Pathogenesis of Post-Lyme Disease Symptoms

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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LHCTom
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by LHCTom » Mon 12 May 2014 20:30

Would metabolites be able to tell us anything if the problem lies in the nervous system?
Duncan,

Absolutely. For example, all your neurotransmitters and neuro-peptides are created by your metabolism. So are many closely related molecules essential to the nervous system. All of the signaling molecules in the immune system are also. There is a nice Sigma Aldrich Chart that shows a simplified diagram of your metabolic pathways. This simplified diagram of the human metabolic system can give you a quick sense as to the complexity but also how almost every system in your body is dependent on its correctly functioning.

http://www.sigmaaldrich.com/content/dam ... poster.pdf

You can take a closeup look here:

http://www.sigmaaldrich.com/technical-d ... s-map.html

If you scan the various pathways you will quickly notice virtually all the molecules that are needed for your central and peripheral nervous systems to function are created by either DNA expression or your metabolism and rely on a correctly functioning metabolism. One excellent way of "looking" at the metabolic process is simply analyzing all the metabolites in your various biological samples like blood or urine. So if there is some problem in the pathways that synthesize these molecules, it will probably show up as an irregularity in some of the the metabolites. You can think of that as a signature. Statistics can be used to eliminate noise and extract meaningful patterns.

I was told that this current technology UCSD is using is able to identify over 800 metabolites and their levels and that the target is about 2000. Your metabolism is the vastly complex but is a fairly tightly regulated process of breaking down the food you eat into all the molecules every part of your body needs to operate in conjunction with molecules produced through DNA expression. So a combination of your DNA, how its being expressed, what your body is taking in and is storing plus the current state of your metabolic system runs your entire body. So a problem with any of these can disrupt you in any number of ways including neurologically.

The beauty of this approach is it "sees" through the noise created by the complex DNA master control and differences between people so long as the cohort studied is "similar". For example, men and women have important differences and should be studied separately. By looking using the right statistical filtering at the intermediate through end product metabolites, one gets a a view of the metabolism one cannot get any other way. So yes, its probably one of the best approaches to look for "why" someone is experiencing chronic symptoms since those symptoms have a good chance of being represented by a metabolic signature that is not normal and reflects on certain pathways somehow involved in the proper functioning of the nervous system.

If you look around, there has been an endless series of papers about the power of metabolomics in studying neurological diseases. Here is a few but I did not review them.... just examples

If you go to Pubmed or Google Scholar and search on "metabolomics central nervous system" or something similar, you will find many papers where its being used to explore this.

http://www.ncbi.nlm.nih.gov/pubmed/18843269

http://www.nature.com/npp/journal/v34/n ... 8174a.html

http://masspec.scripps.edu/publications ... 44_art.pdf
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

velvetmagnetta
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by velvetmagnetta » Tue 13 May 2014 8:31

Wow. Thanks LHCTom! That is a lot of new information for me. I especially liked the "Metabolic Pathways" Poster.

Where on the poster are the nervous system metabolites? Are they near the catecholamines?

This field looks very promising for all mankind. Unfortunately, I don't see how it will help people with post-Lyme anytime soon - but that's probably because I don't truly understand what can happen once a metabolic pathway is found. Care to enlighten me, Tom?

One of your links brought me to the Phoenix Rising website for CFS/ME and I saw this awesome new study:

"First Direct Evidence of Neuroinflammation – ‘Encephalitis’ – in ME/CFS"

http://phoenixrising.me/archives/24936

I was so glad for ME/CFS sufferers - Finally, they have some real proof that they're suffering, what they're suffering from, how much pain they're actually in, and possibly a direction to go in for some relief.

What a simple and clever study! (This is not to say cheap!) It has yet to be reproduced (which is essential for taking study results seriously), but Dr. Yasuyoshi Watanabe and his team are already working on designing another more accurate, much larger, and more stringent study.

I can't wait to see these results.

One part I found really cool about this study was: which sections of the brain were inflamed and how they seemed to correlate with certain symptoms. Perhaps something like this could explain some of what we're all going through. I've always wondered why I can talk just fine about quantum mechanics but I cannot seem to sort my laundry into darks and lights!

Why can't Lyme/post-Lyme patients have research like this on our side? Instead, what we get is 4 seperate studies from the NIH telling us that more antibiotics don't help. Okaaaay? Then, mind doing a study on what MAY help?
Last edited by velvetmagnetta on Tue 13 May 2014 12:18, edited 1 time in total.

duncan
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by duncan » Tue 13 May 2014 12:18

Yes, good stuff.

