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Thesis (D.Phil (Social Work and Criminology))--University of Pretoria, 2005. / Includes abstract in English and Afrikaans. Bibliography.

Immune mechanisms are thought to be involved in the pathological disease process in a number of childhood epileptic syndromes and encephalitis. Of particular interest is the occurrence of autoantibodies to essential neuronal proteins, for example the N-methyl-D-aspartate receptor (NMDAR), in the blood and spinal fluid in some of these patients. The aims of this study were: to examine the sera of newly diagnosed paediatric epilepsy patients for specific neuronal autoantibodies, correlate to epilepsy phenotype and disease outcomes; to investigate the pathogenicity and epileptogenicity of central nervous system autoantibodies (CNS) in vivo; and to test new therapies in vitro and in vivo based on the potential pathogenic mechanisms. In 290 paediatric patients with new-onset epilepsy and seizures tested for CNS autoantibodies, 11.4% were positive (33/290 versus 8/112 in controls; p=0.01, Fisher's exact test). Previously unreported contactin-2 antibody positive and contactin-associated-protein 2 (CASPR2) antibody positive epilepsy patients were described. Patients with 'focal epilepsy of unknown cause' were more likely to be antibody positive. To test the pathogenicity and epileptogenicity of these antibodies, a novel in vivo telemetry system was used to continuously record electroencephalogram (EEG) in mice injected into the cerebral lateral ventricle with NMDAR antibody (NMDAR-Ab) positive immunoglobulin (IgG). Although no spontaneous seizures were seen, mice challenged with the pro-convulsant pentylenetetrazole (PTZ) had increased seizure susceptibility, and more epileptiform "spikes" in the EEG after PTZ compared to healthy control (HC) IgG injected mice. Seizure susceptibility strongly correlated with binding intensity of NMDAR-Ab IgG analysed in post-mortem tissue. Given the hypothesis this epileptogenic effect was mediated by NMDAR-Abs internalising cell surface NMDARs, and to try and rescue this deficit, a neurosteroid, pregnenolone sulphate (PregS) known to increase NMDAR cell surface expression, was therapeutically used. This approach worked in vitro, and although in vivo effects were not yet established, treatment with neurosteroids may be beneficial for autoantibody mediated neurological disease.

This study focuses on the way in which learners living with epilepsy, who attend mainstream schools in the rural areas of the Limpopo Province, experience epilepsy. The results of the study indicate that the needs of learners with epilepsy are not well-catered for in mainstream schools. They often experience fear, anxiety, humiliation, ostracisation, name-calling, scape-goating, blaming and suspicion. Recommendations were made regarding the measures which should be taken to address the needs of rural children living with epilepsy. These recommendations could be used by teachers and the Department of Education. / Educational Studies / M.Ed. (Guidance and Councelling)

This study focuses on the way in which learners living with epilepsy, who attend mainstream schools in the rural areas of the Limpopo Province, experience epilepsy. The results of the study indicate that the needs of learners with epilepsy are not well-catered for in mainstream schools. They often experience fear, anxiety, humiliation, ostracisation, name-calling, scape-goating, blaming and suspicion. Recommendations were made regarding the measures which should be taken to address the needs of rural children living with epilepsy. These recommendations could be used by teachers and the Department of Education. / Educational Studies / M.Ed. (Guidance and Councelling)

Inclusive education is one of the major changes in education, which has occurred since the implementation of Education White Paper 6 Special Needs Education; Building an inclusive education and training system. This inevitable change has resulted in many challenges for both educators and educational institutions. According to this policy, educators are expected to cater for all diverse needs of learners in the classroom including learners with epilepsy. Research indicates that educators find it difficult to cope with the demands of these learners and often experience frustration and failure. Educators have received little or no training to provide meaningful support for these learners. Despite policy changes the needs of learners with epilepsy are not met in the classroom. In this research the support programme is developed to provide practical and comprehensive guidelines to assist educators to support learners with epilepsy. / Social work / M. Ed. (Guidance and Counselling)

