Showing papers on "Epileptogenesis published in 1995"
TL;DR: The results show that BDNF plays an important role in establishing hyperexcitability during epileptogenesis, probably by increasing efficacy in stimulated synapses.
266 citations
TL;DR: The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temprol lobe epilepsy developed 1 year after intoxication indicate that the human hippcampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitOToxic injury in epileptogenesis.
Abstract: We describe the development of temporal lobe epilepsy in an 84-year-old man who had suffered domoic acid intoxication. Following intoxication he had nausea, vomiting, confusion, and coma. Generalized convulsions and complex partial status epilepticus progressively developed. After 3 weeks he improved and was seizure free with severe residual memory deficit. Electroencephalograms initially showed periodic epileptiform discharges, later evolving to epileptic abnormalities over frontotemporal regions with diffuse slow waves. Eight months after the intoxication the electroencephalogram was normal. One year after the acute episode, complex partial seizures developed. Electroencephalograms showed epileptic discharges independently over both temporal lobes, with left-sided predominance. Magnetic resonance imaging revealed a hyperintense T2-weighted signal and atrophy of both hippocampi; a positron emission tomographic scan showed bitemporal decreased glucose metabolism. Pneumonia developed and the patient died 3 1/4 years after the intoxication. Autopsy disclosed severe bilateral hippocampal sclerosis. The seizures following acute domoic acid intoxication, the postmortem pathology, and the fact that temporal lobe epilepsy developed 1 year after intoxication indicate that the human hippocampus is also vulnerable to kainate receptor excitotoxicity, and provide strong evidence supporting the role of excitotoxic injury in epileptogenesis. This report provides a unique human parallel to, and validates the animal model of, kainate-induced epilepsy as an important tool for studying temporal lobe epilepsy.
206 citations
TL;DR: The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons that are involved in chronic epileptogenesis, which evolves in response to limbic seizures.
156 citations
TL;DR: Patients with temporal lobe epilepsy with chronic and postictal psychoses show similar profiles of clinical and seizure variables, suggesting shared etiologic factors.
Abstract: Objective This study sought to elucidate the relation of clinical, neuropsychological, and seizure variables to chronic and postictal psychoses in patients with temporal lobe epilepsy. Method Forty-four patients with treatment-refractory temporal lobe epilepsy were given formal psychiatric evaluations; 29 patients had no psychiatric disorder or a nonpsychotic disorder, eight patients had postictal psychoses, and seven patients had chronic psychoses. Comparisons of clinical, neuropsychological, magnetic resonance imaging, and seizure variables were made between the nonpsychotic and the psychotic patients and, secondarily, between the patients with transient postictal psychoses and those with chronic psychoses. Results Bitemporal seizure foci, clustering of seizures, and absence of febrile convulsions were associated with both postictal psychoses and chronic psychoses. Younger age at onset of epilepsy and lower verbal and full-scale IQs differentiated the patients with chronic psychoses from those with postictal psychoses. Conclusions Patients with temporal lobe epilepsy with chronic and postictal psychoses show similar profiles of clinical and seizure variables, suggesting shared etiologic factors. These factors may increase the propensity to develop psychotic symptoms, while other factors, such as time of onset of epilepsy and underlying neuropathology, may determine whether transient or chronic psychotic symptoms develop. Even among patients with treatment-refractory temporal lobe epilepsy, a specific subgroup of patients, characterized by bitemporal seizure foci, an absence of febrile convulsions, and a history of clustering of seizures, appears to be particularly prone to develop psychotic disorders. A process similar to secondary epileptogenesis may be involved in the development of the psychoses.
143 citations
TL;DR: In vivo evidence is provided for a protective role of BDNF in the regulation of plasticity involved in epileptogenesis in adult brain after convulsive seizures in rats.
Abstract: Recent data have suggested the involvement of neurotrophins in the cascade of events occurring during seizure development. In particular, expression of both brain-derived neurotrophic factor (BDNF) and its receptor mRNAs increases in different brain structures after convulsive seizures. The physiological significance of this increase was investigated by chronic intrahippocampal perfusion of BDNF in the model of dorsal hippocampal kindling in the rat. A 7 day perfusion of BDNF, in the region of the stimulating electrode, blocked the development of kindling during the perfusion period and for the following 15 days. These results provide in vivo evidence for a protective role of BDNF in the regulation of plasticity involved in epileptogenesis in adult brain.
