The Search for a Cause of MS

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The Search for a Cause of MS

Postby questor » Mon Aug 31, 2009 9:05 am

I just came across a short article written by Dr. T. Jock Murray, the author of Multiple Sclerosis: The History of a Disease:

The Search for a Cause of MS

I'd like to know more about the arguments behind the belief that an autoimmune irregularity is the cause of MS, especially given that this is so often taken as fact by organizations like the NMSS.

The link above states:
After World War II, the research on immunology rapidly advanced and it was noted that there was an immunological reaction around the plaques in MS. This led to the idea that this was an immunological disease.

Can anyone point me to a good summary of the arguments for and against an autoimmune etiology for MS?

Thanks in advance...

--Tracy
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Postby cheerleader » Mon Aug 31, 2009 9:35 am

Tracy,

Some thoughts on this (no research referenced, sorry.)
Neurologists point to the oligoclonal bands found in spinal fluid- created by myelin destruction in the CNS- as proof of an immune reaction causing the lesions in MS, and they are correct to do so. This banding and lesions separated in time and space are the current criteria for diagnosing MS. The immune system is indeed activated and attacking myelin in MS. However, the $64,000 question has always been why? The current thinking is this is an auto-immune reaction. Case closed.

We know that the immune system also destroys myelin in other neurovascular diseases- such as stroke and dementia. Neurovascular diseases also show oligoclonal bands in CSF. Yet these are not considered autoimmune diseases. In these scenarios- it is acknowledged that axonal death activates the immune system to come in and clean up. Within the CCSVI paradigm, we can see how axonal death created by slowed perfusion, hypoxia and reflux could activate the immune system, without autoimmunity.

So, how did MS become categorized as autoimmune, and stroke categorized as axonal death? Stroke is an obvious insult to the body, it occurs quickly. MS waxes and wanes. I believe it is because neurologists (following the lead of Charcot) hyper-focused on the lesions, without considering the rest of the body, and how bloodflow in and out of the brain might contribute to axonal death.
More to come...
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Postby notasperfectasyou » Mon Aug 31, 2009 9:43 am

There is a lot of pointing to do.....

I admire your interest and hope you can muster the energy and determination to really do this. Sounds like fun. I want to stir the pot a bit just to get you thinking........

You are right that it's a huge assumption that MS is an autoimmune condition. It might actually be an even more interesting thing to find out what all the assumptions are.

There is a second, important, but oft overlooked assumption .... that MS has a single cause. I feel that part of the reason it's so hard to nail down MS, is that the only thing we have that is certain is the evidence of damage at the end.

I think, with wonderment, of how archeologists can find a 3 inch bone in the ground and tell us, from that one thing, that there was a completely different species of dinosaur that no one ever knew about - and that it was 4 tons, 27 feet tall and walked on 3 clawed legs. I mean, even House doesn't get it right on the first guess!

Science has all but assumed that the myelin is damaged by white blood cells and making assumptions based on what we see at the end can lead to very innaccurate beliefs about how things came to be that way.

Ken

(Just might be one of the best explanatory links EVER!!!)
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Postby cheerleader » Mon Aug 31, 2009 10:29 am

Found it!
Zap posted a terrific research paper on the monster thread- delving into how MS became categorized as autoimmune. The authors believe it is because of the hierarchy in the medical profession. Neurologists and immunologists receive much more attention, fees, research money and clout than their vascular peers. They also develop drugs. They were higher on the food chain, and got to "claim" MS.

link to Social constructionism and medical sociology paper

A recent debate surrounding the pathogenesis of multiple sclerosis is analysed in terms of the skills, interests and backgrounds of the medical personnel involved. It is noted that the proponents of the vascular theory possess developed expertises in interpreting disease in structural, vascular terms, whereas their opponents' skills lie in immunology or neurology. Different observers have produced different conceptions of the disease because modes of observation, and the points from which observation takes place, differ. It is also noted that the debate over the causation and treatment of MS has occurred between a large and powerful social group and a weak and marginal one. The effects of this power inequality on the production and assessment of knowledge about MS are investigated.


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Postby questor » Mon Aug 31, 2009 11:38 am

Ken and Cheer,
Thank you for your responses and links, this information is very useful to me.

Here is a link to a paper I bumped into that discusses arguments pro/con virus-mediated autoimmunity and MS:

Arguments for Virus-Mediated Autoimmunity in MS

--Tracy
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Postby dignan » Mon Aug 31, 2009 12:19 pm

questor, I find this paper really interesting:

http://www.msforum.net/journal/download/20091657.pdf

We talked about it a bit in the "inflammation vs neurodegeneration" thread.
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Postby bibliotekaren » Tue Sep 01, 2009 4:53 pm

These are great articles -- you folks are keeping my printer busy!

