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)

Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct pharmacokinetic profile. In contrast to the oxidative metabolism of carbamazepine, oxcarbazepine is rapidly reduced to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. With the possible exception of the P450IIIA isozyme of the cytochrome P450 family, neither oxcarbazepine nor its monohydroxy derivative induce hepatic oxidative metabolism. Direct comparison of oxcarbazepine and carbamazepine has shown no difference in efficacy between these 2 agents in terms of reducing seizure frequency in patients with partial epilepsy with or without secondary generalisation, or with tonic-clonic seizures. Substitution of oxcarbazepine for carbamazepine in multiple antiepileptic drug regimens improved seizure control in some patients with refractory epilepsy; however, the rise in serum concentrations of concurrent antiepileptic agents secondary to elimination of carbamazepine-associated hepatic enzyme induction may have also played a role. Substitution of oxcarbazepine for carbamazepine was associated with improved cognition and alertness in some patients with epilepsy. Limited data indicate that oxcarbazepine may be a useful alternative to carbamazepine in the management of trigeminal neuralgia. Experience in patients with acute mania is promising, but the value of oxcarbazepine in managing affective disorders, particularly as a prophylactic agent, is not established. Oxcarbazepine may be better tolerated than carbamazepine; however, the current published database is small and the potential for oxcarbazepine to induce the type of serious idiosyncratic reactions occasionally associated with carbamazepine is unknown. Hyponatraemia has been reported in patients treated with oxcarbazepine. Although apparently asymptomatic, fluid restriction may be deemed necessary in some patients to reduce the risk of precipitating seizures secondary to low serum sodium. Thus, oxcarbazepine appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant drug interactions. Wider clinical experience should help clarify the long term efficacy and tolerability of oxcarbazepine. Pharmacokinetic advantages over current antiepileptic drugs, carbamazepine in particular, may then favour oxcarbazepine for consideration as a first-line agent in the management of partial and tonic-clonic epilepsy.
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PMID:Oxcarbazepine. A review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders. 137 59

Antiepileptic drug discovery has made enormous progress from the serendipity and screening processes of earlier days to the rational drug development of today. The modern era of research began with the recognition that enhancement of inhibitory processes in the brain might favorably influence the propensity for seizures, gamma-aminobutyric acid (GABA) being the main inhibitory transmitter. Work in this field led to the development of vigabatrin, which inhibits the enzyme responsible for the degradation of GABA. More recently, research has focused on the therapeutic potential of blocking excitatory amino acids--in particular glutamate. Of the three receptors for glutamate, the N-methyl-D-aspartate (NMDA) receptor is considered the one of most interest in epilepsy, and research on a series of competitive NMDA receptor antagonists--especially those that are orally active--is in the forefront of antiepileptic drug development today. A further alternative for diminishing neuronal excitability is to modulate sodium, potassium, or calcium channels. The latter are especially implicated in absence seizures.
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PMID:New antiepileptic drugs: from serendipity to rational discovery. 137 32