113 citations
TL;DR: It is proposed that EAAC1 is not only involved in the sequestration of glutamate at glutamatergic synapses and in protecting neurons from glutamate excitotoxicity, but also in the cellular metabolism involving glutamate.
Abstract: EAAC1 is a neuronal and epithelial high affinity glutamate transporter previously cloned from rabbit intestine. Here we report the isolation of EAAC 1 from rat brain* and its expression in the central nervous system based on in situ hybridization. Strong signals were detected in brain, spinal cord and retina. Expression of EAAC1 was particularly strong in pyramidal cells of the cerebral cortex, pyramidal cells of the hippocampus, mitral cells of the olfactory bulb, various thalamic nuclei and cells of certain retinal layers. EAAC1 was also expressed in non-glutamatergic neurons such as GABAergic cerebellar Purkinje cells and alpha-motor neurons of the spinal cord. We propose that EAAC1 is not only involved in the sequestration of glutamate at glutamatergic synapses and in protecting neurons from glutamate excitotoxicity, but also in the cellular metabolism involving glutamate.
112 citations
TL;DR: It is concluded that the persistent Na+ current INAP is the most important intrinsic factor for the typical firing properties of IB neurons, while Ca2+ and K+ conductances appear to contribute towards shaping bursts and controlling their recurrence rate.
106 citations
TL;DR: It is suggested that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.
Abstract: PET-demonstrated decreases in [11C]flumazenil binding occur in anterior mesial temporal structures on the side of epileptogenesis in unilateral mesial temporal lobe epilepsy. We performed quantitative autoradiography on anterior mesial and lateral temporal specimens from 11 subjects with unilateral mesial temporal lobe epilepsy and six neurologically normal controls to identify the predominant in vitro correlates of the decreased [11C]flumazenil binding. In anterior mesial temporal regions exhibiting the greatest neuronal cell loss, decreases in agonist and antagonist binding to type 1 and 2 (central) benzodiazepine binding sites were highly correlated with neuronal cell counts. Cell loss and decreased binding were particularly prominent in the lateral portion of hippocampal region CA1, adjacent to CA2. Lateral temporal central benzodiazepine binding was diffusely increased, achieving statistical significance in cortical laminae V and VI. These findings suggest that the predominant source of PET-demonstrated decreases in [11C]flumazenil binding in mesial temporal epilepsy is hippocampal sclerosis, rather than down-regulation of central benzodiazepine binding sites on surviving hippocampal neurons.
93 citations
TL;DR: The decreased GABAAR binding and the attenuation of GABAergic inhibition in CA1, could not be explained by a decrement of receptor subunit expression and may underly the reported increased GABAAR ligandbinding and the increased GABA mediated inhibition.
90 citations
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TL;DR: The Cortical Neuron as an Electrophysiological Unit and Cortical Epileptogenesis in the Developing Human Brain are studied.
Abstract: PART I: GENERAL OVERVIEW 1. Thirty Years Among Cortical Neurons PART II: A CELLULAR AND SYNAPTIC PERSPECTIVE OF THE CORTICAL NEURON 2. Cortical Synaptic Transmission: An Overview 3. The Cortical Neuron as an Electrophysiological Unit 4. Signal Transduction and Protein Phosphorylation 5. Structure and Function of Ligand-Gated Channels 6. Synaptic Actions of Amino Acid Neurotransmitters 7. Synaptic Plasticity in Hippocampus and Neocortex: A Comparison PART III: THE CORTICAL NEURON AS PART OF A NETWORK 8. Overview: Basic Elements of the Cortical Network 9. Functions of Local Circuits in Neocortex: Synchrony and Laminae 10. Inhibition in the Cortical Network 11. Thalamocortical Interactions 12. Models of Cortical Networks PART IV: THE DEVELOPING CORTICAL NEURON 13. Determination of Cellular Phenotype and the Fundamental Organization of Cortical Layering: An Overview 14. Neurotransmitter Signaling Before the Birth of Neurons 15. Gene Control of Cortical Excitability 16. Development of Cortical Excitation and Inhibition 17. Cortical Epileptogenesis in the Developing Human Brain PART V. THE VULNERABLE CORTICAL NEURON 18. Glutamate Receptors and Neuronal Death: A Beginning 19. Measurement of Cortical Neurotransmitter Receptors with Radioligand Binding: Insights into the Mechanisms of Kindling-Induced Epilepsy 20. Pathophysiology of Cortical Synapses and Circuits 21. Pathophysiology of Cortical Areas from Human Epileptics 22. Clinical Strategies for Neuronal Protection
66 citations
TL;DR: The results suggest that loss of neurones is not a prerequisite for establishment of epilepsy-prone state, that seizures of short duration do not necessarily result in neuronal death, and that in kindling, astrocytes are activated by factors that are not related to neuronal degeneration, but which are likely associated with abnormal neuronal activity.
