ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05853.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:Subclinical generalized spike‐wave discharges are often accompanied by transitory cognitive impairment, demonstrable by psychological testing during EEG recording. Transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike‐wave bursts lasting for more than 3 s, but can also be found during briefer and even focal discharges. That this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity: left‐sided focal spiking is more likely to produce errors on verbal tasks, for instance, whereas right‐sided discharges are more often accompanied by impairment in handling nonverbal material. Both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges. However, there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities. The significance of transitory cognitive impairment accompanying subclinical EEG discharges for everyday functioning is uncertain, but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists. In some individuals, suppression of discharges by antiepileptic drugs has demonstrably improved psychological function, but further work is required to determine the indications for such t

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05864.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:From the earliest days of neurology, the classification of epileptic seizures into those generalized from the beginning and those with a definable localization in the cortex from the onset has added to knowledge about the function of the nervous system. Further elaboration of the classification of seizures into those localized to the six‐layered isocortex and those whose elaboration involves regions of the brain involved with consciousness and memory has provided the basic focus for the burgeoning subspecialty of epilepsy surgery. It is increasingly apparent that the etiology of a seizure disorder is of at least equal or of greater significance than the nature of the seizures it spawns and is the product not only of localization in the nervous system but also of causative factors with implications reaching into areas of genetics, higher cortical function, and intelligence. The prognosis concerning the outcome of the epilepsy under consideration is based on all of these facets. This pathophysiological substratum, of which the seizure is only the presenting symptom, constitutes the epilepsy or epileptic syndrome on which the formulation of a rational treatment plan is base

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05856.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05840.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10–20 Hz; duration of stimulus, 0.5‐1 ms; and stimulus strength, 0.2‐0.5 mA/mm2of nerve cross‐section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GAB A and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and e

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05852.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:Cognitive impairment is regarded as the link between epileptic conditions and the inability to learn in school. The neuropsychological approach to learning disabilities in epilepsy, therefore, first concentrates on analyzing the differential effects of epileptic factors on cognitive function. The impact of seizure activity, localization of epileptogenic foci, and antiepileptic treatment on cognitive functioning can be evaluated based upon the results of continuous assessment with a computerized neuropsychological test system. Second, learning disabilities may be evaluated on observations made during classroom performance. Three issues seem to predominate in learning studies among disabled children with epilepsy: test‐retest variability, deterioration, and the supposed specificity of the learning disabilitie

