This Is MS Multiple Sclerosis Community: Knowledge & Support

Bob,
I really don't understand what you're trying to say. You wrote that COB frustrates you. Well, sometimes I can definitely say the same about you.
Of course I should have realized by now that we probably have a complitely different sense of irony, but I won't start using more smileys just because of you.
Then I suppose you're willing and able to explain why researchers have found axonal loss inside healthy myelin?

COB,
thanks for putting this thread back on its tracks.

-finn

_________________
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley

Finn, glad to help, especially if its while I stumble..

Lyon, ok already...

Lyon, ok already...

Finn,

I've got my sensible hat on this morning. The first two links are to summaries of presentations at an MS conference in June. The second suggests that a protein on axons might be the target of the immune response.

The third link is to Dr Coles. Campath 1-H is very good at dampening down inflammation. For those at the RR stage - there has also been a reduction in disability. Dr Coles speculates that this might be because of an increase in neurotrophins. I know that they have take blood from people who have received Campath 1-H and poured it on rat neurons and the neurons have grown.

Inflammation in MS has been viewed as a double-edged sword - destroying invaders (and sometimes our own tissue becomes collateral damage) and promoting repair (signalling to myelin making cells where to come to in the CNS). I'm assuming that although Campath knocks down the T and B cells, the inflammation which encourages repair is not totally irradicated.

Ian


http://www.mssociety.org.uk/go.rm?id=20354

http://www.mssociety.org.uk/go.rm?id=20355

http://www.neuroscience.cam.ac.uk/direc ... php?Alcool

Ian,

if EAE and MS were similar diseases we would have been cured already. Quotes from your links:

"Prof Perry used disease models to look at some of the factors which may be involved in tissue damage and subsequent disease progression during the relapsing remitting phase of the disease."

"Prof Linington’s studies show that the neurofascin on the axon is a primary target of the immune attack in disease models of MS and that these proteins accelerate disease progression and increase its severity. If this process is mimicked in humans, therapies which removed the antibodies which attack neurofascin could offer protection from disease progression."

And what comes to Campath, we'll just have to wait and see how well it works. I'm still far from changing my opinion, but I'm ready to eat my words anytime if it really stops this disease and we can focus on enjoying our lives instead of posting here.

-finn

btw, please, learn how to use shorter links ("hotlinks" or TinyURLs)

_________________
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley

Finn,

I only post what I see - unfortunately, many researchers still use animal models. You have also posted extracts based on animal models:



At least with therapies such as Campath, the researchers are looking at human guinea pigs. They take lots of blood from me and I've had lots of MRIs.

I will also be interested in the results of the Lamotrigine trials as this therapy will hopefully provide some benefit if MS is (i) an inflammatory disease which is then followed by neuro-degeneration or (ii) a neuro-degenerative disease which is followed by inflammation or (ii) both at the same time!

I'm still attracted to the notion of MS being caused by a virus (perhaps EBV). This might explain (i) the so called outbreaks of MS (ii) the age at which may are diagnosed with MS. Whether a virus causes stress on the neurones / axons which leads to degeneration or the immune system gets involved because it recognises there is a virus in the CNS is a matter for debate. I'm hoping that Prof Giovononni may be able to answer this in the near future.

Ian

Geez, talk about being misinterpreted. I was simply saying that I've always been fond of Finns because, statistically, the percentage who are asses is very low.
I suppose it's about time I read Harry's Z's favorite bedtime story, Prineas and Barnett's "Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion". Are you aware of any other research on the face of the earth which seems to confirm "axonal loss inside healthy myelin"?
If you'll scroll about halfway down the past page you'll notice that I put the thread back on its tracks. I'm glad to see that we're on good terms again, and you're more than welcome
Bob

Ian,
you didn't disappoint me, I thought you might refer to that study. I'm afraid you can't really compare it to standard EAE-studies. With a virus induced CNS dysfunction Tsunoda and Fujinami just showed that axonal degeneration can trigger demyelination. I believe you understand that the outcome was far from EAE, which is an inflammatory demyelinating animal model.

Btw, I use Firefox and the long link in your previous post really messes up the page layout and makes it quite difficult to read. It would be nice if you could make the link shorter.

Bob,yes, I am. And after all that time spent on this board you should be, too.

