Erica Menegatti

Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

Background: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. Methods: 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. Results: 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. Conclusion: 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.

A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency

OBJECTIVE Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by combined stenoses of the principal pathways of extracranial venous drainage, including the internal jugular veins (IJVs) and the azygous (AZY) vein, with development of collateral circles and insufficient drainage shown by increased mean transit time in cerebral magnetic resonance (MR) perfusion studies. CCSVI is strongly associated with multiple sclerosis (MS). This study evaluated the safety of CCSVI endovascular treatment and its influence on the clinical outcome of the associated MS. METHODS Sixty-five consecutive patients with CCSVI, subdivided by MS clinical course into 35 with relapsing remitting (RR), 20 with secondary progressive (SP), and 10 with primary progressive (PP) MS, underwent percutaneous transluminal angioplasty (PTA). Mean follow-up was 18 months. Vascular outcome measures were postoperative complications, venous pressure, and patency rate. Neurologic outcome measures were cognitive and motor function assessment, rate of MS relapse, rate of MR active positive-enhanced gadolinium MS lesions (Gad+), and quality of life (QOL) MS questionnaire. RESULTS Outpatient endovascular treatment of CCSVI was feasible, with a minor and negligible complication rate. Postoperative venous pressure was significantly lower in the IJVs and AZY (P < .001). The risk of restenosis was higher in the IJVs compared with the AZY (patency rate: IJV, 53%; AZY, 96%; odds ratio, 16; 95% confidence interval, 3.5-72.5; P < .0001). CCSVI endovascular treatment significantly improved MS clinical outcome measures, especially in the RR group: the rate of relapse-free patients changed from 27% to 50% postoperatively (P < .001) and of MR Gad+ lesions from 50% to 12% (P < .0001). The Multiple Sclerosis Functional Composite at 1 year improved significantly in RR patients (P < .008) but not in PP or SP. Physical QOL improved significantly in RR (P < .01) and in PP patients (P < .03), with a positive trend in SP (P < .08). Mental QOL showed significant improvement in RR (P < .003) and in PP (P < .01), but not in SP. CONCLUSIONS PTA of venous strictures in patients with CCSVI is safe, and especially in patients with RR, the clinical course positively influenced clinical and QOL parameters of the associated MS compared with the preoperative assessment. Restenosis rates are elevated in the IJVs but very promising in the AZY, suggesting the need to improve endovascular techniques in the former. The results of this pilot study warrant a subsequent randomized control study.

The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis

Iron stores in the white and deep grey matter in course of multiple sclerosis (MS) have never been explained and could be related to abnormalities in venous drainage, but this possibility has never before been investigated. From an initial cohort of 320 subjects, after application of exclusion criteria, we selected 109 patients affected by MS, and 177 controls respectively composed by age- and sex-matched, healthy aged, and patients affected by other neurological diseases. They blindly underwent transcranial and extracranial Color-Doppler sonographic examination (TCCS-ECD), aimed at investigating five parameters related to normal cerebral venous outflow haemodynamics. Overall we analyzed 1430 TCSS-ECD parameters. In controls we found 861 normal parameters of cerebral venous return vs. 24 anomalous, whereas in MS 288 parameters were normal and 257 anomalous, respectively. Consequently, each of the considered Doppler haemodynamic parameters, when compared to revised McDonald criteria as a gold standard of MS diagnosis, showed separately a highly significant sensitivity and a noteworthy specificity. However, the detection >or=2 parameters in the same subject, never observed in controls, perfectly overlapped the diagnosis of MS (value, 95%CI: sensitivity 100%, 97-100; specificity 100%, 98-100; positive predictive value 100%, 97-100, negative predictive value 100%, 98-100; p<0.0001). Moreover, this study demonstrates a significant impairment of cerebral venous drainage in patients affected by MS, a mechanism potentially related to increased iron stores.

