CCSVI and the doubtful promise of an endovascular treatment

[MSUK]

CCSVI and the doubtful promise of an endovascular treatment for MS



Introduction
Recently, a radically different concept regarding the pathogenesis of multiple sclerosis (MS) has been proposed. Termed chronic cerebrospinal venous insufficiency (CCSVI), it suggests that macro occlusive abnormalities of the extracranial venous drainage pathways of the brain and spinal cord can cause or contribute to MS.

As a consequence of this theory, it has been suggested that angioplasty and possibly stenting of the internal jugular and/or azygos veins can improve the signs and symptoms of MS. These interventions have been performed sporadically across the globe in an open label fashion and never in the context of a well designed, controlled, randomized and blinded clinical trial.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/2944

[CureOrBust]

I am starting to get a little ... lets say confused... I keep reading references that state that Zamboni's first article was late in 2009, when the one that first presenting the CCSVI concept that I know of (and started the ball off here) was in Nov/Dec 2008.

[MSUK]

From the article..

The CCSVI theory and supportive data
In 2006, Zamboni, an Italian vascular surgeon, in an article titled ‘The big idea: iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis’ suggested that there were similarities between chronic venous disease of the extremities and MS.2 He raised the possibility that venous reflux or obstruction in cerebral and spinal veins might have a relationship to MS.2

Several years later, Zamboni et al reported on blinded transcranial and extracranial color Doppler sonographic findings in patients with MS and matched healthy controls and those with other neurological disorders.3 They focused on five findings: (1) reflux in the internal jugular vein (IJV) or vertebral veins >0.88 s; (2) reflux propagated in at least one out of the three deep cerebral veins >0.55 s; (3) high resolution B mode evidence of proximal IJV stenosis; (4) flow not Doppler detectable in the IJV or vertebral veins despite deep inspirations; and (5) negative difference of the cross sectional area of the IJV comparing the value obtained in the supine versus the sitting position. The authors concluded that detection of two or more of these findings constitutes the diagnosis of CCSVI. They found CCSVI in all MS patients and in none of the controls. The sensitivity, specificity, positive predictive value and negative predictive value of the test were all 100%. They concluded that there was CCSVI in MS patients.3

In a second paper, Zamboni et al published that catheter venography in patients who met CCSVI Doppler criteria showed stenosis in the azygos vein 86% of the time and one or both IJV were affected in 91%. In this study, the venographer was not blinded to the patients' diagnosis.4 The study proposed four venographic patterns: (A) large IJV with one IJV or proximal azygous vein stenosis; (B) both IJV and proximal azygos vein stenosis; (C) both IJV and normal azygous system; and (D) multilevel azygous stenosis with or without IJV involvement.

Finally, in 2009, Zamboni et al reported their results on the endovascular treatment of 65 MS patients with CCSVI.5 No isolated venous lesion was found, and the distribution of venographic patterns was 30%, 38%, 14% and 18% of types A to D, respectively.5 They performed percutaneous transluminal angioplasty (PTA) on all but one azygos lesion that did not respond to PTA alone and required stent placement. Pretreatment pressures beyond the stenosis were not significantly different than normal venous pressure and there was no significant change in pressure after angioplasty. Mean follow-up using extracranial Doppler was 18 months, with an overall restenosis rate of 47%; more common in the jugular than azygos veins. Clinical outcome at 18 months was reported as showing relapse free of 50% versus 27% preoperatively. It is important to note that the interpretation of the clinical results of this uncontrolled study is confounded since patients were continued on ‘immunomodulating’ therapy after endovascular therapy. These medical therapies have been shown to significantly reduce relapse rates as well as the accumulation of MRI detectable enhancing lesions1 Finally, there was no improvement in patients with primary progressive or secondary progressive MS.5

[malden]

...
Finally, in 2009, Zamboni et al reported their results on the endovascular treatment of 65 MS patients with CCSVI.
No isolated venous lesion was found, and the distribution of venographic patterns was 30%, 38%, 14% and 18% of types A to D, respectively.
They performed percutaneous transluminal angioplasty (PTA) on all but one azygos lesion that did not respond to PTA alone and required stent placement.
Pretreatment pressures beyond the stenosis were not significantly different than normal venous pressure and there was no significant change in pressure after angioplasty.
...

That's the key where Zamboni's theory can not keep wather:

No change in presure gradients results in no change in flow. Same blood flow before and after PTA?! Why are we doing PTA if flow is the same (not Liberated)?

