麻豆传媒

Another study of cerebrospinal venous abnormalities has failed to confirm a link to multiple sclerosis (MS), this one conducted primarily by imaging specialists rather than neurologists.

Color Doppler ultrasonography performed on 39 MS patients and 26 healthy controls indicated that chronic cerebrospinal venous insufficiency (CCSVI) was present in most of both groups, with no greater prevalence in the MS patients relative to controls, according to Simone Marziali, MD, of the University of Rome Tor Vergata in Rome, and colleagues.

The researchers also found that the presence of CCSVI in MS patients was unrelated to the severity of disability, they reported online in Radiology.

That the study was published in the flagship publication of the Radiological Society of North America, rather than a neurology journal, distinguishes it from most of the other negative studies of CCSVI. Nine of the study's 11 authors were in the university's diagnostic imaging department.

Advocates of the CCSVI theory in the MS patient community have been skeptical of neurologist-run studies, in part because they suspect neurology researchers of being too cozy with the pharmaceutical industry, which would arguably lose billions of dollars in drug sales if MS were found to be fundamentally a vascular problem.

That is the crux of the CCSVI hypothesis, which 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.

But the CCSVI theory underwent a sudden revival in 2009 with publication by Paolo Zamboni, MD, of the University of Ferrara in Italy, of a case series in which he claimed that he had found CCSVI in all of the MS patients he studied and none of the healthy controls. He also reported that venous angioplasty procedures had reversed MS disability in many patients.

On the other hand, a series of reports by other groups have failed to confirm the findings. Either the researchers failed to find venous abnormalities in either patients or controls or, like the current study by Marziali and colleagues, it was common in all participant groups.

In May, the FDA issued a warning about risks associated with endovascular interventions in MS patients, saying that CCSVI had not been proven to be a factor in MS or even to exist at all.

In the current study, the researchers used the ultrasound imaging criteria established by Zamboni to diagnose CCSVI.

They identified the condition in 25 of the 39 MS patients and in 14 of the 26 controls (64% versus 54%, P-value not reported).

As expected, participants in both groups found to have CCSVI showed significant differences in hemodynamic variables such as cerebral blood flow and volume, measured with dynamic susceptibility contrast-enhanced MRI, relative to those without CCSVI.

However, "no significant interaction between MS and CCSVI was found for any hemodynamic parameters," Marziali and colleagues wrote.

Mean cerebral blood flow and volume in normal-appearing white matter, as identified with MRI scans, were approximately the same in patients versus controls.

Hemodynamic parameters were also not significantly related to severity of disability in the MS patients as measured by EDSS scores, the researchers reported.

One hemodynamic variable that did differ between MS patients and controls was mean transit time of blood in certain brain regions. Transit time appeared to be significantly increased in three of four areas of normal-appearing white matter evaluated, including the semioval center, periventricular, and occipital regions.

But the increased transit time was seen in non-CCSVI patients as well as those with the condition, suggesting that the alteration was a characteristic of MS rather than CCSVI, the researchers indicated.

"These results favor the hypothesis that CCSVI has no role in MS pathogenesis," the authors wrote.

"The results also call into question whether CCSVI can really be considered a pathologic condition or if it simply represents an 'epiphenomenon,'" they added, noting that the condition appeared to be common in study participants irrespective of MS diagnosis.

They noted several limitations of the study, including the small sample size and variability in the MRI hemodynamic scans.

Marziali and colleagues recommended additional studies in larger samples, including enough patients to allow stratification by different forms of the disease. Such studies should also attempt to correlate the hemodynamic results with MRI-measured lesion burdens and with phlebography images, they said.

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