Saturday, 30 March 2013

CCSVI March 2013

Valdueza JM, Doepp F, Schreiber SJ, van Oosten BW, Schmierer K, Paul F, Wattjes MP. What went wrong? The flawed concept of cerebrospinal venous insufficiency. J Cereb Blood Flow Metab. 2013 Feb 27. doi: 10.1038/jcbfm.2013.31. [Epub ahead of print]

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis(MS), coining the term of chronic cerebrospinal venous insufficiency ('CCSVI'). The diagnosis of 'CCSVI' is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of 'CCSVI' could alleviate MS. Many investigators tried to replicate Zamboni's results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the 'CCSVI' concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the 'CCSVI' concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat 'CCSVI' in the care of MS patients, outside of the setting of scientific research.

This is open access so you can read and debate it yourself  but this study indicates that the concept of CCSVI may be based on thin ice
and this paper calls for a "complete halt to therapy".
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"With the ‘old’ ‘CCSVI’ criteria being refuted, the ‘new’ criteria seem to call for new confirmatory studies to confirm or refuse the new results. However, the scientific quality appears unaltered low, as the core statements of our critical discussion also apply to the new modified criteria"

I see the hate campaign will be on its way again however coupled with hints of the blinded trial not being positive then it is going to be increasingly difficult to argue against this view.

CoI: One of the authors works at the Blizard Institute (Neuroscience) & Barts Health


But if a group were going to try to refuse it it may be this next group

Zivadinov R, Magnano C, Galeotti R, Schirda C, Menegatti E, Weinstock-Guttman B, Marr K, Bartolomei I, Hagemeier J, Maria Malagoni A, Hojnacki D, Kennedy C, Carl E, Beggs C, Salvi F, Zamboni P. Changes of Cine Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis Treated with Percutaneous Transluminal Angioplasty: Case-control Study. J Vasc Interv Radiol. 2013 Mar 20. doi:pii: S1051-0443(13)00531-9. 10.1016/j.jvir.2013.01.490. [Epub ahead of print
PURPOSE:To investigate characteristics of cine phase contrast-calculated cerebrospinal fluid (CSF) flow and velocity measures in patients with relapsing-remitting (RR) multiple sclerosis (MS) receiving standard medical treatment who had been diagnosed with chronic cerebrospinal venous insufficiency (CCSVI) and underwent percutaneous transluminal angioplasty (PTA).
MATERIALS AND METHODS: This case-controlled, magnetic resonance (MR) imaging-blinded study included 15 patients with RR MS who presented with significant stenoses (≥50% lumen reduction on catheter venography) in the azygous or internal jugular veins. Eight patients underwent PTA in addition to medical therapy immediately following baseline assessments (case group) and seven had delayed PTA after 6 months of medical therapy alone (control group). CSF flow and velocity measures were quantified over 32 phases of the cardiac cycle by a semiautomated method. Outcomes were compared between groups at baseline and at 6 and 12 months of the study by mixed-effect model analysis.
RESULTS: At baseline, no significant differences in CSF flow or velocity measures were detected between groups. At month 6, significant improvement in flow (P<.001) and velocity (P = .013) outcomes were detected in the immediate versus the delayed group, and persisted to month 12 (P = .001 and P = .021, respectively). Within-group flow comparisons from baseline to follow-up showed a significant increase in the immediate group (P = .033) but a decrease in the delayed group (P = .024). Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group.
CONCLUSIONS: PTA in patients with MS with CCSVI increased CSF flow and decreased CSF velocity, which are indicative of improved venous parenchyma drainage.
If you have angioplasty on stenosed veins then you get increased blood flow. 

