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"Liberation treatment" for chronic cerebrospinal venous insufficiency in multiple sclerosis: the truth will set you free.

Tsivgoulis G, Faissner S, Voumvourakis K, Katsanos AH, Triantafyllou N, Grigoriadis N, Gold R, Krogias C - Brain Behav (2014)

Bottom Line: 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).CCSVI 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.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens Athens, Greece ; International Clinical Research Center, Department of Neurology, St. Anne's University Hospital Brno, Czech Republic ; Department of Neurology, University of Tennessee Health Science Center Memphis, TN.

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.

Methods: A 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.

Results: There 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).

Conclusion: CCSVI 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.

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Related in: MedlinePlus

Flow not-Doppler detectable in the Internal Jugular Vein (Criterion IV) in horizontal color-flow image before (A) and after (B) spectral interrogation.
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fig01: Flow not-Doppler detectable in the Internal Jugular Vein (Criterion IV) in horizontal color-flow image before (A) and after (B) spectral interrogation.

Mentions: Zamboni et al. reported in their pivotal study that neurosonology had 100% accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value) to discriminate MS patients from Healthy Controls (HC) using a set of ultrasound criteria developed to detect impaired cervical or venous drainage (Zamboni et al. 2009b). Consequently, they introduced evidence of two positive out of five proposed ultrasound criteria as necessary condition for CCSVI diagnosis (Table 1, Fig.1) (Zamboni et al. 2009a). Moreover, they recommended a detailed neurosonology protocol for CCSVI screening (Nicolaides et al. 2011). However, it should be noted that blinding of sonographers was suboptimal in the majority of studies of Zamboni's group.


"Liberation treatment" for chronic cerebrospinal venous insufficiency in multiple sclerosis: the truth will set you free.

Tsivgoulis G, Faissner S, Voumvourakis K, Katsanos AH, Triantafyllou N, Grigoriadis N, Gold R, Krogias C - Brain Behav (2014)

Flow not-Doppler detectable in the Internal Jugular Vein (Criterion IV) in horizontal color-flow image before (A) and after (B) spectral interrogation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321389&req=5

fig01: Flow not-Doppler detectable in the Internal Jugular Vein (Criterion IV) in horizontal color-flow image before (A) and after (B) spectral interrogation.
Mentions: Zamboni et al. reported in their pivotal study that neurosonology had 100% accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value) to discriminate MS patients from Healthy Controls (HC) using a set of ultrasound criteria developed to detect impaired cervical or venous drainage (Zamboni et al. 2009b). Consequently, they introduced evidence of two positive out of five proposed ultrasound criteria as necessary condition for CCSVI diagnosis (Table 1, Fig.1) (Zamboni et al. 2009a). Moreover, they recommended a detailed neurosonology protocol for CCSVI screening (Nicolaides et al. 2011). However, it should be noted that blinding of sonographers was suboptimal in the majority of studies of Zamboni's group.

Bottom Line: 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).CCSVI 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.

View Article: PubMed Central - PubMed

Affiliation: Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens Athens, Greece ; International Clinical Research Center, Department of Neurology, St. Anne's University Hospital Brno, Czech Republic ; Department of Neurology, University of Tennessee Health Science Center Memphis, TN.

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.

Methods: A 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.

Results: There 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).

Conclusion: CCSVI 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.

Show MeSH
Related in: MedlinePlus