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05874.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05837.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:Genetic mapping provides a means of understanding the molecular basis of inherited diseases whose biochemistry is unknown. Adequate pedigrees, informative genetic markers, and accurate identification of the disease phenotype are necessary. For dominant inheritance, mapping studies can be done in a single large pedigree; the larger the number of affected individuals sampled, the better the estimate of recombination between the gene causing the disease and one or more nearby genetic markers. For recessive inheritance, nuclear families with more than one affected sibling provide the best information. The development of many polymorphic DNA markers on the human genome has contributed to the success of mapping unknown genes because, as the genome is now densely covered with markers, the probability is good that at least one marker will be linked to the disease locus in a family that is segregating a disease allele. Most genetic markers now in use depend upon restriction fragment length polymorphisms (RFLPs), which are either the result of single‐base‐pair substitution or the presence of a variable number of tandemly repeated oligonucleotide units at a locus (VNTRs). RFLPs can be recognized by digesting DNA with restriction enzymes and separating the fragments by size on an electrophoretic gel. VNTRs can vary widely among individuals, and they provide more linkage information than single‐site polymorphic markers because family members are more likely to be heterozygous. Genetic maps of each chromosome, constructed from linkage data relating marker loci to one another in normal reference families, permit rational choices of markers for disease‐mapping studies. After initial localization of a disease gene to a specific chromosomal region by linkage analysis, one can take advantage of cytogenetic or molecular rearrangements in affected individuals, and test candidate genes known to be in the region, to identify the gene. Genetic heterogeneity–more than one gene causing the same clinical phenotype–and the existence of nongenetic phenotypes within the families being tested can obscure linkage findings, but despite its limitations, gene mapping remains a powerful method of obtaining information about inherited forms

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05854.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05838.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Summary:This study investigated the relationship between lipid peroxidation, subsequent activation of antiox‐idative enzymes, and development of iron‐induced epilepsy in the rat. Epileptic foci were produced in rat cerebral cortex by intracortical injection of ferric chloride (FeCl3). The epileptic foci were identified by electrocor‐ticography (ECoG). Epileptiform ECoG activity was shown to occur in the contralateral homotopic cerebral cortex as well. We measured levels of lipid peroxides and changes in the activities of the enzymes: superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), catalase (CA), and glucoses‐phosphate dehydrogenase (G6P) in the epileptogenic focus (both ipsilateral and contralateral) at days 3, 8, 15, and 23 after FeCI3injection. Biochemical estimations were made in subcellular fractions, and changes in the ipsilateral site were compared with those in the contralateral site. The results of this study showed that large increases in lipid peroxidation were associated with development and buildup of the ECoG epileptiform discharges. Lipid peroxides increased in the ipsilateral focus by –100% as compared with control. In the contralateral site, however, the increase in lipid peroxides was marginal only. The increase in lipid peroxidation was concomitant with development of the high level of epileptiform activity. The time course of changes in lipid peroxidation paralleled the time course of development and persistence of the epileptiform activity. Regarding changes in the enzyme activities accompanying development of iron epilepsy, the data showed that although SOD and G6P increased by ˜60% and GR increased by ˜40%, the increases in the enzyme GP and CA were much lower,<20%. Thus, comparatively less increase in CA and GP activities produces a deficiency of these two enzymes in the iron (ipsilateral) focus. Among the various biochemical disturbances that have been identified as involved in epileptogenesis, peroxidative injury resulting from lipid peroxidation in neural plasma membrane may be causally related to development of paroxysmal epileptiform activity in the iron focus. Since GP is an