Post Hypoxic Demyelination

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

Post Hypoxic Demyelination

Postby cheerleader » Fri Jul 31, 2009 1:42 pm

Another proposed mechanism of how CCSVI creates those many scars. Post hypoxic (after a lack of oxygen to the brain) demyelination-

Here's a study of a man involved in a bad auto accident. He had massive blood loss, and his brain was deprived of oxygen for a while. He develops demyelinated lesions in his brain and has an overactive bladder.

Unlike previous reports of hypoxic-ischemic demyelination, our patient lacked any cortical abnormalities, presumably due to isolated white matter changes. This report alerts physicians to the possibility of hypoxic-ischemic demyelination due to global hypoxia-ischemia as an etiologic factor for neurogenic bladder.

http://www3.interscience.wiley.com/jour ... 9/abstract

Here's a man who suffered from hypoxia due to carbon monoxide poisoning.
A 40-year-old male presented with acutely oncoming neuropsychiatric symptoms in the form of extrapyramidal disturbances, personality change, behavior changes and urinary incontinence. One month prior to this symptomatology, he had been found unconscious in his closed room where a coal fire was burning overnight. He recovered completely in two days with supportive therapy. Magnetic resonance imaging during this presentation showed bilateral white matter changes suggestive of demyelination.

link

Both of these men recover, once the hypoxic incident is over, the brain gets oxygen again, and the lesions eventually heal.

If MS is a chronic, ongoing hypoxic insult to the brain and spine, due to CCSVI...it could be exacerbated by any event when further lessens oxygen to the brain...high altitude, viral or bacterial infection, vasoconstriction. More lesions are formed, the damage continues.

The hypoxia created by CCSVI is chronic, ongoing, but much slower than what happened in the studies above. It takes many years to develop damage. Restore oxygen to the brain and spine, and healing and remyelination should take place.
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Postby Sport » Fri Jul 31, 2009 3:53 pm

The potential for hypoxia and other cardiovascular issues to cause demyleinating lesions as described by Zamboni et al seems intuitively plausible enough.

However, does anyone have any thoughts on the mechanism by which a cardiovascular abnormality would lead to the CSF abnormalities--oligoclonal bands, IgG/albumin ratio, protein synthesis rate, etc.--seen by many/most MS sufferers?

This part is puzzling to me.
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Postby cheerleader » Fri Jul 31, 2009 4:53 pm

Sport wrote:The potential for hypoxia and other cardiovascular issues to cause demyleinating lesions as described by Zamboni et al seems intuitively plausible enough.

However, does anyone have any thoughts on the mechanism by which a cardiovascular abnormality would lead to the CSF abnormalities--oligoclonal bands, IgG/albumin ratio, protein synthesis rate, etc.--seen by many/most MS sufferers?

This part is puzzling to me.


Cerebrospinal fluid which contains higher weight proteins (IgG, IgA, IgM) shows the diffusion of plasma across an altered blood brain barrier. CSF with oligoclonal bands shows intrathecal synthesis. All of these changes to the CSF can occur when the blood brain barrier is breached. In CCSVI, hypoperfusion and slowed transit time of the blood from the brain back to the heart causes endothelial stress, and can create this break in the BBB. If your jugular veins are blocked...the blood still comes into the brain unhindered from your arteries, but takes longer to leave, stressing the vascular system. All sorts of things become deposed into the brain and CSF (via the villi)

After my husband showed CCSVI with 2 blocked jugular veins, and he had the stents put in, he had a huge headache for several days. Dr. Dake said the changes in his cerebrospinal fluid were to blame...that the changes in the fluid levels in his brain was like wringing out a sponge. We're hoping this fluid level change will allow his BBB to heal. Would be interesting to see a new lumbar puncture from him....but I doubt he'll do it!
hope this helps...
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Postby whyRwehere » Fri Jul 31, 2009 5:17 pm

cheerleader wrote: Would be interesting to see a new lumbar puncture from him....but I doubt he'll do it!


Too Right!
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Postby Sport » Fri Jul 31, 2009 6:55 pm

Well, if they find out that my veins are plugged up and I am able to have the procedure AND I feel markedly improved, I'll volunteer to have another one. :)

I had an LP following Rituxan treatment, but no significant change was noted from my pretreatment results.
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Postby patientx » Sat Aug 01, 2009 9:50 am

cheerleader wrote:
Cerebrospinal fluid which contains higher weight proteins (IgG, IgA, IgM) shows the diffusion of plasma across an altered blood brain barrier. CSF with oligoclonal bands shows intrathecal synthesis. All of these changes to the CSF can occur when the blood brain barrier is breached.


