Showing papers on "Epileptogenesis published in 1987"

Epileptogenesis and the Immature Brain

Abstract: Summary: Epidemiological studies indicate that the incidence of seizures is highest early in life. This report discusses the experimental data derived from studies of focal epileptogenesis of the immature brain in tandem with ongoing maturational changes. During development, neurons have characteristic neurophysiological properties. Local interictal discharges are long in duration, lack a stereotypic morphology, and have limited fields. Yet the immature brain is very susceptible to the development of bilateral, although asynchronous, seizures and status epilepticus induced by amygdala kindling or by convul-sant drugs. This increased seizure susceptibility may be due to a functional immaturity of a substantia nigra, GABA-sensitive output system. The morbidity of convulsions occurring early in life may not be as grave as previously thought in terms of subsequent acquisition of “normal” developmental milestones. The propensity to develop recurrent convulsions in adulthood is not related to the severity of a single seizure in infancy. Although multiple severe seizures may predispose animals to the development of seizures later in life, this is not a unique feature of the immature brain, since it also occurs in the adult brain. Finally, there is evidence that the immature brain may respond to anticonvulsant drugs differently from its mature counterpart; these findings emphasize the need to develop new antiepileptic therapies that take into account the maturational state of the brain.

Relevance of kindling and related processes to human epileptogenesis.

Abstract: Schimutz, Markus: Relevance of kindling and related processes to human epileptogenesis. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1987, 11 : 505–525 1. 1. Kindling and related processes belong to the most extensively investigated models of experimental epilepsy. In this paper an attempt is made to outline their significance to human epileptogenesis. Below the most relevant findings are summarized: 2. 2. Animal data: kindling and related processes are progressive in nature and occur in a great number of animal species including Rhesus monkeys and baboons; progressive epileptogenesi s seems dependent on predisposition to seizure susceptibility and develops slower the higher the position of the respective species is in the phylogenetic scale; spontaneously recurrent seizures as well as permanent electroencephalographic, behavioural, electrophysiological and biochemical alterations have been observed following kindling; kindling development can be suppressed by clinically used antiepileptic drugs. These data illustrate the similarity of kindling and related processes to certain aspects of human epilepsy. 3. 3. Human data: one case of human brain kindling and several cases of spontaneously recurrent seizures following electroconvulsive treatment are known; the progressive nature of human epilepsies is exemplified by observations of untreated patients, factors accompanying the failure of monotherapy, and the existence of multiple lesions (mirror foci) in cerebral tumour patients. 4. 4. The material presented clearly indicates that kindling and related processes can occur in man as well as in animals. This should have implications for the treatment of epileptic patients as well as for brain stimulation techniques.

Comparison of penicillin epileptogenesis in rat somatosensory and motor cortex.

Abstract: The relative sensitivities of somatosensory and motor areas of the cerebral cortex in penicillin epileptogenesis were compared in urethane-anaesthetized rats. Penicillin was applied electrophoretically from a fluid-filled micro-electrode. Spontaneous focal interictal epileptiform discharges were detected by a nearby recording electrode. In motor cortex, every cortical layer was less sensitive in penicillin epileptogenesis than the corresponding layer in somatosensory cortex; epileptic spikes occurred later, were of lower amplitude and were less frequent. In motor cortex, the sensitive depth extended from the deep part of layer III to the upper part of layer V. It seemed possible that penicillin applied to motor cortex might be producing its effects by diffusing back to the sensitive somatosensory area. This was excluded by applying penicillin to motor cortex whilst recording from both somatosensory and motor areas and demonstrating that the spikes were found in motor but not in somatosensory cortex.

Etiologic and preventive aspects of epilepsy in the child--bridging the gap between laboratory and clinic.

Abstract: Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of “kindling antagonism” may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.

Calcium Ion Involvement in Epileptogenesis

Abstract: .The equivalent of epileptic EEG discharges on the cellular level are paroxysmal depolarization shifts (PDS). This paper reviews mechanisms involved in the initiation of epileptic discharges, PDS generation, transition from interictal to ictal discharges, and ictal epileptic activity, focussing on the role of calcium ions in these different steps of epileptogenesis. Intrinsic and synaptically elicited transmembranous calcium currents play a critical role in the regulation of neuronal excitability; large intracellular calcium accumulations as found during intense epileptic activity may even lead to cell death. Different approaches to the development of new antiepileptic drugs based on the mechanisms of action of calcium ions in epileptogenesis are discussed.

In Vitro Models of Epilepsy

Abstract: In this chapter, we shall review what is known about the cellular mechanisms of epileptic events in vitro. Our main concern is to understand the electrical events that neurons generate during a fit, and to understand what kinds of interactions (synaptic and nonsynaptic) between neurons underlie the fit. We further seek to comprehend which intrinsic properties of neurons are required for epilepsy or that at least facilitate epileptogenesis. Our method consists of making experimental observations of seizure phenomena in the hippocampal slice, attempting to reproduce the observations with simulation models on a large computer, and testing the models with further experiments. We shall emphasize underlying mechanisms that are as independent as possible of physiological and pharmacological details. This provides a clear conceptual framework in which to interpret diverse experiments. Such an approach is necessary because epilepsy involves understanding the behavior of a population of neurons. Our work has lead to models that illuminate the underlying mechanisms of two types of epileptic events: interictal spikes and tonic seizures.

Kindling models and antikindling effects of mood normalizers.

Abstract: In animal experiments, kindling designates the appearances of increasing EEG and behavioral responses when an initially ineffective stimulus on certain cerebral areas is repeated (Goddard et al., 1969). Its development occurs in association with increasing duration and spread over the major part of the brain of electric afterdischarges. This process may lead to critical changes in behavior. Kindling can be caused by electric stimulation or pharmacological inducement. The nature of the behavioral response varies with that of the stimuli, so different types of kindling have been described, constituting animal models notably for epileptogenesis. Their psychiatric interest stems from evidence of an inhibiting effect of certain substances, such as carbamazepine or phenytoin, which are effective in the treatment of both epilepsy and mental disorders, but this effect is also found for lithium (Post et al., 1982, 1984). Applied to the development of periodic psychoses, kindling models would account for certain unexplained clinical data and precisely explain the mechanisms and the specific action of various mood normalizers.