bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression and Generalization of Seizure Discharge: Anatomical and Neurochemical Substrates
Authors: Gale Karen
Published: November 2007

Summary: Seizure activity is generated and propagated by specific subcortical circuits. The substantia nigra (SN) and the area tempestas (AT) have been identified as two exemplary substrates for the control of experimental seizures. In animal models, GABAergic transmission has been shown to protect against seizures of different origins and methods of induction. Neuroactive peptides and excitatory amino acids may work with GABA in the SN to control the propagation of a wide variety of seizure types. In contrast, inhibition of AT pons selectively protects against seizures associated with limbic circuits. The AT is also a site from which bilaterally synchronous convulsions can be triggered in response to manipulations of cholinergic, GABAergic, and excitatory amino acid receptors. Definition of other pathways of seizure development and the effects of pharmacologic treatments on discrete brain regions await further research efforts.
Antiepileptic Drugs and Cerebral Glucose Metabolism
Authors: Theodore William H.
Published: November 2007

Summary: Using PET with [18‐F]‐2‐deoxyglucose (FDG), we studied the effects of antiepileptic drugs on cerebral glucose metabolism. Serial scans were performed before and after the test drug was added to or removed from the patient's regimen. At least 3 weeks elapsed after achieving steady‐state plasma levels when drugs were added, or after plasma levels were undetectable when drugs were tapered, before repeat scans were obtained. Only a single drug was changed between scans. In the phenobarbital (PB) study, the “on‐drug” scan was performed first in each case. In this instance, a mean of 14 weeks elapsed between the time blood levels were undetectable and repeat scanning in order to avoid the possibility of withdrawal effects. Scanning in each group was performed 30 min after injection of 5 mCi of FDG, with EEG monitoring to exclude ictal activity. Regional glucose metabolic rates were calculated in 8 to 20 regions of interest. PB reduced LCMRglu in seven of eight regions studied, with a mean reduction over all regions of 37 ± 3%. Phenytoin (PHT) reduced LCMRglu in only two of 10 regions (mean =13%). We studied the effect of PHT on cerebellar metabolism in 42 patients using unpaired scans. Cerebellar LCMRglu was lower when patients were taking PHT at the time of scan, as well as in those who were taking PHT for 5 years or more, but the differences were not significant. There was a weak inverse correlation between PHT serum level and cerebellar LCMRglu in patients taking the drug at the time of scan (r = ‐ 0.36; 0.05 < p < 0.1). Carbamazepine (CBZ) reduced LCMRglu in two of 20 regions studied, with a mean metabolic rate reduction of 10.7%. The mean change in LCMRglu in six controls was only 5.2%. Thus, PB has a dramatic effect on human cerebral glucose metabolism at blood levels within the “therapeutic range.” PHT and CBZ appear to cause mild reductions; the effect of these drugs is only slightly higher than the scan‐scan variability in patients whose drug is not changed. The reduction in LCMRglu attributable to PB may be related to the adverse cognitive effect of the drug.
Localization of Cortical Function: New Information from Extraoperative Monitoring of Patients with Epilepsy
Authors: Lüders Hans , Lesser Ronald P. , Dinner Dudley S. , Morris Harold H. , Wyllie Elaine , Godoy Jaime
Published: November 2007

Summary: Intraoperative cortical stimulation for evaluation of cortical function has been used extensively to define the extent of cortical excisions for surgical treatment of epilepsy. With chronic implantation of subdural electrodes, extraoperative cortical stimulation becomes possible, and these favorable testing conditions permit more precise mapping of the cortex. This assists the surgeon in planning details of the surgical removal and also provides additional data about the function of the human cortex. Four aspects in which detailed extraoperative studies have provided information complementing the pioneer studies of Foerster, Penfield, and others will be discussed here: (1) Frontal eye field: In the human, this is always an integral part of the motor strip (most probably located in Brodman's area 4 and/or 6) and elicits only conjugate eye movements to the contralateral side with a variable upward component. (2) Negative motor area: Stimulation of the inferior frontal gyrus immediately in front of the face area and of the supplementary motor area of the dominant and nondominant hemisphere produces “inhibition” of voluntary fine movements. (3) The movement related potentials (bereitschaftpotential, negative slope, and motor potential) are strictly localized to the portion of the sensorimotor strip where the movement is represented. Lower amplitude bereitschaftpotentials can also be detected in the homotopic ipsilateral sensorimotor cortex and in the supplementary motor cortex. (4) Three language areas can be distinguished by electrical stimulation: Broca's, Wernicke's, and the basal temporal language area. Electrical stimulation in all these areas produces a similar deficit, but Broca's area tends to overlap with the inferior frontal negative motor area. This may explain the predominant motor deficit of Broca's aphasia.
Alcohol, Seizures, and Epilepsy
Authors: Hauser W. Allen , Ng Stephen K. C. , Brust John C. M.
Published: November 2007

Summary: Seizures, epilepsy, and alcohol are complexly interrelated. Although it is commonly perceived that patients with epilepsy experience problems with seizure control if they use alcohol, this is not confirmed by the few experimental studies that have tested the hypothesis. The last 30 years have emphasized the role of withdrawal from alcohol as a mechanism of seizure production. However, this is but one of many potential mechanisms by which seizures and epilepsy may be related to alcohol use and abuse. The rare but clear situations in which alcohol can act as a convulsant drug need further study, and mechanisms by which the long‐term neurotoxic effects of alcohol lead to chronic epilepsy also need further elucidation.
Aspects of Antiepileptic Treatment in Children
Authors: Dodson W. Edwin
Published: November 2007

