Screening for chronic cerebrospinal venous

insufficiency (ccsvi) using ultrasound.

Recommendations for a protocol

 

 

Andrew N. Nicolaides, MD, Hon PhDa

Sandra Morovic, MD, PhDb

Erica Menegatti, PhDb

Gisel Viselner, MDc

Paolo Zamboni, MDb

on behalf of the Intersociety Committee1 of the Consensus Conference on

Practical Guidelines for the investigation and screening of CCSVI (Italy, March 2011)

 

a Imperial College, London, UK

b Vascular Disease Center, University of Ferrara, Italy

c IRCCS C. Mondino National Institute of Neurology Foundation, Department of Neuroradiology

University of Pavia, Italy

 

The Consensus Conference was held on March 13, 2011 at the International Society for Neurovascular Diseases Annual Meeting in Bologna in collaboration with the International Union of Angiology (IUA), European Venous Forum (EVF), International Union of Phlebology (IUP), American College of Phlebology (ACP), Austral-Asian College of Phlebology (AAsCP), Italian Society for Vascular and Endovascular Surgery (SICVE), Italian Society of Pathology of the Vascular Apparatus (SIAPAV).

 

Corresponding author: Paolo Zamboni

Vascular Diseases Center

University of Ferrara

44100 Ferrara, Italy

E-mail: zmp@unife.it

 

 

Summary

 

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenoses or obstructions of the internal jugular and/or azygos veins with disturbed flow and formation of collateral venous channels. Ultrasound and venographic studies of the internal jugular and azygos venous systems in patients with multiple sclerosis (MS) have demonstrated a high prevalence of CCSVI (mean 71%, range 0-100%; n=1336) associated with activation of collaterals. By contrast, ultrasound and venographic examinations of normal controls and patients without MS have demonstrated a much lower prevalence (mean 7.1%, range 0-22%; n=505).

Ultrasound in the form of duplex scanning uses a combination of physiological measurements as well as anatomical imaging and has been used for the detection of CCSVI by different centers with variable results. A high prevalence of obstructive lesions, ranging from 62% to 100%, has been found by some teams in patients with MS compared with a low prevalence (0-25%) in controls. However, others have reported absence of these lesions or a lower prevalence (16-52%). This variability could be the result of differences in technique, training, experience or criteria used.

In order to ensure a high reproducibility of duplex scanning with comparable accuracy between centers a detailed protocol with standard methodology and criteria is needed. Also, standardization of the method of reporting of duplex measurements and other findings will facilitate validation of the proposed criteria by different centers. The aim of this document is to produce recommendations for such a protocol and indicate what future research is needed in order to address areas of uncertainty.

 

Key words: chronic cerebrospinal venous insufficiency, consensus conference, Doppler ultrasound, multiple sclerosis

 

 

Introduction

 

Background and aims of the document

Chronic cerebrospinal venous insufficiency (CCSVI) is a syndrome characterized by stenoses or obstructions of the internal jugular vein (IJV) and/or azygos (AZ) vein with disturbed flow and formation of collateral venous channels (1,2). Ultrasound and venographic studies of the internal jugular and azygos venous systems in patients with multiple sclerosis (MS) have demonstrated a high prevalence of CCSVI (mean 71%, range 0-100%; n=1336) associated with activation of collaterals (1-12). By contrast, ultrasound and venographic examinations of normal controls and patients without MS have demonstrated a much lower prevalence (mean 7.1%, range 0-22%; n=505) (Table 1, over).

The origin of venous anomalies is still not completely understood. These lesions are mostly segmental hypoplasia or intraluminal defects, collectively classified as truncular venous malformations (13-15). Truncular lesions are the result of developmental arrest that occurs during the “later” stages of vascular trunk formation in fetal life. Immature or incomplete development of the main axial veins results in aplasia, hypoplasia or hyperplasia of the vessel or in a defective vessel with obstruction by intraluminal lesions (e.g., vein web, spur, annulus, or septum) or dilatation (e.g., jugular vein ectasia/aneurysm). Such lesions were not detected in radiological studies on healthy subjects (16-25); on the contrary, CCSVI-like lesions have been described in association with myelopathies (26,27).

The increased prevalence of obstruction to the drainage of cerebrospinal veins in patients with MS suggests that venous obstruction may be a contributory factor in the development and progression of this disease. It has also been suggested that relief of such obstruction may produce clinical benefit. In two observational studies involving, overall, 80 MS patients with CCSVI, angioplasty reduced the rate of relapse, improved the Multiple Sclerosis Functional Composite in patients with relapsing-remitting MS (28,29), and improved physical and mental quality of life (QOL) in relapsing-remitting and primary progressive MS (28). In another study of 31 patients, followed up for twelve months, angioplasty reduced chronic fatigue as assessed by the Fatigue Severity Scale and the Fatigue Impact Scale (30). Safety was confirmed in more than 500 procedures (31). However, the true clinical benefit will be known only when the results of multicenter studies, now in progress, become available. For a list of clinical trials on CCSVI treatment, both completed and ongoing, see Appendix 1.

