Mirko Tessari

Assessment of cerebral venous return by a novel plethysmography method

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.

CHIVA strategy in chronic venous disease treatment: instructions for users

Along the years, scientific clinical data have been collected concerning the possible saphenous flow restoration without any ablation and according with the CHIVA strategy. Moreover, in 2013 a Cochrane review highlighted the smaller recurrence risk following a CHIVA strategy rather than a saphenous stripping. Nevertheless, the saphenous sparing strategy surely remains a not-so-worldwide-spread and accepted therapeutic option, also because considered not so immediate and easy to perform. Aim of this paper is to provide an easily accessible guide to an everyday use of a saphenous sparing strategy for chronic venous disease, highlighting how even apparently too complicated reflux patterns classifications can be fastly and successfully managed and exploited for a hemodynamic correction.

AN ULTRASONOGRAPHIC TECHNIQUE TO ASSESS THE JUGULAR VENOUS PULSE: A PROOF OF CONCEPT

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.

Human internal jugular valve M-mode ultrasound characterization.

In humans the mechanism governing the internal jugular vein (IJV) valve opening and closure is still unclear. M-mode is used in echo-cardiology for the heart valves assessment. Sometimes it was performed also in deep peripheral veins and in vena cava assessment, but never in the IJV valve. Aim of the present study is to investigate the IJV valves physiology in healthy volunteers, by means of both B and M-mode ultrasound. Eighty-three (83) healthy volunteers (35 Male, 48 Female, 25.7±6.7 y.o.), for a total of 166 IJVs, were enrolled. The entire cohort underwent IJVs high-resolution B and M-mode evaluation, in standardized postural and respiratory conditions. Presence, motility, and number of cusps, as well as their opening and closure mechanism have been assessed. Bilateral valve absence occurred in 13/83 (16%), whereas at least a one side absence was recorded in 38/83 (46‰ of the cohort) (p<0.0356). Valve leaflets were always mobile and respectively bi-cusps in 34%, or mono-cusp in 27%. The latter was significantly more frequent on the left side (35%) than on the right side (19%) (p<0.0013). In supine, M-mode valve opening was synchronous with the cardiac cycle. To the contrary, in an upright position, the valve remained always open and saddled to the wall, independently from the cardiac cycle. In healthy subjects, the IJV valve leaflets are always mobile, but the significant rate of mono and bilateral absence could suggest a progressive phylogenetic importance loss of such apparatus. M-mode ultrasound enhances the characterization of IJV valve, for this reason it should be taken into consideration to routinely add it to the cerebral venous return investigation.

Clinical Applicability of Assessment of Jugular Flow over the Individual Cardiac Cycle Compared with Current Ultrasound Methodology

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.

The calendar of cytokines: Seasonal variation of circulating cytokines in chronic venous insufficiency

Objectives To assess if in chronic venous insufficiency, there is a seasonal variation of cytokines levels which could explain the typical worsening of symptoms during Spring and Summer. Participants From 193 chronic venous insufficiency patients, we selected 32 patients in clinical stage C2–C3 of the Clinical–Etiology–Anatomy–Pathophysiology classification. Design A prospective, comparative and blinded cytokines assessment in two different seasons. Setting We sorted patients by two homogenous groups, 17 Autumn Group and 15 Spring Group. A complete clinical and haemodynamic assessment and laboratory analysis of 22 circulating cytokines were performed on each patient. Main outcome measures Circulating cytokines levels assessment. Results The two groups resulted homogenous for age, gender, clinical class, and haemodynamic parameters. Comparing cytokines expressions in Autumn Group vs. Spring Group, we found a significant difference of 11 out of 22 circulating cytokines (p < 0.05). Particularly Eotaxin, Interleukin-8, Monocyte Chemoattractant Protein-1, Tumour Necrosis Factor-α and Vascular Endothelial Growth Factor were increased in Autumn compared to the Control Group (p < 0.001); while significantly reduced in Spring, within the normal range (p, not significant). Conclusions Symptoms of chronic venous insufficiency are self-reported by patients more intense during warm seasons. Surprisingly, in our study, cytokines levels were significantly higher during Autumn and downregulated in Spring. These variations show for the first time the presence of a ‘Calendar of Cytokines’ in chronic venous insufficiency, which needs to be further investigated.

Femoral vein valve incompetence as a risk factor for junctional recurrence.