enzyme of major importance in detoxification of lipid peroxides in the brain, based on the results presented in this article, it appears reasonable to suggest that GP deficiency causes lipid peroxidation to increase tremendously during iron epileptogenesis.RÉSUMÉLes mécanismes d'action des anttépileptiques efficaces pour le traitement des crises généralisées de type absences (antiabsences) restent méconnus. Les anti‐absences sont généralement efficaces pour les crises expérimentales induites par les pentylènetétrazol (PTZ) et le méthyl‐6,7‐diméthoxyl‐4‐éthyl‐β‐carboline‐3‐carboxylate (DMCM), médicaments qui réduisent l'inhibition GABAergique. On a done suggéré que les anti‐absences pouvaient augmenter l'inhibition GABAergique. Les auteurs ont étudié les effets de plusieurs antiépileptiques sur les réponses GABA enregistrées au niveau de neurones médullaires poussant sur une culture cellulaire primaire dissociée. 4 anti‐absences ont été Studies: l'gthosuximide (ESM), la diméthadione (DMD), le valproate (VPA) et de diazépam (DZP). Deux antiéileptiques expérimentaux, le CGS 9896 et le ZK 91296, dont l'activité anticonvulsivante sur les crises induites par PZT et DMCM a été prouvée, ont aussi étéétudiés. Les auteurs ont évalué aussi les effets des anti‐absences et des drogues exéri‐mentales sur l'inhibition de la réponse GABA induite par PTZ et par DMCM. PTZ et DMCM nt entraîné une réduction réversible et dose‐dépendante des réponses GABA. Le PTZ a inhibe to‐talement les reponses GABA à 10 mM(IC50de 1.1 mM) alors que l'inhibition par la DMCM atteint une valeur plateau de 39%à 1 μ.M (IC50de 33 mM). L'ESM (1200 μM), la DMD (6 mM), le VPA (200 μ. M), le CGS 9896 (2 μ.M) et le ZK 912% (2 μM) n'ont pas modifie les reponses GABA. Le DZP augmente les réponses GABA de façon concentration‐dépendante. L'inhibition des réponses GABA produite par le PTZ à 1 mMn'a pas été modifyée par l'ESM (600 μ.M), la DMD (6 mM), le CGS 9896 (1 μM)ou le ZK 912% (1 μ.M). L'application simultanée de VPA (200 μ.M)et de PTZ (1 mM) a légèrement augmenté l'effet du PTZ. Le DZP (<10 nM), en revanche, a négativé l'induction des réponses GABA entraînée par le PTZ. L'inhibition des réponses GABA entraînée par le DMCM (250 nM) n'a pas été modifyée par l'ESM (600 μ.M), la DMD (2 mM) ou le VPA (200 μM). Cependant, le CGS 98% (2 μ,M) et le ZK 91296 (2 μM)ont antagonisé l'effet du DMCM. Le DZP (<10 nM) a significativement inversé l'inhibition des réponses GABA entraînée par le DMCM. L'absence d'effets du VPA, de l'ESM et de la DMD sur les réponses GABA post‐synaptiques suggère qu'une augmentation directe de l'activité GABA post‐synaptique n'est pas un mécanisme d'action commun des médications anti‐absences. Le DZP, le CGS 98% et le ZK 91296 ont tous annuié l'effet inhibiteur des réponses GABA du DMCM, mais pas celui du PTZ, ce qui suggère que ces antiépileptiques ont inhibe les crises en agissant au niveau des récepteurs aux benzodiazépines. Cependant, comme seul le DZP augmente les réponses GABA, le mécanisme d'action du CGS 98% et du ZK 912% dans l'inhibition des crises au PTZ n'appa‐raît clairement.RESUMENEn este estudio se ha investigado, en la rata, la relaciioAn entre la peroxidación lipídica, la subsiguiente activación de las enzimás anti‐oxidativas y el desarrollo de epilepsyía inducida por el hierro. Los focos epilépticos se produjeron en la corteza cerebral de la rata mediante la inyección intracortical de cloruro férrico (C13 Fe). Los focos epilépticos se identificaron mediante electrocorticografía (ECoG). La actividad epileptiforme en la ECoG se observó tambien en la corteza cerebral contralateral homo‐tópica. En los focos epileptogénicos (homolateral y contralateral) nemos medido, en los dias 3, 8, 15, y 23 después de la inyección de C13 Fe, los niveles de las lipido‐peroxidasas y los cambios en la actividad de las enzimás siguientes: superóxido dismutasa, glutatión‐peroxidasa, glutatión‐reductasa, catalasa y glucosa‐6‐fosfatasa dehidrogenasa. Las estimaciones bioquími‐cas se determinaron en fracciones subcelulares y los cambios en las zonas homolaterales se compararon con las contralaterales. Los resultados de este estudio muestran que los amplios incre‐mentos en la peroxidación de los lípidos se asociaron a un desarrollo e incremento de las descargas