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

This is the first reported case of a major overdose of Lioresal (baclofen or CIBA BA-346467). A 29-year-old woman with known Huntington's disease took from 900 to 970 mg of Lioresal, a cogener of gamma amino butyric acid (GABA) used experimentally to treat muscle spasm. She was admitted in deep coma with absent brain stem reflexes and without spontaneous respiration, and she required cardiovascular support. Her pupils were fixed at 3 mm and unreactive for 48 hours. She continued to require intensive support for a total of 72 hours and had one seizure during the recovery phase. Her eventual recovery was complete. No specific antidotes are currently available for overdose of Lioresal and supportive care is the only method of treatment for overdose.
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PMID:Overdose of lioresal. 13 33

Coma and other neurologic abnormalities are present in patients with either diabetic ketoacidosis (DKA) or nonketotic coma (NKC), and the cause of such phenomena are not known. Patients with NKC also manifest seizures and focal neurologic changes. Treatment of diabetic coma with insulin may induce cerebral edema by as yet undefined mechanism(s). In patients with DKA, cerebral oxygen utilization is impaired, and there is hyperviscosity of the blood. A substantial part of the brain's energy source is derived from ketones, which in themselves can depress sensorium. Extracellular hyperosomolality is present, which may also contribute to the genesis of coma. In addition, most ketoacidotic patients have associated medical conditions, which may further impair consciousness. Biochemical changes in the brains of animals with DKA include impairment of both phosphofructokinase activity and pyruvate oxidation, and accumulation of citrate. The net effect upon sensorium in ketoacidotic patients probably represents the interaction of most of the above factors and differs markedly among individuals. Patients with NKC manifest not only depression of sensorium, but also focal motor seizures, hemiparesis, and other neurologic changes, such as aphasia, hypereflexia, sensory defects, autonomic changes, and brainstem dysfunction. Most of the aforementioned changes revert to normal after correction of hyperosomolality. Gamma amino butyric acid, which has been shown to elevate the seizure threshold, is normal in brains of ketoacidotic animals, but may be low in nonketotic coma. Also, hyperosomolality per se may produce seizures. Cerebral edema may complicate the treatment of either DKA or NKC. The available experimental evidence suggests that many of the commonly held theories for the production of such brain swelling probably do not occur. There is no breakdown of the sodium pump, sorbitol or fructose do not accumulate in brain, and brain glucose is only about 25 percent of that in plasma; Cerebral edema is probably produced largely by a direct action of insulin on brain at a time when plasma glucose is approaching normal values. Cerebral edema can thus theoretically be avoided by stopping insulin when plasma glucose has been lowered to values approaching normal.
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PMID:Neurologic manifestations of diabetic comas: correlation with biochemical alterations in the brain. 80 37

In sheep, administration of a combination of zolazepam and tiletamine hydrochloride resulted in a dose dependent reduction in the duration of epileptic activity induced by an electric stun applied to the head. The compound also lengthened the normal period of reflex suppression that occurs after a stun. Excitatory amino acid receptor antagonists (2-amino-7-phosphonoheptanoic and 2-amino-5-phosphonovaleric acids) also reduced the duration of epileptic activity following an electric stun. These drugs did not alter the time of pedal and ear pinch reflex suppression. Administration of bicuculline (a gamma amino-4-butyric acid [GABA] receptor antagonist) reduced the period of stun induced reflex suppression and increased seizure duration. Administration of a GABA receptor agonist, baclofen, increased the duration of reflex suppression. The results suggest that the development of epileptiform-like activity following application of an electric current to the head is dependent upon excitatory amino acid receptors. The reflex suppression that also arises following an electric stun is contributed to by the activation of GABA receptor mechanisms.
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PMID:Contribution of amino acid transmitters to epileptiform activity and reflex suppression in electrically head stunned sheep. 134 45

