Single-Center Studies Build Case for Venous Angioplasty in Multiple Sclerosis

Download this article's Factoid (Factoid 1, Factoid 2 in PDF (& PPT for Gold Subscribers)

Venous angioplasty can safely improve quality of life in patients with multiple sclerosis (MS), according to 2 abstracts presented March 25, 2012, at the Society of Interventional Radiology (SIR) Scientific Meeting in San Francisco, CA. One study confirmed the presence of venous abnormalities in MS patients, supporting a causal relationship between treatment and symptom relief, while the other found less pronounced benefits after angioplasty among those whose disease was progressing after a prior relapse, emphasizing the importance of patient selection.

Certain Subsets Fare Better

Kiran P. Sekhar, MD, and colleagues at Albany Medical Center (Albany, NY), retrospectively reviewed the outcomes of 213 MS patients who underwent angioplasty for chronic cerebrospinal venous insufficiency (CCSVI) at their center over a 4-month period. Among them, 192 (90%) completed the Multiple Sclerosis Quality of Life (MSQOL)-54 questionnaire before and after treatment. The mean response time was 109.4 days. Researchers divided patients into 3 categories of MS diagnosis:

• Primary progressive: gradually worsening disease without remission
• Relapsing remitting: acute attacks with intervals of slow improvement in symptoms
• Secondary progressive: slow deterioration after previous remission

Venous angioplasty alone was performed in 98.4% of patients, while the remaining 1.6% also underwent stent placement. On average, 2.2 vessels were treated per procedure.

Physical and mental health scores on the MSQOL-54 significantly improved after treatment, both in the study population as a whole and within the 3 diagnostic categories. However, the extent of those gains varied. For example, 59% of those with secondary progressive disease had improvements in physical health, compared with 77% of those with relapsing remitting or primary progressive MS. And only 50% of the secondary progressive group had improvements in mental health, compared with 74% and 70% of the relapsing remitting and primary progressive groups, respectively.

Moreover, there was a trend toward less mental health improvement in patients who had been diagnosed with MS more than 10 years ago compared with those diagnosed more recently (P = 0.071).

“A prospective randomized trial is needed to rigorously evaluate the role of endovascular CCSVI treatment in MS and to understand the implications of the present study in terms of patient selection,” the researchers conclude.

Stenosis Seen in Most Patients

In the second study, researchers led by Hector Ferral, MD, of Rush University Medical Center (Chicago, IL), reviewed their experience in performing 105 venous angioplasty procedures in 94 MS patients between June 2010 and September 2011. Half of the patients were classified as relapsing remitting, 34% as secondary progressive, 6.4% as primary progressive, and 6.4% as unknown.

Selective venography and intravascular ultrasound of the jugular and azygos veins showed stenosis in 94.7% of patients, while the remaining 5.3% had no signs of narrowing. Angioplasty was performed in all of the 179 veins deemed abnormal (> 50% stenosis or reflux). Indications for stent placement, seen in 2.8% of veins, were azygos vein kink and jugular vein occlusion. After venous angioplasty, patients received anticoagulation for 10 days and clopidogrel for 6 weeks.

Reintervention was required for jugular vein thrombosis (3.4%), restenosis on follow-up ultrasound (3.4%), and recurrent symptoms (3.4%). Another 3.4% of patients had bleeding at the puncture site. One patient died 4 months post-angioplasty of an unknown cause.

Over half of the 89 patients surveyed (53.9%) reported symptomatic improvement on the Multiple Sclerosis Impact Scale. The rest had either questionable (16.9%) or no improvement (29.2%). Those with relapsing remitting MS were most likely to see improvement, with 59.6% saying their symptoms had lessened.

“Our results confirm that venous abnormalities are common in patients with MS,” the investigators comment, noting that the procedure appears safe.

