Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential clinical efficacy of tiagabine for control of status epilepticus was evaluated in an experimental model. Tiagabine was administered to cobalt-lesioned rats in which status epilepticus was induced by injection of homocysteine thiolactone. Tiagabine was effective in controlling status epilepticus in this model; the median effective dose for control of generalized tonic-clonic seizures in the model was 8.3 mg/kg. Tiagabine administration produced an abnormal, hypo-reactive behavioral state which was accompanied by an EEG pattern of high-amplitude, frontally dominant, rhythmic, 3-5-Hz spike-wave activity. This EEG and behavioral syndrome could be reproduced by administration of tiagabine to normal, non-epileptic rats. The exact nature of this syndrome remains unclear, but whether it is an epileptic or encephalopathic phenomenon, further study is clearly required before this drug should be considered for use in the treatment of human status epilepticus.
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PMID:Treatment of experimental status epilepticus with the GABA uptake inhibitor, tiagabine. 769

Based on experimental research, since 1982 until 1991 a series of 11 patients diagnosed as suffering from idiopathic focal epilepsy have been treated with stereotactic radiosurgery. Focus location was determined with cortical electrodes and confirmed by stereotactically placed deep electrodes. Stereotactic radiosurgery was performed with photons from a cobalt source with a dose of 10 to 20 Gy, except in two cases in whom a betatron was used. The results were: complete cessation of seizures in four cases and a significant reduction in the number of seizures in five additional cases. Seizures began to decrease gradually after a period of three months of one year, except in two cases in whom there was an immediate response after treatment. In two cases there was no change. No complication related to the irradiation was recorded. The gradual and delayed effect, obtained with low doses, may favour the hypothesis that non-descructive permanent structural changes, possibly related to the neuronal plasticity phenomenon, constitute the mechanism underlying these facts. Although the number of cases so far is too small, the absence of side-effects may make this bloodless method the one of choice specially in those cases in whom eloquent areas are involved.
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PMID:Radiosurgery of epilepsy. Long-term results. 771 26

Brain glucose consumption in rats with unilateral visual cortex implants of epileptogenic cobalt rods was assessed by the 2-deoxyglucose (2-DG) method. Nine days postoperatively, "dark patches" of higher 2-DG uptake, bordered by tissue showing lesser uptake, were observed around the implant site. The dark patches were located just beyond the damaged perifocal zone, in normal-appearing Nissl-stained cortex designated by the electrocorticographic (ECoG) work of other investigators as the focus of epileptic activity. As was also predictable from earlier research, the cortical patches were prominent on day 9 and absent by day 35. Regions of high metabolic activity in thalamus, presumably the result of axonal transport of cobalt ions, were also strikingly evident in the projection nuclei connecting with the cortical implant sites. The abnormal thalamic activity is likely the metabolic counterpart of "secondary foci," a characteristic feature of the cobalt model. The longevity of these thalamic dark patches, which developed between days 2 and 9 and did not disappear until between days 90 and approximately 365, may account for the persistent sensitivity to seizure-inducing drugs that occurs secondary to cobalt implants. The absence of dark patches after control nonseizure-inducing but toxic copper implants argued against the possibility that the dark patches reflected some nonepileptogenic effect of the cobalt. As well, under pentobarbital anesthesia, the patches behaved in a manner suggesting that their 2-DG uptake reflected neural and not glial cell activity. Dark patches are a distinctive autoradiograph signature of tissue made epileptic by cobalt.
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PMID:[14C]2-deoxyglucose autoradiographic technique provides a metabolic signature of cobalt-induced focal epileptogenesis. 792 65

Multiple intracranial arteriovenous malformations are rare. There are a few cases in the literature with up to three malformations in one patient. A child with seven separate cerebral malformations is now described. There was no history of haemorrhage, but only of febrile seizures. The malformations were discovered at CT and verified at angiography. Six were selected for stereotaxic irradiation with the multi-cobalt unit. The seventh was considered too big for irradiation and suitable for surgery.
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PMID:Multiple intracranial arteriovenous malformations: a case report. 818 62

Using ion exchange HPLC and ammonium sulfate precipitation, we have purified a 70-kDa protein (P70) specific to the cobalt-induced epileptogenic cortex of rat cerebrum and determined certain of its biochemical properties. P70 has a similar isoelectric point (pI; 4.6-4.8), amino acid composition and N-terminal amino acid sequence to rat serum albumin (RSA). Intracortical application of purified P70 to the motor area of normal rat cerebrum induces both ECoG seizure discharges and behavioral seizures. The data suggest that P70 is a novel albumin-like protein linked to the generation of seizure activities. However, it can be clearly distinguished from RSA, since it is able to produce seizure, is a glycoprotein and can be readily separated from RSA by 2-dimensional electrophoresis.
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PMID:Purification and characterization of a novel 70-kDa brain protein associated with seizure activities. 858 47

alpha-Guanidinoglutaric acid (alpha-GGA) was first isolated from the cobalt-induced epileptic focus of cat cerebral cortex by us in 1980. alpha-GGA could induce behavioral convulsion as well as electroencephalography-documented epileptic seizures, when it was administered into the brain. alpha-GGA was also found to be a potent nitric oxide synthase inhibitor, suggesting that suppression of this activity may result in epileptic seizures. It is now observed that alpha-GGA generates reactive oxygen species as superoxide and hydroxyl radicals in aqueous solution. These findings suggest that reactive oxygen species may damage cell membranes, thus leading to neuronal depolarization, which is closely related to epileptogenesity.
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PMID:alpha-Guanidinoglutaric acid as a free radical generator. 867 21