I'm not sure what you are trying to say here, but it seems like 2 contradictory things. If the IgG is produced intrathecally, then it doesn't originate in the blood. Further, when the lumbar puncture is performed, the spinal fluid is compared with a sample of serum, to see if the IgG level is different between the spinal fluid and serum.
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Postby cheerleader » Sat Aug 01, 2009 10:36 am

Right...I know how the lumbar puncture works. All I'm saying is that the bands that show antibodies from myelin being destroyed inside the CNS are ultimately due to the break in the blood brain barrier, and how this fits with the CCSVI research.

Immune activation/demyelination can happen after a hypoxic event in the brain...that's all I'm sayin'. That's why I linked to the studies above. They are extreme examples of hypoxic events that cause demyelination. CCSVI creates hypoxia. Sport was asking how proteins could end up in CSF. I hope I answered his/her question. If not, someone else please take a swing at it.
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Postby patientx » Sat Aug 01, 2009 3:01 pm

cheerleader wrote:Right...I know how the lumbar puncture works. All I'm saying is that the bands that show antibodies from myelin being destroyed inside the CNS are ultimately due to the break in the blood brain barrier, and how this fits with the CCSVI research.


As far as I know, the antibody bands seen in the CSF are not a result of demyelination. They are a marker for MS, but I don't think anyone knows why the antibodies are in the CSF.

By the way, unless I missed it, I don't think Zamboni mentions hypoxia in any of his papers.
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Postby cheerleader » Sat Aug 01, 2009 3:39 pm

patientx wrote:
cheerleader wrote:Right...I know how the lumbar puncture works. All I'm saying is that the bands that show antibodies from myelin being destroyed inside the CNS are ultimately due to the break in the blood brain barrier, and how this fits with the CCSVI research.


As far as I know, the antibody bands seen in the CSF are not a result of demyelination. They are a marker for MS, but I don't think anyone knows why the antibodies are in the CSF.

By the way, unless I missed it, I don't think Zamboni mentions hypoxia in any of his papers.


Not to belabor the point, but OCGB include IgM bands against myelin lipids.
Hypoxia is just a hypothetical for now. Dr. Zamboni has only written about iron-dependent inflammation in venous disease and the parallels to CCSVI as a means of injury in MS. This was just something we discussed with Dr. Dake as to how stenting provided immediate relief of fatigue in Jeff's case. I included the papers above to show how hypoxic injury preceded demyelination in these cases.
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Postby jimmylegs » Mon Aug 10, 2009 6:00 am

unexpectedly came across this interesting abstract on selenium, hypoxia, and high altitude:

At high altitudes, the reactive oxygen species are continuously generated as a consequence of low oxygen partial pressure (hypoxia), which causes tissue damage. The body's defence system to combat the oxidative stress (e.g., anti-oxidant enzymes, free radical scavengers such as vitamin C, vitamin E, beta-carotene, reduced glutathione and minerals such as selenium, etc.) may diminish. In the present study, the antioxidant effect of selenium (Se) in reducing the hypoxia-induced oxidative stress was evaluated by exposing male albino rats to hypoxic stress in a decompression chamber. Exposure to hypoxia resulted in an increase in malondialdehyde (MDA) levels in plasma and tissues and a concurrent decrease in blood glutathione (GSH), glutathione peroxidase (GPx), plasma protein and plasma selenium content when compared with controls. Haemoglobin concentration (Hb%), red blood corpuscles (RBC) and white blood corpuscles (WBC) count were also increased in the hypoxia-exposed group. Selenium supplementation to animals reversed the trend. There was a significant decrease (P < 0.001) in MDA and subsequent increase in plasma and tissue GSH levels. Similarly the blood and tissue GPx and plasma protein also increased significantly in the Se supplemented animals compared with control animals. The Hb%, RBC and WBC counts showed no significant difference between Se-fed and control rats. These results suggest that selenium may help in reducing the lipid peroxidation during hypoxia.
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Postby cheerleader » Sat Dec 04, 2010 4:14 pm

bump-
just 'cause.


One specific pattern of demyelination is defined by an oligodendrogliopathy, primarily affecting the most distant processes of these cells and leading to apoptotic cell death of oligodendrocytes at later stages of lesion development (Lucchinetti et al., 2000). These alterations of oligodendrocytes and myelin are similar to those present in acute ischaemic white matter damage and are associated with nuclear expression of hypoxia‐inducible factor‐1α (HIF‐1α).


http://brain.oxfordjournals.org/content/126/6/1347.full

The marker they utilize in this study in CSF, D-110, is found in CSF of MS and ischemic stroke patients.