Of course, I don't think many mainstream Lyme researchers in the United States want to embrace any imaging technology other than MRI's. I believe that has been the case since the Logigian SPECT scan studies from the 90's. So getting them to use PET or SPECT technologies may be easier said than done.

Also, although I agree that this small PET/MRI study from Japan holds promise for the ME/CFS community, I can't get too excited since the history of ME/CFS research has been one replete with important, even potentially seminal studies that seem to sprout in different parts of the world - only to die on the vine because no effort by local government agencies to replicate were made. Last count I am familiar with, there were over 4000 studies in the ME/CFS world demonstrating biological underpinnings to the disease. But most of these just get shelved to gather dust.

I always wondered what the difference would be between Ramsey's ME and Lyme encephalomyelitis, and other than purported etiology, I couldn't figure it out.

Of course, if you're a Lyme patient in the US or Canada, neuro Lyme is supposedly a rare event, so issues of brain infection shouldn't pertain; only, the thing is, anyone who has been active in the Lyme world in North America knows that claim is nonsense. So, PET scans and SPECT scans and any other technology researchers can get hold of should be encouraged, at least I would think so. Not happening, though, at least not that I am aware of.

And while they are looking at our brains to map the damage already wrought, or still being wrought, and while they look south to explore our microbiome, and hunt for the pathogenesis of Post-Lyme Disease Symptoms, maybe they will allocate some research monies toward developing a workable culture test - one that can identify Bb keets outside of an EM, and do so in acute AND late stages and everything in between. Or maybe refine the PCR to make it more effective and usable and reliable instead of the minority of cases it works in now.

Moreover, to me it seems this singular xenodiagnosis effort isn't enough, to demonstrate a government is truly invested in finding if infection is actually eradicated, or if it lingers and ends in catastrophe for many of its citizens. I don't think that's hyperbole either.

So, yes, I applaud these efforts to source the symptoms of Post-Lyme. I just wish we could see the same energies being directed at Lyme and Late Lyme. Bring the whole technology arsenal to bear and generate some new and meaningful studies.

And, if that is done, hope those Lyme efforts don't just wither on the vine the way they have historically for the sufferers of ME/CFS.
Last edited by duncan on Tue 13 May 2014 12:48, edited 5 times in total.

velvetmagnetta
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by velvetmagnetta » Tue 13 May 2014 12:34

Duncan,

There are many similarities between ME/CFS and Lyme/post-Lyme, but I think there are a few really important differences, too. One thing seems to be the neurological manifestations of Lyme especially for those of us who have had it a long time.

Both ME and Lyme people suffer from "brain fog" and fatigue but the spasms seem to be in the Lyme camp only. It is very subjective, but some Lyme people seem to be in a great deal more pain than ME people. There is pain involved in ME as well, but it doesn't seem to take on such a central role as it does for us.

And some poor souls have both diseases!

Another difference I've noticed is that many Lyme patients have trouble gaining weight and often look like stick people while many ME (and also Firbromyalgia) patients have trouble losing weight.

A third difference I've seen is that some people with Lyme (including myself) have dark circles around their eyes whereas I have not seen that in ME people.

I do think both diseases involve inflammation of the brain and spinal cord, so whatever manifestations that creates is what we will see in common.

What do you think? Have you noticed any differences?

duncan
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Re: Pathogenesis of Post-Lyme Disease Symptoms

Post by duncan » Tue 13 May 2014 13:02

The ME/CFS community, as it has been twisted and manipulated over the years, is a heterogeneous group. Estimates range anywhere from 10% to 90% (!) are actually Lyme patients misdiagnosed because their titers didn't reach the level contrived by a few twenty years ago that remains inappropriately in place today.

So ME/CFS'rs in my experience come in many different flavors, as do Lyme sufferers.

And I agree with you, one can have both diseases, although I am real curious about the interplay. Can Lyme trigger ME/CFS? Does ME/CFS make one more susceptible to Lyme?

I'm talking real ME/CFS, not this Reeve's crap or Fukuda. CCC defined, or better yet, ICC.

The similarities between the two are striking. BTW, maybe one distinguishing feature that comes to mind is Lyme arthritis? Not arthralgias, but the actually swelling of knee joints etc? Not sure about that though.

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