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Dinkelacker, Vera. "Network pathology in temporal lobe epilepsy." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066156/document.
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Notre vision de l'épilepsie du lobe temporal avec sclérose hippocampique a beaucoup évolué grâce aux techniques de neuroimagerie multimodale. Initialement perçue comme maladie restreinte à la lésion, à savoir la sclérose hippocampique (SH), elle est aujourd'hui considérée comme un modèle de pathologie en réseau. Cette thèse a pour but d'approfondir les caractéristiques du réseau sous tendant cette épilepsie.Nous avons pour cela recueilli des données de connectivité structurelle, d'EEG et de données cognitives chez une cohorte de 44 patient avec SH unilatérale (22 droite, 22 gauche) et chez 28 sujets contrôle. Nous avons déterminé les régions d'intérêt corticales et le volume hippocampique avec Freesurfer et la connectivité structurelle (locale ou en réseau) avec MRtrix ou FSL.Trois principaux résultats émergent de ces études :1. La connectivité globale montre un pattern de déconnexion très marqué de l'hémisphère gauche en cas de SH gauche. La SH semble donc s'accompagner d'une atteinte de réseau plus importante lorsqu'elle se situe dans l'hémisphère dominant pour le langage.2. La connectivité hippocampo-thalamique est augmentée du côté de la SH. Cette augmentation semble dysfonctionnelle, car corrélée avec une baisse de fonctions cognitives exécutives. 3.L'EEG de ces patients révèle des anomalies interictales ipsi-latérales qui sont corrélées avec une diminution de fonctions cognitives exécutives. Nos données confirment ainsi le concept de l'épilepsie du lobe temporal en tant que pathologie de réseau. L'atteinte structurelle, mais également cognitive s'étend sur des régions à distance de l'hippocampe et affecte notamment les réseaux de langage de l'hémisphère dominantOur vision of temporal lobe epilepsy (TLE) with hippocampal sclerosis has much evolved in recent years. Initially regarded as a disease centered on a single lesion, it is now perceived as a genuine network disease, which we intended to explore with a multimodal approach. We examined structural connectivity, fMRI, EEG and cognitive dysfunction in a cohort of 44 patients with unilateral hippocampal sclerosis (HS, 22 with right, 22 with left HS) and 28 healthy age and gender matched control participants. Cortical regions of interest and hippocampal volumes were determined with Freesurfer, structural connectivity with MRtrix (pairwise disconnections and component effects with Network Based Statistics), or for hippocampal-thalamic connections with FSL. We found a pronounced pattern of disconnections most notably in the left hemisphere of patients with left TLE. Network Based Statistics showed large bi hemispheric clusters lateralized to the diseased side in both left and right temporal lobe epilepsy. We suggest that hippocampal sclerosis is associated with widespread disconnections if situated in the dominant hemisphere. We then determined streamline connections between hippocampus and thalamus and found an increase in connections in relation to the HS. This increase was seemingly dysfunctional as the number of hippocampal-thalamic connections was negatively correlated with performance in executive tasks. EEG analysis revealed predominantly ipsilateral epileptic discharge. The number of sharp waves was highly correlated with a number of executive functions depending on the frontal lobe, hence at distance of the HS. Our data thus confirms the concept of temporal lobe epilepsy as a network disease that finds its expression both in widespread, though lateralized alterations of structural connectivity and in neuropsychological dysfunction way beyond the hippocampus
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Amorim, Barbara Juarez. "Analise estatistica baseada em voxel do SPECT cerebral em pacientes com epilepsia de lobo temporal." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313716.
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Orientadores: Fernando Cendes, Elba Cristina Sa de Camargo EtchebehereTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O statistical parametric mapping (SPM) é uma ferramenta de quantificação que tem sido usada no SPECT de perfusão cerebral (SPECT), mas apenas poucos trabalhos na literatura comparam a sua sensibilidade com a da análise visual em pacientes com epilepsia de lobo temporal (ELT) OBJETIVO: Avaliar a capacidade da análise com SPM no SPECT em detectar o foco epileptogênico e alterações perfusionais em regiões extra-temporais em pacientes com epilepsia de lobo temporal mesial (ELTM), comparando os seus achados com os da análise visual MÉTODOS: Foram realizados SPECTs ictal e interictal em 22 pacientes com ELTM refratários ao tratamento clínico. O lado do foco epileptogênico foi definido com base na história clínica, ressonância magnética, eletroencefaiogramas seriados e telemetria. Os SPECTs foram submetidos à análise visual sendo que os SPECTs interictal e ictal foram analisados em conjunto pelos observadores (SPECT-visual-inter e SPECT-visual-ictal). Foi aplicado o SPM2 que comparou os pacientes com um grupo controle de 50 indivíduos normais. No SPM foram realizadas as seguintes comparações: grupo de SPECT interictal com o grupo controle (SPM-grupo-inter); SPECT interictal de cada paciente com o grupo controle (SPM-indiv-inter); grupo de SPECT ictal com o grupo controle (SPM-grupo-ictal); SPECT ictal de cada paciente com o grupo controle (SPM-indiv-ictal). Foram também comparadas as intensidades das alterações perfusionais nos lobos temporais procurando-se por um aumento da perfusão no SPECT ictal em relação ao interictal (SPM-indiv-ictal/inter). RESULTADOS: Não foi observada nenhuma alteração perfusional significativa no SPM-grupo-inter Já no SPM-grupo-ictal o foco epileptogênico foi a região de hiperperfusão mais significativa No SPM-indiv-inter a sensibilidade na localização do foco foi de 45% e no SPM-indiv-ictal a sensibilidade foi de 64%. O SPM-indiv-ictal/inter apresentou a maior sensibilidade para detectar o foco dentre as análises realizadas no SPM (77%) A sensibilidade do SPECT-visual-inter foi de 68% e para o SPECT-visuai-ictal foi de 100%. Por outro lado, diversas áreas de hiperperfusão e hipoperfusão à distância no SPECT ictal foram detectadas principalmente com o SPM CONCLUSÃO: O SPM é uma ferramenta que não depende do operador e é capaz de demonstrar mais áreas de alteração perfusional à distância do foco epileptogênico do que a análise visual. Ele pode ajudar a entender melhor a patofisiologia das crises epilépticas em pacientes com ELTM estudando a relação das diferentes regiões corticais e subcorticais na gênese e na propagação das crises parciais. Entretanto, essa ferramenta não acrescentou um aumento na sensibilidade na localização do foco epileptogênico em relação á análise visual, tanto do SPECT interictal quanto do SPECT ictal
Abstract: Statistical parametric mapping (SPM) is a quantitative tool which has been used in the brain perfusion SPECT (SPECT) However, few works in literature compare its sensitivity with the visual analysis in patients with temporal lobe epilepsy (TLE). PURPOSE: To investigate the capability of SPM analysis in SPECT to detect the epileptogenic focus and distant perfusion abnormalities in patients with mesial temporal lobe epilepsy (MTLE) and to compare these findings to the visual analysis. METHODS: Interictal and ictal SPECTs of 22 patients with refractory MTLE were performed. Epileptic foci were determined based on clinical history, magnetic resonance, electroencephalograms (EEG) and ictal video-EEG. SPECTs were submitted to visual analysis. Ictal and interictal SPECTs were analyzed together by the nuclear physicians (SPECT-visual-inter and SPECT-visual-ictal). It was also performed the SPM2 analysis which used a control group composed of 50 volunteers. The following comparisons were performed in SPM: interictal SPECT group with control group (SPM-group-inter); interictal SPECT from each patient with control group (SPM-indiv-inter); ictal SPECT group with control group (SPM-group-ictal), ictal SPECT from each patient with control group (SPM-indiv-ictal). It was also compared the perfusion intensity in temporal lobes looking for an increase in perfusion on ictal SPECT in relation to interictal SPECT (SPM-indiv-ictal/inter). RESULTS: No significant perfusion alterations were observed on SPM-group-inter. On the other hand, the epileptogenic temporal lobe was the region with most significant hypoperfusion on SPM-group-ictal. The sensitivity to localize the focus on SPM-indiv-inter was 45% and on SPM-indiv-ictal was 64%. The SPM-indiv ictal/inter revealed the highest sensitivity among the SPM analysis to detect the focus (77%). The sensitivity of SPECT-visual-inter was 68% and to SPECT-visual-ictal was 100%. On the other hand, several areas of distant hypoperfusion and hypoperfusion were detected mainly with SPM. CONCLUSION: SPM is a tool which does not depend on the operator and can detect more distant perfusion abnormalities than the visual analysis. It can improve the understanding of pathophysiology in seizures of patients with MTLE by studying the relation among different cortical and subcortical areas in the genesis and propagation of partial seizures. However, this tool did not increase the visual analysis sensitivity to localize the epileptogenic focus in interictal SPECT as well as in ictal SPECT
Doutorado
Neurologia
Doutor em Ciências Médicas
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Benini, Ruba Sayed. "GABAergic signalling in temporal lobe epilepsy." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111818.
