Interventional Endovascular Therapy for MS Gets Mixed Results
When an Italian doctor named Paoli Zamboni first tried interventional endovascular therapy on more than 60 patients with multiple sclerosis, including his wife, back in 2009, nearly three-quarters of the patients were symptom-free years after undergoing the procedure. Since that time, other studies of this therapeutic approach have met with mixed results.
What is interventional endovascular therapy?
Interventional endovascular therapy is done to correct what Zamboni called chronic cerebrospinal venous insufficiency (CCSVI). This is a condition in which there is a blockage in the blood vessels that are involved in transporting excess iron from the brain.
During performance of interventional endovascular therapy, a clinician unblocks these blood vessels, which in turn restores unrestricted blood flow from the brain. What does this have to do with MS?
Zamboni acted on several pieces of information. One was research that named excessive iron as a possible cause of MS, while his own investigations had revealed how an accumulation of iron could damage the blood vessels in the legs.
Yet another bit of information was added when Zamboni used ultrasound to study the veins that transport blood from the brain; specifically, the internal jugular veins (in the neck) and the azygous vein (in the chest), which drain blood from the brain and spinal cord. He discovered that his wife and most of the other patients had problems with their veins that hindered blood flow.
From these findings Zamboni proposed that iron could not be transported away from the brain, which resulted in a buildup of the mineral and thus damage to the blood vessels in the brain. Once the blood vessels were damaged, they could rupture and release iron and immune cells that could make their way into the cerebrospinal fluid and ultimately attack the myelin sheathing that protects the nerves. The result, he proposed, would be multiple sclerosis.
First, Zamboni performed the procedure on his wife, and later he used the therapy on 65 other individuals who had MS: 35 with relapsing-remitting MS, 20 with secondary progressive MS, ad 10 with primary progressive MS. His wife remained attack-free during the three years following the procedure while 73 percent of the other patients were completely symptom-free two years post-procedure.
To unblock the blood vessels, Zamboni threaded a catheter through blood vessels in the groin up to the affected veins in the neck and inflated a tiny balloon to bust up the clog. This is the same basic type of procedure (often called a percutaneous transluminal angioplasty) used to unblock blood vessels in other areas of the body, including the legs and heart.
Based on the results of this initial study, the researchers reported that the procedure was safe and provided benefits for patients with MS. The risk of reblockage (restenosis) of the internal jugular veins was greater than in the azygous veins, which the authors noted suggested “the need to improve endovascular techniques in the former.”
Another Zamboni study
Zamboni and his team conducted another open trial and published the results in 2012. This study involved 29 patients with relapsing-remitting MS who underwent percutaneous transluminal angioplasty for CCSVI and who were then observed for at least two years both before and after the procedure.
Here’s a brief rundown of the findings:
- A total of 44 procedures were performed in the 29 patients without any complications
- 45 percent (13 of 29) of the patients had more than one treatment because of restenosis
- 11 and 2 patients underwent two and three treatments, respectively, because of restenosis
- The yearly relapse rate of MS was significantly lower after the procedure for all patients except for four, and it increased for these patients
- The Expanded Disability Status Scale (EDSS) scores were significantly lower two years after the procedure compared with two years before treatment in all patients except for four, in whom it was higher
Approximately 30,000 patients with MS around the world have undergone interventional endovascular therapy since Zamboni first tried this approach. The majority of these individuals had the procedure as part of a fee-for-service arrangement and not as part of a clinical trial.
However, the first-ever randomized, placebo-controlled, double-blind trial of endovascular treatment of CCSVI in MS patients was completed by a research team at the University of Buffalo and the results reported in 2013. Part of the reason the University of Buffalo group conducted the trial is because they had found that CCSVI is more common among people with MS than in healthy individuals, but the relationship between the abnormalities and the disease are not understood.
The trial, known as the Prospective Randomized Endovascular Therapy in MS (PREMiSe) trial, found that although the treatment was safe and not associated with any serious side effects, the MS patients did not experience any sustained improvement. According to the study’s principal investigator, Adnan Siddiqui, MD, associate professor of neurosurgery at the UB School of Medicine and Biomedical Sciences, “It was quite the opposite of what we originally expected to find. The study showed that endovascular treatment of stenosed veins had no effect in MS patients.”
It’s important to note, however, that there were only 20 patients participating in the PREMiSe trial, and so larger clinical trials should be conducted to further evaluate the use of this therapeutic approach in MS patients.
The bottom line
Interventional endovascular therapy for MS patients has demonstrated mixed results, but trials that include more patients may shed more light on the potential benefits and risks of this treatment approach.
Salvi F et al. Venous angioplasty in multiple sclerosis: neurological outcome at two years in a cohort of relapsing-remitting patients. Functional Neurology 2012 Jan-Mar; 27(1): 55-59
University of Buffalo
Zamboni P et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. Journal of Vascular Surgery 2009 Dec; 50(6): 1348-58