pH regulatory mechanisms in primary cultures of astrocytes from the cerebral cortex of neonatal audiogenic-seizure-susceptible DBA/2J (DBA) and genetically controlled C57BL/6J (C57) mice were studied with [14C]dimethyloxazolidine-2-4-dione (DMO) and [3H]-methyl-D-glucose (MDG). Effects of changing the concentration of Na+, K+, HCO3- or Cl- in medium, and/or of different transport blockers and metabolite inhibitor on intracellular pH (pHi) of cultured astrocytes were also studied. In nominal HCO3(-)-free HEPES-buffered Hanks' balanced salt solution (HEPES HBSS), when the pH of medium (pHo) was maintained at 7.4, the steady-state pHi of cultured astrocytes from DBA mice was 6.98 +/- 0.03, and that from C57 mice was 7.01 +/- 0.03. When the cells were incubated in HBSS containing 25 mM HCO3- and equilibrated with 5% CO2 (HCO3- HBSS, pHo = 7.4), pHi of both DBA and C57 astrocytes was approximately 0.1-0.15 pH units higher than that in HEPES HBSS. Reducing the pH or the Na+ concentration in media (pHo, [Na+]o) of either HEPES HBSS or HCO3- HBSS, pHi of both DBA and C57 astrocytes decreased markedly (0.25-0.45 pH units lower than the controls). The decrease in pHi was greater in HEPES HBSS than in HCO3- HBSS. Reducing the Cl- concentration ([Cl-]o) in either HEPES or HCO3- HBSS, pHi of astrocytes increased by 0.05-0.1 pH units. Increasing the K+ concentration ([K+]o) of or adding Ba2+ to the media increased the pHi of both DBA and C57 astrocytes accordingly. SITS, an anion transport inhibitor, decreased the pHi of both DBA and C57 astrocytes in HCO3- HBSS but not in HEPES HBSS. It enhanced the response of pHi to reduction in pHo. Amiloride, a Na(+)-H+ exchange inhibitor, decreased the pHi of both DBA and C57 astrocytes more in HEPES HBSS than in HCO3- HBSS. It enhanced the response of pHi to reduction in pHo and [Na+]o. Ouabain, an Na+,K(+)-ATPase inhibitor, decreased the pHi of cultured astrocytes in HEPES HBSS, but not in HCO3- HBSS. It also enhanced the response of pHi to changing pHo and [Na+]o in HEPES HBSS. Acetazolamide, a carbonic anhydrase inhibitor, decreased the pHi of astrocytes in both HEPES and HCO3- HBSS. Both bumetanide, an Na+,K+/Cl- cotransport blocker, and KCN, a metabolic inhibitor, produced no significant effect on the steady-state pHi or the response of pHi to changing ionic concentration in media in both DBA and C57 astrocytes.
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PMID:Studies on pH regulatory mechanisms in cultured astrocytes of DBA and C57 mice. 139 16

Neuropsychological evaluation contributes towards identification of a seizure focus through assessment of function. Tests sample widely among cognitive abilities, usually contrasting language and visuospatial competence. In patients with a temporal-lobe focus, evaluation of memory is crucial and ideally should comprise a variety of tasks tapping different aspects of learning and memory. As a means of predicting and preventing severe postoperative memory impairment, memory is further tested in many cases with the intracarotid sodium amytal (IAP) procedure; hippocampus will be spared in patients who fail IAP memory tests. Performance after temporal lobectomy on three basic memory tests was evaluated in patients who had failed pre-operative IAP memory tests compared to those who had passed. Those who had failed performed significantly worse, confirming fragility of memory function in cases who have been identified as at risk by the IAP procedure.
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PMID:Neuropsychological techniques in the identification of epileptic foci. 141 65

A pedigree of benign familial neonatal convulsions (BFNC) was reported. Seven members of two generations experienced convulsions in the neonatal period and/or in early infancy. All of these members except one had a good prognosis. One member who had infantile spasms was uneventfully delivered at 37 weeks of gestation, with a birth weight of 2,562 g and, without trouble during pregnancy. At the age of 20 days, she began to have adversive seizures. Later, she developed complex partial seizures and infantile spasms at 1 month and 10 days of age. Interictal EEG showed hypsarrhythmia. Biochemical investigations and MRI of the head revealed no abnormality. Treatment with sodium valproate and carbamazepine succeeded in stopping the seizures and she had no seizures after 3 months. But her psychomotor development was moderately delayed at 8 months. No case with severe epilepsy such as infantile spasms has been reported in the previous literature on BFNC. From our experience, early treatment and careful follow-up are considered to be important for BFNC.
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PMID:[Benign familial neonatal convulsions in a family with one member with infantile spasms]. 141 73

This report is a retrospective review of the perioperative management of 56 children who underwent craniofacial surgical procedures. The use of a combination of 5% dextrose in normal saline or 5% dextrose in Ringer's lactate and normal saline resulted in postoperative sodium values in a normal range. In patients receiving a combination of 5% dextrose and electrolyte No. 48 and normal saline, the mean postoperative sodium level was 130 mEq/l with 9 of 18 patients below 130 mEq/l. Two patients in the series suffered clinical seizures on postoperative day 1 as a result of serum sodium levels of 122 and 121 mEq/l, respectively. We recommend that only solutions with a sodium content between 77 and 154 mEq/l be used routinely in the perioperative management of craniofacial patients.
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PMID:Fluid, blood, and blood product management in the craniofacial patient. 141 42

