study shows cerebral venous outflow is abnormal in MS

[Cece]

http://www.ncbi.nlm.nih.gov/pubmed/24610905

AJNR Am J Neuroradiol. 2014 Mar 7. [Epub ahead of print]

A Sonographic Quantitative Cutoff Value of Cerebral Venous Outflow in Neurologic Diseases: A Blinded Study of 115 Subjects.

Monti L1, Menci E, Piu P, Leonini S, Arrigucci U, Bellini M, Zandonella A, Galluzzi P, Casasco A.


Abstract

BACKGROUND AND PURPOSE:

The autonomic nervous system maintains constant cerebral venous blood outflow in changing positions. Alterations in cerebral autoregulation can be revealed by postural changes at quantitative color Doppler sonography. The aim of this study was to reach an optimal cutoff value of the difference between the cerebral venous blood outflow in the supine and seated positions that can discriminate healthy controls from patients with multiple sclerosis and those with other neurologic diseases and to evaluate its specificity, sensitivity, and diagnostic accuracy.

MATERIALS AND METHODS:

One hundred fifteen subjects (54 with MS, 31 healthy controls, 30 with other neurologic diseases) underwent a blinded quantitative color Doppler sonography evaluation of cerebral venous blood outflow in the supine and sitting positions. An optimal difference value between the supine and sitting positions of the cerebral venous blood outflow cutoff value was sought.

RESULTS:

The difference value between supine and sitting positions of the cerebral venous blood outflow was ≤ 503.24 in 38/54 (70.37%) patients with MS, 9/31 (29.03%) healthy controls, and 13/30 (43.33%) subjects with other neurological diseases. A difference value between supine and sitting positions of the cerebral venous blood outflow at a 503.24 cutoff reached a sensitivity at 70.37%, a 70.96% specificity, a 80.85% positive predictive value, and a 57.89% negative predictive value; the quantitative color Doppler sonography parameters yielded significant differences. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 assessed the significant difference between MS versus other neurological diseases.

CONCLUSIONS:

Alteration of cerebral venous blood outflow discriminated MS versus other neurologic diseases and MS versus healthy controls. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 was statistically associated with MS.

1 - this is not done by CCSVI researchers
2 - they attribute the difference in outflow as being due to autonomic impairment in the MS patients
3 - it is confirmation that you can distinguish between people with and without MS by measuring the blood flow
4 - let's say they are right that it is autonomic dysregulation that is causing blood flow abnormalities in the MS patients, then there might be a cumulative effect in those patients if there is also outflow obstructions in the veins
5 - there are reports of improvement in autonomic dysfunction after angioplasty treatment
6 - exciting times, exciting research. This research supports what we've been saying (and acting on) for five years now

[cheerleader]

Thanks for posting, Cece--
I found this on one of my pubmed searches last week---put it up on Facebook and got it to Dr. Zamboni. It seemed to me to be a direct correlation with what he was finding in his plethysmography studies----pwCCSVI have slower or restricted venous outflow when they go from supine to upright position.
http://www.ncbi.nlm.nih.gov/pubmed/22521804

When I posted the study, I didn't realize that these doctors were not affiliated with Dr. Zamboni's lab---but this is blinded and independent research. Very exciting. This group is positing the autonomic connection, and their research was published in the American Journal of Neuroradiology. Assuming the ISNVD will be in touch with these researchers.
cheer

[ThisIsMA]

So are they saying that blood flow from the brain is slower when people with MS are sitting up than when they are laying down? If that's the case, one would think that people with MS should take several naps a day to speed up the delivery of oxygenated blood to their brain by draining the old blood away from the brain more quickly....

Wow, I think I'll go take a nap!

[Cece]

So are they saying that blood flow from the brain is slower when people with MS are sitting up than when they are laying down?

One hundred fifteen subjects (54 with MS, 31 healthy controls, 30 with other neurologic diseases) underwent a blinded quantitative color Doppler sonography evaluation of cerebral venous blood outflow in the supine and sitting positions. An optimal difference value between the supine and sitting positions of the cerebral venous blood outflow cutoff value was sought.

RESULTS:

The difference value between supine and sitting positions of the cerebral venous blood outflow was ≤ 503.24 in 38/54 (70.37%) patients with MS, 9/31 (29.03%) healthy controls, and 13/30 (43.33%) subjects with other neurological diseases.

I don't know if that's the correct interpretation. What's being looked at is the "difference value." In people with MS, there was less of a difference in blood flow when the person switched from lying down to being upright. In a healthy control, there was a larger difference.

Remember Zamboni's five Doppler criteria? One of the criteria was if the jugular vein stayed the same size or increased when a person went upright, rather than shrinking dramatically as flow was diverted to the vertebral plexus. So this study saw the same thing happening.

Taking a nap is still a good idea but exercise is probably what would help get blood flow to the brain because of what happens with the heart pumping faster and more coming in on the arterial side. If there are outflow blockages, I don't think the benefit from exercise is as good as it is for other people but there should still be a benefit.

[ThisIsMA]

Hi Cece,

Thanks for your reply. I really couldn't understand the original study you quoted from, but I was replying to the post just above mine in the thread from Cheer which said:

It seemed to me to be a direct correlation with what he was finding in his plethysmography studies----pwCCSVI have slower or restricted venous outflow when they go from supine to upright position.
http://www.ncbi.nlm.nih.gov/pubmed/22521804

Maybe Cheer was mistaken about whether the two studies found the same thing? But the plethysmography study at the link she provided did find better flow when you're lying down.