Catheter venography is considered the gold standard for determining the anatomical site, type and extent of lesions producing CCSVI. However, venography is invasive and cannot be used as a screening method. By contrast, ultrasound is an ideally suited, non-invasive method of screening and could prove to be a valuable diagnostic test when high sensitivity and specificity are demonstrated. In the presence of high sensitivity and specificity, venography will be needed only when it has already been decided to intervene.

Ultrasound in the form of duplex scanning uses a combination of physiological measurements as well as anatomical imaging and has been used for the detection of CCSVI by different centers with variable results. A high prevalence of obstructive lesions, ranging from 62% to 100%, has been found by some teams in patients with MS compared with a low prevalence of 0-25% in controls (1-7). However, others have reported absence of such lesions (8,9) or a lower prevalence (16-52%) (10-12). This variability could be the result of differences in technique, training, experience or criteria used.

In order to ensure a high reproducibility of duplex scanning with comparable accuracy between centers a detailed protocol with standard methodology and criteria is needed. Also, standardization of the method of reporting duplex measurements and other findings will facilitate validation of the proposed criteria. The aims of this document are to produce recommendations for such a protocol and to indicate what future research is needed in order to address areas of uncertainty.

 

Anatomy of the cerebrospinal venous system

The cerebrospinal venous system is usually asymmetric and has a more variable vessel pattern than the arterial system. The intracranial part is mainly composed of parenchymal veins draining into the dural sinuses. Two main systems are responsible for blood collection, the superficial (cortical) system (blood reaches the dural sinuses by cortical veins and drains blood mainly from the cortex and part of the subcortical white matter), and the deep cerebral venous system, composed of internal cerebral veins, the basal vein of Rosenthal and the great cerebral vein of Galen and their tributaries. They drain the deep “periventricular” white and central gray matter “basal ganglia and thalamus” surrounding the lateral and third ventricles, the brainstem and anterior cerebellum which drains into the straight sinus (2,32). Blood is collected by the dural sinuses and directed towards the main extracranial venous outflow routes: the IJV and the vertebral system. The IJV drains into the superior vena cava via the brachiocephalic vein (Fig. 1 a,b). The vertebral venous system is a valveless system stretching the length of the entire spinal column and it comprises three parts: the internal intraspinal part, the epidural veins, and the extraspinal paravertebral part. The extraspinal part in the neck consists of the vertebral veins (VVs) which accompany the vertebral artery and drain into the innominate vein on the right and into the subclavian vein on the left (Fig. 1a). They are reported to be valveless but venographic studies have shown that valves may be present at the junction of the vertebral and subclavian veins. The rest of the vertebral venous system, which is a rich plexus, communicates with the deep thoracic and lumbar veins, intercostal veins, the azygos (AZ) and hemiazygos veins. The lumbar hemiazygos arch is connected with the left renal vein representing a major outflow route for shunting blood into the inferior vena cava. The AZ vein represents the final collector and drains into the superior vena cava with an outlet on the posterior aspect just one cm below the brachiocephalic trunks (16) (Fig. 1b).

 

Ultrasonographic anatomy of the cerebrospinal venous system

The IJV can be subdivided into three extracranial venous segments: upper (J3), middle (J2), and lower (J1) (Fig. 2). The middle segment is adjacent to the thyroid gland (Fig. 3), and is the segment between the entry of the common facial vein and the beginning of the last 2 cm of the IJV (Fig. 4, over). The IJV can be insonated easily at all three levels. The VVs can be easily insonated at all levels, but more easily between the transverse processes of the 5th and 6th cervical vertebrae.

Pathophysiology of the cerebrospinal venous system and CCSVI

Blood leaves the brain as a result of back propulsion of the residual arterial pressure (vis a tergo), complemented by a respiratory mechanism (vis a fronte) (32,33). The latter is the thoracic pump which produces a negative intrathoracic pressure during inspiration increasing the aspiration of blood towards the right atrium. In addition to the vis a tergo and vis a fronte, changes in posture and gravity play a main role in ensuring correct cerebral venous return (32-38).

In the horizontal position the predominant cerebral venous outflow is through the IJVs, whereas in the upright position the VVs become the predominant pathway. This has been demonstrated by angiographic studies and cerebral blood flow measurements using nitrous oxide, labeled erythrocytes and thermodilution techniques and more recently by volume flow measurements using duplex scanning (32). In a study by Doepp et al. (37) a predominant non-jugular drainage pattern in the supine position was found in only 6% of healthy volunteers.