Absence of Evidence the Issue

In a telephone interview, L. Nelson Hopkins, MD, of University at Buffalo Neurosurgery (Buffalo, NY), told TCTMD that venous angioplasty for CCSVI in MS patients is controversial not because the procedure is particularly high risk, but rather because the evidence base is lacking.

“In theory, it’s a very plausible hypothesis,” he said. Venous abnormalities—both restenosis and valve issues—are often seen in this population, and virtually all the scarring in the brain and spinal cord of MS patients develops near veins. “In addition, there is definite evidence of iron deposits around the veins in MS, often in conjunction with these plaques. What that leads to is the hypothesis that elevated venous pressure or reflux results in increased venous pressure in the deep cerebral veins. That then leads to leakage of . . . red blood cells outside the veins in the brain tissue. That results in a tremendous inflammatory response. And that may eventually lead to an immunological response that is actually the cause of MS.”

Michael D. Dake, MD, of Stanford University Medical School (Stanford, CA), agreed that “from an interventional standpoint, [angioplasty in MS] appears to be generally safe.” However, the mechanism is far from simple, he said in a telephone interview with TCTMD.

“This is a complex issue, . . . and I don’t think anyone would ever say this is curing MS. It may be modifying some of the symptoms,” Dr. Dake noted. “The real question is whether it’s altering the progression or trajectory of the disease. That’s what I think people would like to be in a position to examine and eventually be able to say something authoritative about.”

Dr. Hopkins noted that so far what has been documented is subjective improvement in symptoms such as fatigue, sleep problems, emotional well-being, and cognition. “Those soft findings seem to be the ones that improve the most. Patients with hard, objective neurologic symptoms like a neurologic deficit or weakness in an arm or a leg are much less likely to respond,” he said, as are those who have had MS longer.

Unfortunately, the data from the 2 SIR abstracts is retrospective and lacks objective neurologic evaluation, Dr. Hopkins said. The survey method, he added, “could be fraught with heavy placebo effect.”

Moving Forward

Dr. Hopkins said the PREMISE trial, being conducted at his institution, will address these issues. The single-blind study, which has randomized 20 patients to venous angioplasty or control, involves neurologic evaluation by an independent observer and measures serial MRI changes over time.

Though the SIR abstracts show only subjective improvement, they do use validated surveys and help lay the groundwork for future research, Dr. Dake pointed out. “It’s like a detective story you’re working through a clue at a time,” he said.

Trying to study this indication is “not simple and I’m not sure it should be,” Dr. Dake said of his own experience in designing an upcoming trial.

“Right now we’re trying to get our protocol through the [institutional review board] but more importantly now the [US Food and Drug Administration] has gotten involved and wants [investigational device exemptions] even it’s going to be just a balloon,” he said, explaining that few trials have tested venous angioplasty. “That requires getting the agency to review and approve not just the protocol but the type of device you would use and [the manufacturer].”

Importantly, the PREMISE trial does not include stenting, Dr. Hopkins stressed. “If [angioplasty is] done carefully, this is not a high risk procedure,” he said. “I think if you start dropping stents in everybody, that could be a problem [because the] hardware can get loose and can cause thrombosis. It’s just another level of risk that you’re introducing.”

 

---

Sources:
1. Sekhar KP, Mandato K, Rucker W, et al. Short-term outcomes after endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis. Presented at: Society of Interventional Radiology Scientific Meeting; March 25, 2012; San Francisco, CA.

2. Ferral H, Behrens G, Turner Y, Souman T. Clinical experience in the management of CCSVI: Single-center experience. Presented at: Society of Interventional Radiology Scientific Meeting; March 25, 2012; San Francisco, CA.

 

 

Related Stories:

• Jugular Angioplasty for MS May Improve Perceived Quality of Life
• Study Refutes Venous Hypothesis in Multiple Sclerosis, Weakening Argument for Stenting

Click here for a listing of companies that provide support to the Cardiovascular Research Foundation, owner and operator of TCTMD.