bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttraumatic Pilomotor Seizures: A Case Report
Authors: Ahern G. L. , III G. F. Howard , Weiss K. L.
Published: November 2007

Summary: Pilomotor epilepsy is a rare phenomenon. A 35‐year‐old man suffered a traumatic contusion of the right temporal lobe and subsequently developed spells characterized by diffuse piloerection and sweating. We believe this to be the first reported association between pilomotor epilepsy and posttraumatic head injury. Al‐though pilomotor seizures may result from diverse etiologies, they appear to have a common involvement of tem‐porolimbic structures.

Ľépilepsie pilomotrice est rare. Un homme de 35 ans, qui avait subi une contusion traumatique du lobe temporal droit, a présenté par la suite des accés caractérisés par une pilo‐erection diffuse et une sudation. Les auteurs pensent que ce cas rep‐rtsente la premiere observation d'une association épilepsie pilo‐motrice‐traumatisme cranien. Les crises pilomotrice rtpondent a des Etiologies varices, mais semblent avoir en commun une participation des structures temporo‐limbiques.

La epilepsia “pilomotora” es un fenómeno raro. Un enfermo de 35 años de edad que habi'a sufrido una contuseón traumatica en el lobulo temporal derecho, desarrolUS ataques caracterizados por una piloereccidn y sudoraci6n difusa. Creemos que este es el primer caso publicado en el que se asocia la epilepsia polomotora y un traumatismo craneoencefalico. Aunque los ataques pilomo‐tores pueden ser el resultado de diversas etiologias, parece ser que, en todos ellos, es comun una afectaci6n de las estructuras li'mbicas del lobulo temporal.

Die pilomotorische épilepsie ist selten. Ein 35‐jähriger Patient litt an einer traumatischen Kontusion des rechten Temporallap‐pens und entwickelte Anfälle mit diffuser Piloerektion und Schwitzen. Wir halten dies für eine erstmalig beschriebene Verknüpfung zwischen posttraumatischer Hirnverletzung und pilomotorischer Epilepsie. Da pilomotorische Anfälle durch ver‐schiedene Atiologien verursacht werden, scheint ihnen im allge‐meinen eine Beeinträchtigung temporo‐limbischer Strukturen zugrunde zu liegen.
Morphological and Biochemical Analysis of a Brain Biopsy in a Case of Idiopathic Lennox‐Gastaut Syndrome
Authors: Renier W. O. , Gabreels F. J. M. , Jaspar H. H. J.
Published: November 2007

Summary: The results of a qualitative and quantitative neuromorphological and a biochemical analysis of a brain biopsy from a 7‐year‐old boy with an idiopathic type of Lennox‐Gastaut syndrome (LGS) are reported. A disturbance in cerebral energy metabolism as expressed by the pyruvate pathway could be ruled out. Degenerative or ischemic lesions were not found. However, while the outer layers of the cortex were morphologically normal, the neurons of the inner layers (V and VI) showed a poor dendritic arborization and a diminished number of spines, which can be considered the basis of excessive excitability which in turn may further impair brain development. Thus, the neuromorphological findings suggest a causal rather then a consequential relation to LGS.

Se publican los resultados de un análisis morfológico cuantitativo, cualitativo y bioqui'mico de una biopsia cerebral de un nino de 7 años de edad con un síndrome idiopático de Lennox‐Gastaut. Se pudo excluir un trastorno en el metabolismo ener‐gético cerebral expresado a travel de la via del piruvato. No se encontraron lesiones degenerativas o isquómicas. Sin embargo, mientras que las capas más externas de la corteza aparecfan morfologicamente normales, las neuronas de las capas más inter‐nas (V y VI) mostraron una arborizaci6n dendritica pobre y una reduccion del numero de espinas, lo que puede considerarse coma las bases de una excesiva excitabilidad que, a su vez, puede alterar el desarrollo cerebral subsiguiete. Asi, pues, los hallazgos neuromorfologicos sugieren que deban considerarse más bien como causa que come consecuencia del sindrome de Lennox‐Gastaut.

Es wird berichtet über die qualitativen und quantitativen neu‐romorphologischen und eine biochemische Analyse der Hirnbi‐opsie eines 7‐jährigen Jungen mit idiopathischem Lennox‐Gastaut‐Syndrom. Eine Storung im cerebralen Energiestoff‐wechsel, des Pyruvat‐Metabolismus, konnte ausgeschlossen werden. Degenerative oder ischaemische Laesionen wurden nicht gefunden. Wahrend die auUßeren Kortexschichten morphologisch normal aussahen, boten die Neurone der inneren Schicht V und VI sparliche dentrische Verastelungen und V Urmin‐derung der Synapsen, was als Ursache der Hyperexitabilitat und Beeintrachtigung der Hirnentwicklung gedeutet werden kann. Demnach lassen die neuromorphologischen Befunde eher an eine ursachliche als an eine sekundare Schädigung durch das LGS denken.
Serologic HLA Typing in Infantile Spasms
Authors: Hrachovy Richard A. , Frost James D. , Pollack Marilyn S. , Glaze Daniel G.
Published: November 2007

Summary: Serologic HLA typing was performed on 29 patients with infantile spasms and hypsarrhythmic patterns in their electroencephalograms (EEGs). There were no significant increases in the frequencies of HLA‐A, B, and C antigens in the infantile spasm group as compared with controls. However, there was a significant increase in the frequency of DRw52 in the infantile spasm patients (90%) as compared with controls (72%) (p < 0.05). In addition, 3 of 12 white infantile spasm patients demonstrated the complete B18, DR3 (DRw52) haplotype; none of 150 control white subjects showed this haplotype. These findings contribute to evidence that immunological mechanisms may be involved in the pathophysiology of infantile spasms.

