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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Penicillin is well known as a potent convulsive agent. A cortical topical, intracerebral or systemic administration of penicillin produces abnormal and paroxysmal activity which may lead to seizure, and has been used in the investigation of the mechanisms of epilepsy. This is a report on the studies of an acute effect of potassium penicillin G on two models of experimental focal epilepsy: a) amygdaloid kindling model, and b) kainic acid-induced limbic seizure model. Twelve adult cats for amygdaloid kindling model (kindling group), six for KA-induced limbic seizure model (KA group) and four for a control group were prepared for this study. In kindling group, after completion of kindling procedure, 40-60 X 10(4) unit/kg of potassium penicillin G (PC), dissolved in sterilized normal saline, was injected intraperitoneally during an interictal period. In KA group, 1 micrograms of KA was injected into the left amygdala. Limbic seizures occurred frequently during the initial 5 hours but subsided completely within 3 days. After a latent period, spontaneous secondarily generalized convulsion occurred from 30 to 60 days after KA injection. The cats were completely normal in their behavior during the interictal period. During the interictal stage after the first generalized convulsion has been observed, 15-20 X 10(4) unit/kg of PC was injected intraperitoneally. In the control group, 40-60 X 10(4) unit/kg was injected intraperitoneally. Electroclinical observations were continued until 5 hours after PC injection in three groups. In the control group, no cats developed generalized convulsion. In the kindling group, 4 of 12 cats developed focal amygdaloid seizures with secondary generalization by nearly the identical doses required in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute effect of penicillin G on feline models of focal epilepsy]. 250 15

This article has three goals: (1) to review the evidence that bears upon the occurrence of secondary epileptogenesis in man, (2) to set forth the criteria that distinguish secondary epileptogenesis from multifocal epilepsy--both clinically and by pharmacologic means--and (3) to indicate the importance of an understanding of the pathophysiology of secondary epileptogenesis to clinical decision making in the care of epileptic patients. In Section I, the three different developmental stages of secondary epileptogenesis defined in experimental preparations are outlined, and particular emphasis is placed on the remarkable similarity in the electrographic manifestations reported from animal species ranging from reptile to baboon. The clinical manifestations differ depending, within species, on exactly where in the brain the primary focus is situated and, between species, on the different organizations of the neural substrate within which epileptiform discharge is engendered. Section II is devoted to a review of three separate series of patients whose presenting symptom was epilepsy and in whom the etiology proved to be a histologically verified brain tumor or malformation. The choice of patient material was dictated by the conclusion that the main barrier to acceptance of human secondary epileptogenesis is the difficulty of distinguishing between multiple primary lesions maturing at different rates and those secondarily induced by an already existing single one. In the vast majority of patients where trauma, infection, anoxia, and vascular disease represent the most common etiologies, multiple primary structural injury is an ever-present possibility. Restricting our analysis to tumors of neural, glial, or vascular origin eliminates, as far as practicable, the issue of multiple primary lesions. A significant number of patients with focal epilepsy develop secondary epileptogenic lesions. The evidence presented shows that a primary epileptogenic lesion in man may induce a trans-synaptic and long-lasting alteration in nerve cell behavior characterized by paroxysmal electrographic manifestations and clinical seizures. Furthermore, the more frequent the seizures, the more likely is a secondary focus to become permanent. These observations underscore the importance of rigorous seizure control (electrographic as well as behavioral) and raise the question of earlier surgical intervention where medicinal therapy fails.
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PMID:Varieties of human secondary epileptogenesis. 250 38

The inhibition of seizure activity by behavioural methods is becoming more popular. Lockhart's monkey model of focal epilepsy suggests a theoretical approach to behavioural seizure inhibition. Behaviour, by changing the pattern of excitation and inhibition surrounding a focus, is thus able to inhibit seizure activity. This article describes single case studies in which the behavioural methods of cued arousal, covert desensitization and relaxation have brought about a decrease in seizure frequency.
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PMID:Evoked and psychogenic epileptic seizures: II. Inhibition. 261 81

In this report 17 patients with long-standing non-focal epilepsy underwent callosotomy (this was total in two patients and performed in two stages, and anterior-subtotal in the remaining patients). In all patients the atonic-hypertonic seizures with sudden falls were the most disabling epileptic fits. Callosotomy proved efficient in controlling atonic fits in 10 out of 15 patients in whom surgical results are evaluated. In 3 additional patients the frequency of atonic fits was reduced by more than 50%. In the remaining two patients, no therapeutic effect was observed. Callosotomy was less effective on seizures which were not atonic. Therefore, this procedure appears to be indicated in patients in whom atonic fits are predominant. The main effect of callosotomy is to transform drug-resistant seizures into drug-sensitive ones. Neuropsychological sequels are insignificant unless the splenium is severed. However, considerable psychic and behavioral improvement was nearly always observed after surgery. Despite the fact that on a therapeutic level results were often satisfactory, a number of practical problems still remain. These concern the full spectrum of indications for callosotomy, the extent of corpus callosum section, choice of methods in severely mentally retarded patients and, finally, the age at which the operation should be carried out.
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PMID:[Remarks on callosotomy in the treatment of drug-resistant epilepsy]. 262 17