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Earlier studies on temporal lobe epilepsy (TLE), by focusing on the anatomical and electrophysiological abnormalities of the hippocampus, have attributed a major role to this limbic structure in the process of epileptogenesis and seizure generation. Recently however, there has been increasing evidence from both animal and human studies that other limbic structures, including the subiculum, the entorhinal cortex (EC, perirhinal cortex (PC) as well as the amygdala, are possibly involved in the process of epileptogenesis. With the help of both acute and chronic models of limbic seizures, I have used an electrophysiological approach to gain more insight into the mechanisms through which these structures could participate in the establishment of hyperexcitable neuronal networks. Particularly, my investigations have focused on assessing the role played by the subiculum, the amygdala and the PC in epileptiform synchronization in vitro. My findings demonstrate that seizure-induced cell damage in chronically epileptic mice results in a change in limbic network interactions whereby EC ictogenesis is sustained via a reverberant EC-subiculum pathway ( Chapter 1). Furthermore, I have discovered that the subiculum, which holds an anatomically strategic position within the hippocampus, is capable of gating hippocampul output activity via a GABAA-receptor mediated mechanism (Chapter 2). My investigations in the amygdala have confirmed that this limbic structure contributes to epileptiform synchronization (Chapter 3). Moreover, using a chronic rat model of TLE, I have found novel evidence suggesting that alterations in inhibitory mechanisms play a role in the increased excitability of the lateral amygdalar nucleus (Chapter 4). Finally, my studies in chronically epileptic rats have also led to preliminary data signifying hyperexcitability of the PC as well alterations in the interactions between the amygdala and this cortical structure (Chapter 5).
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Buck, Sarah. "Memory in paediatric temporal lobe epilepsy." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10057610/.
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Temporal lobe epilepsy (TLE) is a common form of epilepsy and is frequently associated with memory and learning impairments. Medically intractable and lesion-based TLE occurs in 20-30% of the patients, in which case a surgical intervention is proposed. However, there is a clear gap in knowledge about pre-operative memory status in children undergoing surgery and post-operative memory outcome. It is unclear whether paediatric patients show material-specific memory impairments associated with side of pathology and whether specific memory processes are affected more than others, i.e. learning, recall and recognition. Lastly, as opposed to language lateralisation, the neural representation of memory is unknown and memory fMRI has never been explored in paediatric TLE. The aim of this project is therefore to investigate the hippocampal-neocortical network that is at risk of compromise given learning and recall deficits in paediatric TLE at the pre-operative level in order to contribute to the prediction of outcome after surgery. I developed a neuropsychological protocol and a neuroimaging protocol for the investigation of pre-operative memory functions. The neuropsychological protocol is a tablet-based version of a paired-associate learning paradigm that allows comparisons between verbal and non-verbal memory. I validated this protocol in normally-developing children (N=130, 8-18 years). The neuroimaging protocol is a combined language and memory fMRI task that allows the investigation of the interaction between the two networks within one scanning session. This protocol was also validated in normally-developing children (N=28, 8-18 years). The feasibility of these protocols for clinical assessments was explored in a representative sample of children with TLE who were being considered for surgery (N=6, 12-18 years). These protocols add value to the diagnosis of memory impairments associated with paediatric TLE and provide a better understanding of pre-operative memory profile at the individual level. The findings also contribute towards the use of memory fMRI in the surgical decision-making process. Combining information from these protocols could provide prognostic indicators of outcome after surgery.
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Morgan, Lisa. "Social cognition in temporal lobe epilepsy." Thesis, University of East London, 2011. http://roar.uel.ac.uk/3675/.
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This study addressed social cognition in patients with temporal lobe epilepsy (TLE). Social cognition encompasses a range of functions, for example, those requiring the attribution of emotional states, and those requiring mental state inferences to be made ('theory of mind'). The area of social cognition has evolved from developmental explanations of theory of mind, which have been extrapolated for their empirical application to adult populations, often using neuroimaging and neuropsychological paradigms. The present study may help to raise awareness of social cognitive difficulties in TLE and may inform clinical neuropsychological assessment protocols. A feature of the existing literature is the lack of consistency in methodologies. This study drew upon methodology described in previous relevant studies in order that findings were more comparable. A range of standardised measures of general intellectual functioning, verbal and visual memory, and verbal and nonverbal executive function tasks were administered alongside social cognition tasks, assessing recognition of emotional expressions, attributing mental states to eyes, attributing mental state inferences in stories and cartoons, and detecting and describing violations of social etiquette. A group of 25 patients with TLE were compared with 42 typically developed and intact (TDI) participants matched for age, education and general abilities. The TLE group scored lower on all social cognition measures, but in the context of similar difficulties in visual and verbal memory, and verbal aspects of executive functioning. There were no significant effects of laterality (hemispheric focus of the TLE). Variables influencing performance on social cognition tasks were examined. The results are discussed in terms of the relevant literature and possible underlying mechanisms of difficulties, and recommendations for future research made on this basis.
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Sidhu, M. K. "Episodic memory in temporal lobe epilepsy." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1471130/.
