Reduced grey matter blood flow detected and measured!

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Reduced grey matter blood flow detected and measured!

Postby NZer1 » Thu Sep 26, 2013 10:43 am

NZ researchers show reduced grey matter blood flow can reveal reduced function before permanent tissue loss is visible and may lead to improved tools for prognosis and clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... +sclerosis
Abstract
BACKGROUND:
Grey matter (GM) pathology in multiple sclerosis (MS) is associated with progressive long-term disability. Detection of GM abnormalities in early MS may therefore be valuable in understanding and predicting the long-term course. However, structural MRI measures such as volume loss have shown only modest abnormalities in early relapsing-remitting MS (RRMS). We therefore investigated for evidence of abnormality in GM perfusion, consistent with metabolic dysfunction, in early RRMS.
METHODS:
25 RRMS patients with ≤5 years disease duration and 25 age-matched healthy controls underwent 3 Tesla MRI with a pseudo-continuous arterial spin labelling sequence to quantify GM perfusion and a volumetric T1-weighted sequence to measure GM volume. Neurological status was assessed in patients and neuropsychological evaluation undertaken in all subjects. Voxel-based analysis was used to compare regional GM perfusion and volume measures in patients and controls.
RESULTS:
There was reduced global GM perfusion in patients versus controls (50.6±5.8 mL/100 g/min vs 54.4±7.6 mL/100 g/min, p=0.04). Voxel-based analysis revealed extensive regions of decreased cortical and deep GM perfusion in MS subjects. Reduced perfusion was associated with impaired memory scores. There was no reduction in global or regional analysis of GM volume in patients versus controls.
CONCLUSIONS:
The decrease in GM perfusion in the absence of volume loss is consistent with neuronal metabolic dysfunction in early RRMS. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early GM perfusion deficits observed.
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Re: Reduced grey matter blood flow detected and measured!

Postby frodo » Thu Sep 26, 2013 11:22 am

Just to complement, one similar, from April

The evidence for hypoperfusion as a factor in multiple sclerosis lesion development.
Juurlink BH.
Source
Department of Anatomy & Cell Biology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5 ; College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Abstract
The evidence that hypoxia is a precipitating factor in causing early MS lesions includes increased protein levels of hypoxia-inducible factor-1 α ; presence of the D-110 hypoxia-inducible protein; increased expression of hypoxia-inducible genes in lesions as well as in adjacent normal-appearing white matter (NAWM); loss of myelin-associated glycoprotein in myelin of early MS lesions; a 50% reduction of blood flow through NAWM with areas of lowest blood flow having the greatest probability of lesion development. Why MS-like lesions develop following hypoxemic insults in some individuals but not in others is likely dependent upon the presence of immune predisposing factors that are governed genetically. Hypoperfusion may be due to decreased arterial supply, restricted venous return, or a combination of these. There are clinical trials ongoing or planned to treat chronic cerebrospinal venous insufficiency (CCSVI) through angioplasty. I suggest that it is important that clinical trials addressing vascular issues in MS should examine how the vascular intervention affects white matter perfusion and determine whether the extent of perfusion recovery and maintenance of this recovery is related to functional recovery and maintenance of functional recovery. Consideration should also be given to the possibility of arterial problems playing a role in hypoperfusion in some MS patients.
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Re: Reduced grey matter blood flow detected and measured!

Postby MarkW » Thu Sep 26, 2013 12:17 pm

NZer1 wrote:NZ researchers show reduced grey matter blood flow can reveal reduced function before permanent tissue loss is visible and may lead to improved tools for prognosis and clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... +sclerosis.

Nigel,
Blood does not enter the grey matter, this paper is discussing perfusion not blood flow.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Reduced grey matter blood flow detected and measured!

Postby 1eye » Thu Sep 26, 2013 12:57 pm

CCSVI treatment for RR"MS" seems preventive.

This new book:
News in phlebology

Allegra C., Antignani P. L., Kalodiki E.
A book of 274 pages with 125 colour and b/w figures and 40 tables (2013)
ISBN-13 978-88-7711-778-6
language: English

contains a section on plethysmography I think was written by Prof. Zamboni.

Dr. Beggs has co-written a paper with P. Zamboni and S. Shepherd in 2012, using the same method to establish that there are higher hydraulic resistances in the veins draining brains of CCSVI patients than in normals:

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

C Beggs*⇑
S Shepherd*
P Zamboni†

*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. Email: c.b.beggs@bradford.ac.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.



These are significant findings in diagnosis of CCSVI, treatment of which may reduce the problems associated with reduced cerebral perfusion, by whatever name they are called. They also give a fairly concrete means of measuring the effect of treatment on the condition. The collar could also be used to assess restenosis or subsequent thrombosis, or whether anything has caused a return of drainage problems.
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Re: Reduced grey matter blood flow detected and measured!