Un typage HLA a été effectué chez 29 patients présentant des spasmes infantiles et une hypsarythmie à l'EEG. II n'a pas été retrouvé d'augmentation de fréquence significative des antigènes HLA A, B ou C dans les groupes des malades par comparaison avec des sujets contrôles. Cependantr, il a éténotl une augmentation significative de DRw52 chez les malades: 90% contre 72% chez les contrdles (p < 0.05). De plus, 3 malades d'origine caucasienne présentant des spasmes infantiles avaient l'haplotype complet B18, DR3 (DRw52); aucun des 150 sujets contrôles d'origine caucasienne ne présentait cet haplotype. Ces constatations contribuent à souligner le rô1e de mécanismes immunologiques dans la physiopathologie des spasmes infantiles.

Se ha realizado un tipaje serológico de HLA en 29 pacientes con espasmos infantiles y patrones hipsarrítmicos en sus EEGs. No se encontraron incrementos significativos en la frecuencia del HLA‐A, B ni en los antígenos C en el grupo de espasmos infantiles compareándolo con los controles. Sin embargo se observó un incremento significativo en la frecuencia del DRw52 en los enfermos con espasmos (90%) compareándolos con los controles (72%) (p < 0.05). Además 3 enfermos de raza blanca con espasmos infantiles demostraron el haplotipo completo B18, DR3 (DRw52) mientras que ninguno de los 150 sujetos control, de raza blanca, lo evidenciaron. Estos hallazgos contibuyen a presentar evidencia de que mecanismos inmunológicos pueden participar en la fisiopatología de los espasmos infantiles.

Die HLA‐Typisierung wurde vorgenommen bei 29 Kindern mit BNS‐Krämpfen und Hypsarrhythmie. Gegenüber den Kontrollkindern ergab sich keine signifikante Häufung von HLA, B‐und C‐Antigen. Jedoch fand sich eine signifikante Erhöhung der Häufigkeit von DRw52 bei BNS‐Krämpfen (90%) gegenüber Kontrollkindern (72%) (p < 0.05). Darüberhinaus zeigten 3 von 12 weißen Kindern mit BNS‐Krämpfen den kompletten B18/DR3 (DRw52) Haplotyp–keiner der 150 weißen Kontrollfälle zeigte diesen Haplotyp. Die Befunde unterstützen die Annahme, daß in der Pathogenese der BNS‐Krämpfe immunologische Mechanismen beteiligt sind.
Right Hemisphere Partial Complex Seizures: Mania, Hallucinations, and Speech Disturbances During Ictal Events
Authors: Gillig P. , Sackellares J. C. , Greenberg H. S.
Published: November 2007

Summary: A patient with right hemisphere complex partial seizures exhibited extreme emotional lability resembling mania, neologisms resembling those found in fluent aphasia, and hallucinations during ictal periods. The electroencephalographic and clinical findings in this case suggest that cortical and subcortical structures of the right hemisphere may play a role in mediating the expression of language content.

Chez un patient présentant des crises partielles complexes de l'hémisphère droit, nous avons observé pendant les crises une labilitéémotionnelle évoquant le diagnostic de manie. des néologismes ressemblant à ceux de l'aphasie de Wernicke et des hallucinations. Nos constatation EEG et cliniques suggèrent que les structures corticales et sous‐corticales de l'hémisphère droit peuvent jouer un rôle dans la médiation de l'expression du contenu linguistique.

Un paciente con ataques parciales complejos originados en el hemisferio derecho mostró una labilidad emocional extrema semejante a la mania, neologismos comparables a los que se encuentran en la afasia fluida y alucinaciones durante los períodos ictales. Los hallazgos clínicos y del EEG en este caso sugieren que estructuras corticales y subcorticales del hemisferio derecho pueden jugar un papel en la función del contenido del lenguaje expresivo.
The Prevention of Chronic Epilepsy
Authors: Reynolds E. H.
Published: November 2007

Summary: : Recent epidemiological and hospital‐based studies of newly diagnosed epileptic patients suggest that the prognosis for epilepsy is much more favourable than had previously been reported and believed. Approximately three‐quarters of such patients may expect to go into prolonged remission with currently available drugs, utilised as monotherapy. For chronic epileptic patients, however, the outlook for seizure control is poor. Factors that contribute to the development of chronic epilepsy are partial or multiple seizure types, brain pathology, neuropsychiatric or social handicaps, poor compliance, and the early response to treatment. Evidence is presented that epilepsy should be viewed as a process in which early effective treatment may be important to prevent the evolution of chronic epilepsy, which is so difficult to control.
Epilepsy in Developing Countries: A Review of Epidemiological, Sociocultural, and Treatment Aspects
Authors: Shorvon S. D. , Farmer P. J.
Published: November 2007

