Premature immunosenescence in rheumatoid arthritis and multi

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Premature immunosenescence in rheumatoid arthritis and multi

Postby Brownsfan » Tue Dec 27, 2005 6:17 pm

I picked this up on Brenda's LDN site http://ldn.proboards3.com/index.cgi

Patients with MS & RA have Weak Immune Systems. Research reported in the Annals of the N.Y. Academy of Sciences ("Premature Immunosene­scence in Rheumatoid Arthritis and Multiple Sclerosis Patients," June 2005) studied immune system elements in over 130 people—60 patients with rheumatoid arthritis, 32 with multiple sclerosis, and 40 healthy controls. The patients showed evidence of premature aging of the immune system, which the investigators state "could be a risk factor for developing autoimmune disorders in genetically predisposed individuals in a susceptible environment." This report offers important further evidence for the correctness of the current view that LDN's action in halting the progression of autoimmune diseases is accomplished through strengthening the immune system.

Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients.

Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P.

Biomedisch Onderzoeksinstituut, Limburgs Universitair Centrum, Universitary Campus, Building A, B-3590 Diepenbeek, Belgium. piet.stinissen@luc.ac.be.

Patients with T-cell-mediated autoimmune diseases show immune system abnormalities that resemble the typical characteristics of autoimmune dysfunction described in the elderly. In addition, the incidence of autoimmune disease increases with advancing age. To evaluate whether patients with rheumatoid arthritis (RA) and multiple sclerosis (MS) have premature immuno-senescence, we measured two indicators of aging: the number of T-cell-receptor excision circles (TRECs) and the percentage of CD4(+)CD28(null) T cells. We studied them in the peripheral blood mononuclear cells (PBMCs) of 60 RA patients, 32 MS patients, and 40 healthy controls (HCs). We found that TREC numbers were lower in RA and MS patients than in age-matched HCs, indicating premature thymic involution. Moreover, a subset of these patients contained age-inappropriate high frequencies of CD4(+)CD28(null) T cells. This study provides evidence of premature immune system senescence in both RA and MS patients. Premature aging could be a risk factor for developing autoimmune disorders in genetically predisposed individuals in a susceptible environment.

PMID: 16126966 [PubMed - in process]
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Postby mrhodes40 » Tue Dec 27, 2005 7:05 pm

Interesting but I'd like to offer a different point of view. immunoscenescence is a result of decreased apoptosis ( the programmed cell death that allows old cells to die and new ones to replace). Decreased apoptosis is a result of a couple of factors well known. Cytomegalovisrus turns down apoptosis and so does chlamydia pneumoniae. This is a stragtegy used by many germs to keep themselves viable in the cell they've taken over. It's well known. If researchers were not so committed to the autoimmune model, they might pick up on this instead of proposing yet another novel way for "autoimmunity" to manifest. I have a non autoimmune bias personally.
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Immunoscenescence and Hormones

Postby Shayk » Tue Dec 27, 2005 8:36 pm

Brownsfan--I find the information intriguing myself. Thanks for posting it.

Here's an abstract on immunoscenescence from another perspective:

Hormones and Immune Function: Implications of Aging

Aging is associated with a decline in immunity described as immunosenescence. This is paralleled by a decline in the production of several hormones, as typically illustrated by the menopausal loss of ovarian oestrogen production. However, other hormonal changes that occur with aging and that potentially impact on immune function include the release of the pineal gland hormone melatonin and pituitary growth hormone, adrenal production of dehydroepiandrosterone and tissue-specific availability of active vitamin D. It remains to be established whether hormonal changes with aging actually contribute to immunosenescence and this area is at the interface of fact and fiction, clearly inviting systematic research efforts.


Marie wrote:

Interesting but I'd like to offer a different point of view. immunoscenescence is a result of decreased apoptosis ( the programmed cell death that allows old cells to die and new ones to replace).


Do you have a link or reference to your statement about immunoscenescence? Is the abstract I posted consistent or inconsistent with your statement? I have no earthly idea myself.

Thanks to both.

