麻豆传媒

The embattled theory that multiple sclerosis is caused by obstructed cerebrospinal veins took another hit, as a much anticipated imaging study found no differences between patients and healthy individuals.

An assessor-blinded analysis of catheter venography images in 65 patients with MS, 46 of their siblings, and 32 unrelated healthy individuals identified just one person in each group as meeting criteria for "chronic cerebrospinal venous insufficiency" (CCSVI), according to , of the University of British Columbia in Vancouver, and colleagues.

Using broader definitions of cerebrospinal venous narrowing or stenosis, most people in each group qualified, whether imaged with catheter venography or ultrasound, the researchers reported online in The Lancet.

Traboulsee and colleagues concluded that CCSVI as proposed by Paolo Zamboni, MD, of the University of Ferrara in Italy, is a "rare finding" and that venous imaging results "do not distinguish patients with multiple sclerosis from healthy controls."

The researchers added that catheter venography is "the gold standard for the assessment of venous stenosis because it details the venous anatomy with high spatial and temporal resolution."

The study had been , who hoped it would support the Zamboni theory. (Skeptics, on the other hand, had already considered it dead after a series of negative studies.)

Zamboni -- himself a vascular surgeon -- and colleagues set off a firestorm with a 2009 report that CCSVI, as they defined it, was versus none of 235 controls. In a subsequent paper, he reported that endovascular treatment (venoplasty plus stenting in some cases) dramatically relieved MS symptoms in most cases.

The CCSVI hypothesis holds that MS results from, or is exacerbated by, occlusions in the veins that drain blood from the brain. The resulting backup of blood in the brain is proposed to cause inflammation and, in turn, the destruction of nerve fibers characteristic of MS.

Vascular theories of MS have been around for decades but had faded into the background in recent years as research pointed to autoimmune processes as the cause of MS, bolstered by the success of drugs targeting immune components in delaying, if not preventing, disease progression and disability.

Although Zamboni's papers were seized upon by many in the MS community as the new way forward, his early studies were not blinded, and attempts by neurologists and radiologists to replicate them have consistently failed.

Most recently, in 2012, a group of Italian researchers reported that blinded analysis of nearly 2,000 patients and controls found CCSVI in only a tiny minority of both groups. Another study from Canada published 2 months ago came to a similar conclusion.

Some other studies yielded results more like those reported Tuesday by Traboulsee and colleagues, with cerebrospinal venous abnormalities found to be relatively common in both MS patients and in controls, with no difference in rates.

Traboulsee and colleagues performed venography and/or ultrasound imaging in a total of 177 MS patients, siblings, and controls at two Canadian centers. Venography data were available for 149 of these individuals. Data were analyzed according to Zamboni's criteria, which gave a diagnosis of CCSVI if any two of five different findings were present, or if there were areas in the internal jugular or azygous veins of more than 50% narrowing seen either on venography or in measurements of venous blood flow.

The ultrasound results were CCSVI-positive by Zamboni's criteria for 44% of the MS patients, 31% of their healthy siblings, and 45% of the unrelated controls, the researchers found.

More than 50% venous narrowing according to venography was found in 74% of MS patients, 66% of siblings, and 70% of controls. When identified by reductions in venous blood flow, narrowing was present in 51% of patients, 45% of siblings, and 54% of controls.

Ultrasound studies disclosed no abnormalities in half the MS patients as well as in half of the non-MS participants. Rates of absent valves, asynchronous valves, immobile valves, and valves that did not close fully were also nearly identical in patients versus controls.

Traboulsee and colleagues also found that ultrasound and venography findings often disagreed. Using the venography results as the standard, they calculated a sensitivity of 40.6% (95% CI 31.1%-50.8%) for ultrasound in detecting 50% venous narrowing and a specificity of 64.3% (95% CI 48.0%-78.0%).

"Our results ... challenge both the validity of ultrasound for the purpose of detecting chronic cerebrospinal venous insufficiency and its existence as a disorder," the researchers wrote -- a direct slap at Zamboni and his supporters, who have relied on ultrasound as the principal method for diagnosing CCSVI.

And, noting the high prevalence of venous narrowing in both patients and controls, they argued that their study "supports the contention that venous narrowing is a common anatomical variant."

Traboulsee is currently leading a intended to recruit 100 MS patients. Results are expected in 2015. A similar but much smaller trial reported earlier this year failed to find any benefit for the procedure.

At the recently concluded annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, that about half of individuals who had undergone endovascular treatments on their own initiative reported symptomatic improvements when interviewed shortly after the procedure.

But 6 months later, fewer than 20% indicated that their mobility, fatigue level, or general health were improved from their presurgical baseline.

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