- Email: [email protected]
Catheter Venography and Endovascular Treatment of Chronic Cerebrospinal Venous Insufficiency
Catheter Venography and Endovascular Treatment of Chronic Cerebrospinal Venous Insufficiency Kenneth Mandato, MD, Meridith Englander, MD, Lawrence Keating, MD, Jason Vachon, MD, and Gary P. Siskin, MD, FSIR Multiple sclerosis (MS) is a disorder characterized by damage to the myelin sheath insulation of nerve cells of the brain and spinal cord affecting nerve impulses which can lead to numerous physical and cognitive disabilities. The disease, which affects over 500,000 people in the United States alone, is widely believed to be an autoimmune condition potentially triggered by an antecedant event such as a viral infection, environmental factors, a genetic defect or a combination of each. Chronic cerebrospinal venous insufficiency (CCSVI) is a condition characterized by abnormal venous drainage from the central nervous system that has been theorized to have a possible role in the pathogenesis and symptomatology of MS (1). A significant amount of attention has been given to this theory as a possible explanation for the etiology of symptoms related to MS patients suffering from this disease. The work of Dr. Zamboni, et al, who reported that treating the venous stenoses causing CCSVI with angioplasty resulting in significant improvement in the symptoms and quality of life of patients with MS (2) has led to further interest in this theory and potential treatment. The article presented describes endovascular techniques employed to diagnose and treat patients with MS and CCSVI. Tech Vasc Interventional Rad 15:121-130 © 2012 Elsevier Inc. All rights reserved. KEYWORDS multiple sclerosis, chronic cerebrospinal venous insufficiency, catheter venography, internal jugular vein, azygos vein, omohyoid muscle, extrinsic compression, angioplasty, Zamboni
C
hronic cerebrospinal venous insufficiency (CCSVI) is a theory described by Zamboni et al1 to elucidate the pathology and clinical manifestations of multiple sclerosis (MS). In this theory, venous stenoses hindering outflow from the central nervous system are potentially contributing to symptoms related to inflammatory plaque within the brain and spinal cord in patients with MS. Zamboni et al2 then used this theory as the basis for treating MS patients in whom stenoses were found in the internal jugular veins (IJVs) and/or the azygos vein with angioplasty, and achieved high rates of clinical improvement with no significant postoperative complications. This, of course, has led to a great deal of interest in this theory and this procedure as a potential treatment option for patients with MS. This article is a description of the endovascular techniques used to diagnose and treat patients with MS and CCSVI in our practice.
Department of Radiology, Albany Medical Center, Albany, NY. Address reprint requests to Kenneth Mandato, MD, Department of Radiology, MC-113, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208. E-mail: [email protected] 1089-2516/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1053/j.tvir.2012.02.005
Preprocedure Evaluation Before venography, a complete review of the patient’s medical history should be performed to evaluate for significant cardiac and renal disease in addition to a previous history of venous disease, including deep venous thrombosis and venous insufficiency. A history of previously placed central venous catheter placement is important to uncover because that may lead to central vein occlusions that may interfere with selective catheterization and angioplasty of the internal jugular and azygos veins. The use of preprocedure noninvasive imaging is typically performed before venography. Both Doppler ultrasound and magnetic resonance venography are potentially helpful in imaging the veins that are to be studied with catheter venography and may, therefore, provide information that may assist with the performance of this procedure.3-5 Although the diagnostic utility of both of these imaging examinations has been called into question,6,7 knowing that one of the veins to be selectively catheterized is occluded or severely stenotic can help prepare an interventionalist for challenges that may 121
122
K. Mandato et al
be encountered during the procedure. In addition, understanding the degree of disease severity before treatment can allow for appropriate comparative follow-up in the future.
Diagnostic Venography for CCSVI Whether performed in a hospital or ambulatory surgery center, continuous cardiac monitoring and oxygen sensitometry are used. Transient arrhythmias can occur during guidewire and catheter placement through the right atrium while moving from the inferior vena cava to the superior vena cava.8 Continuous cardiac monitoring will give the primary operator instant data to reposition guidewires and catheters when necessary. The procedure is often performed with mild-tomoderate procedural sedation, which can be accomplished with oral diazepam (Valium, Roche Pharmaceuticals, Nutley, NJ) or a combination of intravenous midazolam (Versed, APP Pharmaceuticals, LLC, Schaumburg, IL) and fentanyl citrate (Sublimaze, Taylor Pharmaceuticals, Buffalo Grove, IL). Venography for CCSVI is typically performed from right or left common femoral vein access. The right common femoral vein provides a straighter route to the internal jugular and azygos veins, whereas left common femoral vein access makes it easier to assess the common iliac and left ascending lumbar veins for abnormalities. After access into the common femoral vein using standard Seldinger technique with ultrasound guidance, an 8-French introducer sheath (Terumo Medical Corp, Elkton, MD) is used to maintain that access. An 8-French sheath is used to decrease friction-related difficulties in removing large angioplasty balloons that have been recently deflated. Selective catheterization of the IJV may be more difficult than some might anticipate, based on their familiarity with these veins through work in the area of venous access. However, there are significant differences between antegrade catheterization of these veins for venous access as opposed to retrograde catheterization of these veins for diagnostic venography to evaluate CCSVI. A number of angiographic catheters can be used for this purpose. We typically use a 5-French glide Headhunter catheter (Terumo Medical Corp, Elkton, MD) for these catheterizations; it is particularly well suited for catheterization of the azygos vein. A 5-French Glide Berenstein catheter (Terumo Medical Corp) can significantly help catheterize the IJVs when the origins are oblique and/or complex in appearance. This may often be the case with the origin of the left IJV. The vertebral vein, and its termination into the posterior portion of the brachiocephalic vein, may make selective catheterization of the IJV difficult. The absence of valves in the vertebral vein9 may favor catheterization of the caudal portion of the vertebral vein during attempts at catheterizing the IJV. Therefore, it is important for an interventionalist to distinguish between these 2 vessels. The easiest way to know if the caudal portion of the vertebral vein has been catheterized is if the catheter and guidewire course medially toward the spine (Fig. 1). The IJV should maintain a relatively consistent distance from the spine in the lateral soft tissue of the neck. In
Figure 1 Images of a venogram of the left vertebral vein before (A) and after (B) the administration of contrast. This demonstrates the medial course of the catheter position when located within the vertebral vein.