About 300,000 people in the United States suffer from medically uncontrolled focal epilepsy. It is estimated that about 40,000 of these patients are candidates for surgery. Underuse of surgical treatment of epilepsy is reflected by the fact that only about 1% of these candidates are operated on. Candidates for ablative surgery (ie, removal of seizure focus) must have a focus demonstrated by either extracranial or intracranial electrode recordings. Nearly half of the patients who have ablative surgery become seizure-free, and nearly two thirds have no seizures or only rare ones. Candidates for corpus callosotomy are those patients with multiple seizure types and nonfocal EEG abnormalities. Almost half of these patients have at least a 50% reduction in seizure frequency. Patients with infantile hemiplegia and seizures may have marked improvement in seizure control after physiologic hemispherectomy.
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PMID:Surgical management of epilepsy. 266 Feb 91

The precipitation of seizures by external stimulation (evoked seizures) is well known. Less well known is the precipitation of seizures by a change in the patient's thinking or feelings. This artick uses Lockhart's monkey model of focal epilepsy to propose that there is a close relationship between seizures and ongoing brain activity. Thus, seizures precipitated by both voluntary and spontaneous changes in behaviour and thinking must commonly occur. Clinical examples of such seizure precipitation is described.
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PMID:Evoked and psychogenic epileptic seizures. I. Precipitation. 269 27

Previous studies have shown that a loss of GABAergic neuronal somata is associated with a loss of GABAergic terminals at chronic cortical epileptic foci in monkeys. The present study was undertaken to determine whether GABAergic neuronal loss occurs prior to the onset of clinical seizures in monkeys that were treated with alumina gel but did not display seizures. Seven adolescent (Macaca mulatta) monkeys received alumina gel implants into the left pre- and post-central gyri, specifically centered in hand-face regions of sensorimotor cortex. Three other monkeys were used as controls. Two of these were surgical controls and the third was a normal animal. Three monkeys (pre-seizing) were sacrificed 2-4 weeks after the alumina gel implant but prior to clinically active seizures. Three other monkeys with chronic seizure activity (chronically seizing) were sacrificed 3-6 months after the implant. Tissue sections were taken from an area adjacent to the alumina gel granuloma (focus), from a site distal to it (parafocus) and from the non-epileptic contralateral side. Sections from all monkeys were processed for glutamate decarboxylase (GAD) immunocytochemistry and then examined with a light microscope. In addition, adjacent sections were stained with a Nissl stain and the total number of neurons was counted in these sections. Statistical analysis showed a significant decrease in the number of GAD-positive cells in the pre-seizing and chronic animals. The pre-seizing monkeys showed a significant loss of 23-44% at the focus in contrast to the total number of neurons which did not change significantly. The loss of GAD-positive cells was greater in the chronic animals that showed significant losses at both the focus and parafocus, 42-61% and 15-26%, respectively. It is important to note that the chronic monkeys displayed an 11-61% significant loss of total neurons at the epileptic focus. The surgical control animals showed no seizure activity and no significant loss of total neurons or GAD-positive cells. The main finding of this study indicates that a selective loss of GAD-positive neuronal somata occurs in pre-seizing monkeys with alumina gel implants. This finding is consistent with the previously reported loss of GABAergic terminals in pre-seizing monkeys. Since virtually all monkeys treated with alumina gel develop seizures, the results of this study add further support to the hypothesis that GABA neuronal loss plays a causal role in focal epilepsy.
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PMID:A selective decrease in the number of GABAergic somata occurs in pre-seizing monkeys with alumina gel granuloma. 279 67

In studies of focal epilepsy it is frequently assumed that the interictal spike is the elementary form of epileptic activity and that seizure, or ictal, episodes evolve by temporal summation and spatial expansion of interictal paroxysms. We examined this hypothesis in an in vitro model of acute focal epilepsy produced by perfusing rat hippocampal slices with solutions containing moderately elevated concentrations of K+. Some of the preparations treated in this way displayed recurring electrical seizures in the CA1 field. Each seizure episode typically evolved by a seemingly smooth progression of brief interictal bursts into sustained ictal discharge. However, exposure of preparations showing electrical seizures to blockers of synaptic transmission or to cholinergic agonists abolished interictal spiking in all hippocampal fields but did not impede the initiation of ictal episodes in area CA1. Likewise, severing the connections between areas CA3 and CA1 abolished interictal spiking in area CA1 without disrupting the initiation of seizures in this region. These data clearly show that in this model, focal seizures arise independent of interictal spikes and through different cellular mechanisms. While interictal electrogenesis requires chemical synaptic excitation, ictal episodes can be initiated and maintained by nonsynaptic neuronal interactions.
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PMID:The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy. 284 67

