Also arterial flow is abnormal in MS

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Also arterial flow is abnormal in MS

Postby frodo » Wed Oct 16, 2013 3:58 am

While some people declare the relationship between blood flow and MS a dead research path, others find that the relationship is bigger than ever thought. This time, from London UK:

Cerebral arterial bolus arrival time is prolonged in multiple sclerosis and associated with disability.

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.

Edited. The article abstract is here: http://www.ncbi.nlm.nih.gov/pubmed/24045400
Last edited by frodo on Sun Oct 20, 2013 2:26 pm, edited 1 time in total.
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Re: Also arterial flow is abnormal in MS

Postby Cece » Wed Oct 16, 2013 7:23 am

It's great that they're looking at the arterial flow as well. The hypothesis at the end (that the reduced arterial flow is due to inflammation) should be readily testable by seeing if it is more reduced in patients with active inflammation and less reduced in patients without active inflammation. A counter-hypothesis would be that the arterial inflow is reduced because outflow is reduced due to venous obstructions and inflow and outflow are linked in a closed system.
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Re: Also arterial flow is abnormal in MS

Postby frodo » Thu Oct 17, 2013 2:27 am

Cece wrote:It's great that they're looking at the arterial flow as well. The hypothesis at the end (that the reduced arterial flow is due to inflammation) should be readily testable by seeing if it is more reduced in patients with active inflammation and less reduced in patients without active inflammation. A counter-hypothesis would be that the arterial inflow is reduced because outflow is reduced due to venous obstructions and inflow and outflow are linked in a closed system.


Yes. And even if it is due to inflammation, we will have an important biomarker to track the evolution, if this is confirmed.
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Re: Also arterial flow is abnormal in MS

Postby LR1234 » Fri Oct 18, 2013 11:08 am

Where was study done and by whom? If it's on your post apologies for me not seeing it!!
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Re: Also arterial flow is abnormal in MS

Postby Cece » Sat Oct 19, 2013 3:20 pm

This time, from London UK:

Journal of Cerebral Blood Flow & Metabolism advance online publication, 18 September 2013; doi:10.1038/jcbfm.2013.161.

ok that doesn't really answer the question :)
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Re: Also arterial flow is abnormal in MS

Postby 1eye » Sun Oct 20, 2013 11:02 am

I have 3 artery stents in my chest. Why couldn't atherosclerosis happen in brain arteries? It does, and causes stroke. I have heard MS describes as a 'slow stroke'.

From Wikipedia:

Atherosclerosis and Plaque Attacks

Plaques from atherosclerosis can behave in different ways.

They can stay within the artery wall. There, the plaque grows to a certain size and stops. "Because they don't block blood flow, these plaques may never cause any symptoms," says Stein.

They can grow in a slow, controlled way into the path of blood flow. Eventually, they cause significant blockages. Pain on exertion (in the chest or legs) is the usual symptom.

The worst-case scenario: plaques can suddenly rupture, allowing blood to clot inside an artery. In the brain, this causes a stroke; in the heart, a heart attack.

The plaques of atherosclerosis cause the three main kinds of cardiovascular disease:

Coronary artery disease: Stable plaques in the heart's arteries cause angina (chest pain on exertion). Sudden plaque rupture and clotting causes heart muscle to die. This is a heart attack, or myocardial infarction.

Cerebrovascular disease: Ruptured plaques in the brain's arteries causes strokes, with the potential for permanent brain damage. Temporary blockages in an artery can also cause transient ischemic attacks (TIAs), which are warning signs of stroke; however, there is no brain injury.

Peripheral artery disease: Narrowing in the arteries of the legs caused by plaque. Peripheral artery disease causes poor circulation. This causes pain on walking and poor wound healing. Severe disease may lead to amputations.
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Re: Also arterial flow is abnormal in MS

Postby frodo » Sun Oct 20, 2013 2:28 pm

LR1234 wrote:Where was study done and by whom? If it's on your post apologies for me not seeing it!!