[frodo]

...
Finally, in 2009, Zamboni et al reported their results on the endovascular treatment of 65 MS patients with CCSVI.
No isolated venous lesion was found, and the distribution of venographic patterns was 30%, 38%, 14% and 18% of types A to D, respectively.
They performed percutaneous transluminal angioplasty (PTA) on all but one azygos lesion that did not respond to PTA alone and required stent placement.
Pretreatment pressures beyond the stenosis were not significantly different than normal venous pressure and there was no significant change in pressure after angioplasty.
...

That's the key where Zamboni's theory can not keep wather:

No change in presure gradients results in no change in flow. Same blood flow before and after PTA?! Why are we doing PTA if flow is the same (not Liberated)?

Normally venous pressure means pressure against the vein walls, no pressure gradient in the flow

[NHE]

CCSVI and the doubtful promise of an endovascular treatment for MS

From the article:

There is no other model of decreased venous drainage and an organ specific immune response.

I believe this to be incorrect. Perhaps Cheerleader could comment on this, but I seem to recall that she has stated that there is immune activation seen with other organs affected by venous stenosis.

Moreover...

More evidence is needed to establish the association between CCSVI and MS. If more solid clinical evidence can confirm that the CCSVI–MS relationship is real, randomized clinical trials will be required to assess the benefits of endovascular interventions. If these trials establish a benefit for endovascular therapy, then at that point treatment can be made widely available. However, until these steps are taken, in our opinion, there is no role for the endovascular treatment of CCSVI in the MS patient outside of approved clinical trials.

Great, the link between MS and CCSVI is still in question. So what? Does that really matter? Maybe with respect to the long term research objective. However, if people have impaired blood drainage from a major organ of the body, such as the brain, then why should it not be fixed if possible? If impaired blood drainage involved the liver, kidneys, a limb, or some other organ, then fixing it would not be controversial.

One question, why do they seem to conveniently overlook the preliminary results of the work in Kuwait while they cite the preliminary results in Buffalo? The Kuwaiti trial comparing 100 MS patients to 100 controls has shown that CCSVI was found in 87% of MS patients but only in 7% of controls via doppler testing.

http://www.thisisms.com/ftopicp-129801.html#129801

NHE

[Algis]

If only 5 people gets better out of 2,000; it is a way to investigate... Even if 'only' 5% of the peeps with MS owe it to CCSVI; test them and treat them...

And let them enjoy a bit of life ...

[Sotiris]

[...]That's the key where Zamboni's theory can not keep wather:

No change in presure gradients results in no change in flow. Same blood flow before and after PTA?! Why are we doing PTA if flow is the same (not Liberated)?

The answer can be found here:
"A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency"

[cheerleader]

I find these commentaries, quickly published without new research to be curious.

The list of authors on this commentary is interesting. They are neuroradiologists and IRs from around the country, and none have really published....except for the doctor who appears to be the instigator, and most likely put this group together from his professional affiliations...Dr. Robert W. Tarr. Dr. Tarr has published many "position" pieces in the Journal of Neurointerventional Surgery. His specialty is arterial brain issues, clots and strokes, and he has investigated many ways to deal with these, including the use of pharmacological means. This is not to discount his resume, which is very accomplished.

Here is a recent commentary by Dr. Tarr on new technology:
http://jnis.bmj.com/content/2/3/190.full


I feel we have to somehow put these arterially focused doctors together with the venous doctors. Budd Chiari is the example Dr. BB Lee uses for CCSVI...a chronic progressive venous disease that slowly damages the organ (obviously, there is no myelin on the liver, no myelin to destroy as in MS or congestive venous myelopathy of the spine-but there have been an immune response noted, and a link to Bechet's, as well as elevated white blood cells. The reason for liver destruction is ischemia due to venous congestion. Immune activation is viewed as a natural response to this situation....

Dr. BB Lee also addressed the other issues mentioned in this piece: Caucasians have these congenital truncular venous malformations, and have settled further from the equator, and women are 2x more likely to have these venous malformations, which are congenital and grow a lot during puberty, creating organ problems in the 2nd and 3rd decade of life---
http://fondazionehilarescere.org/pdf/03-2518-ANGY.pdf

sigh,
cheer

[malden]

The answer can be found here:
"A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency"

Mea culpa.... Zamboni talk about total presure, measured by manometer, nothing about hemodynamic presure components: static and dynamic hydraulic presure, which are more important for quantification of blood flow. This diagram you provided doesn't show nothing about procedure success... It's global presure drop in global circulation, caused by global vessels expanding or increased hart pumping. Whose causes may be different.

