Must Read Article on Hypoperfusion....

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

Must Read Article on Hypoperfusion....

Postby orion98665 » Mon Apr 02, 2012 4:39 pm

i don't know if article has been posted but should be read.

Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance

This work was supported by MS Anders (Amsterdam, The Netherlands).

Jacques De Keyser1,2, Christel Steen2, Jop P Mostert2 and Marcus W Koch2

1Department of Neurology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
2Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Correspondence: Professor Dr J De Keyser, Department of Neurology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels 1090, Belgium. E-mail: jacquesdekeyser@gmail.com

Received 2 May 2008; Revised 13 June 2008; Accepted 16 June 2008; Published online 2 July 2008.


Accumulating evidence indicates that there is a decreased perfusion throughout the NAWM in patients with MS. It occurs in both relapsing–remitting and primary progressive MS, strongly suggesting that it represents an integral part of the disease process. Ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions). There appears to be a relationship between reduced white matter perfusion and cognitive dysfunction in patients with MS. We provide a hypothetical framework for the reduced perfusion, implicating a key role of astrocyte dysfunction, possibly related to a deficiency in β2-adrenergic receptors resulting in an impaired siphoning and release of K+ in the perivascular spaces. The underlying pathophysiological mechanisms need to be further elucidated as it could ultimately allow us to understand and treat this complex disease better.


http://www.nature.com/jcbfm/journal/v28 ... 0872a.html



Bob
orion98665
Family Elder
 
Posts: 135
Joined: Sat May 29, 2010 3:00 pm
Location: Vancouver, Wa

Advertisement

Re: Must Read Article on Hypoperfusion....

Postby Cece » Mon Apr 02, 2012 7:45 pm

A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss.
Ok, we know one thing the reduced perfusion is not due to (it is not secondary to axonal loss). The article suggests a complicated theory relating to astrocytes as a possibility.

The idea around here has been that the reduced perfusion is due to the blockages in the neck veins. But there is an easy way to test this idea. Perfusion needs to be measured before and after the endovascular treatment of the stenoses of the neck veins. If improving the outflow through the neck veins also improves the cerebral perfusion, then the reduced perfusion was a result of those blockages.

I do not know if there is as easy of a way to test the astrocyte theory.

Great article, orion. I will read it more closely tomorrow. My astrocytes get a little tired at this time of night.
Cece
Family Elder
 
Posts: 9024
Joined: Mon Jan 04, 2010 4:00 pm

Re: Must Read Article on Hypoperfusion....

Postby cheerleader » Mon Apr 02, 2012 8:03 pm

this is a good one, orion.
I wrote a note in Facebook on this paper back in 2009, delving into a bit, and breaking it into bite size chunks. :)
https://www.facebook.com/notes/ccsvi-in ... 9656952210

The researchers spend a great deal of time in the paper hypothesizing over causes for this slowed perfusion, and finally admit that there needs to be further study. They write about research into astrocyte (glial cells in the central nervous system) dysfunction, but admit they don't really know what's going on. They haven't found the specific cause for this slowed perfusion and lack of oxygen in the MS brain, and further research needs to be done. The thing they can show is that MS brains have slowed blood flow, damage due to lack of oxygen that is centered around the veins in the brain, and this happens before lesions form.


cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
User avatar
cheerleader
Family Elder
 
Posts: 5048
Joined: Mon Sep 10, 2007 3:00 pm
Location: southern California

Re: Must Read Article on Hypoperfusion....

Postby 1eye » Thu Apr 05, 2012 2:27 pm

I think there is reduced perfusion if the cerebral bloodflow (sum of all flows going in, which equals the sum of all outflows) is low. It's just a question of which part gets the reduced flow, if it isn't evenly perfused. I believe the p in PWI is perfusion, so yes, it can be measured, with MRI. Measuring the astrocytes, no clue.

Further to the thread on metabolism, I think, though flow is the same on both sides of a stenosis (in the jugular), there must be a difference in pressure. I think the pressure should be higher on the upstream side (brain-wards). Also, if the jugulars are a main route (because of the relative diameters of other veins, and the fourth power relationship between diameter and resistance), then any stenosis or obstruction will reduce the overall flow, and thus perfusion. The jugulars appear in parallel with the other veins and collaterals of the neck. The favoured route is the largest vein. That is why after stenosis is removed, the collaterals appear to vanish. The difference in diameters has such a pronounced effect that they now carry only a miniscule amount of the overall low..

So a) which jugular is affected matters, because they are not the same diameter; and b) together they comprise the favoured route, having direct series connection with large brain vessels. Overall, throughout the brain, flow, pressure, and resistance of blood are affected by a jugular stenosis.

Pressure and resistance to flow are increased, and flow (again, thus perfusion) is reduced, over the whole brain.

You can measure it, but it is a fact.