-finn

_________________
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley

Yes, a smiley face, much better! I guess my first, second, third,etc.... impression of you was wrong!

Admittedly I haven't read the article yet but just now finished downloading it and comments but Prineas and Barnett's reply to Professor Pender's comment seemed worthy of note

Finn,

You're getting grumpy in your old age - moaning about the length of my links!

The following should keep you off the Vodka for a couple of months. ECTRIMS is taking place in October 2007. Two presentations which may interest you are:

Friday 12 October 2007. MS - a neuronal disease? F. Zipp.

Sunday 12 October 2007. Charcot Award Lecture (MSIF):
“A peculiar lesion in the cord with atrophy” – Is multiple sclerosis an inflammatory or neurodegenerative disease? A. Compston (Cambridge, UK)

I'm off to enjoy the rest of a very bad (wet) summer in the UK. I'll return in the autumn after ECTRIMS.

Glad you and Lyon are getting on again.

Ian

Hi finn,
As I suppose you would expect, after reading "Relapsing and Remitting Multiple Sclerosis:Pathology
of the Newly Forming Lesion" I tend to agree with the subsequent responses by Lucchinetti
et al and Pender.

I am glad to have finally read the holy grail of the "non-autoimmune", "primary axon attack,
secondary myelin attack" crowd.

With it in mind that Prineas and Barnett's study was based on 12 subjects, I include the Lucchinetti
et al's response.
Bob

Ian,
I visited PubMed just to see what school of thoughts Zipp and Compston represent. After seeing the studies they've done I wouldn't be surprised if they both would argue that "MS is a inlammatory demyelinating disease with a neurodegenerative component".

Anyway, enough of this now. Enjoy the rest of the summer!

Btw, if you'd give it try, you might be amazed how easy it is to make the link shorter.


Bob,
I haven't read the whole article, either. Actually, to me one of the authors makes more difference than the text itself. John Prineas has been a respected figure in the "autoimmune camp", and his controversial paper finally opened the door to new and more innovative thinking amongst some other researchers, too.


Well, more recently Lucchinetti has been a cowriter in a study where you can find these quotes:

• "a primarily gray matter related process may be the earliest manifestation of MS"
• "Gray matter involvement is associated with physical disability, fatigue, and cognitive impairment in MS"
• "Gray matter disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, white matter gadolinium enhancement, white matter lesion burden) and disease progression."
• "Early cortical involvement seen on imaging studies raises the intriguing possibility that the GM may represent the primary and initial target of the disease process, leading to axonal degeneration and subsequent demyelination (the “inside-out” model of MS)."
• "One of the most important questions regarding GM involvement is whether it is a consequence of WM demyelination with secondary axonal damage leading to neuronal loss in GM structures or whether the GM, in particular neurons, are a direct target of the disease process."
• "Emerging histopathologic and neuroimaging studies support the concept that GM pathology occurs in part independently of WM lesions and may precede WM pathology."
• "It is hotly debated whether a primary neuronal or axonal process could lead to WM demyelination as opposed to WM demyelination leading to secondary axonal and neuronal damage."

-finn

_________________
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley

Hi finn,

I may disagree with your interpretation sometimes but there isn't much room to doubt your knowledge and awareness.

Thanks for the link. I won't have time to read that article today but I look forward to reading it soon.

I'm not sure how to force this thread into the next page.

Bob

Finn,

That's interesting stuff on gray matter from Lucchinetti et al.
I just noticed this related abstract (which was posted by Raven over 2 years ago, yet was just published 2 months ago).
Interferons aren't great MS treatments, but maybe their impacts on gray matter degeneration are significant.

I'll try to space this out to move us to a new page...




Interferon beta-1a slows progression of brain atrophy in
relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy

R. Zivadinov - Department of Neurology, Buffalo Neuroimaging Analysis
Center, The Jacobs Neurological Institute, University at Buffalo, State
University of New York, Buffalo, NY, USA, rzivadinov@thejni.org

L. Locatelli - Department of Clinical Medicine and Neurology, University of
Trieste, Trieste, Italy

D. Cookfair - Department of Neurology, Buffalo Neuroimaging Analysis
Center, The Jacobs Neurological Institute, University at Buffalo, State
University of New York, Buffalo, NY, USA

B. Srinivasaraghavan - Department of Neurology, Buffalo Neuroimaging
Analysis Center, The Jacobs Neurological Institute, University at Buffalo,
State University of New York, Buffalo, NY, USA