addition, guidewire resistance will often be encountered in the lower neck while the vertebral vein is accessed. This is a reflection of the complex branching pattern of the vertebral vein and may cause instant patient feedback in the form of pain. Patients will not typically experience discomfort when the IJV has been catheterized. Once the catheter has gained access into the IJV, the suggested catheter position for the initial venogram is just inferior to C1. Selective venography of the IJV is then performed in the anteroposterior (AP) and lateral projections. When the upper portion of the IJV is studied, it can be challenging to
Chronic cerebrospinal venous insufficiency determine if a significant stenosis is present or if normal anatomic and physiologic features of the IJV and surrounding veins in this area are being visualized. Under normal circumstances, the IJV is the continuation of the transverse and sigmoid sinuses. Therefore, visualization of these sinuses on reflux venography can provide confirmation that the catheter is indeed located within the IJV (Fig. 2). The vertebral veins often originate from the sigmoid sinus and descend as a plexus of veins surrounding the vertebral artery. These veins may overlap with the upper IJV on AP imaging (Fig. 3). Just below the jugular foramen, the IJV may abut the anterior surface of the transverse process of C1, which can lead to extrinsic compression of the vein at this location.10 Venography in the lateral projection is often the best way to evaluate the caliber of the IJV relative to the lateral mass of C1 and can also help separate the visualized portion of the vertebral venous plexus from the upper portion of the IJV. The exact position of the catheter and the force and volume of contrast injections for venography have a significant role in determining how the images obtained in this portion of the IJV are interpreted. If the catheter is positioned above C1, unknowingly placed through an area of anatomic narrowing secondary to extrinsic compression at the level of C1, then this normal “narrowing” may in fact be accentuated. In addition, if the end hole of the catheter is positioned near the origin of the vertebral venous plexus, then contrast may preferentially enter the vertebral veins instead of the IJVs. This may provide the interventionalist with the sense that the vertebral veins are serving as collateral outflow pathways because of a stenotic IJV. In fact, placing the catheter below C1 and limiting the injection rate and volume to match physiologic flow (using an injection rate that limits reflux in the vein) will allow for the most accurate assessment of the upper
Figure 2 Image from a venogram of the internal jugular vein (IJV) in the lateral projection demonstrating continuity of the IJV with the sigmoid sinus as well as the origin of the vertebral venous plexus.
123
Figure 3 Image from a venogram of the left IJV in the anteroposterior projection demonstrating overlap of the IJV and the vertebral venous plexus.
IJV diameter, the direction and rate of outflow from the sigmoid sinus into the IJV, and the possible role of the vertebral venous plexus as a collateral pathway for cerebral venous blood flow (Fig. 4). Similar anatomic features may confound the venographic evaluation of the midportion of the IJV. In this portion of the
Figure 4 Images from a venogram of the internal jugular in the lateral projection demonstrating the effect of catheter position and injection rate on the visualization of the vertebral venous plexus. (A) The catheter is positioned at the origin of the vertebral vein. (B) The catheter is positioned in a more caudal position, and a lower injection rate was used.
K. Mandato et al
124
Figure 5 Images from a venogram of the left IJV without (A) and with (B) contralateral head rotation demonstrating the change in vein diameter with the change in head position.
neck, the IJV runs close to the common carotid artery as well as the omohyoid muscle. Both of these structures can potentially compress the IJV11,12 and mimic pathology intrinsic to the IJV. Therefore, the finding of a stenosis in this region of the vein must be challenged with multiple views combined with head rotation to determine if this is a fixed stenosis or one because of extrinsic compression that is relieved with the head in different position(s) (Fig. 5). In general, contralateral head rotation will help relieve “stenoses” caused by extrinsic compression13 but will not change the appearance of a fixed abnormality within the vein. If head rotation restores a normal and uniform diameter to the vein, and rapid clearance of contrast is visualized, then the initial finding will be deemed to have occurred secondary to compression. There are many tributaries draining into the midportion of the IJV. If the end hole of the catheter is positioned near the origin of these veins, then contrast may be injected preferentially into one of these veins, thereby creating the false impression that collateral vessels are responsible for venous outflow. This is particularly true with the common facial vein (which ultimately leads into the external jugular vein) and the anterior jugular vein, both of which may enter the IJV near the angle of the mandible. Therefore, a catheter position above these veins together with a physiologic injection of contrast is important to assess both the direction of flow in these veins and in the IJV to determine if collateral flow is present in the face of an IJV stenosis that remains present with contralateral head rotation or if the findings represent normal anatomy. An evaluation of the IJVs concludes with studying the caudal aspect of the vein, at its confluence with the subclavian vein to form the brachiocephalic vein. The caudal aspect of the IJV is best visualized in the AP and 30-degree ipsilateral oblique projections, with the catheter repositioned below the angle of the mandible (making sure that it is not directed
toward one of the tributary veins of the IJV described earlier). In general, this tends to be the portion of the vein where stenoses and flow abnormalities are most commonly seen in patients with CCSVI. This is where valves are located in most patients14; these valves typically close during diastole to prevent increased venous pressure in the IJV.15 Flow through the valve annulus is best seen in the ipsilateral anterior oblique projection (Fig. 6). After venography of both IJVs, the azygos vein should be evaluated for CCSVI.3 The azygous system of veins originates in the pelvis from the common iliac veins via the ascending lumbar vein and plexus of iliolumbar veins. The azygous vein typically begins on the right side at L3 and ascends through the aortic hiatus receiving the hemiazygos vein as well as posterior intercostal and paravertebral veins in the chest. At the level of T4, the azygous arch runs anteriorly to empty into the posterior aspect of the superior vena cava just below the junction of the brachiocephalic veins. A bicuspid valve is found in approximately two-thirds of patients within the azygous arch16,17; if malformed or hypertrophic, this valve may contribute to the findings of CCSVI. A catheter with a Headhunter configuration is well suited to selective catheterization of the azygos vein. The vein can often be engaged by directing the end hole of the catheter posteriorly. Once the vein is engaged, moving the image intensifier into a left anterior oblique projection (LAO) can confirm the passage of the guidewire passage posteriorly and then inferiorly into the azygos vein. If the guidewire is seen running anteriorly in this projection, then it likely means that the catheter had been directed anteriorly within the superior vena cava and that the internal mammary vein was inadvertently catheterized (Fig. 7). If locating the origin of the azygos vein is difficult, additional attempts at selective catheterization using lateral fluoroscopy can be helpful. With the patient’s arms in the upright position, the azygos vein can be
Chronic cerebrospinal venous insufficiency
125 Typically, the LAO and lateral views can be used for a complete evaluation of the azygos vein (Fig. 8). The evaluation initially proposed by Zamboni et al consisted of an evaluation of the internal jugular and azygos veins as described previously. However, Zamboni has lately been proposing that additional veins should be studied as part of a venographic evaluation for CCSVI. These other veins include the left renal vein (to evaluate for nutcracker syndrome), the left common iliac vein (to evaluate for May–Thurner syndrome), and the ascending lumbar veins. The rationale for studying these other veins is that they complete the cerebrospinal circuit and that abnormalities of these veins may contribute to the neurologic manifestations of CCSVI.18 It is our position that additional research and reports of clinical success are required before universally treating these veins under the justification provided by the earlier work of Zamboni et al.2
Endovascular Treatment of CCSVI
Figure 6 Image from a venogram of the left IJV in the left anterior oblique position demonstrating a significant stenosis at the valve annulus.
reliably accessed just above the right main-stem bronchus. With the catheter positioned in the distal azygos vein, contrast can often be refluxed into the azygos and hemiazygos veins, which can be best seen in the LAO projection. The catheter should then be pulled back into the ascending azygos vein, where two views of the azygos arch can be obtained.
