CCSVI: What is this all about?
By Robert Velez RT (R) (VI)
Albany Medical Center
Albany, NY

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system that is diagnosed in more than 10,000 patients in the United States per year (1). It has no known origin but is thought to be autoimmune in nature (2). There is no known cure for this disease. Current pharmaceutical treatments have the ability to slow the disease or prevent relapses in some patients, thereby helping MS patients maintain their quality of life. However, there is no known cure for MS.
Chronic Cerebrospinal Venous Insufficiency (CCSVI) is a recently described condition that has been theorized to have a potential role in the development and manifestations of MS (1). This theory claims that stenosis in the veins draining blood from the central nervous system are contributing to the symptoms experienced by patients with MS. This theory has its basis in the observation that lesions associated with MS can be found along the cerebral veins draining the brain and the spinal cord (1-3). Charcot, et al found a relationship between the cerebral outflow veins and patients with MS (3). Several other studies have lent support to this association (4). More recently, Diaconu, et al and Coen, et al have observed differences in the valves and vein wall in post-mortem specimens from MS patients when compared with patients without MS (5,6).
It has been challenging to diagnose CCSVI using non-invasive imaging techniques. Zamboni, et al described an imaging technique to diagnose CCSVI using Doppler ultrasound (7). This technique evaluates the internal jugular, vertebral, and deep cerebral veins for gray-scale abnormalities (such as intraluminal flaps or membranes and valvular abnormalities) and abnormalities of flow (including reflux and absent flow). An in-depth knowledge of the anatomy and physiology of cerebral venous
outflow is necessary to truly evaluate these veins with ultrasound. Special training may also be necessary to evaluate CCSVI in patients, so relying on sonographic findings has proven to be inconsistent (8,9). Magnetic resonance imaging is currently the modality most often used to diagnose patients with MS because it effectively demonstrates the inflammation and the lesions present in this condition (10). In the past, MRI has shown that MS patients have decreased cerebral blood flow, but these findings have been poorly explained or overlooked (11,12). More recently, MR venography has demonstrated flow abnormalities in MS patients and has therefore been advocated as a technique to diagnose CCSVI (13); unfortunately, this technique has been inconsistent (14). Selective catheter venography of the internal jugular (IJV) and azygos veins remains the definitive study for diagnosing CCSVI (15).
To perform catheter venography and endovascular treatment, the patient must be assessed appropriately. A complete medical review must be obtained to evaluate for cardiac and renal disease. The procedure is usually performed under conscious sedation. The right femoral vein is accessed with an 8-French introducer that can accommodate the catheters and balloons used to diagnose and treat these venous stenoses. Many catheter configurations can be used to select the veins being studied, including Berenstein and Headhunter Catheters; the choice of catheter is practitioner specific. Once the IJV is catheterized, images in multiple projections are obtained (typically anteroposterior and lateral) to diagnose reflux or stenosis from the sigmoid sinus through the confluence of the IJV with the subclavian vein. Technically, it is important that the injection rate of contrast matches physiologic flow within the vein to prevent injection-induced reflux. In addition, this will help accurately diagnose venous disease and the presence of collateral vessels seen in response to a significant stenosis. The azygous vein is then imaged from the confluence of the hemiazygos and azygos veins through the superior vena cava in order to demonstrate stenoses and flow abnormalities. This vein is typically evaluated in the lateral and left anterior oblique projections.
Once a venogram has been performed, the images are evaluated to determine a patient’s candidacy for endovascular treatment. Mandato, et al stated that “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 (15).” At the present time, criteria for intervention include the presence of a luminal diameter reduction of at least 50%, visible reflux, intraluminal structural abnormalities, valvular abnormalities, and contour irregularity (15,16). Intravascular ultrasound has also been used to successfully demonstrate these intraluminal and vein wall abnormalities (17). Stenoses are treated with percutaneous transluminal angioplasty catheters that are typically able to accommodate high inflation pressures. Post treatment venography is performed and stent placement should only be considered in the setting of significant residual flow abnormality after angioplasty (15). If stent placement is required, self-expanding stents are typically used and should be appropriately sized to avoid migration (18). Multiple sclerosis patients may be hypercoagulable, so anticoagulant or antiplatelet therapy is appropriate for patients undergoing endovascular treatment (19,20).