As defined above, CCSVI is characterized by stenoses of the IJVs and/or AZ vein which are shown by B-mode ultrasound to be mostly intraluminal defects (1-7,28,29, 31,38,39). These stenoses are associated with the development of collateral veins indicating insufficient drainage.

Perfusion of the brain parenchyma has been studied with MRI to assess cerebral blood flow, blood volume and the mean transit time from the arterial to the venous side of the cerebral circulation. In patients with MS, there is evidence that cerebral blood flow is reduced and the mean transit time increased, suggesting abnormalities at the microcirculation level (40,41). A negative linear relationship between cerebral blood flow measured with MRI perfusion techniques and the Doppler venous hemodynamic insufficiency severity score (VHISS) has been demonstrated (41) (Appendix II). The latter has been used to assess the hemodynamic severity of CCSVI (42,43). Thus, there appears to be a relationship between the severity of extracranial hemodynamic abnormalities and perfusion within the brain parenchyma (41).

CCSVI disturbs the normal postural and respiratory mechanisms of cerebral venous return resulting in an abnormal flow (1-7). Thus, in CCSVI, the main extracranial cerebrospinal veins are obstructed, with venous flow being deviated into collaterals. The main collateral pathways activated are the condylar venous system, pterygoid plexus, and thyroid veins, anterior jugular veins and external jugular veins (2).

Five main patterns of distribution of significant (>50%) venous stenoses have been found in large venographic series of patients with MS (1,31).

• Single jugular lesion (30-36%): a significant stenosis in one of the two IJVs with a compensatory enlargement of the contralateral IJV. No data is available concerning VV lesions (31).

• Double jugular lesion (14-56%): bilateral stenoses of IJVs, with normal AZ venous system.

• Double lesion (23%) involving one of the IJVs and the proximal AZ vein.

• Triple lesion (3-38%): significant stenosis of both IJVs and the proximal AZ vein.

• Multilevel involvement of the AZ and lumbar venous system (18%). Stenosis of IJVs is observed in approximately half of these patients causing additional obstruction (1).

A venographic grading system of obstructive lesions has been suggested by one group based on a series of 564 patients. Stage I consists of outflow delay without reflux towards the brain; stage II – outflow delay with mild reflux and/or prestenotic dilatation of the vein; stage III –  outflow delay with reflux and outflow through collaterals; stage IV – no outflow through the vein with huge outflow through collaterals (31).

 

Technique of duplex scanning for CCSVI

Equipment and presets

Ideally, a sophisticated duplex scanning system with a linear array broad bandwidth transducer suitable for imaging vessels, such as the carotid artery, should be used. Depending on the system and application, frequency ranges will vary (e.g. 7-5 MHz, 9-3 MHz, 10-5 MHz). When visualization of the lower IJV segment (J1) proves technically challenging, the use of a curvilinear/microconvex probe with a smaller footprint may be useful. For transcranial color Doppler (TCD) a phased array transducer should be used with a lower frequency bandwidth – for example 1.5-2 MHz or 2-3 MHz.

A large number of instrumental settings affect the B-mode, color and Doppler images on ultrasound. However, most manufacturers have chosen default values for these various settings that are pre-programmed for particular clinical applications. It is recommended that the system’s venous presets be activated initially; thereafter these starting values can be altered as required for each patient according to their individual pathology.

Venous velocities are much lower than arterial velocities, so for color Doppler imaging discrepancies are likely to occur. A number of technical considerations are listed below that should help achieve reproducibility.

 

Color flow

Pulse repetition frequency (PRF)

This is actually preset and it is related to the expected venous velocities. However, it may need to be lowered in order to detect lower flows or increased to avoid aliasing when the actual velocities appear higher than predicted. Newer systems may not have a PRF control but may be controlled by the color “scale”. Steering angles

To ensure complete color filling of the vessel under examination (if indeed flow is present) one must optimize the color Doppler angle of insonation. This can be done (and generally is done in practice) by using a combination of probe angulation (particularly in transverse plane scanning) and color box steering. The purpose is to avoid an ultrasound beam perpendicular to the vessel which, in turn, would result in no Doppler signal. Therefore one must always steer the color box in a variety of directions in relation to the longitudinal planes of the B-mode image.

In transverse plane scanning the color box must remain at 0 with only probe angulation being used to create the necessary angles.

 

Color gain

It is universally accepted that arterial flow is conventionally displayed as red color and venous flow as blue. The gain control may need to be adjusted for the single clinical setting. If it is set too low there may be incomplete color filling of the vessel of interest; if it is set too high one will see color outside the vessel and there will be “noise” throughout the image.

 

Color wall filter

Color wall filter selection is important to optimize detection of low velocity.