The detection of either a significant stenosis or significant flow abnormality within the veins studied using the technique described previously will lead to a diagnosis of CCSVI and possible endovascular treatment. The challenge at this moment, given the early stage of evolution of CCSVI, is in defining the abnormalities being detected with venography and the criteria being used to make subsequent treatment decisions. One potential issue is that the IJV can vary significantly in both size and symmetry with various factors, including hydration status, cardiac output, and head position, accounting for some of the described variability.11 Lim et al19 described an IJV diameter range from 9.1 to 10.2 mm but that smaller diameters approaching 5 mm have been identified in up to 13% of patients studied.
Figure 7 Images from the same patient demonstrating the internal mammary vein (A), which arises anteriorly from the superior vena cava, and the azygos vein (B), which arises posteriorly from the superior vena cava.
126
Figure 8 Images from a venogram of the azygos vein in the left anterior oblique (A) and lateral (B) projections.
The algorithm that we use for treatment of the internal jugular and azygos veins is presented in Figure 9. The first finding to consider when evaluating a patient for CCSVI is the degree of narrowing within the vein as seen on selective venography. In other words, what should be considered a significant stenosis? In arteries, significant changes in flow and pressure occur when the vessel has been reduced to 50% of its diameter (which corresponds to a 75% reduction in cross-sectional area). When using this same threshold as an
K. Mandato et al indication for angioplasty, Zamboni et al reported significant symptomatic improvement after angioplasty.2 Therefore, a 50% stenosis can be considered a significant finding on venography and one that can serve as an indication for treatment with angioplasty. We typically measure the largest diameter of the IJV below the mandible and compare that diameter with the measurement obtained at the level of stenosis to determine the percentage luminal diameter reduction. Importantly, the algorithm presented in Figure 9 takes into account that a measured reduction in luminal diameter is only one factor that should be considered when deciding on whether or not a studied vein should be treated with angioplasty. As recognized by the ultrasound protocol proposed by Zamboni et al to evaluate patients for CCSVI, flow abnormalities recognized within the IJV are also indicative of this condition.3 Therefore, any algorithm must include an assessment of flow on venography and then use the results of that assessment to determine a patient’s candidacy for angioplasty. Reflux and stasis of flow in the IJV are both secondary signs of abnormal flow that may be seen in conjunction with a significant luminal diameter reduction. The presence of collateral vessels may be evident as well, although care must be taken to avoid the opacification of these vessels due to catheter position and technique. However, these findings may also be seen without a significant stenosis. In that scenario, the findings may be attributed to an intraluminal abnormality poorly visualized with venography or may be “normal” for that particular patient. Intravascular ultrasound may be helpful in this scenario to confirm the presence of an intraluminal web, membrane, and so on, but the use of dilute contrast may also help recognize these abnormalities. Obtaining measurements to assess the pressure gradient across the area in question may be helpful as well.2 In our practice, patients with significant flow abnormalities in conjunction with a stenosis of ⬍50% remain candidates for angioplasty, especially if previous noninvasive imaging has indicated an abnormality within the studied vein. This is particularly true if this is seen on the dominant side (the side with the larger IJV). In our experience, significant stenoses and/or flow abnormalities within the caudal aspect of the IJVs, at the location of the valves, are the most common abnormalities detected during venography in these patients. Stenoses in this portion of the IJV often respond well to high-pressure angioplasty (Fig. 10). Even though the balloons capable of generating higher pressures tend to be more rigid, they are trackable over standard guidewires because of the relatively nontortuous course from the common femoral vein to both of the IJVs. The actual balloon size selected depends on the measured diameter of the vein. This has been a source of relative controversy amongst physicians performing this procedure. It has been our practice to oversize our balloons by 10%-20% relative to the size of the more normal-appearing portions of the vein. It is not recommended that the measurement of the contralateral vein be used as a reference diameter because of the known asymmetry of the IJVs. The most common balloon sizes used to treat abnormalities in the caudal IJV range from 10 to 16 mm in diameter. Moderate-to-low–
Chronic cerebrospinal venous insufficiency
127
Figure 9 Algorithm for diagnosis and treatment of chronic cerebrospinal venous insufficiency within the internal jugular (A) and azygos (B) veins.
pressure angioplasty is used to treat stenoses in the upper and midportions of the IJV when deemed significant and not attributed to anatomic compression by surrounding structures (Fig. 11). The most common balloon sizes used to treat abnormalities higher in the IJV range from 6 to 10 mm in diameter. When evaluating the azygos vein, consideration should be given to evaluating both luminal diameter as well as the ra-
pidity of outflow from the vein and the presence of intercostal veins, suggesting reversal of normal antegrade flow and collateralization. Irregularity of the contour of the vein may be used as a secondary sign of an abnormality as well. The most common area of abnormality within the azygos vein extends from the azygos arch into the proximal portion of the ascending azygos vein (Fig. 12). To treat the azygos vein, 8-10 mm balloons are typically used. Importantly, less rigid and more
K. Mandato et al
128
Figure 10 Images from a venogram of the right IJV before (A) and after (B) dilatation of a moderate-severe stenosis at the valve annulus.
trackable balloons are required to access the IJV because of the 180-degree turn that this vein makes from its confluence with the superior vena cava into its ascending portion. In addition, the length of the balloon should not exceed 2 cm in the azygos arch; balloons with a 4-cm length may create additional tension by straightening the arch and deforming the vein. The usual end point and goal of azygous angioplasty is improvement in luminal diameter as well as in outflow of
contrast from the vein and reduced visualization of intercostal collateral vessels. Venous angioplasty may be associated with immediate recoil or a flow-limiting dissection of the treated vein with the added risk of thrombotic occlusion.8 If venography indicates that this has occurred, immediate intravenous anticoagulation is recommended. Repeat angioplasty with a prolonged inflation is then performed to determine if this impacts the
Figure 11 Images from a venogram of the left IJV before (A) and after (B) dilatation of a stenosis in the midportion of this vein.
Figure 12 Image from a venogram of the azygos vein demonstrating a stenosis at the junction of the ascending portion of the azygos vein with the azygos arch.