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Individuals with temporal lobe epilepsy (TLE) have significant material specific episodic memory impairments with greater verbal and visual memory deficits accompanying left and right TLE respectively. More recently, however, widespread cognitive deficits have been described in patients with TLE in keeping with morphological and functional abnormalities that extend beyond the temporal lobes. Functional magnetic resonance imaging (fMRI) has demonstrated reorganisation of memory encoding networks within the temporal lobe in TLE, but little is known of the extra-temporal networks in these patients. Memory fMRI as a tool for predicting memory decline after anterior temporal lobe resection has been explored but a clinically applicable algorithm has yet to be defined. Fewer studies have described the changes in the memory encoding networks after temporal lobe surgery. This thesis presents methodological developments and novel applications to describe the pre-operative and post-operative verbal and visual memory networks in those with unilateral TLE. Pre-operatively, I investigated extra-temporal areas of memory reorganisation in left and right TLE patients, quantitatively compared to healthy controls. Novel findings include the ‘efficiency’ of extra-temporal reorganisation to successful memory formation. Next, using clinical parameters such as age at onset of epilepsy, epilepsy duration and seizure frequency as continuous regressors, I described the factors affecting verbal and visual memory reorganisation in TLE. In a separate pre-operative study, I used an alternative fMRI analysis method, multi-voxel pattern analysis (MVPA) that focuses on the patterns of activity across voxels 4 in specific brain regions that are associated with individual memory traces. I used MVPA-fMRI to assess the functional integrity of the hippocampi and other medial temporal lobe structures in patients with unilateral TLE. Next, I explored the predictive ability of temporal and extra-temporal activations in predicting post-operative verbal memory decline in left and right TLE patients and described a method of using memory fMRI as a clinically applicable tool in patients who had anterior temporal lobe resection. Finally, I explored memory encoding network plasticity four and 12 months after anterior temporal lobe resection. In this study, controls were also scanned at similar time intervals to patients. I report for the first time, dynamic changes in the memory encoding network four and 12 months after surgery, relative to changes in controls. Novel findings also include the efficiency of these post-operative networks. In this thesis, I also discuss methodological constraints, clinical applications and future directions.
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Testa, S. Marc. "DEPRESSIVE SYMPTOMS IN TEMPORAL LOBE EPILEPSY." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin997801556.
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Arcot, Desai Sharanya. "Multielectrode microstimulation for temporal lobe epilepsy." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/50384.
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Multielectrode arrays may have several advantages compared to the traditional single macroelectrode brain electrical stimulation technique including less tissue damage due to implantation and the ability to deliver several spatio-temporal patterns of stimulation. Prior work on cell cultures has shown that multielectrode arrays are capable of completely stopping seizure-like spontaneous bursting events through a distributed asynchronous multi-site approach. In my studies, I used a similar approach for controlling seizures in a rat model of temporal lobe epilepsy. First, I developed a new method of electroplating in vivo microelectrode arrays for durably improving their impedance. I showed that microelectrode arrays electroplated through the new technique called sonicoplating, required the least amount of voltage in current controlled stimulation studies and also produced the least amplitude and duration of stimulation artifact compared to unplated, DC electroplated or pulse-plated microelectrodes. Second, using c-fos immunohistochemistry, I showed that 16-electrode sonicoplated microelectrode arrays can activate 5.9 times more neurons in the dorsal hippocampus compared to a single macroelectrodes while causing < 77% the tissue damage. Next, through open-loop multisite asynchronous microstimulation, I reduced seizure frequency by ~50% in the rodent model of temporal lobe epilepsy. Preliminary studies aimed at using the same stimulation protocol in closed-loop responsive and predictive seizure control did not stop seizures. Finally, through an internship at Medtronic Neuromodulation, I worked on developing and implementing a rapid algorithm prototyping research tool for closed-loop human deep brain stimulation applications.
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Petty, Karen Hammack. "Pediatric temporal lobe epilepsy versus frontal lobe epilepsy : how does cognitive performance differ ? /." Full text available from ProQuest UM Digital Dissertations, 2007. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1414130851&SrchMode=1&sid=2&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1221160824&clientId=22256.
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Kemper, Birgit. "Neuropsychologische Untersuchung bei Frontallappenepilepsien ein Vergleich kognitiver Leistungen zwischen Patienten mit Frontal- und Temporallappenepilepsie im Rahmen der prächirurgischen Diagnostik /." Münster : Universität Münster, 1995. http://catalog.hathitrust.org/api/volumes/oclc/64528329.html.
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Sheilabi, Marim Abdelghani. "Studies of biomarkers in temporal lobe epilepsy." Thesis, Sheffield Hallam University, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713507.
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Purpose: Refractory temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) affects about 30% of TLE patients, where antiepileptic drugs are not effective in controlling seizures. These patients become candidates for surgical treatment which is effective in only 60-70% of cases. In addition, surgical treatment causes memory and cognitive impairments as well as psychopathological disturbance. Therefore, the aim of this study is to investigate potential biomarkers in surgically resected sclerotic TLE-HS (n = 49) and non-spiking superior temporal gyrus samples (TLE-STG; n = 25) from TLE patients and post-mortem hippocampi (PMC; n = 10), in order to increase our understanding of refractory TLE pathophysiology and help in identifying new potential drug targets for treatment of TLE patients. Methods: GABAb receptor subunits were investigated in TLE-HS, TLE-STG and PMC tissue by quantitative real time polymerase chain reaction (qRT-PCR) and quantitative western blot (WB) techniques. Alterations in expressions of SGK1, SCN4B, IP3R1 and SYNPR were investigated in TLE-HS, TLE-STG and PMC specimens by qRT-PCR and WB. The transcriptome profiling of TLE-HS, TLE- STG and PMC samples was done by microarray analysis (MA). MA was followed by functional annotation clustering analysis (FAC) of the MA differentially expressed genes (DEGs). Genes from FAC analysis were further investigated by qRT-PCR. MA Aquaporin (AQP1, 3, 4, 5, 8, 9, 11) expressions were further validated by qRT-PCR. Results: Expression of the inhibitory GABAB2 receptor subunit was significantly up regulated in TLE-HS compared to PMC but its expression was reduced in TLE-HS compared to TLE-STG.The expression of SCN4B, IP3R1 and SYNPR, which are involved in regulating neuronal excitability, were significantly reduced in TLE-HS compared to TLE-STG and were significantly increased compared to PMC. The expression of SGK1 mRNA was significantly increased in TLE-HS compared to both TLE-STG and PMC. MA analysis revealed 1821 genes were significantly up regulated and 1511 genes were significantly down regulated in TLE-HS compared to TLE-STG and PMC. The first cluster from FAC analysis of DEGs showed that the up regulated inflammatory genes such as cytokines had the highest enrichment score. The qRT-PCR data showed that expression of IL-13, IL-18, Fas, ICAM-1, CCL2, CCL4, CXCL1, CXCL2, CXCL12, CXCR4 and CX3CR1 were significantly higher in TLE-HS compared to TLE-STG and PMC therefore validating MA data. AQP1 and -4, which are involved in water homeostasis, were significantly up regulated in TLE-HS compared to TLE-STG. AQP11 expression was significantly reduced in TLE-HS while AQP3, -5, -8 and -9 were not significantly altered in TLE-HS compared to TLE-STG and PMC. Discussion: The significant dysregulation of biomarker expression investigated in this study indicate that different biological processes such as neuronal excitability, neuronal and astrocytic energy metabolism, neurogenesis, apoptosis, neuroinflammation, intracellular calcium and water homeostasis are affected in the epileptogenic TLE-HS tissue. These biomarkers seem to be associated with TLE-HS pathophysiology. Furthermore, they highlight the role of neuronal, astrocytic, microglia and endothelial cell dysfunction in TLE-HS pathology. In conclusion, the biomarkers investigated increased our understanding of biological processes affected in TLE-HS pathophysiology and they represent potential drug targets for refractory TLE-HS. However, further research is still needed to understand the temporal and spatial changes of those genes and their proteins during TLE.
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Browne, Georgina Emily. "Nonverbal memory assessment in temporal lobe epilepsy." Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429590.