Summary: : In this report, aspects of epilepsy that differ in developing and in developed countries are reviewed. This is inevitably an incomplete and impressionistic survey, because data on many aspects in developing countries are scarce, and because it is difficult to generalise meaningfully about the enormous diversity of countries and populations that make up the developing world. Epidemiological studies of prevalence and incidence are reviewed with an emphasis on the problems inherent in work in this area in developing countries. Data concerning seizure type, aetiology, and severity of seizures in the Third World are contrasted with those from developed countries. Sociocultural aspects of epilepsy have been poorly studied, and yet are fundamental to effective medical management. The social effects of epilepsy and the local perceptions of cause and of treatment are discussed from work in Africa, Asia, and South America. The principles and success of treatment in the Third World may differ considerably in developing and developed countries. In the Third World, medical manpower is scarce, and epilepsy is managed essentially by primary care resources, without specialised investigations or personnel. The principles of drug therapy may not be understood by patients, and the supply of drugs is often erratic; and these are major reasons for poor compliance with treatment. World Health Organisation (WHO) initiatives have stressed the extensive use of paramedical personnel and of an essential drugs list, but this emphasis may be misdirected, and in practice neither proposal has achieved much success. The recommendation that phenobarbital be extensively used in the Third World, because of its cheapness and efficacy, is also of doubtful merit, as there are well‐known and major drawbacks to the widespread use of this drug. Computations of treatment gap figures in three developing countries suggest that between 80–94% of patients with active epilepsy are not receiving anticonvulsant therapy, and cost is only one of a number of reasons for this. The key to improvements in medical treatment lie with a better understanding of the patients' cultural concepts of epilepsy and its treatment, improved drug supply and availability, and efforts to improve education amongst general practitioners and other primary care medical personnel.
William G. Lennox: A Remembrance
Authors: Lombroso Cesare T.
Published: November 2007

Summary: William G. Lennox, author of Epilepsy and Related Disorders, had a lasting effect on our understanding of this illness. He postulated that epilepsy was not a unitary condition and that neuronal chemistries differed from one form of the disease to another. A leader in the use of electroencephalography in epilepsy, he described the first nearly pathognomonic EEG pattern and demonstrated specific features for each of the three most common types of seizure. His pioneering investigations into the biochemical basis of epilepsy helped to identify pathological mechanisms in epileptic attacks. Lennox stood alone in his belief, now generally accepted, that the genetics of epilepsy could be understood only through a multifactorial mode of inheritance. The author presents an affectionate portrait of the physician, the teacher and the man, the founder of the Seizure Unit and the unifying force in the study of epilepsy by both professionals and lay persons.
Corpus Callosum Section and Other Disconnection Procedures for Medically Intractable Epilepsy
Authors: Spencer Susan S.
Published: November 2007

Summary: Corpus callosum section for carefully selected patients with uncontrolled epilepsy has become more acceptable as operative complications have decreased. From consideration of anatomical pathways utilized in the spread of seizure discharges, section of the corpus callosum is expected to decrease, but‐not abolish, bilaterally synchronous EEG abnormalities arising from most cerebral locations, perhaps excluding the temporal lobe. Clinical experience confirms this expectation. Persistence of some bilateral synchrony, presumably through subcortical relays, does not usually diminish the effectiveness of corpus callosum section on clinically generalized seizures that are eliminated or markedly decreased in 85% of patients after total corpus callosum section. Generalized seizure types that respond include tonic, atonic, tonic‐clonic, and absence seizures. Patients who continue to have generalized seizures usually have low IQ and perhaps extensive bilateral cerebral involvement increases the extent to which subcortical structures participate in generalization. Complex partial seizures may cease, usually in patients with well‐circumscribed, often extratemporal seizure foci. Focal seizures intensify in 25% of patients, a predictable consequence of sectioning interhemispheric inhibitory connections. Permanent disconnection syndromes, which are only rarely symptomatic, include sensory disconnection after posterior section, and split‐brain syndrome after total section. A small percentage of patients develop impairments in language, motor, or memory functions. Language and motor deficits are predicted by pre‐existing unilateral mild or moderate central nervous system damage. Partial section of the corpus callosum produces control of generalized seizures half as frequently as complete section. Neurologic sequelae of partial section occur nearly as frequently but are less severe.
Children of School Age: The Influence of Antiepileptic Drugs on Behavior and Intellect
Authors: Trimble M. R. , Cull C.
Published: November 2007

Summary: The role of antiepileptic drugs in behavior and cognitive function in children is well documented in the literature. In general, behavioral problems occur most frequently with phenobarbital and clonazepam, and appear least often with valproate and carbamazepine. Cognitive impairments occur with phenytoin, are less evident with valproate, and minimal with carbamazepine. Monotherapy, as with adults, leads to improvements in both cognitive abilities and behavior.
Comparison of Steady‐State Blood Levels of Two Carbamazepine Formulations
Authors: Jumao‐as Asela , Bella Isabelita , Craig Barbara , Lowe John , Dasheiff Richard M.
Published: November 2007

Summary: The steady‐state plasma level produced by brand‐name carbamazepine (CBZ) (Tegretol, Ciba‐Geigy) was compared with a generic formulation (Parke‐Davis) in 10 subjects with partial epilepsy in a randomized, double‐blind, cross‐over clinical trial. In addition, seizure frequency and clinical and laboratory signs of toxicity were evaluated. Our results failed to show any difference in CBZ blood levels, seizure frequency, or clinical or laboratory signs of toxicity in patients receiving either the brand‐name or generic formulation.

Le taux sanguin en phase équilibre obtenu par la carbamazépine originelle (Tégrétol, Ciba‐Geigy) a été comparé avec celui obtenu par une préparation générique (Parke‐Davis) chez 10 sujets présentant une épilepsie partielle au moyen une étude randomisée en double aveugle avec croisement. La fréquence des crises et les manifestations cliniques et biologiques intolérance ont également étéévaluées. Les résultats ne mettent pas en évidence de différence dans les taux sanguins, la fréquence des crises ou les signes cliniques et biologiques de toxicité entre les patients soumis au médicament origine ou à la préparation générique.

