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Because the internal jugular vein (IJV) valve is the only protective valve between the brain and heart, recent studies have focused on the dynamic behaviour of the valve and its importance in regulating the cerebral blood outflow pathway. However, the mechanism underlying valve opening and closure, as well as the normal opening time, has not been investigated before. The aim of the study described here was to investigate IJV physiology in healthy young adults by means of ultrasound imaging. Twenty-four normal young adults (16 male, 8 female, 21.79 ± 0.79 y of age) were enrolled in this study. Each participant underwent IJV B- and M-mode ultrasound scans of the neck veins in supine position. Data on IJV leaflet movement and IJV blood velocity were extracted from images with the associated electrocardiogram traces to analyze the opening and closure cycles of IJV leaflets. The normal opening time calculated in this study includes 70% of the dynamic valve cycle. The normal opening time of the IJV valve could be a new physiologic metric and serves as a premise for further studies in the field of cerebral venous return., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Patients with idiopathic intracranial hypertension are frequently obese women with normal/slit ventricles. Patients with high-pressure hydrocephalus, instead, present enlarged ventricles. We describe a 63-year-old woman with signs and symptoms of intracranial hypertension. Brain MRI revealed hydrocephalus. Venous Doppler ultrasound showed external compression of the omohyoid muscles on the internal jugular veins. During jugular vein decompression, intracranial pressure dropped from 18 to 6 mmHg. Patient is asymptomatic at 2-year follow-up, with decreased brain ventricles. These findings could represent a novel form of high-pressure hydrocephalus that can be successfully treated without a CSF shunt. We called this syndrome JEDI (jugular entrapment dilated ventricles intracranial hypertension).

Objective: Despite the modern appeal of wearing compressive garments during physical activities, the literature is lacking in quality data and controversial in the investigations dealing with the pathophysiologic mechanism by which graduated compression stockings (GCS) affect the calf pump activation in healthy individuals. The aim of the investigation was to provide insight into the clinical effects of GCS use during a standardized walking exercise., Methods: Twenty physically active healthy volunteers (mean age, 34 ± 5 years; body mass index, 22 ± 2 kg/m 2 ) underwent lower limb ultrasound scanning to exclude vascular impairment. All individuals performed continuous aerobic exercise, walking for 30 minutes on a treadmill, under cardiac monitoring, at 70% of individual estimated maximal heart rate according to the Tanaka equation. The study population performed the standardized walk without GCS (baseline) and at 1 week performed the same standardized walk wearing knee-length 20 to 30 mm Hg GCS (compression). All individuals underwent a lower limb volume assessment by truncated cone formula before and after the walk and a perceived exertion assessment by means of the validated Borg scale at the end of the exercise protocol., Results: All individuals had normal venous and arterial ultrasound examination findings. No significant postural defects were reported. Both legs were assessed in all 20 individuals for a total of 40 cases with and 40 cases without GCS. In the baseline group, the median (interquartile range) lower limb volume changed from 2496 (770) mL before exercise to 2512 (805) mL (P = .2597) after exercise. The compression group reported a significant lower limb volume change from 2466 (670) mL before exercise to 2276 (567) mL (P = .0001) after exercise. Mean perceived exertion was 13 (11) and 11 (1) in the baseline and compression groups, respectively (P = .0001). The interface pressure exerted by the GCS was 24 (2) mm Hg. No complaints in terms of discomfort were reported after use of GCS., Conclusions: In healthy individuals, GCS (24 [2] mm Hg) use during a continuous standardized walk of 30 minutes is associated with a significant decrease in lower limb volume and a decrease in perceived exertion. The mechanism by which GCS impart their effect during physical activity may involve improved muscle pump function and reductions in inflammatory pathways. Further study will need to validate the mechanisms of the function of GCS used during physical exercise., (Copyright © 2019 Society for Vascular Surgery. All rights reserved.)