Summary: About 75% of patients with epilepsy have seizures during childhood, often requiring antiepileptic therapy. Children possess all the drug‐specific pharmacokinetic features of adults (e.g., nonlinearity of phenytoin elimination and autoin‐duction of carbamazepine metabolism), plus other factors (e.g., age, intercurrent illness, comedication) that influence dosage. Kinetic differences are maximal in newborns and infants, with limited drug elimination in premature and full‐term babies, soon followed by accelerated elimination during infancy and childhood, before lower adult elimination rates develop during late childhood or early adolescence. Most children with epilepsy require two‐ to fourfold larger doses relative to bodyweight than adults, to achieve comparable drug levels and therapeutic effects. Although rapid growth may require increased dosage, the need is limited as relative clearance declines with age. Children of any age, but particularly premature and newborn babies, show greater individual variability in drug handling and therefore in dose requirements than adults. Clinical response and antiepileptic drug concentrations should both be monitored carefully in children.
Problems of Combination Drug Therapy in Children
Authors: Bourgeois B. F. D.
Published: November 2007

Summary: Despite the current trend toward monotherapy, polytherapy in children with epilepsy is still common. A drug combination is advantageous only if it achieves a higher efficacy: toxicity ratio (therapeutic index) or if its antiepileptic spectrum is wider. Studies of brain concentrations of antiepileptic drugs have so far shown that a higher efficacy toxicity ratio is not achieved by most combinations. Problems are associated with drug combinations. First, numerous pharmacokinetic interactions are documented. These interactions, which can be associated with significant changes in blood levels at a given dose, make frequent measurements and dosage readjustments necessary. They can also alter the concentration of active metabolites or the free fraction of a drug. Second, toxicity can be assumed to be at least partially cumulative, since reduction in polytherapy has been shown to be associated with a reduction in side effects. Third, the therapeutic range appears to depend on whether a drug is taken alone or in combination, so that polytherapy confuses the interpretation of serum drug measurements. Fourth, the presence of more than one drug will add to the difficulty in evaluating the efficacy or side effects of any single drug. Finally, a pharmacodynamic interaction between valproate and several other antiepileptics, particularly the barbiturates, can lead to a stuporous state. Transition from polytherapy to monotherapy is much more difficult to achieve than the opposite.
Successful Treatment of Massive Carbamazepine Overdose
Authors: Sethna M. , Solomon G. , Cedarbaum J. , Kutt H.
Published: November 2007

Summary: Overdose of carbamazepine (CBZ) can be fatal. We report the case of a patient with near‐lethal toxicity due to delayed absorption of drug. A 36‐year‐old woman was admitted with coma, hypotension, and unusual movements. Carbamazepine (CBZ) level several hours later was 36 mg/L. Gastric lavage revealed no pill fragments, and activated charcoal was administered. CBZ level initially fell, reaching 28 mg/L 36 h after admission. Blood level then rose sharply, reaching 54 mg/L 64 h after admission. The pattern of rise suggested renewed absorption of drug. Vigorous cathartics were given, and further doses of charcoal were administered. Three hours after onset of diarrhea, roving eye movements occurred. Two hours later she grimaced to pain. Eight hours after the onset of diarrhea, she was awake. In CBZ overdose, activated charcoal therapy coupled with aggressive intestinal purging helps prevent continued absorption of drug, late exacerbation of symptoms, and potentially fatal outcome.

lintoxication par la carbamázepine (CBZ) peut être fatale. Les auteurs rapportent le cas une patiente ayant présenté une intoxication presque fatale en raison d'une absorption différée du médicament. Une femme de 36 ans a été admise dans un état de coma avec hypotension et mouvements anormaux. Le taux sanguins de CBZ obtenu quelques heures plus tard était de 36 mg/l. Le lavage gastrique ne permit pas de ramener de fragments de comprimés, et du charbon activé fut administré. Lex taux sanguins de CBZ commencèrent par chuter à 28 mg/l à la 36ème heure, puis montèrent brutalement à 54 mg/l à la 64ème heure. Le profil élévation des taux suggèrait existence lune nou‐velle absorption. Une purge vigoureuse fut administrée. 3 heures après début de la diarrhée, des mouvements pendulaires des yeux furent constatés; deux heures plus tard, réaction de grimace à la douleur. 8 heures après le début de la diarrhée, la patiente était réveillée. Dans intoxication par la CBZ, L'administration de charbon activé associées a une purge intestinale énergique prévient la poursuite de absorption du médicament, de l'exacerbation des symptômes, et le décès éVentuel.
Experience with the International League Against Epilepsy Proposals for Classification of Epileptic Seizures and the Epilepsies and Epileptic Syndromes in a Pediatric Outpatient Epilepsy Clinic
Authors: Eslava‐Cobos Jorge , Naririo Daniel
Published: November 2007

Summary: The International League Against Epilepsy proposals for classification of epileptic seizures (1981) and of the epilepsies and epileptic syndromes (1985) have been used in daily practice in a pediatric epilepsy clinic in Bogota, Colombia. Most patients can be classified by these schemes, and the classifications are useful in everyday diagnosis and management. However, there are some drawbacks and difficulties with the classifications. Some syndromes are unnecessarily separated as different entities, artificially contributing to the complexity of the Classification.

