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Observational Study
. 2013 Aug;34(8):1297-307.
doi: 10.1007/s10072-012-1269-5. Epub 2013 Jan 24.

Italian Multicentre Observational Study of the Prevalence of CCSVI in Multiple Sclerosis (CoSMo Study): Rationale, Design, and Methodology

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Free PMC article
Observational Study

Italian Multicentre Observational Study of the Prevalence of CCSVI in Multiple Sclerosis (CoSMo Study): Rationale, Design, and Methodology

Giancarlo Comi et al. Neurol Sci. .
Free PMC article

Abstract

Chronic cerebro-spinal venous insufficiency (CCSVI) has been proposed as a "congenital malformation" implicated in the pathogenesis of multiple sclerosis (MS). However, numerous studies failed to confirm its presence in MS patients. This paper presents the rationale, design, and methodology adopted in the CoSMo study, conducted with the aim of verifying whether or not CCSVI is linked to MS. The primary endpoint of the CoSMo study is to compare the prevalence of CCSVI in patients with MS versus patients affected by other neurodegenerative diseases (OND) and healthy volunteers. CoSMo is a multicenter, blinded, prevalence study recruiting 2,000 adult subjects, involving 43 MS centers across Italy. Assessment of the presence or absence of CCSVI is performed by color-coded duplex (CCD) sonography and two out of the five criteria according to Zamboni are necessary for the diagnosis of CCSVI. Local CCD examination carried out by a certified sonologist and the central image readings performed by experts in the field are blinded. An advanced protocol is also described in this paper. The application of a rigorous methodological design will definitively confirm whether an association exists between CCSVI and MS. Should an association be observed, this study also further examines the link between CCSVI and the severity of MS. The addition of subgroups without MS and OND also provides information on whether CCSVI is specific to MS only. Results from the CoSMo study will play a crucial role in the possible studies concerning the potential treatment of CCSVI in MS.

Figures

Fig. 1
Fig. 1
Basic operative protocol for the color-coded duplex sonography in supine position. IJV internal jugular vein, J1, J2, J3 distal (from the valve plane to 0.5 cm from it), middle (at the level of the thyroid gland) and proximal (at the level of the carotid bifurcation) jugular vein segments, CSA cross-sectional area, VV vertebral veins, V1, V2 distal and proximal vertebral vein segments, TCCD transcranial color-coded duplex sonography, BVR basal vein of Rosenthal, TS transverse sinus. a Time window, axial scan, mesencephalic and diencephalic plane; examination has to be performed on both sides, in order to insonate both right and left temporal windows
Fig. 2
Fig. 2
Basic operative protocol for the color-coded duplex sonography in sitting position. IJV internal jugular vein, J1, J2, J3 distal (from the valve plane to 0.5 cm from it), middle (at the level of the thyroid gland) and proximal (at the level of the carotid bifurcation) jugular vein segments, CSA cross-sectional area, VV vertebral veins, V1, V2 distal and proximal vertebral vein segments, TCCD transcranial color-coded duplex sonography, BVR basal vein of Rosenthal, TS transverse sinus. a Time window, axial scan, mesencephalic and diencephalic plane; examination has to be performed on both sides, in order to insonate both right and left temporal windows
Fig. 3
Fig. 3
Advanced operative protocol for the color-coded duplex sonography in supine position. IJV internal jugular vein, J1, J2, J3 distal, middle and proximal jugular vein segments, CSA cross-sectional area, VV vertebral veins, V1, V2 distal and proximal vertebral vein segments, TCCD transcranial color-coded duplex sonography, BVR basal vein of Rosenthal, TS transverse sinus. a Doppler waveform spectrum includes PSV peak systolic velocity, EDV end diastolic velocity and TAV time averaged velocity measurements through the automatic or manual selection of at least three cardiac consecutive cycles; blood flow (BF) rate is calculated according to the following formula: BF = CSA × TAV; b Time window, axial scan, mesencephalic and diencephalic plane; examination has to be performed on both sides, in order to insonate both right and left temporal windows; c Doppler waveform spectrum includes PSV and EDV measurements
Fig. 4
Fig. 4
Advanced operative protocol for the color-coded duplex sonography in sitting position. IJV internal jugular vein, J1, J2, J3 distal, middle and proximal jugular vein segments, CSA cross-sectional area, VV vertebral veins, V1, V2 distal and proximal vertebral vein segments, TCCD transcranial color-coded duplex sonography, BVR basal vein of Rosenthal, TS transverse sinus. a Doppler waveform spectrum includes PSV peak systolic velocity, EDV end diastolic velocity and TAV time averaged velocity measurements through the automatic or manual selection of at least 3 cardiac consecutive cycles; blood flow (BF) rate is calculated according to the following formula: BF = CSA × TAV; b Time window, axial scan, mesencephalic and diencephalic plane; examination has to be performed on both sides, in order to insonate both right and left temporal windows; c Doppler waveform spectrum includes PSV and EDV measurements
Fig. 5
Fig. 5
Black-box Linkverse® system. Schematic chart describing the flow of images and video recordings from the local examiner performing the CCD examination to the experts performing the centralized readings for CCSVI diagnosis. The Black-box Linkverse® uses the universal DICOM format (Digital Imaging and COmmunications in Medicine) and a system for consultation, temporary storage and transmission of images stored in native format and sent as compressed files, without loss of information

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