Further Evidence Discredits Venous Hypothesis in Multiple Sclerosis

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Casting doubt on a controversial theory supporting percutaneous treatment for multiple sclerosis (MS), a new study published online August 14, 2013, ahead of print in PLOS ONE finds no evidence of reflux, stenosis, or blockage in the internal jugular or vertebral veins of patients who have the disease.

In 2006, the first of several studies by Paolo Zamboni, MD, of Azienda Ospedaliero-Universitaria di Ferrara (Ferrara, Italy), and colleagues reported evidence of cerebral venous hypertension or chronic cerebrospinal venous insufficiency (CCSVI) in patients with MS but not in control subjects, giving rise to the theory that angioplasty with stenting may help alleviate the condition. Since then, a number of researchers have tried and failed to verify Dr. Zamboni’s results, but despite this, some clinicians continue to use the treatment.

For the current study, researchers led by Ian W. Rodger, PhD, of McMaster University (Hamilton, Canada), matched 100 MS patients with 100 controls who had no known history of MS or other neurological conditions. All subjects underwent same-day ultrasound imaging and MRI from September 2010 to June 2011. Mean age was 48 years, and 74% were female. In addition, MS patients were equally distributed among the various symptom subtypes (benign, relapsing/remitting, secondary progressive, and primary progressive).

Dr. Rodger and colleagues looked for evidence of 5 criteria defined by the Zamboni research as necessary for the diagnosis of CCSVI, and which purportedly increase cerebral venous pressure:

  • Reflux in the internal jugular veins or the vertebral veins in sitting and supine posture
  • Reflux or no flow in the deep cerebral veins
  • High-resolution B-mode evidence of proximal internal jugular vein anomalies or stenosis
  • Flow not detectable by Doppler in the internal jugular or vertebral veins despite numerous deep inspirations in sitting and supine posture
  • Reverted postural control of the main cerebral venous outflow pathways

Evidence for CCSVI Lacking

Using color and duplex Doppler, no evidence of reflux was found in either the internal jugular or vertebral veins in any patient. A deep cerebral vein was not seen in 1 MS patient, but there was no evidence of either reflux or cessation of flow observed.

Flow was seen in all patients, with the exception of 1 control in whom 1 vertebral vein was not seen in the supine position. There was also no evidence of blockage.

Only 1 MS patient met 2 of the 5 Zamboni ultrasound criteria for CCSVI, such that there was no difference between MS patients and controls (P = 0.991). There were also no differences in either the intracranial or extracranial venous flow velocities or venous architecture between cases and controls.

An ‘Unproven Hypothesis’

“We found no evidence to support the hypothesis that CCSVI is associated with multiple sclerosis,” Dr. Rodger and colleagues write. “Furthermore, given the relatively high age of the patient population in our study the data substantiate the view that CCSVI is not a late secondary phenomenon of MS and is not associated with disability.”

The researchers call the Zamboni criteria “arbitrary in number and essentially an unproven hypothesis.” 

In a press release, Dr. Rodger commented: “This is the first Canadian study to provide compelling evidence against the involvement of CCSVI in MS. Our findings bring a much needed perspective to the debate surrounding venous angioplasty for MS patients.”

Source:

Rodger IW, Dilar D, Dwyer J, et al. Evidence against the involvement of chronic cerebrospinal venous abnormalities in multiple sclerosis: A case-control study. PLOS ONE. 2013;Epub ahead of print. 

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Disclosures
  • Dr. Rodger reports no relevant conflicts of interest.

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