Thesis (doctoral)--Westfälischen Wilhelms-Universität zu Münster, 1995. / Includes bibliographical references.

Thesis (Ph. D.)--Columbia University, 1935. / Vita on slip mounted on verso of last leaf. Concerning the relation of ketosis, produced by diet, inanition or injection, to convulsions of experimental origin in cats, with a brief reveiw of the literature pertaining to the problems of ketogenic diet and fasting in the treatment of epilepsy. cf. Introd. and scope. "Read at the nineteenth annual meeting of the American pshchiatric association, Section on convulsive disorders, New York, N.Y., May 28-June 1, 1934." Bibliography: p. 46-47.

Thesis--Wisconsin. / Includes bibliographical references (leaf 100).

Akademische abhandlung--Lund. / At head of title: Aus dem Kaiser-Wilhelm-institut für genealogie und demographie (direktor: prof. dr. E. Rüdin) der Deutschen forschungsanstalt für psychiatrie in München. "Literaturverzeichnis": p. [220]-224.

Thesis (M.L.S.)--University of Toledo, 2006. / Typescript. "A thesis [submitted] as partial fulfillment of the requirements of the Master of Liberal Studies degree." Bibliography: leaves 57-59.

The literature on epilepsy is vast. The first review in this thesis presented a short introduction to the nature of the disease and its relationship to cognitive functioning. The pharmacological treatment of epilepsy by three major anticonvulsant drugs (carbamazepine, sodium valproate and phenytoin) and the possibility of effects of this treatment on cognitive functioning is presented in the second review. This review identified certain areas of cognitive functioning, for example memory, that warrant further investigation. A third review discussed those relevant areas of cognitive functioning, including both theory and suitable methodologies for investigating working memory and attentional resources. The three review chapters provided theoretical and practical frameworks to carry out investigations of the effects of anticonvulsant medication on cognitive functioning. Four experimental studies are presented. The design of the first study was a between-groups comparison, in which four groups of subjects with epilepsy (three on monotherapy and a polytherapy group) and a control group were compared on a battery of memory tests. The only significant group difference was the impaired performance of the polytherapy group compared to the control group. The second study was a between-groups comparison of the performance of four groups with epilepsy (three on monotherapy and one untreated group) and one control group, on a new battery of tests measuring working memory and attentional resources. The sodium valproate group was significantly impaired on two of the working memory tasks compared to the control group. No other group differences were found and increasing task complexity did not significantly affect the drug groups compared to the control group. Of interest in both study one and two was the consistent pattern of results across the test batteries, which did not produce significant differences between the groups. Both studies revealed large variance in the clinical subject groups, such that a number of the subjects with epilepsy, particularly on sodium valproate and phenytoin were performing very poorly compared to control group performance. No obvious reasons were identified for the poor performance. Study three investigated the effects on cognitive functioning of a new anticonvulsant drug (Lamotrogine). The clinical subject group was very impaired compared to a control group, and a small amount of further impairment was present after the subjects began taking Lamotrogine. The fourth study piloted tests designed to measure aspects of perceptual and motor functioning. The only significant result obtained was that the polytherapy group performed significantly worse compared to the control and the monotherapy groups on simple reaction time tasks. The focus of the discussion chapter was a summary of the important aspects of the studies in the thesis with comparisons made to other studies in the published literature.

Epilepsy affects over 450,000 people in the UK and there are over 50 epilepsy phenotypes; genetic generalised epilepsy (GGE) account for up to 30% of seizure types. It is established that GGE and other neurological disorders are, in some cases, caused by channelopathies within post-synaptic inhibitory neurotransmitter systems such as GAB A (epilepsy) and Glycine (hyperekplexia). GAB A is the primary inhibitory neurotransmitter in the brain and is synthesised from glutamate by GAD65 and 67, and is released from the pre-synaptic nerve terminal into the synaptic cleft, where it binds to post-synaptic GABA receptors and initiate neuroinhibition. This inhibition is removed by post-synaptic GABA transporters (GAT1 and GAT3) that uptake GABA back into the cell for re-packaging in presynaptic vesicles or breakdown by transamination. Abnormalities in this system have been linked to diseases including anxiety, psychosis, Parkinsons’s Disease and epilepsy. GABAergic animal models have demonstrated a tendency to seizure, including GABA transporter and enzyme models in relation to epilepsy. Given the above, the aim of this study was to identify GGE causing variants in four GABAergic genes. GGE patient samples (n=101) were recruited from 3 global centres and screened for variations in GAT1, GAT3, GAD65, GAD67 using high-throughput LightScanner analysis and bi-directional Sanger sequencing. Control population studies («=480) were carried out and analysis of online databases to determine the frequency of variants. Twenty novel or very rare variants were identified in 48 patient samples representing a detection rate of 6.8%, where a clustering of phenotypes included a predisposition towards absence seizures. The biological consequences of these variants were predicted using three online predictive programmes, multiple phylogenetic alignments and 3D structural modelling. Mutation expression constructs were prepared and expression levels were validated by immunocytochemistry. Functional characterisation of these variants will hopefully improve genetic diagnosis in GGE and determine causality of GABAergic absence seizures.

