Chronic cerebrospinal venous insufficiency in patients with MS

Vascular Diseases Center, University of Ferrara, Ferrara, Italy.
Journal of neurology, neurosurgery, and psychiatry (Impact Factor: 6.81). 04/2009; 80(4):392-9. DOI: 10.1136/jnnp.2008.157164
Source: PubMed


The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated.
Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement.
CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher.
CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.

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    • "More specifically, the positive agreement between central and local readers in the Italian study was disappointedly low (18%) (Comi et al. 2013). Finally, in an assessor-blinded, case–control, multicentre Canadian study using doppler ultrasound equipment identical to that used in the pivotal study by Zamboni et al. (2009a) and experienced sonographers trained in the center of Zamboni in Ferrara, the prevalence of CCSVI was similar in MS (44%) and HC (45%) (Traboulsee et al. 2014). "
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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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    • "In the previous studies, variable imaging modalities, including extracranial and intracranial ultrasound, digital subtraction venography, and magnetic resonance venography were used to assess the relationship between CCSVI and pathogenesis of multiple sclerosis. Some studies confirmed that the prevalence of CCSVI in multiple sclerosis patients was significantly higher, compared to their control subjects [11–17]. In contrast, the results of other investigations contradicted those of Zamboni et al. [18–35]. "
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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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    • "Many neurological disorders are associated with abnormal IJV flow patterns. (Chung et al., 2006, 2011; Doepp et al., 2008; Hsu et al., 2008; Nedelmann et al., 2009; Zamboni et al., 2009) To elucidate the mechanisms, physiological studies showed that these abnormal IJV flow patterns impair cerebral venous drainage and cause consequent cerebral blood flow (CBF) decrement . (Chung et al., 2010; Wu et al., 2011) IJV lumen would vary at different status of respiration; (Burrows et al., 2003; Schaller, 2004) during inspiration, a negative intrathoracic pressure would increase the flow velocity of IJV and then, due to Bernoulli's principle, reduce the lumen of IJV. "
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    ABSTRACT: Objective: Panic disorder (PD) is characterized by panic attacks accompanied with respiratory symptoms. Internal jugular vein (IJV) alters its hemodynamics in response to respiration and which might cause cerebral blood flow (CBF) changes. In the present study, we compared (1) respiratory-related IJV hemodynamics and (2) CBF changes during Valsalva maneuver (VM) between PD and normal subjects. Methods: 42 PD patients and age/gender-matched controls (14 men; 52.3 ± 11.4 years) were recruited. Duplex ultrasonography measured time-averaged mean velocity (TAMV) and lumen in IJV at baseline and deep inspiration. Lumen area <0.10 cm(2) at deep inspiration was defined as IJV collapse. CBF changes during VM were recorded by transcranial Doppler (TCD). Results: Compared with normal group, PD patients had significantly higher frequency of IJV collapse at deep inspiration (Left: 40.0% vs. 7.0%, p = 0.0003, Right: 17.0% vs. 0%, p = 0.0119). IJV collapse was associated with symptoms of respiratory subtype in our PD patients. PD group also had smaller lumen (Left: 0.53 ± 0.29 vs. 0.55 ± 0.26 cm(2), p = 0.8296, Right: 0.63 ± 0.36 vs. 0.93 ± 0.45 cm(2), p = 0.0014) and slower TAMV of IJV at baseline (Left: 11.8 ± 8.43 vs. 20.6 ± 16.5 cm/s, p = 0.0003, Right: 15.9 ± 9.19 vs. 24.1 ± 15.7 cm/s, p = 0.0062). PD patients with inspiration-induced IJV collapse had more decreased CBF during VM compared with the other PD patients and normal individuals respectively. Interpretation: We are the first to show that PD have less IJV flow at baseline and more frequent collapse at deep inspiration. Inspiration-induced IJV collapsed was associated with CBF decrement during VM in PD patients. These results suggest that venous drainage impairment might play a role in the pathophysiology of PD by influencing CBF.
    Full-text · Article · Aug 2014 · Journal of Psychiatric Research
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