Background Recurrent varicose veins occur up to 80% of procedures. The sapheno-femoral junction can be involved in more than 50% of cases. A detailed pathophysiological explanation of the phenomenon is still missing. The aim of the present work is to evaluate the role of femoral vein incompetence as risk factor for sapheno-femoral junction recurrence. Methods Three-hundred-eighty-one patients presenting an incompetent great saphenous vein system and eventually also an incompetent femoral tract (C2-6EpAsdPr) underwent a great saphenous vein high ligation with flush ligation also of the incompetent tributaries along the leg, sparing the saphenous trunk. Pre-operatively, all patients underwent a sonographic evaluation assessing the superficial and deep venous systems, including a detailed analysis of the iliac-femoral vein tract above the sapheno-femoral junction. A retrospective statistical analysis assessed the recurrence risk associated with iliac-femoral vein tract incompetence. Results In a 5.5 ± 1.9 years follow-up, great saphenous vein trunk reflux recurrence was detected in 45/381 (11.8%) cases. The reflux source was found in a reconnected sapheno-femoral stump in 11/45 cases (24.5%), in the pelvic network in 8/45 cases (17.8%), in a neovascularization process in 7/45 (15.5%) and in a newly incompetent great saphenous vein tributary in 19/45 (42.2%). At the pre-operative assessment, iliac-femoral vein tract reflux was present in 7 (26.9%) of the 26 cases who developed a sapheno-femoral junction recurrence and in 25 (7%) of the 355 patients who did not demonstrate sapheno-femoral junction recurrence (odds ratio: 4.8; confidence interval 95%: 1.8–12.6; p < .003). Discussion Despite many technical diagnostic and therapeutic refinements, varicose veins recurrence remains a frequent event. The present investigation points out the association among iliac-femoral vein tract incompetence and sapheno-femoral junction recurrences after high ligation.

A specifically designed aquatic exercise protocol to reduce chronic lower limb edema.

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.

Cerebral Inflow and Outflow Discrepancies in Severe Sudden Sensorineural Hearing Loss

The aim of this study is to evaluate whether cerebral inflow and outflow abnormalities, assessed by the means of a validated ultrasound model, could be associated with Sudden Sensorineural Hearing Loss (SSNHL). According to Clark, a total of 42 patients affected by severe SSNHL and 19 healthy volunteers matched by gender without any history of sudden hearing impairment have been included in this study. Patients and controls underwent EchocolorDoppler assessment of brain hemodynamics. All subjects affected by SSNHL were also assessed with Auditory Brainstem Responses (ABR) and Magnetic Resonance Imaging (MRI) in order to exclude retrocochlear pathology. The head inflow through the common carotid artery was practically equivalent between groups, but at the level of the carotid bifurcation, the external carotid artery showed a highly significant flow rate in SSNHL 5.4±2 vs 3.9±1.1 ml/s in controls (p=0.01). The brain inflow was similar between patients and controls, but interestingly the flow rate of the vertebral artery was significantly reduced in SSNHL 1.6±0.8 vs 2.8±0.9 ml/s (p=0.01). The brain outflow was found significantly restricted at the level of the jugular outlet 6.6±6 vs 9.9±6 ml/s (p=0.002); consequently, the collateral flow index was significantly increased in SSNHL (p=0.001). The present study shows a discrepant distribution of the brain inflow which seems to penalize the posterior segments of the Willis polygon in patients affected by severe SSNHL. In addition, our study confirms the presence of chronic cerebrospinal venous insufficiency in SSNHL with significant activation of venous collateral circulation.

High Resolution M-Mode Evaluation of Jugular Vein Valves in Patients with Neurological and Neurosensory Disorders.

BACKGROUND High prevalence of valve absence was found in the internal jugular vein (IJV) of healthy volunteers by means of M-mode high-resolution Echo Colour Doppler (ECD). However, the prevalence of valve in neurovascular disorders linked to Chronic Cerebrospinal Venous Insufficiency (CCSVI) is still unknown. METHODS A cohort of 83 Healthy Controls (HC), 71 Multiple Sclerosis (MS), 99 Inner Ear Disorders (IED) underwent ECD investigation of the IJV valve, including M-mode evaluation and related hemodynamics. The primary outcome measure was characterization of valve presence, morphology and motility, whereas the secondary outcome was the rate of flow alteration. RESULTS Bilateral valve presence was found in 38% of HC, 58% of MS and 25% of IED, whereas, bilateral valve absence was recorded in 16% of HC, 10% of MS and 31% of IED (p<0.003). Bicuspid morphology was more prevalent in HC 56%, while monocusp was more prevalent in patients: 75% MS and 57% IED (p<0.0001). The main finding was the presence of mobile valve leaflets in 98% of HC, contrarily fixed valve leaflets were recorded in 82% of MS and in 41% of IED, p< 0.0001. Finally, by stratifying the entire cohort according to the presence of mobile and not mobile valve leaflets, normal monodirectional and phasic flow were commonly found in the mobile leaflets subgroup, p<0.0001. CONCLUSION In patients with miscellaneous neurological disorders, a significant higher rate of defective valves was found with respect to HC. The latter condition is strongly associated to brain outflow abnormalities described in CCSVI condition.