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)

CGP 37849 (1 mg/kg i.p.) enhanced the protective action of carbamazepine, diphenylhydantoin and phenobarbital against maximal electroshock-induced convulsions in mice. At 0.25 mg/kg CGP 37849 was inactive and at 0.5 mg/kg it potentiated the anticonvulsive activity of phenobarbital. CGP 39551 (5 mg/kg i.p.) reduced the ED50 values of diphenylhydantoin and phenobarbital, being without influence on carbamazepine. In the dose of 1.25 mg/kg, CGP 39551 potentiated the antielectroshock action of diphenylhydantoin and at 2.5 mg/kg that of phenobarbital. Neither NMDA receptor antagonist elevated the total plasma levels of antiepileptic drugs. Consequently, a pharmacokinetic interaction (in terms of total plasma levels at least) seems unlikely to be responsible for the observed potentiation of the antiepileptic drugs' activity. Combinations of CGP 37849 with either carbamazepine or phenobarbital resulted in a motor and memory impairment quantified by the chimney test and passive avoidance task, respectively. Moreover, combined treatment with phenobarbital and CGP 39551 caused a memory deficit. In contrast, diphenylhydantoin combined with either CGP 37849 or 39551 was devoid of adverse effects. It may be concluded that NMDA receptor blockade results in enhanced anticonvulsive action of common antiepileptics against maximal electroshock-induced seizures.
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PMID:Competitive NMDA receptor antagonists enhance the antielectroshock activity of various antiepileptics. 790 19

Several traumatic events including brain contusion, electroconvulsive shock therapy, epileptic seizures and others, may cause short-term retrograde amnesia. In spite of much recent attention, pharmacological treatment of memory impairment has not been fully successful. In the present paper we report on the possible antiamnesic action of the L-type calcium channel blocker, nifedipine. Rats trained in the spatial memory task showed gradual improvement in the escape latency to find the submerged platform. After completion of the learning, they also showed a strong spatial bias toward the place that previously contained the target platform. Prolonged post-trial electroconvulsive shock induced memory impairment. The calcium channel blocker, previously reported as a "cognitive enhancer," given either before or after the learning trial revealed no antiamnesic effect. Nifedipine also does not exert any action when given alone. These results suggest that the drug may not have antiamnesic action on human memory disturbed by electroconvulsive therapy.
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PMID:The effect of electroconvulsive shock and nifedipine on spatial learning and memory in rats. 805 9

Quisqualate (Quis) and other excitotoxins such as ibotenate and N-methyl aspartate, have been used to destroy neurons in the area of the nucleus basalis magnocellularis (NBM) in order to study the relationship between loss of cholinergic neurons in the basal forebrain and various behavioral deficits, including learning and memory impairments. The results of several studies suggest that although Quis NBM lesions may produce greater depletions in cortical choline acetyltransferase levels than ibotenate lesions, the learning/memory deficits tend to be milder following Quis lesions. In these studies, it was often assumed that the lesions induced by Quis were restricted to the local vicinity of the injection. However, in the present study, we found that an injection of Quis into the NBM/substantia inominata (SI) region often induces limbic seizures and disseminated brain damage. Specifically, we found that an injection of Quis into the NBM/SI area of female rats at a dose (120 nmol) used by others in previous behavioral studies produced massive damage in areas distant from the lesion site, particularly in the amygdala and piriform cortex. This disseminated damage occurred in 50% of the rats treated with Quis, was typically more severe than damage at the injection site, and was often accompanied by equally severe "mirror" lesions in the contralateral amygdala and piriform cortex. Injecting rats with MK-801 (1 mg/kg) 30 min before the Quis injection protected against the disseminated damage. These data underscore the need for careful histological evaluation of excitotoxic lesions and for caution in interpreting the relationship between altered transmitter markers and learning/memory impairment seen following these lesions.
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PMID:Quisqualate injection into the nucleus basalis magnocellularis produces seizure-related brain damage that is prevented by MK-801. 815 20

We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of the disease, several patients developed myoclonus and generalized epileptic seizures and eventually died with profound dementia. The "Torino family" shows several genealogic and clinical similarities with other large multigenerational familial Alzheimer's disease pedigrees originating from the Calabria region.
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PMID:A new Italian pedigree with early-onset Alzheimer's disease. 819 27

Early onset Familial Alzheimer's Disease (FAD) is an autosomal dominant disease with apparent complete penetrance. It is genetically heterogeneous with some families carrying mutations in the amyloid precursor protein (APP) gene which segregate with the disease. In addition, there is allelic heterogeneity with four mutations associated with FAD. Three mutations have been reported at APP 717, just distal to the C-terminus of the beta-amyloid domain, APP 717 val-ile, APP 717 val-phe, and APP 717 val-gly, which are associated with autopsy-proven Alzheimer's disease (AD). APP 670/671 lies at the N terminus of the beta-amyloid domain and is associated with clinically diagnosed FAD in two Swedish families. FAD tends to have prominent myoclonus and this is shared by the cases with APP mutations. In two unrelated UK families with APP 717 val-ile mutations there was early prominent memory impairment with dyscalculia proceeding to generalized cognitive impairment with a lack of insight. There was a late development of a gait disturbance with extrapyramidal features in some members. Positron emission tomography (PET) with fluorodeoxyglucose demonstrated posterior bitemporal biparietal hypometabolism in one case. Magnetic resonance imaging (MRI) showed generalized cerebral atrophy particularly affecting the temporal lobes and hippocampus. At autopsy, a single case showed extensive beta-amyloid deposition with congophilic angiopathy and widespread senile plaques and neurofibrillary tangles. The cytoskeletal pathology associated with abnormally phosphorylated tau was similar to cases of sporadic AD. In addition, there were widespread cortical and subcortical Lewy bodies. A single family with the APP 717 val-gly mutation also showed prominent myoclonus, lack of insight, and seizures, PET, in a single case, showed classical biparietal bitemporal hypometabolism. Autopsy, in a single case, showed diffuse deposits of beta-amyloid throughout the cortex with frequent neuritic plaques and neurofibrillary tangles. No other inclusion bodies were seen. There was severe congophilic angiopathy. The age at onset of APP mutations is around 50 years of age by contrast to other early onset FAD pedigrees.
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PMID:Alzheimer's disease families with amyloid precursor protein mutations. 823 83

