Friday, June 18, 2010

Featured Masters Questions and Answers
June 2010
Please visit our archived questions and answers from previous Masters of MS by clicking here.
Robert Zivadinov, MD, PhD
Director, Buffalo Neuroimaging Analysis Center (BNAC)
Associate Professor of Neurology With Tenure
University of Buffalo, The State University of New York

What is the current status of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis?
Right now, procedures to evaluate and treat CCSVI are still in the early research stages. It is important to emphasize that only through carefully controlled research can we truly understand the effect of venous insufficiency in people with MS and how treatments related to the condition might benefit these patients.
In a small pilot study we conducted jointly with Dr. Paolo Zamboni’s group in Italy, 16 MS patients with severe documented CCSVI were given intravascular treatment with percutaneous transluminal angioplasty (PTA) either immediately or following a 6-month delay. The one-year findings of that study will be presented at the 2010 ECTRIMS meeting in Sweden in October. In this trial, the primary outcomes were change in volume of lesions on MRI and number of MS relapses.
Our group in Buffalo is undertaking a larger placebo-controlled trial (PTA versus a “fake” treatment) in 30 RRMS patients. This study will compare many of the standard outcomes in MS but will also include important quality of life measures such as pain, fatigue, and mobility. This study will soon begin enrolling patients at the University of Buffalo.
Suggested reading:
Zamboni P, Galeotti R, Weinstock-Guttman B, et al. Endovascular treatment for chronic cerebrospinal venous insufficiency in multiple sclerosis: a longitudinal, magnetic resonance imaging, blinded pilot study. J Vasc Surg. 2010;51:794 (abstract).
How is CCSVI related to the pathogenesis of MS, based on what is known right now?
The basic theory behind CCSVI is that blood is not properly draining from the brain and spinal cord. CCSVI can include several different types of venous anomalies, including constrictions external to the vein and intraluminal anomalies. The internal jugular and azygous veins are among those involved.
Vascular abnormalities in patients with MS are not a new concept—they were first identified in the 1800s and have been described since the 1930s. Nor are venous insufficiencies specific to MS. Our studies have found CCSVI in about 25% of normal individuals and about 40% of those with neurologic diseases. It could be that an abnormality of the blood vessels triggers an immune response leading to the inflammation and myelin degradation seen in MS, possibly related to deposits of iron in the brain.
My view at this point is that CCSVI is associated with MS; however it is yet to be determined whether CCSVI is among the risk factors that, along with others, increase a person’s susceptibility to developing this disease. The fact that CCSVI prevalence is about 38% in patients with a first clinical attack of MS and almost 90% in those with secondary progressive MS and a disease history of 20 years suggests to me that venous insufficiency has a high likelihood of affecting people with MS over time.
Suggested reading:
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.
University at Buffalo, The State University of New York. First blinded study of venous insufficiency prevalence in MS shows promising results. Press release, Feb 10, 2010.

  Should people with MS seek diagnosis and/or treatment for this condition?
In my opinion, there is currently no role for “open-label” treatment outside of well-designed research studies. Any vascular procedure carries a certain degree of risk, including risk of morbidity and mortality. Vascular surgical risks may be compounded if a patient travels long distances to undergo a procedure and returns via air travel without adequate recovery time, on anticoagulant therapies, etc.
Clearly, more research is needed to determine the best methods for treating CCSVI in patients who are diagnosed with this condition. A study in California was halted because of deaths in patients whose jugular veins were opened with stents, which are designed for arteries rather than veins. We don’t know at this time whether some form of stenting may be an approach to treatment. At this time we are not recommending stenting.
Research is also needed to determine the best approach to diagnosis and what groups of patients might be screened. Doppler ultrasound is an excellent noninvasive diagnostic method and may be useful for screening purposes, but this must be done by experts with appropriate training in identifying venous anomalies. Selective venography is the gold standard for CCSVI diagnosis but is currently not appropriate for screening purposes because of the invasive aspects, costs, and risks associated with this procedure.
Suggested reading:
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.

 What should neurologists tell their patients about CCSVI?
Research to determine how to diagnose CCSVI, how and whether it should be treated, and whether the treatment benefits patients with MS is just getting under way. So the only thing neurologists can do is either wait and see, or send the patients to one of the few centers where studies are being conducted.
I predict the debate about the role of CCSVI in MS may get even hotter as more centers attempt to do Doppler exams on patients without the proper training, thus obtaining negative findings.
On the other hand, we have to understand that people with MS have a right to information and an urgent need for answers to these questions. It was only a few years ago that many people doubted the benefit of stem cell treatments in MS, yet now this is emerging as a feasible option. So we can’t shoot down revolutionary types of treatments that may offer hope for patients. We need to listen to our patients, understand that our existing treatments do not completely manage the daily burden of MS, and keep an open mind to any new approaches that might help these patients. Before any new treatment can be recommended, it must first be examined in rigorous research studies.

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