Gulf War veterans with self-reported symptoms of autonomic dysfunction have objective evidence of underlying damage to central and peripheral cholinergic function, a study shows.
This may imply neurotoxic damage to cholinergic neurons or receptors, say the researchers, led by Robert Haley (University of Texas Southwestern Medical Center, Dallas, USA).
But Roy Freeman (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA), the author of an editorial accompanying the study in the Archives of Neurology, cautions against creating a "false dichotomy" between physical and psychologic causes of illness. "Objective manifestations do not preclude a central role for stress in the disorder," he says, pointing to a large evidence-base for physical manifestations of stress.
Peripheral nerve dysfunction in the 65 Gulf War veterans in the study was seen on the Quantitative Sudomotor Axon Reflex Test (QSART). Small-fiber dysfunction was greatest in 23 patients with the confusion-ataxia variant of Gulf War syndrome, and worsened with the length of peripheral nerve fiber. In the QSART, sweat production at the foot was 0.40 L in these patients versus 0.79 L in 31 controls (15 soldiers not deployed to the Gulf, and 16 deployed with no symptoms). There were smaller, but still significant, differences at the ankle and leg, and no difference at the arm.
The Composite Autonomic Severity Score (CASS), based on the QSART plus a range of other objective tests of autonomic dysfunction, was significantly higher in patients with the confusion-ataxia variant of the Gulf War syndrome (1.90 points) than in controls (0.71 points), nonsignificantly higher in 21 patients with the impaired-cognition variant (1.15 points), and did not differ in 21 patients with the central neuropathic pain variant (0.57 points).
All patient groups also had central parasympathetic dysfunction; the expected nighttime increase in high-frequency heart-rate variability did not occur in the Gulf War syndrome patients, regardless of which variant they had. During the day, variability was reduced in patients with the confusion-ataxia variant relative to controls, but increased in those with the central neuropathic pain variant.
Patients' self-reported scores for autonomic dysfunction on the weighted Composite Autonomic Symptom Scale were significantly associated with objective measures - inversely with heart-rate variability and positively with CASS scores.
"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 impact of the syndrome," says Freeman, in his editorial.
"On the contrary, it provides a framework for valid scientific analysis, study, and rational dissection of the clinical features of the disorder."
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