Showing papers on "Epileptogenesis published in 1991"

Bursting-induced epileptiform EPSPs in slices of piriform cortex are generated by deep cells.

Abstract: Previous study revealed that bursting activity generated by a variety of means in slices of piriform cortex induces persistent epileptiform EPSPs in superficial pyramidal cells by an NMDA-dependent process. The present study was undertaken to test the hypothesis that the observed epileptiform EPSPs in superficial pyramidal cells are driven by deep cells. This hypothesis was suggested by recent findings from in vitro studies of the properties of deep cells and in vivo studies indicating that the deep part of the piriform cortex or neighboring deep structures are involved in the generation of seizure activity in animal models of epilepsy. Results from simultaneous cell-pair recordings, examination of subdivided slices, and local application of excitatory and inhibitory agents provided strong evidence in support of this hypothesis. It was concluded that the endopiriform nucleus, a collection of cells immediately deep to the piriform cortex, plays a central role in generation, but that cells in the deep part of layer III and the claustrum may also contribute. Furthermore, it was found that generation of prolonged ictal-like activity only occurs in slices of piriform cortex in which the endopiriform nucleus is present. Implications of these findings for epileptogenesis are discussed.

Scope and contribution of genetic models to an understanding of the epilepsies.

Abstract: Studies of the genetic models of the epilepsies emphasize that some seizure disorders result from an aberrant "wiring diagram" coupled with abnormal activity of individual neurons. These defects cause the unique seizer-triggering mechanisms operative within the epileptic nervous system but which are inactive or do not exist in normal subjects. Moreover, causes of epilepsy reside not only within the brain area, wherein initial appearance of epileptic EEG discharge occurs, but also outside that region. Etiologically significant neurochemical dysfunctions may be common features of the epileptic condition in genetic models across species. Accordingly, genetically determined convulsive epileptogenesis in rats, baboons, and humans may result partially from noradrenergic and GABAergic deficits. In contrast, genetically derived absence seizures in the rat and perhaps also humans may occur in response to GABAergic excess. The unique features of the genetically epileptic animals emphasize their usefulness in developing novel drugs that selectively ameliorate seizure predisposition.

Neurobiological evidence for epilepsy-induced interictal disturbances.

Abstract: It is not in the best interest of persons with epilepsy to deny the possibility that seizures could cause enduring behavioral disturbances. Rather, it is essential to pursue clinical and animal investigations in order to identify any such changes that might occur and to elucidate their mechanisms. Many testable hypotheses can be developed from existing evidence. Antiepileptic medication may produce interictal behavioral disturbances in patients with epilepsy by indirect mechanisms. Some aberrant behaviors could be due to medication-induced systemic disorders, neuroendocrine dysfunction, or REM deficit, whereas depression following successful treatment with drugs, as well as with surgery, may be related more specifically to cessation of seizures. The underlying neuropathological process also induces neurological and mental deficits, but it is not always possible to differentiate those behavioral disturbances due to destructive effects of the lesion from those due to recurrent epileptic seizures. Behavioral disturbances are associated more frequently with epileptogenic lesions in limbic structures than with those elsewhere in the brain, but a relationship between hemispheric lateralization of the epileptogenic lesion and specific interictal behavioral symptoms remains controversial. When considering the effects of seizures per se on interictal behavior, it is important to realize that some "interictal" behavioral disturbances may actually be ictal events. Prolonged affective, autonomic, and psychic disturbances can occur in clear consciousness with unilateral limbic seizures that are not associated with scalp EEG changes. When epilepsy is acquired as a result of cerebral damage, the epileptogenic process takes time to develop before spontaneous seizures appear. It is more reasonable to assume that this progressive process continues than to postulate that it stops completely at the time the first seizure occurs. Epilepsy-induced protective homeostatic mechanisms that act to terminate ictal events, prevent ictal spread, and maintain the interictal state may also disrupt interictal function. Furthermore, seizures could indirectly influence interictal behavior as a result of their effects on neuroendocrine function and sleep. Because of confounding biological factors, it is difficult to document the association of any epilepsy disorder, by itself, with progressive behavioral disturbances in humans. Secondary epileptogenesis, protective homeostatic mechanisms, and epilepsy-induced disturbances in development can be readily demonstrated, however, in experimental animal models. In experimental animals, endogenous opoids are released during seizures and mediate some postictal behaviors. A physiological dependency on high levels of endogenous opioids released during seizures could produce depression as a withdrawal symptom interictally or when seizures no longer occur as a result of successful therapy. Experimental animal models of depression exist to test hypotheses concerning pro- and antidepressant effects of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

