Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential hepatotoxicity resulting in fatal liver failure is of major concern in treating patients with valproate (VPA). Until now there is no relevant laboratory parameter allowing early detection of impending liver failure. The major routes of VPA biotransformation are glucuronidation and beta-oxidation. There are several other pathways of degradation with formation of mono- und di-unsaturated derivates. VPA dose, patients age, co-medication (anticonvulsants, aspirin), fasting and glucose supply influence the VPA metabolism. The clinical spectrum of VPA-associated hepatotoxicity reaches from slight increases of liver enzymes without clinical manifestations over reversible slight to severe liver dysfunction to fatal liver failure. With respect to pathogenesis attention has focused on depletion of beta-oxidation and change of biotransformation to other pathways with increased synthesis of toxic unsaturated VPA derivates. Several inborn errors of metabolism, acute infections and status epilepticus seem to predispose to liver failure. Another hypothesis lies in the possible VPA-induced depression of free radical scavenging enzyme activities. On this basis N-acetylcysteine has been used successfully in treating children with severe hepatotoxicity. In the presence of certain risk factors VPA should be avoided.
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PMID:[Valproate-associated hepatotoxicity--pathogenesis, clinical aspects, therapy and prevention]. 175 43

Current knowledge suggests integration of cerebral perfusion and metabolism as enabling normal neuronal function, and their pertubations explaining the brain damage of hypoxia, hypoglycaemia, hypoperfusion and status epilepticus. Similar mechanisms appear operative in the viral encephalopathies and cause psychomotor dysfunction and epilepsy. A transient inhibition of plasma membrane glucose transport is central to the understanding of the metabolic abnormalities of these encephalopathies, the ensuing cell energy crisis resulting from neuroglycopoenia being evidenced by electroencephalographic changes, lactic and ketoacidosis, hyperuricaemia and ionic aberrations. Failure of Na+ and Ca2+ pumps cause cerebral oedema and neuronal death respectively, the selective nature of the latter being due to alpha-adrenergic vasoconstriction. Management with hyperglycaemia-producing infusions and the judicious use of lactate and steroids can overcome the transport dysfunction and enable complete recovery. The temporal profile of the metabolic aberrations of febrile convulsions, which are the result of adaptation, provide a template supporting this mode of management of the severe encephalopathies.
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PMID:The probable mechanisms of brain damage and epilepsy in febrile convulsions, Singapore syndrome and Reye's syndrome. 250 20

The authors studied the availability of parenteral solutions of diazepam in glass bottles or polyethylene (PE) containers during infusion through polyvinyl chloride (PVC) administration sets. Diazepam solutions in concentration of 1000 mg/500 ml in 0.9% sodium chloride (NS) and 5% glucose (G5W) injection were infused at a flow rate of 30 ml/h, and samples were taken from the bottle and at the end of the administration set, till 12 hours of infusion. The samples were tested in triplicate using ultraviolet spectrophotometry. The greatest loss of diazepam was observed in all solutions at 30 minutes of infusion (63.5% G5W glass, 60.5% NS glass, 55% G5W PE and 58% NS PE from the original concentration of 200 micrograms/ml). The diazepam concentrations in the containers did not significantly changed. The loss of diazepam from solutions infused through PVC administration sets should be kept in mind in severe clinical situations as status epilepticus, tetanus and eclampsia.
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PMID:Factors affecting diazepam availability from intravenous admixture solutions. 261 6

The effect of bicuculline-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) was studied in 2-wk-old ketamine-anesthetized marmoset monkeys, using the 2-[14C]-deoxy-D-glucose autoradiographical technique. To estimate LCMRglc in cerebral cortex and thalamus during SE, the lumped constant (LC) for 2-deoxy-D-glucose (2-DG) and the rate constants for 2-DG and glucose were calculated for these regions. The control LC was 0.43 in frontoparietal cortex, 0.51 in temporal cortex, and 0.50 in thalamus; it increased to 1.07 in frontoparietal cortex, 1.13 in temporal cortex, and 1.25 in thalamus after 30 min of seizures. With control LC values, LCMRglc in frontoparietal cortex, temporal cortex, and dorsomedial thalamus appeared to increase four to sixfold. With seizure LC values, LCMRglc increased 1.5- to 2-fold and only in cortex. During 45-min seizures, LCMRglc in cortex and thalamus probably increases 4- to 6-fold initially and later falls to the 1.5- to 2-fold level as tissue glucose concentrations decrease. Together with our previous results demonstrating depletion of high-energy phosphates and glucose in these regions, the data suggest that energy demands exceed glucose supply. The long-term effects of these metabolic changes on the developing brain remain to be determined.
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PMID:Local cerebral glucose utilization during status epilepticus in newborn primates. 273 93