Chronic cerebrospinal venous insufficiency
129
Postprocedure Management
Figure 13 Image from a venogram of the right IJV after angioplasty (A) and after stent placement (B). Stent placement was performed because of the refractory nature of the stenosis and persistent visualization of collateral vessels after angioplasty.
appearance of the vein and improves antegrade flow. Downsizing the balloon and repeating the angioplasty may also be an effective treatment. If repeat angioplasty fails to accomplish this goal, consideration can be given to stent placement (Fig. 13). At this time, it is our opinion that stent placement should be limited to this scenario. More widespread use of stents or surgery to treat IJV stenoses secondary to extrinsic compression may make intuitive sense but is not supported by the outcomes data available at this time. If stent placement is required, self-expanding stents are used. Sizing of the stent with oversizing is important because of the known risk of stent migration in association with CCSVI.20
After sheath removal and manual pressure to the groin, patients remain in the supine position for 2 hours followed by gradual progression to ambulation. Vital signs with observation of the femoral access site are performed at 15-minute intervals during the 2-hour recovery period. Patients are typically discharged after the 2-hour recovery and observation period. Activity limitations and follow-up instructions are given to each patient. When considering an antithrombotic drug regimen for use in association with this procedure, one has to take into consideration the historical use of these drugs in association with peripheral arterial and venous angioplasty, the potential for venous thrombosis in association with this particular intervention, and the potential hypercoagulability of the patient population being treated. Several studies have reported elevated homocysteine and D-dimer levels in MS patients, which may increase thrombogenic potential.21-23 In addition, MS patients may have increased platelet activation and adhesiveness24,25 as well as elevated levels of antiphospholipid antibodies,26 which may contribute to a hypercoagulable state. Antiplatelet and anticoagulant drugs have historically been an important component of the management of patients after peripheral or coronary arterial interventions. In coronary artery interventions, antiplatelet agents are felt to be necessary because of the activation of platelets caused by damage to the endothelium and deeper layers of the vessel wall during the procedure.27,28 However, one cannot rely solely on coronary artery data when seeking guidance about the role of these drugs in the venous system. It is known that the pressure and flow are less in veins than they are in arteries. In addition, angioplasty can lead to endothelial disruption, and veins may be more sensitive to disruptions in the wall than arteries, which can ultimately affect venous flow.29 With all of these factors in mind, it is possible that patients with MS, who are potentially hypercoagulable, undergoing a procedure, which may lead to a defect in the inner layers of the wall of the internal jugular and/or azygos veins, may be at increased risk for periprocedural thrombosis. Therefore, we are presently recommending that patients undergoing angioplasty take full-strength aspirin (325 mg daily) for 3 months followed by low-dose aspirin (81 mg) for life. Intraprocedural anticoagulation may be indicated when a stenosis is visibly flow limiting. Given the circumstances under which stents are placed in our practice, it is our opinion that these patients are at a significant risk for thrombosis. Therefore, more considerable anticoagulation is recommended and initiated with Enoxaprin (Lovenox, Sanofi-Aventis, Bridgewater, NJ) followed by conversion to Warfarin Sodium (Coumadin, Bristol-Myers Squibb, New York, NY) for 6 months. Follow-up ultrasounds are performed on all patients within 24 hours of their procedure to demonstrate patency and flow dynamics after intervention. We then suggest that at least 1 additional ultrasound be performed 3 months after the intervention to confirm venous patency after intervention. We remain uncertain at this time if lifelong ultrasound exam-
K. Mandato et al
130 inations are indicated. Instead, we believe at this time that additional imaging may be indicated if there is significant symptom progression after angioplasty to assess the veins and determine if changes in flow may be contributing to this symptom change. At that point, a decision can be made as to whether or not repeat intervention is indicated.
10.
11.
12.
Conclusions At this time, treatment decisions for patients with CCSVI are being based largely on the findings of catheter venography. This examination requires an understanding of the venous anatomy of the head and neck and the challenges inherent in selectively catheterizing the veins to be studied in these patients. Technical issues, such as catheter positioning and the rate and volume of contrast injected during venography may significantly impact the findings. These facts, together with criteria for angioplasty that have not yet been universally accepted, have increased the complexity of this examination and the decision to treat patients with CCSVI. The protocol presented in this article represents one view of this procedure. It is clear that additional research is required to gain consensus about the nuances of this technique as well as with the entity of CCSVI in general.
13.
14.
15. 16.
17. 18.
19.
20.
References 1. Zamboni P: The big idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med 99:589593, 2006 2. Zamboni P, Galeotti R, Menegatti E, et al: A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 50:1348-1358, 2009 3. Zamboni P, Galeotti R, Menegatti E, et al: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg, Psychiatry 80:392-399, 2009 4. Zivadinov P, Mark K, Cutter G, et al: Prevalence, sensitivity and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 77:138-144, 2011 5. Haacke EM, Feng W, Utriainen D, et al: Patients with multiple sclerosis with structural venous abnormalities on MR imaging exhibit an abnormal flow distribution of the internal jugular veins. J Vasc Interv Radiol 23:60-68, 2012 6. Doepp F, Paul F, Valdueza JM, et al: No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 68:173-183, 2010 7. Mayer C: The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 82:436-440, 2011 8. Mandato K, Hegener P, Siskin G, et al: Safety of outpatient diagnostic venography and endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis: Experience in 240 patients. J Vasc Interv Radiol 23(1):55-59, 2012 9. Morimoto A, Takase I, Shimizu Y, et al: Assessment of cervical venous
21.
22.
23.
24.
25. 26.
27.
28.
29.
blood flow and the craniocervical venous valve using ultrasound. Leg Med 11:10-17, 2009 Seoane E, Rhoton AL: Compression of the internal jugular vein by the transverse process of the atlas as the cause of cerebellar hemorrhage after supratentorial craniotomy. Surg Neurol 51:500-505, 1999 Escott EJ, Branstetter BF: It’s not a cervical lymph node, it’s a vein: CT and MR imaging findings in the veins of the head and neck. Radiographics 26:1501-1515, 2006 Patra P, Gunness TK, Robert R, et al: Physiologic variations of the internal jugular vein surface, role of the omohyoid muscle, a preliminary echographic study. Surg Radiol Anat 10:107-112, 1988 Suarez T, Baerwald JP, Kraus C: Central venous access: The effects of approach, position, and head rotation on internal jugular vein crosssectional area. Anesth Analg 95:1519-1524, 2002 Lepori D, Capasso P, Fournier D, et al: High-resolution ultrasound evaluation of internal jugular venous valves. Eur Radiol 9:1222-1226, 1999 Brownlow RL, McKinney WM: Ultrasonic evaluation of jugular venous valve competence. J Ultrasound Med 4:169-172, 1985 Yeh BM, Coakley FV, Sanchez HC, et al: Azygos arch valves: Prevalence and appearance at contrast-enhanced CT. Radiology 230:111-115, 2004 Ranniger K: Retrograde azygography. Radiology 90:1097-1104, 1968 Aboulker J, Aubin ML, Leriche H, et al: Intraspinal venous hypertension due to multiple anomalies in the caval system. A major cause of myelopathies [in French]. Acta Radiol Suppl 347:395-401, 1976 Lim CL, Keshava SN, Lea M: Anatomical variations of the internal jugular veins and their relationship to the carotid arteries: A CT evaluation. Australas Radiol 50:314-318, 2006 Qiu J: Venous abnormalities and multiple sclerosis: Another breakthrough claim? Lancet Neurol 9:464-446, 2010 Aksungar FB, Topkaya AE, Yildiz Z, et al: Coagulation status and biochemical and inflammatory markers in multiple sclerosis. J Clin Neurosci 15:393-397, 2008 Nappo F, De Rosa N, Marfella R, et al: Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 281:2113-2118, 1999 Kuch B, Bobak M, Fobker M, et al: Associations between homocysteine and coagulation factors—A cross-sectional study in two populations of central Europe. Thromb Res 103:265-273, 2001 Nathanson M, Savitsky JP: Platelet adhesiveness index studies in multiple sclerosis and other neurologic disorders. Bull N Y Acad Med 28:462-468, 1952 Sheremata WA, Jy W, Horstman LL, et al: Evidence of platelet activation in multiple sclerosis. J Neuroinflammation 5:27, 2008 Sugiyama Y, Yamamoto T: Characterization of serum anti-phospholipid antibodies in patients with multiple sclerosis. Tohoku J Exp Med 178:203-215, 1996 Silber S, Albertsson P, Avilés FF, et al: Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 26: 804-847, 2005 Garg R, Uretsky BF, Lev EI: Anti-platelet and anti-thrombotic approaches in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 70:388-406, 2007 Martinez R, Fierro CA, Shireman PK, et al: Mechanical buckling of veins under internal pressure. Ann Biomed Eng 38:1345-1353, 2010
C
hronic cerebrospinal venous insufficiency (CCSVI) is a theory described by Zamboni et al1 to elucidate the pathology and clinical manifestations of multiple sclerosis (MS). In this theory, venous stenoses hindering outflow from the central nervous system are potentially contributing to symptoms related to inflammatory plaque within the brain and spinal cord in patients with MS. Zamboni et al2 then used this theory as the basis for treating MS patients in whom stenoses were found in the internal jugular veins (IJVs) and/or the azygos vein with angioplasty, and achieved high rates of clinical improvement with no significant postoperative complications. This, of course, has led to a great deal of interest in this theory and this procedure as a potential treatment option for patients with MS. This article is a description of the endovascular techniques used to diagnose and treat patients with MS and CCSVI in our practice.
