'Liberation therapy' may make MS worse



SAN DIEGO – Percutaneous transluminal venous angioplasty – also known as "liberation therapy" – doesn’t help people with multiple sclerosis and may increase MS brain activity in the short term, according to a small, randomized, sham-controlled trial from the State University of New York at Buffalo, the first randomized trial to investigate the procedure.

It "was ineffective in correcting" chronic cerebrospinal venous insufficiency (CCSVI), the recently described condition it targets. "The results ... caution against widespread adoption of venous angioplasty in the management of patients with MS outside of rigorous clinical trials," the investigators concluded.

The findings follow a recent Food and Drug Administration warning that PTVA (percutaneous transluminal venous angioplasty) can cause deaths and injuries, including strokes, damage to the treated vein, blood clots, cranial nerve damage, abdominal bleeding, and detachment and migration of stents.

The idea is to use balloon angioplasty and stents to widen veins in the chests and necks that appear to be narrowed in some MS patients. Proponents of the procedure say that those narrowed veins impair blood flow and lead to disease progression. The researchers who discovered the problem dubbed it CCSVI. A cottage industry has since sprung up to offer PTVA to MS patients.

The FDA noted in its warning that there have been no "controlled ... rigorously conducted, properly targeted" studies of the issue; that may have changed when Dr. Robert Zivadinov, a professor in the department of neurology at SUNY-Buffalo, presented his team’s findings at the annual meeting of the American Academy of Neurology.

"When you reopened those veins in the neck, I think something happened in reperfusing the brain and re-exacerbating disease activity. The message of this is clear. The majority of patients who are relapsing-remitting should not undergo this treatment," he said in an interview.

Ten patients got PTVA in the first phase of the study. The second phase randomized 9 to PTVA and 10 to a sham intervention. Most had relapsing-remitting MS.

There were no MS relapses in the first phase, but PTVA patients had more relapses (4 vs. 1; P = .389) and more MRI disease activity (cumulative number of new contrast-enhancing lesions (19 vs. 3; P = .062) and new T2 lesions (17 vs. 3; P = .066) in the 6 months following treatment in phase II.

PTVA patients also didn’t fare any better on Expanded Disability Status Scale (EDSS) scores, Multiple Sclerosis Functional Composite scores, 6-minute walk tests, or measures of cognition and quality of life.

"We chose very active patients who had one relapse in the previous year or [gadolinium-] enhancing lesions in the 3 months before. The sample size is small, but [more than half] of patients in the treatment group showed increased activity," Dr. Zivadinov said.

The majority of the subjects were women. On average, they were about 45 years old, had been diagnosed with MS for 11 years, and were mildly to moderately disabled (mean EDSS score about 4). Most were on interferon, glatiramer acetate, or both.

Venous angioplasty didn’t cause any serious complications, and it restored venous outflow to at least 50% of normal in most patients. Phase I patients had a better than 75% improvement overall. Phase II patients had less benefit; there were no differences in venous hemodynamic insufficiency scores between treated and sham patients.

The treatment "failed to provide any sustained improvement in venous outflow as measured through duplex and/or clinical and MRI outcomes," and "more sizable changes in venous outflow [were] associated with increased disease activity primarily noted on MRI," Dr. Zivadinov and his colleagues concluded.

The work was funded primarily by SUNY-Buffalo’s Neuroimaging Analysis Center and Baird MS Research Center. Dr. Zivadinov receives personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Bayer, Genzyme-Sanofi, Novartis, Bracco Imaging, and Questcor Pharmaceuticals.