

Based on this 'blind' analysis, the same sonologist draws up and sends a report to the coordinating centre along with examination images. The coordinating centre, in turn, using a computerized system, sends video clips of the exam random to one of the three expert sonologists of the central reading committee.

The central expert uses a total blind testing, i.e. without knowing where the exam comes from or who underwent it (healthy control, patient affected by multiple sclerosis or another neurological disorder). Then he draws up his assessments along with diagnostic conclusions without being influenced.

The coordinating Centre checks if there is a match between the two reports made by the sonologist of the peripheral centre and by the expert sonologist of the central reading committee. If diagnosis coincide, the report is considered as final.

On the contrary, if reports do not coincide, the test is sent to the other two experts of the  central reading committee, each of whom made a report. The final diagnosis is drawn up according to the agreement of the three expert sonologists.

The CoSMo results summarize local and central readings.

The double blinded examination mechanism guaranteed the absolute accuracy of the exam and of the possible diagnosis of CCSVI, normalizing the variability of the reading made by the local participating centres.

The three central readers of the study are Prof. Erwin Stolz, one of the leading international experts in MS, Neurology Clinic, Giessen, Germany, Dr Massimo Del Sette – Chairman of SINSEC , Italian Society of Neurosonology and Cerebral Hemodynamics - and Dr. Giovanni Malferrari, Chairman of SINV - Italian Interdisciplinary Neurovascular Society.

 

Reliability of CoSMo results: local readings and centralized reading
The above-mentioned CoSMo conclusive data summarizes the central and local readings, highlights the presence of CCSVI in 3% of patients with MS, in 2% of healthy controls, 3% of patients with other neurological diseases.

However, if the total local readings are considered, the presence of CCSVI is observed in 16% of patients with MS, 15% of people with other diseases and in 12% of healthy controls. The differences are not significant.

It appears that, even with different values at local level compared to final CoSMo data, CCSVI always occurs with similar rates in all the three groups studied (MS, healthy controls, other neurodegenerative disorders). This means that there is no correlation between CCSVI and MS, from all viewpoint that CoSMo results are observed.

 

The characteristics of the reading

The CoSMo study consists in a basic exam, lasting about two hours, to evaluate the presence or absence of CCSVI. Approx. 80 images and clips were gathered and filed per patient during the basic exam.

In the advanced protocol of the CoSMo protocol, that number of images and clips almost doubled (about 160). On average, there are about 120 images and video clips per exam.

Central readers analyzed both basic and advanced exams. Useful information were obtained for a more accurate identification of the criteria needed to diagnose CCSVI. Data obtained using the extended protocol are currently being analysed.

 

 

 

STEERING COMMITTEE OF  THE ITALIAN MULTICENTRE OBSERVATIONAL STUDY OF THE PREVALENCE OF CCSVI IN MULTIPLE SCLEROSIS (COSMO STUDY)

 

Giancarlo Comi
Division of Neurology and Neurophysiology Service, “San Raffaele” Hospital, Milan, Italy
Principal investigator

 

Gianluigi Mancardi
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy
Principal investigator

 

Mario Alberto Battaglia
Italian Multiple Sclerosis Foundation, Genoa, Italy

 

Antonio Bertolotto
Multiple Sclerosis Center, “San Luigi” Hospital, Orbassano, Italy

 

Massimo Del Sette
Neurology Unit, “Sant’ Andrea” Hospital, La Spezia, Italy

 

Angelo Ghezzi
Multiple Sclerosis Research Center, “Sant’ Antonio Abate” Hospital, Gallarate, Italy

 

Giovanni Malferrari
Neurology Unit - Stroke Unit, Dpt. of Neuromotor Physiology, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy

 

Marco Salvetti
Center for Experimental Neurological Therapies, Sapienza University of Rome, Italy

 

Maria Pia Sormani
Department of Health Sciences, University of Genoa, Italy

 

Luigi Tesio
Department of Biomedical Sciences for Health, Universita degli Studi and Istituto Auxologico Italiano, Milan, Italy

 

Erwin Stolz
Department of Neurology, Justus-Liebig-University, Giessen, Germany