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Neurodegenertion continues after myeloablative strategies also.

Autopsy samples from these patients revealed that in
all cases there was an almost complete absence of inflammatory
markers in the brain, notably of T cells. On
the other hand, there was significant staining for amyloid
precursor protein (APP) inclusions, a marker of
acute axonal damage (Fig. 5). This suggested that even
though inflammation had been abolished, neurodegeneration
was still proceeding in the brains of these patients,
and thus that neurodegeneration was not a direct
consequence, at least in the short-term,of inflammatory
damage to the nervous system.These data are consistent
with the observation from MRI studies that the rate of
brain atrophy is high in patients who have received
hematopoietic stem cell grafts in spite of an apparent
complete cessation of inflammatory lesion activity

From Bruck W J Neurol (2005) 252 [Suppl 5]: V/10–V/15
DOI 10.1007/s00415-005-5003-6 I own a copy of that paper.

The case study posted by Dignan is most certainly of value taken together with other material such as this autopsy work.

Those of us in the 'degenerative not autoimmune' camp are perfectly justified in taking that position.

However I'd like to be clear that saying degenertive does not exclude the immune system activity being there after the fact and even being a problem. I believe that in the end it will be clarified that there is a triggering factor to the immune activation (perhaps Zambonis mechanical trauma hypothesis) and eventually some clarity that the immune activataion even though "justified" from a physiologic point of view, was over active and part of what causes the eventual damage.

here's a good example; spinal cord injury. If you get a broken back they now know that the inflammatory response causes a lot of the damage. Mitigating that effectively is going to be part of the solution to better outcomes.

however if you never broke it in the first place you'd do best of all

That's probably why every PwMS recently diagnosed has elevated liver enzymes including my wife, I am more than 90% sure this happens in almost all MSers, from five friends with MS all have or have had elevated liver enzymes!
And that's another reason for every individual to add milk thistle in his regimen.

i just posted on liver enzymes in 'the ms liver' dim, but i forgot to mention milk thistle it was more about zinc. if you don't mind my asking, what did you say your wife's zinc level was again?

Forgot Jimmy but it was slightly above the middle of normal range and she takes 50mg Zinc almost daily the last two years, imagine what her levels were when diagnosed without zinc supplementation!!

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wow dim. yea when i got mine tested it was 8.6. i supplemented no more than 100mg max in any one day for about three months (some days i took none, some days i took 50) and on followup i was up to 20 and had to back off.
optimal is 18.2 details at http://www.thisisms.com/ftopict-5486.html

Bob, you're absolutely right, nobody should put too much stock in this one case with unique characteristics, but it's still interesting. A lot of possible explanations...

Cheer, the study you posted definitely seems like one real possibility: we think the immune system is completely regenerated from the donor, but it isn't really.

Given how quickly the demyelination took place, it seems possible that it was some kind of infection, especially since the immune system was down.

As mentioned in the bit Bob posted, maybe graft vs. host was a problem in the brain in this case.

I'm not sure, but I don't see how rebooting the immune system would change venous insufficiency, so that still seems possible as a cause. But in this case maybe the immune activity was a bit too sudden and aggressive to be caused by a chronic disorder?

The quote from Finn that Hub posted about metabolic dysfunction in oligodendrocytes also seems to be in play since it presumably(?) isn't dependent on the immune system.

Other possibilities include the position of Venus in the night sky, the price of tea in China and don't even get me started on the potential role of a vast, right-wing conspiracy...

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This is still a hot topic. This research group seems to be very active in investigating inflammation and neurodegeneration. They come to some interesting and (for me) surprising conclusions.


The relation between inflammation and neurodegeneration in multiple sclerosis brains.

Brain. 2009 Mar 31
Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H.
1 Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria.

Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis.

The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological disease or brain lesions.

We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone. In older patients (median 76 years) with long-disease duration (median 372 months), inflammatory infiltrates declined to levels similar to those found in age-matched controls and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimer's or vascular disease.

Our study suggests a close association between inflammation and neurodegeneration in all lesions and disease stages of multiple sclerosis. It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.

http://www.ncbi.nlm.nih.gov/pubmed/19339255

Being in the autoimmune camp, this data is incredibly interesting. Given this data, I wonder how PPMS patients would respond, longterm, to HiCy therapy? ...Especially if the immunoablation were done in the early stages of PPMS. I would love to stop hearing that nothing can be done for this form of the disease. Though not as glamorous, for many of us, just stopping disease progression would be defined as a treatment success.

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Bob, you have me rolling on the floor. I'll be thinking of you at my dentist appointment tomorrow.

Sandy

mommasan wrote:Though not as glamorous, for many of us, just stopping disease progression would be defined as a treatment success.

I personally think that its getting a bit "greedy" to expect a single "treatment" to stop the disease AND push repair. Maybe using something such as HyCy to stop progression, followed by some of the newer stuff in the pipeline like Anti-Lingo1 to push repair is what it will take for some, for now.

Cureorbust, I couldn't agree more.

It's not beyond the realms of possibility that in the next ten years we could see ultra high res imaging showing deep grey matter inflammation, hicy/campath like treatment to stop the process, a more effective copaxone like treatment to retrain the emergent immune system and stem cell therapy/drug therapy to encourage neuron/myelin growth.

The technology isn't there right now but the path is becoming clearer. And one thing we know about technology is that its exponential, the political climate is positive for this too.

Take out your false teeth Momma because I want to suck on your gums!

EWWWWWWWWWWWWWWWWW!!!!!!!!!!

hicy/campath like treatment to stop the process, a more effective copaxone like treatment to retrain the emergent immune system and stem cell therapy/drug therapy to encourage neuron/myelin growth

I like the way your thinking Jaime!

Marcia