Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five enzymes involved in glutamic acid, GABA, and catecholamine metabolism were measured in epileptic human brain. Electrocorticographically defined areas of focal spiking were compared with samples from surrounding nonspiking cortex. Comparative enzyme activities were as follows (mumol/h/g wet wt): glutamic acid dehydrogenase (GDH)--spiking 135.77 +/- 10.22 (mean +/- SEM), nonspiking 118.58 +/- 9.42 (p less than 0.001, N = 17); glutamic acid decarboxylase--spiking 10.63 +/- 0.95, nonspiking 9.96 +/- 1.10 (NS, N = 13); GABA-aminotransferase--spiking 36.49 +/- 1.05, nonspiking 36.46 +/- 1.48 (NS, N = 12); glutamine synthetase--spiking 96.94 +/- 3.81, nonspiking 96.52 +/- 4.10 (NS, N = 20); and tyrosine hydroxylase (TH; nmol/h/g)--spiking 16.23 +/- 2.39, nonspiking 10.67 +/- 1.95 (p less than 0.001, N = 14). Increased activity of GDH and TH may prove useful to characterize further areas of active spiking in human focal epilepsy.
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PMID:Enzyme changes in actively spiking areas of human epileptic cerebral cortex. 614 16

Impaired GABA-mediated inhibition is probably one of the cellular abnormalities leading to Focal Epilepsy. The role of GABA in generalized seizures, particularly of Petit Mal type, is unknown. Various approaches are available to potentiate GABA function. Merits and flaws of each one of them are critically evaluated. In some forms of epilepsy, GABA agonists may replenish depleted pools, and in some others may nonspecifically raise the general excitability threshold of the brain, yet in other forms they may exert a glutamate/aspartate antagonistic effect. The available experimental evidence suggests that in bilaterally synchronous spike and wave epilepsies, GABA agonists are either ineffective or pejorative.
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PMID:The perspective of GABA replenishment therapy in the epilepsies: a critical evaluation of hopes and concerns. 631 78

Homotaurine and taurine are two powerful inhibitory aminoacids with anticonvulsant properties against various experimental models of focal epilepsy. This study reports on their effects in the feline model of corticoreticular epilepsy induced by parenteral administration of large amounts of penicillin. Both aminoacids, but particularly homotaurine, remarkably potentiate epileptiform discharges in cats. Brainstem transection at the precollicular level does not modify the activation, thus ruling out the intervention of mesoromboencephalic structures in the observed effect. The opposing action of these two amino acids on focal epilepsy as compared to corticoreticular epilepsy suggests that the two types of epileptiform activity stem from very different pathophysiological mechanisms. Homotaurine is a powerful GABA agonist that exerts a central action upon parenteral administration. Other GABA analogs such as muscimol, imidazole acetic acid, and gamma-hydroxybutyrate have been reported to potentiate experimental models of spike and wave epilepsy. Thus, the activating effects of homotaurine in this epilepsy model are in keeping with the demonstrated GABAmimetic properties of the compound.
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PMID:Activating effects of homotaurine and taurine on corticoreticular epilepsy. 678 94

We compared amino acid contents of 54 epileptogenic foci removed neurosurgically from temporal or frontal cortex of 35 patients with focal epilepsy with those of biopsies from the same cortical regions of 14 nonepileptic patients. Neither taurine nor GABA content was reduced in epileptogenic foci. Glycine content was elevated markedly in some foci, whereas aspartic acid content was normal. Mean glutamic acid content was significantly higher in epileptogenic foci than in control cortex, and six foci contained amounts of glutamate more than 2 SD above the control mean. Our findings do not support hypotheses that deficiencies of taurine or GABA are involved in the pathogenesis of focal epilepsy but do suggest a possible etiologic role for the excitatory neurotransmitter, glutamic acid.
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PMID:Amino acid abnormalities in epileptogenic foci. 678 61

The initial objective of the present study was to investigate the role of excitatory and inhibitory amino acids in generalized as compared to focal epilepsy, both forms being induced by the same convulsant agent, i.e. penicillin. Our attempts to obtain in the rat the generalized epilepsy, constantly induced in cats by systemic administration of penicillin, were unsuccessful. This is probably due to the rudimentary development of the cerebral cortex in rodents as compared to the feline cortex. The tentative conclusion was drawn that the cortex is the brain structure mainly involved in the genesis of petit mal seizures. Penicillin was applied to the cortex of 40 white Wistar rats and the electrical cortical activity was registered. The concentrations of glutamate, aspartate, glycine, GABA and serine were determined in the cerebral cortex, the brain stem and the cerebellum. The same amino acids were determined in the brain of 20 controls. No significant changes in the amino acid contents were obtained in the cerebral cortex. In the brain stem the glutamate level was significantly increased while the glycine content was markedly decreased. These findings are consistent with the involvement of the brain stem structures in seizure activity.
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PMID:Amino acid content of the brain in rats focal penicillin induced epilepsy. 754 74

In the context of a study of the effects of gamma-vinyl-GABA (GVG) on seizure occurrence and on EEG abnormalities we present three cases with focal epilepsy in which new clinical and EEG paroxysmal manifestations were observed during GVG therapy. At that time, whereas an amelioration or no change in patients' habitual seizures were observed, myoclonic jerks appeared with related changes in the EEG paroxysmal abnormalities, represented by generalized polyspike and wave complexes. An electroclinical correlation was recorded in one case. These data indicate that, although occurring rarely, it is possible to have epileptic myoclonus during GVG treatment. Mechanisms underlying these manifestations are difficult to explain. Probably a shift in the anti/proconvulsant GABAergic balance towards the latter may compromise the therapeutic effect of GVG.
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PMID:Development of myoclonus in patients with partial epilepsy during treatment with vigabatrin: an electroencephalographic study. 773 67