epileptiformes en el ECoG. La peroxidación de los lipidos se incremento en el foco homolateral en un 100% comparándola con el control. En la zona contralateral, sin embargo, se observó solamente un incremento marginal de esta peroxidación. El incremento de la peroxidación file congruente con el desarrollo de un alto nivel de actividad epileptiforme. El curso temporal de la peroxidación de los lípidos siguió un proceso paralelo al curso temporal del desarrollo y persistencia de la actividad epileptiforme. En relación con los cambios de las actividades enzimáticas que acompañan al desarrollo de la epilepsia inducida por el hierro, esta información muestra que, a pesar de que la superóxido‐dismutasa y la glu‐cosa‐6‐fosfato dehidrogenasa se incrementaron en un 60% y la glutatidn‐ieductasa en un 40%, los incrementos de las enzimás glutatión‐peroxidasa y catalasa fueron mucho menores, menos del 20%. Asf pues, son necesarios incrementos comparativa‐mente menos importantes de las actividades de catalasa y gluta‐tión‐peroxidasa para producir un déficit de estas dos enzimás en los focos homolaterales producidos por el hierro. Entre las diversas alteraciones bioquímicas que se han identificado como participantes en la epileptogénesis, la lesión peroxidativa que resulta de la peroxidación de los Upidos en la membrana plasmátics de las neuronas puede estar relacionada causalmente al desarrollo de actividad epileptiforme paroxfstica en el foco pro‐ducido por eidación de los Upidos en la epileptogénesis producia por el hierro.ZUSAMMENFASSUNGIn dieser Arbeit wurde die Beziehung zwischen Lipidperoxi‐dation, damit verbundener Aktivierung von antioxydativen En‐zymen und die Entwicklung von Eisen induzierter Epilepsie bei der Ratte untersucht. Die epileptischen Foci wurden durch in‐tracorticale Injektion von Eisenchlorid (FeCB) im Rattencortex erzeugt. Sie wurden durch Elektrocorticographie (ECOG) iden‐tifiziert. Im kontralateralen homotopen cerebralen Cortex wurde ebenso das Auftreten von epileptiformer ECOG Aktivität ge‐funden. Wir bestimmten die Lipidperoxydase‐Spiegel und Veränderungen in den Enzymaktivitäten von Superoxyd‐Dismutase, Glutathion‐Peroxydase, Glutathion‐Reduktase, Katalase und Glukose‐6‐Phosphat‐Dehydrogenase im epilepto‐genen Fokus sowohl ipsi‐ als auch kontralateral an den Tagen 3, 8, 15 und 23 nach der FeCe3‐Injektion. In den subzellulären Fraktionen wurden biochemische Schätzungen gemacht und Verändeningen im ipsilateralen Cortex wurden mit denen der kontralateralen Seite verglichen. Die Ergebnisse dieser Untersu‐chungen zeigen, daß große Steigerungen der Lipidperoxydation mit der Entwicklung von cortikalen epileptiformen Entladungen im EEG assoziiert sind. Lipidperoxyde stiegen im ipsilateralen Fokus um 100% im Vergleich zu Kontrollen an. Auf der kontralateralen Seite war dagegen nur ein marginaler Zuwachs an Lipidperoxyden festzustellen. Der Anstieg der Lipidperoxydation ging mit der Entwicklung von starker epileptiformer Aktivitat einher. Der Zeitverlauf in den Änderungen der Lipidperoxydation verlief parallel zum Zeitverlauf der Entwicklung und dem Fortbestehen von epileptiformer Aktivität. In Bezug auf Veränderungen der Enzymaktivitäten, die die Entwicklung der Eisenepilepsie begleitétén, zeigen die Daten, daß bei einem Anstieg von SuperoxydDismutase und Glukose‐6‐Phosphat‐Dehydrogenase um 60% und von Glutathion Reduktase um 40% der Anstieg von Glutathion‐Peroxydase und Katalase geringer, weniger als 20%, war. Das heifit ein verhältnismäßig geringer Anstieg von Katalase und Glutathion Peroxydase Aktivität führte zu einem Mangel der beiden Enzyme beim ipsilateralen Eisenfokus. Unter den verschiedenen biochemischen Störungen, die bei der Epileptogenese involviert sind, dürfte eine peroxydative Stöning der Lipidperoxydation in der neuronalen Plas‐mamembran ursächlich zur Entwicklung von epileptiformer Aktivitat im Eisenfokus in Beziehung stehen. Da Glutathion‐Peroxydase ein wichtiges Enzym in der Entgiftung von Lipidperoxyden im Gehirn ist, scheint aufgrund der in dieser Arbeit geschilderten Resultate die Schlußfolgerung gerechtfer‐tigt, daß ein Glutathion‐Peroxydase‐Mangel zu einer starken E

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1990.tb05354.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY