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Hopefully this works . . . If not I'll try a tinyurl. Nope . . .

Voila . . .

http://tinyurl.com/79juk7u

Assessment of cerebral venous return by a novel plethysmography method

Paolo Zamboni, MD, Erica Menegatti, PhD, Paolo Conforti, MD, Simon Shepherd, PhD, Mirko Tessari, VT, Clive Beggs, PhD

Background

Magnetic resonance imaging and echo color Doppler (ECD) scan techniques do not accurately assess the cerebral venous return. This generated considerable scientific controversy linked with the diagnosis of a vascular syndrome known as chronic cerebrospinal venous insufficiency (CCSVI) characterized by restricted venous outflow from the brain. The purpose of this study was to assess the cerebral venous return in relation to the change in position by means of a novel cervical plethysmography method.

Methods

This was a single-center, cross-sectional, blinded case-control study conducted at the Vascular Diseases Center, University of Ferrara, Italy. The study involved 40 healthy controls (HCs; 18 women and 22 men) with a mean age of 41.5 ± 14.4 years, and 44 patients with multiple sclerosis (MS; 25 women and 19 men) with a mean age of 41.0 ± 12.1 years. All participants were previously scanned using ECD sonography, and further subset in HC (CCSVI negative at ECD) and CCSVI groups. Subjects blindly underwent cervical plethysmography, tipping them from the upright (90°) to supine position (0°) in a chair. Once the blood volume stabilized, they were returned to the upright position, allowing blood to drain from the neck. We measured venous volume (VV), filling time (FT), filling gradient (FG) required to achieve 90% of VV, residual volume (RV), emptying time (ET), emptying gradient (EG) required to achieve 90% of emptying volume (EV) where EV = VV-RV, also analyzing the considered parameters by receiver operating characteristic (ROC) curves and principal component mathematical analysis.

Results

The rate at which venous blood discharged in the vertical position (EG) was significantly faster in the controls (2.73 mL/second ± 1.63) compared with the patients with CCSVI (1.73 mL/second ± 0.94; P = .001). In addition, respectively, in controls and in patients with CCSVI, the following parameters were highly significantly different: FT 5.81 ± 1.99 seconds vs 4.45 ± 2.16 seconds (P = .003); FG 0.92 ± 0.45 mL/second vs 1.50 ± 0.85 mL/second (P < .001); RV 0.54 ± 1.31 mL vs 1.37 ± 1.34 mL (P = .005); ET 1.84 ± 0.54 seconds vs 2.66 ± 0.95 seconds (P < .001). Mathematical analysis demonstrated a higher variability of the dynamic process of cerebral venous return in CCSVI. Finally, ROC analysis demonstrated a good sensitivity of the proposed test with a percent concordant 83.8, discordant 16.0, tied 0.2 (C = 0.839).

Conclusions

Cerebral venous return characteristics of the patients with CCSVI were markedly different from those of the controls. In addition, our results suggest that cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool.

Love it!
Dr. Simka is working on a comparison of plethysmography, MRV and doppler but I would also like to see academic research on plethysmography in CCSVI. It is too good to ignore or go sloooooow in getting this replicated. We could also use research on patients after their treatment for CCSVI, to see if we achieve normal measurements, and if plethysmography is a good detector of restenosis. Dr. Sclafani mentioned that plethysmography could even be of use during the procedure!

This could be the technique that ends the controversy about whether or not MS patients have impaired cerebrospinal drainage. Then the researchers can get on to doing something about it!

Let's break down the study somewhat:
It's a blinded study. It was done on MS patients and on healthy controls. All the patients were scanned using doppler ultrasound and divided into a CCSVI group and a non-CCSVI group. So there could be nonMS patients in the CCSVI group? Or MS patients in the healthy control group if doppler was negative for CCSVI?

All patients underwent plethysmography. They were tipped flat so that they were lying down, then given some time for blood flow to stabilize in that position, and then they were abruptly raised up to a sitting position.

