Saturday, 29 June 2013

CCSVI June



OBJECTIVE. The purpose of this study is to report the 30-day morbidity and mortality associated with the endovascular diagnosis and management of chronic cerebrospinal venous insufficiency. MATERIALS AND METHODS. The medical records of 95 consecutive patients (60 women and 35 men) with a mean age of 48 years (age range, 25-66 years) who underwent diagnostic endovascular evaluation and intervention for chronic cerebrospinal venous insufficiency between June 2010 and September 2011 were reviewed retrospectively. All patients had a diagnosis of multiple sclerosis by McDonald criteria. Endovascular evaluation of the internal jugular and azygos veins was performed with digital subtraction venography and intravascular ultrasound. Indications for percutaneous transluminal angioplasty (PTA) were venographic findings of a greater than 50% diameter stenosis, the presence of reflux on digital subtraction venography, greater than 50% cross-sectional area stenosis by intravascular ultra-sound, or a finding of abnormal thick valves or webs by either method. The primary endpoint of this study was the 30-day mortality, and the secondary endpoint was the presence of major complications. Results are presented as means and percentages. 
RESULTS. A total of 107 procedures were performed in 95 patients. Endovascular evaluation showed venous lesions requiring intervention in 90 of 95 patients (94.7%) and was negative in five of 95 patients (5.3%). A total of 193 venous lesions were treated; angioplasty was technically successful in 188 of 193 (97.4%) lesions. Internal jugular vein thrombosis after PTA was identified in three of 95 (3.2%) of the treated patients. Bleeding at the puncture site not requiring transfusion occurred in four of 95 patients (4.2%). There were no reported procedure-related deaths. 
CONCLUSION. The results of the current study suggest that endovascular evaluation and management of chronic cerebrospinal venous insufficiency is safe, with low morbidity and no procedure-related mortality

CCSVI treatment has low frequency of side-effects in this study 

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear.

The last line says it all. This open source so you can read and agree/disagree if you want.

Djordje R, Nenad I, Jovo K, Dragan S, Zelimir A, Slobodan T, Nikola A, Srdjan B, Petar O Incidence and distribution of extravascular compression of extracranial venous pathway in patients with chronic cerebrospinal venous insufficiency and multiple sclerosis. Phlebology. 2013 May. [Epub ahead of print]

OBJECTIVE:To examine the incidence and distribution of extravascular compression of the extracranial venous pathway (the jugular and/or azygous veins) in multiple sclerosis patients with chronic cerebrospinal venous insufficiency evaluated by mulitislice computer tomographic angiography.
METHODS AND RESULTS: Study group consisted of 51 consecutive patients with multiple sclerosis in whom chronic cerebrospinal venous insufficiency was diagnosed by colour Doppler sonography (CDS). Mulitislice computer tomographic angiography was performed in all patients, and it revealed significant extravascular compression (>70%) of extracranial venous pathway in 26 patients (51%), while in 25 patients (49%) no significant extravascular compression was seen. Extracranial compression due to transverse processus of cervical vertebrae was seen in 23 patients, carotid bulb compression was seen in two patients, and in one case, compression presented as a thoracic outlet syndrome.
CONCLUSION: Our data indicate that extravascular compression of the extracranial venous pathway is frequent in multiple sclerosis patients with chronic cerebrospinal venous insufficiency, and that it is mainly due to compression caused by transverse process of cervical vertebrae. Further studies are needed to evaluate potential clinical implications of this phenomenon.

Yet further evidence that the vascular problems are not causal otherwise it would be 100%. What is going on?

Mezei Z, Olah L, Kardos L, Kovacs RK, Csiba L, Csepany T. Cerebrovascular hemodynamic changes in multiple sclerosis patients during head-up tilt table test: effect of high-dose intravenous steroid treatment. J Neurol. 2013 Jun 12. [Epub ahead of print] 
Demyelination in multiple sclerosis (MS) may cause damage to the vegetative nervous system. Our objective was to examine cerebral autoregulation assessed via blood pressure and cerebral blood flow velocity fluctuations during head-up tilt table testing. We also investigated the effects of high-dose intravenous corticosteroid treatment. Transcranial Doppler registration of middle cerebral artery blood flow velocity and continuous blood pressure and heart rate monitoring were performed at rest and during tilt table testing in 30 MS patients. Ten age-matched healthy subjects were also examined as controls. Correlations between mean arterial blood pressure (MBP) and cerebral blood flow velocity (CBF) fluctuations were averaged, yielding the correlation coefficient index Mx. For a subgroup of 11 patients with acute exacerbations, results were also evaluated before and after methylprednisolone treatment (1 g/day intravenously for 5 days). No significant differences in the autoregulatory indices were seen between patients and controls, or between pre- and post-steroid results. Modeling CBF velocity changes associated with a 1-mmHg increase in MBP, significant differences (p < 0.05) were detected in patients vs. controls, and also after vs. before steroid administration. We conclude that cerebrovascular autoregulation impairments are detectable in early phase MS. Corticosteroid treatment has a significant effect on haemodynamic changes in acute exacerbations.

