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Another negative study in Annals of Neurology

Posted: Tue Apr 05, 2011 5:01 am
by Mathd
http://onlinelibrary.wiley.com/doi/10.1 ... 6/abstract

it's funny how fast a negative study can be published in the Annals of Neurology!! and and the funnyest thing is how fast the can do a research!!

I am the only one that think it's just bullshit and that is now enough to balance all the finding we saw at the ISNVD meeting??

Posted: Tue Apr 05, 2011 5:21 am
by jay123
I was told by my doctor last week that every positive study they have been submitting is rejected, they are only interested in publishing negatives. The same holds true for presentations at their conference in Hawaii this week.

They are definitely worried about losing 'customers' to vein docs!

Posted: Tue Apr 05, 2011 5:57 am
by Cece
Proposed CCSVI criteria do not predict MS risk nor MS severity

Diego Centonze1,2,*,†, Roberto Floris3,†, Matteo Stefanini3, Silvia
Rossi1,2, Sebastiano Fabiano3, Maura Castelli1,2, Simone Marziali3, Alessio Spinelli3, Caterina Motta1,2, Francesco G. Garaci3, Giorgio Bernardi1,2, Giovanni Simonetti3DOI: 10.1002/ana.22436

Abstract
Objective:
It is still unclear if chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS), because substantial methodological differences have been claimed by Zamboni to account for the lack of results of other groups. Furthermore, it is still fully unexplored the potential role of venous malformations in influencing MS severity. This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses.

Methods:
In the present study, CCSVI was studied in 84 MS patients and in 56 healthy subjects by applying Zamboni method for CCSVI identification.

Results:
We found no significant differences (p=0.12) in CCSVI frequency between MS and control subjects. Furthermore, no differences were found between CCSVI-positive and CCSVI-negative patients in terms of relevant clinical variables such as disease duration, time between onset and first relapse, relapsing or progressive disease course, risk of secondary progression course. No statistically significant differences were also found between CCSVI-positive and CCSVI-negative MS subjects by analyzing direct measures of disability such as mean EDSS (p=0.07), mean progression index (p>0.1), and mean MS severity score (p>0.1). The percentage of subjects who reached EDSS 4.0 and 6.0 milestones was not different among CCSVI-negative and CCSVI-positive subjects, and no significant correlation was found between severity of disability and number of positive CCSVI criteria.

Interpretation:
Our results indicate that CCSVI has a role neither in MS risk nor in MS severity. Ann Neurol 2011.
The researchers were from Rome, Italy, at the Università Tor Vergata department of Neuroscience.

Here is the speed with which it was received, edited, and published. Is it abnormally fast?
Publication History
Accepted manuscript online: 30 MAR 2011 08:07AM EST
Manuscript Accepted: 22 MAR 2011
Manuscript Revised: 14 MAR 2011
Manuscript Received: 7 DEC 2010
By Zamboni method, they must mean the doppler ultrasound. If as was suggested by Zamboni's earlier work and by some of the clinical findings, the azygos is more severely stenosed in patients with higher EDSS, the azygous really can't be measured by doppler ultrasound. That means doppler is not a good tool for determining if worse CCSVI is associated with worse MS since it is only looking at the jugulars.

I had about as blocked of jugulars as you can get (80% and 100% closed, a factoid relevant to nearly every discussion :) ) but very low EDSS; I would have worked against their hypothesis.

Of course they did not even get that far, since they could not find a greater percentage of CCSVI in MS patient as compared to normals. Ten out of fourteen of the papers presented at the Neurology conference last fall did find the association between CCSVI and MS, so this one is in the minority there, but papers will continue to come in.
This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses.
I am so glad that the procedures are being offered. Remember last winter, when a person couldn't get treated for trying? Difficult times.

Posted: Tue Apr 05, 2011 8:47 am
by codefellow
jay123 wrote:I was told by my doctor last week that every positive study they have been submitting is rejected, they are only interested in publishing negatives. The same holds true for presentations at their conference in Hawaii this week.
That is a very serious allegation, and I would imagine difficult to prove. Can you tell us a little more about your doctor? Does he have some real inside information or is he just speculating like the rest of us?

Posted: Tue Apr 05, 2011 9:05 am
by bruce123
While I have no end of praise for Dr. Zamboni and everything he has done and continues to do for us, I cannot believe that all aspects of his far reaching hypothesis regarding the the relationship between CCSVI and MS will be proven to be true. His hypothesis is fascinating and makes sense but it is unlikely to be exactly as he theorises.

One area where he may be wrong is the statistical occurrence of CCSVI in pwMS. This is the area where many of the studies are focusing, including the studies that are funded by the money that we raised for the MS Societies.

I suggest that we keep our eyes on the prize. We know the procedure can help pwMS. We know it can provide relief from debilitating symptoms that no drug can even touch. We know it is relatively safe. There are many things we don't know but remember that negative findings on the many imaging studies does not lessen the importance of what this procedure can do for us and the promise that it holds for the future.

Bruce.

Posted: Tue Apr 05, 2011 9:15 am
by 1eye
From outside, how can one even know the rate of occurrence of negative and positive papers (might be difficulty in defining that) or surmise that either they are being rejected or they are not being submitted? Wouldn't you have to be an editor to know for sure?