Kainic acid administration induces status epilepticus seizures in the rat which damage CA1 and CA3 hippocampal neurons. Rats made hypoglycemic prior to seizure had enhanced volumes of damage, when compared to normo- or hyperglycemic rats. The mild hypoglycemia was not in the range which, itself, typically produces hippocampal damage. This suggests that limited energy availability compromised the ability of neurons to survive seizures. Our data also suggest that the CA1 damage seen after status epilepticus is not hypoxic-ischemic in origin, since elevating pre-seizure glucose concentrations to a range which typically exacerbates hypoxic-ischemic CA1 damage did not augment status-epilepticus CA1 damage.
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PMID:Status epilepticus-induced hippocampal damage is modulated by glucose availability. 291

Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus.
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PMID:Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus. 308 38

The cerebral metabolic response to bicuculline (BC)-induced status epilepticus (SE) was studied in two-week-old ketamine-anesthetized marmoset monkeys. During 30-min clonic seizures, mean blood pressure, plasma glucose and paO2 did not decrease and plasma lactate doubled. Brains were funnel-frozen and punch biopsies of frontoparietal cortex, temporal cortex and thalamus were analyzed for ATP, phosphocreatine (PCr), glucose and lactate. There were marked reductions of ATP (to 56-77% of controls), PCr (to 23-28% of controls) and glucose (to 1-4% of controls), and lactate increased 3- to 6-fold in seizure animals. NADH fluorescence increased during seizures in cerebral cortex, thalamus, amygdaloid nuclei, hippocampus, posterior striatum and hemispheric white matter. This suggests a reduced tissue redox state in these regions and is correlated with the high energy phosphate depletion and elevated lactate in cortex and thalamus. Our results demonstrate a significant depletion of energy reserves and glucose in cerebral cortex and thalamus during neonatal seizures in the absence of adverse systemic factors. These seizure-induced metabolic changes in brain could have adverse long-term effects on brain development and function.
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PMID:Generalized seizures deplete brain energy reserves in normoxemic newborn monkeys. 313 58

Positron Emission Tomography (PET) with the oxygen-15 steady state inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen consumption (CMRO2) and oxygen extraction ratio (OER) in 25 patients with partial complex seizures during the interictal state, in 1 patient with recurrent temporal seizures and in 3 patients whose EEGs were characterized by periodic lateralized epileptiform discharges (PLEDs). Interictal scans showed temporal zone(s) of hypoperfusion and hypometabolism in 80% of patients with normal X-ray CT Scan. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the EEG abnormalities. Comparison of the different values of CBF, CMRO2 and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease in OER, the latter was always the most prominent in the region of the focus determined by serial EEG recordings. The observed imbalance between blood flow and oxidative glucose metabolism could suggest an impairment of O2 utilization by the mitochondria in the epilepticus focus during seizures or status epilepticus.
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PMID:[Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography]. 349 37

By means of radioimmunoassay procedures, cholecystokinin-(CCK) and somatostatin-(SRIF) like immunoreactivity have been studied in the dorsal hippocampal formation and in the frontoparietal cortex of the male rat in insulin-induced hypoglycaemia, leading to an isoelectric EEG pattern. It has been demonstrated that severe hypoglycaemia of 40-min-duration produces a disappearance of SRIF but not of CCK-like immunoreactivity in both cortical regions. It was found that an i.v. injection of uridine but not of saline could significantly counteract the disappearance of SRIF-like immunoreactivity induced by severe hypoglycaemia in both cortical areas. Uridine did not by itself change plasma glucose levels. It is suggested that uridine may prevent release and/or increase synthesis of cortical SRIF peptides in severe hypoglycaemia, possibly due to an action on the metabolism (e.g. by enhancing the resynthesis of phosphatidyl inositol) within the tissue of the cerebral cortex and/or on putative pyrimidine binding sites in the brain controlling SRIF synthesis and/or release. It is possible that uridine in this way may improve recovery of neuronal function within SRIF-immunoreactive neurons of the cerebral cortex after severe hypoglycaemia (which also may be true in other states of reduced metabolic support). These findings suggest a possibility to use uridine in the treatment of Alzheimer's disease and Status epilepticus.
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PMID:Intravenous uridine treatment antagonizes hypoglycaemia-induced reduction in brain somatostatin-like immunoreactivity. 352 Dec 3

This report concerns three patients in whom continuous intravenous infusion of Diazemuls (diazepam dissolved in soya bean oil and emulsified) diluted in 5.5% glucose was used for the controlling of epileptic seizures (status). Diazemuls infusion was effective in one patient with complex partial status epilepticus; in another patient with convulsion secondary to a brain stem infarct, the convulsions were abolished; while only reduced jerking was achieved in the third patient suffering from myoclonic jerks caused by anoxic brain damage. Infusion time ranged from 15 to 33 h. The serum concentrations of diazepam obtained during the infusions were higher than recommended in the literature for treatment of status epilepticus, but could not be correlated to either clinical efficacy or infusion rate.
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PMID:Intravenous infusion of Diazemuls in the control of status-like epileptic seizures of different etiology. 363 May 96


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