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)

We studied the pharmacological mechanism of zonisamide (ZNS) using an electrophysiological and autoradiographical method in a limbic seizure model in rats. Limbic seizure status epilepticus was induced by a unilateral microinjection of kainic acid (KA) into the amygdala. Initially, observed seizures were limited to the side of the injected amygdala and then propagated to bilateral sensorimotor cortex. Eighty minutes after injection, secondarily generalized seizure status epilepticus was induced, with each seizure lasting approximately 30 s and recurring every 5 min. ZNS 100 mg/kg was administered intravenously (i.v.) during the generalized seizure. Forty minutes after ZNS administration, epileptic activity was observed only at the KA-injected amygdalar site and spikes were not observed in the bilateral sensorimotor cortex. We studied local cerebral glucose utilization (LCGU) after ZNS or saline administration using an autoradiographical method in the same limbic seizure preparation. In the ZNS group, LCGU decreased in the ipsilateral sensorimotor cortex and hippocampus, whereas in the controls LCGU increased in these structures. On the other hand, ZNS did not suppress the epileptic activity of the primary focus and no decrease in LCGU was observed in the KA-injected amygdala. ZNS inhibited seizure propagation from the epileptogenic focus but did not suppress the epileptic activity of the focus. Our results suggest that ZNS is effective for the treatment of secondarily generalized seizure.
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PMID:Zonisamide: electrophysiological and metabolic changes in kainic acid-induced limbic seizures in rats. 755 79

Pilocarpine administration to lithium chloride-pretreated rats results initially in discrete convulsive seizures, each behaviorally and electroencephalographically terminated, which then progress to convulsive activity with waxing-and-waning behavioral and electrographic severity; finally, a continuous convulsive state ensues, associated electrographically with continuous fast spiking. This stage does not last indefinitely but is followed by a dramatic electrographic change to periodic epileptiform discharges. The purpose of the present study was to determine with the 14C-2-deoxyglucose functional mapping technique what changes occur in the seizure anatomic substrate during and after this transition, in order to enable inferences about underlying mechanisms. Behavior associated with early and late continuous fast spiking consisted of head twitching; corresponding deoxyglucose autoradiographs displayed seizure-induced intense glucose utilization in most forebrain areas; extranigral brainstem was normal. At 2-3 h of status, fast spiking became interrupted by flat periods; periodic complexes soon dominated the electroencephalogram. Behaviorally, convulsive severity increased. Despite this dramatic electrographic evolution, little change in generalized forebrain metabolic hyperactivation occurred, except that the zona incerta/pretectal/superior colliculus complex displayed markedly increased activity. Deoxyglucose studies in late stages of periodic epileptiform discharges established a sequence of further changes. In late periodic discharges with clonic jerks, at 4 h after status entry, generalized forebrain hyperactivation still prevailed, but to a lesser degree than in early periodic discharges with clonic jerks. At a still later stage, late periodic discharges, subtle convulsive, autoradiographs revealed constriction of the seizure-activated anatomic substrate: hyperactivation was lost in most of neocortex and thalamus, and in caudal olfactory structures, cortical amygdala, and entorhinal areas, but retained in deep occipital cortex and many limbic areas. In the last stage, late periodic discharges, electrical, not associated with convulsive behavior, autoradiographs revealed residual activation in only Ammon's horn; in contrast, much of the forebrain displayed below-normal glucose utilization. These results demonstrate that in the later stages of status epilepticus, the transition from fast spiking to periodic complexes is not associated with a reduction in the seizure anatomic substrate. The electrographic entity of periodic epileptiform discharges is not anatomically or behaviorally homogeneous, but proceeds through successive stages characterized initially by a reduction of glucose utilization within generalized seizure-activated forebrain, then a contraction of the seizure anatomic substrate. Possible mechanisms underlying the transition to periodic complexes are discussed.
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PMID:Functional mapping of the late stages of status epilepticus in the lithium-pilocarpine model in rat: a 14C-2-deoxyglucose study. 775 76

We report the historical, clinical, and laboratory findings in 5 patients after crack cocaine ingestion. All patients exhibited adrenergic crisis as a result of their ingestion. Analysis of their history revealed a latency period before signs and symptoms occurred as well as a wide variation in the number of crack cocaine nuggets ingested. Signs of intoxication were hypertension, tachycardia, hyperthermia, agitation, and generalized seizure activity. Treatment included therapeutic sedation with lorazepam and adrenolysis with esmolol infusion. The majority of patients showed electrocardiographic evidence of cardiac ischemia, but not elevations in serum creatinine phosphokinase enzymes--MB fraction. One patient died of complications associated with subclinical status epilepticus. The toxicities of crack cocaine ingestion are seldom appreciated. Prompt reversal of both cardiovascular and neurological signs and symptoms with appropriate pharmacologic agents is indicated.
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PMID:Adrenergic crisis from crack cocaine ingestion: report of five cases. 759 78