Many measurements were made. The emptying gradient was the rate at which venous blood emptied when the patients were raised to the sitting position. In the healthy controls, the veins emptied at a rate of 2.73 mL/second and in patients with CCSVI, the veins emptied at a rate of 1.73 mL/second. Statistically this had a p-value of P = .001 which is very significant.

In addition, filling time and filling gradient and residual volume and emptying time were all significantly different between the two groups.

this is the type of information that is well worth waiting for.

I see no reason why this ''non-invasive'' test cannot be applied to thousands of
pwMS and healthy controls. How expensive could the test be ?

Bottom line : A huge step forward in CCSVI research.


Well done .


MrSuccess

MrSuccess wrote:How expensive could the test be ?

According to Dr. Zamboni: inexpensive!

In addition, our results suggest that cervical plethysmography has great potential as an inexpensive screening device and as a postoperative monitoring tool.

I am very happy with this one. We've been mired in dopplers too long. It would be nice to see plethysmography, and all the imaging methods, tested against the gold standard of ivus+venography!
Why can't we get ten years of research done in every one year of research!! With more funding and more researchers, it might not be impossible. We need to get past the tipping point where CCSVI is proven enough.

I think this will fix the URL.

PointsNorth wrote:Here is full link:

http://www.jvascsurg.org/article/S0741- ... 9/abstract

Hopefully this works . . . If not I'll try a tinyurl.

And this one seems very much related, which I think is what triggered the original post (It has the same diagram) http://ccsvism.xoom.it/ISNVD/Abstract-Z ... eening.pdf

Hi everyone, has there been any news whether the collar will go into commercial production?
Imagine the paradym shift in thinking when these become available and the entire MS population world wide wants to know more about the effects this is having on our Health!

NZer, I could be wrong, but I think it's already available. This is just a new use of it. It needs to be validated by another study or two. I have been getting ahead of myself for a year now waiting for more data on this, since I think it has tremendous potential.

Thanks Cece,
I asked Dr.S on his FB site and his thought at the time was that it wasn't available at this time. I am waiting for an answer from him when Dr. Z will be producing something that can be used by the likes of me to travel the country and get awareness going to drive the research.

Flow vs Pressure: to maintain flow in the presence of a higher resistance to flow (stenosis, obstruction, ligation, etc.) you have to have a higher pressure above. Flow = Pressure divided by Resistance. It depends where you measure Pressure. If Resistance stays the same, and Pressure increases (due to Gravity, when you go from supine to upright), then Flow must have decreased. Confounding this might be that some of the pressure measurement is not measurable due to vessels being encased in bony structures, or that the path of bloodflow changes when the patient goes from vertical to prone and vice-verse.

The measurement is at the skin. Can all of the blood volume from one subject be said to absolutely correspond to pressure, as is implied by labeling the Y axis with absolute volume numbers? Only if from one subject to the next, total volume in the head is always the same. Neither that, nor blood density remaining the same, are likely in all cases. But we can say what the mean and standard deviations are for CCSVI vs healthy controls. The pressure in the IJVs above the stenosis (therefore the volume at least relative to full or empty) is higher in CCSVI, when IJVs are empty, or when full.

This value is not easily measured as absolute volume. However some values are measurable vs time. The differences between patients are fixed by using the time required to achieve some fraction of the filled or empty (steady) states. That determines the slopes of the filling and emptying gradients, and these are shown to be different between the two cohorts. That proves the existence of the stenosis, as surely as the images on a Doppler sonogram, and its effect on CCSVI patients vs. healthy controls, is reduced flow, measurable by the mean pressures, but also by the increased transition times between empty and full.

One can confound the transition time measurement by varying the transition time itself between vertical and prone, i.e, the time it takes to move the chair between vertical and upright, assuming it is greater than zero. Common sense says that it must remain the same, or be measured and subtracted from the blood-flow transition times. Figure 3 shows that that is the case.

What seems to me to be shown is that the pressure (therefore volume?) approaches zero for healthy controls, and seems to get there much quicker. The steady, emptiest state, where there is significant residual venous volume, seems to me to be the unhealthy condition of CCSVI, due to stenosis, obstruction or whatever. This incompleteness of venous return is the real problem. The blood will eventually all return, just on average, about 20% slower for CCSVI.