Les propositions de Classification des crises (1981) et des épilepsies et syndromes épileptiques (1985) de la Ligue Internationale Contre Epilepsie ont été utilisées en pratique quotidienne dans le cadre consultation épileptologie infantile à Bogota (Colombie). La majorité des patients peut être classée selon ces recommandations et les classifications sont utiles dans la pratique quotidienne du diagnostic et du traitement. Cependant, les auteurs ont constaté existence de carences et de difficultés. Certains syndromes sont tronçonnés de façon inutile en différentes entités, et ceci contribue artificiellement à rendre complexes ces classifications.
Ictal Cortical Blindness with Permanent Visual Loss
Authors: Aldrich Michael S. , Vanderzant Chris W. , Alessi Anthony G. , Abou‐Khalil Bassel , Sackellares J. Chris
Published: November 2007

Summary: Cortical blindness is rarely an ictal manifestation. We report the case of a man who developed transient cortical blindness followed by permanent visual deficits during repeated partial seizures. Intermittent visual impairment began at age 14 years. After he had the first generalized seizure at age 28 years, neurologic, ophthalmologic, angiographic, and brain computed tomographic (CT) examinations were normal. Several EEGs showed almost continuous biposterior spike‐waves. Over the next several years, frequent partial seizures were associated with transient visual loss and left body twitching or paresthesias. When he was 32, transient blindness occurred during several days of repeated occipital seizures. Permanent left homonymous hemianopia, right homonymous central scotoma, dyschromatopsia, and altered stereopsis followed these seizures. Brain CT demonstrated a new right occipital lesion. Partial seizures arising posteriorly may cause transient cortical blindness and result in permanent visual deficits.
Pyruvate Metabolism in Lafora Disease
Authors: Busard H. L. S. M. , Renier W. O. , Gabreëls F. J. M. , Trijbels J. M. F. , Janssen A. J. M. , Lamers K. J. B.
Published: November 2007

Summary: Lafora disease is an autosomal recessive and progressive degenerative disorder of the central nervous system (CNS). The pathogenic mechanism has been presumed to be an inborn error of carbohydrate metabolism, although this has never been proved. In a case of proven Lafora disease, pyruvate metabolism, which has a central position in carbohydrate metabolism, was studied in body fluids under various conditions and in brain biopsy material. No abnormalities in this metabolic pathway were found. This finding plus earlier reports in the literature exclude a defect in glycolysis; thus, a disturbance of carbohydrate metabolism as the pathogenic mechanism of Lafora disease is unlikely

La maladie de Lafora est une affection autosomique récessive dégénérative et progressive du système nerveux central. Le mécanisme pathogènique est vraisemblablement représenté par une erreur innée du métabolisme qui n'a jamais été prouvée. Dans un cas de Lafora confirmé, les auteurs ont étudié le méta‐bolisme du pyruvate, qui occupe une position centrale dans le métabolisme des glucides, dans les liquides biologiques et à par‐tir une biopsie cérébrale. lis n'ont pas constaté anomalie dans le méltabolisme du pyruvate. Ces résultats, joints a des travaux antérieurs de la Littérature, excluent hypothése un

La enfermedad de Lafora consiste en un proceso degenerativo del Sistema Nervioso Central de naturaleza progresiva y debido a mecanismos hereditarios autósdmicos recesivos. Los mecanismos patogénicos parecen corresponder a un defecto congenita del metabolismo de los carbohidratos a pesar de que nunca nan sido probados. En un caso de enfermedad de Lafora compro‐bado patológicamente, se ha estudiado el metabolismo del piru‐vato, que ocupa un lugar central en el metabolismo de los carbohidratos, en diversos fluidos corporales bajo condiciones di‐versas y tambtén en material cerebral de biopsia sin que se encontraran anomalfas de las vías metaólicas. Estos hallazgos unidos a informes previos de la literature excluyen un defecto en la glicolisis por lo que un trastorno en el mecanismo de los carbohidratos, como mecanismo patogénico en la enfermedad de Lafora parece improbable.

Die Lafora‐Erkrankung ist eine autosomal rezessive und progressiv‐degenerative Erkrankung des ZNS. Als pathogenetischer Mechanismus wird bislang unbewiesen eine angeborene Stoning des Kohlehydratstoffwechsels vermutet. Bei einem erwiesenen Fall einer Lafora‐Erkrankung wurde der Pyruvat‐Metabolismus, der eine zentrale Stelle im Kohlehydrat‐Metabolismus einnimmt, sowohl in Körperflüssigkeiten unter unterschiedlichen Bedin‐gungen als auch im bioptischen Hirngewebe untersucht. Es wur‐den keine Abnormalitäten dieses Stoffwechselweges gefunden. Dies läßt zusammen mit älteren Berichten der Literatur einen Glycolysedefekt ausschließen. Somit scheint eine Stöning des Kohlehydrat‐Stoflwechsels als pathogenetischer Mechanismus für die Lafora‐Erkrankung unwahrscheinlich
Sensory Stimulation for Inhibition of Epileptic Seizures
Authors: Rajna Peter , Lona Cristina
Published: November 2007

Summary: Simple acoustic stimuli were delivered at the onset of absence seizures in 23 investigations of 19 patients. In 79 of 139 observations, the stimulation promptly inhibited the seizure. The most effective inhibition was achieved in the first 3 s of the absence seizure. An automatic system of self‐stimulation is recommended for further investigations. Following solution of some theoretical questions and technical problems, the suggested method can become a new therapeutic modality in seizure treatment.