In a companion article (see this issue), the proconvulsant properties of the pesticide endosulfan in electrical kindling of the amygdala are described. In the present report, an evaluation of the chemical kindling properties of endosulfan is presented. Repeated administration (3 times per week for a total of 21 doses) of endosulfan (5 and 10 mg/kg in corn oil, PO) was found to induce behavioral seizures in rats. Behavioral seizure development was most apparent in the high dose group (10 mg/kg). Heightened seizure responsiveness to a challenge dose was maintained following a two-week, drug-free period, arguing against cumulative toxicity as a mechanism for seizure induction. Electrical kindling induced by once daily stimulation of the amygdala began approximately 4 weeks after the final dose of endosulfan. In the absence of further dosing, a significant facilitation in the rate of kindling development was evident as a function of prior treatment with endosulfan. An enhancement in the rate of kindling was also evident in the low dose group (5 mg/kg) in the absence of clonic seizure development during dosing. A history of endosulfan treatment failed to affect threshold for inducing an afterdischarge (AD) and had equivocal effects on the development of AD with repeated stimulation. Pretreatment with a single high dose of endosulfan 2 weeks prior to electrical kindling was without effect on the development of the kindled response. Endosulfan has been reported to decrease binding of gamma-amino-butyric acid (GABA). Chemical kindling with endosulfan may result from the interaction of this pesticide with GABA-mediated neurotransmission in the central nervous system (CNS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A characterization of chemical kindling with the pesticide endosulfan. 159 89

The activity of glutamate related enzymes and the concentration of glutamine, glutamate and gamma-amino n-butyric acid (GABA) were investigated in the cerebral cortex of rats, in different stages of insulin-induced hypoglycemia. Hypoglycemia was produced by intraperitoneal injection of insulin 0.05-100 units per kg body weight. The minimum required dose to produce irreversible severe hypoglycemia was 0.5 units/kg. In 85% of the cases an insulin induced hypoglycemic convulsion, was achieved 130-150 minutes after injection. Blood glucose levels during insulin induced seizures ranged between 8-15 mg%. In the range of 0.5-100 u insulin/kg the degree of hypoglycemia and the onset of convulsions were identical. The concentration of glutamine was significantly reduced during convulsive and postconvulsive stages. Glutamate and GABA concentrations were reduced significantly in all stages of insulin-induced hypoglycemia. The decrease in glutamine concentration was concurrent with an increase in the activity of its degradative enzyme, glutaminase. This was apparent at the preconvulsive, convulsive and postconvulsive stages. The activity of other enzymes related to energy production such as glutamate dehydrogenase (GDH), glutamate transaminase (GPT) and aspartate aminotransferase (AAT) were also increased. The activity of glutamine synthase (GS) was unaffected by hypoglycemia. Insulin induced changes in glutamine, glutamate and their related enzymes could not be attributed to convulsion since a similar pattern of changes was observed in the preconvulsive and postconvulsive stages, and no changes were detected following picrotoxin-induced seizures.
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PMID:Changes in the activity of glutamate related enzymes in cerebral cortex, during insulin-induced seizures. 257 18

The effects of the convulsants L-allylglycine and bicuculline on the distribution of gamma-amino-butyric acid (GABA), glutamate and aspartate in rat brains were assessed immunocytochemically, using antisera raised against glutaraldehyde-protein conjugates of the respective amino acids. In accord with previous biochemical studies of GABA content, L-allylglycine treatment was followed by a decreased immunoreactivity for GABA in the hippocampus and cerebellum, whereas treatment with bicuculline led to an increased immunoreactivity in the hippocampus, but not in the cerebellum. Different cells and zones were affected differentially. With both convulsants the hippocampus showed the most pronounced changes in the neuropil of the pyramidal and granular cell layers. L-Allylglycine treatment led to a substantial decrease in the concentration of detectable GABA-immunoreactive bouton-like dots in the stratum oriens, radiatum and lacunosum-moleculare and in the deep hilar region, but did not produce statistically significant changes in this parameter in the outer and intermediate zones of the dentate molecular layer. In the cerebellum, the decrease in GABA immunoreactivity after L-allylglycine treatment was less in the basket cell terminals than in other GABA-containing elements. Neither convulsant altered the average staining intensity for aspartate or glutamate in the two regions studied, but L-allylglycine reduced the level of aspartate-like immunoreactivity in hippocampal hilar cells. All the changes described were evident after 20 min of seizure activity and were qualitatively similar after 60 min of seizure (animals paralysed and ventilated). Our results indicate that L-allylglycine or bicuculline given intravenously exerts specific effects on cerebral amino acid metabolism. The nature and magnitude of these effects show inter-regional variations and also differ among cellular compartments within each region. Amino acid immunocytochemistry may prove to be a valuable tool for the investigation of metabolic changes associated with epileptic seizures and should be particularly useful in regions showing heterogeneous changes that would tend to cancel each other in biochemical analyses.
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PMID:Redistribution of transmitter amino acids in rat hippocampus and cerebellum during seizures induced by L-allylglycine and bicuculline: an immunocytochemical study with antisera against conjugated GABA, glutamate and aspartate. 288 43

