Assessment of cerebral venous return by a novel plethysmography method

Vascular Diseases Centre, 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). 04/2012; 56(3):677-85.e1. DOI: 10.1016/j.jvs.2012.01.074
Source: PubMed


Magnetic resonance imaging and echo color Doppler (ECD) scan techniques do not accurately assess the cerebral venous return. This generated considerable scientific controversy linked with the diagnosis of a vascular syndrome known as chronic cerebrospinal venous insufficiency (CCSVI) characterized by restricted venous outflow from the brain. The purpose of this study was to assess the cerebral venous return in relation to the change in position by means of a novel cervical plethysmography method.
This was a single-center, cross-sectional, blinded case-control study conducted at the Vascular Diseases Center, University of Ferrara, Italy. The study involved 40 healthy controls (HCs; 18 women and 22 men) with a mean age of 41.5 ± 14.4 years, and 44 patients with multiple sclerosis (MS; 25 women and 19 men) with a mean age of 41.0 ± 12.1 years. All participants were previously scanned using ECD sonography, and further subset in HC (CCSVI negative at ECD) and CCSVI groups. Subjects blindly underwent cervical plethysmography, tipping them from the upright (90°) to supine position (0°) in a chair. Once the blood volume stabilized, they were returned to the upright position, allowing blood to drain from the neck. We measured venous volume (VV), filling time (FT), filling gradient (FG) required to achieve 90% of VV, residual volume (RV), emptying time (ET), and emptying gradient (EG) required to achieve 90% of emptying volume (EV) where EV = VV - RV, also analyzing the considered parameters by receiver operating characteristic (ROC) curves and principal component mathematical analysis.
The rate at which venous blood discharged in the vertical position (EG) was significantly faster in the controls (2.73 mL/second ± 1.63) compared with the patients with CCSVI (1.73 mL/second ± 0.94; P = .001). In addition, respectively, in controls and in patients with CCSVI, the following parameters were highly significantly different: FT 5.81 ± 1.99 seconds vs 4.45 ± 2.16 seconds (P = .003); FG 0.92 ± 0.45 mL/second vs 1.50 ± 0.85 mL/second (P < .001); RV 0.54 ± 1.31 mL vs 1.37 ± 1.34 mL (P = .005); ET 1.84 ± 0.54 seconds vs 2.66 ± 0.95 seconds (P < .001). Mathematical analysis demonstrated a higher variability of the dynamic process of cerebral venous return in CCSVI. Finally, ROC analysis demonstrated a good sensitivity of the proposed test with a percent concordant 83.8, discordant 16.0, tied 0.2 (C = 0.839).
Cerebral venous return characteristics of the patients with CCSVI were markedly different from those of the controls. In addition, our results suggest that cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool.

