Abnormal brain response to cholinergic challenge in chronic encephalopathy from the 1991 Gulf War.
Several case definitions of chronic illness in veterans of the 1991 Persian Gulf War have been linked epidemiologically with environmental exposure to cholinesterase-inhibiting chemicals, which cause chronic changes in cholinergic receptors in animal models. Twenty-one chronically ill Gulf War veterans (5 with symptom complex 1, 11 with complex 2, and 5 with complex 3) and 17 age-, sex- and education-matched controls, underwent an 99mTc-HMPAO-SPECT brain scan following infusion of saline and >48 h later a second scan following infusion of physostigmine in saline. From each SPECT image mean normalized regional cerebral blood flow (nrCBF) from 39 small blocks of correlated voxels were extracted with geostatistical spatial modeling from eight deep gray matter structures in each hemisphere. Baseline nrCBF in symptom complex 2 was lower than controls throughout deep structures. The change in nrCBF after physostigmine (challenge minus baseline) was negative in complexes 1 and 3 and controls but positive in complex 2 in some structures. Since effects were opposite in different groups, no finding typified the entire patient sample. A hold-out discriminant model of nrCBF from 17 deep brain blocks predicted membership in the clinical groups with sensitivity of 0.95 and specificity of 0.82. Gulf War-associated chronic encephalopathy in a subset of veterans may be due to neuronal dysfunction, including abnormal cholinergic response, in deep brain structures.
Haley
Robert W
RW
Epidemiology Division, Departments of Internal Medicine and Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX, USA. Robert.Haley@UTSouthwestern.edu
Spence
Jeffrey S
JS
Carmack
Patrick S
PS
Gunst
Richard F
RF
Schucany
William R
WR
Petty
Frederick
F
Devous
Michael D
MD
Bonte
Frederick J
FJ
Trivedi
Madhukar H
MH
D000328:Adult; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004292:Dominance, Cerebral / Q000502:physiology; D004781:Environmental Exposure; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D020258:Neurotoxicity Syndromes / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018923:Persian Gulf Syndrome / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D010830:Physostigmine; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon; D014728:Veterans
D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; D019690:Technetium Tc 99m Exametazime; D010830:Physostigmine