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Postby mrhodes40 » Wed Dec 28, 2005 9:45 am

Here are references
http://www.immunityageing.com/content/2/1/5 is one reference, this one focused on cytomegalo virus. potentially EBV might do this also, I know the fact that boston cure is interested in funding EBV research has got some people interested in possible connections so I'll throw that in

http://www.pcom.edu/Research/Research_a ... holar.html is another this one is a list of studies being done. In this list is a study on immunosenescence and CPn funded by the NIH, so this is not a weak study nor is it unsupported by other data already. The study is not done but I wanted you to see it's there
In spite of the fact individual doctors are largely unaware of new research unless it's being offered and explained in person by the pharmaceutical guy in the suit in his office, in other words research done by companies the DIRECTLY impact his prescriptive decisions today, this kind of interesting non clinical research will eventually filter down but it wil take a long long time. Your doctor does not know that immunosenescence might be caused by CPn so if he read the study above he doesnot go "hey, my patient told me she was doing abx for MS...is it connected?" He does not have time for this kind of thing. If you click the name of the woman doing the research you can read a bit about her other work.

http://iai.asm.org/cgi/content/full/73/3/1723 is a citation that oulines the aging of systems related to CPn (chlamydia pneumoniae) You can finds lots more if you look.

Here's my bias: I read the prineas and barnett paper: Barnett, M H Prineas, J W. Relapsing and remitting Multiple Sclerosis: pathology of the Newly Forming lesion. Annals of Neurology Vol 55 No 4 April 2004, about 1.5 years ago and it was a mental water shed for me. I literally fell over the autoimmune fence and became a non autoimmune believer. The nerves die THEN the immune system comes in. This work has been followed up by others all over the world supporting the findings. All this stuff about how to stop the immune system is totally moot, and this is why EAE is curable (it has been for decades) and MS is not. the problem is the model. EAE is curable because it is a pure autoimmune disease created by researchers. Things that cure it do not cure people with MS. Copaxone cures mice of EAE for example. But even if you stop the immune system altogether people with MS still progress. Did you know that progressive people have very little inflammation at all? The campath trials looked good at first, then the people got worse. Why? because it is not their immune system doing this. Something else is killing the nerves then the immune system comes in just as it is supposed to and does what it is supposed to do, namely clean up the damaged area and stimulate repair which results in inflammation, scar tissue and lesions. Stopping that process has not resulted in better outcomes. If it did we'd all be on steroids and not progressing.

SO after I came to believe the autoimmune model is incorrect, I stumbled into the CPn material on David Wheldon's site. After reading that I thought it was a plausible possibility in the non autoimmune areana as a contender for the cause of this nerve death. As I studied I became more interested in how oddly CPn behaves. It is not a normal germ and it causes inflammation and trouble wherever it goes though it is a germ that is very quiet and stealthy in the body because it hides inside your own cells. Because of this you do not react to it aggressively it is what is called a slow infection and it is hard to detect. You accomodate to it as it gains an ever increasing foothold, though individual cells are greatly impacted, you as a person are not aware of it. The centers for disease control call it an emerging pathogen in the disease of atherosclerosis because study after study finds it in the atherosclerotic plaques where it causes local inflammation. This is an important designation. You might wonder what kind of cells they invade: among others there is microglia, oligodendrocytes, monocytes, red blood cells, and are particularly fond of attaching to blood vessel walls and able to go through into tissue beyond.

So I am honest about my bias here. As I read more research on this interesting germ, it has more and more areas of connection to MS, and frequently things like the immunosenescence work above turn out to be connected. This is hard not to share with others, so I am here telling oyu my point of view. I know some people reading this have different biases, I hope not to offend but to share the things I see. CPn Help.org has a vast library of resarch on CPn including many actual citations you can read.
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Immunosenescence and MS

Postby Shayk » Wed Dec 28, 2005 8:53 pm

No Marie you haven’t offended at all and I certainly have my own biases. I appreciate you diligence and the links.

Unfortunately I don’t think I phrased my question correctly. Since you stated that immunosenescence was the result of decreased apoptosis I was primarily interested in a reference for that specific statement. Even though I don’t have any scientific or medical background or training I somehow thought there might be more to immunosenescence than just decreased apoptosis, or programmed cell death.

