Animal studies have significantly contributed to our understanding of epileptogenesis and action mechanisms of antiepileptic drugs. The relevance of animal models to human epilepsies depend on how faithfully they reproduce the clinical and EEG features of human forms. In principle the definition of animal model of epilepsies should be reserved to animals presenting with recurrent seizures, either spontaneous of experimentally induced, persisting over time. Therefore acute experimental procedures designed to induce seizure and in vitro preparations should be referred to as models of seizures and models of epileptogenic mechanisms respectively rather models of epilepsies. The adequacy of a given animal model to study basic mechanisms of epilepsies and/or drug efficacy depend on the type of information that the investigator want to draw from it.

Animals↗

PubMedDate not supplied

Changes in excitability of CA1 pyramidal neurons in slices prepared from AlCl3-treated rabbits.

Intracellular recordings in 'in vitro' hippocampal slices, prepared from intracisternally AlCl3-intoxicated rabbits, were obtained from 43 CA1 pyramidal neurons. The experiments were performed 12-20 days after aluminum administration. The electrotonic length was significantly shorter than that of 33 control neurons, in agreement with morphological evidence of an Al-induced dendritic impairment. Both postsynaptic and Ca2(+)-dependent K+ hyperpolarizing potentials were also found to be significantly decreased, with reciprocal enhancement of excitatory postsynaptic potentials and depolarizing after-potentials. The former finding is ascribed to a selective neurotoxic effect of aluminum on GABAergic interneurons; the latter can be accounted for by an Al-induced increase in cyclic AMP, which is known to block the Ca2(+)-activated K+ conductance responsible for after-hyperpolarizing potentials. It is concluded that aluminum can exert its epileptogenic effect through multiple neurotoxic mechanisms involving membrane electrotonic properties, K+ conductances, and synaptic influences, thus resulting in a neuronal hyperexcitable state. Such changes are detectable in the early stages of the Al-induced encephalopathy, when there is only slight evidence of cytoskeleton alterations (i.e., neurofibrillary degeneration).

Action Potentials↗

PubMedDate not supplied

Calcium-dependent regulation of genetically determined spike and waves by the reticular thalamic nucleus of rats.

The pathophysiologic role of the reticular thalamic nucleus (RT) in rat generalized nonconvulsive epilepsy was investigated in the selected strain GAERS (genetic absence epilepsy rats from Strasbourg). After the RT was lesioned by the excitotoxic agent ibotenic acid stereotaxically injected in previously callosotomized rats, a disruption of ipsilateral spike and wave discharges (SWD) was observed in freely moving animals. In a second group of animals Cd2+ (0.5-1.5 microliter, 1 mM), which is known to block Ca2+ and Ca(2+)-dependent K+ conductances (gK+ (Ca2+)), was injected into the thalamus. Cd2+ reversibly suppressed ipsilateral SWD when injected in RT, whereas it slightly reduced SWD expression when injected in the ventrobasal (VB) complex. The difference was highly significant. We conclude that Ca(2+)-dependent oscillatory properties of the RT are critical for expression of genetically determined SWD in GAERS.

Animals↗

PubMedDate not supplied

Ethosuximide plasma concentrations: influence of age and associated concomitant therapy.

The relationship between oral dose and plasma concentration of ethosuximide was evaluated retrospectively in 198 epileptic patients aged 2.5 to 34 years. Age appears to be a major factor in determining the ethosuximide plasma level/dose (L/D) ratio. Children younger than 10 years had men L/D ratios significantly lower (p less than 0.0003) than adolescents (10 to 15 years of age) and adults (16 to 34 years of age). Associated antiepileptic therapy reduced the ethosuximide L/D ratio: mean ethosuximide L/D ratios were significantly lower in patients also taking primidone (p less than 0.0005) or valproic acid (p less than 0.02). The correlation between the dose of ethosuximide administered and the plasma concentration was significant in the 3 age groups considered (p less than 0.0004), but the wide scattering of individual plasma concentrations makes it impossible to predict what plasma concentration of ethosuximide will be obtained after a given dose. For this reason, routine monitoring of ethosuximide plasma concentrations still appears to be necessary, especially in children and patients on polytherapy.

Administration, Oral↗

PubMedDate not supplied

Changes in primidone/phenobarbitone ratio during pregnancy and the puerperium.

Plasma concentrations of primidone and its metabolite phenobarbitone were monitored in 9 pregnant epileptic patients treated with primidone (and in 3 cases other antiepileptic drugs) given at constant doses throughout pregnancy and the puerperium. Phenobarbitone plasma concentrations were monitored in another 6 patients given phenobarbitone itself. A trend towards increasing primidone plasma concentrations during the second quarter of pregnancy was evident in all patients, with a concomitant significant decrease in primidone-derived phenobarbitone plasma concentrations. A trend towards a lowering of plasma concentrations of phenobarbitone administered as such was confirmed. These results suggest the usefulness of a careful monitoring of primidone and primadone-derived phenobarbitone during pregnancy and the puerperium. Discrepancies of findings with primidone and phenobarbitone are discussed in view of the possible mechanism involved.

Adolescent↗

PubMedDate not supplied

Plasma concentrations of carbamazepine and carbamazepine 10,11-epoxide during pregnancy and after delivery.

Plasma concentrations of carbamazepine were monitored in 9 pregnant epileptic patients treated with the drug alone at constant doses during pregnancy and for at least 3 months after delivery. In addition, plasma concentrations of the metabolite, carbamazepine 10,11-epoxide were measured in 6 of the 9 patients. Plasma carbamazepine concentrations were fairly stable during pregnancy, and carbamazepine relative plasma clearances were significantly higher in weeks 4 to 24 than in weeks 25 to 32. After the end of the second trimester, there were no variations in plasma carbamazepine 10,11-epoxide concentrations and carbamazepine 10,11-epoxide:carbamazepine ratios. Both parameters were significantly higher in weeks 4 to 24 than in weeks 25 to 32 of pregnancy.

Adult↗

PubMedDate not supplied

[The definition of a reference protocol for the clinical study of vertigo drugs].

The aim of this paper is to define the problems that arise in the clinical evaluation of drugs for the treatment of vertigo. Among these are the objective criteria used in defining vertigo and those used in evaluating efficacy of the drugs. The resulting protocol for a clinical study of vestibular drugs is a document that clarifies the debated points in the field, and above all furnishes guidelines for establishing uniformity in clinical studies. This, therefore, may become the reference protocol in Italy for clinical evaluations of drugs for the treatment of vertigo.

Clinical Protocols↗

PubMedDate not supplied

[Study of ocular pursuit movements in neurology. Examination technic and evaluation criteria].

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Brain Diseases↗