TL;DR: The use of the tetanus toxin model in developing rats may facilitate a better understanding of the unique features of epileptogenesis in the developing brain and the consequences early-life seizures have on brain maturation and the genesis of epileptic conditions in later life.
TL;DR: A new approach to the development of clinically effective anticonvulsants through the developed of presynaptic glutamate receptor agonists which could be administered systemically to control the extent of synaptic release of glutamate is suggested.
Book•
01 Jan 1995
TL;DR: A clinician's look at the developmental neurobiology of epilepsy and candidate genes in the childhood epilepsies and development of new age-specific, antiepileptic drugs.
Abstract: Introduction 1. A clinician's look at the developmental neurobiology of epilepsy 2. Partial (focal) seizures in developing brain 3. Absence seizures in developing brain 4. Developmental neuropathology and childhood epilepsies 5. Neuronal identity, neuronal migration and epileptic disorders of the cerebral cortex 6. Regulation of excitability in developing neurons 7. Candidate genes in the childhood epilepsies: Molecular biology of channels and receptors 8. Synaptogenesis and epileptogenesis in developing neural networks 9. Plasticity and repair in the immature central nervous system 10. Seizure-induced changes in the immature brain 11. Age-specific antiepileptic drug treatment and development of new age-specific, antiepileptic drugs Epilogue
TL;DR: It is concluded that the piriform cortex is the epileptogenic focus of limbic seizures, at least during the first stages of electrical kindling.
TL;DR: It is unlikely that alterations in N-methyl-Daspartate or kainate receptor gene expression play an important role in kindling acquisition or maintenance.
TL;DR: Fyn is the first gene identified to be required for normal epileptogenesis, a Fyn-dependent biochemical pathway in the induction but not the maintenance of normal amygdala kindling.
TL;DR: The development and spread of afterdischarges in the ipsilateral limbic system during amygdala kindling, a model of complex partial seizures, was studied in male and female rats and the effect of common antiepileptic drugs was tested.
Abstract: The development and spread of afterdischarges in the ipsilateral limbic system during amygdala kindling, a model of complex partial seizures, was studied in male and female rats. Kindling stimulation was performed in the basolateral amygdala, and afterdischarges were recorded from the stimulation electrode and electrodes in the nucleus accumbens, the posterior piriform cortex and the ventral hippocampus, all implanted on the right side of the brain. All structures showed primary afterdischarges already after the first stimulation, indicating a close anatomical and physiological connection to the epileptogenic focus. The development of robust secondary afterdischarges, which occurred after the end of the primary afterdischarges in the amygdala and which always originated in the hippocampus but also spread to one or more of the other recording sites, is described. The secondary afterdischarges initially occurred after about nine kindling stimulations in both male and female rats, and were associated with an increase in primary afterdischarge duration and a progression from focal to motor seizures. In order to test the effect of common antiepileptic drugs on the secondary afterdischarges, a group of female rats were treated with valproate, carbamazepine or phenytoin. All drugs suppressed the secondary afterdischarges, although they had a different anticonvulsant efficacy on motor seizures and afterdischarge duration after amygdala stimulation. While valproate and carbamazepine dose-dependently reduced all parameters of the kindled seizure, including the secondary afterdischarges in the hippocampus, phenytoin suppressed the secondary afterdischarges also in the absence of any anticonvulsant effect, suggesting that recurrent hippocampal activation is not crucial for the kindled state. Recording of secondary afterdischarges in the hippocampus may offer the possibility of studying the conditions for development and pharmacological suppression of recurrent hippocampal activation in amygdala-kindled rats.