Thirty-one patients with a mean age of 18.9 years (range 3 to 53 years) who underwent temporal lobe surgery for tumor-related epilepsy over a 14-year period are presented. All had suffered chronic drug-resistant temporal lobe seizures (mean age at onset 6.9 years, range 0 to 30 years; mean duration of condition 11.9 years, range 3 to 39 years). Preoperative interictal scalp electroencephalography tracings indicated unilateral localized epileptic foci in 90% of patients, and computerized tomography scans showed abnormalities within the temporal lobe in 87%. All patients underwent en bloc temporal lobectomy. No patient received adjuvant radiotherapy or chemotherapy. Review of the histological material showed dysembryoplastic neuroepithelial tumor in 27 (87%) of the specimens and microscopic evidence of incomplete removal of tumor in 22 (71%). At long-term follow-up evaluation (mean duration 5.8 years, range 1 to 14 years), 81% of patients were completely free of seizures (Engel grade I) and 10% were almost seizure free (Engel grade II) with no deaths reported in either early or late follow-up review. Only one patient in the series failed to benefit from the surgery. Four patients suffered permanent neurological deficit causing a mild disability. Psychological assessment showed no significant fall in verbal or performance intelligent quotient for the group, but a mild memory impairment was evident in 32%. Behavioral and social aspects improved in nearly all (94%) cases. Relief of seizures could not be predicted by intraoperative electrocorticography, and outcome was independent of the completeness of tumor resection. Postoperative electroencephalographic findings identified epileptiform potentials in 65% of patients, which were associated with a worse seizure-control outcome grade.
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PMID:Control of temporal lobe epilepsy following en bloc resection of low-grade tumors. 841 37

Sixty patients with intractable complex partial seizures underwent surgery between 1969 and 1990, and 58 of these underwent a temporal resection. Of 39 patients who had chronic subdural electrocorticography (ECoG) 37 subsequently underwent an anterior temporal lobectomy (ATL) and two had the electrodes removed without resection. Two patients had bilateral depth electrodes placed and then had an ATL. Fourteen patients with evidence of temporal structural lesions had temporal resections with intraoperative ECoG and five had resection without ECoG. Mean length of follow-up for all patients was 6 years. Fifty-five per cent of cases were seizure-free postoperatively, 7% almost seizure-free, 21% had worthwhile improvement and 17% no improvement. The outcome for patients with structural lesions was particularly good. Nine patients complained of mild memory impairment postoperatively and one had a severe amnestic problem. One patient with an unsuspected tumour developed a hemiparesis and dysphasia. One other patient had persistent dysphasia. No mortality was attributable to the surgery. It is concluded that ATL is an excellent operation for the treatment of intractable epilepsy arising from the temporal lobe and chronic subdural ECoG is a safe and reliable method for localizing the seizure origin.
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PMID:Temporal lobectomy for intractable epilepsy: experience with 58 cases over 21 years. 843 41

We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted.
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PMID:Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy. 847 48

Benzodiazepines have a wide variety of indications. However, CNS and psychiatric adverse reactions, tolerance, and withdrawal effects of benzodiazepines are becoming increasingly recognized and must be better understood for proper drug use. Certain benzodiazepines are associated with memory impairment and other cognitive defects and hyperexcitability phenomena during treatment (early-morning insomnia, daytime anxiety) and following withdrawal (rebound insomnia and anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal (HPA) axes, and the interaction of these factors appear to be major determinants of frequency and severity of these untoward effects. Rapid drug elimination and high receptor-binding affinity were initially suggested as primary underlying factors which determine frequency, severity, and type of the side effects of benzodiazepines during administration and withdrawal. Newer data and information on triazolobenzodiazepines indicate that these psychiatric adverse reactions also relate to whether the benzodiazepine has strong direct effects on the LC-NE and HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an interdose basis, by a significant rebound and activation. This repetitive pattern of suppression followed by rebound results in a neurophysiologic and behavioral sensitization (kindling) of the limbic system and consequently contributes to central nervous system and psychiatric adverse reactions. The tendency of certain of these side effects to worsen over time supports empirically this neurophysiologic and biochemical model.
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PMID:Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics. 857 15

Findings from studies involving both rat models of epilepsy and humans with temporal lobe epilepsy suggest that epileptic seizures may induce hippocampal neuronal damage. This damage appears to be progressive over time and has been shown to be associated with memory impairment. Vigabatrin has been shown to protect against hippocampal neuronal cell death in experimental models of epilepsy. Because of the protection it provides against neuronal loss and functional impairment, vigabatrin may be a useful component of antiepileptic polytherapy.
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PMID:Treatment with antiepileptic drugs: possible neuroprotective effects. 867 31


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