Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure

Abstract

In the present study, we have investigated whether the peripheral cholinergic abnormalities that we have reported previously [Spence, Khan and Belch (2000) Am. J. Med. 108, 736-739] in patients with chronic fatigue syndrome (CFS) are also present in those with Gulf War syndrome (GWS) and agricultural workers exposed to organophosphate pesticides, where cholinesterase inhibition is specifically implicated. We also looked at whether these abnormalities might be due to a reduction in the activity of cholinesterase expressed on the vascular endothelium. We used laser Doppler imaging to measure the forearm skin blood flow responses to iontophoresis of acetylcholine and of methacholine (which is resistant to breakdown by cholinesterase) in patients with CFS, GWS and those with a history of ill health after definite organophosphate exposure, as well as in matched healthy controls. The response to acetylcholine was significantly higher in patients with CFS than in controls ( P =0.029, repeated-measures ANOVA), but was normal in those with GWS and those exposed to organophosphates. The methacholine response was higher than the acetylcholine response in all patient groups except for those with CFS, where there was no difference between the responses. Although there are many clinical similarities between these three illnesses, our results indicate peripheral cholinergic abnormalities in the vascular endothelium of only patients with CFS, suggesting that this syndrome has a different aetiology, which might involve inhibition of vascular cholinesterase.

Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning

“…Autonomic effects are prominent in dynamic cerebral autoregulation, whereas vasomotor effects dominate static or steady‐state cerebral autoregulation. An impaired cerebral blood flow might be due to previously observed blood flow abnormalities in CFS, like prolonged acetylcholine‐induced vasodilatation in the microcirculation . In line with this, autonomic dysfunction may explain POTS and related cerebral blood flow impairment in CFS.…”

Acetylcholinesterase inhibitors and Gulf War illnesses

“…This is analogous to evidence in ill GWV, in which there are low-activity levels of PON and increased prevalence of low-activity variants of BChE [in ill GWV, the PON variant that is less effective may depend on the OP(s) to which the specific veteran was exposed]. Interestingly, GWV with chronic fatigue show a different bloodflow response to acetylcholine iontophoresis than do civilians with chronic fatigue syndrome, but they match the response of persons with chronic fatigue after OP exposure (49).…”

Modulation of microvascular function following low-dose exposure to the organophosphorous compound malathion in human skin in vivo

“…In these patients, Khan et al (15) reported the response to ACh to be significantly higher and the time to decay to 50% peak to be ϳ40% longer than in healthy controls. They were, however, unable to demonstrate a similar phenomenon in patients with Gulf War Syndrome or in agricultural workers exposed to OP-containing pesticides (14).…”