Background: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels., Methods: We studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI). Microarray-based transcriptome analysis was conducted on specimens of IJV wall from MS patients and from subjects undergoing carotid endarterectomy, as controls. Protein levels were determined by multiplex assay in: i) jugular and peripheral plasma from 17 MS/CCSVI patients; ii) peripheral plasma from 60 progressive MS patients, after repeated sampling and iii) healthy individuals., Results: Of the differentially expressed genes (≥ 2 fold-change, multiple testing correction, P < 0.05), the immune-related CD86 (8.5 fold-change, P = 0.002) emerged among the up regulated genes (N = 409). Several genes encoding HOX transcription factors and histones potentially regulated by blood flow, were overexpressed. Smooth muscle contraction and cell adhesion processes emerged among down regulated genes (N = 515), including the neuronal cell adhesion L1CAM as top scorer (5 fold-change, P = 5 × 10 - 4 ). Repeated measurements in jugular/peripheral plasma and overtime in peripheral plasma showed conserved individual plasma patterns for immune-inflammatory (CCL13, CCL18) and adhesion (NCAM1, VAP1, SELL) proteins, despite significant variations overtime (SELL P < 0.0001). Both age and MS disease phenotypes were determinants of VAP1 plasma levels. Data supported cerebral related-mechanisms regulating ANGPT1 levels, which were remarkably lower in jugular plasma and correlated in repeated assays but not between jugular/peripheral compartments., Conclusions: This study provides for the first time expression patterns of the IJV wall, suggesting signatures of altered vascular mRNA profiles in MS disease also independently from CCSVI. The combined transcriptome-protein analysis provides intriguing links between IJV wall transcript alteration and plasma protein expression, thus highlighting proteins of interest for MS pathophysiology.

Objectives: The aim was to assess more accurately the net flow of the lower limb perforating veins (PVs)., Material and Methods: This was an observational prospective study. Two hundred and twenty one limbs with chronic venous disease (C1-6EpAs,pPr) of 193 patients underwent a duplex ultrasound (DUS). All identified PVs were scanned also by means of quality Doppler profile (QDP) multigate analysis in order to determine their net inward and outward flow direction. A comparison between the traditional pulsed wave Doppler analysis and QDP was performed to detect potential discrepancy between the traditional definition of PV incompetence and a net outward flow., Results: The DUS investigation identified 774 PVs. Only 7.7% of the PVs showed an outward flow lasting more than 500 ms. Among the PVs showing a longer than 500 ms outward flow, QDP assessment revealed net outward flow in only 84% of the PVs along the thigh and in 28.6% along the lower leg. Among the PVs showing a shorter than 500 ms outward flow, QDP assessment reported a net outward flow in 2.4% of the PVs along the thigh and in 47.3% of those along the lower leg. The sensitivity of an outward flow lasting more than 500 ms in detecting an actual net outward flow was 13.9% (9-20.1%). The specificity of an outward flow lasting less than 500 ms in detecting a net inward flow was 96.4% (93.2-98.3%)., Conclusions: A lack of overlap exists between the finding of a PV outward flow lasting more than 500 ms and the net outward flow of the same vessel. The traditional definition of PV incompetence is challenged by the reported data and further investigations are required to identify a gold standard assessment., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background Literature concerning the lower limbs physiological venous haemodynamics is still lacking of reference velocity values and consequent impact on drainage direction. Aim of the present study is to assess the flow velocities in the different venous compartments, evaluating the possible Venturi effect role, thus finding clues for the identification of the physical model governing the flow direction. Methods Thirty-six lower limbs underwent a velocity and diameters echo-color-Doppler assessment in several anatomical point of analysis along both the deep and superficial venous systems. The investigation protocol included and compared two different manoeuvres to elicit the flow: manual calf compression/relaxation (CR) and active foot dorsiflexion (AFD). Both peak systolic (PSV) and time average velocities (TAV) were measured. Results The different venous segments demonstrated an overlap among the velocity values and the anatomical subdivision of the deep and superficial compartments. At the CR, TAV was 34 ± 12 cm/s in the deep venous system (N1), 15 ± 7 cm/s in the saphenous system (N2), 5 ± 2 cm/s in the saphenous tributaries (N3); PSV was 89 ± 35 cm/s in N1, 34 ± 16 cm/s in N2, 11 ± 4 cm/s in N3, p < 0.05. At the AFD, TAV was 33 ± 13 cm/s in N1, 15 ± 7 in N2, 9 ± 5 in N3; PSV was 83 ± 35 in N1, 32 ± 17 in N2, 15 ± 4 in N3, p < 0.05. A diameter decrease was reported from N1 to N3 ( p < 0.05). Conclusion This investigation provides evidences of the velocity decrease from the deepest to the most superficial compartments. These data introduce the Venturi effect as potential factor in the flow aspiration from the tributary to the deeper veins. The reported data represent a first step towards an objective evaluation of the physic laws governing the drainage. These values can constitute the basis for further investigations in pathological and post-procedural scenarios.

