title: Hippocampal dysfunction in Gulf War veterans: investigation with ASL perfusion MR imaging and physostigmine challenge.
abstract: OBJECTIVE
  To determine, with arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging and physostigmine challenge, if abnormal hippocampal blood flow in ill Gulf War veterans persists 11 years after initial testing with single photon emission computed tomography and nearly 20 years after the 1991 Gulf War.
  
  
  METHODS
  The local institutional review board approved this HIPAA-compliant study. Veterans were screened for contraindications and gave written informed consent before the study. In a semiblinded retrospective protocol, veterans in three Gulf War illness groups-syndrome 1 (impaired cognition), syndrome 2 (confusion-ataxia), and syndrome 3 (central neuropathic pain)-and a control group received intravenous infusions of saline in an initial session and physostigmine in a second session, 48 hours later. Each infusion was followed by measurement of hippocampal regional cerebral blood flow (rCBF) with pulsed ASL. A mixed-effects linear model adjusted for age was used to test for differences in rCBF after the cholinergic challenge across the four groups.
  
  
  RESULTS
  Physostigmine significantly decreased hippocampal rCBF in control subjects (P < .0005) and veterans with syndrome 1 (P < .05) but significantly increased hippocampal rCBF in veterans with syndrome 2 (P < .005) and veterans with syndrome 3 (P < .002). The abnormal increase in rCBF was found to have progressed to the left hippocampus of the veterans with syndrome 2 and to both hippocampi of the veterans with syndrome 3.
  
  
  CONCLUSIONS
  Chronic hippocampal perfusion dysfunction persists or worsens in veterans with certain Gulf War syndromes. ASL MR imaging examination of hippocampal rCBF in a cholinergic challenge experiment may be useful as a diagnostic test for this condition.
authors.affiliation: Departments of Radiology, Division of Neuroradiology, Internal Medicine, Clinical Sciences, Psychiatry, and Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8874, USA.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Li
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Spence
authors.forename: David M
authors.initials: DM
authors.lastname: Buhner
authors.forename: John
authors.initials: J
authors.lastname: Hart
authors.forename: C Munro
authors.initials: CM
authors.lastname: Cullum
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Biggs
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Hester
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Odegard
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Carmack
authors.forename: Richard W
authors.initials: RW
authors.lastname: Briggs
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haley
mesh_terms: D002560:Cerebrovascular Circulation; D002800:Cholinesterase Inhibitors; D047830:Gulf War; D006624:Hippocampus / Q000098:blood supply* / Q000503:physiopathology*; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods; D008875:Middle Aged; D010830:Physostigmine; D012039:Regional Blood Flow; D012189:Retrospective Studies; D014481:United States; D058014:Veterans Health
chemical_list: D002800:Cholinesterase Inhibitors; D010830:Physostigmine