Most currently available antiepileptic drugs (AEDs) were developed by testing new compounds in animal models of seizures. Increased knowledge of the cellular and molecular mechanisms underlying normal CNS function and seizure phenomena is now being used to design new AEDs specifically to interfere with epileptic mechanisms. Focal epilepsy develops in areas of cortex that are damaged and in which aberrant recurrent excitatory circuits develop, producing spike discharges in the EEG. Occasionally, normal membrane conductances and inhibitory synaptic currents break down and excess excitability spreads, either locally to produce a focal seizure or more widely to produce a generalized seizure. Both original synchronous activation and seizure spread appear to utilize normal synaptic pathways and mechanisms. Much new development of AEDs is targeted at modulating these excitatory and inhibitory synaptic effects, focusing directly on multiple components of glutamate and GABA receptors. Intrinsic, voltage-dependent currents are also involved in the pathophysiology of epileptic processes. Calcium currents act to amplify excess neuronal depolarization during hypersynchronous activation, are involved in neurotransmitter release, and play a role in the development of longer-term changes in synaptic efficacy, which may be involved in some seizure phenomena. They also appear to be involved in some forms of primary generalized epilepsy, in which burst discharges due to calcium currents in deep diencephalic neurons with widely ramifying axons may act as synchronizing influences. Neuromodulatory agents, including purines, peptides, cytokines, and steroid hormones, also play important roles in regulating brain excitability. Adenosine in some experimental models act as an endogenous antiepileptic substance, and agents that enhance the actions of adenosine are often antiepileptic in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Emerging insights into mechanisms of epilepsy: implications for new antiepileptic drug development. 817 19

Tiagabine blocks the uptake by neurons or glia of synaptically released GABA resulting in prolonged GABAergic activity and decreased likelihood of epileptic seizures. We evaluated the cognitive and quality of life effects of tiagabine in a double-blind, add-on, placebo-controlled, parallel, multicenter, dose-response efficacy study in patients with focal epilepsy whose complex partial seizures were difficult to control. One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments: placebo (n = 57), 16 mg/d tiagabine (n = 34), 32 mg/d tiagabine (n = 45), or 56 mg/d tiagabine (n = 26) at a fixed-dose for 12 weeks after a 4-week dose titration period. Eight cognitive tests and three measures of mood and adjustment were administered during the baseline period and again during the double-blind period near the end of treatment (or at the time of dropout). The patient groups were similar at entry into the study. Results showed no clinically important changes with the addition of tiagabine on the test battery. Although this is an encouraging finding, it remains for future investigations to determine the cognitive and behavioral effects of tiagabine either as monotherapy or in relation to other antiepileptic drugs.
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PMID:Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. 910 94

The effect of lesionectomy depends on the reversibility of the epileptogenic changes in the perilesional cortex. We studied how the perilesional GABAergic neuronal changes are related to the effect of lesionectomy in the alumina cream-induced focal epilepsy model in cats. Sequential changes of GABAergic neurons and spike activities were measured after the micro-injections of alumina cream (AC). Alumina granulomas were excised 15 days and 40 days after the injections. At day 20 following the AC injection, GABAergic neurons were decreased 25 to 40% compared with those in the contralateral intact cortex. At day 40, a significant increase of spike activities occurred. GABA positive cells were decreased more than 50% compared with those in the contralateral cortex. At day 80, significant cell loss in perilesional cortex was demonstrated. The effect of lesionectomy was greater in the early excised group than in the late excised group. Decrease of GABAergic neuron was more severe in the late excised group compared to the early excised group. Our results indicate that more than 50% reduction of perilesional GABA neurons may be a critical point in epileptogenesis in this model. Lesionectomy alone prior to a 50% reduction in perilesional GABAergic neurons may be sufficient for seizure control. With these data it is still unclear whether these findings contribute to the choice between lesionectomy alone and lesionectomy with resection of the perilesional cortex. Further study is needed to understand the difference between the AC epilepsy model and human chronic epilepsy.
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PMID:The effect of lesionectomy and the perilesional GABAergic neuronal changes in alumina cream-induced focal motor epilepsy in cats. 958 88

Tetanus Toxin is widely used as a model of chronic focal epilepsy and is assumed to act by blocking neurotransmitter release with high selectivity for inhibitory synapses. However, the exact mechanisms are not fully understood, since, e.g., GABA release is only temporarily decreased although epileptiform activity persists pointing towards a change in the interplay of excitation and inhibition. Furthermore there have been reports about different effects of tetanus toxin after injection in separate brain areas. Therefore, we investigated the functional inhibition after injecting tetanus toxin either in the motor or sensory cortex of adult rats by using a paired-pulse paradigm as a measure of excitatory and inhibitory drive. Tetanus toxin injection into the motor cortex (n=10) induced a marked, long-lasting reduction in inhibition which was highly significant in most parts of the injected cortical area. Injections into the sensory cortex, however, showed less marked changes in inhibition which were more widespread and significant only in 3 of 14 animals injected. These results give further evidence for a prominent effect of tetanus toxin on functional inhibition and strengthen the idea of a differential effect in separate cortical areas. They may be accounted for by the different cytoarchitecture of cortical areas with variable inhibitory and excitatory intracortical connections.
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PMID:Effects of tetanus toxin on functional inhibition after injection in separate cortical areas in rat. 991 45


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