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The science available to date supports the idea there may be a link between a condition called CCSVI and multiple sclerosis, says a new study that nevertheless warns it is too soon to draw "definitive conclusions."

The study, which informed the federal government's decision to go ahead with clinical trials into a possible treatment for the condition, was published Monday in the Canadian Medical Association Journal.

"I think the striking thing is just this incredible inconsistency, which is almost greater than anything I've seen in any meta-analysis I've done," Laupaucis said.

"Which I think means — I hate to say this as a researcher because it drives people crazy — but this is one of those areas where I think more research is needed. Because it's not clear why that difference is so large."

...should not have known if the subjects they were checking for vein abnormalities had MS or not. But blinding was not undertaken in three of the trials and in the others it was unclear how well the blinding actually worked, Laupaucis and his co-authors wrote.

"Ultrasound is a fairly subjective test. You can push a little harder or a little less hard on the neck when you're assessing the veins (and) it affects the results," Laupaucis said.

"If you know that a patient has MS or you know that a patient doesn't have MS, it might inadvertently affect your judgment about whether a subtle difference or a subtle abnormality is CCSVI or not."

Laupaucis and others cautioned that seeing a link or an association between a condition and a disease doesn't mean that the one caused the other. In fact, a commentary also published Monday warned against drawing that conclusion.

Dr. Robert Fox, a neurologist at the Mellon Center for Multiple Sclerosis at the Cleveland Clinic, noted the blocked veins could be the result of dehydration. MS often affects the bladder and as a result MS patients often prefer to remain a bit dehydrated so that they don't have to constantly run off to the bathroom, Fox noted in an interview from Cleveland, Ohio.

That may cause veins to look different in an ultrasound, he said. But that doesn't mean opening the blockages will resolve the symptoms that plague MS patients.

"If it (CCSVI) is there more commonly in MS patients, it doesn't mean that fixing it is going to help people feel better. We think a lot of MS is from permanent nerve injury from the inflammation. Permanent nerve injury to the spinal cord, to the brain, to the optic nerve," said Fox.

Fox's work is one of the studies being funding by the MS societies. He has also done consultancy work for several drug companies. Laupaucis's study was funded by CIHR. He has received honoraria for serving as a member of data safety monitoring boards for two drugs for MS; the trials were funded by Novartis Pharmaceuticals. Laupaucis is also on the editorial board of the Canadian Medical Association Journal.

1eye wrote:

"If it (CCSVI) is there more commonly in MS patients, it doesn't mean that fixing it is going to help people feel better. We think a lot of MS is from permanent nerve injury from the inflammation. Permanent nerve injury to the spinal cord, to the brain, to the optic nerve," said Fox.

Oh, well. We all might as well all give up and go home, then. Since there is no such thing as redundancy or plasticity... We're all corpses in the final analysis.

What's odd about Dr. Fox's argument is that a very large subset of MS patients have relapsing-remitting MS. During the remitting phase, there is healing and rerouting going on, neurologically speaking. Plasticity, as 1eye points out.

Dr. Robert Fox, a neurologist at the Mellon Center for Multiple Sclerosis at the Cleveland Clinic, noted the blocked veins could be the result of dehydration. MS often affects the bladder and as a result MS patients often prefer to remain a bit dehydrated so that they don't have to constantly run off to the bathroom, Fox noted in an interview from Cleveland, Ohio.

That may cause veins to look different in an ultrasound, he said. But that doesn't mean opening the blockages will resolve the symptoms that plague MS patients.

Jugular wrote:

Dr. Robert Fox, a neurologist at the Mellon Center for Multiple Sclerosis at the Cleveland Clinic, noted the blocked veins could be the result of dehydration. MS often affects the bladder and as a result MS patients often prefer to remain a bit dehydrated so that they don't have to constantly run off to the bathroom, Fox noted in an interview from Cleveland, Ohio.

That may cause veins to look different in an ultrasound, he said. But that doesn't mean opening the blockages will resolve the symptoms that plague MS patients.

It never ceases to amaze me how far in life some people can go missing a brain. Dr. Fox's brilliant supposition reminds me of a rhyme I often read in bathroom stalls. Sung to the tune of "Here I Sit Broken-hearted":

~Here I sit thirsty and crushed
The Doppler said my veins refluxed

Next time I think I'll take a chance
No CCSVI but pee my pants~

MarkW wrote:Ask a researcher to answer the CCSVI and MS question - the answer is 'more data is needed'.
Ask a business analyst the same question - the answer is 'I recommend diagnosis and treatment for CCSVI syndrome ......'

I feel sorry for Canadians with MS who have to deal with this. If you can afford to pay for yourself then travel to the closest clinic which offers catheter venograms and intravascular ultrasound and an experienced interventionalist. Then go home by land transport.