The involvement of excitatory amino acids in neocortical epileptogenesis: NMDA and non-NMDA receptors.

Abstract: Conventional intracellular recording techniques were used to investigate the N-methyl-D-aspartate (NMDA) and non-NMDA mediated synaptic mechanisms underlying the stimulus-induced paroxysmal depolarization shift (PDS) generated by cells in rat neocortical slices treated with bicuculline methiodide (BMI). The NMDA receptor antagonists CPP or MK-801 were ineffective in abolishing the PDS. However, both drugs were able to attenuate the late phase of the PDS and delay its time of onset. In contrast, the non-NMDA receptor blocker CNQX demonstrated potent anticonvulsant property by reducing the PDS into a depolarizing potential that was graded in nature. This CNQX-resistant depolarizing potential was readily blocked by CPP. Voltage-response analysis of the PDS indicated that the entire response (including its NMDA-mediated phase) displayed conventional voltage characteristics reminiscent of an excitatory postsynaptic potential that is mediated by non-NMDA receptors. We conclude that the activation of non-NMDA receptors is necessary and sufficient to induce epileptiform activity in the neocortex when the GABAergic inhibitory mechanism is compromised. The NMDA receptors contribute to the process of PDS amplification by prolonging the duration and reducing the latency of each epileptiform discharge. However, the participation of NMDA receptors is not essential for BMI-induced epileptogenesis, and their partial involvement in the PDS is dependent upon the integrity of the non-NMDA mediated input. The lack of NMDA-like voltage dependency observed in the PDS's late phase might reflect an uneven distribution of NMDA receptors along the cell and/or an association of this excitatory amino acid receptor subtype in the polysynaptic pathways within the neocortex.

Secondary Epileptogenesis in Cerebral Arteriovenous Malformations

Abstract: • There is debate as to whether secondary epileptogenesis occurs in humans. As part of a series of patients with cerebral arteriovenous malformations and epilepsy, we identified two patients with probable secondary epileptogenesis in the mesiotemporal regions, ipsilateral but anatomically distant from an arteriovenous malformation causing seizures. Both patients had arteriovenous malformations outside the mesiotemporal region and resection of the arteriovenous malformation and epileptogenic areas identified by electrocorticography produced initial freedom from seizures. Three to 6 months later both patients developed a different seizure pattern that proved to be mesiotemporal in origin by video/electroencephalogram (one with depth electrodes) and both patients are seizure free after a second resection of anterotemporal and mesiotemporal regions. Findings indicating a secondary epileptogenic focus include (1) different seizure type by patient history, (2) second seizure type by ictal video/electroencephalographic recordings, and (3) lack of pathologic abnormalities in the resected mesiotemporal specimens.

Ontogenetic features of audiogenic seizure susceptibility induced in immature rats by noise.