Objective Despite the fact that muscle pump activation is known to positively impact chronic lower limb edema, objective measurements of standardized exercises for venous-lymphatic rehab are lacking. The aim of this investigation is to determine the effectiveness of an addressed physical activity exploiting the advantages of an aquatic environment. Material and methods Thirty-two lower limbs of 16 patients affected by bilateral chronic leg swelling were included (12 females, 4 males). All the patients underwent a protocol of five sessions of physical exercises specifically conceived inside a pool. Volumetry, subcutaneous thickness, ankle range of motion and symptomatology were assessed as outcome measures. Results One week after the end of the protocol, the average reduction in lower limb volume was 303.13 ± 69.72 ml ( p = 0.00002) and 334.38 ± 62.50 ml ( p = 0.000003) in the right and left legs, respectively. Ankle range of motion and feeling of heaviness significantly improved. Conclusion A specifically designed aquatic protocol is able to positively impact chronic leg swelling offering a first line rehab for this medical condition.

Objective: Increased ventricle volume and brain hypoperfusion are linked to neurodegeneration. We hypothesized that in patients with restricted jugular flow, surgical restoration may reduce brain ventricle volume, because it should improve the pressure gradient, hence promoting cerebrospinal fluid reabsorption into the venous system., Methods: The effects of restoring the jugular flow were assessed by means of a validated echocardiography with color Doppler (ECD) protocol of flow quantification, magnetic resonance venography, and single-photon emission computed tomography combined with computed tomography (SPECT-CT). The main outcome measurement was the cerebral ventricle volume blindly assessed at SPECT-CT. Secondary outcomes were brain perfusion in the whole brain and in another 12 cerebral regions. The mean follow-up of the SPECT-CT and ECD parameters was 30 days. Patency rate was subsequently monitored by means of the same ECD protocol every 3 months., Results: Among 56 patients (28 male and 28 female; mean age, 44 ± 10 years) with ECD screening positive for chronic cerebrospinal venous insufficiency due to nonmobile jugular leaflets, 15 patients were excluded from the initial cohort because they did not meet the inclusion and exclusion criteria. Of the remaining 41 patients, 27 patients (14 male, 13 female; mean age, 48 ± 7 years) underwent endophlebectomy and autologous vein patch angioplasty. Omohyoid muscle section was performed when appropriate. The control group comprised 14 patients matched by age and gender (8 male, 6 female; mean age, 44 ± 11 years) who were not treated. Comorbidity was multiple sclerosis without significant differences in relapsing remitting (RR) and secondary progressive (SP) clinical course among groups. In the control group, neither ECD nor SPECT-CT showed any significant changes at follow-up. On the contrary, in the group operated on, the collateral flow index went from 70% to 30% (P < .0003) thanks to improved flow through the internal jugular vein. Correspondingly, ventricle volume dramatically decreased in the treated group (from 34 ± 14 cm(3) to 31 ± 13 cm(3); P < .01). The effect was much more evident in the RR subgroup (P = .009), whereas in the SP subgroup, it was not significant. Perfusion was found to be improved in the surgical group with respect to controls, particularly in the occipital and parietal regions of the RR subgroup (P < .0001 and P = .017, respectively), but not in the SP subgroup. The probability of reducing ventricle size is increased by 13-fold (P < .03) when restoration of the jugular flow achieves a postoperative collateral flow index ≤20%. Finally, the 18-month patency rate was 74%., Conclusions: Fixing the flow in the jugulars in patients with chronic cerebrospinal venous insufficiency might significantly reduce brain ventricle volume and improve cerebral perfusion. These changes are more evident in patients in the earlier stages of neurodegenerative disease., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

