Tuesday, November 27, 2012

Nerve Deficits May Drive Gulf War Syndrome

It is the *first part* of this article may be of interest to ill Gulf War veterans and their medical care providers.  

The end of this article, however, is sadly focused on the"stress" theory of causation for Gulf War veterans' illnesses.   The presence of the long ago discredited "Stress" theory in this otherwise important article is indicative that the old forces in DoD, VA, MoD, and beyond that we Gulf War veterans have been fighting since the get go remain alive and well.  

It should go without saying that stress can play a supplementary or synergistic role in Gulf War Illness, as well as in any other known physical, psychological, or psychosocial condition ranging from cancer to workplace violence to heliobacter pylori stomach ulcers.  Everything is made worse by stress; few conditions have stress as the primary cause.  

For stress to even be mentioned as possibly the primary cause of Gulf War veterans' physiological illnesses (in the case of the majority of ill Gulf War veterans' who are not also concurrently suffering from PTSD) is an insult.  Its inclusion in this article suggests its proponents have either been living under a rock for the last two decades or are blissfully or willfully ignorant of the large and growing body of medical evidence of the intricate details of the physiological nature of the chronic multisymptom illness plaguing as many as one in three U.S. veterans of the 1991 Gulf War, as well as other U.S. and other military forces.   

It would be an outrage if MedPage Today's editors were to publish an article that, without reliance on any disease-relevant medical research, explicitly stated that multiple sclerosis, Alzheimer's Disease, Parkinson's, or any other neurological disease could have "stress" as a primary cause.  It is no less an outrage in this instance, and serves only to suggest that MedPage Today may not be a fully credible source of scientific news.  


Source:  MedPage Today

Nerve Deficits May Drive Gulf War Syndrome

Dysfunction of the autonomic nervous system may underlie the myriad symptoms experienced by veterans with Gulf War syndrome and its variant subtypes, a case-control study suggested.
On the self-administered Autonomic Symptom Profile (ASP) questionnaire, the mean score for orthostatic intolerance among controls was 2.4 out of a maximum of 40, compared with a score of 22.2 among cases with the syndrome subtype in which confusion and ataxia predominate, according to Robert Haley, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues.
For the Gulf War syndrome variant in which impaired cognition is the dominant symptom, the mean ASP score for orthostatic tolerance was 12.9, and for the variant characterized mainly by central neuropathic pain the mean score was 13.7 (P<0.001 for all), the researchers reported online in Archives of Neurology.
Moreover, the Composite Autonomic Severity Scores, which combine objective measures of autonomic deficits on a scale of zero to 10, also were higher overall in cases than in controls, again most notably with the confusion/ataxia variant (1.90 versus 0.71, P=0.045).
During the 2 decades since 700,000 members of the U.S. military were deployed to the Persian Gulf after Iraq's invasion of Kuwait, an estimated one-fourth have reported multiple chronic symptoms including pain, fatigue, diarrhea, sexual dysfunction, and cognitive abnormalities.
Hypotheses as to the cause of the illness have included neurotoxic exposures and stress, but few objective correlations such as laboratory or pathologic tests or biomarkers have been identified.
This has, in some quarters, "reinforced the notion that this constellation of symptoms is trivial and unworthy of attention," wrote Roy Freeman, MBChB, of Harvard Medical School in Boston, in an accompanying editorial.
Haley and colleagues previously found evidence implicating central cholinergic parasympathetic dysfunction in a small group of veterans afflicted with the syndrome.
To further explore this possible underlying explanation for multiple seemingly unrelated symptoms, the researchers enrolled 66 cases and 31 controls, who were also military veterans but who had not been deployed in the Gulf War.
Scores on several domains of the ASP other than orthostatic intolerance also were significantly higher among cases, including secretomotor symptoms, sleep abnormalities, urinary symptoms, and upper gastrointestinal motility problems (P<0.001 for all).
Those domains related to cholinergic activity, and accounted for much of the difference between cases and controls (R2≥0.20).
In contrast, symptoms relating primarily to the adrenergic system, including vasomotor and pupillomotor symptoms, sexual dysfunction, and reflex syncope, explained less of the difference (R2<0.20), the researchers found.
"The pattern of autonomic symptoms and objective test findings points predominantly to dysfunction of both central and peripheral cholinergic functions, possibly from neurotoxic damage to cholinergic neurons or cholinergic receptors," explained Haley and colleagues.
In another objective test of autonomic function, which measures axonal sweat gland stimulation, reductions were seen in distal postganglionic function, with diminished sudomotor sweat production in the foot:
  • Controls: 0.79 µL
  • Impaired cognition variant: 0.53 µL (P≤0.05)
  • Confusion/ataxia variant: 0.40 µL (P≤0.001)
  • Neuropathic pain variant: 0.55 µL (P≤0.05)
This reduction in sweat was less in the ankle and leg and was not present in the arm, "indicating nerve length-related damage to the peripheral autonomic nervous system affecting the distal small cholinergic sudomotor fibers," the authors observed.
Additional tests included investigations of circadian changes in parasympathetic tone using 24-hour electrocardiograms, in which the normal nocturnal increase in high-frequency heart rate variability was lacking in cases but not controls.
The confusion/ataxia variant group also had lower daytime high-frequency heart rate variability compared with controls, while the daytime variability was higher than controls in the neuropathic pain group.
A moderate inverse correlation was seen between nocturnal heart rate variability and scores on objective autonomic tests (r = −0.41, P<0.001), while a weak correlation was seen for daytime variability (r = −0.22, P=0.04).
This blunting of the expected nocturnal rise in high-frequency heart rate variability "clearly demonstrated" impairment of the autonomic nervous system, the researchers stated.
"These results confirm dysfunction among Gulf War veterans of both central control of parasympathetic function and peripheral cholinergic autonomic nerves, further implicating underlying damage to the cholinergic components of the central and peripheral nervous system," they concluded.
In his editorial, Freeman argued in favor of stress as a major underlying factor in these disturbances of autonomic function, pointing to animal models showing alterations in nerve circuitry, catecholamine and serotonergic function, and impairments of the hypothalamic-pituitary-adrenal axis.
Similar findings have been seen in human stress-induced hypoglycemia.
"Taken together, these preclinical and clinical data demonstrate a wide array of objective structural, physiological, and clinical manifestations of stress," Freeman wrote.
"Proposing a primary, supplementary, or synergistic role for stress in the Gulf War syndrome neither invalidates nor minimizes the associated symptoms, suffering, health outcomes, and public health import of the syndrome," he stated.
Increased understanding of the "neurobiology of stress" in current and future research "will maximize the likelihood of effective prevention and treatment of this and related disorders," Freeman wrote.
The study was funded by the Department of Veterans Affairs, the U.S. Army Medical Research and Materiel Command, and NIH.
The lead author has received an honorarium from Targeted Medical Pharma for reviewing a new drug application for a medication to treat fatigue.

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