 

Focal zones

Ideally the focal zone must be set to the region of interest. In color mode there normally exists one focal zone (due to frame rate issues) and this may be preset as the image center. The focal zone can be adjusted manually, therefore one should be prepared to alter it when appropriate.

 

Persistence/frame averaging

Most modern systems have automated frame averaging. For example, when velocities are low, persistence will be high, making pulsatile flow in veins harder to detect. It is important to keep the color box width and depth adjusted to the region of interest as this will result in the best/highest frame rate.

 

Spectral Doppler

Pulse repetition frequency (PRF)

This will be preset as per manufacturer’s values for a venous setting, but, as with color flow, clinical situations may arise that require the operator to alter these values in order to ensure an optimum Doppler spectral display. If the Doppler PRF setting is too high the slower-moving blood will not be displayed across the spectral display. Therefore one should set the Doppler PRF so that the resultant spectral waveform fills the display without aliasing the scale.

 

Focal depth

Normally, focal depth is set automatically to follow the sample volume. If it is not, it should be adjusted manually.

 

Positioning of sample volume and angle of insonation

When examining venous flow the sample volume must be positioned in the center of the vessel under examination. However, to include the full range of velocities, including all areas of reflux in the vein, the gate needs to be open completely to cover the entire lumen.

Ideally, the angle of Doppler beam insonation to the direction of flow should be 60° to keep absolute velocity measurement errors to a minimum. However, because this may be difficult to achieve in the IJV and VVs without applying pressure on the skin when changing the angle of the probe, reducing the angle to 45° is acceptable. The angle must never exceed 60°. Irrespective of the width of the gate, cursor in the middle of the Doppler gate should be positioned in the center of the vessel and parallel to the flow axis.

 

Patient positioning and technical aspects of ultrasound examination

The CCSVI examination should be performed with the patient in both supine and sitting positions and breathing normally, starting the examination in the supine position. A tilting chair is advisable in order to avoid muscular contractions when changing position. As previously mentioned, each of these positions is associated with a different outflow route (32,34,35,44). The patient has to be comfortably positioned on an electro-mechanical chair or a standard examination table. After changing position, an adaptation period of at least 2 minutes should be allowed before any further measurements are made. More than one posture change, from supine to sitting and vice versa, should be avoided, so as not to perturb the distribution of blood volume. A sufficient level of hydration within the twelve hours before the examination must be assured.

We recommend that the subjects breathe normally and where possible through the nose. This allows activation of the thoracic pump without undesirable muscle contraction in the neck. Also, it reduces contraction of the thoracic muscles thereby reducing artifacts, especially when examining the lower segment of the IJV (J1). The pump activation allows the assessment of flow direction. The cross-sectional area (CSA) and the flow direction are measured at the end of the expiratory phase, ensuring that there has been activation of the thoracic pump.

The examiner should pay attention to the inclination of the patient’s neck and employ appropriate means of neck support to avoid neck flexion, hyperextension or rotation to the left or right. This will avoid erroneous measurements of the CSA and allow better visualization of the IJV when the patient is in the sitting position.

The operator should use appropriate arm support (especially when the patient is in the sitting position) in order to avoid arm, hand, wrist, back or shoulder strain. A pillow across the patient’s chest, where the operator can rest his/her elbow whilst scanning, will provide good support. The problem of shoulder and arm fatigue is particularly significant when the examination is performed with the patient in the sitting position.

Use a large amount of ultrasonic gel to ensure complete coupling between the transducer and the patient’s skin, thereby avoiding black cones and dark areas on the image. Also, a thick layer of ultrasonic gel avoids excessive pressure on the patient’s neck that may change the shape and dimension of the IJV. Practical maneuvers that may help control the pressure of the transducer against the skin include placing the ring or little finger on the thyroid cartilage in order to ensure better control of applied pressure.

How to perform CCSVI examination of the internal jugular vein (supine and sitting positions)

Investigation of cerebrospinal venous return must be performed with the patient really at rest. In other words, the patient, who may use the deep breathing technique, needs to be calm, not agitated, and with a normal heart rate. The evaluation begins with the patient in the supine position.

 

B-mode evaluation

With the linear array transducer in the transverse position (with respect to the IJV itself), perform a B-mode evaluation of the IJV from the base of the neck to the angle of the jaw. Although routine use of the Valsalva maneuver is not recommended for CCSVI evaluation, on occasions it can help to visualize the IJV. This is particularly true with the patient in the sitting position (in which the CSA is normally at its smallest), or in situations in which the IJV is completely collapsed as a result of the CCSVI. If a lumen can be opened by the Valsalva maneuver, this means that the lumen is normal. If a lumen cannot be opened by Valsalva this could indicate hypoplasia or agenesis of the IJV.