While the ability to diagnose MS patients with CCSVI has proven to be inconsistent, the published and presented reports describing outcomes after treatment has been much more consistent. Many patients with this condition undergoing endovascular treatment report improvement in many of the symptoms associated with MS (21). Zamboni, et al treated 65 MS patients diagnosed with CCSVI (22). At 18-month follow up, 96% of treated azygous veins and 53% of treated internal jugular veins were patent. All patients with relapsing remitting MS with patent internal jugular veins were relapse-free at 18 months. In addition, improvements were demonstrated in quality of life, disease severity, and MRI abnormalities. Malagoni, et al reported on 31 MS patients with CCSVI who were treated with angioplasty (23). One year after treatment, these patients experienced significant improvement in fatigue and all patients were able to walk farther within a six-minute time frame. Dake, et al treated 38 patients and found significant improvement in fatigue and heat tolerance (18). At the 2011 meeting of the International Society for Neurovascular Disease (ISNVD), Metha, et al treated 150 MS patients and demonstrated improvement in fatigue and quality of life 3, 6, and 12 months after treatment (24). At the 2012 meeting of the Society of Interventional Radiology (SIR), Sekhar, et al reported significant
improvement in physical and health-related quality of life at 3 months post treatment (25). This study also noted that patients with secondary-progressive MS report these improvements less often than do patients diagnosed more than 10 years before receiving treatment.
Understanding the safety of this procedure remains an important priority for patients and physicians. Ludyga, et al studied 331 patients treated for CCSVI and found no major complications and a low minor complication rate (26). Only 2 out of 152 stents placed became occluded, and one patient required surgery to remove a balloon from the common femoral vein. Petrov, et al studied 461 patients and also found no major complications (27). Mandato, et al reported on 240 patients, with 87% of patients treated with angioplasty alone and 11% of patients requiring stent placement (28). Minor complications were limited to transient pain (62/257), minor site bleeding (2/257) and cardiac arrhythmias (3/257). One major complication was a stress-induced cardiomyopathy that resolved within a few days. These studies demonstrate that endovascular treatment of CCSVI is a safe procedure with low risk of significant complications.
At the present time, CCSVI has shown some early promise as a treatment option for patients with Multiple Sclerosis. However, the studies performed to date have been preliminary in nature. Therefore, FDA-approved clinical trials need to be developed and carried out so that CCSVI and its relationship to MS can be better understood (29). These trials will also help determine if endovascular treatment of these venous abnormalities makes a significant different in the lives of these patients. There is much more work that needs to be done.
REFERENCES
1) Zamboni P. The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis. J Royal Soc Med 2006; 99:589-593
2) Barnett MH, Sutton I. The pathology of multiple sclerosis: a paradigm shift. Curr Opin Neurol 2006; 19:242-247
3) Charcot JM. Histology of “sclerose en plaque” (in French). Gazette Hosp (Paris) 1868l 41:554-566
4) Dake MD. Chronic cerebrospinal venous insufficiency and multiple sclerosis: history and background. Tech Vasc Interventional Rad 2012; 15:94-100
5) Diaconu C,,Staugaitis J, McBride C, et al. Anatomical and histological analysis of venous structures associated with chronic cerebrospinal venous insufficiency. Presented at: the 5th Joint Triennial congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis; October 21, 2011; Amsterdam, the Netherlands.
6) Coen M, Menegatti E, Salvi F, et al. Altered collagen expression in jugular veins in multiple sclerosis. Cardiovasc Pathol. 2012. http://www.cardiovascularpathology.com/article/S1054-8807(12)00059-2/abstract. Accessed July 12, 2012.
7) 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.
8) Doepp, F, et al. No cerebrospinal venous congestion in patients with multiple sclerosis. Ann Neurology 2010; 68:173-183.
9) Menegatti E, Genova V, Tessari M, et al. The reproducibility of colour Doppler in chronic cerebrospinal venous insufficiency associated with multiple sclerosis. Int Angiol 2010; 29:121-126
10) Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58:840-846

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