Sorry. I forgot to put the link to the pubmed entry. I have edited to add it. Anyway, the information you ask for is:

J Cereb Blood Flow Metab. 2013 Sep 18. doi: 10.1038/jcbfm.2013.161. [Epub ahead of print]
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.
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Re: Also arterial flow is abnormal in MS

Postby David1949 » Sun Oct 20, 2013 7:57 pm

Venoplasty helps about 1/3 of the people who get it. Maybe it doesn't help the others because they have a different problem; possibly a restriction on the arterial side. That could give the appearance of a flattening of veins because veins are somewhat like a fire hose. They collapse simply because there isn't sufficient blood in them to hold them open.
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Re: Also arterial flow is abnormal in MS

Postby 1eye » Mon Oct 21, 2013 8:18 am

If there is a bolus whose arrival time at, say the deep grey matter, can be measured, could it not also be timed as to it's exit from the neck? That would give a definite cerebral transit time. Other things might be done, such as bolus transit time from the time of its arrival at the capillaries to the time it reaches the jugulars, and on out. Is it not so? Being able to fairly accurately visualize and measure vein size we should be able to determine (at least relative) pressure changes all the way down to the lower jugulars, vertebral veins and other collaterals.

That would give an accurate picture of arteries, arterioles, capillaries, venules, and veins. Such a picture could be drawn from stenosed and non-stenosed cases, in both normal populations and controls. Being able to determine pressure, even relative to the other end of a vessel, if not in fairly absolute numeric terms, should reveal if there are any stenotic places.

Why would such a study be solely the province of Neurologists? Sounds to me like something radiologists need to be involved in too. They might have a contribution to make. Someone like Dr. Haacke might also be key, as a scientist, with the aid of radiologists.
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Re: Also arterial flow is abnormal in MS

Postby ttucker3 » Tue Oct 22, 2013 10:17 am

Here are some thoughts on the relationship between scleroses on artery walls and scleroses on cerebral vein walls.

a. A venous obstruction (doesn't really matter why or where) that causes pulsatile reflux back into the brain would cause a standing pressure wave within the vein and sinuses - with successive narrow high pressure regions (probably each less than a cm long) of large pressure fluctuation and hence, hypertensive maxima, separated by regions of lower pressure, little fluctuation. Successive regions of hypertension are probably separated by perhaps 4 to 6 cm - half a wavelength.

b. If, because of the right combination of pulse rate, flow velocity and distance from the reflux-causing obstruction, there are any hypertensive maxima within the small veins approaching the venules, then the veins would be stretched or distended at those points. These would be stable, localized, hypertensive points and, while they would shift in position with changes in pulse rate, they would likely stay relatively stationary for extended periods of time (perhaps hours to even days).

c. At those localized hypertensive points, because the venous pressure is at a maximum, the gradient in pressure would be zero or close to zero.

d. Fluids do not flow at points of zero pressure gradient!!! (To help visualize this zero blood flow concept - think of Dr. Mark Haacke's flow quantification MRI plots where in an obstructed IJV the flow reverses from negative (toward the heart) to positive (away from the heart) each cardiac cycle. Note that in his measured flow reversal there is a stable point of zero blood flow, and this is measured over a number of cardiac cycles!!! While Dr. Haacke's measurements are taken (I believe) usually somewhere between C2 and C6, half a wave length (4 to 6 cm) away and again a full wavelength (8 to 12 cm) away (into the brain, through the transverse sinus etc) there would be another point of zero blood flow and hypertensive maxima.

e. (Note also that blood flow is non-Newtonian and at very slow flow rates, its viscosity increases substantially, creating additional flow resistance.)

f. Note also that such hypertensive, zero-flow conditions could likely occur for extended periods (hours, days, perhaps longer) in the fine veins (for example, the interior cerebral veins).

g. Under such conditions, leukocyte cell flow within the blood would certainly be substantially affected. The combination of very low flow rates and distended endothelial cells (that exist in specific, localized narrow vein regions) would offer natural conditions for the initiation of a cascade of leukocyte flow, rolling, capture, activation, aggregation, adhesion, inflammation, transendothelial-migration sequence (but only in the select hypertensive regions). (Simon and Goldsmith, 2001, provide a good review of this cascade) (Note also Lawrence et al, 1997, on Threshold Levels of Fluid Shear Promoting Leukocyte Adhesion…)


h. The above leukocyte sequence would also be consistent with the reported leukocyte/endothelial sequence origins of arterial scleroses (for example, Sloop 1996 and the book by Kensey and Cho "The Origin of Atherosclerosis - What Really Initiates the Inflammatory Process", 2nd Edition 2007), thus producing scleroses of similar apparent appearance in both arteries and in veins – all a result of irregular and slowed blood flow.

One or two follow-up thoughts:

The viscosity of blood would play into this sequence. Hence, is there any correlation between blood viscosity and risk of MS?