Postby NZer1 » Thu Sep 26, 2013 2:28 pm

MarkW wrote:
NZer1 wrote:NZ researchers show reduced grey matter blood flow can reveal reduced function before permanent tissue loss is visible and may lead to improved tools for prognosis and clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... +sclerosis.

Nigel,
Blood does not enter the grey matter, this paper is discussing perfusion not blood flow.
Kind regards,
MarkW


No love lost Mark,
here is the article that I copied that quote from, I guess you will be wanting to tell them where they have gone wrong to?
From the FB page; https://www.facebook.com/MSResearchAust ... ts&fref=ts


;)
Nigel
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Re: Reduced grey matter blood flow detected and measured!

Postby NZer1 » Thu Sep 26, 2013 3:48 pm

From Cheerleader, conference speaker, Joan :)

Dr. Zivadinov and Dr. Zamboni showed how reduced perfusion in gray matter was related to CCSVI severity back in 2010, and the Hubbard Foundation fMRI BOLD technology showed how venoplasty corrected this hypoperfusion.

for papers and links:
http://ccsviinms.blogspot.com/2011/03/dr.html

http://ccsviinms.blogspot.com/search?q=fMRI
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Re: Reduced grey matter blood flow detected and measured!

Postby NZer1 » Thu Sep 26, 2013 4:04 pm

So is this an indication that the blood cannot get in to the brain, or an indication it cannot leave the brain? Either way it will also mean the CSF is also effected!

"Cerebral arterial bolus arrival time is prolonged in multiple sclerosis and associated with disability.
Paling D, Thade Petersen E, Tozer DJ, Altmann DR, Wheeler-Kingshott CA, Kapoor R, Miller DH, Golay X.
Source
Department of Neuroinflammation, UCL Institute of Neurology, Queen Square MS Centre, London, UK.
Abstract
Alterations in the overall cerebral hemodynamics have been reported in multiple sclerosis (MS); however, their cause and significance is unknown. While potential venous causes have been examined, arterial causes have not. In this study, a multiple delay time arterial spin labeling magnetic resonance imaging sequence at 3T was used to quantify the arterial hemodynamic parameter bolus arrival time (BAT) and cerebral blood flow (CBF) in normal-appearing white matter (NAWM) and deep gray matter in 33 controls and 35 patients with relapsing-remitting MS. Bolus arrival time was prolonged in MS in NAWM (1.0±0.2 versus 0.9±0.2 seconds, P=0.031) and deep gray matter (0.90±0.18 versus 0.80±0.14 seconds, P=0.001) and CBF was increased in NAWM (14±4 versus 10±2 mL/100 g/min, P=0.001). Prolonged BAT in NAWM (P=0.042) and deep gray matter (P=0.01) were associated with higher expanded disability status score. This study demonstrates alteration in cerebral arterial hemodynamics in MS. One possible cause may be widespread inflammation. Bolus arrival time was longer in patients with greater disability independent of atrophy and T2 lesion load, suggesting alterations in cerebral arterial hemodynamics may be a marker of clinically relevant pathology.Journal of Cerebral Blood Flow & Metabolism advance online publication, 18 September 2013; doi:10.1038/jcbfm.2013.161."
http://www.ncbi.nlm.nih.gov/pubmed/24045400
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Re: Reduced grey matter blood flow detected and measured!

Postby 1eye » Thu Sep 26, 2013 11:31 pm

I think: the statement that what goes in must come out (or the brain explodes), has a corollary, that the harder it is for the brain to drain, the harder it's going to be to pump blood into it. A stenosis in a neck vein means either the heart has to work harder to get blood in at the same rate, or if it doesn't, or can't, tissue will have to live with a lower rate of fresh oxygen, and glucose, potentially all over the brain. Supplies likely are not distributed equally, and some areas will therefore have to lose out more than others. Dr. Beggs has demonstrated a higher hydraulic resistance of neck veins in afflicted people vs. controls. If your heart cannot keep up, you will get sick. Maybe the barrier to things like T cells will have to become more permeable, just to try to compensate. And maybe, for a time, new veins can lower the resistance enough that you recover. You won't get valves with that.

CSF, not being propelled the same way, could slow down, if drainage via veins has increased in resistance. Maybe the production of fresh CSF will have to slow down too. The percentage of available drainage capacity taken by CSF vs blood, I have no clue. Perhaps there too, the effect will be widely felt, and some areas will be more affected than others. Perhaps spine function will be affected.

Maybe if the heart can provide enough pressure, to keep the flow rate at a good level, the third ventricle will have to get bigger.

All of these issues can be addressed at the same time veins of sufferers are being treated. That just might be a good thing for their cardiac health as well.
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Re: Reduced grey matter blood flow detected and measured!

