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Australian results published on prevalence of CCSVI in early MS

17th September, 2012

Australian researcher, A/Prof Brian Chambers of the Austin Hospital, Melbourne, has published the results of his MSRA-funded study into the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in early MS (view the abstract here).

CCSVI is a condition where drainage of blood from the brain and spinal cord is impeded. It is thought CCSVI may contribute to the development or symptoms of MS and was originally described by Dr Zamboni of Italy in 2009. In his sample, all people with MS had CCSVI whereas healthy individuals showed no evidence of CCSVI. Subsequent studies have been unable to replicate this marked difference in CCSVI prevalence. Some studies have found an increased prevalence of CCSVI in MS, but have also shown that it is present in healthy individuals and in people with other neurological diseases (OND). For earlier round-ups of CCSVI news, please type ‘CCSVI’ into the search box of this website.

Australian results

A/Prof Chamber’s study tested whether CCSVI was more prevalent in people with CIS or mild MS, which would imply a role for CCSVI in the development of MS. The study examined 70 people, made up of 94% with relapsing remitting MS with an expanded disability score (EDSS) of 2 or less and 6% with clinically isolated syndrome (CIS – a first attack of MS-like symptoms) and compared them to 70 healthy individuals. Controls were unrelated to the people with MS and were matched for age and sex.

All subjects were examined by ultrasound using the criteria published by Dr Zamboni, with CCSVI defined as the presence of two or more Zamboni criteria. A/Prof Chambers communicated closely with Dr Zamboni to ensure he was interpreting the criteria according to Dr Zamboni’s descriptions. The Australian team also derived their own criteria for venous abnormalities, which were closely related to the Zamboni criteria, but with defined parameters in relation to flow alterations and internal jugular vein narrowing.

The venous flow parameters were studied with subjects lying down on their backs (supine position) and sitting postures. Careful measures were taken to ensure that the sonographer did not know whether participants had MS, including no discussion of clinical status with the subject and the sonographer being absent from the room while subjects were positioned on, and removed from, the couch. A questionnaire conducted with the sonographer after each subject confirmed that blinding was successful.

Only one individual, a person without MS, satisfied the Zamboni definition of CCSVI. However, 19 MS subjects and 13 controls had Zamboni criteria abnormalities, this difference was explained by an increased prevalence of internal jugular vein narrowing, defined as cross-sectional area 0.3cm2 or less. Using the teams’ more clearly defined measure of stenosis, the difference disappeared. This more rigorous method was designed to avoid potential errors introduced by vein compression or normal side to side variation in vein diameter. Further analysis revealed an abnormal internal jugular vein valve in 7 people with MS and one control.

The team concluded that CCSVI does not have a causal role in MS. However, an apparent increase in internal jugular vein abnormalities in people with MS warrants further investigation.

Due to copyright conditions we are not able to provide the full paper. For those who wish to view the full details of the paper, it can be requested through the MSA-ACT/NSW/VIC MS Library, library@msaustralia.org.auor view the abstract via the website of the Multiple Sclerosis Journal

Results from other recent CCSVI prevalence studies

The results of some previous studies have indicated that people with more severe MS or a longer duration of MS may have an increased prevalence of CCSVI compared to those in the earlier stages of MS. This has led to the suggestion that CCSVI may be a consequence of MS rather than a cause.

A recently published paper by Simka and colleagues from Poland aimed to investigate this possibility. The group devised criteria to describe the severity of CCSVI, including number of affected veins and degree of abnormality. They looked to see if CCSVI severity was linked to disease duration in 353 people with MS who were part of a clinical trial of endovascular treatment for CCSVI. They observed no correlations between the severity of CCSVI and duration of MS. They conclude that MS had no significant impact on the development of venous pathology and venous malformations are most likely to be congenital (present at birth).

In contrast to this study, another recently published study by Patti and colleagues from Italy concluded that CCSVI is related to the severity of MS disability. They looked at the prevalence of CCSVI in 148 people with MS compared to 20 people with CIS, 40 with other neurological diseases (OND) and 172 healthy controls. The sonographer attended a training session on CCSVI criteria with Dr Zamboni and careful measures were taken to ensure the sonographer did not know the subjects’ clinical status. They found that CCSVI was more common in people with MS compared to healthy controls, CIS and OND. They found that the association of CCSVI with MS was much stronger in those who had the disease for more than 144 months and those with secondary progressive and primary progressive forms of MS.

A team of radiologists from Italy have also recently published results that suggest there is no association of CCSVI with MS. The group led by Garaci published their results in the journal Radiology in August (click here to view the abstract). The study examined a small group of 39 patients with MS and 26 healthy controls. Just over half of each group had CCSVI, suggesting that CCSVI is not more prevalent in people with MS. The results indicate that CCSVI is associated with reductions in cerebral blood volume and cerebral blood flow, but this occurred irrespective of the presence or absence of MS. They found no association between CCSVI and neurological function or disability progression in people with MS. The study also revealed that people with MS had a reduction in the mean transit time of blood in the normal appearing white matter (white matter with no evidence of lesions) of the brain, but that this occurred in all people with MS regardless of CCSVI status. The authors conclude that CCSVI has no role in the pathology of MS.

The journal Neurological Research has devoted its current issue, available on-line this week, to vascular aspects of MS. The series of articles include a number of reviews of the current status of knowledge relating to CCSVI in MS, cardiovascular risk factors in MS and MRI imaging techniques. A new technique for the post-mortem assessment of vascular pathology is described. One study using MRI with phase contrast to image blood flow in the internal jugular veins of people with MS suggested stenosis is associated with reduced blood flow.

CCSVI treatment study

Dr Hubbard from the USA has published results of the clinical effects following venoplasty for CCSVI in MS. The results are published in Journal of Vascular and Interventional Radiology (view the abstract here). 259 patients were treated for CCSVI with venoplasty. Magnetic resonance venography was performed prior to treatment. 2.5% of patients also received stents. Patients were assessed using the Multiple Sclerosis Impact Scale (MSIS) before and after treatment. The results indicate an improvement in the physical component of the MSIS of 67% at 1 month and 53% at 6 months after treatment compared to the pre-treatment score. The psychological scale improved by 53% at 1 month and 44% at 6 months post-treatment. Women appeared to receive more benefit than men and people with primary progressive MS showed less improvement. Only one serious adverse event was recorded of deep vein thrombosis at the catheter insertion point. The authors conclude that venoplasty is a safe procedure which produces significant clinical improvement. However, there was no comparison with a placebo control group (such as sham surgery in which the catheter is inserted, but the balloon is not inflated). The group plan to conduct further follow-up analysis at 12 months following treatment.

Further results of other ongoing prevalence studies, including the large North American studies, are expected to be released in October at the European Committee for Treatment and Research in MS (ECTRIMS) conference.

For information on the planned clinical trial of venoplasty in MS to be undertaken at the Alfred Hospital, Melbourne, please click here