Department of Radiology, Albany Medical Center, Albany, NY. Address reprint requests to Kenneth Mandato, MD, Department of Radiology, MC-113, Albany Medical Center, 47 New Scotland Avenue, Albany, NY 12208. E-mail: [email protected] 1089-2516/12/$-see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1053/j.tvir.2012.02.005
Preprocedure Evaluation Before venography, a complete review of the patient’s medical history should be performed to evaluate for significant cardiac and renal disease in addition to a previous history of venous disease, including deep venous thrombosis and venous insufficiency. A history of previously placed central venous catheter placement is important to uncover because that may lead to central vein occlusions that may interfere with selective catheterization and angioplasty of the internal jugular and azygos veins. The use of preprocedure noninvasive imaging is typically performed before venography. Both Doppler ultrasound and magnetic resonance venography are potentially helpful in imaging the veins that are to be studied with catheter venography and may, therefore, provide information that may assist with the performance of this procedure.3-5 Although the diagnostic utility of both of these imaging examinations has been called into question,6,7 knowing that one of the veins to be selectively catheterized is occluded or severely stenotic can help prepare an interventionalist for challenges that may 121
122
K. Mandato et al
be encountered during the procedure. In addition, understanding the degree of disease severity before treatment can allow for appropriate comparative follow-up in the future.
Diagnostic Venography for CCSVI Whether performed in a hospital or ambulatory surgery center, continuous cardiac monitoring and oxygen sensitometry are used. Transient arrhythmias can occur during guidewire and catheter placement through the right atrium while moving from the inferior vena cava to the superior vena cava.8 Continuous cardiac monitoring will give the primary operator instant data to reposition guidewires and catheters when necessary. The procedure is often performed with mild-tomoderate procedural sedation, which can be accomplished with oral diazepam (Valium, Roche Pharmaceuticals, Nutley, NJ) or a combination of intravenous midazolam (Versed, APP Pharmaceuticals, LLC, Schaumburg, IL) and fentanyl citrate (Sublimaze, Taylor Pharmaceuticals, Buffalo Grove, IL). Venography for CCSVI is typically performed from right or left common femoral vein access. The right common femoral vein provides a straighter route to the internal jugular and azygos veins, whereas left common femoral vein access makes it easier to assess the common iliac and left ascending lumbar veins for abnormalities. After access into the common femoral vein using standard Seldinger technique with ultrasound guidance, an 8-French introducer sheath (Terumo Medical Corp, Elkton, MD) is used to maintain that access. An 8-French sheath is used to decrease friction-related difficulties in removing large angioplasty balloons that have been recently deflated. Selective catheterization of the IJV may be more difficult than some might anticipate, based on their familiarity with these veins through work in the area of venous access. However, there are significant differences between antegrade catheterization of these veins for venous access as opposed to retrograde catheterization of these veins for diagnostic venography to evaluate CCSVI. A number of angiographic catheters can be used for this purpose. We typically use a 5-French glide Headhunter catheter (Terumo Medical Corp, Elkton, MD) for these catheterizations; it is particularly well suited for catheterization of the azygos vein. A 5-French Glide Berenstein catheter (Terumo Medical Corp) can significantly help catheterize the IJVs when the origins are oblique and/or complex in appearance. This may often be the case with the origin of the left IJV. The vertebral vein, and its termination into the posterior portion of the brachiocephalic vein, may make selective catheterization of the IJV difficult. The absence of valves in the vertebral vein9 may favor catheterization of the caudal portion of the vertebral vein during attempts at catheterizing the IJV. Therefore, it is important for an interventionalist to distinguish between these 2 vessels. The easiest way to know if the caudal portion of the vertebral vein has been catheterized is if the catheter and guidewire course medially toward the spine (Fig. 1). The IJV should maintain a relatively consistent distance from the spine in the lateral soft tissue of the neck. In
Figure 1 Images of a venogram of the left vertebral vein before (A) and after (B) the administration of contrast. This demonstrates the medial course of the catheter position when located within the vertebral vein.
addition, guidewire resistance will often be encountered in the lower neck while the vertebral vein is accessed. This is a reflection of the complex branching pattern of the vertebral vein and may cause instant patient feedback in the form of pain. Patients will not typically experience discomfort when the IJV has been catheterized. Once the catheter has gained access into the IJV, the suggested catheter position for the initial venogram is just inferior to C1. Selective venography of the IJV is then performed in the anteroposterior (AP) and lateral projections. When the upper portion of the IJV is studied, it can be challenging to
Chronic cerebrospinal venous insufficiency determine if a significant stenosis is present or if normal anatomic and physiologic features of the IJV and surrounding veins in this area are being visualized. Under normal circumstances, the IJV is the continuation of the transverse and sigmoid sinuses. Therefore, visualization of these sinuses on reflux venography can provide confirmation that the catheter is indeed located within the IJV (Fig. 2). The vertebral veins often originate from the sigmoid sinus and descend as a plexus of veins surrounding the vertebral artery. These veins may overlap with the upper IJV on AP imaging (Fig. 3). Just below the jugular foramen, the IJV may abut the anterior surface of the transverse process of C1, which can lead to extrinsic compression of the vein at this location.10 Venography in the lateral projection is often the best way to evaluate the caliber of the IJV relative to the lateral mass of C1 and can also help separate the visualized portion of the vertebral venous plexus from the upper portion of the IJV. The exact position of the catheter and the force and volume of contrast injections for venography have a significant role in determining how the images obtained in this portion of the IJV are interpreted. If the catheter is positioned above C1, unknowingly placed through an area of anatomic narrowing secondary to extrinsic compression at the level of C1, then this normal “narrowing” may in fact be accentuated. In addition, if the end hole of the catheter is positioned near the origin of the vertebral venous plexus, then contrast may preferentially enter the vertebral veins instead of the IJVs. This may provide the interventionalist with the sense that the vertebral veins are serving as collateral outflow pathways because of a stenotic IJV. In fact, placing the catheter below C1 and limiting the injection rate and volume to match physiologic flow (using an injection rate that limits reflux in the vein) will allow for the most accurate assessment of the upper
Figure 2 Image from a venogram of the internal jugular vein (IJV) in the lateral projection demonstrating continuity of the IJV with the sigmoid sinus as well as the origin of the vertebral venous plexus.
