Visual event-related potentials in cirrhotic patients without overt encephalopathy: The effects of flumazenil

The P300 complex was derived from the electroencephalogram (EEG) as subject s mentally counted infrequent large checkerboard visual stimuli, presented randomly among frequent small checkerboard stimuli. Use of low contrast (10 %) stimuli and four midline scalp electrodes, facilitated separation of cog nitive and sensory components and enabled the P300 complex to be resolved i nto three distinct components-N200, P3a, and P3b. In 20 healthy adult subje cts normative data were established and the P3a and P3b components were sho wn to depend on cognitive function. In 19 age-matched cirrhotic patients wi thout overt hepatic encephalopathy (HE) the EEG and visual evoked potential s (VEPs) were normal, but latencies of P3a and/or P3b were prolonged in 9. Prolonged latencies were not associated with an abnormal number connection test. Ten additional age-matched cirrhotic patients without overt HE, who w ere alcohol, drug, and caffeine free, were randomized to receive flumazenil (1 mg) and placebo intravenously, double-blind. After flumazenil or placeb o, latencies of P3a and P3b and psychometric test results did not change si gnificantly. These findings suggest that in cirrhotic patients without over t HE (i) impaired cognitive sensory function may occur in the absence of ab normalities of a standard psychometric test, the EEG, or VEPs. and (ii) inc reased latencies of P3a and P3b may constitute a component of subclinical H E, which is not mediated by increased brain levels of central benzodiazepin e receptor agonist ligands.