Steady State Plasma‐Konzentrationen wurden bei 10 Patienten mit partieller Epilepsie in einer randomisierten Doppelblind‐Cross Over‐Studie verglichen unter der Therapie mit Tegretol (Ciba‐Geigy) und einem Generic von Parke‐Davis. Zusätzlich wurde die Anfallsfrequenz sowie klinische Zeichen und Labor‐werte hinsichtlich Toxizität ausgtewertet. Wir fanden keine Differenzen bezüglich der Carbamazepin‐Blutspiegel, Anfallsfrequenz, klinischer Zeichen, beziehungsweise Laborwerte für eine Toxizität bezüglich beider Medikationen.
Effect of Felbamate on Phenytoin and Carbamazepine Serum Concentrations
Authors: Graves Nina M. , Holmes Gregory B. , Fuerst Robin H. , Leppik Ho E.
Published: November 2007

Summary: Felbamate (FBM) is a novel antiepileptic drug (AED) undergoing clinical trials in the United States. During a double‐blind, cross‐over clinical trial, patients received concomitant phenytoin (PHT) and carbamazepine (CBZ). Dosages of PHT and CBZ were adjusted to maintain serum concentrations ±20 and ±25% of baseline values. All patients required a PHT dosage decrease of 10–30% during active FBM treatment to maintain stable concentrations. CBZ serum concentrations decreased significantly in patients receiving active FBM. The mean decrease was 1.3 u.g/ml and occurred in 30 of 32 patients. Therefore, FBM apparently causes a bidirectional effect on the serum concentrations of PHT and CBZ when all three drugs are taken concomitantly.

Le felbamate (FBM) est un nouvel antiépileptique actuelle‐ment soumis à des essais cliniques aux USA. Pendant une étude croisée en double aveugle, les patients ont reçu de façon con‐comittante de la phénytoïne (PHT) et de la carbamazépine (CBZ). Les doses de PHT et de CBZ ont été ajustées afin de maintenir les taux sanguins entre ±20% et ±25% des concentrations basales. Chez tous les patients, il a été nécessaire, pour maintenir les taux sanguins, de réquire la dose de PHT de 10 à 30% pendant la phase de traitement actif par FBM. Les taux de CBZ ont significativement diminué chez les patients recevant le FBM. La diminution moyenne a éié de 1.3 μg/ml et a été con‐statée chez 30 patients sur 32. Ainsi, le FBM semble entraîner un effet divergent sur les taux sanguins de PHT et de CBZ lorsque ces trois médications sont administrées en association.
Neuroimaging in Patients with Seizures of Probable Frontal Lobe Origin
Authors: Swartz Barbara E. , Halgren Eric , Delgado‐Escueta A. V. , Mandelkern M. , Gee M. , Quinones N. , Blahd W. H. , Repchan J.
Published: November 2007

Sumary

Twenty‐two patients whose electroclinical ictal characeristics suggested frontal lobe seizure foci were studied. Computed tomography (CT) scans showed abnormalities in only 32% of patients whereas magnetic resonance imaging was informative in 45%. 18FDG‐Positron emission tomography (PET) scanning revealed decreased metabolism in 64% of the group. The areas of hypometabolism were focal, regional, or hemispheric. Focal frontal hypometabolism was significantly correlated with the electroclinical (semiologic) ictal localization. Therefore, FDG‐PET scanning is a sensitive and specific technique for investigating patients with seizures of probable frontal lobe origins.

22 patients présentant des phéitomènes électro‐cliniques évocateurs de l'origine focale frontale des crises ont étéétudiés. La tomodensitométrie a mis en évidence des anomalies chez suelement 32% des patients, contre 45% pour la RMN. Le PET‐SCAN au FDG 18 a mis en évidence une diminution du métabolisme chez 64% des patients. Les zones d'hypométabolisme étaient focales, régionales ou hémisphériques. l'hypométabolisme frontal focal a pu être significativement coirélé avec la localisation électroclinique (séméiologique) des crises. Les auteurs démontrent ainsi que le PET‐SCAN au FDG 18 est une technique d'évaluation sensible et spécique pour les patients présentant des crises partielles d'origine frontale probable.

Se han estudiado 22 pacientes con characterísticas ictales electroclínicas que surgerían la existencia de ataques focales de lóbulo frontal. La Tomografía Computarizada mostró anomalías solamente en el 32% de los enfermos mientras que la Resonancia Magnética ofreció información en el 45%. Los scanner con FDG‐PET revelaron una reducción del metabolismo en el 64% de los casos. Las áreas de hipometabolismo eran focales, regionales o hemisféricas. El hipometabolismo focal frontal se correlacionó significativamente con la localización electroclínica (semiológica) ictal. Por lo tanto, el FDG‐PET es una técnica sensible y específica para la investigación de pacientes con ataques de probable origen en el lóbulo frontal.

22 Patienten, deren iktales‐EEG auf einen Fokus im Frontallappen schließen ließ, wurden untersucht. Das CAT zeigte Auffälligkeiten bei 32%, das NMR bei 45% der Patienten. Das 78 FDG‐PET entdeckte bei 64% der Patienten einen verminderten Metabolismus. Die Legalisation des Hypometabolismus war fokal, regional oder hemisphärisch Der frontale Hypometabolismus war signifikant mit den iktalen elektroklinischen Befunden korreliert. Deshalb stellt das FDG‐PET eine sensible, spezifische Technik dar, um Patienten mit Anfällen, möglicherweise firon‐taler Genese, zu untersuchen.
Serum Bilirubin Levels with Antiepileptic Drugs
Authors: Gough H. , Goggin T. , Crowley M. , Callaghan N.
Published: November 2007

Summary: The incidence of reduced bilirubin levels in 168 outpatients with epilepsy, compared with levels in 69 controls, has been investigated. Highly significant (p < 0.001) reductions in average bilirubin levels were noted for carbamazepine (CBZ), phenytoin (PUT), phenobarbi‐tal (PB), and multiple drug groups. A marginally significant (p < 0.05) reduction in bilirubin levels occurred in patients treated with valproate (VPA) which, unlike the other drugs, has not been shown to induce hepatic enzymes.