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Gibb, Catherine Elizabeth. "Temporal lobe epilepsy : the effects on language." Thesis, University of Newcastle Upon Tyne, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362519.
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Bonelli-Nauer, S. B. "Cognitive functional MRI in temporal lobe epilepsy." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1455537/.
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Anterior temporal lobe resections (ATLR) provide an effective treatment option for patients with medically refractory temporal lobe epilepsy (TLE) rendering up to 70% of them seizure free. The goal of epilepsy surgery is to remove the brain areas generating the seizures without causing neuropsychological deficits such as language or memory dysfunction. Furthermore up to 60% of patients with TLE suffer from emotional disturbances following surgery. The principle aim of the work presented in this thesis was to improve presurgical evaluation of patients with TLE by using cognitive functional MRI (fMRI) to non-invasively localise brain areas that are essential for processing cognitive function such as language and memory function and emotional and social behaviour. 150 consecutive patients and 40 healthy controls were included in our experiments. Different fMRI paradigms for the evaluation of cognitive functions have been implemented on a 3 Tesla scanner. All subjects underwent language and memory fMRI and standard neuropsychological assessment; those patients who proceeded to have temporal lobe surgery were reinvestigated 4 months following ATLR. We studied the efficiency of reorganisation of language and memory function due to the underlying disease and in particular following ATLR. Amygdala fMRI was used to investigate potential implications on emotional and social outcome. A major part of the work included in this thesis has concentrated on the use of fMRI for the exploration and prediction of postoperative complications such as language and memory impairment but also emotional disturbances. When used in concert with other MR imaging modalities the results of these methods can be used to improve surgical strategies tailored to individual patients with regard to functional outcome, by virtue of definition of epileptic cerebral areas that need to be resected and eloquent areas that need to be spared.
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Fischer, Mark. "Working Memory Intervention in Temporal Lobe Epilepsy." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447689793.
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Gonçalves, Eleonora Borges. "Transtornos depressivos em pacientes com epilepsia do lobo temporal mesial, refratários às drogas antiepiléticas." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309277.
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Orientador: Fernando CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivos: Avaliar os transtornos depressivos em comorbidade com a epilepsia do lobo temporal (ELT), em pacientes com crises refratárias às drogas antiepilépticas (DAEs). Pacientes e métodos: Realizamos um estudo transversal, entrevistando e coletando informações dos prontuários de pacientes que procuraram atendimento no Ambulatório de epilepsia de difícil controle do HC-UNICAMP. A população foi de adultos, com idade igual ou maior de 24 anos, em acompanhamento no HC-UNICAMP, com diagnóstico de ELT refratária, em uso adequado da medicação instituída e ausência de rebaixamento intelectual, demência ou problemas de linguagem. Os pacientes foram submetidos a uma entrevista psiquiátrica semiestruturada, o que conferiu diagnóstico segundo a Classificação Internacional de Doenças (CID-10)-OMS. Aplicamos os seguintes instrumentos: (1) Mini Entrevista Neuropsiquiátrica Internacional (MINI) e (2) Inventário de Depressão de Beck (IDB). Resultados: Foram incluídos 40 pacientes com idade de 24-60 anos, trinta e um dos 40 pacientes (77,5%) apresentaram transtornos depressivos: 14 (45,2 %) com distimia, 11 (35,5%) com transtorno depressivo recorrente e 6 (19,3%) com transtorno bipolar, na ocasião depressivo. Dois (5%) apresentaram transtorno misto de ansiedade e depressão. Os outros 7 pacientes (15%) apresentaram eventuais manifestações de depressão e ansiedade, sem constituírem um diagnóstico de depressão, sendo um deles com transtorno orgânico de ansiedade. Apenas 8 dos 31 pacientes (25,8%) receberam tratamento antidepressivo satisfatório prévio. A duração da epilepsia apresentou uma tendência a ser maior nos pacientes com transtorno depressivo (p=0.10); não houve associação entre depressão e frequência de crises. Conclusões: Este trabalho confirma que o transtorno depressivo é frequente e subdiagnosticado em pacientes com ELTM refratária às DAEs. A duração da epilepsia apresenta uma tendência a ser maior nos pacientes deprimidos. Não houve associação entre depressão e frequência de crises
Abstract: Objectives: To assess depressive disorders in patients with temporal lobe epilepsy (TLE), refractory to antiepileptic drugs (AEDs). Patients and methods: We performed a cross-sectional study, interviewing and collecting information from records of patients who sought treatment at the Epilepsy Clinic of the HC-UNICAMP. The population consisted of adults aged greater than 24 years followed at UNICAMP, diagnosed with refractory TLE, in appropriate use of AEDs and lack of established mental retardation, dementia or language problems. Patients underwent a semi-structured psychiatric interview, which gave diagnosis according to the International Classification of Diseases (CID-10) - WHO. We applied the following instruments: (1) Mini International Neuropsychiatric Interview (MINI) and (2) the Beck Depression Inventory (BDI). Results: There were 40 patients aged 24-60 years. Thirty-one of these (77.5%) had depressive disorders: 14 (45.2%) with dysthymia, 11 (35.5%) with recurrent depressive disorder and 6 (19.3%) with bipolar disorder who had depression at the time of evaluation. Two (5%) had mixed anxiety disorder and depression. The other 7 patients (15%) showed signs of depression and anxiety, without imposing a diagnosis of depression, one of them with organic anxiety disorder. Only 8 of the 31 patients (25.8%) had received prior satisfactory antidepressant treatment. The duration of epilepsy tended to be higher in patients with depressive disorder (p = 0.10). There was no association between depression and seizure frequency. Conclusions: This study confirms that depressive disorder is common and underdiagnosed in patients with TLE refractory to AEDs. The duration of epilepsy had a tendency to be higher in depressed patients. There was no association between depression and seizure frequency
Doutorado
Neurologia
Doutora em Ciências Médicas
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Lippincott, Cynthia E. Williams J. Michael. "An investigation of extra-temporal deficits in temporal lobe epilepsy /." Philadelphia, Pa. : Drexel University, 2010. http://hdl.handle.net/1860/3269.
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Santos, Renato Oliveira dos. "Investigando o papel de genes candidatos na epilepsia do lobo temporal mesi = genes PTPRM e IL1B = Investigating candidates genes in mesial temporal lobe epilepsy : PTPRM and IL1B genes." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312709.