Intracranial Venous Haemodynamics in Multiple Sclerosis

In multiple sclerosis (MS) plaques are known to be venocentric; in addition, MS lesions and peripheral venous disorders share a number of key features. To date, however, despite the anatomical relationship between MS lesions and the venous system, no information on the intracranial venous haemodynamics of MS is available. Eighty-nine consecutive MS patients (58 relapsing-remitting, 31 secondary progressive) matched with 60 controls underwent transcranial color-coded duplex sonography (TCCS). We assessed, in supine as well as in sitting positions, the direction of flow at the activation of the thoracic pump in the deep middle cerebral veins (dMCVs), and in the transverse sinus (TS). In the dMCVs, we also measured peak systolic velocity (PSV), peak diastolic velocity (PDV), as well as the resistance index (RI). Reflux/bidirectional flow rate was significantly higher in the MS population determining also significant differences in PDV, characterized by negative values (16.2+/-1 cm/sec in controls vs. -1.3 +/-2.6 cm/sec in MS, respectively, p<0.0001). Consequently, RI was dramatically increased in the MS group, affecting impedance of cerebral venous drainage (0.48+/-0.04 in controls vs. 1.1 +/-0.08 in MS, respectively p<0.0001). Therefore, the detection of reflux directed toward the subcortical grey matter was significantly associated to highest disability scores (p < 0.0001). Our study of MS patients demonstrated significant haemodynamic alterations detected in veins anatomically related to plaque disposition. Our findings should contribute towards understanding the role of altered venous flow and tissue drainage in the MS inflammatory chain, as well as in the neurodegenerative process.

Venous Collateral Circulation of the Extracranial Cerebrospinal Outflow Routes

A new nosologic vascular pattern that is defined by chronic cerebrospinal venous insufficiency (CCSVI) has been strongly associated with multiple sclerosis. The picture is characterized by significant obstacles of the main extracranial cerebrospinal veins, the jugular and the azygous system, and by the opening of substitute circles. The significance of collateral circle is still neglected. To the contrary, substitute circles are alternative pathways or vicarious venous shunts, which permit the drainage and prevent intracranial hypertension. In accordance with the pattern of obstruction, even the intracranial and the intrarachidian veins can also become substitute circles; they permit redirection of the deviated flow, piping the blood toward available venous segments outside the central nervous system. We review the complex gross and radiological anatomy of collateral circulation found activated by the means of EchoColor-Doppler and selective venography in the event of CCSVI, focusing particularly on the suboccipital cavernous sinus (SCS), the condylar venous system, the pterygoid plexus, the thyroid veins, and the emiazygous-lumbar venous anastomosis with the left renal vein.

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report

BackgroundSeveral studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI).MethodsWe investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities.ResultsThere was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.ConclusionsThis pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.

Doppler Haemodynamics of Cerebral Venous Return

Physiologic functioning of the cerebrovenous system is indispensable for maintaining normal brain function. However, in contrast to the cerebroarterial system, the cerebral venous return is not routinely investigated. Combined high-resolution echo-colour-Doppler (ECD) and transcranial colour coded Doppler sonography (TCCS) represents an ideal method to investigate the haemodynamics of cerebral venous return. TCCS-ECD is noninvasive, repeatable, cost-effective and permits to investigate the cerebral venous outflow in its dependence upon changes in posture and the alternating pressure gradients of the thoracic pump. Several authors reported normal parameters concerning related aspects of cerebral venous return. However, there is no ECD-TCCS standardization of what can be considered a normal venous return. The authors have summarized the current knowledge of the Doppler haemodynamics of the cerebrovenous system and propose a list of reproducible clinical parameters for its sonographic evaluation. In future, the development of this diagnostic technique could be of singular interest in iron-related inflammatory and neurodegenerative disorders like multiple sclerosis.

An ultrasound model to calculate the brain blood outflow through collateral vessels: a pilot study

BackgroundThe 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.MethodsWe 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.ResultsIn HC the HBinF was 956+-105ml/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).ConclusionsOur 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.

Great saphenous varicose vein surgery without saphenofemoral junction disconnection

The aim of this case–control study was to determine whether preoperative duplex imaging could predict the outcome of varicose vein surgery without saphenofemoral junction (SFJ) disconnection. The duplex protocol included a reflux elimination test (RET) and assessment of the competence of the terminal valve of the femoral vein.

Does thoracic pump influence the cerebral venous return

We assessed the hemodynamic effects induced by the thoracic pump in the intra- and extracranial veins of the cerebral venous system on healthy volunteers. Activation of the thoracic pump was standardized among subjects by setting the deep inspiration at 70% of individual vital capacity. Peak velocity (PV), time average velocity (TAV), vein area (VA), and flow quantification (Q) were assessed by means of echo color Doppler in supine posture. Deep respiration significantly increases PV, TAV, and Q, but it is limited to the extracranial veins. To the contrary, no significant hemodynamic changes were recorded at the level of the intracranial venous network. Moreover, at rest TAV in the jugular veins was significantly correlated with Q of the intracranial veins. We conclude that the modulation of the atmospheric pressure operated by the thoracic pump significantly modifies the hemodynamics of the jugular veins and of the reservoir of the neck and facial veins, with no effect on the vein network of the intracranial compartment.