L'incidence d'un abaissement des taux sanguins de bilirubine chez 168 consultants épileptiques a été compareée avec les taux observés chez 69 sujets contrôles. Les taux moyens de Bilirubine étaient trés significativement abaissés (p < 0.001) parmi les patients traités par carbamazépine, phénytoine, phénobarbital et polythérapie. line diminution à peine significative (p < 0.05) des taux de Bilirubine a été constatée chez les patients traités par valproate, médicament qui, à l'inverse des autres, n'est pas in‐ducteur enzymatique.

Se ha investigado la incidencia de los niveles de bilirrubina reducida en 168 pacientes con epilepsyía compareándolos con 69 controles. Se observaron reducciones áltamente significativas (p < 0.01) en la bilirrubina media, en los tratamientos con carbam‐acepina, fenitoina, fenobarbital o múltiples drogas. Se encon‐traron reducciones marginalmente significativas (p < 0.05) de los niveles de bilirrubina en pacientes tratados con valproate el cual, contrariamente a las otras medicaciones, no ha mostrado ca‐pacidad de inducir enzimas hepáticas.

Die Häufigkeit verminderter Bilirubinwerte bei 168 ambu‐lanten Patienten mit Epilepsie und von 69 Kontrollpersonen wurde untersucht. Eine hochsignifikante Reduktion der durchschnittlichen Bilirubinwerte (p < 0.001), wurde bei Car‐bamazepin, Phenytoin, Phaenobarbital und Kombinationen ge‐funden. Als gering signifikant (p < 0.05) wurden erniedrigte Bilirubinwerte bei Valproattherapie festgestellt. Im Gegensatz zu den anderen Substanzen scheint Valproat keine Enzyminduktion zu bewirken.
Pharmacokinetics and Clinical Use of Parenteral Phenytoin, Phenobarbital, and Paraldehyde
Authors: Ramsay R. Eugene
Published: November 2007

Summary: Intravenous phenytoin, phenobarbital, and paraldehyde are effective and safe for the treatment of acute seizures such as status epilepticus. All of these drugs should be infused in a diluted solution and at a slow rate to minimize the occurrence of adverse effects.
Intermittent Home Treatment of Status and Clusters of Seizures
Authors: Lombroso Cesare T.
Published: November 2007

Summary: Clinical trials in children and adults indicate that the intermittent oral or rectal administration of diazepam is an effective and safe alternative for the acute management of recurrent paroxysmal disorders. Prompt home treatment of dangerous or upsetting relapses can prevent the morbid effects of prolonged seizures and offer the patients and their families a sense of control over the illness.
Bioavailability of ACC‐9653 (Phenytoin Prodrug)
Authors: Browne Thomas R. , Davoudi Hamid , Donn Karl H. , Dougherty Carol L. , Dukes George E. , Evans Barbara , Evans James E. , Jamerson Brenda , Kres Jan , McEntegart Carol M. , Messenheimer John A. , Powell J‐ Robert , Quon Check Y. , Szabo George K.
Published: November 2007

Summary: The bioavailability of phenytoin from ACC‐9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC‐9653 to healthy volunteers. Absolute bioavailability of phenytoin derived from ACC‐9653 in each subject was calculated as the ratio of the phenytoin area under the plasma concentration time curve for time 0 to infinity [AUC(0‐inf)] after ACC‐9653 divided by the phenytoin AUC(O‐inf) after intravenous sodium phenytoin. The mean absolute bioavailability of ACC‐9653 was 0.992 after intravenous administration and 1.012 after intramuscular administration. These data establish that the bioavailability of ACC‐9653 is complete following intravenous or intramuscular administration in single‐dose volunteer studies. The absolute bioavailability of phenytoin derived from ACC‐9653 in subjects with therapeutic plasma phenytoin concentrations is being studied in patients given simultaneous infusions of stable isotope‐labeled tracer doses of ACC‐0653 and sodium phenytoin.
Pharmacokinetic Effects of Vigabatrin on Cerebrospinal Fluid Amino Acids in Humans
Authors: Ben‐Menachem Elinor
Published: November 2007

Summary: A study was conducted to assess the impact of single dosing and different dosing intervals of vigabatrin [gamma vinyl GABA (GVG)] in 11 patients with drug‐resistant complex partial seizures. Cerebrospinal fluid (CSF) concentrations of total GABA, free GABA, homocarnosine, homovanillic acid (HVA), GVG, and 5‐ hydroxyindolacetic acid were measured up to seven days after a single dose. GVG levels were maximal within 24 h, suggesting that GVG acts to inhibit GABA‐transami‐nase, and may also increase biogenic amines.
Specificity of Vigabatrin for the GABAergic System in Human Epilepsy
Authors: Riekkinen Paavo J. , Pitkanen Asia , Ylinen Aarne , Sivenius Juhani , Halonen Toivo
Published: November 2007