Nonetheless, I followed a couple of the links and it’s my impression those studying cpn and the immune system do seem to embrace “immunosenescence.” From Dr. K. L. Fresa-Dillon’s article about cpn:

“as that immune system starts to decline as a function of age, it allows the infection to flourish.’ ”

From the AIA article by Little, et al,
Many of these diseases linked to C. pneumoniae ……..are more common or more serious in aged individuals.


You asked:
Did you know that progressive people have very little inflammation at all?


Yes, actually, based upon what I’ve read about MS it’s been my understanding that people with progressive MS have very little inflammation. That’s why I was surprised (and still am) that so many people on the abx regimen are so elated about and/or anxious to have MRIs and see the results, since, as you’ve noted, there’s typically less or very little inflammation in people with progressive MS and/or as the disease itself progresses.

You also noted:
frequently things like the immunosenescence work above turn out to be connected.

I’m assuming from your initial post on the topic that you firmly reject the notion that there might be premature “immunosenescence” in people with MS. With that assumption, I’ve got a couple of questions I’d like your perspective on. If, per the links you posted, the cpn infection flourishes as one gets older, and cpn is the cause of MS,

1. Wouldn’t you expect to see more and not fewer inflammatory lesions on MRI in aging individuals with SPMS or PPMS? and

2. Wouldn’t you expect to see more people diagnosed with MS at an older age (since that’s when the infection flourishes) instead of a much younger age, 20-40, as seems to be the case in MS? What am I missing or not understanding? Something obvious I’m guessing since I frequently miss “the obvious”.

Thanks Marie. As an FYI I’m also in the “not auto-immune” camp (have been from the gitgo) and hopefully honest about my bias as well, that is an interest in possible connections between hormones and MS. So, on that note, here’s a tidbit: Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo

These results suggest that sex hormones may modulate cytokine production in vivo and contribute to gender-related differences in normal and pathological immune responses.


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Postby mrhodes40 » Thu Dec 29, 2005 7:25 pm

I will backchannel you. I am reluctant to hijack the general board with cpn talk.
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Postby Melody » Fri Dec 30, 2005 5:53 am

Hijack away this is interesting to say the least. I have stated many times that I'm not frightened of immune booster's such as garlic as I don't believe John's immune system was the cause I believe it was the result of trying to fix something that went wrong due to anaphylactic shock. That's just John's case. I realize copaxone fights against that but John made that choice and I of course support his choice first :D
John was diagnosed Jan 2005. On lipitor 20mg .On Copaxone since July 4,2005. Vitamin D3 2000iu-4000iu (depending on sunshine months)June 10 2005(RX::Dr. O'Connor) Omega 3 as well Turmeric since April 2005. Q10 60mg. 1500mg liquid Glucosamine Nov 2005.
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Postby mrhodes40 » Sat Dec 31, 2005 9:53 am

Gosh I wrote a reply to you Sharon but it's not in my sent box. Since Melody asked for an open reply I'll do that.

Senescence on a cellular level is a cell which is old enough it no longer divides or functions. Ordinarily old cells like this undergo apoptosis also called programmed cell death. They simply breakdown and die, but without an inflammatory angle to it as a cell dying, say, of a virus would which would be necrotic death. programmed cell death is an orderly way for cells to be exchanged for young cells. If a cell is senescent it is speculated to have lost enough telomeres that it no longer can divide. This is well established in vitro(petri dishes) but still undergoing research in vivo (in bodies) Cells that divide and live on without stopping or apotosis are out of control cancer cells. If apoptosis is stopped by default old cells will be senescent. Immunosenescence is aging of the immune system specifically. My comment had to do with the fact that it is known that CMV causes senescence of immune cells (first ref in my earlier post read it all) and I speculated that CPn would also cause this as it is known to turn off apopotosis in immune cells which are one of the cell types it likes to inhabit and sure enough reference 2 in my earlier post showed a woman doing research on immunosenescence and CPn thus supporting my educated guess. I hope that is a better explanation.