TL;DR: Evidence is presented that during kindling opposite changes occur in the CA1 and the fascia dentata in terms of the balance between excitation and inhibition due to contrasting changes in GABA-mediated inhibitory function.
Abstract: Kindling epileptogenesis was induced by periodic electrical stimulation of the Schaffer collateral/commissural pathway in the CA1 area of the rat hippocampus The progressive nature of hippocampal kindling is demonstrated by a detailed description of the behavioral signs and the progressive increase of the after-discharge duration in the course of kindling acquisition Furthermore, the evolution of the alterations in the paired-pulse local evoked field potentials and the modifications of the GABAA receptor binding and of the expression of mRNAs encoding for the subunits of the GABAA and glutamate receptors are considered Evidence is presented that during kindling opposite changes occur in the CA1 and the fascia dentata in terms of the balance between excitation and inhibition due to contrasting changes in GABA-mediated inhibitory function
TL;DR: It is concluded that the increased sensitivity for the induction of seizures characteristic for Schaffer collateral kindled animals is not related to a less selective or less efficient mRNA editing process of the different glutamate receptor subunits in the hippocampus.
TL;DR: The results indicate an involvement of specific PKC-isoform gene expression in the induction of an epileptogenic focus, but not in the maintenance of the long-lasting kindled state.
TL;DR: The electrophysiological properties of human neocortical neurons are very similar to those observed in animal experiments, the mechanisms of neuronal communication are qualitatively mature within the first year of life, and synaptic transmission and local neuronal circuits appear qualitatively normal, even in the most abnormal tissue from children with catastrophic epilepsy.
TL;DR: It is believed that the clinical evidence weighs against early treatment with antiepileptic drugs affecting natural course at a practical level, and the issue of heterogeneity can be partly addressed by looking at the prognosis for epilepsy syndromes and the likelihood of their being influenced by antIEpleptic drugs.
Abstract: The most important question in epilepsy is whether antiepileptic drugs not only reduce susceptibility to seizures in someone with epilepsy but also modify the natural course of the condition. The concept of a process of epileptogenesis is strongly grounded in the large volume of work on the kindling model of epilepsy1 and is supported by some circumstantial clinical evidence. However, I believe that the clinical evidence weighs against early treatment with antiepileptic drugs affecting natural course at a practical level.
Epilepsy is a group of disorders in which seizures occur and not a homogeneous disease entity. The response to antiepileptic drugs may therefore differ. The issue of heterogeneity can be partly addressed by looking at the prognosis for epilepsy syndromes and the likelihood of their being influenced by antiepileptic drugs. One clear cut children's epilepsy syndrome is that of benign rolandic epilepsy, in which focal motor seizures, usually affecting the face, throat, and arm, occur during sleep in children between the ages of 7 and 12. Seizures stop by mid-adolescence,2 and many paediatricians no longer give such children antiepileptic drugs since the outcome seems to be entirely benign whether or not treatment is given.
A rather different picture arises in …
TL;DR: The results support the hypothesis that seizure-induced damage of neurons may lead to formation of new synaptic connections that produce abnormal hyperexitability and result in seizures.
TL;DR: There are two distinct phases in the development of epileptic activity in this in vitro model of neocortical epileptogenesis, namely, induction (mediated by NMDA receptor activity) and maintenance (supported largely by non-NMDA receptors).
TL;DR: The hypothesis that pentylenetetrazol has a specific action within the entorhinal cortex that may facilitate the synchronization and spread of epileptiform activity in the hippocampal-parahippocampal circuit is supported.
TL;DR: A modified hypothesis is proposed in which neuronal connectivity itself is postulated to be the primary motive force in both cerebral morphogenesis and epileptogenesis in cases of cortical dysgenesis, leading to the generation of a model for cortical development and directly testable predictions of intercellular connectivity.