Summary: The therapeutic action of vigabatrin (gamma vinyl GABA, GVG) has been reported to be mediated by GABAergic neurotransmission. In the present study, we evaluated different neurotransmitter systems in the cerebrospinal fluid (CSF) of patients with complex partial epilepsy, before and during GVG treatment. The markers of the GABAergic system (free GABA, total GABA, homocarnosine) showed a two‐ to threefold elevation. There was also an increase in glycine during the 6 months of GVG treatment. In contrast, we did not find any constant CSF changes in either excitatory amino acids or in markers of the cholinergic (acetylcholinesterase), dopaminergic (homovanillic acid), serotonergic (5‐hydroxyin‐doleacetic acid), or peptidergic (somatostatin, prolactin, β‐endorphin) systems. This finding (except an elevation in glycine) was in agreement with previous studies which suggest a specific action of GVG on the GABAergic system. The role of glycine in antiepileptic efficacy of GVG needs further evaluation.
Mapping the Gene for Juvenile Myoclonic Epilepsy
Authors: Delgado‐Escueta Antonio V. , Greenberg David A. , Treiman Lucy , Liu Amy , Sparkes Robert S. , Barbetti Aida , Park Min Sik , Terasaki Paul I.
Published: November 2007

Summary: The practice of epileptology at a molecular level, where gene products are identified by gene mapping, will soon be possible for a growing number of epilepsies. Juvenile myoclonic epilepsy (JME) is the first of such epilepsies to be mapped to a chromosome, namely chromosome 6p21.3. Family studies of 68 JME probands from California revealed 50% of all families reported seizures in first‐ or second‐degree relatives. Twelve percent of all family members other than the proband had epileptic seizures. Eighty percent of symptomatic siblings and 6% of asymptomatic siblings had diffuse 4‐ to 6‐Hz multi‐spike‐wave complexes. Twelve percent of asymptomatic parents had diffuse, nonspecific slow waves mixed with spikes or sharp waves. JME is tightly linked to the Bf‐HLA loci in chromosome 6. No matter what mode of inheritance is assumed, linkage to the clinical manifestations of JME and its associated EEG traits is indicated by lod scores over 3.0, as long as “EEG affected” but clinically asymptomatic family members are counted as affected during LIPED analysis. Studies are now being done to further localize the JME site. At the same time, further linkage studies should decide if JME is heterogeneous within itself and whether the same JME site in 6p21.3 underlies absence and grand mal epilepsies.
Unilateral Truncal Seizures: Frontal Origin
Authors: Rosenbaum David H. , Rowan A. James
Published: November 2007

Summary: The locus of origin of seizures involving the muscles of the trunk is unresolved. The brainstem has been postulated by some investigators, whereas others have implicated the parietal cortex. We report a patient with epilepsia partialis continua involving the rectus ab‐dominus of one side in whom each contraction correlated with an epileptiform complex in the contralateral central‐vertex scalp region. This appears to be the first instance in which ictal EEG has localized truncal seizures to an area that probably corresponds to the precentral cortex.

Le lieu d'origine des crises qui impliquent les muscles du tronc reste problematique. Certains auteurs ont proposé une origine au niveau du tronc cérbral, d'autres ont impliqué le cortex pariétal. Les auteurs de ce travail rapportent l'observation d'un patient présentant une épilepsie partielle continue dont l'expression motrice se situait au niveau d'un muscle droit abdominal; chez ce patient, chaque contraction était cottéAtéà la survenue d'un complexe épileptique recueilli au niveau de la région centrale contro‐latgrale et du vertex. Ce cas semble représenter la première observation dans laquelle l'EEG critique a permis de loc‐aliser l'origine d'une crise du tronc au niveau d'une région qui correspond vraisemblablement au cortex pré‐central.

Todavía no se ha determinado el lugar donde se inician los ataques que afectan a los músculos del tronco. Algunos autores nan postulado que es en el tronco cerebral mientras que otros lo localizan en la corteza parietal. Publicamos un enfermo con epilepsia parcial contfnua afectando al musculo recto abdominal de un lado. Cada contractión muscular correlacionó con complejos epileptiformes en la region central‐vertex contralateral de cuero cabelludo. Este parece ser el primer ejemplo en el que un EEG ha mostrado descargas que localizan los ataques localizados en los músculos del tronco en un área que probablemente corre‐sponde a la corteza pre‐central.

ZUSAMMENFASSANG

Welchen Ursprung Anfälle mit Beteiligung der Rumpfmusku‐latur haben, ist unbekannt. Einige Autoren halten den Hirn‐stamm für verantwortlich, andere den parietalen Kortex. Wir berichten über einen Patienten mit Epilepsia partialis continua am M. rectus abdominis einseitig. Jede Kontraktion war mit einem epileptiformen Komplex der kontralateralen zentralen Vertex‐region korrelliert. Dies scheint das erste Beispiel zu sein, wo das iktale EEG RumpfAnfälle einer Region zuordnet, die moglicherweise mit dem praezentralen Kortex korrespondieren.
Clinical and Neuropathologic Findings in a Case of Severe Myoclonic Epilepsy of Infancy
Authors: Renier W. O. , Renkawek K.
Published: November 2007

Summary: The autopsy of a 19‐month‐old boy with severe myoclonic epilepsy of infancy (SMEI) and sudden unexpected death (SUD) revealed several developmental brain abnormalities. The most striking features were mi‐crodysgenesis of cerebellum and cerebral cortex and threefold spinal cord channels with surrounding ectopic tissue. Hippocampus and brainstem were normal

L'autopsie d'un petit garcon âgé de 19 mois suivi pour épilepsie myoclonique sévère du nourrisson (EMSN) et ayant présenté une mort subite, a mis en évidence plusieurs anomalies du développement cérébral. Les constatations les plus caractéristiques ont été la présence de microdysgénésies du cervelet et du cortex cérébral, et de canaux médullaires triples entourés de tissu ectopique. l'hippocampe et le tronc cérébral étaient normaux.