As for the PPMS and SPMS people wanting MRI's did you think that MRI's appear clean in SPMS because they have less inflammation? They do not. The natural course of the disease is for an increase in lesion load in these folks. The process contiues, but the body is not responding to the lesions with inflammation any more. There is less repair when less inflammation also, a good reason for RRMS to result in remissions is that inflammation does happen and thus repair. It is known that inflammation is repairative in the MS brain. If you look at research of any of the drugs they have tried to use on SPMS which had MRI outcomes as a measure, every one will show an increase in lesion load in spite of whatever treatment was tried. We can conclkude that progressive MS brains always accumulate lesion load
People doing abx are wanting to see their MRI to see if any new lesions are there or if in fact there is a reduction in lesion load. Sarah had an MRI after abx treatment and some lesions were gone ( a reduction in lesion load) while other old lesions appear to be permanent. Her diagnosis was SPMS pre treatment.
Only a few people doing abx have this kind of data to share. People who have done well on abx, like Katman who after 10 years of continuous losses with PPMS and who had to use an adult tricycle to get round and who now has given her canes and walkers to goodwill and walks unaided, are very interested in what the MRI might show since there is a clear and huge physical improvement in her case. She was an EDSS 8 or so and is now a 2.5 according to her neuro. Imagine that happened to you, you'd be darned excited also. You'd also want to tell the world.

As far as why not the older you get the more MS if it's CPn I can only offer an opinion based on what I know since clearly the general medical community does not accept that CPn plays a role in MS and there is no research to answer that. I will start by offering that the research links on CPn Help.org offer whole citations (not abstracts) of the research tying CPn to MS. This is peer reviewed research, and it's done by several different people in several journals. Other researchers seem not to find it. The reader is free to go either way and have support. I believe based on a wider understanding of the CPn liecycle and how it works in the body it's a good contender for the cell death that Prineas noted. I have read extensively of CPn literature.

It appears to me that what we are looking at is a rare manifestation of CPn reaction. Most people who are exposed rid themselves of the germ without anything we might cal MS happening or what does happen along those lines is invisible to them ( research shows that many people undiagnosed have MS like lesions in their brain). You might think that this sounds like nonsense as if to get a certain germ means a certain thing should happen. NOt so. Strep can cause rheumatic fever and rheumatic heart disease. If twins get strep and one develops RHD, 82% of the time the other twin will not get this terrible and life threatening complication. Clearly something makes twin one safe, and it's not her genes in this case. (Although there does appear to be a gentic component becasue in our twins where one gets RHD their sibling who also gets strep is only 2.5% likely to ge the RHD, not the 18% incidence of the twins studies) For some reason she just fights it off better. Maybe she got a nap and a good lunch on the critical day for her immunity. How would we know? Yet the second twin will live the rest of her life with the consequences of her system somehow letting the RHD happen posibly needing heart valve replacement. This is really similar to MS where if one twin gets it the other will only have a 30% chance of it happening. But notice that we can cure this problem with early abx intervention.
So here is what I propose as a possibility: If you will get Cpn manifesting as MS it will happen early. If you have the genes that will allow it, and the situation is right, then it can occur. There's another possibility: it's known that if you have the APOE4 gene and you have alzheimers you will have CPn in your lesions research indicates (CPn Help.org alzheimers link). Some research also indicates the APOE gene is present in MS CPn also. It is possible that if you mount an inflammatory response then you have MS and this happens more often in younger people, and if your immune system is less effective as the infection begins and it can't mount an inflammatory response (perhaps beccause the immune system is already so hampered by CPn in it) then you get SPMS or PPMS if young and alzheimers if older. Crumb, for lots of peple CPn is in their blood vessel plaques, which is why it is an emerging disease in atherosclerosis.

This si speculative of course, though it is known tha CPn likes to hide in immune cells thus accounting for my idea of the effective vs ineffective response. As we started out saying, these infected immune cels are likely senescent.

Just as an aside older people very rarely get rheumatic fever (6-15 is the average age for this problem) either and carrier states occur where in the person has the bug but is not sick at all.