Mistry N, Dixon J, Tallantyre E, Tench C, Abdel-Fahim R, Jaspan T, Morgan PS, Morris P, Evangelou N.Central Veins in Brain Lesions Visualized With High-Field Magnetic Resonance Imaging: A Pathologically Specific Diagnostic Biomarker for Inflammatory Demyelination in the Brain. JAMA Neurol. 2013 Mar:1-6. doi: 10.1001/jamaneurol.2013.1405. [Epub ahead of print]

IMPORTANCE There is no single test that is diagnostic for multiple sclerosis (MS), and existing diagnostic criteria are imperfect. This can lead to diagnostic delay. Some patients require multiple (sometimes invasive) investigations, and extensive clinical follow-up to confirm or exclude a diagnosis of MS. A diagnostic biomarker that is pathologically specific for the inflammatory demyelination in MS could overhaul current diagnostic algorithms. OBJECTIVE To prospectively assess the diagnostic value of visualizing central veins in brain lesions with magnetic resonance imaging (MRI) for patients with possible MS for whom the diagnosis is uncertain. DESIGN Prospective longitudinal cohort study. The reference standard is a clinical diagnosis that is arrived at (after a mean follow-up of 26 months) by the treating neurologist with a specialist interest in MS. The 7-T MRI scans were analyzed at baseline, by physicians blinded to the clinical data, for the presence of visible central veins. 
PARTICIPANTS A consecutive sample of 29 patients referred with possible MS who had brain lesions detected on clinical MRI scans but whose condition remained undiagnosed despite expert clinical and radiological assessments. 
EXPOSURE Seven-Tesla MRI using a T2*-weighted sequence. MAIN OUTCOMES AND MEASURES The proportion of patients whose condition was correctly diagnosed as MS or as not MS, using 7-T MRI at study onset, compared with the eventual diagnosis reached by treating physicians blinded to the result of the MRI scan. 
RESULTS Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions. 
CONCLUSIONS AND RELEVANCE In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms.

This is not really CCSVI, but it just says that veins are at the centre of lesions in those that get diagnosed with MS.

17 comments:

  1. Controvercy continues and continues, but surely some day there will consensus. Buffalo University was involved in Premise study, which showed no beneficial effets with PTA and also this CSF study, which showed positive results when CSF flow was improved: "Altered CSF flow and velocity measures were associated with worsening of clinical and MR outcomes in the delayed group."

    In premise study researcher didn't find better flow after PTA. The idea of PTA is to affect flow, so no wonder with the result.

    In premise study PTA was done by A.Siddiqui and CSF study by Roberto Galeotti: just like in dopppler studies, one element is "operator dependency" (expertise, experience). MD S.Sclafani commented Premise study result:
    "It does document scientifically what happens when someone who has treated only 9 patients does a study"

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  2. Profits neurolandia doctors have repeatedly cited the Italian study on CCSVI that found a prevalence rate of CCSVI in patients with Ms of 3.26 percent. It was enthusiastically praised at ECTRIMS, where talking heads essentially stated that the CCSVI doesn't really even exist.

    Recently some of the media have included this prevalence of CCSVI of 3.26% in their brilliant articles.

    If this statistic is true, what do these new numbers?

    It is estimated that in recent years at least 40,000 people have been treated for CCSVI. Suppose that the prevalence rate of 3.26% is correct and apply that rate to those who received the treatment for CCSVI.

    This would mean that to have 40,000 treaties, 1,226,994 people should have tested the veins, to see if they were one of the 3.26% who really CCSVI.

    Basically what they're saying is that almost half of the 2.5 million people with Ms on planet Earth would be subjected to an examination ultrasound Doppler of the veins, to see if they qualified for the angioplasty treatment for CCSVI.

    The prevalence rate of 3.26 per cent is a complete invention. A total farce. The numbers simply don't add up. It's so absurd. They think we are so stupid?

    Neurolandia physicians continue to support the old theory of autoimmune SM of the middle of the last century. They continue their campaign of lies, bragging of their studies on medicines. Drugs that offer zero benefits, as shown in several long-term studies.

    JAMA: "among patients with relapsing-remitting multiple sclerosis, administration of interferon beta has not been associated with a reduction in the progression of disability.

