|
|
| View previous topic :: View next topic |
| Author |
Message |
agate
Site Admin
Joined: 17 May 2006
Posts: 5694
Location: Oregon
|
 Posted: Sun Oct 14, 2012 12:45 pm Post subject: ECTRIMS: CCSVI & global venous hemodynamics in MS |
 |
|
Presented at ECTRIMS, October 13, 2012:
| Quote: |
Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study
G. Comi, M.A. Battaglia, A. Bertolotto, M. Del Sette, A. Ghezzi, G. Malferrari, M. Salvetti, M. Sormani, E. Stolz, L. Tesio, G.L. Mancardi on behalf of the CoSMo study group
Introduction:
Chronic cerebrospinal venous insufficiency (CCSVI) has been recently described as a condition characterized by chronically impaired cerebral venous drainage associated to multiple sclerosis (MS). Subsequent studies failed to confirm the association between CCSVI and MS and even questioned whether CCSVI exist[s] at all.
The CoSMo study is a large, multicenter case-control study promoted by the Italian MS Foundation to investigate the relationship between CCSVI and MS.
Materials and method:
This study was conducted in 35 Italian clinical centers. 1871 subjects aged 18-55 years were enrolled (55 were excluded for major protocol violations) so that the final analysis was based on 1816 subjects: 1202 with MS (72.6% Relapsing Remitting, 13.5% Secondary Progressive, 5.2% Primary Progressive and 8.7% Clinically Isolated Syndromes), 382 healthy controls (HC) and 232 subjects with other neurological diseases (OND). An informed consent was obtained for all the enrolled subjects.
Eco Color Doppler (ECD) was performed according to a pre-defined protocol, and all sonologist[s] were specifically trained to standardized ECD criteria for CCSVI. The exam was recorded and sent for a central blind evaluation performed by one of 3 expert central sonologists. These had blind access to the ECD imaging. The diagnosis was compared between the local and one central sonologist. In case of agreement, a final report was issued. In case of disagreement, the ECD examination was sent independently to the other two central sonologists and the diagnosis made by a majority. Centralized data collection and monitoring was managed by an independent CRO. The results presented here include 1678 examinations with completed local and central assessment.
Results:
The prevalence of CCSVI was 3.24% (95% Confidence Interval (CI)= [2.35%; 4.45%]) in MS patients, 1.98% (95%CI= [0.96%; 4.03%]) and 2.80% (95%CI=[1.29%; 5.98%]) respectively in HC and in patients with OND. The difference between MS patients and HC was not statistically significant (OR=1.66, 95%CI= [0.73;3.77], p=0.28), as well as the difference between MS patients and OND patients (OR=1.16 [0.48,2.78], p=0.99). There was no association between CCSVI and any MS subtype.
Conclusion:
The prevalence of CCSVI detected in a multicenter setting by a shared local and central assessment was very low and not significantly associated with MS. These results do not support the role of CCSVI as a potential causal factor in the development of MS.
----------------------------------------------------
Dr. Battaglia has no conflicts of interest to declare. Dr A. Bertolotto has been on steering committees in clinical trials sponsored by Biogen Idec, Roche, and has received speaker honoraria from Biogen Idec, Merck Serono, TEVA, Bayer Schering, Sanofi-aventis, and Novartis; and has received research support from Biogen Idec, Bayer Schering, Merck Serono, Sanofi-Aventis, from the Italian Multiple Sclerosis Society, and the European Union Sixth Framework Programme. Dr. Comi has received consulting fees for participating on advisory boards from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, and Bayer Schering; lecture fees from Novartis, Teva Pharmaceutical Ind. Ltd., Sanofi-Aventis, Merck Serono, Biogen Dompè, Bayer Schering and Serono Symposia International Foundation. He is member of the Board of the Italian MS Foundation. Dr. M. Del Sette has no conflicts of interest to declare. Dr A. Ghezzi received honoraria for speaking from Bayer-Schering, Biogen-Dompè, Merck-Serono, Novartis, Sanofi-Aventis and Allergan, for consultancy from Actelion, Merck-Serono, Teva and Novartis, received support for participation to National and International Congresses from Bayer-Schering, Biogen-Dompè, Merck- Serono, Novartis and Sanofi-Aventis. Dr G. Malferrari has no conflicts of interest to declare. Dr. GL Mancardi received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Bayer Schering, Biogen Idec, Sanofi-Aventis, Novartis and Merck Serono Pharmaceuticals. He is member of the Board of the Italian MS Foundation. Dr. M Salvetti declares grant support from Bayer-Schering, Merck-Serono, Sanofi-Aventis and Biogen Idec. Dr. MP Sormani has received consulting fee or honoraria from Biogen Idec, Merck Serono, Actelion, Synthon and TEVA. Dr. E. Stolz has received lecture fees from Boehringer Ingelheim, Bracco and Sanofi-Aventis and support from Schering. Dr. L. Tesio is member of the Board of the Italian MS Foundation.
|
The abstract can be seen here. |
|
| Back to top |
|
 |
agate
Site Admin
Joined: 17 May 2006
Posts: 5694
Location: Oregon
|
| Posted: Sun Oct 14, 2012 12:52 pm Post subject: MedPage Today: Largest CCSVI study fails to support theory |
|
|
From MedPage Today, October 12, 2012
| Quote: |
Largest CCSVI Study Fails to Support Theory
.
By John Gever, Senior Editor, MedPage Today
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston
LYON, France -- The largest study to date testing the venous-obstruction theory of multiple sclerosis failed to support it, leading the Italian Multiple Sclerosis Society to declare the theory dead.
Reported here by leaders of the group, known by its Italian abbreviation AISM, the study of nearly 2,000 individuals with blinded central imaging analysis found the condition in only about 3% of MS patients and in only slightly fewer healthy controls or patients with other neurological conditions.