The bottom line is that CPn infects many cells of a person's body and changes their ability to do what they were meant to do. What is infected makes a difference to how it affects the person. The research is interesting and wide, with only a little bit of it in the MS field. It is early days and the link is unproven at this point. But try to tell that to Katman or Anecdote. They can walk.
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Postby MacKintosh » Sat Dec 31, 2005 11:40 am

Marie - Also try to tell it to me, who was diagnosed 19 August 2005 with MS. Intravenous steroids and prednizone failed to stop the ongoing assault I experienced. First, ongoing 'brain fog' for several months, a very sudden decrease in overall strength, optic neuritis and a thirty percent loss of vision in one eye, then an MRI showed three lesions on the brain (one apparently a few years old) and a spinal tap showed one oligoclonal band (wish I'd known to have them test for CPN back then), then extreme physical exhaustion hit and I couldn't do much of anything at all, then my left foot tingled whenever you ran a finger across it and ultimately developed a burning sensation, then swallowing became weird, then my jaws felt like they were locking up, then both feet went numb and subsequently felt like I was walking on wet sponges, then fingers were going numb, then a sudden loss in my ability to walk because the muscles just wouldn't drag the leg.
Almost all of this STOPPED within the first two weeks of antibiotic treatment. My vision returned, though my depth perception is still a bit off. The exhaustion went away immediately and my ability to concentrate returned perfectly. Numbness is GONE. Unfortunately for the purposes of medical study, I am an imperfect case study. I am healing before I went down the road of severe disability, so I'm 'just a fluke', as several doctors have told me.
As for fewer diagnoses in older people, first off, I think a lot of CPN infection/MS is misdiagnosed the older one gets. There is an expectation that things will deteriorate with age and I think a lot of people don't pursue an answer the way you do when you're twenty-five. And as for our hanging our hats on the MRI results/reversals, one must understand we don't just base whether we are still progressive on the MRIs!!! It wouldn't matter WHAT the MRI showed, if I could walk last week and am using a cane or wheelchair THIS week! I'd know I was still progressing and declining! The combination of remarkable recovery and no new lesions is what tells the tale. (No plans for a new MRI for me until a year from diagnosis. I don't feel the need now and when I do one, it'll be to wave it in the diagnosing neurologist's face as the best proof I can offer.)
The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi
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Cpn and MS

Postby Shayk » Mon Jan 02, 2006 6:09 pm

Marie—the message wasn’t in my inbox either. It got lost in technological thin air I guess. I’ll respond first to your post and then a bit to MacKintosh’s.

Immunoscenescence, Apoptosis and Cpn: Immunoscenescence is aging of the immune system. Apoptosis is orderly and natural cell death. That I think I understood. What I didn’t understand was that you believe Cpn may interfere with orderly and natural cell death (including that of immune cells) because it may stall apoptosis.

I also want to be crystal clear I certainly believe and respect the testimonials of the people with MS who are on abx, as well as those who are on Tovaxin and Tysabri, or, anything else for that matter. I think it’s great people got better and are doing so well.

Marie, you have read extensively about Cpn and you also have a medical background. You seem to conclude Cpn, although not proven, is a likely cause of MS. I have not read extensively about Cpn nor do I have a medical background, as so many advocating Cpn and abx treatment do. So, here’s some of my rationale, as a lay person with MS who has not read extensively about Cpn, for seriously questioning whether or not Cpn is the cause of MS.

One reason I tend not to believe Cpn is the cause of MS is that just as there is genetic vulnerability to MS, I suspect there is environmental vulnerability to it. As such, there may not be a single “pathogen”, be it viral or bacterial that “causes” MS. That of course is total speculation on my part.

I also try not to allow testimonials, no matter how great they are, be the sole source of information about deciding on a possible course of action vis a vis how to better manage MS. It seems to me there’s no shortage of testimonials and theories about various things that cause/ cure MS. Time will tell about all of them. MS lasts a lifetime and we all want a cure. I have done some minimal reading about Cpn though.

From the limited information I’ve read about Cpn (on the Cpn site and elsewhere) Cpn is widespread and implicated in a number of diseases, i.e., Cpn is not disease specific to MS or only found in people with MS. That being the case, one way for me to assess whether or not Cpn has a potential role in MS has been to reverse the process if you will, to try and find out whether or not, in general, what is known about Cpn is consistent with and/or mirrors the little bit that is known about MS.

Is what is know about Cpn consistent with what is known about MS?
Per the Cpn web site, Cpn infection appears to be widespread.

Chlamydia pneumoniae is the most commonly occurring intracellulari bacterial pathogen…….According to seroepidemiologic surveys, C. pneumoniae infection seems to be both endemic and epidemic.


