![The sensitivity of ultrasound
CCSVI criteria for detection of
>50% narrowing seen on
catheter venography was 0.40
[0.31-0.50]
The agreement was equally
poor in MS patients and healthy
controls.](https://image.slidesharecdn.com/noevidenceofccsviinmultiplesclerosis-150319041445-conversion-gate01/85/No-evidence-of-ccsvi-in-multiple-sclerosis-27-320.jpg)
No evidence of ccsvi in multiple sclerosis
- 1. NO EVIDENCE OF CCSVI IN MULTIPLE SCLEROSIS Jean-Baptiste Ricco Vascular Surgery Department University of Poitiers, France
- 2. CCSVI HYPOTHESIS Raised venous pressures Damage to intracranial vascular endothelium Incite inflammatory response and breach of blood‐brain barrier Develop into MS lesions
- 3. ZAMBONI CRITERIA DOPPLER CRITERIA FOR CCSVI
- 4. ZAMBONI CRITERIA DOPPLER CRITERIA FOR CCSVI
- 7. ZAMBONI CRITERIA ZAMBONI CRITERIA FOR CCSVI ZAMBONI CRITERIA FOR CCSVI DOPPLER CRITERIA FOR CCSVI ZAMBONI CRITERIA
- 8. 2 POSITIVE ZAMBONI CRITERIA FOR CCSVI DOPPLER CRITERIA FOR CCSVI
- 9. • CCSVI criteria fulfilled in all MS patients (n=109) • and none of the controls (n=177) CONCLUSIVE ANALYSIS MS CONTROL SENSITIVITY SPECIFICITY (95% CI) ≥ 2 POSITIVE CRITERIA 109/109 0/177 100% (97-100) 100% (98-100)
- 10. • 65 MS patients compared to 235 controls • “MS was strongly associated with CCSVI” CRITERIA MS CONTROL Odds ratio 1 46/65 0/235 1123 (p<0.0001) 2 40/65 0/235 748 (p<0.0001) 3 24/65 1/235 137 (p<0.0001) 4 34/65 7/235 36 (p<0.0001) 5 36/65 25/235 10 (p<0.0001) J Neurol Neurosurg Psychiatry 2009
- 11. METHODOLOGICAL ISSUES • Potential observer bias in the US measurements, • No description of blinding was provided • The principal interpreting physician was identified as PZ in the article. • No description of any methods to limit intraobserver or interobserver bias
- 12. • The rate of relapse-free patients improved from 27% to 50% (p<0.001) • The rate of gadolinium-enhancing lesions on MRI decreased from 50% to 12% (p<0.01) • The Multiple Sclerosis Functional Composite score improved significantly in this MS cohort. (p<0.01) AFTER PTA J VASC SURG 2009
- 13. MAJOR FLAWS • Open-label study, no blinding of neurologists • No control group • A 66% of subjects with MS who had not previously received DMT (disease-modifying-therapy) at the time of baseline data collection were asked to start standard DMT in order to enroll in the PTA study. A major confounding factor
- 14. - Zamboni P. Curr Neurovasc Res 2007 - Zamboni P. J Neurol Neurosurg 2009 - Zamboni P. Funct Neurol 2009 -Zamboni P. J Vasc Surg 2009 -Zamboni P. Eur J Vasc Endovasc Surg 2011 - Baracchini C et al. Ann Neurol 2011 - Centonze D et al. Ann Neurol 2011 - Doepp F et al. Ann Neurol 2010 - Mayer CA et al. J Neurol Neurosurg 2011 - Zivadinov R et al. Neurology 2011 - Marder E et al. Arch Neurol 2011 - Tsivgoulis et al. Neurology 2011 - Auriel et aL. J Neurol Sciences 2011 - Blinkenberg et al. Acta Neurologica Scandinavia 2012 - Comi et al (CosMo study) ECRIMS 2012 - Laukentaus SJ EJVES 2013 - Imperiale D Clinical Neurology and Neurosurgery 2013 - Traboulsee AL Lancet 2013 CCSVI BY OTHER AUTHORS
- 15. FOREST PLOT Estimate Lower bound Upper bound p-Value 1.56 0.95 2.56 0.08 Heterogeneity tau^2 Q(df=12) Het. p-Value I^2 0.45 34.56 < 0.01 65%
- 16. • Case-control study • 35 centers • 1202 patients with MS • 382 healthy controls • 232 with other neurological diseases G. Comi, G Mancardi for the CoSMo study Sponsor: Italian Multiple Sclerosis Foundation