    The campaign of misinformation continues to neurolandia. They continue to praise the medications to the SM still attacking this new theory.

    These helpful neuro had for decades owned by SM, but this now has changed. Were set aside by modern social media tools. Their entry was replaced and they know it ...

    The so-called experts talking about how dangerous the angioplasty. Or the prevalence of CCSVI in MS of 3.26 percent.

    Think they have an influence. But they didn't! Are simply showing their true face, in an attempt to stop the advance of the biggest medical discovery associated with a long list of neurological disorders, including Ms.

    When spreading trash studies, all they do is make themselves look ridiculous. They're so elitist, and absorbed into their perceived status, when they try to explain their cryptic and not proven autoimmune theory of the middle of the last century. Just do not understand.

    The disinformation campaign of neurolandia continues ... They are playing a nasty game of numbers, but no one supports them!

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    Replies
    1. False logic used to rubbish the three percent

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    2. False uneducated MOUSEDOCTOR who doesnt know anything other than copy n pasting links

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  3. Comments left on by accident?
    I wanted to ask you guys about the second study, Dr. Zivadinov's, showing increase in cerebrospinal fluid flow and decrease in cerebrospinal fluid velocity. Putting aside all thoughts of blood flow, what impact if any would these changes in CSF flow have on the brain?

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    1. Ok I thought so.
      I found a 1994 article just now that might answer might my question.
      "The pathological increase of plasma protein concentrations in CSF in neurological diseases could also be explained quantitatively by a decrease of CSF flow rate due to its bifunctional influence on CSF protein concentration: reduced volume exchange, and as newly stated, increased molecular net flux into CSF without change of permeability coefficients."
      http://www.sciencedirect.com/science/article/pii/0022510X94902984

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  4. At first Zivadinov was a darling of the CCSVI nutters because he jumped on the Zamboni machine. Now he is being questioned whether he can even perform the correct procedure to detect CCSVI after the results of his last study.

    Ultimately if you want to know if you have CCSVI, you are going to need to be checked by Zamboni himself.

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    Replies
    1. Dr. Zivadinov is a neurologist and does not perform the procedure himself.

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    2. Of course Zivadinov does not perform the procedure, but he does run the trial. The point is if his results were favorable to the CCSVI nutters there would be no questions asked. But since they are not quite what is expected, the methods need to be questioned even though Zivadinov was once a on team Zomboni. Maybe all of the other studies that were pro CCSVI by Zivadinov should be reevaluated.

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    3. Does Zamboni do the procedure himself? I thought he had some trouble with his hands?

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    4. Yeah, Dr. Zamboni cannot physically perform the procedure, so he has from the beginning had Dr. Galleoti doing the procedures.

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  5. One thing that is always concerned me regarding CCSVI is that the misdiagnosis rate of MS is generally regarded to be between 5%-15%. However, patients undergoing PTA are almost universally found to have tenosis and/or intraluminal or venous valve anomalies. Logically, 5%-15% of these patients don't even really have MS, so the near Universal finding of venous abnormalities during PTA is troublesome.

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    Replies
    1. Please excuse the typos in the above comment. Because of my disabilities, I must use voice recognition software to make these comments, and the VR abilities on the iPad I am using sucks…

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    2. Don't worry Kamikaze, compared to the good MouseDoctor, your comments read like Jane Austen by comparison! ;-)I suspect he is an undiagnosed dyslexic.
      All the best MD2

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    3. Whilst you think that some people getting angioplasty do not have MS, I think the Itlian group maybe be inferring that 96% of MSers getting venoplasty do not have CCSVI.

      and TWK your writing is much better than mine, so no need to excuse typos.

      Now back on internet rather than phone, comments have been turned off.

      However, I am not aware that there were any posts removed, so maybe it is possible to post on this subject without a tirade of abuse. Well done..I thnk

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