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    • "Abnormal cerebral venous reflux is peculiar to MS and was not found in a miscellaneous of patients affected by other neurodegenerative disorders characterized by iron stores, such as Parkinson's, Alzheimer's, amyotrophic lateral sclerosis. Several recently published cellular, radiological and histopathological studies support the hypothesis that MS progresses along the venous vasculature and oxidative stress plays a central role in this perspective.[25262728] The peculiarity of CCSVI-related cerebral venous blood flow disturbances, together with the histology of the perivenous spaces and recent findings from advanced magnetic resonance imaging techniques, support the hypothesis that iron deposits in MS are a consequence of altered cerebral venous return and chronic insufficient venous drainage.[29] "
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    ABSTRACT: Multiple sclerosis (MS) is an autoimmune neurological disorder, which has impacted health related quality of life (HRQoL) more intensively than any other neurological disorder. The approaches to improve the health standard in MS patient are still a subject of primary importance in medical practice and seek a lot of experimental exploration. The present review briefly explains the anomaly in neuron anatomy and dysfunction in signal transmission arising in the context with the chronic cerebrospinal venous insufficiency (CCSVI), a recent hypothesis related with MS pathophysiology. Subsequently, it insights brain‑machine interface (BMI) as an alternative approach to improve the HRQoL of MS subjects. Information sources were searched from peer‑reviewed data bases (Medline, BioMed Central, PubMed) and grey‑literature databases for data published in 2000 or later. We also did systemic search in edited books, articles in seminar papers, reports extracted from newspapers and scientific magazines, articles accessed from internet; mostly using PubMed, Google search engine and Wikipedia. Out of approximately 178, 240 research articles obtained using selected keywords, those articles were included in the present study which addresses the latest definitions of HRQol and latest scientific and ethical developments in the research of MS and BMI. The article presented a brief survey of CCSVI mediated MS and BMI‑approach as a treatment to serve the patients suffering from disabilities as a result of MS, followed by successful precedence of BMI approach. Apart from these, the major findings of selected research articles including the development of parameters to define HRQoL, types and development of BMIs and its role in interconnecting brain with actuators, along with CCSVI being a possible cause of MS have formed the foundations to conclude the findings of the present review article. We propose a perspective BMI approach and promises it holds for future research to improve HRQoL in MS patients. In addition, we propose that brain‑computer interfaces will be the core of new treatment modalities in the future for MS disabilities.
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    • "Despite the lack of higher-class evidence, this treatment ('Liberation procedure') has gained a considerable amount of attention and emotional comments by patients with MS worldwide [Chafe et al. 2011] and has started to be tested in patients with MS in nonrandomized, uncontrolled and unblinded studies [Ludyga et al. 2010; Hubbard et al. 2012; Denislic et al. 2012]. Only recently, a group of investigators led by Zamboni has embarked in a multicenter, randomized, blinded, parallel-group, sham-controlled trial aiming to assess the safety and efficacy of the Liberation procedure in a sample of 679 patients with MS [Zamboni et al. 2012b]. "
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    ABSTRACT: Chronic cerebrospinal venous insufficiency (CCSVI) has recently been implicated in the pathogenesis of multiple sclerosis (MS). This comprehensive meta-analysis of case-control studies investigates the association of CCSVI with MS. Through Medline, EMBASE and Cochrane database searches, case-control ultrasound studies comparing CCSVI frequency among patients with MS and healthy controls were identified. We identified 19 eligible studies including 1250 patients with MS and 899 healthy controls. The pooled analysis showed that CCSVI was associated with MS [odds ratio (OR) 8.35; 95% confidence interval (CI) 3.44-20.31; p < 0.001) with considerable heterogeneity across studies (I (2) = 80.1%). This association was substantially attenuated in sensitivity analyses excluding studies that were carried out by the group that originally described CCSVI, included investigators who had also been involved in publications advocating endovascular procedures for CCSVI treatment, or were conducted in Italy. Our most conservative sensitivity analysis combining different exclusion criteria yielded no association of CCSVI with MS (OR 1.35; 95% CI 0.62-2.93; p = 0.453) without any heterogeneity (I (2) = 0%). There is considerable heterogeneity across different case-control studies evaluating the association of CCSVI and MS. The greatest factor contributing to this heterogeneity appears to be the involvement of investigators in other publications supporting endovascular procedures as a novel MS treatment.
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    • "This may help the interpretation of several findings assessed with different techniques, where it was not possible to assess the outflow contribution of the collateral network, as well as the rate of the inflow going in the main venous paths. For instance, the higher flow in the collateral network may explain the longer cerebral circulation time measured by means of contrast-enhanced US, as well as the slower discharge and increased resistance measured in MS [32-34]. Our preliminary report needs to be further corroborated by reproducibility analysis, wider number of subjects and pathological conditions, and possibly, by a multicenter design. "
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    ABSTRACT: The quantification of the flow returning from the head through the cervical veins and the collaterals of the internal jugular vein (IJV), is becoming of prominent interest in clinical practice. We developed a novel model to calculate the cerebral venous return, normalized to the arterial inflow, in the different segments of the IJV. We assessed, by established Echo Colour Doppler (ECD) methodology, the head inflow (HBinF) defined as the sum of common carotids and vertebral arteries, as well as the cerebral flow (CBF) defined as the sum of internal carotid and vertebral arteries. We also assessed the head outflow (HBoutF) defined as the sum of the measurements at the junction of the IJV and the vertebral veins. In addition, we also calculated the collateral flow index (CFI) by estimating the flow which re-enters directly into the superior vena cava as the amount of blood extrapolated by the difference between the HBinF and the HBoutF. We preliminarily tested the model by comparing ten healthy controls (HC) with ten patients affected by chronic cerebral spinal venous insufficiency (CCSVI), a condition characterized by some blockages in the IJV which are bypassed by collateral circulation. In HC the HBinF was 1040+/-125 ml/min, whereas the HBoutF was > 90% of the HBinF, leading to a final CFI value of 1%. The last result shows that a very small amount of blood is drained by the collaterals. In upright we confirmed a reduction of the outflow through the IJV which increased CFI to 9%. When we applied the model to CCSVI, the HBinF was not significantly different from controls. In supine, the flow of CCSVI patients in the IJV junction was significantly lower (p < 0.001) while the correspondent CFI value significantly increased (61%, p < 0.0002). Our preliminary application of the novel model in the clinical setting suggests the pivotal role of the collateral network in draining the blood into the superior vena cava under CCSVI condition.
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