- 17. Illustration of the vascular abnormalities comprising the proposed entity chronic cerebrospinal venous insufficiency. Figure adapted from R. Fox, Neurology 2011. DIAGNOSIS of CCSVI 1 2 3 4 5 ≥ 2 out the 5 CCSVI criteria have to be met
- 18. CENTRALIZED BLINDED EXAMINATION • Duplex images were sent to an independent central expert who performed a second blinded reading • In case of disagreement, the exam was sent to the two other central Duplex experts and the final diagnosis was made by a majority • Data collection and monitoring were carried out by an independent organization and centralized Independent central DU evaluation Prof. Erwin Stolz, Neurologische Klinik-Giessen (Germany) Prof. Massimo Del Sette, Ospedale S. Andrea - Italy Dott. Giovanni Malferrari, Arcispedale S. Maria Nuova -Reggio Emilia - Italy
- 19. CCSVI PREVALENCE 3.26 2.13 3.10 0 2 4 6 8 10 12 14 16 18 20 MS HC OND CCSVIprevalence(%) ns MS: Multiple Sclerosis, HC: Healthy Controls, OND: Other Neurological Diseases NS (p=0.30) NS (p=0.99)
- 20. CoSMo STUDY These results do not support the hypothesis of the role of CCSVI as a potential causal factor in the development of MS
- 21. CCSVI - THE FINAL CURTAIN Traboulsee AL et al. Lancet, 2013 published on line October 9
- 22. This study aimed to establish the prevalence of extracranial venous narrowing in people with MS, unaffected full siblings, and unrelated healthy volunteers. Traboulsee AL et al. Lancet, 2013 published on line October 9
- 23. Blinded, case-control, multicentre study 177 adults: 79 with MS, 55 siblings, and 43 controls, The authors assessed narrowing of the IJV and azygous veins with catheter venography and ultrasound criteria for CCSVI by Zamboni Traboulsee AL et al. Lancet, 2013 published on line October 9
- 24. 79 with MS 98 controls 177 enrolled • Ultrasound • Venography All assessing study team were masked to participant status
- 25. MS (N=79) UNAFFECTED SIBLINGS (N=54) HEALTHY CONTRO LS (N=38) P VALUE ULTRASOUND ≥2/5 POSITIVE 44% 31% 45% 0.27 ZAMBONI VENOGRAPHY CRITERIA 2% 2% 3% 1.0 > 50% NARROWING ON VENOGRAPHY 74% 66% 70% 0.81 > 50% NARROWING WITH ABNORMAL FLOW 51% 45% 70% 0.51
- 26. 0% 10% 20% 30% 40% 50% 60% 0 1 2 3 4 5 Controls Siblings MS ① High-resolution B-mode anomalies ② Reflux in the deep cerebral veins / Flow not doppler- detectable in the IJV/ vertebral vein ③ Reflux in the IJV / vertebral veins ④ Reversed postural control of the main cerebral venous outflow CCSVI ULTRASOUND CRITERIA
- 27. The sensitivity of ultrasound CCSVI criteria for detection of >50% narrowing seen on catheter venography was 0.40 [0.31-0.50] The agreement was equally poor in MS patients and healthy controls.
- 29. This review provides no evidence that extracranial venous anatomy differs between patients with MS and healthy controls These results also challenge both the validity of ultrasound for the purpose of detecting CCSVI and its existence as a disorder
- 30. The angioplasty for CCSVI which was tendentiously termed liberation treatment earned Internet coverage and kindled the hopes of desesperate patients. It is clear that no reason exists to allocate further resources to CCSVI research, be they financial or intellectual
- 31. Liberation Treatment India A no Obligation, No Cost, Patient Helpline for Liberation Treatment in India www.liberationtreatmentindia.co For more info or any queries write to us at: help@liberationtreatmentindia.com hospitalindia@gmail.com Call us US/Canada Toll Free Number:1-888-771-6965 International Helpline Number: +91-9198993637