Sixty-seven patients who underwent resection of the amygdala and temporal neocortex for intractable temporal lobe epilepsy were analyzed. Forty-four of them failed memory tests during the intracarotid sodium amytal procedure or showed severe impairment of contralateral material specific memory. Surgical outcome ratings were seizure-free or rare seizure, 51%; worthwhile improvement, 15%; failure, 34%. The least successful outcome was noted in the group with mandatory corticoamygdalectomy and seizure origin in the dominant hemisphere. There was no postoperative exacerbation of memory deficit, whether preoperative memory was normal or impaired. When hippocampal resection is inadvisable, corticoamygdalectomy may be considered.
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PMID:Corticoamygdalectomy in memory-impaired patients. 143 34

The intracarotid amobarbital procedure (IAP) is frequently used to determine hemispheric language dominance and memory competence in individuals with intractable epilepsy before surgical intervention. The present study focused on outcome results concerning use of this technique in children. The IAP was an effective tool in determining their hemispheric language dominance. Seven characteristics, including age, gender, dose level of sodium amobarbital, Full-Scale I.Q., hemispheric side of injection (left or right), language dominance of hemisphere injected, and order of injection (first or second) were examined as possible factors predictive of memory performance on the IAP. Results suggest that after injection of the hemisphere suspected of containing the primary seizure origin, children aged < 13 years who had the left language-dominant hemisphere injected were significantly less likely to pass IAP memory tasks than were older children or younger children who had the nondominant hemisphere injected. These findings suggest that the IAP is a reliable indicator of hemispheric memory competence in children aged > 13 years or younger children whose suspected seizure focus is located in the nondominant language hemisphere.
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PMID:Factors in children that predict performance on the intracarotid amobarbital procedure. 146 60

Eighteen women and five men had typical absences. These included 10% of a consecutive hospital series of 200 adult patients with epileptic disorders. The absences began between the ages of seven and 46 years and varied in type and severity. Twenty patients also had generalised tonic-clonic seizures, ranging in frequency from one in a lifetime to one per month. Myoclonic jerks of the limbs occurred in 11 patients but were not associated with the absence attacks. Eyelid myoclonus consistently occurred with absence attacks in four patients and perioral myoclonus in two patients. Absence status occurred in five patients. Absence seizures were frequently unrecognised or misdiagnosed as complex partial seizures. Satisfactory control was achieved with sodium valproate. Electroencephalography, particularly video-electroencephalography, was invaluable in the diagnosis, but focal abnormalities in seven patients might have been erroneously interpreted as indicating partial seizures. This series showed that clinical and EEG manifestations are often syndrome-related and that there are more epileptic syndromes with typical absences than those presently recognised.
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PMID:Typical absence seizures in adults: clinical, EEG, video-EEG findings and diagnostic/syndromic considerations. 146 93

Information from standardised tests of intelligence, school attainments, attention, memory and visuomotor function, together with parent and teacher questionnaire information about various aspects of behaviour, was obtained for 63 schoolchildren with newly diagnosed epilepsy before treatment with sodium valproate or carbamazepine, and again at intervals for a total period of 12 months. The same information was collected on 47 matched controls. The children with epilepsy represented those under non-specialised paediatric care. The result showed that both drugs were effective in most cases at modest dosage without causing notable psychological effects 12 months into treatment. Modest and temporary adverse cognitive effects seen earlier in treatment could have been the result of uncontrolled seizure discharge. Improved function was the same in children with epilepsy and controls. Some psychological abnormalities in the children with epilepsy were evident before treatment suggesting early unwanted effects of the epileptic process itself.
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PMID:Psychological effects of sodium valproate and carbamazepine in epilepsy. 147 83


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