The Committee recommends performing the Valsalva maneuver at the end of the examination to check for agenesis, especially if no flow was noted in the upright position. Performing Valsalva at the end of the examination avoids redistribution of blood volume, which may affect the entire investigation.

After the evaluation in the transverse plane, the IJV must be completely evaluated in the longitudinal plane.

 

Valve abnormalities on B-mode

A valve is usually present at the termination of the IJV just before its junction with the subclavian vein. Valves in the lower portion of the IJVs (J1) have been found in 93% of post-mortem studies and in 87% of normal individuals (45). Valves were not present in other segments. When a valve is detected it should be evaluated in both the transverse and the longitudinal planes. The cusps of a normal valve should be oriented in the direction of the blood flow and they should move freely with respect to the respiration phases. When the leaflets are open they should be parallel and close to the jugular wall.

The major anomalies that can be found at the level of the IJV valve are: flap, septum, annulus, immobile leaflets, immobility limited to one of the two leaflets, double channels, anomalous orientation of the valve leaflets (e.g. inverted position of the leaflets, leaflets positioned on the lateral side of the jugular wall) (1-7,30,31,39). Similarly to cardiac valve evaluation by echo-cardiography and/or in the deep venous system of the lower extremity (46,47), mobility of the valve cusps can be further documented by using the M-mode function, as shown in figure 5.

Artifacts on B-mode

Two major artifacts can be found during the B-mode examination of the IJV. They are believed to be produced by lymph and by the vagus nerve. The thoracic duct, especially after food intake, creates streams of lymph which are seen as hyperechoic filaments within the vessel lumen (Fig. 6). These filaments should not be mistaken for venous valve cusps because they do not show the periodically repeated movements typical of a valve cusp.

The vagus nerve is located posterior to the IJV, but on B-mode imaging it may produce an artifact in the middle of the IJV. The vagus nerve may appear as parallel linear echoes within the IJV, which can be misinterpreted as an intraluminal defect (Fig. 7a). This artifact may be avoided by angling the probe away from the vagus nerve. Alternatively, this artifact can be provoked by positioning the probe in the longitudinal position, in which the nerve becomes visible on ultrasound because of longitudinal hyperechoic thickening of the neural guaina and fibers. In figure 7a and b the echoes emitted by the transducer reflect a false image of the vagus nerve appearing inside the IJV.

Another artifact, called the mirror artifact, is due to high acoustic reflection of the front wall of the vein. When the sound beam hits a strong interface (such as the anterior wall of the IJV) at an angle other than 90°, it is re-routed. This change in the sound beam course means that it takes longer to return to the machine, which results in the object appearing deeper than it truly is. In the figure, some of the echoes emitted by the transducer reflect a false image of the anterior wall of the vein, which appears as an intraluminal structure (Fig. 7b).

 

Hemodynamic evaluation

Hemodynamic evaluation starts from the lower end of the middle segment of the IJV (J2) which is imaged in transverse view in the color mode. It is suggested that one should follow the IJV upwards to J3, observing the flow direction by means of color mode, asking the patient to breathe quietly through the nose. Any irregularities that may appear (absence of flow, turbulences, reflux) in the color mode (Fig. 8), will require verification by longitudinal imaging (Fig. 9, over) in order to study the flow direction and duration of reflux/bidirectional flow by means of Doppler spectral analysis recordings (Fig. 10 a-c, over) and/or spectral analysis using multi-angle Doppler (Fig. 11, over).

In the longitudinal plane, careful attention should be paid to the steering of the color flow box, to guarantee the angle of insonation in relation to the vessel (Fig.s 9 and 10, over). Although 0.88 sec has been suggested as the cut-off value for reflux through the jugular valve (48), this value was originally recorded under Valsalva at J1. By contrast, reflux associated with CCSVI is elicited by activation of the thoracic pump and may last for several seconds (1,49). Reflux or absence of flow may occur and can be detected in any segment of the IJV. Flow recording of both abnormalities is particularly significant at the end of the expiratory phase; flow evaluation does not require the Valsalva maneuver at all. Recording of flow abnormalities should be made with the Doppler sample gate open wide (Fig. 10). Our suggestion is to insonate the lower part of the IJV (J1) last, after careful evaluation of the J2 and J3 segments.

At J1 level, turbulence and short time reflux (<0.88 sec) should be considered normal because they are the physiological expression of flow close to valve cusps. This reflux is usually confined around the leaflets, and can be increased by respiration. If this reflux can also be seen in the IJV above the origin of the widening (bulb), this has to be considered a pathological reflux (Fig. 9). The optimum cut-off point for the duration of reflux is under review and needs to be established. The value of >0.88 sec for IJV reflux/bidirectional flow has been defined and used in prior studies for Criterion 1. In order to determine the optimum cut-off point for the duration of reflux associated with CCSVI, it is recommended that, in prospective observational studies in which patients undergo venography, recordings be made as shown in figure 10, together with measurements of duration of reflux.