Des stimuli acoustiques simples ont été administrés au début d'absences lors de 23 enregistrements chez 19 patients. Dans 79 des 139 observations, la stimulation a rapidement inhibé la crise. L'inhibition la plus efficace a été obtenue pendant les 3 premieres secondes de l'absence. Les auteurs envisagent un sys‐tema automatism pour l'autostimulation. Lorsque quelques prob‐lemes thioriques et pratiques auront été résolus, cette méthode peut devenir une nouvelle modalité thérapeutique dans le traite‐ment des crises épileptiques.

Estímulos acústicos simples fueron aplicados al comienzo de un ataque de ausencia en 23 investigaciones de 19 pacientes. En 79 de 139 observaciones la estimulación inhibió rápidamente el ataque. La inhibitión más eficaz se consiguio durante los 3 pri‐meros segundos de la ausencia. Para investigaciones subsigu‐ientes se ha recomendado la utilización de un sistema automático de auto‐estimulación. Una vez superadas algunas cuestiones te‐óricas y problemas ténicos el método sugerido puede con‐vertirse en una nueva modalidad terapéutica de los ataques.
Can Sharp Waves Localized at the Sphenoidal Electrode Accurately Identify a Mesio‐temporal Epileptogenic Focus?
Authors: III Harold H. Morris , Kanner Andres , Lüders Hans , Murphy Doni , Dinner Dudley S. , Wyllie Elaine , Kotagal Prakash
Published: November 2007

Summary: In our patient population that had undergone antero‐temporal lobectomy, we found 20 patients with a unilateral sphenoidal/antero‐temporal interictal focus. All patients had normal computed tomography (CT) scans. Invasive recordings with subdural electrode arrays placed over and under the temporal lobe were used in every patient. We found that the scalp interictal focus predicted for all patients that both the interictal sharp waves and ictal onset would be mesiobasal/anterotemporal in location on the subdural arrays. Seventy‐five percent of these patients had an excellent outcome with temporal lobectomy.

Parmi leur population de patients opérés par lobectomie temporale antérieure, les auteurs ont retenu 20 observations chez lesquelles ils avaient mis en évidence un foyer intercritique temporal unilatéral antérieur ou sphénoïdal. Tous ces patients avaient une tomodensitométrie normale. Les enregistrements invasifs au moyen d'électrodes sous‐durales placées sur et sous le lobe temporal ont été pratiqués chez chacun de ces patients. Les auteurs ont trouvé que le foyer intercritique superficiel permettait de prédire chez tous les patients que les éléments paroxystiques intercritiques et que le début des crises auraient une localisation temporale médio‐basale ou antérieure lors de l'enregistrement sous‐dural. 75% de ces patients ont évolué très favorablement après lobectomie temporale.

En nuestra población de pacientes que habían sido sometidos a una lobectomía temporal anterior, encontramos 20 casos que tenían un foco interictal temporal esfenoidal/anterior, unilateral. Todos los pacientes tenían CT's normales. En cada paciente se utilizaron registros invasivos con series de electrodos subdurales implantados por encima y por debajo del lóbulo temporal. Encontramos que el foco interictal, registrado desde el cuero cabelludo, predijo en todos los casos que, tanto las ondas agudas interictales como su comienzo ictal, serían de localización mesial‐basal/anterior temporal en las series de electrodos subdurales. El 75% de estos pacientes tuvieron resultados excelentes tras una lobectomía temporal.

Unter unseren Patienten mit anteriorer Temporolobektomie fanden wir 20 Patienten mit einem einseitigen interiktalen Fokus sphenoidal‐temporal‐vorne. Alle Patienten boten ein normales CT. Jeder Patient wurde mit subduralen Elektrodenanordnungen im Bereich des Temporallappens untersucht. Es stellte sich heraus, daß der interiktale Skalp‐Fokus bei alien Pantienten zu einer richtigen Voraussage geführt hatte, sowohl bezüglich interiktaler sharp‐waves, als auch iktalem Beginn entsprechend der mesio‐basalen/temporo‐anterioren Lokalisation der subduralen Elektrodenplaziemng.
Relief of Seizures from a Predominantly Posterior Temporal Tumor with Anterior Temporal Lobectomy
Authors: Sperling Michael R. , Cahan Leslie D. , Brown W Jann
Published: November 2007

Summary: We report the relief of intractable complex partial seizures in a patient with a posteromesial temporal lobe hamartoma after anterior temporal lobectomy, despite minimal tumor removal. We suggest that the key to successful treatment is the mainly medial, or limbic, location of the tumor, which apparently requires anterior limbic structures for full clinical expression of seizures. We conclude that excision anterior to a posterior temporal lesion can result in seizure relief and that a medial tumor location may be important for successful treatment.

Les auteurs rapportent l'amélioration de crises partie les complexes rebelles chez un patient qui présentait un hamartome de la partie postéro‐mésiale du lobe temporal, et qui a été traité par lobectomie temporale antérieure n'emportant qu'une petite partie de la tumeur. Les auteurs suggèrent que l'explication à ce succès thérapeutique réside dans la localisation principalement médiane, ou limbique, de la tumeur, qui nécessitait apparemment les structures limbiques antérieures pour l'expression clinique complète des crises. Les auteurs concluent qu'une excision antérieure à une lésion temporale postérieure peut entraîner une amélioration des crises et que la localisation médio‐temporale d'une tumeur peut‐être un facteur important de succès chirurgical.

