As mentioned above, the proposal of CCSVI as an etiological factor or disease modifier in MS is controversial. Subsequent to the initial observations, other investigators conducted their own studies to determine the existence and prevalence of CCSVI in patients with MS and control cohorts.
One positive study by Al-Omari and Rousan showed that in 25 patients with MS there was evidence of CCSVI in 84%, whereas none of the 25 controls displayed evidence of cerebral or cervical venous abnormalities [Al-Omari and Rousan, 2010
]. There was no blinding of the investigators in this study.
All other published studies, however, could not reproduce the findings published by Zamboni and coworkers [Doepp et al. 2010
; Krogias et al. 2010
; Sundstrom et al. 2010
; Wattjes et al. 2010
; Yamout et al. 2010
]. Doepp and colleagues found no evidence of CCSVI in patients with MS using Doppler criteria [Doepp et al. 2010
]. Using magnetic resonance venography (MRV) and flow-quantification study, Wattjes and colleagues found no evdience of venous back flow in patients with MS, and no difference between patients with MS and controls in terms of outflow abnormalities [Wattjes et al. 2010
]. Lastly, in a case–control study, Sundström and colleagues found no differences in internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux in patients with MS [Sundstrom et al. 2010
]. In their cohort, Krogias and colleagues found that only 20% of patients had the required neurosonological features of CCSVI. Yamout and colleagues performed selective extracranial venography on 42 patients with MS. Extracranial venous stenosis was seen in seven of 29 patients with early MS and 12 of 13 patients with late MS. Only three of 42 patients (all in the late MS group) demonstrated two vessel stenoses.
Worthington and colleagues conducted a cerebrospinal (CSF) study that showed normal ferritin levels in the CSF of patients with MS [Worthington et al. 2010
]. The findings argue against the CCSVI-related CNS iron accumulation in MS.
Mayer and colleagues found no evidence of CCSVI in 20 patients with MS and only healthy controls fulfilled the criteria for CCSVI [Mayer et al. 2011
Zivadinov and colleagues investigated the differences in the extracranial venous system in patients with MS and healthy controls by using MRV [Zivadinov et al. 2011
]. Fifty-seven patients, 41 with RRMS and 16 with secondary progressive MS (SPMS), and 21 healthy controls were imaged with 3-T MRV. No significant differences in morphological features of flow in the internal jugular veins and vertebral veins were found between patients with MS and healthy controls in any of the examined MRV parameters.
Baracchini and colleagues studied the occurrence of CCSVI in clinically isolated syndromes (CISs). A total of 50 patients presenting with a CIS and evidence of dissemination in space of the inflammatory lesions underwent a comprehensive diagnostic workup, including extracranial and transcranial venous echo-color Doppler sonography. Patients who showed evidence of CCSVI were further evaluated by selective venography. A total of 50 healthy controls that matched the patients with CIS, 60 patients with transient global amnesia (TGA), and 60 healthy controls that matched the patients with TGA made up the control groups. The control groups also underwent extracranial and transcranial venous echo-color Doppler sonography. Interestingly, transcranial venous echo-color Doppler was normal in all patients with CIS. One or more abnormal extracranial venous echo-color Doppler findings were observed in 26 of 50 (52.0%) of the patients with CIS, 35 of 110 (31.8%) of the controls and 41 of 60 (68.3%) of the patients with TGA. The eight (16%) patients with CIS who fulfilled the diagnosis of CCSVI were further evaluated for selective venography. Selective venoography was completed in seven of these patients and did not disclose any venous anomalies or abnormalities.