Epilepsia
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To investigate the association between valproate metabolism (VPA) and VPA-induced hyperammonemia together with the contribution of VPA hepatotoxicity risk factors such as young age, polypharmacy, and high serum VPA levels to VPA-induced hyperammonemia, plasma ammonia (NH3) levels, serum levels of VPA and its metabolites, and biochemical parameters were determined in 98 patients treated with VPA (53 monopharmacy cases and 45 polypharmacy cases). In monopharmacy patients, plasma NH3 levels did not depend on age, VPA dosage or serum levels. Serum level of 2-propyl-4-pentenoic acid (4-en) showed a negative correlation with plasma NH3 level in the monopharmacy group. ⋯ These results suggest that young age and relatively high VPA serum levels within the therapeutic range were unlikely to be risk factors for common hyperammonemia associated with VPA therapy and that 4-en was not causally related to this adverse effect. The decreased serum level of 2-en-VPA in polypharmacy patients may be a reflection of a certain mitochondrial dysfunction, which might be a mechanism of the increased NH3 levels. The changes in biochemical parameters in polypharmacy patients were considered results of the enzyme-inducing activity of coadministered antiepileptic drugs (AEDs).
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The role of gamma-aminobutyric acid (GABA) transmission in the control of convulsive epileptic seizures is considered from the perspective of the actions of drugs that augment GABA transmission in the brain. In particular, the effects of a directly acting GABAA receptor agonist, muscimol, is compared with the effects of a GABA-elevating agent, gamma-vinyl GABA (GVG, vigabatrin), in animal models of convulsive seizures. Evidence indicates that there are certain regions of the brain where enhanced GABA transmission is anticonvulsant; in other regions, blockade of GABA transmission exerts anticonvulsant actions. ⋯ The direct stimulation of postsynaptic GABA receptors (by direct receptor agonists) bypasses normal mechanisms of synaptic transmission and can evoke abnormal neurological symptoms, whereas the enhancement of presynaptic availability of GABA avoids these complications. GVG acts to boost presynaptic GABA stores, which can then be utilized physiologically; this may account for the relatively low incidence of CNS-related side effects with anticonvulsant doses of GVG. It is suggested that greater attention be focused on ways of enhancing endogenous GABA availability in future drug development for the control of seizure disorders.
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Thirteen patients with "epileptic amnesic syndrome" (EAS) presented with adult-senile onset of a severe memory complaint that started before or at the same time as seizures. All were diagnosed as temporal lobe epilepsy (TLE). The seizures were stereotyped, with only short loss of contact and oral automatisms, and because they were not obvious or disturbing, they remained underdiagnosed for a long time. ⋯ Neuropsychological investigation ruled out global mental deterioration, showing only selective memory impairment in a few long-term tasks and dissociation between formal findings and the relevant memory complaint. These cases have uniform anamnestic, clinical, and neuropsychological characteristics and represent a particular clinical expression of TLE, namely EAS. We suggest that an epileptic origin be entertained in patients presenting repeated amnesic attacks resembling TGA or who complain of persistent memory disturbance, after more common etiologies have been excluded.
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The hypothalamic-pituitary-gonadal axis is a complex system within which both positive and negative feedback occur among its elements and higher brain systems. The occurrence of seizures and changes in the secretion of pituitary hormones can affect the feedback loop. ⋯ Once conception occurs, live birth rates are not diminished. Prospective studies of men and women with epilepsy are needed.
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To study the differences between epileptic and nonepileptic head drops, 351 episodes in 24 children were analyzed by EEG-videotelemetry monitoring. Drops were classified as either epileptic or nonepileptic depending on the presence or absence of concomitant ictal EEG discharges. Ictal discharges included generalized spike-wave, polyspike-wave, bilateral sharp wave, generalized delta, and generalized beta activity. ⋯ Drops characterized by rapid head descent followed by slow recovery to the upright position were significantly more common in group I patients, whereas drops in which the velocity of recovery matched that of head descent (head nods) were equal in the two groups. Repetitive nods (head bobs) were observed exclusively in group II patients. These clinical and electrophysiologic features may assist in differentiating epileptic from nonepileptic head drops in children.