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Orientadores: IÍscia Teresinha Lopes Cendes, Cláudia Vianna Maurer-MorelliTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: As epilepsias formam um grupo de doenças neurológicas crônicas caracterizadas por crises epilépticas, as quais podem ser definidas como um distúrbio intermitente do sistema nervoso causado por descarga elétrica anormal, súbita e sincronizada dos neurônios cerebrais. A epilepsia de lobo temporal (ELT) é a mais frequente, representando aproximadamente 50% dos casos em adultos e tem como manifestação típica, a crise parcial complexa. Além disso, é frequentemente refratária ao tratamento medicamentoso. Os principais sintomas gerados pela ELT são predominantemente pelo acometimento das estruturas mediais do lobo temporal, sendo a ELT mesial (ELTM), a forma mais comum de ELT. Atualmente é ainda controversa a participação de fatores genéticos contribuindo na etiologia das epilepsias, principalmente da ELTM, que não teve até hoje nenhum gene inequivocamente associado a sua predisposição. O objetivo deste trabalho foi investigar o papel de dois genes candidatos: o PTPRM e o IL1B na predisposição à ELTM. Para tanto utilizamos as seguintes modalidades de estudo em pacientes com ELTM (i) estudo de associação genética através da genotipagem de polimorfismos de nucleotídeo único (SNPs) localizados nos referidos genes candidatos (esta etapa do estudo foi realizada durante o mestrado); (ii) quantificação dos transcritos de ambos os genes, por PCR em tempo real em tecido das estruturas mediais do lobo temporal (principalmente hipocampo) que foi obtido através da realização de cirurgia para tratamento das crises refratárias. (iii) Para o PTPRM, foi também realizada a localização do transcrito pela técnica de hibridação "in situ" em tecido hipocampal de pacientes e de controle. Além disso, como existem evidências do envolvimento do PTPRM em etapas importantes do desenvolvimento cerebral, e pouco se conhece da função específica desse gene no cérebro realizamos (iv) a quantificação do transcrito de PTPRM durante o desenvolvimento em cérebro de camundongos. (v) Finalmente, com o objetivo específico de avaliar se o aumento de expressão de IL1B no tecido hipocampal se refletia também na circulação realizamos a quantificação do transcrito e proteica do IL1B no plasma de pacientes com ELTM. Nossos resultados revelaram associação genética entre SNPs localizados em ambos os genes investigados e o fenótipo estudado. No entanto, em nenhum dos estudos uma variante funcional pode ser identificada. A quantificação dos transcritos em tecido hipocampal dos pacientes com ELTM indicou que ambos os genes PTPRM e IL1B estão hiper-regulados em pacientes quando comparados ao tecido controle. Não identificamos variação significativa na expressão do transcrito de PTPRM no cérebro de camundongos nas diferentes etapas de desenvolvimento. Não identificamos variação significativa na quantificação do transcrito e proteica de IL1B no plasma dos pacientes com ELTM quando comparados aos controles. Em conclusão, nossos resultados dos estudos de associação indicam um papel de PTPRM e de IL1B na predisposição à ELTM, porém não fomos capazes de encontrar uma variante funcional associada ao fenótipo. Corroborando o papel de ambos os genes nosso estudo de expressão gênica no tecido acometido indicou um aumento de expressão de ambos os genes. No entanto, o aumento de expressão de IL-1beta no tecido hipocampal não se traduziu pelo aumento no plasma dos pacientes. Finalmente, nosso estudo do perfil de expressão de PTPRM durante o desenvolvimento cerebral não aponta para um papel desse gene em etapas específicas do desenvolvimento
Abstract: The epilepsies are a group of chronic neurological disorders characterized by seizures, which can be defined as an intermittent disorder caused by an abnormal and sudden electrical discharge of neurons in the brain. Temporal lobe epilepsy (TLE) is the most frequent form, representing approximately 50% of cases in adults, and it is often refractory to drug treatment. The main symptoms in TLE are generated by the involvement of the medial temporal lobe structures, characterizing mesial TLE (MTLE). The contribution of genetic factor to MTLE it is still controversial and to date, no gene has been unequivocally associated with the predisposition to MTLE. Therefore, the aim of this study was to investigate the role of two candidate genes: PTPRM and IL1B in the predisposition to MTLE. To achieve this we use the following type study modalities in patients with MTLE (i) genetic association study by genotyping of single nucleotide polymorphisms (SNPs) located in these two candidate genes; (ii) quantification of the transcripts of both genes by real-time PCR in hippocampal tissue obtained from epilepsy surgery for the treatment of refractory seizures. (iii) For PTPRM we also performed in situ hybridization experiments in order to localize the transcript in hippocampal tissue from patients and controls. Furthermore, since there is evidence that PTPRM could be involved in key stages of brain development and little is known about the specific role of this gene in the brain, we performed (iv) quantification of its transcript during development in mouse brain. (v) Finally, with the specific objective of assessing whether the increase of IL1B expression in hippocampal tissue was also seen outside the central nervous system we quantified IL1B transcript and protein in plasma of patients with MTLE. Our results revealed genetic association between SNPs located in both genes and the phenotype. The quantification of transcripts in hippocampal tissue of patients with MTLE indicated that both genes are hyper-regulated when compared to control tissue. We did not find any significant variation in transcript expression of PTPRM in mouse brain during developed. In addition, no difference in transcript expression and protein levels of IL1B was observed in plasma of patients with MTLE. In conclusion, our results indicate an involvement of PTPRM and IL1B in the predisposition to MTLE; however, we are unable to find a functional variant associated with the phenotype. Corroborating the role of both genes in MTLE gene expression in affected tissue (hippocampus) indicated an up-regulation of both genes. However, the increase in IL1B expression in hippocampal tissue was not reflected by an increase of transcript or protein in plasma of patients with MTLE. Finally, our expression profile of PTPRM during brain development does not point to a role for this gene in specific stages of development
Doutorado
Fisiopatologia Médica
Doutora em Ciências
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Campos, Bruno Augusto Goulart 1980. "Estudo dos concentrações de N-Acetil Aspartano na espectroscopia por ressonancia magnetica em pacientes com epilepsia de lobo temporal : correlação com resposta ao tratamento clinico." [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309293.
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Orientador: Fernando CendesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Objetivos: Comparar as medidas relativas de N-Acetil Aspartato (NAA) em pacientes com epilepsia do lobo temporal (ELT) entre aqueles com resposta adequada a primeira droga anti-epiléptica (DAE) com aqueles que não responderam a primeira DAE, requerendo outra monoterapia ou politerapia. Métodos: Nós estudamos 27 indivíduos no grupo-controle, 25 pacientes com ELT com resposta a primeira DAE (grupo-resposta) e 21 que não responderam a primeira DAE (grupo-falência) e que eram regularmente acompanhadas no nosso serviço de epilepsia. Todos foram submetidos a estudo por imagem e espectroscopia pela RNM e a razão NAA/Creatina foi calculada. Resultados: A razão NAA/Creatina foi testada por análise de variância (ANOVA) entre os grupos, mostrando uma significativa redução tanto no hipocampo ipsilateral quanto no contralateral relacionado ao EEG (p<0,001 e p=0,021 respectivamente). A análise post hoc não mostrou diferença significativa entre o grupo-resposta e o grupo-controle, mas com diferença entre o grupo-falência e os outros grupos. A análise individual mostrou uma redução maior que dois desvios-padrão abaixo da média dos controles em nove dos 21 (42,8%) pacientes no grupo-falência, mas em nenhum dos pacientes no grupo-resposta. Discussão: Nosso trabalho mostrou uma redução significativa na razão NAA/Cre no grupo com falência à primeira DAE, mas não no grupo com que apresentou resposta à primeira DAE comparado aos indivíduos do grupo controle. Estes resultados indicam que pacientes com ELT com resposta à primeira DAE têm menos evidência de dano ou disfunção neuronal/axonal comparado a aqueles refratários a primeira DAE.