Venous scleroses (as opposed to white or grey matter scleroses) could then build up gradually over extended periods of time following increasing venous inflammation. Note that such inflammation and scleroses may not be directly traceable to a specific traumatic event, (but such could certainly exacerbate things).

The very localized regions of hypertension and slow blood flow predicted by standing pressure waves would occur only if the venous obstruction were abrupt, not gradual, since a gradual narrowing (perhaps over several cm) would not give rise to the reflux phenomena - like a sea wave being absorbed on a sandy beach vs a sea wave being reflected from a hard, vertical sea wall.

I think that regions of non-flowing blood, through the above leukocyte cascade, probably lead to the inflammation of veins which is the first domino in the MS creation sequence. I suspect that the inflammation that occurs on the arterial side as a result of irregular blood flow is similar to that occurring on the venous side for similar reasons.
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Re: Also arterial flow is abnormal in MS

Postby Cece » Tue Oct 22, 2013 6:37 pm

ttucker3 wrote:The viscosity of blood would play into this sequence. Hence, is there any correlation between blood viscosity and risk of MS?
Red Cell and Hemorheological Changes in Multiple Sclerosis

1987, Vol. 19, No. 1 , Pages 51-55

Leslie O. Simpson1†, Brett I. Shand1, Robin J. Olds1, Peter W. Larking2 and Michael J. Arnott2
1Pathology Department, University of Otago Medical School, Dunedin, New Zealand

Blood rheology in multiple sclerosis (MS) was investigated in 15 subjects with varying degrees of locomotor difficulties who were members of the local MS Society. Control data were obtained from blood samples from 25 male and 25 female normal blood donors. Whole blood viscosity was measured and blood filterability was assessed. Six MS females provided blood samples for scanning electron microscopy. Erythrocyte membrane fatty acids and phospholipids were assayed.

Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p < 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s−1 (p<0.05). MS erythrocyte filtration rates were significantly lower than controls (p<0.001). Leucocyte counts in MS were greater than controls both in males (p <0.01) and females (p < 0.001). MS erythrocyte morphology was greatly different from controls (p<0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p<0.01) but more phosphatidylinositol plus phosphatidylserine (p<0.02).

We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.

http://informahealthcare.com/doi/abs/10 ... 8709065135

That was from 1987. A newer one from 2012:
http://www.scirp.org/journal/PaperInfor ... erID=21173
The Haematological Profile of Patients with Multiple Sclerosis
Full article is available. Platelets are increased and hemoglobin decreased in the MS group.

An older one, from 1990:
http://iospress.metapress.com/content/r7x1q20504541181/
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Re: Also arterial flow is abnormal in MS

Postby Cece » Tue Oct 22, 2013 6:52 pm

ttucker3 wrote:The very localized regions of hypertension and slow blood flow predicted by standing pressure waves would occur only if the venous obstruction were abrupt, not gradual, since a gradual narrowing (perhaps over several cm) would not give rise to the reflux phenomena - like a sea wave being absorbed on a sandy beach vs a sea wave being reflected from a hard, vertical sea wall.

This could be a potential explanation for why intraluminal abnormalities seem to be associated with MS but vein wall narrowings may not be. (The intraluminal abnormalities are stuck out in the lumen of the vein, causing abrupt blockage, while the venous wall narrowings are gradual.)

So if this line of reasoning turns out to be accurate, then CCSVI has been misnamed and misunderstood, as it is a hypertension and not an insufficiency, and this may explain the difficulty in researching CCSVI. Measuring overall flow and narrowings might be a red herring. Instead researchers would need to look for abrupt blockages.
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Re: Also arterial flow is abnormal in MS

Postby ttucker3 » Wed Oct 23, 2013 9:31 am

Thanks for surfacing these Cece. More reading tonight. Joan was right. You're bright and articulate.
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Re: Also arterial flow is abnormal in MS

Postby ttucker3 » Wed Oct 23, 2013 12:37 pm

Thought I should clarify my point about zero flow - an interval of zero flow would occur at the same point in the cardiac cycle and at the same point in the veins for many, many cardiac cycles, but flow would be positive on one size of the zero for part of the cycle and negative for the other part. The total volume of flow in each cardiac cycle, of course, must be toward the heart. However, it means that in each cardiac cycle the leukocytes are dragged back and forth across that one point in the view.
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Re: Also arterial flow is abnormal in MS

Postby Cece » Wed Oct 23, 2013 8:16 pm

Thanks. :)

I'm still thinking about your post. There are new ideas there.
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