The notion that you will stay alive after ligation of the two largest vessels draining the brain may be technically true, but QOL is definitely in jeopardy.

The way they work in upright humans is mainly when we are lying down. They are a main reason we don't like to sleep standing up.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2931
Joined: Wed Mar 17, 2010 4:00 pm
Location: Kanata, Ontario, Canada

Re: Must Read Article on Hypoperfusion....

Postby David1949 » Thu Apr 05, 2012 4:25 pm

If we assume that low perfusion is the cause of MS then the $64,000 question is what causes the low perfusion rate and more importantly

HOW CAN WE FIX IT?

This article discusses factors that control the cerebral blood flow.
https://en.wikipedia.org/wiki/Cerebral_blood_flow
David1949
Family Elder
 
Posts: 645
Joined: Mon Aug 23, 2010 3:00 pm

Re: Must Read Article on Hypoperfusion....

Postby David1949 » Thu Apr 05, 2012 5:01 pm

Here is an article on autoregulation of blood flow.
http://www.cvphysiology.com/Blood%20Flow/BF004.htm
Certain organs including the brain, have a means of compensating for a fall in blood pressure by dilating the small arteries and arterioles to allow more blood flow.

So as I see it there are five categories of things that could cause low blood
low:

Low blood pressure.
Blockage or stenosis in the veins
Blockage or stenosis in the arteries
Malfunction of the autoregulation system in the brain.
High viscosity of the blood.

We could probably rule out low blood pressure. I don't have low blood pressure and I think many other MSers also have normal pressure.
David1949
Family Elder
 
Posts: 645
Joined: Mon Aug 23, 2010 3:00 pm

Re: Must Read Article on Hypoperfusion....

Postby munchkin » Thu Apr 05, 2012 5:58 pm

I asked Dr.Arata about MS patients having high blood pressure and he stated that most of his MS patients have low blood pressure. My bp is low and has been low normal for years.
User avatar
munchkin
Family Elder
 
Posts: 309
Joined: Fri Apr 01, 2011 3:00 pm
Location: Canada

Re: Must Read Article on Hypoperfusion....

Postby David1949 » Thu Apr 05, 2012 6:18 pm

munchkin wrote:I asked Dr.Arata about MS patients having high blood pressure and he stated that most of his MS patients have low blood pressure. My bp is low and has been low normal for years.


Sounds like we need a poll.
David1949
Family Elder
 
Posts: 645
Joined: Mon Aug 23, 2010 3:00 pm

Re: Must Read Article on Hypoperfusion....

Postby Cece » Tue May 28, 2013 5:15 pm

http://www.ncbi.nlm.nih.gov/pubmed/23428956
Mult Scler. 2013 Feb 21. [Epub ahead of print]
Cerebral white matter blood flow and energy metabolism in multiple sclerosis.
Steen C, D'haeseleer M, Hoogduin JM, Fierens Y, Cambron M, Mostert JP, Heersema DJ, Koch MW, De Keyser J.
Source
Department of Neurology, Universitair Medisch Centrum Groningen, The Netherlands.
Abstract
BACKGROUND:
Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown.
OBJECTIVE:
The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism.
METHODS:
Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging. CBF was measured using pseudo-continuous arterial spin labeling. N-acetylaspartate/creatine (NAA/Cr) ratios (axonal mitochondrial metabolism) were obtained using (1)H-MR spectroscopy and PCr/β-ATP ratios using (31)P-MR spectroscopy. In centrum semiovale NAWM, we assessed correlations between CBF and both NAA/Cr and PCr/β-ATP ratios.
RESULTS:
Subjects with MS had a widespread reduction in CBF of NAWM (centrum semiovale, periventricular, frontal and occipital), and gray matter (frontoparietal cortex and thalamus). Compared to controls, NAA/Cr in NAWM of the centrum semiovale of MS subjects was decreased, whereas PCr/β-ATP was increased. We found no correlations between CBF and PCr/β-ATP. CBF and NAA/Cr correlated in controls (p = 0.02), but not in MS subjects (p = 0.68).
CONCLUSIONS:
Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

Does this get interpreted the same way? The reduced perfusion in MS is not due to the impaired axonal mitochondrial metabolism or astrocytic PCr Metabolism, and thus we need a different explanation for why there is reduced perfusion in MS? Or is it that the reduced perfusion in MS is not causing impairment in metabolism in the axons or astrocytes, and thus we shouldn't worry about reduced perfusion because it is not doing harm in this way?
Cece
Family Elder
 
Posts: 9024
Joined: Mon Jan 04, 2010 4:00 pm

Re: Must Read Article on Hypoperfusion....

Postby Rogan » Tue May 28, 2013 6:51 pm

Cece,

Thanks for the link to this paper. The body of evidence is growing in supporting CCSVI as the cause of MS.