Se publica la majoría de ataques parciales complejos resistentes a terapia en un paciente con un hamartoma de la región posteromedial del lóbulo temporal después de realizar una lobectomía temporal a pesar de que la extirpateón del tumor fue mínima. Se sugiere que la clave del éxito terapeútico fue la localización del tumor, fundamentalmente medial o límbica. Aparentemente esta localización requiere estructuras límbicas anteriores para la máxima expresión clínica de los ataques. Se concluye que la exciseón de segmentos anteriores a una lesión temporal posterior puede resultar en una majoría de los ataques y que una localización medial del tumor puede ser importante para un tratamiento con éxito.

Wir berichten über die Verminderung kimplexer Partial‐Anfälle bei einem Patienten mit einem Hamartom im posteromesialem Temporallappen–es wurde eine anteriore temporale Lobektomie vorgenommen und nur wenig Tumorgewebe entfernt. Wir vermuten, daß der Schlüssel zum Verständnis dieser erfolgreichen Behandlung darin liegt, daß hauptsächlich mediale und limbische Tumoranteile entfemt wurden. Zur vollen klinischen Manifestation der Anfälle bedurfte es vermutlich der anterioren limbischen Strukturen. Die Exzision der vorderen Anteile bei posteriorer Temporal‐lappenlaesion kann somit zu Anfallsminderung führen, besonders bei medialer Tumorlokalisation.
Treatment of Infantile Spasms with Methysergide and α‐Methylparatyrosine
Authors: Hrachovy Richard A. , Frost James D. , Glaze Daniel G. , Rose Diana
Published: November 2007

Summary: Twenty‐four newly diagnosed and previously untreated infantile spasm patients were treated for 3 weeks with either methysergide (12 patients) or a‐methylparatyrosine (12 patients). Response to therapy was determined objectively with 24‐h polygraphic/video monitoring techniques and was defined as cessation of spasms and disappearance of the hypsarrhythmic EEG pattern. Two (17%) of the patients treated with a‐methylparatyrosine responded to therapy, and one (8%) of the methysergide‐treated group showed a response.

Vingt‐quatre patients non traités chez lesquels des spasmes infantiles venaient d'être diagnostiquls ont bénéficié pendant trois semaines d'un traitement par méthysergide (12 patients) ou α‐méthylparatyrosine (12 patients). La réponse au traitement a été jugée de façon objective, au moyen d'une surveillance poly‐graphique et vidéo de 24 heures, et a été définie comme l'arrêt des spasmes et la disparition de l'activité EEG hypsarythmique. Deux des patients traités par α‐méthylparatyrosine ont répondu au traitement (soit 17%), et un des patients traités par méthyser‐gide a répondu au traitement (soit 8%). La signification de ces constatations est discutée.

RESUMES

Durante tres semanas, un grupo de 24 enfermos recientemente diagnosticados de espasmos infantiles sin tratmiento previo, ha sido tratado con metisergida (12 pacientes) o alfa‐metiloparatirosina (12 casos). La respuesta a la terapeútica se determineó objetivamente utilizando técnicas de monitorización poligráfica/video durante 24 horas y se definió como una inter‐rupción de los espasmos y una desaparición del partón ipsarrít‐mico del EEG. Dos de los pacientes (17%) tratados con alfa‐metilparatirosina mostraron buena respuesta y uno (8%) del grupo tratado con metisergida tembtén respondió. Se discute el significado de los resultados.

24 neu auftetretene und nicht vorbehandelte Kinder mit BNS‐Krämpfen wurden für 3 Wochen entweder mit Methysergide (12 Pat.) oder Alpha‐Methylparatyrosin (12 Pat.) behandelt. Der Therapie‐erfolg wurde objektiviert durch: 24‐h‐Polygraphie und Videoaufnahmen. Als Anfallsfreiheit wurde definiert das Versch‐winden von Krämpfen und Hypsarrhythmie im EEG. 2 (17%) mit Alpha‐Methylparatyrosin behandelte Patienten und 1 (8%) mit Methysergide sprachen auf die Therapie an. Die Signifikanz des Ergebnis wird diskutiert.
Antiepileptic Drug Actions
Authors: Macdonald Robert L.
Published: November 2007

Summary: Antiepileptic drugs (AEDs) vary in their efficacy against generalized tonic‐clonic, myoclonic, and absence seizures, suggesting different mechanisms of action. Phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) reduced the ability of mouse central neurons to sustain high‐frequency repetitive firing of action potentials (SRF) at therapeutic free serum concentrations. Phenobar‐bital (PB) and the benzodiazepines (BZDs), diazepam (DZP), clonazepam (CZP), and lorazepam (LZP), also reduced SRF, but only at supratherapeutic free serum concentrations achieved in treatment of generalized tonic‐clonic status epilepticus. These AEDs interact with sodium channels to slow the rate of recovery of the channels from inactivation. The BZDs and PB enhanced γ‐aminobutyric acid (GABA) responses evoked on mouse central neurons by binding to two different sites on the GABAA receptor channel. BZDs increased the frequency of GABA receptor channel openings. In contrast, barbiturates increased the open duration of these channels. VPA enhanced brain GABA concentration and may enhance release of GABA from nerve terminals. Ethosuximide (ESM) reduced a small transient calcium current which has been shown to be involved in slow rhythmic firing of certain neurons. Reduction of SRF, enhancement of GABA‐ergic inhibition, and reduction of calcium current may be, in part, the bases for A ED action against generalized tonic‐clonic, myoclonic, and absence seizures, respectively.
Pharmacokinetics of Old, New, and Yet‐to‐Be‐Discovered Antiepileptic Drugs
Authors: Levy René H. , Kerr Bradley M.
Published: November 2007