Generalized seizures can induce both hypertension and hyperglycemia which may aggravate preexisting cerebral or medical conditions in patients. In vivo fluorescent imaging of regional cortical blood flow and brain intracellular pH (pHi) was performed in fasted New Zealand rabbits (n = 35) in which either mean arterial blood pressure (MABP) or serum glucose was the covaried factor during pentylenetetrazole induced status epilepticus under 1.5% inspired halothane. Baseline brain pHi and regional cortical blood flow were 7.02 +/- 0.02 and 51.1 +/- 1.7 ml/100 g/min, respectively. Following seizure induction, MABP increased to 105 mm Hg and brain pHi fell to 6.79 +/- 0.03 within 15 min and remained at this level for 1 h (P < 0.001). With normalization of MABP during ongoing seizures, there was no worsening in brain pHi despite a significant decrease in regional cortical blood flow. Hyperglycemia decreased pHi to 6.71 +/- 0.02 compared to 6.84 +/- 0.04 in normoglycemic animals (P < 0.001). Using pHi as a cerebral metabolic index, these data suggest that normalization of MABP does not increase metabolic injury while hyperglycemia does significantly worsen brain acidosis. Therefore, administration of glucose to patients with status epilepticus should be avoided unless there is documented hypoglycemia.
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PMID:Effect of arterial blood pressure and serum glucose on brain intracellular pH, cerebral and cortical blood flow during status epilepticus in the white New Zealand rabbit. 845 50

The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.
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PMID:Expression of c-fos protein in the experimental epilepsy induced by pilocarpine. 851 14

The clinical course of a 9-year-old diagnosed with attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's disorder and treated with a combination of methylphenidate, clonidine, and fluoxetine is described. The patient experienced over a 10-month period, signs and symptoms suggestive of metabolic toxicity marked by bouts of gastrointestinal distress, low-grade fever, incoordination, and disorientation. Generalized seizures were observed, and the patient lapsed into status epilepticus followed by cardiac arrest and subsequently expired. At autopsy, blood, brain, and other tissue concentrations of fluoxetine and norfluoxetine were several-fold higher than expected based on literature reports for overdose situations. The medical examiner's report indicated death caused by fluoxetine toxicity. As the child's adoptive parents controlled medication access, they were investigated by social welfare agencies. Further genetic testing of autopsy tissue revealed the presence of a gene defect at the cytochrome P450 CYP2D locus, which results in poor metabolism of fluoxetine. As a result of this and other evidence, the investigation of the adoptive parents was terminated. This is the first report of a fluoxetine-related death in a child with a confirmed genetic polymorphism of the CYP2D6 gene that results in impaired drug metabolism. Issues relevant to child and adolescent psychopharmacology arising from this case are discussed.
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PMID:Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency. 1075 79

Brainstem auditory evoked potentials (BAEPs) were recorded from a patient simultaneously experiencing non-convulsive generalized status epilepticus (NGSE). Waves I, III and V were normal but all subsequent waves were absent. This finding indicates that structures within the brainstem adjacent to the generators for the BAEP are likely not affected by NGSE and also illustrates the resilient nature of the BAEP. This is the first report of the recording of an evoked potential during a naturally occurring generalized seizure.
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PMID:Preservation of the brainstem auditory evoked potential in non-convulsive status epilepticus. 1088 Aug 10

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.
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PMID:Enhanced excitability induced by ionizing radiation in the kindled rat. 1131 62

A 5-year-old boy with a peculiar type of post-encephalitic/encephalopathic epilepsy is reported. He had been healthy showing normal development before its onset. Five days after the onset of an upper respiratory infection, he had a severe generalized seizure, that evolved into intractable seizures. They were highly resistant to almost all anticonvulsants and occasionally resulted in status epilepticus. High-dose phenobarbital therapy successfully controlled the convulsions, but was discontinued because of drug-induced aplastic anemia. Alternative bromide therapy was markedly effective in controlling the seizures.
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PMID:[A case of peculiar type of post-encephalitic/encephalopathic epilepsy: efficacy of bromide in the control of intractable seizures]. 1149 80

CAROLE is a prospective survey of 1942 children and adults presenting at least one unprovoked epileptic seizure first diagnosed between May 1 1995 and June 30 1996 by 243 French neurologists and neuropediatricians. In half these cases, the patient had already experienced more than one seizure at the time of diagnosis. Patients presenting only one seizure but either a case history or significant EEG or neuroimaging abnormalities suggestive of a high risk of recurrence were classified as cases of epilepsy. Drug treatment was prescribed to 73 p. 100 of the cohort. Treatment was far more frequent in cases where seizure had recurred (90 p. 100) than in cases of first seizure (54 p. 100) (p < 0.0001). In the latter category, the older the patients, the more likely they were to be treated (69 p. 100 of patients > or = 60 years old versus 49 p. 100 of those under 24 years of age, p = 0.001). Those with multiple onset were more often treated than those with single onset (48 p. 100 of cases of single seizure versus 80 p. 100 of clustered seizures and 90 p. 100 of status epilepticus, p < 0.0001), as were cases of complex partial seizure (68 p. 100 versus just under 50 p. 100 of cases of generalized seizure, p = 0.0001), those with epileptiform EEG abnormalities (67 p. 100 of cases of cryptogenic partial epilepsy and 63 p. 100 of idiopathic generalized epilepsy versus 42 p. 100 of isolated seizure, p < 0.0001) and those with cerebral lesions visible by neuroimagery (89 p. 100 of cases of symptomatic partial epilepsy). The decision not to treat was generally based on clinical signs of non-gravity. Understandably, cases of idiopathic partial epilepsy were less treated than other syndromes, 22 p. 100 in the group of first seizure patients, 67 p. 100 in the group where seizure had recurred before diagnosis. A single-drug therapy was recommended to 1389 of the 1411 patients treated, in 63 p. 100 of cases sodium valproate, in 30 p. 100 carbamazepine. These data reveal not only the attitude to treatment of the specialists concerned, but also the desires or refusals of patients or patients' parents. The present study was limited to this question of treatment or no treatment. A further study will be necessary to investigate to what extent patients followed the treatment prescribed and how these cases evolved.
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PMID:[Treatment of newly diagnosed epileptic crises. A French experience]. 1192 46


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