Key data were released at a press briefing by principal investigator Giancarlo Comi, MD, of the University of Milan, and other study leaders in advance of Comi's formal presentation, scheduled for Saturday at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
They characterized the study as the largest yet conducted on the so-called chronic cerebrospinal venous insufficiency theory (CCSVI), advanced in 2009 by Paolo Zamboni, MD, of the University of Ferrara in Italy.
The CCSVI theory quickly took the MS community by storm, leading many patients to seek venous angioplasty and stenting procedures in hope of obtaining relief or even a cure, as Zamboni and some other vascular surgeons claimed was possible.
But the theory also drew substantial criticism, especially after numerous other researchers were unable to reproduce Zamboni's original findings of 100% presence of CCSVI in MS patients and 0% in non-MS controls. Some groups were unable to detect CCSVI in more than a small fraction of patients, while others found that it was relatively common but without specificity for MS.
In the new study, sponsored by AISM and called CoSMo, ultrasound analyses were performed on 1,874 individuals at 35 clinics throughout Italy. A total of 107 were subsequently excluded because of technical problems with the images or because participants were found not to meet the specified inclusion criteria (such as age or disease duration).
The analysis included 1,165 patients with MS (including 104 with clinically isolated syndrome), 376 healthy controls, and 226 patients with other neurological diseases.
All participants were evaluated for MS under standard diagnostic criteria.
Initial diagnoses of CCSVI or its absence were made by the sonographers at each clinic, who had received special training in cerebral venous imaging. Some of them had previously trained in Zamboni's clinic. The local sonographers were blinded to participants' diagnoses.
The local clinic diagnoses were then reviewed by one of three blinded central imaging experts: Erwin Stolz, MD, of Justus-Liebig University in Giessen, Germany; Massimo Del Sette, MD, chairman of the Italian Society of Neurosonology and Cerebral Hemodynamics; and Giovanni Malferrari, MD, chairman of the Italian Interdisciplinary Neurovascular Society.
When there was disagreement between the local and central readers, all three of the central readers reviewed the images, with the opinion shared by two counted as the final diagnosis. Analyses in the two-year study were completed last month.
The prevalence of CCSVI as determined under this process was as follows in the three groups of participants:
MS patients: 3.26% (95% CI 2.38% to 4.45%)
Healthy controls: 2.13% (95% CI 1.10% to 4.14%)
Other neurological disorders: 3.10% (95% CI 1.58% to 6.44%)
On the basis of these small values, and the lack of significant (P<0.05) differences between them, the AISM issued a statement declaring that "CCSVI is not a disease connected to multiple sclerosis."
Moreover, it continued, "for people affected by MS, there is no need to carry out additional tests to diagnose CCSVI, nor is vein surgery required."
The AISM is the first national MS society to make such a conclusive determination. In the U.S. and Canada, research on CCSVI commissioned by the major organizations in those countries is still under way, and no similar declaration is likely until those studies are completed.
Comi said that Zamboni had been invited to participate in CoSMo, and did for a time. But he quit before all the sonographers had been trained, objecting to multiple aspects of the study design that he believed would bias the results against finding a relationship between CCSVI and MS.
Stolz said that the sonographers were not trained specifically in Zamboni's method, but that he and others who had conducted the training had extensive experience in cerebrovascular ultrasound imaging.
He noted that this had also been the case with other groups that failed to replicate Zamboni's findings, despite having been trained in his clinic. Stolz added that a diagnostic procedure is only meaningful if it can be taught and used reliably by other experienced practitioners.
"If it is not repeatable, it has no value," he said.
Comi said that other researchers would be permitted to conduct their own evaluations of sonograms collected during the study, as long as the blinding to clinical diagnosis was maintained.
Initial diagnosis of CCSVI in the individual clinics in fact varied widely, Comi said. At one clinic, the condition was found in 60% of participants; in two others, the prevalence was 0%.
Overall, the detection rate at the initial step was considerably higher than after central review: 15.9% among MS patients, 12% in healthy controls, and 15% in patients with non-MS neurological disorders. Comi noted that even at these higher prevalences, there was still no meaningful difference between MS patients and other participants.
He also indicated that central reviewers rarely overruled the local clinic sonographers on negative diagnoses. In only 3% of cases in which the local sonographer found no CCSVI did the central reviewers say it was present.
Agreement was poorer for positive diagnoses. Central reviewers overturned 89% of the CCSVI diagnoses made by local sonographers.
Stolz attributed the lack of concordance on positive findings to the fact that "local sonographers are not on the moon." He suggested that seeing participants, and noting any physical or mental impairments, could have biased them toward diagnosing CCSVI.
Gianluigi Mancardi, MD, head of the AISM's scientific committee and co-principal investigator on the study with Comi, said he hoped the study would put the CCSVI theory permanently to rest.
"In our opinion, this is the final answer," he said.
Noting that the AISM had spent some $2 million to conduct the CoSMo study, he said the group now hoped to direct its attention to more fruitful areas of research in MS and its treatments.
|
The article can be seen here. |
|
| Back to top |
|
|
agate
Site Admin
Joined: 17 May 2006
Posts: 5694
Location: Oregon
|
| Posted: Sat Sep 07, 2013 4:02 pm Post subject: More from the CoSMo study |
|
|
"Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: results from the CoSMo study" by G. Comi et al. is available in the Multiple Sclerosis Journal, September 6, 2013, as an open-access article:
http://msj.sagepub.com/content/early/2013/09/05/1352458513501231.full |
|
| Back to top |
|
|
|
|
You can post new topics in this forum
You can reply to topics in this forum
You can edit your posts in this forum
You can delete your posts in this forum
You cannot vote in polls in this forum
|
|
|
