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Chronic cerebrospinal venous insufficiency (CCSVI) was recently described in multiple sclerosis patients. CCSVI is characterized by impaired brain venous drainage due to outflow obstruction in the extracranial venous system, mostly related to anomalies in the internal jugular and azygos veins. The current CCSVI diagnosis is based on Doppler sonography of extracranial and transcranial venous hemodynamics criteria. To date, prevalence estimates of CCSVI, provided by different groups using various imaging methods of assessment, vary widely from none to 100%. There is an urgent need to define and validate the spectrum of cranial/extracranial venous anomalies and to establish reliable, diagnostic gold-standard test(s). The potential usefulness of endovascular treatment for CCSVI in multiple sclerosis patients is still unknown.

In our view, a major methodological point is that the CCSVI diagnosis is mainly based on extracranial and transcranial echo- color Doppler criteria, which are operator-dependent, suggesting a need for standardized training....

The CCSVI diagnosis combines functional and structural intra- and extra-cranial venous abnormalities in a single composite. Previous CV studies in MS [17,18,23,25] proposed that the extracranial venous anomalies are likely to be truncular venous malformations [48] characterized by intraluminal defects (such as flaps, webs, septums, membranes and malformed valves) or by extraluminal abnormalities represented by stenoses of the venous wall. In a recent study, 150 MS patients showed a significantly higher number of total and intraluminal structural and functional abnormalities on Doppler sonography compared with 63 healthy controls, while 46 progressive MS patients presented with significantly more extraluminal abnormalities than 104 nonprogressive MS patients [46]. These findings suggest that the majority of CCSVI pathology is confined to the intraluminal portion of the extracranial veins, which requires high-resolution B-mode imaging for visualization of these abnormalities.

Our group established that the assessment of possible prominence or collateralization of the remaining veins in the neck by MRV is more accurate than with Doppler sonography [34,46]. In addition, we found that MS subjects tend to have more collaterals than controls, but collaterals are also frequent in subjects with normal Doppler or MRV findings [34,46]. This suggests that collaterals prob- ably represent physiological variations of the venous system that may play a compensatory role when there are more venous extracranial stenoses present.

In a recent prospective, 12-month Endovascular Venous Treatment for MS (EVTMS) follow-up study that enrolled 15 MS patients, we investigated whether percutaneous trans luminal angioplasty (PTA) can reduce disease activity when used in addition to standard medical treatment [82]. Although we did not assess quality of life or neuropsychological out- comes in that study, we noticed that the majority of the treated patients reported immediate temporary improvements in subjective complaints of fatigue and cognitive impairment post- intervention [82]. In another recent study, the re-establishment of cerebral venous return reduced chronic fatigue perception in a group of 31 MS patients with CCSVI who underwent the endovascular procedure, suggesting that fatigue could probably be associated with CCSVI.

These data may suggest that reduced cerebral perfusion in MS patients is related to the presence and severity of venous out- flow blockages characterizing CCSVI. To test this hypothesis, a recent pilot study of 16 patients with MS and eight healthy subjects [81] investigated whether hypoperfusion of brain parenchyma is related to impaired venous outflow. It was found that hypoperfusion of the brain parenchyma in MS, but not in healthy controls, was associated with the presence and severity of CCSVI. Decreased CBF GM and WM regions of the brain parenchyma showed a strong relationship with increased severity of CCSVI. These preliminary findings are from a small group of subjects and should be confirmed in a larger cohort of MS patients [84].

The EVTMS pilot study was neither randomized nor blinded and, because its sample size was small, no conclusions can be drawn regarding clinical efficacy [82]. However, there was a trend for lower T2 lesion volume and relapse accumulation in the immediate, compared with the 6-month delayed, treatment arm over 12 months, indicating that PTA could potentially enhance the effect of medication given to patients with MS. Another pilot, double-blinded, pla cebo-controlled, randomized study (PREMiSe) of 30 MS patients organized to preliminarily assess the safety and efficacy of PTA for venous stenoses in MS patients presenting with CCSVI over 1 year was initiated (Figure 7). A larger multicenter, double-blinded, randomized, placebo-controlled trial, entitled BRAin VEnous DRainage Exploited Against MS (BRAVE DREAMS), will assess the safety and efficacy of PTA treatment for CCSVI over 1 year.

Is it necessary to be an external exam?

The safety of inspection only by IVIS/ catheter inspection is safe, is it not?

jean-la-grenouille wrote:Thanks Cheer for this post, I'm waiting for the results of the canadian studies...is there any critical data to be released soon ?

Cece, you were really decided to get treated...I prefer wait and see before taking any risk...maybe I'm a coward !

Cece wrote:If I'd had to find $10,000 before I could be treated, that would have slowed me down some. But yes, I was determined. CCSVI made a lot of sense with my particular symptoms. I think people with more severe stenoses are more affected by the hypoxia itself, not the MS lesions, but directly the hypoxia. I have not felt ill since the procedure the way I used to, all the time. Chronically ill meant chronically ill. Ill-being instead of well-being. Oh, the good ol' days.... It feels good to be better.

I don't think it's cowardice at all to wait. Fools rush in where angels dare to tread and all that. I have no doubts that CCSVI is real and that it is deeply entwined with the disease of multiple sclerosis but I do have doubts that the treatment of it is at its best yet and also not standardized, so patients get different versions of treatment from different doctors.

Risk is very changeable. Certainly one's opinion changes after the first disability that won't go away. Risk for some is in waiting, if there is anything else that can be done.

cheerleader wrote:I have to say, this review is worth the $ to get the whole paper.
Dr. Zivadinov goes thru the entire history, how he and his team trained the doppler protocol with Zamboni, how they added MRV, what they found (mostly intraluminal defects) and how they've treated these with angioplasty. It discusses results of PTA and the need for large scale clinical trials. And it's written by a team of neuros for a neurological journal. Saying that CCSVI is real. A good publication,
cheer

On 8/24/11 Expert Reviews: Neurotherapeutics released a demyelinated diseases themed article, “Chronic cerebrospinal venous insufficiency in multiple sclerosis: diagnostic, pathogenetic, clinical and treatment perspectives.” Dr. Robert Zivadinov is the lead author of the article that appears in the September 2011 edition of this journal, available by subscription.

For the benefit of MS patients and readers who are not neuroscientists, The Buffalo Neuroimaging Analysis Center Advisory Council is preparing a digest of the article that will be posted on BNAC Facebook sites “BNAC CCSVI Study” and “BNAC Study.” Thank you for your interest in BNAC’s research.

BNAC is a division of University at Buffalo’s Neurology Department: The Jacobs Neurological Institute