Abnormal venous drainage of the brain and spinal cord in patients with MS

Investigators

A/Prof Brian Chambers, Austin Hospital
Ms Heather Cameron, Austin Health (Sonographer)
Ms Jayne Chambers, Austin Health (Sonographer)
Prof Richard Macdonell, Austin Health

Funding

• $35,000 for 2010

Project Summary

There are recent reports that patients with MS may have abnormal venous drainage of the brain and spinal cord compared to control subjects. This has been termed chronic cerebrospinal venous insufficiency (CCSVI). Furthermore, it is claimed that balloon dilatation or stenting of veins results in clinical recovery. Although these findings have yet to be confirmed by rigorous scientific study, patients with MS in Australia are seeking diagnostic testing and treatment.

This is a case-control study comparing the results of venous ultrasound examination in patients with MS with age and sex matched controls. It is the first study to be undertaken where the sonographer is unaware which subjects are patients with MS, achieved by recruiting only those patients without residual disability.

The project aims to use an established ultrasound service in an academic environment in Melbourne to study the venous drainage of the brain in patients with MS and, by comparison with the findings in healthy subjects, to independently demonstrate whether there is a significantly higher prevalence of venous drainage abnormalities in patients with MS.

Progress to date 

In 2010 A/Prof Brian Chambers was awarded a $35,000 project grant by MS Research Australia to investigate venous drainage in people with MS. This research was instigated following reports by overseas investigators that people with MS have abnormal venous drainage of the brain and spinal cord compared to people without MS. In addition, early findings suggested that balloon dilatation or stenting of veins results in clinical recovery of MS. Although these findings have yet to be confirmed by rigorous scientific study, MS patients in Australia are already seeking diagnostic testing and treatment.

A/Prof Brian Chambers and his colleagues at the University of Melbourne and Austin Hospital have designed a case-control study comparing ultrasound findings in people with MS with controls without MS that are matched by age and sex. The aim of the study is to independently demonstrate whether the prevalence of venous abnormalities varies in those with MS compared to the matched controls. The study is a ‘blinded’ design, or in other words, the sonographer does not know whether they are diagnosing a case or a control.

“To date we have studied 35 people with MS and 35 healthy control subjects, so we are just over one third of the way towards completion,” reports A/Prof Chambers. “Preliminary blinded analysis of the whole 70 cases, using the criteria proposed by Zamboni, indicates that CCSVI (chronic cerebrospinal venous insufficiency) is less prevalent than expected.” In fact, preliminary analysis has revealed that no subjects so far studied have CCSVI according to the criteria proposed by Zamboni. “Since our MS cohort are in the early stages of disease, this would imply that if CCSVI does occur in MS, it does not have a causal role, and it may only develop in more advanced MS,” explains A/Prof Chambers. “It is possible that CCSVI is mainly observed in advanced MS. This is supported by our observations in out-of-trial advanced MS patients.”

Analysis of preliminary results, before the completion of a study, must always be interpreted with caution and final conclusions can only be drawn at study completion. The investigators will continue to recruit their planned sample size of 100 patients and control pairs. Discussions with international investigators, including Zamboni, at the recent

Australasian Phlebology College meeting in Melbourne indicated that others use broader ultrasound criteria for diagnosing CCSVI. However, as yet there are no standardised validated criteria.

“Our data set includes a number of ultrasound parameters not included in the Zamboni definitions,” explains A/Prof Chambers. “We intend to apply advanced statistical methods to determine which if any ultrasound variables are more prevalent in MS. Our results in healthy controls will also provide the best available venous ultrasound data to give a ‘normal range’ for comparison.”

Based on the present recruitment rate we expect to complete recruitment by early 2012. The investigators also plan to present these findings at ECTRIMS (Congress of the European Committee for Treatment and Research in Multiple Sclerosis) in Amsterdam, October 2011.
 

Updated: 23/05/2011