A. Bertolotto - Centro Riferimento Regionale Sclerosi Multipla (CReSM)
and Laboratori di Neurobiologia Clinica, Ospedale Universitario San Luigi,
Orbassano, Italy

M. Ukmar - Department of Clinical, Morphological and Technological
Sciences, University of Trieste, Trieste, Italy

A. Bratina - Department of Clinical Medicine and Neurology, University of
Trieste, Trieste, Italy

C. Maggiore - Department of Clinical Medicine and Neurology, University
of Trieste, Trieste, Italy

A. Bosco - Department of Clinical Medicine and Neurology, University of
Trieste, Trieste, Italy

A. Grop - Department of Neurology, Buffalo Neuroimaging Analysis
Center, The Jacobs Neurological Institute, University at Buffalo, State
University of New York, Buffalo, NY, USA

M. Catalan - Department of Clinical Medicine and Neurology, University of
Trieste, Trieste, Italy

M. Zorzon - Department of Clinical Medicine and Neurology, University of
Trieste, Trieste, Italy

Background
Brain atrophy, as assessed by magnetic resonance imaging (MRI), has
been correlated with disability in patients with multiple sclerosis (MS).
Recent evidence indicates that both white matter (WM) and gray matter
(GM) are subject to atrophy in patients with MS. Although neurological
deficiencies in MS are primarily due to loss of WM, the clinical significance
of GM atrophy has not been fully explored in MS.

Methods
We have undertaken a three-year, open-label study, comparing 26
patients who elected to receive intramuscular interferon beta-1a (IFN
ß-1a) therapy, with 28 patients who elected not to receive therapy. Both
groups had quantitative cranial MRI scans at study entry and after three
years, and standardized clinical assessments every six months. Brain
parenchymal fraction (BPF), GM fraction (GMF), and WM fraction (WMF)
percent changes were calculated, and T2- and T1-lesion volumes (LVs)
assessed.

Results
After three years, mean percent (%) change in BPF favored the IFN ß-1a
treatment group (IFN ß-1a —1.3% versus the control group —2.5%,
P=0.009), as did the mean percent change in GMF (+0.2 versus —1.4%,
P=0.014), and the mean percent change in T1-LV (—9.3 versus +91.6%,
P=0.011). At the end of the study, there was a significant within-patient
decrease in BPF for both groups (P=0.02 for the IFN ß-1a treatment group,
and P<0.001 for the control group), a significant within-patient decrease
in WMF for the IFN ß-1a treatment group (P=0.01), and a significant
decrease in GMF for the control group (P=0.013) when compared with
baseline.

Conclusion
Over a three-year period, treatment with IFN ß-1a significantly slowed the
progression of whole-brain and GM atrophy, and of T1-hypointense LV
accumulation, when compared with the control group.

http://msj.sagepub.com/cgi/content/abstract/13/4/490

Bob, Dignan,
I appreciate your efforts, but I assume it's the number, not the length of posts that will take us to the next page. Luckily the link in Ian's post is shorter now, and this page looks good on Firefox again.

Dignan,
thanks for sharing another interesting study. According to it there might be a weak correlation between T1-lesion volumes (T1-LVs) and gray matter fraction (GMF). Between treatment and control group there was a 100.9% difference in the mean percent change in T1-LV (-9.3 versus +91.6%) and 1.6% difference in the mean percent change in GMF (+0.2 versus -1.4%).

-finn

_________________
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley

Not to discredit the article dignan supplied because I do think it was interesting. Not at all specific to this article it's often discouraging to read the financial disclosures at the end. I suppose since the researchers disclose their financial interests we shouldn't doubt the findings of the studies, but I'm afraid it always makes me wonder.

Considering the situation, I think, researchers should be required to post conflict of interest information at the end of their abstract.




Thanks for the link to that other Lucchinetti you provided finn. It was very interesting and one of the most disheartening articles I've read recently, in that it seems that MS damage might be quite a bit more extensive upon diagnosis and affect far more aspects of the brain than I was formerly aware of.

I don't consider it to injure your argument that the body of the Lucchinetti article actually only mentions that it's currently contentious as to whether inflammation or neurodegeneration is first and actually doesn't specifically address that particular aspect much.
Bob