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
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,
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.