If Cpn is so widespread, I’d think the incidence/prevalence of MS would be much higher than is currently estimated. I would think the majority of people with Cpn don’t get MS, so I think other factors, including genetics, etc. are at work.

From the Cpn web site:
The antibody prevalence worldwide is higher in adult males than in females.

MS is definitely more prevalent in women than men so in that regard Cpn is definitely inconsistent with the profile of MS as a disease.

From the Cpn web site:
Currently available data suggest that C. pneumoniae is primarily transmitted from human to human.

I don’t think MS is primarily transmitted from human to human. Nor, as we’ve already discussed is the age of diagnosis in MS (20-40) consistent with most Cpn diseases (older), when the infection flourishes. Thus, based on limited epidemiological information, when one compares Cpn generally to the epidemiological profile of MS, I find it hard to conclude that Cpn is a risk factor for MS. In my cursory read, I also haven’t seen anything to suggest that the risk for Cpn infection is more common in Northern areas, etc. As you said, what we might be looking at is a rare manifestation of Cpn reaction. I also have other reasons for my conclusion though.

To the best of my knowledge Cpn has not been isolated in brain lesions of people with MS. Per this abstract, Is cpn present in the brain lesions of patients with MS?
All results were negative.


Is there any association between Cpn and MS? The jury is definitely still out on any association between Cpn and MS, never mind Cpn as the cause. These are quotes from a recent exchange on the topic:

The Role of cpn in MS: Fictitious or Real?

Margaret R. Hammerschlag,1 Petra Apfalter,4 Jens Boman,5 M. Lucia Tondella,2 and Charlotte Gaydos3
1Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Brooklyn, 2Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and 3Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; 4Department of Clinical Microbiology, Vienna General Hospital, Vienna, Austria; 5Department of Virology, Umea University, Umea, Sweden

When in-house produced laboratory methods are developed and implemented, as in the study by Sriram et al., it is important that the investigators provide validation that the methods are specific and appropriate for the purpose for which they are being used. In summary, until more or new research studies indicate differently, we cannot scientifically support a biological association between C. pneumoniae infection and MS.


I think that’s quite an array of Cpn expert investigators who don’t support an association between Cpn infection and MS. To be fair though,

Sriram Reply to Hammerschlag, et al
Thus, we argue that our data and those of others support an association between C. pneumoniae infection and MS.

Notice that even Sriram doesn’t use the word “cause”. It’s a long way between association and cause.

In summary, from my perspective, there are testimonials that a number of people have gotten better on abx, which is excellent (abx and MS is another discussion), few if any general similarities exist between Cpn and MS (epidemiologically) and the scientific evidence that there’s even an association between MS and Cpn is highly debatable. So, from what I’ve read, I’m not convinced that Cpn causes MS and conclude, as a lay person, the existing scientific evidence to support that statement is thin. I do believe (relying on your expertise Marie) that bacterial endotoxins from Cpn can kill oligodendrocytes that are no doubt very important cells in MS. It would be interesting to know if there are other bacterial (or viral) pathogens being investigated for the “cause” of MS that possess similar qualities and/or can damage neurons and axons.

MRIs and MS: It may surprise you, but I do know that MRI’s and lesion load are outcome measures of clinical trials. From what I’ve read to what extent they should be is another question. Bromley started a thread: MRIs are worthless with a link on the topic. Based upon what I’ve read I do not conclude as you do that people with progressive MS (SPMS or PPMS) necessarily accumulate lesion load. Here’s the title of information I read on the topic shortly after I was diagnosed:

“T2 Lesion Burden on MRI Plateaus as MS Disability Accumulates”, Multiple Sclerosis, Vol. 9, 1, p 58, Sep 2003”, Li DKB, Filippi M., Petkau J., Daumer M. Unfortunately, I can’t give you a direct link to the abstract itself, but it was presented at ECTRIMS 2003 and here’s a link to follow to all abstracts from that conference. (It may require access to the journal through a library.)