There is growing interest in measuring cerebral venous outflow with ultrasound (US). However, results obtained with the current US Doppler methodology, which uses just a single value of cross-sectional area (CSA) of the vessel, are highly variable and inconclusive. The product of CSA and time-averaged velocity in the case of pulsatile vessels may be a possible source of error, particularly for a pulsatile vein like the internal jugular vein (IJV), where the cardiac pump transmits a sequence of well-established waves along the conduit. We herein propose a novel technique for US IJV flow assessment that accurately accounts for IJV CSA variations during the cardiac cycle. Five subjects were investigated with a high-resolution real-time B-mode video, synchronized with an electrocardiography trace. In this approach, CSA variations representing the pulsatility of the IJV are overlapped with the velocity curve obtained by the usual spectral Doppler trace. The overlap is then phased point by point using the electrocardiography pacemaker. This allows us to experimentally measure the velocity variation in relation to the change in CSA precisely, ultimately enabling calculation of IJV flow. (i) The sequence of CSA variation with respect to the electrocardiography waves corresponds exactly to the jugular venous pulse as measured in physiology. (ii) The methodology permits us to phase the velocity and CSA, which is ultimately what is currently lacking to precisely calculate the flow in the IJV with US. (iii) The time-averaged flow, calculated with the described technique, is very close to that calculated assuming a constant IJV CSA, whereas the time-dependent flow shows differs as much as 40%. (iv) Finally, we tested the accuracy of the technique with a methodology that may allow for universal assessment of the accuracy of each personal US-based evaluation of flow rate., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA)., Materials and Methods: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis., Results: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group., Conclusions: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: Venous abnormalities have been associated with different neurological conditions, and the presence of a vascular involvement in multiple sclerosis (MS) has long been anticipated. In view of the recent debate regarding the existence of cerebral venous outflow impairment in MS due to abnormalities of the azygos or internal jugular veins (IJVs), we have studied the morphological and biological features of IJVs in MS patients., Methods: We examined (a) IJVs specimens from MS patients who underwent surgical reconstruction of the IJV and specimens of the great saphenous vein used for surgical reconstruction, (b) different vein specimens from an MS patient dead of an unrelated cause, and (c) autoptical and surgical IJV specimens from patients without MS. Collagen deposition was assessed by means of Sirius red staining followed by polarized light examination. The expression of collagen type I and III, cytoskeletal proteins (α-smooth muscle actin and smooth muscle myosin heavy chains), and inflammatory markers (CD3 and CD68) was investigated., Results: The extracranial veins of MS patients showed focal thickenings of the wall characterized by a prevailing yellow-green birefringence (corresponding to thin, loosely packed collagen fibers) correlated to a higher expression of type III collagen. No differences in cytoskeletal protein and inflammatory marker expression were observed., Discussion: The IJVs of MS patients presenting a focal thickening of the vein wall are characterized by the prevalence of loosely packed type III collagen fibers in the adventitia. Further studies are required to determine whether the observed venous alterations play a role in MS pathogenesis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)