Thesis (MEdPsych (Educational Psychology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: This study was conducted within historically black schools in the Western Cape. According to (HSRP@historicsschools.org.za) historically Black schools are identified as schools which under the apartheid government were racially segregated schools, situated mainly in residential areas populated by people classified as black, for the exclusive use of people in this racial classification category. The purpose of this study was to explore educators', parents' and learner understands of epilepsy. This study uses an interpretive research framework to obtain in-depth data on educators', parents' and learner’s knowledge of epilepsy, reactions of educators towards learners with epilepsy, the effect of epilepsy on learning and the inclusion of learners with epilepsy in a regular class. The thematic content analysis was the method of analysis. Participants’ experiences with regard to epilepsy were reconstructed according to themes. Recurring themes were linked with the literature. This study found that educators, parents and learners had little idea what epilepsy entails and their beliefs were often moulded by inaccurate information. Educators have received little or no training to provide meaningful support for learners with epilepsy. Despite policy changes the needs of learners with epilepsy are not met in the classroom. Educators and parents insist that they need information, skills and clear guidelines regarding epilepsy. Research indicates that educators find it difficult to cope with the demands of these learners, and often experience frustration and failure. It could benefit the schools if a supporting programme is developed to provide practical and comprehensive guidelines to assist educators to support learners with epilepsy. / AFRIKAANSE OPSOMMING: Hierdie navorsing is in histories swart skole in die Weskaap onderneem. HSRP@historicschools.org.za beskryf ‘histories swart skole’ as skole wat tydens die apartheid-regime op grond van ras gesegregeer was, hoofsaaklik binne residensiële areas wat bewoon is deur mense wat as swart geklassifiseer is, vir die eksklusiewe gebruik van mense van hierdie rasseklassifikasie. Die doel van hierdie navorsing is om opvoeders, ouers en leerders se begrip van epilepsie te ondersoek. ’n Interpretatiewe navorsingsraamwerk is gebruik om in-diepte gegewens rakende opvoeders, ouers en leerders se kennis van epilepsie, opvoeders se reaksie teenoor leerders met epilepsie, die uitwerking van epilepsie op leer, en die insluiting van leerders met epilepsie in gewone klasse, in te win. Die tematiese inhoudsanalise is gebruik as ondersoekmetode. Deelnemers aan die studie se ervaringe van epilepsie is volgens temas gerekonstrueer. Herhalende temas is met die literatuur oor die onderwerp verbind. Die navorsing het bevind dat opvoeders, ouers en leerders weinig benul het van wat epilepsie is, en dat hulle begrip daarvan dikwels deur onakkurate inligting gevorm is. Opvoeders ontvang weinig of geen opleiding om betekenisvolle ondersteuning aan leerders met epilepsie te gee. Ten spyte van beleidsveranderinge word daar nie aan die behoeftes van leerders met epilepsie in die klaskamer voldoen nie. Opvoeders en ouers hou vol dat hulle inligting, vaardighede en duidelike riglyne rakende epilepsie nodig het. Navorsing wys dat opvoeders dit moeilik vind om raad te weet met hierdie leerders se behoeftes, en dat hulle dikwels frustrasie ervaar en voel dat hulle misluk het in hulle pogings. Die ontwikkeling van ’n ondersteuningsprogram, wat praktiese en omvattende riglyne daarstel om opvoeders met die behoeftes van leerders met epilepsie te assisteer, kan tot die voordeel van skole wees.

Inclusive education is one of the major changes in education, which has occurred since the implementation of Education White Paper 6 Special Needs Education; Building an inclusive education and training system. This inevitable change has resulted in many challenges for both educators and educational institutions. According to this policy, educators are expected to cater for all diverse needs of learners in the classroom including learners with epilepsy. Research indicates that educators find it difficult to cope with the demands of these learners and often experience frustration and failure. Educators have received little or no training to provide meaningful support for these learners. Despite policy changes the needs of learners with epilepsy are not met in the classroom. In this research the support programme is developed to provide practical and comprehensive guidelines to assist educators to support learners with epilepsy. / Social work / M. Ed. (Guidance and Counselling)

Epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) are age-related epileptic encephalopathy characterized by the development of various psychomotor regressions in close temporal concordance with the appearance of the electroencephalogram (EEG) pattern of CSWS (Tassinari et al. 2000). This EEG pattern consists in sleep-related activation and diffusion of spike-wave discharges during usually more than 85% of non-rapid eye movement (non-REM) sleep (Tassinari et al. 2000). <p>A minority of the CSWS cases has been associated to cortical or thalamic lesions (symptomatic cases), while in the other cases, the aetiology is unknown. We reported two families combining benign childhood epilepsy with centro-temporal spikes (BCECS), which is the most common form of idiopathic epilepsy in childhood, and cryptogenic epilepsy with CSWS in first-degree relatives. As idiopathic epilepsies are by definition epilepsies related to a genetic predisposition, these data suggests the existence of a continuum ranging from asymptomatic carriers of centro-temporal spikes to cryptogenic epilepsies with CSWS. This hypothesis is further supported by common clinical characteristics between BCECS and epilepsies with CSWS (Fejerman et al. 2000).<p>Epileptic syndromes with CSWS are characterized by an acute phase defined by the emergence of psychomotor deficits, various types of seizures and CSWS activity at around three to eight years of age (Holmes and Lenck-Santini, 2006; Veggiotti et al. 2001). This acute phase is followed by a recovery phase in which patients’ clinical condition improves together with the remission of CSWS pattern, which spontaneously occur at around 15 years of age but may be prompted by using antiepileptic drugs (AED) including corticosteroids (Holmes and Lenck-Santini, 2006; Veggiotti et al. 2001). This biphasic evolution suggests that CSWS activity largely contributes to the psychomotor deficits observed in these patients (Holmes and Lenck-Santini, 2006; Van Bogaert et al. 2006). However, some authors still consider CSWS activity as an epiphenomenon reflecting the underlying brain pathology, rather than the direct cause of the psychomotor regression (Aldenkamp and Arends, 2004). The pathophysiological mechanisms of how CSWS activity could actually lead to psychomotor regression are still poorly understood.<p>Functional cerebral imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), represent unique ways to non-invasively study the impact of epileptic activity on normal brain function. The PET technique using [18F]-fluorodeoxyglucose (FDG) gives information about the regional neuronal glucose consumption via the neurometabolic coupling while the fMRI technique studies the regional perfusional changes directly related to specific events of interest via the neurovascular coupling. We applied both FDG-PET and EEG combined with fMRI (EEG-fMRI) techniques to epileptic children with CSWS to better approach the functional repercussions of CSWS activity on neurophysiological functions and to determine the potential pathophysiological link between CSWS activity and psychomotor regression.<p>In a first FDG-PET study, we determined the regional cerebral glucose metabolic patterns at the acute phase of CSWS in 18 children. We found three types of metabolic patterns: the association of focal hypermetabolism with distinct hypometabolism in 10 patients, focal hypometabolism without any associated area of increased metabolism in five children, and the absence of any significant metabolic abnormality in three patients. The hypermetabolic brain areas were anatomically related to an EEG focus. This anatomical relationship was clearly less consistent for hypometabolic regions. The metabolic abnormalities involved mainly the associative cortices. The metabolic heterogeneity found in these children could be due to the use of corticosteroids before PET as it was significantly associated with the absence of focal hypermetabolism. At the group level, patients with at least one hypermetabolic brain areas showed significant increased metabolism in the right parietal region that was associated to significant hypometabolism in the prefrontal cortex. This finding was interpreted as a phenomenon of remote inhibition of the frontal lobes by highly epileptogenic and hypermetabolic posterior cortex. This hypothesis was supported by effective connectivity analyses which demonstrated the existence of significant changes in the metabolic relationship between these brain areas in this group of children compared to the control group or to the group of children without any significant hypermetabolic brain area. <p>This remote inhibition hypothesis would be reinforced by the demonstration, at the recovery phase of CSWS, of a common resolution of hypermetabolism at the site of epileptic foci and hypometabolism in distant connected brain areas. We thus performed a second FDG-PET study to determine the evolution of cerebral metabolism in nine children recovering from CSWS. At the acute phase of CSWS, all children had a metabolic pattern characterized by the association of focal hypermetabolism with distinct focal hypometabolic areas. The evolution to CSWS recovery was characterized by a complete or almost complete regression of both hypermetabolic and hypometabolic abnormalities. At the group level, the altered effective connectivity found at the acute phase between focal hypermetabolism (centro-parietal regions and right fusiform gyrus) and widespread hypometabolism (prefrontal and orbito-frontal cortices, temporal lobes, left parietal cortex, precuneus and cerebellum) markedly regressed at recovery. These results were of particular interest because they strongly suggested that the metabolic abnormalities observed during the acute phase of CSWS were mainly related to the neurophysiological effects of CSWS activity and not to the underlying cause of the epileptic disease. Moreover, this study confirmed that phenomena of remote inhibition do occur in epileptic syndromes with CSWS. <p>EEG-fMRI is a functional cerebral imaging technique that allows non-invasive mapping of haemodynamic changes directly associated to epileptic activity. In a first EEG-fMRI study, we determined the clinical relevance of the perfusional changes linked to interictal epileptic discharges in a group of seven children with pharmacoresistant focal epilepsy. This study showed that the EEG-fMRI technique is a promising tool to non-invasively localize the epileptic focus and its repercussion on normal brain function in children with epilepsy. Then, to further demonstrate the involvement of CSWS activity in the neurophysiological changes detected by FDG-PET, we used the EEG-fMRI technique to study the perfusional changes directly related to the epileptic activity in an epileptic girl with CSWS. This patient developed a cognitive and behavioural regression in association with a major increase in frequency and diffusion of the spike-wave discharges during the awake state (spike index: 50-75%) and non-REM sleep (spike index: 85-90%). The patient’s neuropsychological profile was dominated by executive dysfunction and memory impairment. During runs of secondarily generalized spike-wave discharges, EEG-fMRI demonstrated deactivations in the lateral and medial fronto-parietal cortices, posterior cingulate gyrus and cerebellum together with focal relative activations in the right frontal, parietal and temporal cortices. These results suggested that the neuropsychological impairment in this case could be related to specific cortical dysfunction secondary to the spread of the epileptic activity from focal hypermetabolic foci. <p>Taken together, both FDG-PET and EEG-fMRI investigations performed in epileptic children with CSWS have shown increases in metabolism/perfusion at the site of the epileptic focus that were associated to decreases in metabolism/perfusion in distinct connected brain areas. These data highly suggest that the neurophysiological effects of CSWS activity are not restricted to the epileptic focus but spread to connected brain areas via a possible mechanism of surrounding and/or remote inhibition. This mechanism is characterised by an epilepsy-induced inhibition of neurons that surround or are remote from the epileptic focus and connected with it via cortico-cortical or polysynaptic pathways (Witte and Bruehl, 1999). The existence of surrounding and remote inhibition phenomena have been well documented in different types of animal models of focal epilepsy using various functional cerebral imaging methods such as autoradiography or optical imaging (Bruehl et al. 1998; Bruehl and Witte, 1995; Witte et al. 1994). Their occurrence in human epilepsy have also been suspected in temporal or extra-temporal lobe epilepsies using FDG-PET, EEG-fMRI or single photon emission computed tomography (SPECT) (Blumenfeld et al. 2004; Schwartz and Bonhoeffer, 2001; Van Paesschen et al. 2003; Van Paesschen et al. 2007). Moreover, the demonstration of the regression of distant hypometabolic areas after surgical resection or disconnection of the epileptic focus further suggest that such inhibition mechanism do occur in epilepsy (Bruehl et al. 1998; Jokeit et al. 1997). On a clinical point of view, the demonstration of the existence of such inhibition mechanisms in epilepsies with CSWS brings new important insights for the understanding of the pathophysiological mechanisms involved in the psychomotor regression observed in these conditions. Indeed, these data highly suggest that the psychomotor regression is not only related to the neurophysiological impairment at the site of the epileptic foci but also to epilepsy-induced neurophysiological changes in distant connected brain areas. <p><p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

After the dispensation of the White Paper 6 in schools, there were no detailed guidelines to accommodate the learners with invisible impairments like absence epilepsy, especially those who live in underprivileged communities. Affected learners are still struggling and not receiving proper instruction in ordinary schools because of the nature of absence epilepsy. It seems like it is unknown that they are suffering, because the symptoms are absent. These learners are performing poorly; they are having learning and behavioural problems. At home parents are ignorant of their plight, teachers are oblivious of their problems and at schools they are being discriminated against by other children. As a result, they repeat grades and some end up leaving school to join the unemployed. They have a low self-esteem and remain unsociable. This is because they suffer from absence epilepsy which is a medical problem. Absence epilepsy is unknown to both parents and teachers in these communities. Cultural beliefs and ignorance prevent parents from taking these children to clinics for identification, which results in them not being supported in schools. / Inclusive Education / M. Ed. (Inclusive Education)