Abstract: Cerebral cortical dysgenesis has been found by magnetic resonance imaging to be the second most common pathology underlying medically refractory chronic partial epilepsy. Patients with the latter condition form the largest group in specialist epilepsy clinics. The pathogenesis of the epilepsy in cortical dysgenesis remains largely obscure. The most popular current hypothesis holds neuronal misconnection secondary to neuronal malpositioning culpable for seizure activity. However, a review of the published literature of cortical dysgenesis and an analysis of newer magnetic resonance and histopathological data, suggests that this view is no longer tenable. A modified hypothesis is proposed in which neuronal connectivity itself is postulated to be the primary motive force in both cerebral morphogenesis and epileptogenesis in cases of cortical dysgenesis. This hypothesis leads to the generation of a model for cortical development and directly testable predictions of intercellular connectivity, as well as a potential tool for the prediction of the possibility of freedom from seizure activity after surgical resection of dysgenetic lesions in individual cases.
TL;DR: Experimental animal models of human partial seizures and localization-related epilepsy can be used to further investigations on basic mechanisms that cannot be pursued in patients, and to develop hypotheses concerning the fundamental neuronal processes underlying epilepsy and epilepsy-related phenomena that subsequently can be validated in patients.
Abstract: There are many forms of human partial seizures and many human localization-related epilepsies. Idiopathic epilepsies undoubtedly have pathophysiologic substrates different from those of symptomatic epilepsies, and there is evidence that some forms of limbic epilepsy involve different epileptogenic mechanisms than neocortical epilepsies. Although these mechanisms are best studied and understood by direct investigations of patients, this is often impractical and experimental animal models are also necessary. The use of experimental animals requires that the relevance of each model to a human condition be determined. Human epilepsies are comprised of multiple component parts which can be modeled independently. For instance, acute animal models provide opportunities to study epileptic seizures, but chronic models are necessary for investigation of processes relevant to epileptic conditions, such as epileptogenesis, transition from interictal to ictal state, and long-term consequences of epilepsy. Interactions between localized epileptic activity and cerebral maturation can also be studied in the animal laboratory. Experimental animal models of human partial seizures and localization-related epilepsies can be used to further investigations on basic mechanisms that cannot be pursued in patients, and to develop hypotheses concerning the fundamental neuronal processes underlying epilepsy and epilepsy-related phenomena that subsequently can be validated in patients. In addition, it would be of great clinical utility to develop animal models of partial seizures or localization-related epilepsy that could be used cost-effectively to screen potential antiepileptic drugs.
TL;DR: Prevention may be practiced at various levels in the hierarchy of epilepsy; at the level of epilepsy itself, the individual epileptic seizures, or in the avoidance of the consequences of the epilepsies or their component seizures.
Abstract: Prevention may be practiced at various levels in the hierarchy of epilepsy; at the level of epilepsy itself (epileptogenesis), the individual epileptic seizures (ictogenesis), or in the avoidance of the consequences of the epilepsies or their component seizures. Moreover, it also applies in the arena of psychosocial predicaments, the neurologic or other injurious side effects of recurrent seizures, and the unwanted side effects of drug therapy or surgery employed in management, where attention to the risk/benefit analysis of the treatment employed may greatly influence outcome not only of life itself but also its quality.
TL;DR: A speculative correlation is proposed between AED effects on the mechanism of epileptogenesis and their known clinical effect on seizures.
Abstract: This paper analyzes the effect of conventional (phenobarbital, phenytoin, carbamazepine, ethosuximide, valproate) and some novel (vigabatrin, lamotrigine, felbamate) AEDs on some basic mechanisms involved in focal and/or generalized epileptogenesis (Na+ voltage-dependent channels and sustained repetitive firing, L-, N-, and T-type Ca2+ currents, GABA-mediated inhibition, Glu/Asp-mediated excitation, after-hyperpolarization). According to this analysis, AEDs can be divided into two main categories, those with only one specific action and those with multiple actions. A speculative correlation is proposed between AED effects on the mechanism of epileptogenesis and their known clinical effect on seizures.