Thanks for starting this Tracy and good luck at Stanford. And NAPAY -- not what I expected from you!

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Postby notasperfectasyou » Tue Sep 01, 2009 6:41 pm

bibliotekaren wrote:And NAPAY -- not what I expected from you!


Hey Donna, call me Ken. I'm not sure what was so out of character:

1) Willingness to be squishy about the cause
2) My rant about Indiana Jones
3) My linking to something cute

I actually think #3 illustrates something we should all take heed of. Ken
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Postby questor » Wed Sep 02, 2009 8:41 am

Understanding what autoimmunity is, and how its underlying mechanisms operate, is pretty interesting stuff as background reading related to the autoimmune theory behind MS. I just took a look at the wikipedia entry for autoimmunity, and it looks like it provides some understandable info for the layman, of which I am one. I'm assuming what it says is accurate and correct:

Wikipedia Article on Autoimmunity

I post this here in hopes others may find it interesting as well, and as a way to collect the link for future bedtime reading for myself...

(Also, checkout the wikipedia article on antibodies.)

--Tracy
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Postby notasperfectasyou » Wed Sep 02, 2009 9:06 am

Layman's explanation - read the 101 thread below...
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Postby questor » Wed Sep 02, 2009 9:59 am

Thanks, Ken,
I took a deeper look just now into the 101 link, and see a lot of useful information there. I'll add the 101 link to my reading list. Much of that discussion was posted fairly recently, so I'll start there to avoid unnecessary duplication. I'm sure we're all busy enough as it is (thanks to the march of technology)...

--Tracy
_______________________________________________________

Thanks for your suggestion in the post below, Cheer,

My reading list is growing.

I don't know anything about this author, or the reason why this paper was written (I didn't see a date and it doesn't appear to have been published), but several things caught my eye, including endothelial dysfunction, multiple sclerosis, nitric oxide, and magnesium:

MS and the Role of Nitric Oxide
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Postby cheerleader » Wed Sep 02, 2009 10:11 am

Tracy-
Another connection I found when reading the latest research on autoimmune disease was the relationship to "endothelial dysfunction." Every single autoimmune disease has this problem. The endothelium is the lining of our blood vessels, and nitric oxide is the molecule in control of vasodilation, the immune system and coagulation. Many things can upset the balance of nitric oxide (toxins, vitamin deficiencies, heavy metals, pollution, glucose, stress, viruses and bacteria)....the list of nitric oxide disruptors is a veritable laundry list of modern life, which might explain why autoimmune diseases are on the rise at an alarming rate. I know, we're all really busy...but when you get a sec, look into the correlation. PM me if you want more resources....I don't want to beat a dead endothelium :)
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We are all scientists and researchers now!

Postby GiCi » Thu Sep 03, 2009 6:25 am

I apologise, I cannot help but intervene in the discussion.
The debate whether MS is an autoimmune disease or due to many other imaginific causes has been going on for decades and where did it lead us? To this: MS is incurable. This discussion is as productive as to choose the weapon to use to kill yourself.
We have a strong positive correlation between MS and defective drainage of blood from the brain and this has been proven in every patient tested.
Are we frightened to hope? Does it sound too good?
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Postby SarahLonglands » Thu Sep 03, 2009 9:31 am

Charcot's pupil, Pierre Marie, focused on infection as being the cause of MS. One problem, many causes of infection weren't known then, so this theory fell by the wayside and the auto-immune theory took hold. The first antibiotic didn't become available until World War 2 and it is no use against the prime bacterial infection thought to cause MS: chlamydia pneumoniae, (see the antibiotics forum.)

