GWI is neurological: claim that GWI is a cholinergic disorder

[alex3619]

http://archneur.jamanetwork.com/article.aspx?articleid=1397621

Cholinergic Autonomic Dysfunction in Veterans With Gulf War Illness
Confirmation in a Population-Based Sample

Robert W. Haley, MD; Elizabeth Charuvastra†, RN; William E. Shell, MD; David M. Buhner, MD; W. Wesley Marshall, MD; Melanie M. Biggs, PhD; Steve C. Hopkins, BS; Gil I. Wolfe, MD; Steven Vernino, MD, PhD

Abstract

Background The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction.
Objective To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans.
Design Nested case-control study.
Setting Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas.
Participants Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey.
Main Outcome Measures Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram.
Results The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P < .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P = .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length–related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P < .001).
Conclusion Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.


This paper is very interesting in that all the factors they use to infer GWI is a neurological rather than a psychological disease are at play in ME.

Thanks go to Kelly who posted a notice on this on Co-Cure today.

 

[Marco]

I can't access the full paper.

Any idea why they conclude the symptoms are due to cholinergic autonomic deficits?

 

[alex3619]

I also have not seen the full paper due to a firewall. However my interpretation is they were looking at the severity of symptoms directly associated with cholinergic deficits. My guess, and I can't be sure without the full paper, is that they think that a cholinergic problem in the brain could explain it all. Here is part of what Kelly on Co-Cure quoted a little while ago:

""It suddenly takes this out of the realm of a psychological illness and
into the realm of a brain illness," said Dr. Haley. "Now we need to turn
our attention to looking at treatments that neurologists and internists and
other doctors can provide for conditions that involve abnormalities in the
cholinergic parts of the nervous system."

Although the study doesn't make any conclusions about the cause of the
illness, Dr. Haley believes it's due to exposure to low doses of nerve gas
and to pesticides."

If we have any doubts or questions, its quite possible we can contact one or more of the authors directly.

 

[Marco]

I also have not seen the full paper due to a firewall. However my interpretation is they were looking at the severity of symptoms directly associated with cholinergic deficits. My guess, and I can't be sure without the full paper, is that they think that a cholinergic problem in the brain could explain it all. Here is part of what Kelly on Co-Cure quoted a little while ago:

""It suddenly takes this out of the realm of a psychological illness and
into the realm of a brain illness," said Dr. Haley. "Now we need to turn
our attention to looking at treatments that neurologists and internists and
other doctors can provide for conditions that involve abnormalities in the
cholinergic parts of the nervous system."

Although the study doesn't make any conclusions about the cause of the
illness, Dr. Haley believes it's due to exposure to low doses of nerve gas
and to pesticides."

If we have any doubts or questions, its quite possible we can contact one or more of the authors directly.

Thanks Alex

Reason I asked is I'd just finished reading this that suggests a slightly different mechanism :

Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum.


http://www.ncbi.nlm.nih.gov/pubmed/21848865

.... still neurological of course!

 

[Aileen]

Here is part of what Kelly on Co-Cure quoted a little while ago:
""It suddenly takes this out of the realm of a psychological illness and
into the realm of a brain illness," said Dr. Haley. "Now we need to turn
our attention to looking at treatments that neurologists and internists and
other doctors can provide for conditions that involve abnormalities in the
cholinergic parts of the nervous system."

Wasn't Simon Wessley also heavily involved in trying to psychologize this in the UK? Seems to me he did a bunch of his typical shoddy studies in this area too. Don't tell me this might put that "good science" award he just received in jeopardy (although he didn't win for messing with GWI patients lives).

 

[Katherine]

Wasn't Simon Wessley also heavily involved in trying to psychologize this in the UK? Seems to me he did a bunch of his typical shoddy studies in this area too. Don't tell me this might put that "good science" award he just received in jeopardy (although he didn't win for messing with GWI patients lives).

Yes. Curious isn't it? US and UK used the same tactic (PTSD) to try and dismiss GWI. It was deliberate and they knew their illness was not psychological. What is more disturbing is that they got away with it.

 

[xrayspex]

so if its a cholinergic problem, is it advised or contraindicated to use anticholinergics for mast cell or sleep etc?

 

[lansbergen]

My immunemodulator is an acethylcholine agonist.

 

[Marlène]

Wasn't Simon Wessley also heavily involved in trying to psychologize this in the UK? Seems to me he did a bunch of his typical shoddy studies in this area too. Don't tell me this might put that "good science" award he just received in jeopardy (although he didn't win for messing with GWI patients lives).

Hope he doesn't use the shell shock treatments anymore.

 

[alex3619]

xrayspex, I think the answer is we don't know, we only know that it might be a problem. As a precaution I don't use such drugs, but for all I know they could be very safe for a large subset of us.

 

[AFCFS]

This article, Nerve Deficits May Drive Gulf War Syndrome, published November 26, 2012, draws off two similar:

Primary source: Archives of Neurology
Source reference:
Haley R, et al "Cholinergic autonomic dysfunction in veterans with Gulf War illness: confirmation in a population-based sample" Arch Neurol 2012; DOI: 10.1001/jamaneurol.2013.596.