123
Figure 3 Image from a venogram of the left IJV in the anteroposterior projection demonstrating overlap of the IJV and the vertebral venous plexus.
IJV diameter, the direction and rate of outflow from the sigmoid sinus into the IJV, and the possible role of the vertebral venous plexus as a collateral pathway for cerebral venous blood flow (Fig. 4). Similar anatomic features may confound the venographic evaluation of the midportion of the IJV. In this portion of the
Figure 4 Images from a venogram of the internal jugular in the lateral projection demonstrating the effect of catheter position and injection rate on the visualization of the vertebral venous plexus. (A) The catheter is positioned at the origin of the vertebral vein. (B) The catheter is positioned in a more caudal position, and a lower injection rate was used.
K. Mandato et al
124
Figure 5 Images from a venogram of the left IJV without (A) and with (B) contralateral head rotation demonstrating the change in vein diameter with the change in head position.
neck, the IJV runs close to the common carotid artery as well as the omohyoid muscle. Both of these structures can potentially compress the IJV11,12 and mimic pathology intrinsic to the IJV. Therefore, the finding of a stenosis in this region of the vein must be challenged with multiple views combined with head rotation to determine if this is a fixed stenosis or one because of extrinsic compression that is relieved with the head in different position(s) (Fig. 5). In general, contralateral head rotation will help relieve “stenoses” caused by extrinsic compression13 but will not change the appearance of a fixed abnormality within the vein. If head rotation restores a normal and uniform diameter to the vein, and rapid clearance of contrast is visualized, then the initial finding will be deemed to have occurred secondary to compression. There are many tributaries draining into the midportion of the IJV. If the end hole of the catheter is positioned near the origin of these veins, then contrast may be injected preferentially into one of these veins, thereby creating the false impression that collateral vessels are responsible for venous outflow. This is particularly true with the common facial vein (which ultimately leads into the external jugular vein) and the anterior jugular vein, both of which may enter the IJV near the angle of the mandible. Therefore, a catheter position above these veins together with a physiologic injection of contrast is important to assess both the direction of flow in these veins and in the IJV to determine if collateral flow is present in the face of an IJV stenosis that remains present with contralateral head rotation or if the findings represent normal anatomy. An evaluation of the IJVs concludes with studying the caudal aspect of the vein, at its confluence with the subclavian vein to form the brachiocephalic vein. The caudal aspect of the IJV is best visualized in the AP and 30-degree ipsilateral oblique projections, with the catheter repositioned below the angle of the mandible (making sure that it is not directed
toward one of the tributary veins of the IJV described earlier). In general, this tends to be the portion of the vein where stenoses and flow abnormalities are most commonly seen in patients with CCSVI. This is where valves are located in most patients14; these valves typically close during diastole to prevent increased venous pressure in the IJV.15 Flow through the valve annulus is best seen in the ipsilateral anterior oblique projection (Fig. 6). After venography of both IJVs, the azygos vein should be evaluated for CCSVI.3 The azygous system of veins originates in the pelvis from the common iliac veins via the ascending lumbar vein and plexus of iliolumbar veins. The azygous vein typically begins on the right side at L3 and ascends through the aortic hiatus receiving the hemiazygos vein as well as posterior intercostal and paravertebral veins in the chest. At the level of T4, the azygous arch runs anteriorly to empty into the posterior aspect of the superior vena cava just below the junction of the brachiocephalic veins. A bicuspid valve is found in approximately two-thirds of patients within the azygous arch16,17; if malformed or hypertrophic, this valve may contribute to the findings of CCSVI. A catheter with a Headhunter configuration is well suited to selective catheterization of the azygos vein. The vein can often be engaged by directing the end hole of the catheter posteriorly. Once the vein is engaged, moving the image intensifier into a left anterior oblique projection (LAO) can confirm the passage of the guidewire passage posteriorly and then inferiorly into the azygos vein. If the guidewire is seen running anteriorly in this projection, then it likely means that the catheter had been directed anteriorly within the superior vena cava and that the internal mammary vein was inadvertently catheterized (Fig. 7). If locating the origin of the azygos vein is difficult, additional attempts at selective catheterization using lateral fluoroscopy can be helpful. With the patient’s arms in the upright position, the azygos vein can be
Chronic cerebrospinal venous insufficiency
125 Typically, the LAO and lateral views can be used for a complete evaluation of the azygos vein (Fig. 8). The evaluation initially proposed by Zamboni et al consisted of an evaluation of the internal jugular and azygos veins as described previously. However, Zamboni has lately been proposing that additional veins should be studied as part of a venographic evaluation for CCSVI. These other veins include the left renal vein (to evaluate for nutcracker syndrome), the left common iliac vein (to evaluate for May–Thurner syndrome), and the ascending lumbar veins. The rationale for studying these other veins is that they complete the cerebrospinal circuit and that abnormalities of these veins may contribute to the neurologic manifestations of CCSVI.18 It is our position that additional research and reports of clinical success are required before universally treating these veins under the justification provided by the earlier work of Zamboni et al.2
Endovascular Treatment of CCSVI
Figure 6 Image from a venogram of the left IJV in the left anterior oblique position demonstrating a significant stenosis at the valve annulus.
reliably accessed just above the right main-stem bronchus. With the catheter positioned in the distal azygos vein, contrast can often be refluxed into the azygos and hemiazygos veins, which can be best seen in the LAO projection. The catheter should then be pulled back into the ascending azygos vein, where two views of the azygos arch can be obtained.
The detection of either a significant stenosis or significant flow abnormality within the veins studied using the technique described previously will lead to a diagnosis of CCSVI and possible endovascular treatment. The challenge at this moment, given the early stage of evolution of CCSVI, is in defining the abnormalities being detected with venography and the criteria being used to make subsequent treatment decisions. One potential issue is that the IJV can vary significantly in both size and symmetry with various factors, including hydration status, cardiac output, and head position, accounting for some of the described variability.11 Lim et al19 described an IJV diameter range from 9.1 to 10.2 mm but that smaller diameters approaching 5 mm have been identified in up to 13% of patients studied.
Figure 7 Images from the same patient demonstrating the internal mammary vein (A), which arises anteriorly from the superior vena cava, and the azygos vein (B), which arises posteriorly from the superior vena cava.