Abstract: Purpose: To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of AED (an important prognostic factor) to TLE patients who failed the first AED trial and required further AED trials with monotherapy or polytherapy. Methods: We studied 27 individuals in control-group, 25 TLE patients who responded to the first AED (response-group) and 21 who did not (failure-group) that were regularly seen at our Epilepsy Service. They were submitted to both MRI and proton spectroscopy, and NAA/Creatine ratio calculated. Results: ANOVA of NAA/Cre demonstrated significant reduction in both ipsilateral and contralateral hippocampus related to EEG focus (p<0.001 and p=0.021), and post hoc analysis of ipsilateral and contralateral hippocampus did not reach statistic significance between response-group and control-group, but we found difference between failuregroup and the others groups. Individual analysis showed NAA/Cre ratios lower than 2 SD below the mean of controls in nine of 21 (42.8%) patients in the first AED failure group (six with unilateral and three with bilateral NAA/Cre reduction) but in none of patients who responded to first AED. Discussion: Our study demonstrated observed in refractory and mild TLE patients with HA. These results indicates that patients with TLE who respond well to first AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to first AED.
Mestrado
Neurociencias
Mestre em Fisiopatologia Médica
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Bilevicius, Elizabeth. "Análise de fatores relacionados à resistência ao tratamento com drogas anti-epilepticas em epilepsia de lobo temporal mesial." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309306.
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Orientadores: Fernando Cendes, Íscia Lopes-CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O objetivo foi realizar uma análise multifatorial dos aspectos clínicos e de ressonância magnética (quantitativos e qualitativos) relacionados à resistência ao tratamento com drogas anti-epilépticas (DAES) em pacientes com epilepsia de lobo temporal mesial e melhor caracterizar o grupo de resposta intermediário a DAES, aqui denominado remitente-recorrente. Foram incluídos 165 pacientes e divididos em 3 grupos de acordo com a resposta medicamentosa: 50 respondedores (31 mulheres) , 87 não respondedores ao uso de DAES (53 mulheres) e 28 remitentes-recorrentes (17 mulheres) . Estes foram avaliados quanto à idade, freqüência de crises e idade no início destas, presença de crises febris, presença e lateralidade da atrofia hipocampal à análise visual, fatores precipitantes e DAES utilizadas. A quantificação dos volumes hipocampais foi realizada através de volumetria manual pelo software DISPLAY e as comparações dos volumes médios de ambos os hipocampos foi realizada entre os 3 grupos e 30 controles sadios por ANOVA. As imagens de ressonância magnética também foram avaliadas através da técnica de Morfometria Baseada em Voxel (VBM) com o software SPM 5 (Statistical Parametric Mapping)/MATLAB 7.7.0, comparando os três grupos com 75 indivíduos normais e entre si através de Teste -T. Observamos que idade de início das crises foi menor (p=0,005) e a freqüência das crises ao início foi maior (p=0,018) em farmacorresistentes quando comparado aos outros 2 grupos. As DAES mais utilizadas foram a carbamazepina e o clobazam (em associação) em todos os grupos. As doses de carbamazepina utilizadas foram maiores em farmacorresistentes (p<0,001) e remitentes-recorrentes (p=0,02) em comparação aos responsivos. Em relação ao clobazam, observamos dose significativamente maior somente nos farmacorresistentes em comparação aos outros dois grupos (p=0,017). A comparação da média dos volumes hipocampais entre os 3 grupos e controle evidenciou diferenças somente entre farmacorresistentes e controles bilateralmente (esquerda ,p = 0,004; direita, p=0,02). A análise por VBM evidenciou atrofia de substância cinzenta em todos os grupos. No grupo farmacorresponsivo tal atrofia foi mais restrita a áreas ipsilaterais ao foco epileptigênico, ao passo que nos grupos farmacorresistente e remitente-recorrente esta atrofia apresentou-se mais difusa. A comparação entre os grupos evidenciou as seguintes áreas com maior redução de substância cinzenta nos grupos farmacorresistente e remitenterecorrente quando comparados aos farmacorresponsivos: frontal periorbital bilateral (p<0,01), cíngulo (p<0,05) e temporal contralateral ao foco epileptogênico (p<0,05). Desta forma, observamos que embora as características clínicas demonstrassem mais similaridades entre os grupos respondedor e remitente-recorrente, a análise de VBM mostrou redução de substância cinzenta mais difusa em farmacorresistentes e remitentesrecorrentes. Assim pudemos observar que as variáveis clínicas relacionadas ao pior prognóstico foram idade e freqüência de início de crises. Em relação às variáveis estruturais, embora a atrofia de substância cinzenta (SC) se apresentasse mais difusamente em pacientes de pior resposta medicamentosa, também ocorre em áreas extra-hipocampais e mesmo extratemporais em pacientes considerados farmacorresponsivos mesmo que ipsilateralmente ao foco epileptogênico. Por último, conseguimos caracterizar clínica e estruturalmente o grupo remitente-recorrente, observado na prática clínica, porém até então muito pouco reconhecido na literatura
Abstract: The objective of the present work was to investigate the relationship between brain MRI and clinical characteristics and patterns of antiepileptic drug (AED) response in patients with mesial temporal lobe epilepsy (MTLE).In order to do that,one hundred sixty five MTLE patients were divided into seizure-free with AED (50 AEDresponders, 31 women), 87 pharmacoresistants (53 women), and 28 remitting-relapsing seizure control group (17 women). All groups were evaluated regarding age, frequency of seizures and age at epilepsy onset, duration of epilepsy, febrile seizures (FS), presence and side of hippocampal atrophy on visual inspection (HA), initial precipitating injuries (IPIs), type and quantity of AEDS used. The right and left hipoccampi from 99 patients belonging to all three groups (43 pharmacoresistants, 31 pharmacoresponsive and 25 remitting-relapsing subjects). were submitted to manual morphometry by DISPLAY software (Brain Imaging Centre, Montreal, Canada) as well as hipoccampi selected from 30 healthy controls. The calculated mean from those hipoccampi were compared within subjects and with controls. For gray matter (GM) MRI voxel-based morphometry (VBM) we selected only patients with unilateral HA on visual MRI analysis (n=100). Comparisons were made between all groups and 75 healthy controls. Age at epilepsy onset was lower (p=0,005) and initial frequency of seizures was higher in pharmacoresistants compared with the other two groups (p=0,018). The most used AEDS were carbamazepine and clobazam (always in association). The highest carbamazepine dose was observed in pharmacorresistants (p<0,001) and remitting-relapsing group (p=0,02). The highest dose of clobazam occurred only in pharmacoresistant group (p=0,017). The comparison between the mean hippocampi volumes from three groups and controls showed differences only on the pharmacoresistants left (p=0,004) and right(p=0,02) hippocampus comparing to controls. All groups showed GM atrophy compared to controls in ipsilateral hippocampus, bilateral parahippocampal gyri, frontal, occipital, parietal and cerebellar areas. In the AED-responders group such findings were more restricted to areas ipsilateral to the epileptic focus and more widespread in pharmacoresistants and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in pharmacoresistants and remitting-relapsing compared with AED-responders in bilateral periorbital frontal (p< 0,01), cingulum (p<0,05), and temporal lobe contralateral to the epileptic focus (p< 0,05). We may conclude that, pharmacoresistants and remittingrelapsing patients presented a similar pattern of GM atrophy which was more widespread compared with AED-responders on VBM. We could also observe that age at epilepsy onset was lower (p=0,005) and initial seizure frequency was higher in pharmacoresistants
Doutorado
Neurociencias
Doutor em Ciências
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Riano, Barros Daniela Alexandra. "PET studies of neurotransmission in temporal lobe epilepsy." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/25001.