La autopsia de un nino de 19 meses de edad con epilepsía mioclónica de la infancia (SMEI) y muerte repentina inesperada (SUD) reveló anomalías severas en el desarrollo cerebral. Los hallazgos más Uamativos fueron la microdisgenesia del cerebelo y de la corteza cerebral y canales en el interior de la médula espinal aumentados, con tejido ectópico a su alrededor. El hipocampo y el tronco cerebral no mostraron anomalías

Die Autopsie eines 19 Monate alten Knaben mit schwerer frühkindlicher myoklonischer Epilepsie (SME) und plötzlichem Kindstod entdeckte verschiedene Entwicklungsanomalien des Gehirns. Den eindrücklichsten Befund stellten Mikrodysgene‐sien von Kleinhirn und Hirnrinde dar, sowie ein auffälliger Rück‐enmarkskanal mit umgebendem ektopischen Gewebe. Hippocampus und Hirnstamm waren normal.
Interaction of Carbamazepine‐10,11‐Epoxide, an Active Metabolite of Carbamazepine, with Valproate: A Pharmacokinetic Study
Authors: Pisani F. , Caputo M. , Fazio A. , Oteri G. , Russo M. , Spina E. , Perucca E. , Bertilsson L.
Published: November 2007

Summary: The mechanism responsible for the valproate (VPA)‐induced elevation of serum carbamazepine‐10,11‐epoxide (CBZ‐E) levels was investigated in 6 normal subjects who received single oral doses of CBZ‐E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ‐E terminal half‐life (t± from 6.3 ± 1.2 to 9.0 ± 2.0 h, mean values ± SD) and decreased CBZ‐E clearance (from 90.6 ± 18.8 to 63.2 ± 16.1 ml h ‐1 kg‐1, mean values ± SD) without affecting CBZ‐E apparent volume of distribution (from 0.82 ± 0.19 to 0.81 ± 0.241 kg‐1, mean values ± SD). These findings indicate that VPA impairs the elimination of CBZ‐E, presumably by inhibiting its metabolism.

En seis enfermos normales que recibían dosis orales únicas de 100 mg de carbamacepina‐10,11‐epóxido (CBZ‐E), se ha inves‐tigado el mechanismo responsable de la elevación de los niveles séricos de la CBZ‐E inducida por el valproate (VPA). Esto se realizó en una sesión control y durante el tratamiento concomi‐tante con 500 mg, dos veces diarias de VPA. El VPA causó una prolongatión significativa de la vida media terminal del CBZ‐E (de 6.3 ± 1.2 a 9.0 ± 2.0, valores medios ± SID), redujo el aclaramiento del CBZ‐E (de 90.6 ± 18.8 a 63.2 ± 16.1 ml h“1 kg‐1 valores medios ± SD) sin alterar el volumen aparente de distribución (de 0.82 ± 0.19 a 0.81 ± 0.24lkg1, valores medios ± SD). Estos hallazgos indican que el VPA altera la eliminación del CBZ‐E, probablemente debido a una inhibitión de su meta‐bolismo.

Es wurden die Mechanismen untersucht, die für den Anstieg von Carbamazepin‐Epoxid bei Valproatgabe verantwortlich sind. Sechs gesunde Personen erhielten eine Einzeldosis CBZ‐E (lOOmg) in der Kontrollphase und eine Kombinationstherapie mit VPA (500mg) in der Untersuchungsphase. VPA verursachte eine signifikante Verlängerung der terminalen CBZ‐E Halbwertzeit (von 6.3 ± 1.2 auf 9.0 ± 2.0 Studen), verminderte CBZ‐E Clearance (von 90.6 ± 18.9 auf 63.2 ± 16.1 ml/Std./kg), ohne das Verteilungsvolumen zu beeinträchtigen (0.82 ± 0.19 bzw. 0.81 ± 0.24 1/kg). Diese Befunde zeigen, daß VPA die Elimination von CBZ‐E verschlechtert, möglicherweise durch Inhibition des Ab‐baus.
Neurotransmitter Receptors in Adult Tottering (tg/tg) Mice
Authors: Dusser Anne E. , Peroutka Stephen J.
Published: November 2007

Summary: :Neurotransmitter receptor binding was analyzed in adult tottering (tg/tg) and control wild‐type mice. Saturation studies were performed to analyze the density of muscarinic cholinergic receptors in whole brain, cortical, and hippocampal homogenates of 8–9‐week‐old animals. Scatchard plot analysis was also performed to determine the density and affinity of a‐adrenergic and β‐adrenergic receptors. No significant difference in Bmax or Kd values was identified between adult tottering and control mice in any of the tissue preparations. The amount of radioligand binding to 5‐hydroxytryptamine, 1A (5‐HT1A), non‐5‐HT1A, 5‐HT2, dopamine D2, and benzodiazepine receptors was also identical in tottering and control mice. These findings suggest that the epilepsy expressed by adult tottering mice does not result from alterations in the density or affinity of the neurotransmitter receptors studied

