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

The P300 complex was derived from the electroencephalogram (EEG) as subjects 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 cognitive and sensory components and enabled the P300 complex to be resolved into three distinct components--N200, P3a, and P3b. In 20 healthy adult subjects normative data were established and the P3a and P3b components were shown to depend on cognitive function. In 19 age-matched cirrhotic patients without overt hepatic encephalopathy (HE) the EEG and visual evoked potentials (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 were alcohol, drug, and caffeine free, were randomized to receive flumazenil (1 mg) and placebo intravenously, double-blind. After flumazenil or placebo, latencies of P3a and P3b and psychometric test results did not change significantly. These findings suggest that in cirrhotic patients without overt HE (i) impaired cognitive sensory function may occur in the absence of abnormalities of a standard psychometric test, the EEG, or VEPs, and (ii) increased latencies of P3a and P3b may constitute a component of subclinical HE, which is not mediated by increased brain levels of central benzodiazepine receptor agonist ligands.

Visual event-related potentials in cirrhotic patients without overt encephalopathy.

UNLABELLED: Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. IN CONCLUSION: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy.

The effect of flumazenil on visual event-related potentials of clinically non-encephalopathic patients with cirrhosis.

The effects of flumazenil on the latencies and amplitudes of visual event-related potentials (ERPs), number-connection test (NCT) and visual and auditory reaction times (VRT and ART) were evaluated in ten patients with cirrhosis without clinically overt encephalopathy (HE). Delayed latencies of the ERP component P3a and/or P3b were found in three patients and the time to complete NCT was prolonged in two other patients. Changes in the latencies and amplitudes of the ERP components (N200, P3a and P3b) during 40 min following infusion of flumazenil (1 mg) and placebo were similar. Results of the three psychometric tests did not change significantly after either flumazenil or placebo infusion. Eight of the ten patients felt more alert for several minutes after the administration of flumazenil, whereas no patient experienced any change of perception after infusion of placebo. Prolongation of the latencies of P3a and P3b may be a component of the syndrome of subclinical HE. However, these neuro-electrophysiological abnormalities in cirrhotic patients may not be attributable to increased brain levels of natural benzodiazepines.