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Introduction: Epilepsy, defined as the recurrence of unprovoked seizures, is one of the commonest serious conditions in neurology. The World Health Organisation (WHO) estimates a prevalence of 50 million people worldwide, with a temporal lobe focus being the commonest cause of complex partial seizures. Patients with temporal lobe epilepsy (TLE) often have reduced GABAA receptors at their seizure focus, and poor memory performance. Blockade of GABAA receptors containing alpha5 subunits is promnestic. Animal models have also demonstrated alterations in cannabinoid type 1 (CB1) receptor availability in response to seizures. The studies presented in this thesis were designed to first determine the reliability of measurement with two novel PET tracers for the expression of alpha5 subunits of GABAA receptors ([11C]Ro15 4513) and CB1 receptors ([11C]MePPEP). These were then used in human TLE to try and elucidate mechanisms of memory impairment and minimally invasive characterisation of the seizure focus. Methods: Adult healthy volunteers underwent paired scans with [11C]Ro15 4513 (GABAA alpha5 receptor partial inverse agonist) and [11C]MePPEP (CB1 receptor mixed inverse agonist and antagonist). Test-retest variability was characterised for both radiotracers with quantification in regions spanning high and low receptor concentrations by regional compartmental modelling and a variety of regional and voxel-wise model-free analyses (spectral analysis and variants). Semiquantification with modified standard uptake values (mSUVs), in widespread clinical use, was also explored. In the clinical studies, healthy volunteers were compared with TLE patients using Statistical Parametric Mapping software. Paired post-ictal and interictal studies were obtained with [11C]MePPEP to determine changes in response to seizures. Single PET scans were obtained with [11C]Ro15 4513 to determine changes in relationship to memory impairments. Results: [11C]Ro15 4513 could be reliably quantified with voxel-wise spectral analysis, and the simplified reference tissue model, but not mSUVs or compartmental models. For [11C]MePPEP, voxel-wise spectral analysis, a one tissue compartment model and simple mSUVs were the most reliable methods in controls, while preserving between-region differences. CB1 availability in TLE was higher, at the group level, in the ipsilateral temporal lobe in post- ictal scans than in controls, and negatively correlated with time since last seizure. In individual patients, however, focal increases were not consistently found in the epileptogenic temporal lobe. [11C]Ro15 4513 scans could be obtained in 12 patients but have not yet been fully analysed. Discussion: I demonstrated that two novel PET tracers can be reliably quantified, using a much larger cohort and a much greater variety of methods than available in the literature in the case of [11C]MePPEP, and performing such an analysis for the first time for [11C]Ro15 4513. This laid the foundation for the clinical study of CB1 receptor availability in TLE patients. The hypothesis of an upregulation of this inhibitory G-protein coupled receptor type in response to single spontaneous seizures could be confirmed, but the method was not so far useful in individual patients. [11C]Ro15 4513 PET holds promise for the investigation of the mechanisms of memory impairment in TLE.
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Tang, Yuang. "Detection and Suppression of Mesial Temporal Lobe Epilepsy." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1323464608.
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Fukao, Kenjiro. "Magnetoencephalographic Characteristics of Psychosis in Temporal Lobe Epilepsy." Kyoto University, 2009. http://hdl.handle.net/2433/124338.
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Mitsueda, Takahiro. "Amygdalar enlargement in patients with temporal lobe epilepsy." Kyoto University, 2011. http://hdl.handle.net/2433/142541.
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Rodrigues, Claudimar Amaro de Andrade. "Expressão gênica das subunidades e subtipos de receptores para neurotransmissores excitatórios e inibitórios no Complexo Basolateral de Amígdala de pacientes com Epilepsia Intratável do Lobo Temporal Mesial (ELTM)." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17137/tde-10012017-093358/.
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Introdução: A epilepsia é uma doença de grande relevância médica e social, trazendo grande impacto aos pacientes e a sociedade como um todo. A Epilepsia do Lobo Temporal Mesial (ELTM) é a epilepsia refratária mais prevalente, tendo em sua causalidade o impacto do desequilíbrio entre circuitos neuronais excitatórios e inibitórios, necessitando da remoção cirúrgica das estruturas alteradas e da interrupção das suas vias para melhor controle das crises e qualidade de vida dos pacientes. Objetivo: Buscando ampliar o esclarecimento do papel da amígdala junto as modificações intrínsecas nos receptores de neurotransmissores e em suas subunidades nos mecanismos de ictogênese e epileptogênese, possibilitando o aprimoramento das técnicas cirúrgicas atualmente empregadas, além de novas modalidades terapêuticas, o presente estudo analisou as expressões gênicas das subunidades de receptores excitatórios, NMDA (NR2C e NR3A, genes GRIN2C e GRIN3A), Cainato (GluK1 e GluK2, genes GRIK1 e GRIK2), e subunidade de receptor inibitório GABAA (?4 e ?5, genes GABRA4 e GABRA5) e subtipos de receptor de neuropeptídio Y (Y2 e Y5, com genes NPY2R e NPY5R), em núcleos basolaterais de amígdalas humanas de pacientes com ELTM. Material e Métodos: Foram utilizados fragmentos de amígdala de 20 pacientes que fizeram amigdalohipocampectomia junto ao Serviço de Neurocirurgia do HC-FMRP-USP, sendo 10 pacientes com controle efetivo pós-operatório (Engel 1) e 10 pacientes com controle inadequado das crises(Engel 3 e 4), 10 amígdalas obtidas de autópsias (controle), utilizando a qPCR. Resultados: Foram evidenciadas diferenças da expressão nas subunidades NR2C (p=0,006) e ?4 do GABAAr (p=0,008), subtipo de NPYr Y2(p=0.013), com tendência junto a subunidade NR3A(p=0,077). Não evidenciando significância estatísticas nas análises das subunidades GluK1(p=0,147), GluK2(p=0,182) e?5 do GABAAr (p=0,272), para o subtipo NPYr Y1(p=0,242). Conclusão: As análises sugerem diferenças na expressão de receptores de neurotransmissores em pacientes com epilepsia em relação ao controle contendo as subunidadeNR2C e ?4 do GABAAr, com tendências a subunidade NR3A, indicando modificações neuronais amigdalianas possivelmente envolvidas com a zona epileptogênica, possibilitando aprimoramentos terapêuticos junto ao tratamento dasepilepsias refratárias. Também podemos inferir que os mecanismos neuronais envolvendo as subunidades?4 doGABAAr e GRIN2C, e do subtipo Y2 do NPYr na epileptogênese e ictogênese da ELTM podem ser semelhantes entre amígdala e hipocampo, enquanto os envolvendo as subunidades GLUK1 e GLUK2 parecem ser diferenciados; o gene GABRA5 pode ser utilizado como gene de controle endógeno em estudos com amigdala e hipocampo na ELTM.Introduction: Epilepsy is a disease whith highly medical and social relevance, bringing impact on patients and society as a whole. Mesial Temporal Lobe Epilepsy (MTLE) is the most prevalent refractory epilepsy, in its causality the impact of the imbalance between excitatory neuronal circuits and inhibitory, needing a surgical removal of the altered structures and the interruption of their way to better seizure control and quality of life pacientes. Goal: Searching to increase understanding the role of the amygdala with intrinsic changes in neurotransmitter receptors and their subunits in ictogenesis mechanisms and epileptogenesis, enabling the improvement of surgical techniques currently used, as well as new therapeutic modalities, this study analyzed gene expression on the subunits of excitatory receptors, NMDA (NR2 and NR3A, GRIN2C and GRIN3A genes) and kainate (GluK1 and GluK2, GRIK1 and GRIK2 genes), and inhibitory receptor subunit GABA (?4 and ?5, genes GABRA4 and GABRA5 ), neuropeptide Y receptor subtypes (Y2 and Y5, and NPY5R with NPY2R gene) in the basolateral nucleus of human amygdala of patients with MTLE. Material and Methods: Amygdala fragments were used in 20 patients who made amigdalohipocampectomia with the Service neurosurgery HC-FMRP-USP, 10 patients with postoperative effective control (Engel 1) and 10 patients with inadequate control of seizures (Engel 3:04), and 10 amygdalas obtained from autopsies (control) using qPCR. Results: Were differences evidenced expression in NR2C subunits (p = 0.006) e?4 the GABAAr (p = 0.008), and subtype NPYr Y2 (p = 0.013), along with a tendency of NR3A subunits (p = 0.077). Showing no statistical significance in the analysis of GluK1 subunits (p = 0.147), GluK2 (p = 0.182) e?5 the GABAAr (p = 0.272), and the NPYr Y1 subtype (p = 0.242). Conclusion: The analyzes suggest differences in expression of neurotransmitter receptors in epilepsy patients on control containing the NR2C subunits and ?4 of GABAAr with NR3A subunits trends indicating amygdala neuronal modifications possibly involved in the epileptogenic zone, enabling therapeutic improvements with the refractory epilepsy treatment. As well can infer that the neural mechanisms involving the subunits ?4 GABAAr, GRIN2C and Y2 NPYr subtype in epileptogenesis and ictogenesis of TLE can be similar between the amygdala and hippocampus, while involving GLUK1 and GLUK2 subunits appear to be different; the GABRA5 gene can be used as endogenous control gene in studies of hippocampus and amygdala in TLE.