Summary: The pharmacokinetics of antiepileptic drugs have been investigated extensively during the last two decades. It has become evident that the therapeutic management of epileptic patients would be significantly improved with the elimination of the drawbacks associated with existing antiepileptic drugs. Based on the information accumulated to date, the following set of principles is proposed: (1) The requirement of central nervous system (CNS) penetration automatically creates vulnerability to CNS toxicity. (2) The narrower the therapeutic range of a given drug, the more limiting its pharmacokinetic properties become. (3) The requirements of chronic administration and compliance place narrow limits on the optimum half‐life (24 h). (4) The practice of polytherapy and the potential for pharmacodynamic and pharmacokinetic interactions make it necessary to simplify metabolic schemes (i.e., use of meta‐bolically directed design approaches). (5) New antiepileptic drugs have shown that widely different structures are associated with anticonvulsant properties–it becomes important to minimize toxicity and optimize pharmacokinetic characteristics early in the development of future antiepileptic drugs. (6) Yet‐to‐be‐discovered antiepileptic drugs will probably include biotechnology‐based pharmaceuticals. Such biologic agents as neuropeptides present a new set of pharmacokinetic requirements because they are generally receptor targeted, they do not cross absorption barriers easily, and they are labile and subject to degradation.
Antiepileptic Drug Development Program: A Cooperative Effort of Government and Industry
Authors: Kupferberg Harvey J.
Published: November 2007

Summary: The most important step in antiepileptic drug discovery is the choice of an appropriate animal model for the initial screening as well as for the more complex procedures that elucidate mechanisms of action. The currently available models fall short in their inability to identify ail drugs for all types of seizures in a mechanism‐independent manner. Nevertheless, spontaneous models of epilepsy are the most commonly used, and chemically or electrically induced seizures in rodents can also identify potential anticonvulsants. In the latter models, the intensity of the seizure stimulus is of paramount importance. The Antiepileptic Drug Development Program evaluates approximately 800 compounds each year, using two models for preliminary screening. One model assesses the ability of a compound to prevent seizure spread; the other weighs the ability to raise seizure threshold. In vivo tests, featuring amygdala‐ and corneal‐kindled seizures, and in vitro assays, employing γ‐aminobutyric acid (GABA) receptors and synaptosomal uptake of adenosine, define drug‐drug interactions and elucidate the pharmacological profiles of potential anticonvulsants.
Phenytoin Prodrug: Preclinical and Clinical Studies
Authors: Leppik Ilo E. , Boucher R. , Wilder B. J. , Murthy V. Shrinivas , Rask Cynthia A. , Watridge Clarence , Graves Nina M. , Rangel R‐ J‐ , Turlapaty P.
Published: November 2007

Summary: The currently available phenytoin (PHT) solution has many disadvantages stemming from poor aqueous solubility of PHT. A novel approach to solve the problem has been the synthesis of a phosphate ester of PHT (PHT prodrug ACC‐9653). This water‐soluble compound is metabolized rapidly into P04 and PHT. A four center open‐label, baseline‐controlled study of 43 patients with epilepsy maintained on oral twice‐daily PHT monotherapy was performed to evaluate the safety and pharmacokinetic profile of the prodrug. Patients received an i.v. or i.m. dose of ACC‐9653 at a dose equivalent to the patients' morning dose of PHT. Intravenous dosages were infused at a rate of 75 mg/min, and i.m. dosages were given as one or two injections. After a period of 6 days, during which patients were again maintained with oral PHT, they were given a dose of ACC‐9653 via whichever route they had not yet received. The Tmsx of the prodrug averaged 5.7 and 36 min (0.095 and 0.606 h) after i.v. and i.m. administrations, respectively. The elimination half‐life of ACC‐9653 (conversion from prodrug to PHT) after i.v. and i.m. administration was 8.4 and 32.7 min (0.140 and 0.545 h), respectively, and both were independent of the dose. The plasma clearance of ACC‐9653 was not dependent on dose or route of administration and averaged 19.8 ± 1.16 and 17.8 ± 0.83 L/h after i.v. and i.m. administrations, respectively. The area under curve ratio of PHT after i.m. and i.v. ACC‐9653 was 1.17 ± 0.13 which was not significantly different from 1. These findings indicate that both i.v. and i.m. administrations of ACC‐9653 maintained stable levels of PHT. Unlike i.v. PHT infusion, serious cardiovascular and respiratory adverse reactions were not observed during the administration of i.v. ACC‐9653. Postural hypotension was reported in two patients. Paresthesia was the most frequent adverse experience reported during the i.v. infusion of ACC‐9653. The tingling sensation was transient and localized to the groin, lower back, abdomen, head and neck regions. Phlebitis, tissue necrosis, induration, cording and sclerosis were not observed in this patient population following either i.m. or i.v. ACC‐9653 administration. In summary, PHT plasma levels in patients with epilepsy who were receiving chronic oral PHT monotherapy were maintained by the i.m. or i.v. administration of ACC‐9653. Both i.v. and i.m. ACC‐9653 were well tolerated by the patients as evidenced by the absence of serious cardiovascular events, laboratory variable abnormalities, or adverse experiences.
Emergency Management of Seizures: An Overview
Authors: Uthman Basim M. , Wilder B. J.
Published: November 2007

