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LYON, France -- Patients undergoing cranial venoplasty as a multiple sclerosis therapy rarely showed improvement in objective disease measures, although half said they felt better, according to a large Italian study reported here.

Among 462 patients who had endovascular procedures in an attempt to cure or relieve their disease, the vast majority had no change or worsening in disability as measured by EDSS scores, and approximately one-third had relapses and/or new MS-type brain lesions visible on MRI scans, said Angelo Ghezzi, MD, of the University of Milan in Italy.

Fifteen patients in the cohort experienced serious adverse effects following the procedures that could have been treatment-related, including a fatal MI, a nonfatal stroke, and seven cases of jugular thrombosis.

However, 53% of the patients told their neurologists that their symptoms had improved, Ghezzi said at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.

He said that the latter finding most likely reflected the "high expectations" that patients had from the treatment, which is often billed as "liberation therapy" in Italy and elsewhere. But he also emphasized that patients could have realized genuine improvements in symptoms such as fatigue that are not well measured in the EDSS system.

The findings came from a registry involving 33 MS clinics across Italy, in which neurologists contribute data on their patients who had undergone venoplasty procedures for their MS.

These procedures are based on the controversial theory that a condition called chronic cerebrovascular venous insufficiency (CCSVI) is responsible for MS.

Under this theory, obstructions in large veins draining the skull cause increased vascular pressure within the brain, which in turn causes inflammation that leads to the immune derangements and nervous-system damage characteristic of MS.

It was first advanced by Paolo Zamboni, MD, of the University of Ferrara in Italy, whose 2009 published report galvanized the MS clinical and patient communities. In that report, he claimed that every MS patient he examined met criteria for CCSVI, whereas the condition was not present at all in a control group.

Zamboni, a vascular surgeon, also reported that all patients undergoing venoplasty in his clinic showed substantial improvements in MS symptoms.

But the theory has been widely attacked by other researchers. Numerous attempts by neurologists and radiologists to replicate Zamboni's findings have failed, either because they could not find CCSVI in their patients or because it was commonly present in controls as well as in patients.

Nevertheless, some endovascular surgeons have been willing to perform jugular venoplasty on MS patients, with a number aggressively advertising the procedure.

The controversy prompted the Italian Society of Neurology to establish a database on patients undergoing such procedures. Data are contributed by MS clinics and include patients' demographic information, presurgical diagnoses and neurological status, objective and patient-reported outcomes, and adverse effects.

Of the 462 patients with at least 3 months of follow-up after surgery, 222 had been diagnosed with relapsing forms of MS, 133 had primary progressive MS, and 107 had a secondary progressive form. Mean disease duration ranged from 12 to 17 years for these three groups.

About 80% of the relapsing-remitting and secondary progressive patients had received standard MS drug therapies, as had 24% of those with primary progressive disease for which no treatment has been proven effective.

Mean EDSS scores before surgery in the three diagnostic groups were 3.7 (SD 1.9), 6.2 (SD 1.2), and 6.0 (SD 1.5) for the relapsing-remitting, secondary progressive, and primary progressive patients, respectively.

Ghezzi reported that, for the whole cohort, the mean EDSS score of 5.2 (SD 2.0) at postsurgical follow-up was essentially unchanged from the presurgical mean of 4.9 (SD 2.0).

This was true as well for subgroups of patients stratified by duration of follow-up. The mean score among 248 patients evaluated more than 6 months after the procedure was 5.1 compared with 4.8 prior to surgery. Similarly, for those assessed less than 3 months after surgery, the mean EDSS score was 5.2 versus 5.1 preoperatively.

Only about 30 patients in the cohort showed an EDSS improvement of at least 0.5 points after the procedure. Scores were unchanged in some 260 patients. The remainder had scores worsen by at least 0.5 points.

Among 171 patients with pre- and postsurgical MRI scans, new lesions were seen in 36% and gadolinium-enhancing lesions were seen in 26%. About 20% of patients with relapsing MS developed relapses during a median 29 weeks of follow-up (interquartile range 9 to 33 weeks).

In contrast to these objective measures, though, about half of patients believed their symptoms had improved, the database indicated. Some 6% of the entire cohort indicated that they had only transitory improvement, but 47% rated their condition as definitely improved. Only 13% indicated that symptoms had worsened.

The researchers examined objective data in the patients who had reported subjective improvement. In this group, as in the entire cohort, there was no change in mean EDSS scores.

Adverse effects of any severity were uncommon, Ghezzi reported. Fewer than 8% of patients had mild effects such as bruising at the catheter insertion site or asthenia.

Only 3% of patients had events considered serious, but these were very concerning, Ghezzi suggested.

They included a fatal MI 10 weeks after surgery, one nonfatal stroke 12 weeks later, and seven cases of jugular thrombosis diagnosed from 2 days to 10 months after surgery (five occurring within 6 weeks). Other serious events included tetraventricular hydrocephalus, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, and severe bleeding from a decubitus ulcer while taking a postsurgical anticoagulant.

Ghezzi said the disconnect between subjective and objective efficacy measures "can be largely explained as a placebo effect, considering the high expectations for a procedure called liberation."

But he also acknowledged several significant limitations of the analysis -- its retrospective nature, lack of control group and blinding, and what he called the "possible bias of patient inclusion."

On the other hand, he said, the results reflected what he considered "the real life of clinical practice."

A separate Italian study reported here also sought to shed light on the value of the CCSVI theory in MS.

Unveiled at a press conference in advance of its scheduled presentation here on Saturday, the imaging study examined nearly 2,000 individuals, including patients with MS and other neurological diseases as well as healthy controls.

Led by Giancarlo Comi, MD, of the University of Milan, it found that CCSVI was present in fewer than 5% of MS patients and in only slightly lower percentages of the healthy controls and patients with other conditions.

Based on those results, the Italian Multiple Sclerosis Society, which funded the approximately $2-million study, issued a statement declaring that "CCSVI is not a disease connected to multiple sclerosis."

Consequently, it continued, "there is no need [in clinical practice] to carry out additional tests to diagnose CCSVI, nor is vein surgery required."

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