PPMS can be passed to mice by CSF. IS PPMS DIFFERENT?

[frodo]

"DMD"s could also make a measureable difference. But we will remain ignorant if we continue to treat this as more than one disease.

I agree partially. The problem is that neuros are treating different clinical courses as if they were different diseases. And that is obviously a mistake.

On the other hand, it is important to make a difference when they really are different diseases, as it happened with NMO. Even before NMO-IGg was discovered they knew that the disease was different because of the shape of the lesions.

A classification must be done, but for sure it should not be based in clinical courses.

[1eye]

"DMD"s could also make a measureable difference. But we will remain ignorant if we continue to treat this as more than one disease.

I agree partially. The problem is that neuros are treating different clinical courses as if they were different diseases. And that is obviously a mistake.

On the other hand, it is important to make a difference when they really are different diseases, as it happened with NMO. Even before NMO-IGg was discovered they knew that the disease was different because of the shape of the lesions.

A classification must be done, but for sure it should not be based in clinical courses.

Whatever it is that is causing my disease, it is the same thing that has caused it since 1982. I very strongly believe this. Moreover, I believe strongly that no help for me will come from anyone who thinks otherwise. Maybe I am being my own worst enemy. I do not think I am.

If anyone is ever going to find the cause of MS, they must stop thinking it is different when there is a different disease course. What if we were to test for a significant difference between the two cases of mice-injected-with-CSF of progressive MS patients who are not taking DMDs versus mice-injected-with-CSF of progressive MS patients who are being treated with DMDs. Never mind that DMDs don't improve progressive patients. Maybe they'll improve the mice! I think it is too often forgotten or ignored that just because a person doesn't heal at the same speed as another does not mean no healing is taking place.

[Cece]

A classification must be done, but for sure it should not be based in clinical courses.

The different courses, at their extremes, are so different, I find it hard to believe that they are the same disease, but that's comparing mild RR to severe PPMS.

RR that progresses into SP is the same disease as it was when it began, with the addition of the neurodegeneration that has accumulated and less inflammation.

[frodo]

The different courses, at their extremes, are so different, I find it hard to believe that they are the same disease, but that's comparing mild RR to severe PPMS.

RR that progresses into SP is the same disease as it was when it began, with the addition of the neurodegeneration that has accumulated and less inflammation.

OK. From that point of view I agree. It could be interesting to have a classification based in the clinical course, but only according to the GLOBAL clinical course. And there are only two. (RRMS/SPMS vs. PPMS)

To separate RRMS and SPMS as two diseases is quite bad, but sometimes it gets worse than that. Sometimes they even treat CIS as a different disease. Or consider that having MS is the same than having a positive in McDonalds criteria. Or other criteria. Besides they don't even use the same criteria in different articles.

At least it should be avoided to classify the disease according the stage in the evolution.

[1eye]

I remember the last time I saw my friend who died at 30 with ppms. His voice had an unmistakeable ms hoarseness. I never thought I would, but I hear it in myself. ppms is faster but it does a lot of the same stuff. if you are lying down a lot, and your jugulars are not working, things go pretty slow up there.

It all ends up the same way if you live long enough. I remember when I was rrms. Didn't think a lot of stuff would ever happen.

[Cece]

Medpage had an article about this today, suggesting that MS be viewed on a continuum.
http://www.medpagetoday.com/MeetingCoverage/AAN/51114

The "topographical" model could provide a new way of looking at disease course, Stephen Krieger, MD, of Mount Sinai in New York City, told MedPage Today.

if you are lying down a lot, and your jugulars are not working, things go pretty slow up there.

It all ends up the same way if you live long enough.

There is hope that fixing the jugulars might change the disease course. Knock on wood...

[1eye]

http://www.medpagetoday.com/MeetingCoverage/AAN/51048

https://www.youtube.com/watch?v=6H5Goh_yGfs

[frodo]

New article somehow related to the previous one. This time is about RRMS been passed by B-cells (from peripheral blood)

For sure if this is true, this would make a much better model than EAE

B Lymphocytes from MS Patients Induce CNS Pathology in a Murine Brain Slice Model

http://www.neurology.org/content/86/16_ ... .321.short


Objective: Discover mechanisms by which B cells may drive MS pathogenesis. Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), featuring demyelination, activated lymphocytes, astrogliosis, and axonal loss. Suppression of disease progression via B cell-targeted therapies indicates important roles for B cells, requiring further studies of B cell mechanisms.

Design/Methods: Cerebellar slice cultures were generated from P10 mice and cultured for 12 days. CD19+ B cells were isolated from peripheral blood mononuclear cells of patients and controls, then added to cerebellar slice cultures or astrocyte cell cultures for 24-96 hours. Slices or cells were fixed and immunostained; media was collected for cytokine analysis. In other studies, B cells were isolated from mice and exposed to stimuli before culturing with cortical murine astrocytes, then analyzed for GFAP reactivity and iNOS production.

Results: B cells from MS patients, but not controls, induced astrocyte and microglia morphological changes, oligodendrocyte loss, and demyelination. In order to analyze astrocyte responses, we treated primary astrocyte cultures with murine B cells stimulated under different conditions, or human B cells isolated from MS patients. Under specific activating conditions, murine B cells altered astrocyte morphology, upregulated GFAP expression and intracellular iNOS. Evaluating the astrocyte responses to B lymphocytes from untreated MS patients or controls is currently in progress, as well as identifying mechanisms of B lymphocyte mediated CNS pathology.

Conclusions:

B cells from MS patients mediate CNS pathology in organotypic slices similar to that observed in histological studies of MS tissue. These effects include morphological changes in astrocytes, oligodendrocyte death, and demyelination.

This system will allow for the identification of the target cell(s), as well as assist in identifying key unknown biological mechanisms underlying MS.

This study was funded by an Independent Medical Grant from EMD Serono and the Rocky Mountain Multiple Sclerosis Center.