126
Figure 8 Images from a venogram of the azygos vein in the left anterior oblique (A) and lateral (B) projections.
The algorithm that we use for treatment of the internal jugular and azygos veins is presented in Figure 9. The first finding to consider when evaluating a patient for CCSVI is the degree of narrowing within the vein as seen on selective venography. In other words, what should be considered a significant stenosis? In arteries, significant changes in flow and pressure occur when the vessel has been reduced to 50% of its diameter (which corresponds to a 75% reduction in cross-sectional area). When using this same threshold as an
K. Mandato et al indication for angioplasty, Zamboni et al reported significant symptomatic improvement after angioplasty.2 Therefore, a 50% stenosis can be considered a significant finding on venography and one that can serve as an indication for treatment with angioplasty. We typically measure the largest diameter of the IJV below the mandible and compare that diameter with the measurement obtained at the level of stenosis to determine the percentage luminal diameter reduction. Importantly, the algorithm presented in Figure 9 takes into account that a measured reduction in luminal diameter is only one factor that should be considered when deciding on whether or not a studied vein should be treated with angioplasty. As recognized by the ultrasound protocol proposed by Zamboni et al to evaluate patients for CCSVI, flow abnormalities recognized within the IJV are also indicative of this condition.3 Therefore, any algorithm must include an assessment of flow on venography and then use the results of that assessment to determine a patient’s candidacy for angioplasty. Reflux and stasis of flow in the IJV are both secondary signs of abnormal flow that may be seen in conjunction with a significant luminal diameter reduction. The presence of collateral vessels may be evident as well, although care must be taken to avoid the opacification of these vessels due to catheter position and technique. However, these findings may also be seen without a significant stenosis. In that scenario, the findings may be attributed to an intraluminal abnormality poorly visualized with venography or may be “normal” for that particular patient. Intravascular ultrasound may be helpful in this scenario to confirm the presence of an intraluminal web, membrane, and so on, but the use of dilute contrast may also help recognize these abnormalities. Obtaining measurements to assess the pressure gradient across the area in question may be helpful as well.2 In our practice, patients with significant flow abnormalities in conjunction with a stenosis of ⬍50% remain candidates for angioplasty, especially if previous noninvasive imaging has indicated an abnormality within the studied vein. This is particularly true if this is seen on the dominant side (the side with the larger IJV). In our experience, significant stenoses and/or flow abnormalities within the caudal aspect of the IJVs, at the location of the valves, are the most common abnormalities detected during venography in these patients. Stenoses in this portion of the IJV often respond well to high-pressure angioplasty (Fig. 10). Even though the balloons capable of generating higher pressures tend to be more rigid, they are trackable over standard guidewires because of the relatively nontortuous course from the common femoral vein to both of the IJVs. The actual balloon size selected depends on the measured diameter of the vein. This has been a source of relative controversy amongst physicians performing this procedure. It has been our practice to oversize our balloons by 10%-20% relative to the size of the more normal-appearing portions of the vein. It is not recommended that the measurement of the contralateral vein be used as a reference diameter because of the known asymmetry of the IJVs. The most common balloon sizes used to treat abnormalities in the caudal IJV range from 10 to 16 mm in diameter. Moderate-to-low–
Chronic cerebrospinal venous insufficiency
127
Figure 9 Algorithm for diagnosis and treatment of chronic cerebrospinal venous insufficiency within the internal jugular (A) and azygos (B) veins.
pressure angioplasty is used to treat stenoses in the upper and midportions of the IJV when deemed significant and not attributed to anatomic compression by surrounding structures (Fig. 11). The most common balloon sizes used to treat abnormalities higher in the IJV range from 6 to 10 mm in diameter. When evaluating the azygos vein, consideration should be given to evaluating both luminal diameter as well as the ra-
pidity of outflow from the vein and the presence of intercostal veins, suggesting reversal of normal antegrade flow and collateralization. Irregularity of the contour of the vein may be used as a secondary sign of an abnormality as well. The most common area of abnormality within the azygos vein extends from the azygos arch into the proximal portion of the ascending azygos vein (Fig. 12). To treat the azygos vein, 8-10 mm balloons are typically used. Importantly, less rigid and more
K. Mandato et al
128
Figure 10 Images from a venogram of the right IJV before (A) and after (B) dilatation of a moderate-severe stenosis at the valve annulus.
trackable balloons are required to access the IJV because of the 180-degree turn that this vein makes from its confluence with the superior vena cava into its ascending portion. In addition, the length of the balloon should not exceed 2 cm in the azygos arch; balloons with a 4-cm length may create additional tension by straightening the arch and deforming the vein. The usual end point and goal of azygous angioplasty is improvement in luminal diameter as well as in outflow of
contrast from the vein and reduced visualization of intercostal collateral vessels. Venous angioplasty may be associated with immediate recoil or a flow-limiting dissection of the treated vein with the added risk of thrombotic occlusion.8 If venography indicates that this has occurred, immediate intravenous anticoagulation is recommended. Repeat angioplasty with a prolonged inflation is then performed to determine if this impacts the
Figure 11 Images from a venogram of the left IJV before (A) and after (B) dilatation of a stenosis in the midportion of this vein.
Figure 12 Image from a venogram of the azygos vein demonstrating a stenosis at the junction of the ascending portion of the azygos vein with the azygos arch.
Chronic cerebrospinal venous insufficiency
129
Postprocedure Management
Figure 13 Image from a venogram of the right IJV after angioplasty (A) and after stent placement (B). Stent placement was performed because of the refractory nature of the stenosis and persistent visualization of collateral vessels after angioplasty.