Another piece of information which can be gleaned from these measurements (the graphs shown are not identical in every patient), is that emptying is not as complete in the CCSVI/MS cohort. That in itself is an indication, I would think, of a very serious problem. Blood will all eventually circulate, but some seems to remain in the brain over a time longer than this test took (on the order of minutes, perhaps?).

This looks new.
http://phleb.rsmjournals.com/content/ea ... 2039.short

Cerebral venous outflow resistance and interpretation of cervical plethysmography data with respect to the diagnosis of chronic cerebrospinal venous insufficiency

C Beggs*⇓, S Shepherd* and P Zamboni†
+ Author Affiliations

*Medical Biophysics Laboratory, University of Bradford, UK
†Vascular Diseases Centre, University of Ferrara, Italy
Correspondence: C Beggs PhD
, Medical Biophysics Laboratory, School of Engineering, Design & Technology, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK.

Abstract

Objective
While chronic cerebrospinal venous insufficiency (CCSVI) can be characterized using cervical plethysmography, much remains unknown about the haemodynamics associated with this procedure. The aim of the study was therefore to gain a deeper understanding of the observed haemodynamics.

Method
Forty healthy controls and 44 CCSVI patients underwent cervical plethysmography, which involved placing a strain-gauge collar around their necks and tipping them from the upright (90o) to supine position (0o) in a chair. Once stabilized, they were returned to the upright position, allowing blood to drain from the neck. A mathematical model was used to calculate the hydraulic resistance of the extracranial venous system for each subject in the study.

Results
The mean hydraulic resistance of the extracranial venous system was 10.28 (standard deviation [SD] 5.14) mmHg.s/mL in the healthy controls and 16.81 (SD 9.22) in the CCSVI patients (P < 0.001).

Conclusions
The haemodynamics of the extracranial venous system are greatly altered in CCSVI patients.

Are there any schematics of what and how the collar actually works?

Dr Zamboni talks about plethysmography in this video interview recorded at the ISNVD 2012 conference

I would be very interested in seeing exactly what the machine looks like. There's a graphic on the first page of this thread but it is taken from another research paper and might not be the plethysmography machine that is in use by Zamboni.

I think the gauntlet is once again thrown down. Forget dopplers and MRIs for now. Let's see plethysmography used as an operator-independent diagnostic tool, and let's see if research can be done that replicates these findings, and let's see the association between CCSVI and MS finally well-established using plethysmography, so that we can move on from that question and into the more pressing questions of endovascular treatment.

Great link from Sharon!

I believe the shift in thinking will come because of other associated diseases being named in this way of assessing blood flows in any disease.
Alzheimers for instance may get the interest of other Medical Specialities and bypass the hold of Neurology in MS.
Neurology lives in an alternate Reality that is driven by the Almighty Dollar, once more diseases are tested for flow irregularities there will be a paradigm shift (or employment shift of Neurologists).

My comment cross-posted from CCSVI Locator:

Why does this measurement matter?

Hydraulic resistance is affected in large part not only by cross-sectional area of a vein (narrower in a stenosis), but also by the geometry of the vein (whether it bends and how much, whether it is flattened and by how much). Ambient temperature, along with thickness (of blood) are also factors. The thinner the blood, the lower the resistance.

If there is a higher resistance to blood flow in veins, as a result of CCSVI, that matters more than a similar narrowing would in arteries, because pressure is way lower in veins than it is in arteries.

For blood to have the same overall flow rate, at the vein end of things, as it does in the arteries, there must be lower resistance in veins, to compensate for the lower pressure.

That's why neck veins are bigger and more voluminous than neck arteries, and why collateral veins matter. Gravity, and whether a person is prone or upright also changes the pressure, therefore the need for low resistance. The overall result is that veins need low hydraulic resistance, so they won't slow the flow. You need it more when you are lying down.

If it is higher in CCSVI than in normals, that will be a problem for those patients.

(Why do 'MS' patients ever lie down? Some do because they cannot get up.)