Abstract: Although numerous models are currently used for systematic study of the mechanisms of epileptogenesis in mature brain, few animal models have been developed that allow similar explorations in the developing nervous system. One experimental model of epilepsy supports a premise that perinatal experience can lead to eventual seizure susceptibility, however. Audiogenic seizure (AGS) susceptibility can be induced during a critical developmental period in normal mice by auditory deprivation and therefore by cochlear trauma. We studied the developmental parameters that affect success of both induction and testing of AGS-susceptibility in the rat. Intense high-frequency noise exposure was used as the traumatizing agent. The Wistar rat strain used is inherently seizure-resistant because in greater than 400 trials, untreated rats have never exhibited susceptibility at any age. Although single prolonged exposures to high-intensity noise were administered to groups of rats at ages between postnatal days (PNDs) 12 and 36, PND 14 was the age when exposure was most likely to result in eventual seizure susceptibility. Furthermore, duration of initial exposure on PND 14 determined the rate of susceptibility when measured 2 weeks later. Accordingly, we noted that single noise exposures at an intensity of 125 dB and ranging between 6 and 10 min in duration induced susceptibility in 100% of rats tested on PND 28; nonetheless, seizures among the rats exposed for 8 min were the most severe. Typically, these seizures began as wild running attacks and were followed by tonic/clonic convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Self-Regulation of Slow Cortical Potentials and Its Role in Epileptogenesis

Abstract: The prevalence of epileptic disorders is estimated to be around 1%, amounting to 15 million people in the United States In at least one-third of all cases the epileptic seizures cannot be adequately controlled through antiepileptic medication About 20% of the epileptic population is considered refractory to anticonvulsant management And even if the seizures can be brought under control by antiepileptic medication, the side effects of the drugs put considerable strains on the patient’s life (Penry & Rahel, 1986) Research has been conducted on alternative approaches relying on behavioral treatment alone or in combination with pharmacological treatment Behavioral techniques generally have negligible side effects, which of course is highly desirable

Experimental limbic epilepsy: models, pathophysiologic concepts, and clinical relevance.

Abstract: Complex partial seizures originating in the temporal lobe are one of the most common types of seizures in patients with epilepsy. They are frequently intractable to medical treatment and are increasingly considered for surgical therapy. These seizures are often associated with focal epileptogenicity in limbic structures (amygdala and hippocampus) or with rapid spread of seizure activity to these areas. Much research is being undertaken to better understand this disorder and to develop more effective approaches to diagnosis and treatment. Experimental work in animals has contributed to the understanding of epileptogenesis, the interictal state, and the homeostatic mechanisms that limit seizure activity.

Language-apparent reflex epilepsy.

Abstract: An adolescent with photosensitive epilepsy had absence seizures reproduced by forced voluntary eye closure in light or in darkness, independent of eyelid immobilization or ocular elevation. Attacks preferably occurred while speaking Spanish, her second language, mediated through brief, strong, automatic closing of the eyes during difficult word retrieval. Complex other multidirectional ocular movements or blinking, cognitive and language tasks were ineffective. Frontorolandic cortical epileptogenesis is seemingly responsible for light-provoked seizures in Papio papio, acting via hyperexcitable neuronal facial aggregates (i.e. Baba and Wada). Since orbicularis oculi muscle fibers mediating strong and weak contractions are differentially innervated by the facial nuclei, we submit that critical threshold tonic activation of specific nuclear aggregates explains this language-apparent reflex epilepsy, triggered by extreme eye closure. A "dopamine connection hypothesis" linking periodic eye closure, effortful memory and photosensitivity, based on its putative evolutive significance, is discussed.

Magnesium Suppresses Seizurelike Discharges in Cultured Neurons

Abstract: To the Editor. —In the September 1990 issue of theArchives, Kaplan et al 1 discount the use of magnesium sulfate for eclamptic seizures for two reasons: first, magnesium sulfate has not been shown to be as effective as phenytoin in a controlled clinical trial, and second, "magnesium sulfate has no anticonvulsant properties. It could only be argued in a more general sense that... magnesium sulfate might prevent secondary seizures." While agreeing wholeheartedly with their first point, I would like to suggest that the experimental basis for a possible anticonvulsant action of the magnesium ion (Mg ++ ), as well as for its antiepileptic properties, is stronger than the authors allow. Hippocampal slice models of epilepsy have shown that the N -methyl-d-aspartate (NMDA) subtype of glutamate receptor, which is the type blocked by Mg ++ , is involved in epileptogenesis (ie, the generation of a state prone to seizurelike uncontrolled discharges). In