The normal Doppler blood velocity in the IJV (lying or sitting) has been quoted as less than 70 cm/sec (8). Since a very high velocity in one IJV (Fig. 12) can point to a stenotic lesion, in such cases it is necessary to conduct a careful assessment for such a lesion, if this was not identified on the initial B-mode evaluation. Although this is not a criterion for CCSVI, it can be a helpful tool. Further research is required, and more data, in order to determine optimum velocity cut-off points. For this reason, it is recommended that in prospective observational studies including normal individuals and patients with MS, velocities be measured in all segments of the IJV (see reporting form in Appendix III).

In a large number of cases, no flow can be detected within the IJV, which may suggest the presence of severe obstruction. There are two main possibilities: i) flow is not detected because the IJV is almost completely collapsed and cannot be distended by a Valsalva maneuver (this is compatible with a hypoplastic IJV); ii) flow is not detected (the velocity is too low to be detected even at very low PRF) but the lumen of the IJV is clearly visible. This is compatible with absent flow in a filled IJV.

However, absence of flow in color Doppler mode should always be confirmed by Doppler spectral analysis and absence of thrombosis by compression (Fig. 13). Sometimes, especially when the Doppler sample is placed above the septum/immobile cusps, the spectrum may show very low velocities related to little intraluminal movements and velocity cannot be increased by thoracic pump activation.

An IJV blood flow “block” (despite deep inspirations) must be considered a CCSVI criterion if no flow can be detected within an IJV either in the supine or in the sitting position. Alternatively, reflux within a jugular is considered a positive criterion if coupled with absence of flow in the other position, or vice versa.

Stenosis in the lower IJV may activate collateral circulation. Collateral circulation may be observed at the levels of the IJV’s junctions with the anterior branch of the retromandibular vein, the common facial vein and the lingual vein, or commonly, at the level of the superior thyroid vein (Fig. 14).

Absence of flow in the upper IJV may also activate collateral circulation; one of the more common examples is that of the shunting flow from the IJV to the superior thyroid vein. The shunt runs through the thyroid gland and re-enters the superior vena cava system through the inferior thyroid vein (Fig. 14).

 

Measurements of the cross-sectional area (csa)

Measurements of the CSA must be performed in transverse B-mode scans of the middle segment (J2) using the appropriate ellipsoid area measuring tool (Fig. 15). Measurement can be performed with or without activation of the color mode. If the color mode is used, the color gain should be adjusted so that the color does not obscure the vessel wall.

The measurement must be performed at the same point in both supine and sitting positions, initially in the supine position then in the sitting position. The middle section (J2) of the IJV can be identified through the relationship with the thyroid gland or by marking the measurement point on the skin. The transducer must be kept almost perpendicular to the patient’s neck in order to produce a “perfect” transverse section of the IJV (a certain inclination with respect to the 90° angle is still needed in order to get a sufficient color Doppler signal). The perfect circular shape of the common carotid artery can be used as a reference for the correct positioning.

How to perform CCSVI examination of vertebral veins (VVs)

The VVs must be evaluated with the transducer positioned longitudinally. When the patient is in the supine position, the blood flow within the VVs is slower and a lower color Doppler PRF and lower wall filter is needed (with respect to the color Doppler examination of the IJV). Visualization of the VVs is not easy in B-mode and therefore a color Doppler examination should be used from the beginning. The VVs must be examined in visible segments (the easiest segment to examine is between C5 and C6) (Fig. 16, over).

Reflux within VVs is usually activated during the expiratory phase of the respiratory cycle. Reflux within VVs is represented by a complete reversal of blood flow direction lasting more than one second. A Doppler spectral waveform should be recorded. A continuous reversed flow may sometimes be seen (opposite to the direction of physiological flow). This reversed flow, which is also considered abnormal (reflux), may be the result of activation of collaterals connecting extravertebral with intravertebral veins.

Reflux within VVs must be considered a positive CCSVI criterion if it is present in the same VV both in the supine and in the sitting position. Alternatively, a positive criterion can be assigned if reflux in one position is associated with absence of flow in the other position.

A VV blood flow “block” (despite deep inspirations and low PRF) (Fig. 17) must also be considered a positive CCSVI criterion if no flow can be detected in a VV both in the supine and in the sitting position. VV reflux and/or “block” must be assessed in the same segment at the end of the respiratory phase.