Summary: The drugs currently used in the emergency management of seizures are chiefly phenytoin, phenobarbital, diazepam, lorazepam, and paraldehyde. The combination of intravenous phenytoin and lorazepam has the advantages of rapid onset of action, sustained efficacy, and freedom from drug interactions. The intermittent oral or rectal administration of diazepam is especially useful for acute home treatment of recurrent seizures. Phenytoin prodrug (ACC‐9653), an investigational new drug, is promptly absorbed after intramuscular injection. Unlike phenytoin, it does not require propylene glycol and high alkalinity for solubility and therefore does not produce soft‐tissue injury after parenteral administration. It appears to be close to an ideal drug for the emergency management of seizures.
Pharmacokinetics and Clinical Use of Benzodiazepines in the Management of Status Epilepticus
Authors: Treiman David M.
Published: November 2007

Summary: Benzodiazepines are potent and effective drugs for the management of acute seizures and status epilepticus. Lorazepam, diazepam, and clonazepam have been the most widely studied of the benzodiazepines in the treatment of status epilepticus. In 47 studies of these drugs involving 1,455 patients, lasting control of status epilepticus was achieved in 79% of the patients. None of these benzodiazepines is clearly superior to another for the effective control of status epilepticus. Differences in pharmacokinetic parameters, therefore, will influence the choice of drug. All three benzodiazepines are lipid‐soluble and enter the brain within seconds to minutes after intravenous administration. Diazepam, however, is very lipid‐soluble and highly protein‐bound and thus has a very large volume of distribution of unbound drug. As a result, the effective duration of action of diazepam in status epilepticus is only 20 to 30 min, whereas that of lorazepam, which has a much smaller volume of distribution of unbound drug, is at least several hours after a single intravenous injection. This allows the orderly administration of an antiepileptic drug for long‐term seizure control after status epilepticus has been controlled. For this reason, lorazepam is preferable for the initial management of status epilepticus. Continuous intravenous infusion of diazepam has been used successfully in the management of some patients with status epilepticus refractory to initial treatment.
Effects of Long‐Term Vigabatrin on Somatosensory‐Evoked Potentials in Epileptic Patients
Authors: Liegeois‐Chauvel C. , Marquis P. , Gisselbrecht D. , Pantieri R. , Beaumont D. , Chauvel P.
Published: November 2007

Summary: Vigabatrin (gamma vinyl GABA, GVG) has been shown to be an effective antiepiieptic agent. GVG specifically and irreversibly inhibits GABA‐transaminase (GABA‐T). Long‐term animal toxicology studies have demonstrated that GVG can induce nonprogressive, reversible intramyelinic edema in central white matter tracts. The response to GVG varies among species, with rodents being the most dramatic and monkeys showing an equivocal effect even at high doses. The response in dogs is marked and measurable. The detection of these subtle findings requires the use of sophisticated technology. Evoked potentials are becoming reliable and sensitive tools in clinical neurology. This study, involving 54 patients for 11 months, was undertaken to assess the effect and safety of GVG in humans with refractory epilepsy. No data from this investigation indicate prolongation of neuronal conduction time in CNS pathways, suggesting that this agent is safe in humans.
Neuroendocrinology and Limbic Epilepsy: Relationships to Psychopathology, Seizure Variables, and Neuropsychological Function
Authors: Leiderman Deborah B. , Csernansky John G. , Moses James A.
Published: November 2007

Summary: Correlations were sought among neuroendocrine, psychopathologic, neuropsychological, and seizure variables in 16 male patients with limbic epilepsy. Plasma prolactin and luteinizing hormone levels were directly correlated with seizure frequency. Plasma prolactin was inversely correlated with thought disorder. Post hoc findings included a strong direct correlation between total plasma testosterone levels and aggression. These relationships may help to elucidate mechanisms related to interictal symptomatology in patients with limbic epilepsy.

Se nan buscado las correlaciones entre variables neuroendocrinológicas, psicopatológicas. neuropsicológicas y ataques en 16 pacientes con epilepsía límbica. Los niveles plasmáticos de prolactina y de hormona luteinizante, se correlacionaron directamente con la frecuencia de los ataques. La prolactina plasmática se correlacionó inversamente con los trastomos de pensamiento. Los hallazgos posteriores incluyeron una fuerte correlación directa entre los niveles plasmáticos totales de testosterona y la agresión. Estos datos pueden ayudar a aclarar los mecanismos relacionados con la sintomatología interictal en enfermos con epilépsia límbica.

Bei 16 männlichen Patienten mit einer limbischen Epilepsie (LE) wurde nach Korrelationen zwischen Endokrinium, Psychopathologie, neuropsychologischen Veränderungen und unter‐schiedlichen Anfallstypen gesucht. Das Plasma‐Prolaktin korrelierte umgekehrt mit Denkstörungen. Postiktale Befunde zeigten eine deutliche direkte Korrelation zwischen Gesamt‐Plasma‐Testosteron und Aggression. Diese Abhängigkeiten könnten Mechanismen aufdecken, die mit den intenktalen Symptomen bei Patienten mit limbischer Epilepsie zusammenhängen.
Psychopathology and Limbic Epilepsy: Relationship to Seizure Variables and Neuropsychological Function
Authors: Csernansky John G. , Leiderman Deborah B. , Mandabach Mark , Moses James A.
Published: November 2007

Summary: Correlations were sought among psychopathologic, neuropsychological, and seizure variables in 21 patients with limbic epilepsy. Observer‐based assessments, such as the Bear‐Fedio Inventory, and self‐report assessments of psychopathology were used. Self‐reported psychotic experiences were associated with increased seizure frequency. Increased religiosity was noted in patients whose epileptic focus included the left side. Increased neuropsychological impairment was associated with several measures of psychopathology, including those related to thought disorder, psychoticism, and affective disturbance.