Because titanium is widely used in neurosurgical procedures, we compared spontaneous and induced epileptiform activity in 12 rabbits with titanium clips implanted in the subarachnoid space with 12 rabbits with cobalt alloy clips and 6 rabbits that were not operated on that served as controls. Beginning 1 week after surgery, 30-minute electroencephalographic recordings were made at monthly intervals for 6 months. Recordings were scored by an electroencephalographer unaware of which treatment group was being recorded. In 48 recordings made during 6 months, no epileptiform activity was observed in any animal. Seizure threshold was evaluated by continuous intravenous injection of the convulsant drug, pentylenetetrazole (2 mg/kg/min), with continuous electroencephalographic recording. Time to spiking for the nonsurgical control group was 327 mean seconds +/- 181 standard deviation (SD), 216 mean seconds +/- 135 SD for the titanium group, and 389 mean seconds +/- 290 SD for the cobalt group. There were no significant differences among the groups (P = 0.17). Latency to behavioral tonicoclonic seizure was 1031 seconds +/- 537 SD for the group not operated on, 875 seconds +/- 334 SD for the titanium group, and 1267 seconds +/- 764 SD for the cobalt group. This study suggests that titanium clips are well tolerated within the brain and will not induce seizures.
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PMID:Titanium aneurysm clips: Part II--Seizure and electroencephalographic studies in implanted rabbits. 872 48

The newly introduced antiepileptic drug, lamotrigine, has been reported to have a mechanism of action similar to that of phenytoin. Because phenytoin is a standard clinical treatment for convulsive status epilepticus, we compared the efficacy of lamotrigine to that of phenytoin in a model of secondarily generalized convulsive status epilepticus in rats that responds to drug concentrations similar to those that have been reported to be clinically useful for this purpose. Status epilepticus was induced in rats with actively epileptogenic cortical cobalt lesions by administration of homocysteine thiolactone. While phenytoin-controlled generalized tonic clonic seizures in this model with a median effective dose of 100.5 mg/kg (16.0 micrograms/ml in serum), lamotrigine was ineffective at doses ranging from 10 to 100 mg/kg, with serum drug concentrations (2.5-43.5 micrograms/ml) within or above the reported 'therapeutic' concentration for LTG treatment of chronic epilepsy. Lamotrigine also failed to prevent the onset of generalized tonic clonic seizures when given prior to homocysteine, while phenytoin was effective in this test. Studies of lamotrigine kinetics in serum and brain revealed that the drug was well-absorbed following i.p. injection and that it entered brain rapidly enough to have exerted an anti-status effect in these experiments. These results suggest that lamotrigine and phenytoin have differences in their mechanisms of anticonvulsant action, leading to very different abilities to control status epilepticus.
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PMID:Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. 880 Jun 32

Interictal epileptiform EEG activity was recorded in 10 rats with pentylenetetrazol-induced generalized seizures and in 10 rats with cobalt-induced partial epilepsy. Thirty spikes were averaged for each rat, and morphological parameters of the average waveform (such as amplitude, duration, and 1st derivative of the rising and falling spike deflections, and sharpness at peak) were measured. Pentylenetetrazol rats showed significantly higher and longer spikes than cobalt animals with a faster 1st derivative of both deflections; sharpness at peak was also higher in this group. The second spike deflection was higher and longer than the first in both groups of animals. The conclusion is that morphological spike parameters, when studied in groups of animals not treated with antiepileptic drugs, show significant differences between different experimental groups, probably reflecting a different cortical involvement and/or different epileptogenic mechanisms. The study of spike morphology can be extended to human epilepsy if etiopathogenetically homogeneous and untreated groups of patients are considered.
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PMID:Spike morphology in PTZ-induced generalized and cobalt-induced partial experimental epilepsy. 911 66

Nine days after insertion of a pure cobalt metal rod into the visual cortex, regions of increased 2-DG uptake are observed both in relatively normal Nissl-staining tissue lying around the implant site and in the connecting dorsal lateral geniculate nucleus of the thalamus. These hypermetabolic regions have been claimed to be the metabolic 'signatures' of tissue made epileptogenic by the cobalt. The present study showed, however, that while the 'dark patches' develop following posterior cortex implants, they do not appear after anterior cortex cobalt implants. Moreover, the dark patches were not detectable after cortical implants of other seizure-inducing metals such as antimony and nickel. These new findings indicate that the dark patches occur too idiosyncratically to make them the metabolic 'signatures' of tissue made epileptic by cobalt.
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PMID:Effects of neocortical implants of cobalt and other seizure-inducing metals on brain C-14 2-deoxyglucose uptake. 916 87


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