The whole thing is cofusing to me though because does it mean better flow altogether, or just better flow through the jugulars? You would think it wouldn't matter so much what route the blood is taking, just that it does get out of the brain so that fresh oxygenated blood can get back into the brain to "feed' it.

M.A.

[Cece]

Yeah I am confused too.
Here's a quote from the plethysmography study:

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

So when upright, the rate of blood flow is slow in MS patients when compared to controls, but this has to do with the emptying of the jugulars right after transitioning from lying down to upright. The plethysmography measures how the body adjusts when going from lying down to upright. In healthy patients, the jugulars are full and in use when lying down and empty and unused when upright. In CCSVI patients, the jugulars can be full and in use in both positions, or they might empty like a healthy control's jugulars but not as quickly which is evidence for the outflow obstruction within the jugulars and evidence that there was congestion within the jugular while lying down that took awhile to clear once upright and the body switched to the vertebral plexus pathway of cerebral outflow with gravity assisting.

If there is congestion in the jugular veins while lying down but not while upright, that might suggest that being upright is better. If outflow obstructions also exist in the vertebral plexus or the azygous, then it would get more complicated.

[1eye]

Things work ok in healthy patients, because there is a big enough difference between sitting and lying down. If there is not enough difference it is likely to be (due to 'MS') a jugular problem, since the presence of this difference turns out to be diagnostic for 'MS'. Especially in light of "Internal Jugular Vein Blood Flow in Multiple Sclerosis
Patients and Matched Controls".

Note that in their CONCLUSIONS they were careful not to be more specific about the 'alterations'. If somebody scales the paywall they can read whether there were ever reductions in total flow when the patient lay down. Things more likely agree with Dr. Zamboni's model showing that there is greater collateral flow in patients with jugular blockage.

I think the amount of the difference between supine and sitting likely comes from differences in individuals' collateral adaptation to jugular sufficiency problems. This difference may be due to relative adaptation success via new collateral capacity. When draining blood is re-routed, as normally happens going from sitting to supine, the re-routing is likely because of capacity and resistance differences between jugular and collateral routes.

I think there is likely an average total blood flow through the neck in weight and age-matched (and maybe BMI-matched) normals. If a method can be agreed upon to determine the volumetric flow rate in both postures (and maybe also standing?), it may be found that there is a quantitative difference between different 'types' ('CIS', 'RR'', 'SP', 'PP') of 'MS'.

[1eye]

i hate like hell to distract anyone from the real significance of this paper's results, but

cerebral venous blood outflow at a 503.24 cutoff

got me puzzled. First of all this paper repeatedly uses numbers with four digits of significance, indicating they are direct measurements with no accumulated error. I suspect the real results have an outstanding two or three digits of accuracy, and that's plenty to draw conclusions from. There is a lot of highfalutin math being done in these studies but I doubt five digits are coming from very many measurements. i always see statistical significance but I seldom see an estimate of the range of possible errors. See http://www.idomaths.com/sigfig.php. You can't let your calculator improve the accuracy of your results. Two digits works just fine for me.

[Cece]

If a method can be agreed upon to determine the volumetric flow rate in both postures (and maybe also standing?), it may be found that there is a quantitative difference between different 'types' ('CIS', 'RR'', 'SP', 'PP') of 'MS'.

That's been a fascinating possibility from the beginning and I wish research went faster. I think CCSVI sets up the unhealthy conditions at the blood-brain barrier but how our immune system responds may be what determines what clinical category of MS a person lands in. A person with the same degree of flow abnormality could have their immune system come in all guns blazing or not much of a response at all, depending on individual genetics and immune systems.

[1eye]

It may not be the immune system that makes the BBB more permeable. My money is on clotting factors. At least in cognition, because of this second immune response from inside the brain (that why some get PML?) it may be better not to depress the whole enchilada.

[brocktoon]

CONCLUSIONS:

Alteration of cerebral venous blood outflow discriminated MS versus other neurologic diseases and MS versus healthy controls. The difference value between supine and sitting positions of cerebral venous blood outflow ≤ 503.24 was statistically associated with MS.

Great news, this is basically what the Haacke group established in three different MRI papers, that < 8ml/sec of total IJV flow is a potential marker. The 4th in progress of acceptance with a large cohort of controls. I will keep everyone posted when it does happen.

[1eye]

brocktoon, I agree, great news, and please do let us know... thanks.

There will always be those simple-minded individuals who say that 'MS' is the cause of everything, including the autonomic (or stenotic) problems that cause the difference in sitting versus supine venous outflow. To me, the real crux of the problem with circulation is total throughput. If patient A has the same volume of similar blood as patient B, and weighs the same, there can still be a grave difference in how fast patients A and B get the whole volume through the circulation, whether supine or not. If the one with less throughput, moves around much less, as a result of a circulation/energy problem, it will be self-reinforcing. If as a result of a throughput problem the whole body is not getting enough rest, the problem will again reinforce itself.

Is there a significant difference in total blood throughput between pw'MS', 'RR', 'SP', 'PP', 'CIS', etc., and healthy, weight and age-matched 'normal's? Is there a difference in head throughput, vs rest-of-body? Are hearts usually (resting and standing) weaker in some groups? Is this autonomic, capacity, stenosis, all three?

The guy who saw my doppler scans said "Just don't lie down." Was he very right or very wrong?

[brocktoon]

Does anyone have a copy of this paper they could send me in a pvt message? I have a version, but the scan quality is very poor and hard to read,

thank you!

[MrSuccess]

thanks for posting this study.

Does anyone know how the "upright MRI" is progressing ? Any UPRIGHT MRI's being
used by hospital's and such ....... ?

And just as important ..... how is the invention of measuring blood flow [ neck collars ] progressing?

MrSuccess