There was a follow up presentation on this research at the ECTRIMS conference this past fall. At the 2005 ECTRIMS presidential symposium, “Advances in Multiple Sclerosis”, I Milonas noted:
MRI findings are useful for the diagnosis of MS, they cannot be correlated to the clinical disability measured by EDSS, though. This finding raises questions about whether the so-called “MRI burden of the disease outcome” may have any clear value in the every day clinical practice.


Another ECTRIMS presentation was entitled Longitudinal changes in T2 lesion volume in multiple sclerosis: possible restricted utility as a clinical trial outcome by
B. Mair, U. Held, J.Wolinsky, M. Daumer, L.Held
Sylvia Lawry Centre for Multiple Sclerosis Research, University of Texas
Health Science Centre, Ludwig-Maximilians University (Munich, D; Houston,
USA).

The research was based on a large multinational database of the Sylvia Lawry Center for Multiple Sclerosis Research, which at that time consisted of 85% of all available MS placebo patients observed in clinical trials over the past 15 years (per their abstract). It states in part:

The aim of this study was to determine factors that influence the longitudinal relationship between MRI changes of T2 lesion volume over time and a set of clinical and demographic variables…….MRI activity over time varies more between patients than within patients…..

EDSS and disease duration emerged as the variables that remained in the model to explain T2 lesion volume. We found the relationship to be non-linear, with positive but weak correlation in the early years after MS onset, and a plateauing relationship of T2 burden of disease for patients having MS for more than 10 years. This association confirms earlier crosssectional analyses from the Sylvia Lawry database. The positive association between EDSS, disease duration, and T2 lesion volume for MS patientswith short to medium disease durations could have important implications for the design of future clinical trials that consider the change in T2 lesion volume as an outcome. The confirmation of the plateauing effect in this longitudinal analysis suggests that the utility of T2 lesion volume as a potential surrogate marker for disability may be limited to selected cohorts of patients only within well defined phases of the disease.

Although it doesn’t specifically address lesion load in SPMS or PPMS, it does seem to suggest that lesion load, as defined by volume in this study, definitely “plateaus” in MS patients who’ve had the disease for more than 10 years. There’s also more recent information that I find intriguing on the topic of MRIs.

Age-related gadolinium-enhancement of MRI brain lesions in MS
There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent…

Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004).

The main changes in enhancement risk occurred after 35 years of age.


I think this study might reinforce the abstract that started this thread and found that people with MS may have premature immunoscenescence.

I find it extremely interesting that the inflammatory process in MS may in part be age-related. On that dimension, the risk of enhancing lesions on MRI seems to be higher in younger people (under the age of 35), rather than older (over the age of 35) people with MS, at least as far as I understand it. (That could be not far at all. :) )

It also seems to suggest in general that MRIs as an indicator of disease progression, may be most meaningful for people under the age of 35, with short disease duration, and a high rate of relapses in the preceding 2 years. It also suggests that MRIs as an indicator of disease progression are less meaningful for people over 35, with fewer relapses in the preceding 2 years and with longer disease duration.

In short, people will certainly read the same, different and/or more information about Cpn and MS and about MRIs and MS and come to different conclusions than I do at this point. It certainly seems all the people with medical expertise and/or affiliation posting on ThisIsMS do. That’s to be expected and I certainly respect it. As the saying goes, “MS Sucks” and trying to find solutions and decide what to do or not do when you have the disease is IMO quite the challenge.

MacKintosh, I agree with you about MRIs, the better proof is in how one is doing. You wrote:
As for fewer diagnoses in older people, first off, I think a lot of CPN infection/MS is misdiagnosed the older one gets. There is an expectation that things will deteriorate with age and I think a lot of people don't pursue an answer the way you do when you're twenty-five.


I tend to disagree. It’s true older people probably have more non-MS lesions than younger people, but because MS is primarily a disease diagnosed between the ages of 20-40 and precisely because older people are more likely to have more non-MS lesions, I think neurologists are reluctant to consider MS as a differential diagnosis in older individuals. Since testimonials are “in”, I’ll speak from personal experience. I am definitely senescent, 59. I spent two years ruling out differential diagnoses for MS. After that, I had to ask for an MRI of my brain to rule out MS. My MS diagnosis was confirmed at Johns Hopkins.

Lastly, you know :) I can’t write all of this without putting in a plug for sex hormones since I think they may be a risk factor for MS. Melody and others interested in diet and fats might also find this abstract of interest.