The generation of focal cortical epilepsy as observed in human partial complex seizures is presumably due to enhanced physiologic responses or paroxysmal depolarization shifts (PDSs). However, the molecular mechanism that underlies these phenomena remains unknown. It could be due to a genetically determined error in a structural or regulatory protein or to posttranslational events that modulate membrane excitability. Since neither neuronal PDSs or interictal EEG spikes are sufficient to produce clinical epilepsy, the clinical expression of epilepsy may need the breakdown of neuronal or glial mechanisms that limit the spread of seizures. Hence, biochemical membrane studies of neurons and glia are necessary to understand the expression of human and experimental epilepsy. This chapter will review the role of glia in controlling neuronal excitability and neuron-glia relationships in experimental and human epilepsy. Data exploring the hypothesis that glial control of extracellular K+ or (K+)o is deficient in focal epilepsy induced by cold lesions will be reviewed. The role of glial carbonic anhydrase (CA) and glial control of putative amino acid transmitters in audiogenic epilepsy will be discussed. In the cold lesion, (K+)o activation constants of synaptosomal (Na+,K+)-ATPase are significantly decreased in the actively firing chronic focus, suggesting that the apparent affinity of the synaptosomal enzyme for K+ was increased within epileptic tissue that was actively firing. Interestingly, while sustained focal paroxysms could raise synaptosomal (Na+,K+)-ATPase, glial (Na+,K+)-ATPase and its activation by (K+)o remained decreased during sustained paroxysms in both acute and chronic lesions. Moreover, while the decrease of the absolute level of glial enzyme activity was less evident 45 days after lesion production, the poor response of glial enzyme to (K+)o never reversed to "normal" values. Hence, these experiments provided new information that glial (Na+,K+)-ATPase responds to K+ in a different manner when compared to synaptic enzyme. Glial ATPase and its activation by (K+)o remain decreased in either actively discharging acute lesions or in the indolent chronic foci. This could mean a reduction in the ability of glial membranes to maintain (K+)o homeostasis. As already suggested by Dichter, the impairment in glial control of elevated (K+)o could be mainly responsible for the transition of interictal discharges to ictal episodes, within the primary and the secondary foci.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuron-glia relationships in human and experimental epilepsy: a biochemical point of view. 287 19

This chapter reviews the chemical kindling model of epilepsy and speculates on its significance. Both human and experimental epilepsies are extremely heterogeneous, and it is unlikely that a single molecular or cellular mechanism can account for such a diversity of behavioral manifestations. Recent studies of chemical kindling favor the view that in this model, epilepsy is a property of neuronal networks that can take place in a structurally intact brain and does not depend on the presence of gross or microscopic brain damage. Kindling can be obtained by daily injections of nanomolar amounts of multiple muscarinic agonists in selective brain regions such as the amygdala and, once acquired, it is very persistent and frequently accompanied by spontaneous seizures. No evidence exists for creation of a novel pathway, and studies of seizure threshold suggest the need for a critical mass of neurons even on initial stimulation. The amounts of muscarinic agents injected are small enough to have little recordable effect initially, and the number of stimulations needed varies directly with the dose and inversely with the interstimulus interval. Carbachol kindling is inhibited by picomolar amounts of muscarinic antagonists, and the relative potencies of drugs on the kindling behavior in vivo parallel their affinity for muscarinic receptors in vitro. The (+) isomer of acetyl-beta-methylcholine, with good affinity for the muscarinic receptor, can induce kindling, whereas the (-) stereo isomer with poor affinity for the receptor cannot. No morphological differences are observed between animals injected with the (+) or the (-) isomer. These experiments suggest that the development of chronic focal epilepsy can take place in a structurally intact brain, be independent of the production of brain damage, and totally dependent on synaptic excitation. In other words, in this model, epilepsy may be a disease of cell-cell communication in which structurally normal neurons develop epileptiform responses as their interactions are modified through synaptic activation. A study of the relationships between carbachol and electrical kindling of the same site gave different results depending on the site of stimulation. In the amygdala, no interaction was found, but when both stimuli were aimed at the cholinoceptive hippocampal cells, a strong facilitation in both directions was observed. Thus, it appears that chemical and electrical kindling share similar mechanisms and that cross-facilitation depends on the existence of a common anatomy. The same anticonvulsants that block electrical kindling also inhibit chemical kindling.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Synaptic mechanisms in the kindled epileptic focus: a speculative synthesis. 287 22


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