MarkW

Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a meta-analysis

Andreas Laupacis,
Erin Lillie,
Andrew Dueck,
Sharon Straus,
Laure Perrier,
Jodie M. Burton,
Richard Aviv,
Kevin Thorpe,
Thomas Feasby,
Julian Spears

+ Author Affiliations

From the Keenan Research Centre (Laupacis, Lillie, Straus, Perrier, Thorpe, Spears), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ont.; the Faculty of Medicine (Laupacis, Dueck, Straus, Aviv, Spears), University of Toronto, Toronto, Ont.; the Schulich Heart Centre (Dueck), Sunnybrook Health Sciences Centre, Toronto, Ont.; the Office of Continuing Education and Professional Development (Perrier), Faculty of Medicine, University of Toronto, Toronto, Ont.; the Department of Clinical Neurosciences (Burton), Hotchkiss Brain Institute, University of Calgary, Calgary, Alta.; the Department of Medical Imaging (Aviv), Sunnybrook Health Sciences Centre, Toronto, Ont.; the Dalla Lana School of Public Health (Thorpe), University of Toronto, Toronto, Ont.; and the Faculty of Medicine (Feasby), University of Calgary, Calgary. Alta.


Abstract


Background: It has been proposed by Zamboni and colleagues that multiple sclerosis is caused by chronic cerebrospinal venous insufficiency, a term used to describe ultrasound-detectable abnormalities in the anatomy and flow of intra- and extracerebral veins. We conducted a meta-analysis of studies that reported the frequency of chronic cerebro spinal venous insufficiency among patients with and those without multiple sclerosis.


Methods: We searched MEDLINE and EMBASE as well as bibliographies of relevant articles for eligible studies. We included studies if they used ultrasound to diagnose chronic cerebrospinal venous insufficiency and compared the frequency of the venous abnormalities among patients with and those without multiple sclerosis.


Results: We identified eight eligible studies: all included healthy controls, and four of them also included a control group of patients with neurologic diseases other than multiple sclerosis. Chronic cerebrospinal venous insufficiency was more frequent among patients with multiple sclerosis than among the healthy controls (odds ratio [OR] 13.5, 95% confidence interval [CI] 2.6–71.4), but there was extensive unexplained heterogeneity among the studies. The association remained significant in the most conservative sensitivity analysis (OR 3.7, 95% CI 1.2–11.0), in which we re moved the initial study by Zamboni and colleagues and added a study that did not find chronic cerebrospinal venous insufficiency in any patient. Although chronic cerebrospinal venous insufficiency was also more frequent among patients with multiple sclerosis than among controls with other neurologic diseases (OR 32.5, 95% CI 0.6–1775.7), the association was not statistically significant, the 95% CI was wide, and the OR was less extreme after removal of the study by Zamboni and colleagues (OR 3.5, 95% 0.8–15.8).


Interpretation: Our findings showed a positive association between chronic cerebrospinal venous insufficiency and multiple sclerosis. However, poor reporting of the success of blinding and marked heterogeneity among the studies included in our review precluded definitive conclusions.

“I think it does require more study — and that’s me speaking, not the group — but we’re at the stage where many MS patients are getting this procedure anyway,” said Laupaucis.

“I think it’s time to do a study where some patients get the procedure and some don’t.”

Dr. Andreas Laupacis, Li Ka Shing Knowledge Institute of St. Michael's Hospital in Toronto and his co-authors write:


"We found a strong and statistically significant association between chronic cerebrospinal venous insufficiency and multiple sclerosis. However, the large amount of heterogeneity among the study results prevents a definitive conclusion. The source of the heterogeneity is not clear. It is not obviously caused by differences in the definition of chronic cerebrospinal venous insufficiency, patient characteristics or the methodologic quality of the studies."


They continued writing:


"We also could not identify any factor that accounted for the large and problematic difference between the studies in the frequency of chronic cerebrospinal venous insufficiency among patients with multiple sclerosis."


According to the researchers, the difference could be due to the fact that the analysis included small sample sizes of the studies and also because of differences in ultrasound techniques and quality control, as ultrasonography results can vary depending on the training absolved and level of competence of each operator.

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: Clinical Correlates from a Multicentre Study

Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated.MethodWe analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian).

All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al.

Results: Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al.

Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS.

Conclusion: The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high.

Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

Author: Stefano BastianelloAlfredo RomaniGisela ViselnerEnrico Colli TibaldiElisabetta GiugniMarta AltieriPietro CecconiLaura MendozziMassimiliano FarinaDonatella MarianiAntonio GalassiClaudio QuattriniMarcello ManciniVincenzo BresciamorraAngela LagaceSan