Zamboni, P. et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J. Vasc. Surg. 50, 1348-1358

Vascular Diseases Center, University of Ferrara, Ferrara, Italy.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.02). 12/2009; 50(6):1348-58.e1-3. DOI: 10.1016/j.jvs.2009.07.096
Source: PubMed


Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS.
Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire.
Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP.
PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.

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    • "This hypothesis was based on specifically developed ultrasound features which were stated to detect cervical or cerebral abnormalities of venous drainage leading to increased intracranial venous pressure, subsequently followed by blood–brain barrier breakdown causing iron deposition in brain parenchyma initiating the development of MS (Zamboni 2006). Moreover, percutaneous transluminal angioplasty of extracranial veins (termed " Liberation treatment " ) has been proposed (based on nonrandomized data) as an alternative therapy for MS by the same group of investigators introducing CCSVI hypothesis (Zamboni et al. 2009c). Despite the lack of higher class evidence " Liberation treatment " has gained a considerable amount of attention and emotional involvement by MS patients worldwide (Chafe et al. 2011) and has started to be offered as a potential therapeutic option in MS patients in nonrandomized and uncontrolled studies (Hubbard et al. 2012; Mandato et al. 2012; Ghezzi et al. 2013b). "
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    ABSTRACT: Background Chronic cerebrospinal venous insufficiency (CCSVI) has recently been introduced as a chronic state of impaired cerebral or cervical venous drainage that may be causally implicated in multiple sclerosis (MS) pathogenesis. Moreover, percutaneous transluminal angioplasty of extracranial veins termed “Liberation treatment” has been proposed (based on nonrandomized data) as an alternative therapy for MS.MethodsA comprehensive literature search was conducted to identify available published, peer-reviewed, clinical studies evaluating (1) the association of CCSVI with MS, (2) the reproducibility of proposed ultrasound criteria for CCSVI detection (3) the safety and efficacy of “Liberation treatment” in open-label and randomized-controlled trial (RCT) settings.ResultsThere is substantial heterogeneity between ultrasound case–control studies investigating the association of CCSVI and MS. The majority of independent investigators failed to reproduce the initially reported high prevalence rates of CCSVI in MS. The prevalence of extracranial venous stenoses evaluated by other neuroimaging modalities (contrast or MR venography) is similarly low in MS patients and healthy individuals. One small RCT failed to document any benefit in MS patients with CCSVI receiving “Liberation treatment”, while an exacerbation of disease activity was observed. “Liberation treatment” has been complicated by serious adverse events (SAEs) in open-label studies (e.g., stroke, internal jugular vein thrombosis, stent migration, hydrocephalus).ConclusionCCSVI appears to be a poorly reproducible and clinically irrelevant sonographic construct. “Liberation treatment” has no proven efficacy, may exacerbate underlying disease activity and has been complicated with SAEs. “Liberation treatment” should stop being offered to MS patients even in the settings of RCTs.
    Full-text · Article · Nov 2014 · Brain and Behavior
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    • "The latter may cause perivenous iron deposits with venotopic location typical of multiple sclerosis plaques. Zamboni et al. [2,4] claimed a strong association between multiple sclerosis and CCSVI, and based on their findings, several attempts have been made to treat multiple sclerosis patients with percutaneous transluminal angioplasty [5,6]. Nevertheless, given the controversial results from some other studies, the role of CCSVI in multiple sclerosis is still debated, and further investigations seem to be necessary for this controversy. "
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    ABSTRACT: Background The purpose of this study was to compare patients with multiple sclerosis and healthy control subjects as regards hemodynamics of cerebral venous drainage. Material/Methods Between December 2012 and May 2013, 44 consecutive patients with multiple sclerosis and 44 age- and sex-matched healthy subjects underwent the B-mode, color Doppler, and duplex Doppler evaluations of the internal jugular vein (IJV) and vertebral vein. The following four parameters were investigated: IJV stenosis, reversal of postural control of the cerebral venous outflow pathways, absence of detectable blood flow in the IJVs and/or vertebral veins, and reflux in the IJVs and/or vertebral veins in the sitting or supine position. Results In the study group, IJV stenosis, postural control reversal of the cerebral venous outflow pathways, and absence of flow in the IJVs and/or vertebral veins were found in 3 (6.8%), 2 (4.5%), and 3 (6.8%) patients, respectively. In the control group, IJV stenosis (P=0.12), postural control reversal of the cerebral venous outflow pathways (P=0.50), and absence of flow (P=0.12) were not detected. Abnormal reflux was found neither in multiple sclerosis patients nor in healthy subjects. Conclusions No significant difference in the cerebral venous drainage through the IJV or vertebral vein was found between patients with multiple sclerosis and healthy subjects within any of the investigated ultrasonographic parameters.
    Preview · Article · Sep 2014 · Polish Journal of Radiology
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    • "In contrast to the majority of research in MS, the recent hypothesis of chronic cerebrospinal venous insufficiency (CCSVI) proposed that anomalous venous blood flow from the brain and spinal cord created iron deposition leading to MS-related neuropathology.2 The CCSVI condition could then be treated using endovascular venoplasty to open obstructed areas of the jugular and azygous veins, coined the “liberation procedure”.3 Results of randomized controlled trials of the liberation procedure have yet to be reported, and it is likely that its long-term efficacy and safety will only be assured after several years of observation. "
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    ABSTRACT: BackgroundThe debate within the multiple sclerosis (MS) community initiated by the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis and the subsequent liberation procedure placed some people with MS at odds with health care professionals and researchers.ObjectiveThis study explored decision making regarding the controversial liberation procedure among people with MS.Subjects and methodsFifteen people with MS (procedure, n=7; no procedure, n=8) participated in audiotaped semistructured interviews exploring their thoughts and experiences related to the liberation procedure. Data were transcribed and analyzed using an iterative, consensus-based, thematic content-analysis approach.ResultsParticipants described an imbalance of motivating factors affirming the procedure compared to hesitating factors that provoked the participant to pause or reconsider when deciding to undergo the procedure. Collegial conversational relationships with trusted sources (eg, MS nurse, neurologist) and ability to critically analyze the CCSVI hypothesis were key hesitating factors. Fundraising, family enthusiasm, and the ease of navigation provided by medical tourism companies helped eliminate barriers to the procedure.ConclusionKnowledge of factors that helped to popularize the liberation procedure in Canada may inform shared decision making concerning this and future controversies in MS.
    Full-text · Article · Sep 2014 · Patient Preference and Adherence
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