Chronic infection can cause endothelial dysfunction:

C pneumoniae is known to patchily parasitize the cells which line small blood-vessels, causing episodes of vasculitis. This is a local inflammatory process characterised by tiny punctures in the vessel walls and leakage of blood-components into the surrounding tissue space. It can be visualized directly in the retinal veins, where the vessels appear to be coated with a thin greyish sheath. This sheath is comprised of T lymphocytes. A very similar pathology takes place in the brain in early MS. The association between sheathing of retinal veins and MS was first made in 1944. The anatomical distribution of lesions within the brain in MS is often centred on small veins; elongated plaques may follow the sinuous curves of the vessels they surround. [Esiri MM, ed. Oppenheimer's Diagnostic Neuropathology, 2nd edition, 1996 Blackwell: 256-9.] Vasculitic phemomena were recognised surprisingly early: in 1873 Rindfleisch commented: "If one looks carefully at freshly altered parts of the white matter in the brain, one sees with the naked eye a red point or line in the middle of each individual focus, the transversely or obliquely cut lumen of a small vessel engorged with blood. . . All vessels running inside the foci, but also that traverse the immediately surrounding but still intact parenchyma are in a state of chronic inflammation." Rindfleisch had recognized, over 130 years ago, that inflammation of small vessels — vasculitis — precedes neural damage.

Examination of the eye reveals retinal vasculitis in about a third of persons with early MS, but it is probably present in far more. It is especially common following optic neuritis (a common precursor of MS), and is characterised by leakage of dye in a fluorescein dye test, blood cells, and cuffing of the vessel walls by inflammatory cells. Where it is seen, there is a raised likelihood that MS will follow. I have noted that episcleritis (an inflammatory condition of the connective tissue between the conjunctiva and sclera involving vasculitic features) is also a frequent finding in those with MS. (Unpublished data.)


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There seem to be a number of factors which need to be in place before MS develops, including chronic C. pneumoniae infection and a genetic inheritance which determines a certain kind of response to this infection. Some people have a disease-form which is primarily driven by the infection; it is characterised by rapid progression and intoxication with bacterial metabolites. Untreated it results in a swift decline; it is rapidly fatal. This is the form that Sarah had. Paradoxically, it seems very responsive to treatment. Other people seem to have a disease-form where the host reaction predominates; the infection is slow, bacterial numbers are probably few. This seems to be less amenable to antibacterial treatment, and the disease may remain active until the remains of the dead bacteria (endotoxins) are removed. This may be problematic in an enclosed area like the brain. One might speculate that there are even some disease forms where autoimmunity persists autonomously. I think that most people with MS fall somewhere within these extremes. My own experience from advising many people with MS is that those with relapsing-remitting disease and early progressive disease can do well. Patients with later progressive disease respond less well, though this is not always the case. Generally speaking, the earlier that treatment is begun the better the result is likely to be and the more complete the resolution.

People with dense neurological deficits which have been in place for many years and which are situated in confined anatomical bottlenecks such as the cord or cerebellum may recover little function, but treatment may halt disease progression.


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A historic study was published by workers at the Vanderbilt School of Medicine in 1999. CSF samples from 17 patients with relapsing-remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND) were examined by culture, by PCR and by antibody detection. C pneumoniae was isolated from CSF in 64% of MS patients against 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. [Sriram S, Stratton CW, Yao S, Tharp A, Ding L, Bannan JD, Mitchell WM. Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis. Ann Neurol. 1999 Jul;46(1):6-14.] It should be noted that the methodology used by the Vanderbilt workers is fastidious. In tissue-culture isolation, for instance, repeated centrifugation and prolonged incubation was carried out; this is very important as in chronic infection the organism may produce few of the spore-like elementary bodies, and those that are produced may be damaged. (It is interesting to note that the discovery of Helicobacter pylori was made possible by extending traditional incubation times.)

http://www.davidwheldon.co.uk/ms-treatment1.html

Sarah
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Re: We are all scientists and researchers now!

Postby questor » Thu Sep 03, 2009 5:28 pm

GiCi wrote:I apologise, I cannot help but intervene in the discussion.
The debate whether MS is an autoimmune disease or due to many other imaginific causes has been going on for decades and where did it lead us? To this: MS is incurable. This discussion is as productive as to choose the weapon to use to kill yourself.
We have a strong positive correlation between MS and defective drainage of blood from the brain and this has been proven in every patient tested.


Interesting take. My understanding is that although CCSVI is related to MS, it has not yet been shown to be the single primary cause of CNS damage in MS. One theory I've grokked from my reading here is that the immune system is still the entity that causes that damage, not CCSVI per se. In that sense, CCSVI serves as a "missing antigen" in the cascade of events that leads to CNS damage. But, CCSVI may be only one of many triggers.

So, aside from the point that cheer made in her earlier post, I think it is also useful to better understand the immune system (at least in my case, as I know very little). Assuming I have stents put in place on Sept 16th, I plan to continue my use of copaxone, and LDN, when I recover.

I'm not yet ready to believe that CCSVI answers all the questions.

But, I'll be very happy if I learn that it does.

--Tracy
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