Les auteurs ont recherché l'existence de corrélations entre les paramètres psychopathologiques, neuropsychologiques et critiques chez 21 patients présentant une épilepsie limbique. lls ont utilisé des outils de mesure fondés sur l'observateur, comme l'inventaire de Bear‐Fedio, et une auto‐évaluation, pour les paramètres psychopathologiques. La survenue d'épisodes psychotiques signalés par les patients était associée à une augmentation de fréquence des crises. Une religiosityé plus importante a été constatée chez les patients dont le foyer épileptique incluait le côté gauche. Une gêne fonctionnelle neuropsychologique plus importante était associée à plusieurs paramètres psychopathologiques, incluant ceux qui sont reliés à une perturbation de la pensée, un psychoticisme, et une perturbation affective.

Se han buscado las correlaciones entre las variables psicopatológicas, neuropsicológicas y los ataques en 21 pacientes con epilepsía límbica. Han sido utilizadas evaluaciones psicopatológicas realizadas por el observador y por el propio enfermo, como el Inventorio Bear‐Fedio. Las experiencias psicóticas descritas por el enfermo se asociaron a un incremento de la frecuencia de los ataques. Se encontró un incremento de la religiosidad en enfermos cuyo foco epiléptico incluía el lado izquierdo. Se ha observado un incremento del trastorno neuropsicológico que se asoció a varias determinaciones de la psicopatología incluyendo las que se relacionaban con trastoraos de pensamiento, psicoti‐cismo y alteraciones afectivas.

Bei 21 Patienten mit limbischer Epilepsie (LE) wurde nach Korrelationen zwischen Psychopathologie, Neuropsychologie und Anfallsvariablen gesucht. Der Untersucher benutzte das Bear‐Fedio‐Material, der Patient einen Selbsteinschätzungsbo‐gen zur Dokumentation der Psychopathologie. Selbst berichtete psychotische Erlebnisse waren mit einer erhöhten Anfallsfrequenz vergesellschaftet. Starke Religiosität fand sich bei Patienten mit linksseitigem epileptischem Fokus. Die Zunahme neuropsychologischer Schwächen ging mit verschiedenen psychopathologischen Störungen wie Denkstörungen, Psychosen und Affektstörungen einher.
Clinicoelectrographic Concordance Between Monozygotic Twins with Severe Myoclonic Epilepsy in Infancy
Authors: Fujiwara Tateki , Nakamura Hitoshi , Watanabe Masako , Yagi Kazuichi , Seino Masakazu , Nakamura Hitoshi
Published: November 2007

Summary: Clinical features of a pair of monozygotic male twins, both with severe myoclonic epilepsy in infancy (SME), are described. They were almost completely concordant with respect to seizure onset, clinical seizure symptomatology, interictal, and ictal EEG expressions and seizure prognosis. The existence of such twins suggests the possibility that a genetic factor is determinant in the etiology of this particular epileptic syndrome.

Les auteurs rapportent l'observation d'une paire de jumeaux monozygotes masculins, qui ont présenté l'un et l'autre une épilepsie myoclonique sévère de l'enfance (EMS). Ces enfants étaient presque totalement concordants en ce qui concerne le début de l'épilepsie, la symptomatologie critique clinique, l'EEG intercritique et critique et le pronostic des crises. l'existence d'une telle observation de jumeaux suggère qu'un facteur génétique est peut‐être déterminant dans l'étiologie de ce syndrome épileptique particulier.

Se presentan los datos de una pareja de gemelos varones monocigóticos que padecieron una epilepsyía mioclónica severe (SME). Ambos presentaban una concordancia prácticamente total con respecto al comienzo de los ataques, la sintomatología clínica de los mismos, el EEG ictal e interictal y el pronóstico. La existencia de tales gemelos sugiere la posibilidad de que un factor genético sea determinante de la etiología de este síndrome tan particular.

Die klinischen Befunde eines männlichen monozygoten Zwillingspaares mit schwerer kindlicher myoklonischer Epilepsie (SME) werden dargestellt. Beide Kinder waren fast vollständig konkordant bezüglich Anfallsbeginn, klinischer Symptomatologie, iktalem und interiktalem EEG und Anfallsverlauf. Die Existenz derartiger Zwillinge spricht für die Möglichkeit, daß ein genetischer Faktor für die Auslösung diese epileptischen Syndroms ätiologisch bestimmend ist.
Adjunctive Therapy for Intractable Epilepsy with Ethotoin
Authors: Biton Victor , Gates John R. , Ritter Frank J. , Loewenson Ruth B.
Published: November 2007

Summary: In a retrospective study, records of 46 patients (24 women and 22 men aged 17–51 years; mean 29.2 years), who had been treated with ethotoin (EHN) as adjunctive therapy for control of intractable seizures were reviewed. Overall, ∽51% of this highly selected patient population had a reduction >50% in overall seizure frequency 1 month after initiation of treatment. This was reduced to ∽25% for the last 3 months of follow‐up (mean follow‐up period 10.6 months). Tonic seizure frequency was reduced most dramatically, by >50%, in 60% of patients at 1 month and in 35% of patients for the last 3 months of follow‐up. This study suggests that prospective controlled trials of EHN, especially for tonic seizures, are needed.