Additional source: Archives of Neurology
Source reference:
Freeman R "Objective evidence of autonomic dysfunction and the role of stress in the Gulf War syndrome" Arch Neurol 2012; DOI: 10.1001/jamaneurol.2013.1494.

 

[xrayspex]

Alex, what could be the risk of using anticholinergic meds?

 

[beaverfury]

GULF WAR VETERANS AND CFS
http://aje.oxfordjournals.org/content/157/2/141.full

Rates of CFS-like illness did show a relation to stressor intensity, but the pattern was quite different from that for PTSD. The rate of CFS-like illness was 0.8 percent for the nondeployed, while the rate for veterans deployed elsewhere but not in the Gulf was 1.7 percent. Rates again increased to 5.4 percent for veterans deployed to the Gulf but in noncombat roles. Rates of CFS-like illness did not change significantly for Gulf veterans in the more stressful situations related to combat. It appears that deployment-related stress has a role in the genesis of CFS in a veteran population. However, the data do not rule out the possibility that, in addition to stress, some unmeasured factors specific to serving in the Gulf could be responsible for the high rates of CFS among Gulf War veterans.
This overall pattern indicates some parallels between CFS-like illness and PTSD in that both have a relation to stress. However, the pattern of that relation—linear for PTSD and linear for CFS only at lower stressor intensities—suggests that the two conditions are not merely variants of one another. Except for the data presented here, which were collected from a Gulf-War-era veteran population, no study has clearly shown an existing relation between stress and CFS in civilians.

Wiki
The Locus Coeruleus neurons are probably the origin of the first or second “leg” of the "PTSD circuit." An important 2005 study of deceased American army veterans from World War II, was shown combat-related PTSD to be associated with a postmortem diminished number of neurons in the locus coeruleus (LC) on the right side of the brain.[7]

The locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will alter cognitive function (through the prefrontal cortex), increase motivation (through nucleus accumbens), activate the hypothalamic-pituitary-adrenal axis, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor from the hypothalamus, which induces adrenocorticotropic hormone release from the anterior pituitary and subsequent cortisol synthesis in the adrenal glands.

My brain's a bit fuzzed at the moment. This is not directly about acetylcholine, but if we dig further we find that no one neurotransmitter system and no single brain area is responsible for conditions like PTSD.
(I realise GWI may implicate chemical stressors as well as psychological)

I dont think many PWC would say they're free of some sort hyperarousal in the body. It would be nice if they could tie it all in with cortisol findings and tell us....what the hell to do about it.

Signing off, Private fuzzyfury.

At ease!

 

[beaverfury]

Alex, what could be the risk of using anticholinergic meds?

To confuse matters further, check out
http://forums.phoenixrising.me/inde...acetylcholine-toxicity-the-cause-of-cfs.9757/

I've been taking nicorettes for 6 months, which are cholinergic. I find i function much better cognitively on them.
However, i dont imagine they're that good for me because,

By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.[42] wiki

..And maybe this causes further hyperarousal of our system, releasing more cortisol bla bla bla.
But....Whatever gets me through the day.

Another option could be, taking nothing at all! Dan Nueffer's book http://cfsunravelled.com/ might recommend taking nothing at all in this regard, and let your body normalise without stimulants and medications.

Choose your weapon:thumbdown:

 

[alex3619]

Alex, what could be the risk of using anticholinergic meds?

Short answer: we don't know. Thats the primary risk. Its a gamble. We do know that there is something wrong with acetylcholine related regulation of the blood vessels in ME, we know that from Vance Spence's work in a number of studies dating back to about 2000. If the excessive cholinergic response is pathological then taking anti-cholinergics might help us. If on the other hand its an adaptation to the pathology, then anti-cholinergics might harm us. So without more data we can only speculate. To confound the issue further different people might respond differently to any given drug, and might be different again to a different type of anti-cholinergic drugs. Too much speculation involved, not enough data.

Bye, Alex

 

[lansbergen]

Alex, what could be the risk of using anticholinergic meds?

I do the opposite. If you have what I have it would not be a good idea. The med I use has opposite effects with low and high dosis. I take a low dosis. In high dosis it can kill.

 

[xrayspex]

hey lansberger, I am curious now, if you could say more detail on whats wrong and what med tx you use?

 

[lansbergen]

hey lansberger, I am curious now, if you could say more detail on whats wrong and what med tx you use?

In my case on ground of my observtions I conclude the acethylcholine system is understumilated.. That would at least explain the muscle problems and the immunesystem not calming down.

Levamisole binds to acethylcholine receptors at a different spot as acethylcholine does.

Receptor desensitisation could be part of it.
http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor
Ligand-bound desensitisation of receptors was first characterised by Katz and Thesleff in the nicotinic acetylcholine receptor.[15]

Prolonged or repeat exposure to a stimulus often results in decreased responsiveness of that receptor toward a stimulus, termed desensitisation .

So overdo and you will be punished.

You could google acetylcholine receptor subunit alpha-7 for more informaton. .

. . .

 

[xrayspex]

thanks. what did you over do?

levamisole is interesting at wikipedia. not allowed in US anymore, except in coke.....wonder if parasites are at the root of a lot more probs than western med realises...

 

[lansbergen]

thanks. what did you over do?..

Push, push, push. Running on adrenline.

Parasites have nothing to do with it except that levamisole is used to paralize them.