Dr. Ge at ISNVD

[1eye]

It may be unrelated to CCSVI but don't rule it out. I bought a book called "Vascular Dementia" that has a lot of papers on this. The problem in this case seems to be that we have too much oxygen our brains can't use. And you know what happens when free radicals get together with O2. Plus there is this hypoxia that is really mitochondria not being able to breathe. I think this guy's onto something...

Add CCSVI (slow drainage) to this problem of too much O2, and you have disaster, dementia, degeneration, etc.

From Dr. Ge:

In MS, the presence of a tonically high NO level (even during resting) may alter endothelial function (vascular habituation) with a consequence of decreased vasodilatory capacity and limited blood supply when neurons perform a demanding task. This deficit in cerebral vascular reactivity (CVR) may in turn cause more neuronal damage (activity induced hypoxia) as a result of transient but frequent ischemic attacks during daily life, which is another result of excessive NO that cause damage to previously healthy neurons, thereby a progression of neurodegeneration.

Somebody lately posted something about microbleeding only visible under 7T MRI.

Sounds like the treatment for this (beyond exercise and ballooning jugulars) might be tres tricky.

Now I have to stay away from those "demanding neuronal tasks". I knew I should never have given up my laid-back stoner lifestyle!

[cheerleader]

Hi Chris--
I was the one who posted Dr. Ge's other study, which showed microbleeds in the MS brain using 7 Tesla. Jeff and I heard him present his reseach (not yet published) at ISNVD, and it was sobering.
http://www.thisisms.com/forum/chronic-c ... 24352.html

More researchers are noting this break in the endothelium, and detecting these microscopic bleeds in the MS brain. At the ISNVD conference, Dr. Yulin Ge recently discussed how 7T MRI technology is allowing us to see tiny hemorrhages in the MS brain which occur before demyelination. This further elucidates the microvascular connection to MS.
From his abstract at the ISNVD:

Being the most common demyelinating disease of the central nervous system, multiple sclerosis (MS) MS has a significant microvascular pathological component as a consequence of the perivascular inflammation. The role of vascular pathology in MS was suggested long ago. Now there is accumulating evidence of a primary vascular pathogenesis in MS. In vivo studies of vascular and hemodynamic impairment in MS may provide insights into the etiology and pathophysiology of MS and offer the potential metrics for assessment of outcome of the disease.

http://ccsviinms.blogspot.com/2014/03/b ... tters.html

Ge's other research is about an underutilization of oxygen by the MS brain. And underutilization of O2 happens in diabetes, CFS, RA and other disease states. But maybe using the brain more, and keeping those neurons active, might be a better idea than zoning out.

Our results are consistent with the findings of the prior PET study (1), suggesting that significant underutilization of oxygen in MS might reflect the diffuse neuronal cells inactive state due to diffuse nature of the disease rather than neuronal tissue loss. The study may raise important questions regarding oxygen metabolism in MS as a component of neurodegeneration that leads to progressive and global neuronal cells dysfunction.

http://cds.ismrm.org/protected/11MProce ... es/601.pdf

We see this underutilization of O2, or decreased O2 uptake, after stroke:
http://stroke.ahajournals.org/content/30/7/1424.full
This also happens in people with very low blood Ph levels, and decreased ability to extract glucose from blood.
http://ccforum.com/content/pdf/cc9072.pdf
People with CSF have this problem, too. It causes exercise intolerence.
http://www.translational-medicine.com/content/12/1/20
lots more to learn.


cheer

[1eye]

When I was 26 or so I devised an experiment to measure the efficiency of the human body on a bicycle ergometer. I was my own test subject, and I have tabular and graphical data from that test. At various cadences, I measured my exhaled carbon dioxide and my oxygen uptake (!!). I'm sure I could repeat that test, because the same guy who helped me with it at Carleton University still works there. I'm sure my cellular uptake in my brain is different from what we measured (whole body, during exercise versus still in an MRI machine), by collecting gases in a neoprene balloon, but it might be very interesting to repeat it 35 years later and compare the results, using myself as a healthy control!

[1eye]

The other fact I know about this pathological state is that it is definitely, without a doubt, affected by heat. I had thought heat must be affecting the viscosity of my blood, but another thing that might be happening is that heat (also inflammation, which includes heating) speeds up chemical reactions. The fact that iNOS can come from inflammation may be very meaningful. Perhaps the effect of a hot bath in "MS" is to increase iNOS and prevent mitochondrial respiration, a process which seems to be greatly accelerated by temperature.

If a chemical reaction can be identified it should be simple to test for it. It seems the culprit may well not be NO itself, but one of those NOS's.

-Chris

Sure could be, Chris. I dunno. Looks like cooling pwMS reduces iNOS production (leukocytes create inducible NO) Seems like cooling garments would help.

http://www.ncbi.nlm.nih.gov/pubmed/11552024

Neurology. 2001 Sep 11;57(5):892-4.
Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production.
Beenakker EA, Oparina TI, Hartgring A, Teelken A, Arutjunyan AV, De Keyser J.

Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 degrees C (active cooling) and 26 degrees C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production This effect on NO could be relevant because it blocks conduction in demyelinated axons.

Anecdotal--Jeff had terrible heat intolerence (couldn't move when hot, fell asleep) which completely went away after stenting of dural sinus and jugular veins. We've thought it was due to brain cooling affect....but honestly, who the hell knows? Here's the upright doctor on heat intolerence in MS and the "radiator theory."
http://www.upright-health.com/brain-cooling.html

wish the way was clearer for you, Chris.
cheer

This is a fascinating result. I think this might be a significant finding. The microbleeds Dr.Ge has seen on 7T MRI might be the source of the leukocytes that produce the NO when you are overheated. It could be what is causing the mitochondrial dysfunction. Demyelinated axons are common in "MS". So these could maybe be causing both brain hypoxia and overheating, all by iNOS production?

If somebody told me when I was too hot that my demyelinated axons were blocked, I'd say right on. Plus it improves when you cool off.

[1eye]

I'm booked to do a re-test of my oxygen efficiency on a bicycle ergometer test. I was thinking of adding a phase after a hot shower, to see what difference that makes. I can't get any Diamox in time, or I'd try that too. Has anyone got any other suggested wrinkles?

http://sullivanweb.me/pdfdocs/EffOnABic ... graphs.pdf

Apparently they now have breath-by-breath gas analysis, so I'll have a lot more data points!

[1eye]

Did the exercise testing this morning. No results yet, but I have the impression my exhaled O2 was very high (I wasn't absorbing it). If true that might go along with the theory that immune cells are inducing NO and starving the mitochondria of oxygen. To tell whether the mitochondrial hypoxia is a temperature sensitive phenomenon I did an extra run with a cooling bandana to see if this had the same effect as Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production (40% NO reduction leading to better O2 utilization). But nothing was numerically known, so it is a very subjective test. I will think about doing an improved, repeat test. The heat, I subjectively maintain, did make the work harder.