Safety of endovascular treatments for CCSVI and future perspectives
M Simka
Marian Simka
Euromedic Specialist Clinics, Department of Vascular & Endovascular Surgery, Katowice, Poland
Association of multiple sclerosis (MS) with impaired venous outflows from the central nervous system, the so-called chronic cerebrospinal venous insufficiency (CCSVI), has shed new light on the cause and potential treatment of this incurable neurologic disease.1 Nowadays it is widely thought that MS is an autoimmune disease, which means that that it is caused by immune attack against nervous tissue. But how such an autoimmune reaction is initiated and maintained, remains unclear. Hypothetical role for venous blockages in the pathogenesis of MS is not necessarily contrary to the currently accepted model of this disease, since it is known that chronic venous insufficiency in the lower extremities also triggers inflammatory reaction in the skin,2 with cellular infiltrate similar to that found in the setting of MS.
Already published reports of small open-label trials have demonstrated positive effects of endovascular treatments for CCSVI in MS patients,3,4 thus warranting further studies on this topic. However, some doctors are aware of potential serious complications that may occur during or after these procedures,5 although such interventions in other venous territories are known to be very safe. Paper by Petrov et al. discusses this problem of safety. The authors reported very low incidence of minor adverse events and no serious, life-threatening complications related to endovascular treatment for CCSVI. These observations are in line with others already published reports, which also demonstrated only minor and infrequent complications.3,6,7
Several questions should be, however, answered by future observational studies and randomized trials. Firstly, it is not known if alleviation of venous blockages will result in a long lasting (i.e., three or five years) clinical improvement of MS symptoms. In this context, also no further progression of MS would be regarded as a success, but to validate such long-term efficacy, the trials with a long follow-up should be planned. Secondly, current endovascular techniques and strategies for the treatment of CCSVI are probably far from perfection. While less aggressive treatments, like balloon angioplasty, are very safe, they are also associated with unacceptable high rate of re-stenoses.3 Stents have been found more efficient in a short-term perspective, but problems with long-term patency, due to thrombosis and intimal hyperplasia, have already been reported. It is hoped that the use of cutting balloons (see Figure), instead of stents, will be a better solution in some cases, but also other techniques, like drug-coated balloons, drug-eluting stents or dissolvable stents may play a role in the future. In addition, an optimal post-procedural antithrombotic and antiaggregation medication scheme should be established by ongoing clinical trials.
The discovery of CCSVI has another potential clinical consequence. It is known that only a minority of MS patients improve after administration of immunomodulating drugs. It cannot be ruled out that these “responders” actually represent a unique subset of CCSVI. If it were the case, these drugs should be given only to this group of MS patients. However, the rationale for this hypothetical paradigm shift in the current immunomodulatory treatment should be verified by ongoing studies.
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. Simka M. Cellular and molecular mechanisms of venous leg ulcers development--the "puzzle" theory. Int Angiol 2010;29:1-19.
3. Zamboni P, Galeotti R, Menegatti E, et al. Endovascular treatment of chronic cerebrospinal venous insufficiency, a prospective open-label study. J Vasc Surg. 2009;6: 1348-1358.
4. Ludyga T, Kazibudzki M, Latacz P, et al. Early results of a prospective open-label study on endovascular treatments for chronic cerebrospinal venous insufficiency in the patients with associated multiple sclerosis Przeg Flebol. 2011;19:9-14.
5. Khan O, Filippi M, Freedman MS, et al. Chronic cerebrospinal venous insufficiency and multiple sclerosis. Ann Neurol. 2010;67:286-290.
6. Ludyga T, Kazibudzki M, Simka M, et al. Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe? Phlebology 2010 25:286-295.
7. Mandato K, Hegener P, Siskin G, et al. Safety of outpatient endovascular treatment of the internal jugular and azygos veins for chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis: a retrospective analysis. (abstract) J Vasc Intervent Radiol 2011;22: S4.
Figure. The use of cutting balloon for angioplasty of stenotic valve in the ostium of right internal jugular vein.