Postby MarkW » Fri Sep 27, 2013 6:06 am

NZer1 wrote:
MarkW wrote:
NZer1 wrote:NZ researchers show reduced grey matter blood flow can reveal reduced function before permanent tissue loss is visible and may lead to improved tools for prognosis and clinical trials.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... +sclerosis.

Nigel,
Blood does not enter the grey matter, this paper is discussing perfusion not blood flow.
Kind regards,
MarkW

No love lost Mark,
here is the article that I copied that quote from, I guess you will be wanting to tell them where they have gone wrong to?
From the FB page; https://www.facebook.com/MSResearchAust ... ts&fref=ts
;)
Nigel

The basic medical science is:
-blood does not eter the brain
-blood brain barrier stops it
-CSF surronda the brain
-brain includes white and grey matter
Facebook is hardly a medical reference book, Wikipedia (with references) is better but there are many texbooks to verify this.
The published paper does not use the phrase "grey matter blood flow" because it is edited for accuracy.
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Reduced grey matter blood flow detected and measured!

Postby 1eye » Fri Sep 27, 2013 7:10 am

Correct me if I'm wrong. Doesn't perfusion require the blood to flow, if it is to continue? Isn't it exchange of gases and nutrients that happens when blood flows through fine vessels known as capillaries, where arterial blood becomes venous? The larger the vein gets, by recombining bifurcations, the smaller the ratio of blood vessel size to the sheer number of possible exits in the fine sieve of the BBB, until it needs to be flowing with far less pressure, or some is bound to find its way across?

Are we certain how many angels fit on our respective pins?
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Reduced grey matter PERFUSION detected and measured

Postby MarkW » Fri Sep 27, 2013 8:45 am

1eye wrote:Correct me if I'm wrong. Doesn't perfusion require the blood to flow, if it is to continue? Isn't it exchange of gases and nutrients that happens when blood flows through fine vessels known as capillaries, where arterial blood becomes venous? The larger the vein gets, by recombining bifurcations, the smaller the ratio of blood vessel size to the sheer number of possible exits in the fine sieve of the BBB, until it needs to be flowing with far less pressure, or some is bound to find its way across?
Are we certain how many angels fit on our respective pins?

Hello 1eye,
It is true to say that blood flow and blood pressure outside the blood brain barrier impacts perfusion in the brain. However I have not seen published papers which define the relationship precisely. It is important not to take Dr Beggs proposition as agreed facts which some on this thread appear to do. The BBB is far more complex than a simple sieve. My main concern is that lack of precision allows neuros to shoot holes in the logic of performing balloon venoplasty to correct valve issues, I am simply attempting to reduce the ammunition available to neuros.
Kind regards,
MarkW
PS there are no blood vessels inside the brain.
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Reduced grey matter blood flow detected and measured!

Postby 1eye » Fri Sep 27, 2013 8:55 am

I'm wearing my post-proof vest. Works good, too. Not well, just good. Lost count of those angels, though.
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Reduced grey matter PERFUSION detected and measured!

Postby MarkW » Fri Sep 27, 2013 9:01 am

Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Reduced grey matter blood flow detected and measured!

Postby Cece » Fri Sep 27, 2013 10:10 am

I feel as if we are trying to master the fine details of neurology and hemodynamics, and that those who have already mastered it (the neurologists, the interventional radiologists) are so badly needed.

We aren't all going to get all the science right, although we try. We are not doctors. We need the doctors to step up and be the doctors and help us. I have great respect for those who have done so, and those who have a plan to get CCSVI established sooner rather than later, because there is such need.
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Re: Reduced grey matter blood flow detected and measured!

Postby cheerleader » Fri Sep 27, 2013 10:26 am

Cerebral blood flow and perfusion can be measured with new MRI technology, venography, angiography and doppler assessment.
I always cite peer-reviewed and published research, (that's why the Stanford doctors talked to me in the first place.)
http://www.nature.com/jcbfm/journal/v19 ... 0565a.html

Perfusion, CSF and CBF are most certainly part of the ongoing CCSVI research. That's why Dr. Zivadinov, Dr. Zamboni, Dr. Haacke, Dr. Hubbard and others are including these measurements in their assessments of CCSVI. I didn't make it up.

http://www.ncbi.nlm.nih.gov/pubmed/23845008
http://www.ncbi.nlm.nih.gov/pubmed/22971468
http://www.ncbi.nlm.nih.gov/pubmed/22640499
http://www.ncbi.nlm.nih.gov/pubmed/22521804
http://www.ncbi.nlm.nih.gov/pubmed/22357458
http://www.ncbi.nlm.nih.gov/pubmed/22011402
http://www.ncbi.nlm.nih.gov/pubmed/21385345

For all of the published research, please visit CCSVI Alliance's searchable data base.
http://www.ccsvi.org/index.php/componen ... ask=search
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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