Although animal models consistently indicate that gamma-amino-butyric acid (GABA) synaptic function (GABA levels, synthesis, uptake and/or receptors) is decreased in seizure states, there is little evidence to date in support of such a hypothesis for human epilepsy. This chapter presents the results of an in-depth study of the activity of the GABA-synthesizing enzyme L-glutamic acid decarboxylase (GAD) in brain tissue removed during neurosurgical resection for intractable epilepsy. The tissue studied is unique in that identified (by stereo EEG) foci were excised (rather than large blocks of tissue containing mixtures of foci and nonepileptic material) and compared with nonepileptic (stereo EEG and morphological definitions) tissue from the same patients. In patients in which there was no indication of a tumor, GAD activity in the foci was low in more than 50% of the patients examined. Furthermore, when the population distribution of GAD was compared in epileptic versus nonepileptic tissue fragments from all patients, the peak distribution of epileptic tissue fragments occurred at much lower GAD activities than for the nonepileptic fragments (0-20 versus 41-80 nmol CO2/mg protein X hr, respectively). A small subgroup of epileptic fragments occurred with a normal GAD distribution, indicating that the presence of an epileptic focus was not invariably associated with low GAD activity. When the low levels of GABA "A" binding sites in these epileptic tissue fragments are taken into consideration in combination with the low GAD levels, then it can be estimated that 60 to 70% of the present patient population had deficient GABAergic transmission in epileptic foci as compared to nonepileptic brain tissue from the same patients. It follows that the GABA hypothesis of human epilepsy is not an exclusive or unitary hypothesis, and some patients appear to have normally functioning GABA synapses (as assessed biochemically) in epileptogenic areas. Thus, other neurotransmitter and neurohumoral systems certainly play a role in the epileptic process.
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PMID:Alterations of GABA-mediated synaptic transmission in human epilepsy. 301 Jun 75

Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.
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PMID:Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures. 306 61

A series of sulfur-containing congeners have been prepared from alpha-ethyl-alpha-methyl-gamma-butyrolactone, beta-ethyl-beta-methyl-gamma-butyrolactone, and alpha,alpha,beta,beta-tetramethyl-gamma-butyrolactone as potential neuropharmacologic agents. The lactones were treated with benzyl mercaptide anion to form 4-(benzylthio)butyric acid, which, on treatment with trifluoroacetic acid, cyclized to yield thiololactones. The thiono- and dithiolactones were prepared by treating the corresponding lactones either with Lawesson's reagent or with phosphorus pentasulfide, respectively. As had been observed previously for the lactones, the beta-substituted and alpha,beta-substituted congeners were potent convulsants that caused generalized clonic and tonic seizures in mice. The alpha-substituted congeners were effective in inhibiting pentylenetetrazole-induced seizures in mice. alpha-Ethyl-alpha-methylthiolo-gamma-butyrolactone showed an increase in potency over the congeneric alpha-ethyl-alpha-methyl-gamma-butyrolactone and, additionally, was effective against maximal electroshock seizures. In no cases was a convulsant converted to an anticonvulsant or vice versa by sulfur-for-oxygen substitution.
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PMID:Alkyl-substituted thiolo-, thiono-, and dithio-gamma-butyrolactones: new classes of convulsant and anticonvulsant agents. 376 17

The authors describe the anticonvulsant activity of a new gamma-amino-butyric acid (GABA) derivative in several animal models of generalized epilepsy including photoepileptic baboons. In all the studies, 4,9-dioxo-5,10-diazatetradecane (CM 40 142) revealed potencies against chemically, electrically and photic-induced seizures very similar to those observed with sodium valproate. In chemically elicited seizures in mice, CM 40142 exhibited a higher potency than sodium valproate in antagonizing anti-GABAergic agents. Although CM 40142 was synthesized as a compound which would cross the blood-brain barrier and liberate GABA within the central nervous system, preliminary biochemical investigations in mice failed to demonstrate a rise in brain GABA levels after treatment with CM 40142. Furthermore, CM 40142 increased spontaneous motility in mice at anticonvulsant doses. The data suggest that CM 40142 could be a broad spectrum nonsedative antiepileptic agent.
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PMID:Anticonvulsant activity of 4,9-dioxo-5,10-diazatetradecane (CM 40142), a new GABA derivative, in mice and photosensitive baboons). 643 27


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