Interestingly these researchers were not able to link cranial hypoperfusion in the brain with intercellular chemicals. If I am reading this right. Is that really a big deal? So the mitochondria don't care whether or not there is low blood flow?

But the bigger news are these quotes from the paper.


These findings suggest that a decreased cerebral NAWM perfusion is an integral part of the disease process.


Thus, other mechanisms are likely to play a role in reducing CBF in NAWM of subjects with MS. Possible hypothetical mechanisms include astrocyte dysfunction resulting in a reduced dilation of arterioles,25 or an increase in vasoactive substances into the cerebral circulation.6


I just want to interject and say CCSVI at this point. Couldn't a stenosis in the veins be considered a "vasoactive substance". Why does it have to be so micro? Why can't anatomical problems be a big deal?


And finally they conclude...

Further research is required to investigate the mechanisms underlying global cerebral hypoperfusion in MS, and whether this has clinical and pathological implications.


Circulation is life. Without proper circulation we don't exist. Hell cancer won't even kill you. It's the trauma it causes to your vital organs that gets you. It's the only thing that hurts people. I am convinced. If any doctor can ever link a disease to circulation the burden of proof should be on others.
Rogan
Family Member
 
Posts: 74
Joined: Fri Dec 23, 2011 12:18 pm

Re: Must Read Article on Hypoperfusion....

Postby cheerleader » Wed May 29, 2013 7:42 am

Researchers continue to talk in hypothetical circles about hypoperfusion---stating that the disease process of MS is what causes slowed blood flow, and using MRIs. But when we look at actual brain tissue, we can see that these vascular changes are happening before demyelination, before inflammation, before immune cell activation, before "MS."

-To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition. METHODS--Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen. RESULT Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues. CONCLUSION--It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

http://jcp.bmjjournals.com/content/47/2/129.abstract

I put together info on the perfusion/reperfusion cycle on Facebook, for those who might be interested in learning more about the potential cause of this injury in MS. We know about reperfusion injury in ischemic stroke, and it looks a lot like the inflammatory phase of RRMS.

What's reperfusion? Most of us know the word hypoperfusion---meaning the slowed or less than normal blood flow we see in the MS brain. Reperfusion simply means to perfuse again, or redeliver blood. Reperfusion is a good thing and a bad thing. Reperfusion is a natural occurrence; it returns blood to tissue after there is an event which stops or slows blood flow, like a stroke or ischemia. Reperfusion brings essential O2 and glucose to cells after such an event, but it also brings inflammation and the immune system with it. Blood returns to the area of tissue where it had been absent, at a cost.

Dr. Dake mentioned in a presentation at ISNVD how hyperperfusion (otherwise known as reperfusion injury) occurs BEFORE an MS lesion forms. He referenced this paper, which discusses how this perfusion change happens before the break in the blood brain barrier, before the immune system entry, before demyelination. The very first step is a change in perfusion. I wanted to know--why?
http://brain.oxfordjournals.org/content ... 1.full.pdf

I believe reperfusion injury explains the relapsing remitting course of early MS and ties together Dr. Zamboni's research into CCSVI and hypoperfusion in the MS brain. There will be an explanation as to how this theory functions in progressive MS at the end of this note.

https://www.facebook.com/notes/ccsvi-in ... 0894457211

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
User avatar
cheerleader
Family Elder
 
Posts: 5048
Joined: Mon Sep 10, 2007 3:00 pm
Location: southern California

Re: Must Read Article on Hypoperfusion....

Postby 1eye » Fri Aug 02, 2013 10:24 am

David1949 wrote:
munchkin wrote:I asked Dr.Arata about MS patients having high blood pressure and he stated that most of his MS patients have low blood pressure. My bp is low and has been low normal for years.


Sounds like we need a poll.


I don't think this is an issue that democracy will solve, but let's get this straight. Blood pressure in your arm, as measured with a cuff, does not necessarily have to be the same as blood pressure in your head. Blood pressure is driven mostly by the heart, and drops every time it perfuses through an organ. Until it reaches veins, where it is much lower.

The reason the arm measurement is useful is that it is routinely compared to similar measurements in your arm, as well as those in millions of other people.

The arm measurement has only a limited-to-nonexistent relationship with your cerebral blood pressure, which is what a strain-gauge type plethysmograph measures. In both the case of the arm, and in Dr. Zamboni's measurements with plethysmography, the measurement does not necessarily generalize to pressure anywhere else in circulation of blood. It can be compared to normals and to others from the same person, to make inferences about heart pressure. That is all. It is not a direct or even very localized measurement.
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'MS' is over - if you want it
Patients sans/without patience
User avatar
1eye
Family Elder
 
Posts: 2931
Joined: Wed Mar 17, 2010 4:00 pm
Location: Kanata, Ontario, Canada


Return to Chronic Cerebrospinal Venous Insufficiency (CCSVI)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service