 

CCSVI examination of the intracranial veins

The presence of reflux in the petrosal sinuses detected through the supracondylar window has been proposed as a diagnostic criterion for CCSVI. Because insonation of the petrosal sinuses can be achieved with the Doppler angle close to 90°, detection of reflux in the form of bidirectional flow can be achieved only using a multi-angle Doppler system, such as quality Doppler processing technology (QDP, Esaote Biomedica, Genoa, Italy). QDP enables the operator to identify the blood flow direction in the examined cerebral veins: a proper adjustment of the PRF is necessary in order to visualize the direction clearly, without background Doppler noise (Fig.18 a,b).

Because QDP technology is not available on all ultrasound scanning systems, and because more data are needed to define the contribution of intracerebral reflux to the diagnosis of CCSVI, it is not currently recommended as part of the routine procedure. For details see Appendix IV.

 

 

References

1.         Zamboni P, Galeotti R, Menegatti E et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392-399

2.         Zamboni P, Consorti G, Galeotti R et al. Venous collateral circulation of the extracranial cerebrospinal outflow routes. Curr Neurovasc Res 2009;6:204-212

3.         Zivadinov R, Galeotti R, Hojnacki D et al. Value of MR venography for detection of internal jugular vein anomalies in multiple sclerosis: a pilot longitudinal study. AJNR Am J Neuroradiol 2011;32:938-946

4.         Zivadinov R, Marr K, Cutter G et al.Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 2011;77:138-144

5.         Al-Omari MH, Rousan LA. Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. Int Angiol 2010;29:115-120

6.         Simka M, Kostecki J, Zaniewski M, Majewski E, Hartel M. Extracranial Doppler sonographic criteria of chronic cerebrospinal venous insuffitiency in the patients with multiple sclerosis. Int Angiol 2010;29:109-114

7.         Bastianello S, Bergamaschi F, Viselner G et al. An international multicenter observatory on prevalence of CCSVI in MS. BMC Neurology 2011 (In press)

8.         Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010;68:173-183

9.         Mayer CA, Pfeilschifter W, Lorenz MW et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 2011;82:436-440

10.       Yamout B, Herlopian A, Issa Z et al. Extracranial venous stenosis is an unlikely cause of multiple sclerosis. Mult Scler 2010;16:1341-1348

11.       Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset. Ann Neurol 2011;69:90-99

12.       Wattjes MP, van Oosten BW, de Graaf WL et al. No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study. J Neurol Neurosurg Psychiatry 2011:82:429-435

13.       Lee BB, Laredo J, Neville R. Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebrospinal venous insufficiency. Int Angiol 2010;29:95-108

14.       Lee BB, Bergan J, Gloviczki P et al; International Union of Phlebology (IUP). Diagnosis and treatment of venous malformations - Consensus document of the International Union of Phlebology (IUP)-2009. Int Angiol 2009;28: 434-451

15.       Lee BB, Laredo J, Lee TS, Huh S, Neville R. Terminology and classification of congenital vascular malformations. Phlebology 2007;22:249-252

16.       Uflacker R. Atlas of Vascular Anatomy. An Angiographic Approach. Philadephia; Lippincot, Williams and Wilkins 1997

17.       Hamoud S, Nitecky S, Engel A, Goldsher D, Hayek T. Hypoplasia of the inferior vena cava with azygous continuation presenting as recurrent leg deep vein thrombosis. Am J Med Sci 2000;319:414-416

18.       Gates J, Hartnell GG. Demonstration of inferior vena cava patency by retrograde azygous venography. Cardiovasc Intervent Radiol 1995;18:419-421

19.       Lane EJ, Heitzman ER, Dinn WM. The radiology of the superior intercostal veins. Radiology 1976;120:263-267

20.       Chasen MH, Charnsangavej C. Venous chest anatomy: clinical implications. Eur J Radiol 1998;27:2-14

21.       Mammen T, Keshava SN, Eapen CE et al. Transjugular liver biopsy: a retrospective analysis of 601 cases. J Vasc Interv Radiol 2008;19:351-358

22.       Dilenge D, Perey B, Geraud G, Nutik S. Angiographic demonstration of the cervical vertebral venous plexus in man. J Can Assoc Radiol 1975;26:77-81

23.       Zelli GP, Messinetti S, Condorelli S. Original technique of internal jugular phlebography by puncture of the external jugular vein with retrograde emission of the contrast media. Prog Med 1964;15:681-688 [Italian]

24.       Gejrot T, Lauren T. Retrograde venography of the internal jugular veins and transverse sinuses; technique and roentgen anatomy. Acta Otolaryngol 1964;57:556-570

25.       Gejrot T. Retrograde jugularography in the diagnosis of abnormalities of the superior bulb of the internal jugular vein. Acta Otolaryngol 1964;57:177-180