And here's some more info on myelin reactive T-cells---they are NOT exclusive to MS (although they are not often tested in strokes and cerebral vascular disease--why would they be? It's obvious if you have a stroke, it would not be classified as "MS" )
In this study, those with ischemic cerebrovascular disease showed myelin reactive T-cells in their cerebral spinal fluid---

T cell reactivities to the putative autoantigens myelin basic protein (MBP), MBP peptides with amino acid residues 110-128 and 148-165, and myelin proteolipid protein (PLP) were examined in patients with acute ischaemic cerebrovascular disease (CVD) and, for comparison, in patients with inflammatory neurological diseases and other neurological diseases. A quantitative measure of these T cell reactivities was obtained by assessing numbers of T cells among blood and cerebrospinal fluid (CSF) mononuclear cells that secreted IFN-gamma in response to antigen in vitro. Higher numbers of T cells reactive with each of these four antigens were detected in peripheral blood from patients with CVD compared with patients of the two control groups. Among blood cells from the CVD patients, their average number was 2.3-4.2/10(5) mononuclear cells. MBP reactive T cells were several-fold enriched in the CSF of CVD patients. The findings strongly suggest that brain damage in context with acute CVD leads to an in vivo expansion of myelin reactive T cells.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1554378/
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Postby cheerleader » Sat Dec 04, 2010 9:15 pm

The Auto-Immune response after stroke--

To date, there has been little interest in exploring the possibility that autoimmune responses to brain antigens might affect outcome from stroke. There are, however, studies that document the fact immune responses to brain antigens do occur following stroke. For instance, lymphocytes from stroke survivors show more activity against MBP than the lymphocytes from patients with multiple sclerosis.18,19 In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease.20

These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke. Furthermore, there are increased titers of antibodies to brain antigens, including neurofilaments and portions of N-methyl-D-aspartate receptor, following stroke, indicating that there is also the development of a humoral response to these antigens.21,22 The immune response to CNS antigens after stroke is likely just an epiphenomena of stroke given that cerebral ischemic injury to the blood–brain barrier allows for the systemic immune system to come into contact with the antigens that are normally sequestered from it. Nonetheless, it is possible that this response leads to "collateral damage"; whether these immune responses affect outcome from stroke is largely an unanswered question.

http://stroke.ahajournals.org/cgi/conte ... uppl_1/S75

More myelin reactive t-cells in those with stroke than MS? More activity agains MBP? Why isn't there more study into MS as a vascular disease? Bueller? Anyone not busy arguing and still interested in research?
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Postby Johnson » Sat Dec 04, 2010 11:58 pm

Great bump, bump.

Thanks.
My name is not really Johnson. MSed up since 1993
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Postby TMrox » Sun Dec 05, 2010 6:09 am

Docs have known for a long time that trauma and vascular issues can cause demyelization.

Here a video of a 2010 symposium of rare neuro conditions.
The speaker is Dr Pardo (Johns Hopkins)
http://tinyurl.com/29qo895

The video is about my condition (Transverse Myelitis) but talks at length that arteriovascular malformations, blood clots (like a stroke), trauma can cause demyelinization. How the symptoms appear might help neurologist establish the cause.

Also the video shows MRIs scans of people with lesions caused by trauma, arteriovascular malformations, MS and Transverse Myelitis. These lesions might look different depending on the cause. Of course other tests are needed such as spinal taps.

Dr Pardo believes that some people with the current labels of MS or TM might actually suffer from other conditions (like the vascular issues he mentions). Interestingly he predicts that new conditions will be distinguished within the groups we currently know as MS, TM and NMO.
Diagnosed with Transverse Myelitis in December 2008. Inflammatory demyelination of the spinal cord (c3-c5). No MS, but still CCSVI.
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Postby cheerleader » Sun Dec 05, 2010 10:25 am

Thanks, Rox--
great video. It's so interesting to note that the immune system is activated after trauma, injury, break in blood brain barrier, hypoxia.

It's just that in most instances--who takes a lumbar puncture??? If you have a stroke, it's pretty obvious what's wrong with you. Why would the doctors look to the lymphocytes and MBP antigens for treatment??? It's only been in MS that the "mystery" has been dragged on for years, since taking on the body's NATURAL reaction to a break in the BBB has made lots of money and careers. Instead of looking for why the BBB is broken in MS the first place. (hypoperfusion and venous stasis and reflux, anyone?)

I'm really frustrated with this site...no more discussion of research, and more interest with male-dominated bickering and arguing. No research cited, just opinion. Me thinks a vacation is in order. I'm over at Facebook and thru the Alliance.

I'll try to pop in to keep bumping the research threads now and then (hypoperfusion and hypoxia) Because that's how this discussion started....with research. And that's how it will continue-
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