Se ha analizado la captación en receptores de neurotransmisores en ratones “temblorosos” (tg‐tg) y en ratones control en libertad. Para analizar la densidad de los receptores muscarnicos colinérgicos en el cerebro total, en la corteza y en prepara‐ciones homogeneizadas de hipocampo en animates de 8 a 9 semanas de edad, se practicaron estudios de saturación. También se realizaron análisis “scarehard plot” para determinar la densidad y afinidad de los receptores aifa‐adrenérgicos y beta‐adrenérgicos. No se encontraron diferencias significativas en los valores Bmax, y Kd entre los ratones “temblorosos” y los controles en ningún tipo de tejido. La cantidad de acoptamiento del radio‐ligando a los receptores 5‐hidroxitriptamina1A (5‐HT1A), a los de non‐5‐HT1A, a los 5 HT1A, a los D2 de dopamina y a los benzodiacepina, file también idéntica en amobs tipos de ratones. Estos hallazgos sugieren que la epilepsía expresada por el ratón “tembloroso” no se debe a una alteración de la densidad o afinidad de los receptores estudiados.

Bei erwachsenen “tottering” (tg/tg)‐Mäusen sowie Kontrolltieren (Wildstämme)wurden Neurotransmitter‐Rezeptor‐Bindungsstudien durchgeführt. In Sättigungsstudien wurde die Dichte der Muskarin cholinergen Rezeptoren des gesamten Gehirns, sowie in kortikalen und hippokampalen Homogenaten von 8–9 Wochen alten Tieren bestimmt. Urn die Dichte und Affinität von alpha‐adernergen und beta‐adrenergen Rezeptoren zu bestimmen, wurde eine “scatchard” Plot‐Analyse durchgeführt. Zwischen den erwachsenen Tottering‐ und Kontrollmäusen be‐stand keine signifikante Differenz in Bmax, und KD Werten in alien Präparationen. Zusätzlich wurde die Höhe der Radioli‐ganden‐Bindung zu 5‐Hydroxytryptamin (5‐HT1A), zu non‐5‐HT1A, zu 5‐HT2, Dopamin D2 und Benzodiazipin‐Rezeptoren bei beiden Mäusepopulationen bestimmt. Die Befunde legen nahe, daβ die bei den erwachsenen “tottering” Mäusen auftretende Epilepsie nicht auf einer Änderung in der Dichte oder Affinität zu den untersuchten Neurotransmitter‐Rezeptoren besteht.
Considerations for Safety with Chronically Implanted Nerve Electrodes
Authors: Agnew William F. , McCreery Douglas B.
Published: November 2007

Summary: Electrical stimulation of cranial and peripheral nerves has been used to ameliorate a variety of neurologic disease states and neural injuries over the past 20 years. In this review, clinical applications and the histopathologic results of chronic implants in animals and humans are discussed, and the results of neural damage models developed at Huntington Medical Research Institutes are summarized. Chronically implanted electrode arrays may produce neural injury by either mechanical factors or by continuous, high‐frequency electrical stimulation. The margin of safety to avoid electrically induced injury may be increased by minimizing the frequency or total stimulation time, and by the use of an intermittent duty cycle. The protocols presently being used for the stimulation of the vagus nerve to effect inhibition of seizures appear to have an adequate margin of safety.
Efficacy and Safety of Vagus Nerve Stimulation in Patients With Complex Partial Seizures
Authors: Uthman Basim M. , Wilder B. J. , Hammond Edward J. , Reid Steven A.
Published: November 2007

Summary: A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire‐electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow‐up period make this a pilot study, but the results are promising.
Vagus Nerve Stimulation in Humans: Neurophysiological Studies and Electrophysiological Monitoring
Authors: Hammond Edward J. , Uthman Basim M. , Reid Steven A. , Wilder B. J. , Ramsay R. Eugene
Published: November 2007

Summary: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus‐nerve‐evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 μV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep.
Gene Mapping and Other Tools for Discovery
Authors: Leppert Mark F.
Published: November 2007

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 of epilepsy.
Gene Mapping in the Idiopathic Generalized Epilepsies: Juvenile Myoclonic Epilepsy, Childhood Absence Epilepsy, Epilepsy with Grand Mai Seizures, and Early Childhood Myoclonic Epilepsy
Authors: Delgado‐Escueta Antonio V. , Greenberg David , Weissbecker Karen , Liu Amy , Treiman Lucy , Sparkes Robert , Park Min S. , Barbetti Aida , Terasaki Paul I.
Published: November 2007

Summary: Idiopathic generalized epilepsies, i.e., juvenile myoclonic epilepsy (JME), childhood absence epilepsy, and epilepsy with grand mal [generalized tonic‐clonic seizures (GTCS)], are the most common genetic epilepsies. Linkage studies using Bf, HLA serologic, and DNA markers by three independent investigators, one from Los Angeles and two from Berlin, have localized the JME locus to the short arm of chromosome 6 (6p). Because members of the same JME family have the same JME phenotype of childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or early childhood myoclonic epilepsy (ECME), our observations give evidence for a single‐locus etiology in 6p for JME and for at least some of the childhood absence seizures, epilepsy with grand mal (GTCS) seizures, and ECME. Studies should now address whether locus heterogeneity exists within childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or ECME. Markers linked to JME (Bf, HLA serologic, and DNA markers in the DQ region) can be used to resolve etiologic heterogeneity. Using such markers, both linked and unlinked forms of phenotypes that are clinically indistinguishable may be detected and provide evidence for etiologic heterogeneity. Studies should also concentrate on narrowing the JME locus to 2 to 3 cm by screening families with recombinant events using RFLPs, candidate genes, and new expressed sequences on chromosome 6.