A Systematic Review of Several Potential Non-Genetic Risk Factors for MS

We reviewed the literature published in the English language to determine the weight of evidence for several potential non-genetic risk factors for multiple sclerosis, including solar ultraviolet radiation (UVR), sex hormones and dietary fat/fatty acids…..

Based on our criteria, the plausibility for solar UVR and sex hormones is good and fair for dietary fat/fatty acids. However, the body of epidemiologic evidence is insufficient for these three sets of risk factors.


Happy 2006 everyone. Here’s hoping everyone stays (or gets) well on whatever course(s) of action they've chosen or are still in the process of deciding. I have a hectic winter schedule so won't be able to post much.

Sharon
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Postby MacKintosh » Mon Jan 02, 2006 8:32 pm

Sharon - On re-reading the following, I realize it really belongs in the abx discussion, but in the body I do address a couple of your points/questions. I am sure Marie and others with medical backgrounds will read over your cites and respond more specifically in that vein than I. I am not a medical professional, just a lay person who nonetheless has an IQ equal to or greater than most of the doctors I've seen since diagnosis. After months of studying MS, I came to the conclusion that the autoimmune theory makes no real logical sense. Exposure to some other, seemingly random, cause made far more sense to me. Fortunately, I found the cpn rationale. (Yes, I wanted to believe it worked, but I was not naive enough to jump on a bandwagon made of fluff. I did my homework and continue to do so.)
There is much discussion on the CPn Help.org board, as well as numerous citations, references and studies, addressing the reasons earlier studies didn't find cpn, the reason antibiotics were dismissed in times past and the frustration at finding facilities with the advanced knowledge and wherewithal to properly test for the disease. It strikes me that you are pointedly looking for reasons NOT to believe cpn bacteria is a cause. (They teach us in statistics class that one can use the same set of stats to prove or disprove just about anything, depending on your personal bias or the point you are required to make.) You may, however, want to read up a bit more on current cpn studies, particularly those now using advanced methods of identifying cpn presence. Few researchers use (or are even AWARE of) the best methods to locate and identify cpn, thus they resolve there is no cpn present and rule it out as a cause. (The public then relies on these folks' studies to 'prove' cpn isn't a factor.) They didn't find it because they didn't know how to look for it. That doesn't mean it wasn't there! If I used a dowsing rod instead of a metal detector, I could not locate a railroad track a foot below the earth, either. Doesn't mean it's not there; it means my method was flawed. The railroad track still exists.

As for why cpn would cause chronic fatigue in one person and MS in another, I think I have the credentials to answer that one, as I am the poster child for both. MS occurs when cpn enters the brain, as in the blood/brain barrier goes 'down', which should not normally happen. Vitamin D and sunshine play a huge role in protecting the blood/brain barrier. I believe I've had chronic fatigue syndrome for nearly twenty years. BUT - MS hit only in the last year. Coincidentally, it was a year in which I literally 'saw' the sun on occasion, but was out in it ONCE, sleeping days and working nights for eighteen months. It was also the year in which I foolishly neglected to take even a multivitamin most of the time. CPN is a bacteria of opportunity and, in normal situations, one can fight it off, one can eradicate it at the outset and one can keep it out of the brain/nervous system.
Cpn can and does attack different tissue and manifest itself in a variety of ways. It's the same as mercury entering the body; various manifestations occur in different people, but the causative agent is the same. Eradicate the mercury and the various symptoms subside, no matter who the patient is or where it manifested itself in their body. Eradicate the CPN and the various symptoms recover, despite the unique variations from individual to individual.
Okay, enough; as I say, I need to return to the abx discussion, from whence I came. :wink: I chose what made logical sense to me. If someone chooses another path, that is their choice. I only know I stabilized and immediately improved with abx and I have pointedly NOT taken any other drug or course of action, in order to know with certainty that it IS the abx that's causing the recovery. I didn't have TIME to waste, waiting for the 'one study that will prove without a doubt' that I am right, before trying to heal myself.
The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi
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Postby mrhodes40 » Tue Jan 03, 2006 4:59 pm

I am porting my answer to the abx forum under immunosenecsense
Marie
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