Maybe someone should ask?

Where did you get this information, Cece? Have I been missing that it is commonly supplied?
Publication History
Accepted manuscript online: 30 MAR 2011 08:07AM EST
Manuscript Accepted: 22 MAR 2011
Manuscript Revised: 14 MAR 2011
Manuscript Received: 7 DEC 2010

Posted: Tue Apr 05, 2011 9:24 am
by Cece
I clicked something on the abstract page, let me see:
Proposed CCSVI criteria do not predict MS risk nor MS severity

Diego Centonze1,2,*,†, Roberto Floris3,†, Matteo Stefanini3, Silvia Rossi1,2, Sebastiano Fabiano3, Maura Castelli1,2, Simone Marziali3, Alessio Spinelli3, Caterina Motta1,2, Francesco G. Garaci3, Giorgio Bernardi1,2, Giovanni Simonetti3DOI: 10.1002/ana.22436

Copyright © 2011 American Neurological Association

Issue

Annals of Neurology

Accepted Article (Accepted, unedited articles published online for future issues)

Additional Information(Show All)
I don't know if this is common or not, I hadn't paid any attention to this sort of thing until the discussion about negative articles being published more hastily than is the norm.

Posted: Tue Apr 05, 2011 10:46 am
by David1949
Maybe they should call it the "Anals of Neurology".

Posted: Tue Apr 05, 2011 6:20 pm
by Jugular
Anuses of Neurology?

Posted: Tue Apr 05, 2011 7:48 pm
by CureIous
And yet some worry about "scaring neurologists away from this website?", seems the more they are embraced and asked to the table, the more of the good silverware begins to disappear.

Could just be coincidence of course. It's just too bad that the good ones who are going to bat for us are so few and far between, but the other ones are "on mic" the second they step up to the podium.

As they say, if you can't blind em with brilliance, baffle em with bs.

Posted: Wed Apr 06, 2011 12:55 am
by sou
Cece wrote:By Zamboni method, they must mean the doppler ultrasound. If as was suggested by Zamboni's earlier work and by some of the clinical findings, the azygos is more severely stenosed in patients with higher EDSS, the azygous really can't be measured by doppler ultrasound. That means doppler is not a good tool for determining if worse CCSVI is associated with worse MS since it is only looking at the jugulars.
Per Dr. S. and Dr. Menegati, doppler ultrasound can not directly image the azygous vein, however it can give relatively good indication that there is some occlusion ar flow disturbance to it through the flow of vertebral veins.

Posted: Wed Apr 06, 2011 3:44 am
by frodo
sou wrote: Per Dr. S. and Dr. Menegati, doppler ultrasound can not directly image the azygous vein, however it can give relatively good indication that there is some occlusion ar flow disturbance to it through the flow of vertebral veins.
Besides all these negative studies forget one thing. It is enough that the MS of a subset of patients has a vascular origin to justify the treatment, because there could be more than one type of MS. Some years ago Neuromyelitis optica was considered inside the MS spectrum and now it is appart.

Posted: Wed Apr 06, 2011 6:19 am
by Cece
Good point, sou.

Posted: Wed Apr 06, 2011 11:59 am
by thornyrose76
Jugular wrote:Anuses of Neurology?
Arses of Neurology works for me!

Posted: Wed Apr 06, 2011 8:44 pm
by CureIous
frodo wrote:
sou wrote: Per Dr. S. and Dr. Menegati, doppler ultrasound can not directly image the azygous vein, however it can give relatively good indication that there is some occlusion ar flow disturbance to it through the flow of vertebral veins.
Besides all these negative studies forget one thing. It is enough that the MS of a subset of patients has a vascular origin to justify the treatment, because there could be more than one type of MS. Some years ago Neuromyelitis optica was considered inside the MS spectrum and now it is appart.
That was a good read on my break at work on my phone, I truly believe that one day, the broad brush term of MS will be related to a set of pathologies far narrower than it is now, as many of the patients now categorized as MS will be reclassified into some vein specific syndrome.

I have zero doubt, that if the CCSVI I had then, had been found, and corrected then, even after the first presenting symptom, the past 7 years would have been vastly different than they were.

I believe that the venous problems alone were enough to cause many of my symptoms, what else to explain why they went away and so far, have not come back at all?

Therefore, it is my opinion that in the future we will have have CIS and first presenters, who will be (beyond SOP MRI's and such), screened for AVS or anomalous vein syndrome (bored, making up terms), achieving an early disease course "course correction" and mitigating future damage. This of course encompassing a broad range of venous issues we are all familiar with, but too idiosynchratic to define narrowly.

Then there will be those who are 100% in the autoimmune category or "other" column and will comprise most of what we consider today to be PWMS.

The further along things go, the closer we will be to standardized early detection for high risk people (not sure how one would define that), or those at risk (say via trauma for instance), catching many thousands of cases and nipping them in the bud, mitigating the chances of future neurological damage.

As time goes on, and the knowledge and experience base grows, and the cases are caught earlier and earlier (think CIS people, who never progress further, and never need drugs due to early CCSVI intervention), the MS landscape of the future will look very very different.

But for now, treat those who want it, period.