appearance of the vein and improves antegrade flow. Downsizing the balloon and repeating the angioplasty may also be an effective treatment. If repeat angioplasty fails to accomplish this goal, consideration can be given to stent placement (Fig. 13). At this time, it is our opinion that stent placement should be limited to this scenario. More widespread use of stents or surgery to treat IJV stenoses secondary to extrinsic compression may make intuitive sense but is not supported by the outcomes data available at this time. If stent placement is required, self-expanding stents are used. Sizing of the stent with oversizing is important because of the known risk of stent migration in association with CCSVI.20
After sheath removal and manual pressure to the groin, patients remain in the supine position for 2 hours followed by gradual progression to ambulation. Vital signs with observation of the femoral access site are performed at 15-minute intervals during the 2-hour recovery period. Patients are typically discharged after the 2-hour recovery and observation period. Activity limitations and follow-up instructions are given to each patient. When considering an antithrombotic drug regimen for use in association with this procedure, one has to take into consideration the historical use of these drugs in association with peripheral arterial and venous angioplasty, the potential for venous thrombosis in association with this particular intervention, and the potential hypercoagulability of the patient population being treated. Several studies have reported elevated homocysteine and D-dimer levels in MS patients, which may increase thrombogenic potential.21-23 In addition, MS patients may have increased platelet activation and adhesiveness24,25 as well as elevated levels of antiphospholipid antibodies,26 which may contribute to a hypercoagulable state. Antiplatelet and anticoagulant drugs have historically been an important component of the management of patients after peripheral or coronary arterial interventions. In coronary artery interventions, antiplatelet agents are felt to be necessary because of the activation of platelets caused by damage to the endothelium and deeper layers of the vessel wall during the procedure.27,28 However, one cannot rely solely on coronary artery data when seeking guidance about the role of these drugs in the venous system. It is known that the pressure and flow are less in veins than they are in arteries. In addition, angioplasty can lead to endothelial disruption, and veins may be more sensitive to disruptions in the wall than arteries, which can ultimately affect venous flow.29 With all of these factors in mind, it is possible that patients with MS, who are potentially hypercoagulable, undergoing a procedure, which may lead to a defect in the inner layers of the wall of the internal jugular and/or azygos veins, may be at increased risk for periprocedural thrombosis. Therefore, we are presently recommending that patients undergoing angioplasty take full-strength aspirin (325 mg daily) for 3 months followed by low-dose aspirin (81 mg) for life. Intraprocedural anticoagulation may be indicated when a stenosis is visibly flow limiting. Given the circumstances under which stents are placed in our practice, it is our opinion that these patients are at a significant risk for thrombosis. Therefore, more considerable anticoagulation is recommended and initiated with Enoxaprin (Lovenox, Sanofi-Aventis, Bridgewater, NJ) followed by conversion to Warfarin Sodium (Coumadin, Bristol-Myers Squibb, New York, NY) for 6 months. Follow-up ultrasounds are performed on all patients within 24 hours of their procedure to demonstrate patency and flow dynamics after intervention. We then suggest that at least 1 additional ultrasound be performed 3 months after the intervention to confirm venous patency after intervention. We remain uncertain at this time if lifelong ultrasound exam-
K. Mandato et al
130 inations are indicated. Instead, we believe at this time that additional imaging may be indicated if there is significant symptom progression after angioplasty to assess the veins and determine if changes in flow may be contributing to this symptom change. At that point, a decision can be made as to whether or not repeat intervention is indicated.
10.
11.
12.
Conclusions At this time, treatment decisions for patients with CCSVI are being based largely on the findings of catheter venography. This examination requires an understanding of the venous anatomy of the head and neck and the challenges inherent in selectively catheterizing the veins to be studied in these patients. Technical issues, such as catheter positioning and the rate and volume of contrast injected during venography may significantly impact the findings. These facts, together with criteria for angioplasty that have not yet been universally accepted, have increased the complexity of this examination and the decision to treat patients with CCSVI. The protocol presented in this article represents one view of this procedure. It is clear that additional research is required to gain consensus about the nuances of this technique as well as with the entity of CCSVI in general.
13.
14.
15. 16.
17. 18.
19.
20.
References 1. Zamboni P: The big idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J R Soc Med 99:589593, 2006 2. Zamboni P, Galeotti R, Menegatti E, et al: A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 50:1348-1358, 2009 3. Zamboni P, Galeotti R, Menegatti E, et al: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg, Psychiatry 80:392-399, 2009 4. Zivadinov P, Mark K, Cutter G, et al: Prevalence, sensitivity and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 77:138-144, 2011 5. Haacke EM, Feng W, Utriainen D, et al: Patients with multiple sclerosis with structural venous abnormalities on MR imaging exhibit an abnormal flow distribution of the internal jugular veins. J Vasc Interv Radiol 23:60-68, 2012 6. Doepp F, Paul F, Valdueza JM, et al: No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 68:173-183, 2010 7. Mayer C: The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry 82:436-440, 2011 8. Mandato K, Hegener P, Siskin G, et al: Safety of outpatient diagnostic venography and endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis: Experience in 240 patients. J Vasc Interv Radiol 23(1):55-59, 2012 9. Morimoto A, Takase I, Shimizu Y, et al: Assessment of cervical venous
21.
22.
23.
24.
25. 26.
27.
28.
29.
blood flow and the craniocervical venous valve using ultrasound. Leg Med 11:10-17, 2009 Seoane E, Rhoton AL: Compression of the internal jugular vein by the transverse process of the atlas as the cause of cerebellar hemorrhage after supratentorial craniotomy. Surg Neurol 51:500-505, 1999 Escott EJ, Branstetter BF: It’s not a cervical lymph node, it’s a vein: CT and MR imaging findings in the veins of the head and neck. Radiographics 26:1501-1515, 2006 Patra P, Gunness TK, Robert R, et al: Physiologic variations of the internal jugular vein surface, role of the omohyoid muscle, a preliminary echographic study. Surg Radiol Anat 10:107-112, 1988 Suarez T, Baerwald JP, Kraus C: Central venous access: The effects of approach, position, and head rotation on internal jugular vein crosssectional area. Anesth Analg 95:1519-1524, 2002 Lepori D, Capasso P, Fournier D, et al: High-resolution ultrasound evaluation of internal jugular venous valves. Eur Radiol 9:1222-1226, 1999 Brownlow RL, McKinney WM: Ultrasonic evaluation of jugular venous valve competence. J Ultrasound Med 4:169-172, 1985 Yeh BM, Coakley FV, Sanchez HC, et al: Azygos arch valves: Prevalence and appearance at contrast-enhanced CT. Radiology 230:111-115, 2004 Ranniger K: Retrograde azygography. Radiology 90:1097-1104, 1968 Aboulker J, Aubin ML, Leriche H, et al: Intraspinal venous hypertension due to multiple anomalies in the caval system. A major cause of myelopathies [in French]. Acta Radiol Suppl 347:395-401, 1976 Lim CL, Keshava SN, Lea M: Anatomical variations of the internal jugular veins and their relationship to the carotid arteries: A CT evaluation. Australas Radiol 50:314-318, 2006 Qiu J: Venous abnormalities and multiple sclerosis: Another breakthrough claim? Lancet Neurol 9:464-446, 2010 Aksungar FB, Topkaya AE, Yildiz Z, et al: Coagulation status and biochemical and inflammatory markers in multiple sclerosis. J Clin Neurosci 15:393-397, 2008 Nappo F, De Rosa N, Marfella R, et al: Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA 281:2113-2118, 1999 Kuch B, Bobak M, Fobker M, et al: Associations between homocysteine and coagulation factors—A cross-sectional study in two populations of central Europe. Thromb Res 103:265-273, 2001 Nathanson M, Savitsky JP: Platelet adhesiveness index studies in multiple sclerosis and other neurologic disorders. Bull N Y Acad Med 28:462-468, 1952 Sheremata WA, Jy W, Horstman LL, et al: Evidence of platelet activation in multiple sclerosis. J Neuroinflammation 5:27, 2008 Sugiyama Y, Yamamoto T: Characterization of serum anti-phospholipid antibodies in patients with multiple sclerosis. Tohoku J Exp Med 178:203-215, 1996 Silber S, Albertsson P, Avilés FF, et al: Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 26: 804-847, 2005 Garg R, Uretsky BF, Lev EI: Anti-platelet and anti-thrombotic approaches in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 70:388-406, 2007 Martinez R, Fierro CA, Shireman PK, et al: Mechanical buckling of veins under internal pressure. Ann Biomed Eng 38:1345-1353, 2010