26.       Leriche H, Aubin ML, Aboulker J. Cavo-spinal phlebography in myelopathies. Stenoses of internal jugular and azygos veins, venous compressions and thromboses Acta Radiol Suppl 1976;347:415-417 [French]

27.       Tzuladze II. The selective phlebography of the large tributaries of the vena cava system in the diagnosis of venous circulatory disorders in the spinal complex. Zh Vopr Neirokhir Im N N Burdenko 1999;2:8-13 [Russian]

28.       Zamboni P, Galeotti R, Menegatti E et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009;50:1348-1358

29.       Zamboni P, Galeotti R, Weinstock-Guttman B, Kennedy C, Zivadinov R. Venous angioplasty in patients with multiple sclerosis: results of a pilot study. Eur J Vasc Endovasc Surg 2012;43:116-122

30.       Malagoni AM, Galeotti R, Menegatti E et al. Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study. Int Angiol 2010;29:176-182

31.       Ludyga T, Kazibudzki M, Simka M et al. Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe? Phlebology 2010;25:286-295

32.       Schaller B. Physiology of cerebral venous blood flow: from experimental data in animals to normal function in humans. Brain Res Brain Res Rev 2004;46:243-260

33.       Singh AV, Zamboni P. Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab 2009;29:1867-1878

34.       Menegatti E, Zamboni P. Doppler haemodynamics of cerebral venous return. Curr Neurovasc Res 2008;5:260-265

35.       Valdueza, JM, von Münster T, Hoffman O, Schreiber S, Einhaüpl KM. Postural dependency of the cerebral venous outflow. Lancet 2000;355:200-201

36.       Schreiber SJ, Lurtzing F, Gotze R, Doepp F, Klingebiel R, Valdueza JM. Extrajugular pathways of human cerebral venous blood drainage assessed by duplex ultrasound. J Appl Physiol 2003;94:1802-1805

37.       Doepp F, Schreiber SJ, von Münster T, Rademacher J, Klingebiel R, Valdueza JM. How does the blood leave the brain? A systematic ultrasound analysis of cerebral venous drainage patterns. Neuroradiology 2004;46:565-570

38.       Zamboni P, Menegatti E, Galeotti R et al. The value of cerebral Doppler venous haemodynamics in the assessment of multiple sclerosis. J Neurol Sci 2009;282:21-27

39.       Zamboni P. Regarding "no cerebrocervical venous congestion in patients with multiple sclerosis. Intraluminal jugular septation". Ann Neurol 2010;68:969

40.       Law M, Saindane AM, Ge Y et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology 2004;231:645-652

41.       Zamboni P, Menegatti E, Weinstock-Guttman B et al. Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report. BMC Med 2011;7:9-22

42.       Zamboni P, Menegatti E, Weinstock-Guttman B et al. The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol 2009;24:133-138

43.       Zamboni P, Menegatti E, Weinstock-Guttman B et al. CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study. Int Angiol 2010;29:140-148

44.       Gisolf J, van Lieshout JJ, van Heusden K, Pott F, Stok WJ, Karemaker JM. Human cerebral venous outflow pathway depends on posture and central venous pressure. J Physiol 2004;560:317-327

45.       Lepori D, Capasso P, Fournier D, Genton CY, Schnyder P. High-resolution ultrasound evaluation of internal jugular venous valves. Eur Radiol 1999;9:1222-1226

46.       Kotani A, Hirano Y, Yasuda C, Ishikawa K. A new ultrasonographic technique for diagnosing deep venous insufficiency – imaging and functional evaluation of venous valves by ultrasonography with improved resolution. Int J Cardiovasc Imaging 2007;23:493-500

47.       Feigenbaum H. Role of M-mode technique in today’s echocardiography. J Am Soc Echocardiogr 2010;23:240-257;335-337

48.       Nedelmann M, Eicke BM, Dieterich M. Functional and morphological criteria of internal jugular valve insufficiency as assessed by ultrasound. J Neuroimaging 2005;15:70-75

49.       Zamboni P, Galeotti R. The chronic cerebrospinal venous insufficiency syndrome. Phlebology 2010;25:269-279

50.       Baumgartner RW, Nirkko AC, Müri RM, Gönner F. Transoccipital power-based color-coded Duplex sonography of cerebral sinuses and veins. Stroke 1997;28: 1319-1323

51.       Stolz E, Kaps M, Kern A, Babacan SS, Dorndorf W. Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference Data From 130 volunteers. Stroke 1999;30:1070-1075

52.       Walter U. Transcranial sonography-assisted stereotaxy and follow-up of deep brain implants in patients with movement disorders. Int Rev Neurobiol 2010;90:274-285

53.       Zamboni P, Menegatti E, Viselner G, Bastianello S. Fusion imaging technology of the intracranial veins. Phlebology 2011 (In press)