Research has demonstrated that prenatal exposure to antiepileptic drugs is associated with an increased risk of physical malformations. The potential risk such exposure conveys to the developing brain and therefore the later cognitive functioning of the child is now the focus of both national and international research. This thesis investigated the relationship between prenatal exposure to antiepileptic drugs and child cognitive functioning. This investigation was undertaken in three phases: a systematic review of the published literature; an original research piece investigating prenatal exposure to sodium valproate and levetiracetam and finally a critical review of the research undertaken as part of this thesis and in the wider published literature. The systematic review identified 30 studies which had investigated the cognitive abilities of children with a history of prenatal exposure to antiepileptic drugs. Methodological quality of the studies was considered against the criteria of the Newcastle Ottawa Scale. Differential findings were noted across the antiepileptic drug types, with the largest number of studies documenting increased risks associated with prenatal exposure to sodium valproate. A lack of high quality research across all antiepileptic drugs, and in particular the more recently licensed antiepileptic drugs is highlighted. In the research paper presented here children aged between five and nine years of age exposed to either levetiracetam (n=37), sodium valproate (n=40) or who were born to women with epilepsy but did not require medication (n=43) were recruited from throughout the UK. Demographic and health information was collected from prospective records and supplemented with maternal interview. Formal standardised neuropsychological assessments were undertaken to inform on the child's current level of intellectual, memory, language, attentional and executive functioning. Following adjustment for variables likely to influence child cognitive ability, prenatal exposure to sodium valproate was found to be associated with poorer intellectual and language functioning in a dose dependent manner. When stratified by dose, 57.9% of children exposed to doses of sodium valproate above 800mg daily scored below the average range for their global intellectual ability. Prenatal exposure to levetiracetam was not found to be associated with poorer cognitive functioning. The critical review highlighted a number of methodological strengths of this research, despite time and resource implications. However, consideration should be given to the retrospective nature of this cohort and the potential for recruitment bias. This thesis concludes that women who require continuation of their treatment during pregnancy to control their seizures should be counselled regarding the risks and the benefits of their treatment to allow them to make informed decisions.

Medical science has done much to bring epilepsy out of the realm of mysticism and misconception, into the area of normal and natural diseases; but many persons subject to seizures experience difficulty in their attempts to live as others do. It is the purpose of this thesis to examine the ways in which medical social work can help them achieve this end. The setting-up and the purpose of the Seizure Clinic of the Vancouver General Hospital is described. An examination of the social situations of fifty-three persons who were referred to the social worker during a period of seventeen months, for various kinds of help, reveals the problems which epilepsy presents to this group of people. There are numerous examples of difficulties associated with (a) parental attitudes, (b) social relationships, (c) employment, and (d) marriage. The material indicates-clearly, that blanket statements regarding "epileptics" in general, are unfair and untrue. Each is an individual who requires help with his particular difficulties. Analysis of the cases reveals that the medical social worker can contribute to the treatment of epilepsy by (a) enabling the physician to understand the patients social .situation as it affects his medical condition and his attitude toward medical treatment; (b) correcting the patient's misconceptions toward his illness, alleviating anxiety regarding treatment, and generally enabling him to obtain the greatest benefit from medical treatment; (c) helping the patient understand and accept his handicap; (d) helping parents develop healthy, attitudes toward handicapped children, in order that they may be prepared to assume the responsibilities of adulthood; (e) familiarizing persons in the community with the facts regarding epilepsy and thus eventually reducing the stigma associated with the illness. The casework methods used by the social worker include, (a) modifying the environment, (b) psychological support, (c) clarification, and (d) insight. There is sufficient evidence in this study that medical social work can in various ways and to varying degrees, help epileptic persons to be useful members of the communities in which they live. / Arts, Faculty of / Social Work, School of / Graduate

The role of the forebrain commissures in the developing and developed kindled amygdaloid seizure in the rat was investigated. In the first two experiments, bisection of the corpus callosum, hippocampal commissure, and anterior commissure prior to kindling caused a significant facilitation in the rate of primary-site kindled seizure development. In the last experiment, bisection of the corpus callosum and hippocampal commissure after primary-site kindling facilitated the subsequent rate of secondary-site kindling. It is evident, that in the intact animal, the nonstimulated hemisphere is able to exert an inhibitory influence over the development of seizure activity in a stimulated hemisphere and that this effect is, in turn, mediated via the forebrain commissures. The corpus callosum and hippocampal commissure were found to participate in the interference phenomenon since bisection of these structures either before or after primary-site kindling caused a facilitation in the rate of primary-site rekindling. In the first two experiments, an extracommissural, possibly brainstem, mechanism is suggested to mediate the transfer effect between the primary and secondary sites since bisection of the forebrain commissures prior to kindling had no effect on the rate of secondary-site kindling. The development of primary generalized motor seizures is in part dependent on the integrity of the corpus callosum and hippocampal commissure. Bisection of these structures after primary-site kindling, however, abolished the subsequent development of primary generalized seizures in a significant number of rats. Therefore, it appears that if the commissures are bisected prior to kindling, alternate pathways able to mediate the development of primary generalized seizures evolve. / Medicine, Faculty of / Graduate