van Zuuren EJ, Fedorowicz Z, Pucci E, Jagannath V, Robak EW.
BACKGROUND: It has been recently hypothesised that chronic cerebrospinal venous insufficiency (CCSVI) may be an important factor in the pathogenesis of multiple sclerosis (MS). The proposed treatment for CCSVI is percutaneous transluminal angioplasty, also known as the 'liberation procedure', which is claimed to improve the blood flow in the brain, thereby alleviating some of the symptoms of MS. Our objective was to determine the effects of percutaneous transluminal angioplasty used for the treatment of CCSVI in people with MS.
METHODS:We searched the following databases up to June 2012 for randomised controlled trials: The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Specialised Register, CENTRAL, in The Cochrane Library 2012, Issue 5, MEDLINE (from 1946), EMBASE (from 1974) and reference lists of articles. We also searched several online trials registries for ongoing trials.
RESULTS:Our searches retrieved 159 references, six of which were related to ongoing trials. No randomised controlled trials met our inclusion criteria.
CONCLUSIONS:There is currently no high level evidence to support or refute the efficacy or safety of percutaneous transluminal angioplasty for treatment of CCSVI in people with MS. Clinical practice should be guided by evidence supported by well-designed randomised controlled trials: closure of some of the gaps in the evidence may be feasible at completion of the six ongoing clinical trials. 

Systematic review of the literature says the stuff in the literature on CCSVI is weak so what’s new. 

Elsankari S, Balédent O, van Pesch V, Sindic C, de Broqueville Q, Duprez T. Concomitant analysis of arterial, venous, and CSF flows using phase-contrast MRI: a quantitative comparison between MS patients and healthy controls. J Cereb Blood Flow Metab. 2013 Jun 19. doi: 10.1038/jcbfm.2013.95. [Epub ahead of print]

Venous dysfunction has recently been hypothesized to contribute to the pathophysiology of multiple sclerosis (MS). 2D phase-contrast (PC) magnetic resonance imaging (MRI) is a non-invasive and innocuous technique enabling reliable quantification of cerebrospinal fluid (CSF) and blood flows in the same imaging session. We compared PC-MRI measurements of CSF, arterial and venous flows in MS patients to those from a normative cohort of healthy controls (HC). Nineteen MS patients underwent a standardized MR protocol for cerebral examination on a 3T system including Fast cine PC-MRI sequences with peripheral gating in four acquisition planes. Quantitative data were processed using a homemade software to extract CSF and blood flow regions of interest, animate flows, and calculate cervical and intracranial vascular flow curves during the cardiac cycle (CC). Results were compared with values obtained in 21 HC using multivariate analysis. Venous flow patterns were comparable in both groups without signs of reflux. Arterial flows (P=0.02) and cervical CSF dynamic oscillations (P=0.01) were decreased in MS patients. No significant differences in venous cerebral and cervical outflows were observed between groups, thereby contradicting the recently proposed theory of venous insufficiency. Unexpected decrease in arterial perfusion in MS patients warrants further correlation to volumetric measurements of the brain.

So another study not finding a difference. The CCSVI hypothesis is fuelling a lot of negative data. Is it time to call a halt to these futile studies?

2 comments:

  1. "Is it time to call a halt to these futile studies?"

    With all respect, absolutely not :) Recently Italian researcher wrote very good article about "learning curve". Different results are very propaply related to different skills and methods. There should be lots of more co-operation betveen different scientists and science fields. http://www.ajnr.org/content/early/2013/03/21/ajnr.A3570.extract

    There are quite many clinical trials that show promising results about 50-75 % with treated patients. Of course placebo controlled studies will finally give more precise answers.

    Some anecdotal evidence.. short video of my wife's situation now. 3 yrs after procedure and she still has benefits, and could exercise again. Before fatique, weakness in muscles, balance and some other issues were big problem, but these issues disappeared in june 2010. Absolutely fantastic!

    http://www.youtube.com/watch?v=eLeqLps8XR8

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  2. OK after that positive note I have forgotten to turn off comments

    I will do in case it becomes a CCSVI meeting spot like a few weeks ago

    Anecdote is not the antidote we need class I evidence

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