[cheerleader]

Normal internal jugular pressure is measured in cm of H2O. Normal internal jugular venous pressure is 5-9 cm H20. It can be as low as 2 cm H2O and still "normal."
http://www.turner-white.com/pdf/hp_may02_veins.pdf
As you can see from Dr. Zamboni's study, the pressure pre-angioplasty is the IJVs he treated was up around 14. That is NOT normal. It is too high.


Dr. Zamboni uses the exact same venous measurements that are taken in Budd Chiari disease, a disease of venous congestion of the liver due to hepatic vein occlusion...this is how venous pressure is measured pre and post angioplasty---in cm of H2O

All three hepatic veins were reopened in 23 patients (Table 2). The average pressure in the IVC was 25.1 cm H2O preoperatively and 11.8 cm H2O at the time of discharge.

http://ats.ctsnetjournals.org/cgi/conte ... 711#TABLE2

What Dr. Zamboni found was a significant change in internal jugular and azygos vein pressure after angioplasty. THis cannot be denied. This is the way venous pressure is measured. period.
cheer

[MrSuccess]

this topic and discussion clearly demonstrates the value of this website .

As in life ...... one expert challenges another expert.

This is normal ...... no need to '' sigh ''.

As we proceed ....more and more expert pro-CCSVI information comes to light. These people provide solid data to support their position .

Those opposing CCSVI ...... have not provided much more than .... '' here are my credentials '' ..... '' this is who I am " ...... and of course no hard facts or data to support their position .

'' This won't work '' ...... is hardly evidence .


Bottom line . You can sense the fear in those diminishing Dr. Zamboni's discovery . Most of us get a good sense of why .

There is far and away too much positive and exciting CCSVI work being done ....... to give any small- time CCSVI critic ...... any credence .


That's how I see it , anyway .



Stay Calm ...... and Carry On





Mr. Success

[Gordon]

Ignore this.. His credentials speak Volumes

The MS societies have infested our governments just like the drug companies have infested them...

One word

Evil

[Sotiris]

[...]
As you can see from Dr. Zamboni's study, the pressure pre-angioplasty is the IJVs he treated was up around 14. That is NOT normal. It is too high.[...]

Seeing the numbers in isolation without taking into account the haemodynamic picture, they appear to be normal or only slightly elevated. However, these pressures are not normal as pointed out in "Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis"

Venous pressure
Pressures measured in patients and controls respectively were not significantly different (Mann–Whitney) (superior vena cava 13 (SD 4) vs 13 (4), azygous 16 (7) vs 14 (4), IJVs 14 (4) vs 12 (5)). In contrast, the pressure gradient measured in CDMS across the stenosies was significantly different. For instance, pressure in the stenotic proximal azygous vein was 3.9 cm/H2O higher as compared with the pressure measured in the adjacent superior vena cava of the same subjects (p,0.01; Mann–Whitney); equally, pressure in the stenotic IJVs was 1.8 cm/H2O higher with respect to the cava (p,0.04; Mann–Whitney).

The statement

Pretreatment pressures beyond the stenosis were not significantly different than normal venous pressure and there was no significant change in pressure after angioplasty.

seems to me as particularly misleading.

[scorpion]

this topic and discussion clearly demonstrates the value of this website .

As in life ...... one expert challenges another expert.

This is normal ...... no need to '' sigh ''.

As we proceed ....more and more expert pro-CCSVI information comes to light. These people provide solid data to support their position .

Those opposing CCSVI ...... have not provided much more than .... '' here are my credentials '' ..... '' this is who I am " ...... and of course no hard facts or data to support their position .

'' This won't work '' ...... is hardly evidence .


Bottom line . You can sense the fear in those diminishing Dr. Zamboni's discovery . Most of us get a good sense of why .

There is far and away too much positive and exciting CCSVI work being done ....... to give any small- time CCSVI critic ...... any credence .


That's how I see it , anyway .



Stay Calm ...... and Carry On





Mr. Success

This is an absolute ridiculous thing to say and I believe statements like this have hurt the CCSVI cause. Most of us of are critical of CCSVI want further investigation for one reason or another and to try and marginalize the "skeptics" just means they will be less invested than they already are.