Ammonia-independent modifications of the background EEG signal and paradoxical enhancement of epileptic abnormalities in EEG after acute administration of valproate to epileptic patients.

The effects on the background quantitative EEG (power spectral analysis) and concentration of valproate in plasma were studied after single-dose (14.3-33.3 mg/kg) oral administration in 12 epileptic patients with generalized nonconvulsive or partial seizures. An increase of the amplitude of the background EEG (diffuse and preponderant on anterior scalp areas) and a decrease of the 12.5-32.0 Hz relative power (limited to the posterior electrode deviations) were observed; the increase in the EEG total power was paralleled by a definite increment in incidence of epileptic phenomena in the EEG. Both effects proved unrelated to shifts in vigilance or changes in the concentration of ammonia or serum glucose in plasma and confirm previous observations from superimposable study designs. These findings are qualitatively opposite to those observed during long-term treatment at comparable doses and are suggested to reflect a direct CNS action of acute administration of valproate.

Human flash-VEP and quantitative EEG are independently affected by acute scopolamine.

Scopolamine in acute intramuscular doses of 0.25-0.75 mg reduced the P2-N3 flash-VEP amplitude and, in the quantitative EEG, the 8.5-12.0 Hz power and total power in 8 healthy young male volunteers. The effects on flash-VEP and EEG total power were dose dependent and were evident 30 min and 90 min respectively after drug administration, regardless of dose. The reduction in 8.5-12.0 Hz power was limited to the 0.50 and 0.75 mg doses. No systematic effects on the pattern-VEP were observed. Possible interferences with flash- or pattern-VEP amplitude of the scopolamine-induced EEG changes were identified and removed by regression analysis and computation of VEP residuals from the regression function. The P2-N3 flash-VEP residuals proved EEG independent and showed relationships with dose and time after drug administration that were superimposable on those of the original data, with comparable significance levels at the drug/placebo and pre/postdrug statistical comparisons. The results indicate that VEP estimates of drug effects which are independent from EEG changes can be identified in human studies and allow some inference on the cholinergic specificity of the systems affecting late flash-VEP components. The statistical approach used in this study is suitable for application in VEP studies when effects of interacting factors are to be expected.

Placebo effects in standard human neuropharmacological studies: effects of physiological variations of blood glucose and ammonia concentration on the electrophysiology of the visual system.

The effects on retinal and cortical visual evoked phenomena of the stimulus intensity/spatial frequency and of the spontaneous, physiological blood glucose/ammonia fluctuations were investigated comparatively in a pilot study on young male volunteers. Flash ERG and flash OPs to 5 different stimulus intensities and pattern VECP to 3 spatial frequencies were recorded at 2-hour intervals during a standard acute pharmaco-EEG experimental session (8 h) with administration of placebo; glucose and ammonia blood concentration levels were assessed concomitantly. The effects of the stimulus intensity/spatial frequency were statistically defined for each amplitude/latency measure by nonlinear regression analysis and were removed by computing the residuals from the regression function, which were then tested separately versus the glucose/ammonia concentration by linear regression. Glucose/ammonia statistically significant effects on the visual system were detected at concentration levels within the range of normality and were representative of a nonnegligeable portion of the data overall variance. These effects were selective on retinal/cortical evoked phenomena and it is conceivable that physiological or pathological metabolic changes might account for a still underestimated source of individual variability in human neuropharmacological studies otherwise adequately controlled.