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Lantz, Göran. "Source localisation of epileptiform activity in epilepsy of temporal lobe origin." Lund : Dept. of Clinical Neuroscience, Division of Clinical Neurophysiology, Lund University Hospital, 1997. http://books.google.com/books?id=V8xrAAAAMAAJ.
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Kim, Hosung. "Advanced morphometry of mesiotemporal structures in temporal lobe epilepsy." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106418.
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Background. Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy. While TLE is associated with mesiotemporal atrophy on MRI, hippocampal volumes are normal in 30% of patients. There is also growing evidence that developmental anomalies altering mesitotemporal lobe morphology participate in the pathogenesis of this condition. Indeed, about 40% of TLE patients show atypical shape of the hippocampus and collateral sulcus, commonly referred to as malrotation. To date, morphometric analysis of such pathology in TLE has been limited to MR volumetry. Objective. The overall goal was to develop advanced morphometric methods to statistically model aspects of pathology that are not evident in measurement of total volume. We first developed surface-based techniques that independently quantify focal atrophy, positioning and sulcal variants, and investigated their clinical significance. We then evaluated the impact of these morphological features on the performance of state-of-the-art hippocampal segmentation algorithms. Lastly, we developed a novel automatic hippocampal segmentation method based on a multi-template approach that relies on statistical parametric surface models and locoregional texture features. Methods and Results. In simulation, Our surface-based Jacobian determinant analyses could disentangle local volume from positional changes by quantifying independently both characteristics. Our analysis showed that in TLE patients atrophy and positional changes co-occurred at the level of the posterior hippocampus. Compared to volumetry, our technique showed increased sensitivity by unveiling subtle mesiotemporal atrophy/hypertrophy in TLE, in particular ipsilateral hippocampal atrophy in patients with normal hippocampal volume (TLE-NV). A combined analysis of all three mesiotemporal surfaces correctly lateralized the seizure focus in 94% of patients with TLE-NV. Analysis of basal temporal sulcal morphology using 3D sulcal models revealed that significantly more TLE patients exhibit an unbroken long collateral sulcus relative to healthy subjects. Our correlation analysis revealed that developmental anomalies and atrophy negatively impacted on the automated segmentation performance in general. Finally, we developed a novel segmentation algorithm (SurfMulti) to statistically estimate vertex-wise locoregional texture and shape. To account for inter-subject variability, we used a multi-template library derived from a large database of controls and patients. Our proposed hippocampal segmentation technique achieved a level of accuracy in TLE patients virtually identical to healthy controls, with a Dice index of 86.1%. Such performance has not yet been paralleled in epilepsy. Furthermore, we achieved the same sensitivity as manual volumetry in detecting atrophy ipsilateral to the seizure focus. Significance. The analytical framework we developed is intended to substantially improve MRI analysis so that it can fulfill its role for surgical target localization and post-surgical outcome prediction, the two main challenges of contemporary epilepsy surgery. Our results show that a better understanding of mesiotemporal lobe pathology lies in the evaluation of various brain morphological characteristics. By statistically assessing aspects of mesiotemporal pathological variations across the spectrum of drug-resistant TLE, we showed the ability of advanced post-processing of anatomical MRI to unveil anomalies that are not identified using volumetric analysis. The developed techniques can be extended to assess structural changes in neurological and neuropsychiatric disorders in which the temporal lobe is involved.Contexte. L'épilepsie du lobe temporal (ELT) est l'épilepsie pharmaco-résistante la plus commune chez l'adulte. Généralement associée à une atrophie temporo-mésiale visible par IRM, les volumes hippocampiques sont pourtant normaux dans 30% des cas d'ELT. De plus, il y a de plus en plus d'indices montrant que des anomalies du développement, qui altèrent la morphologie hippocampique et les motifs sulco-gyraux temporo-mésiaux, participent à la pathogénèse de cette épilepsie. En effet, 40% des ELT exhibent une forme et un positionnement atypiques de l'hippocampe et du sillon collatéral, effet communément appelé "malrotation". Jusqu'à présent, l'analyse morphométrique de la pathologie ELT du lobe mésiotemporal s'est limitée à de la volumétrie sur IRM. Objectifs. Le but général de cette thèse a été le développement de méthodes de morphométrie avancées qui permettront de modéliser statistiquement des aspects de la pathologie qui n'ont pas été évalués antérieurement par IRM, et qui n'apparaissent pas de manière évidente par des mesures de volume total. Nous avons tout d'abord développé des techniques surfaciques qui quantifient, indépendemment, des atrophies focales de petite étendue, des écarts de position ainsi que des variantes de formes de sillons, et nous avons étudié leur significativité clinique. Nous avons ensuite évalué quantitativement l'impact de ces caractéristiques morphologiques (l'atrophie et les anomalies développementales de forme et de position) sur la performance des algorithmes de segmentation de l'hippocampe les plus avancés du moment. Enfin, nous avons développé une nouvelle méthode de segmentation de l'hippocampe basée sur une approche de type "multi-templates" (modèles multiples), qui s'appuie sur des modèles statistiques paramétriques surfaciques et des caractéristiques locorégionales de textures. Méthodes. Nous avons réalisé les expériences suivantes: 1) Après avoir extrait les harmoniques sphériques combinées à des modèles de distribution de points (SPHARM-PDM) à partir de segmentations hippocampiques manuelles, nous avons calculé des vecteurs de déplacement entre les surfaces individuelles et le modèle. Nous avons alors calculé des déterminants jacobiens surfaciques (SJD, Surface-based Jacobian Determinants) à partir de ces vecteurs afin de localiser des changements de volume. Pour analyser les différences de position, nous avons construit un axe méridien médian (MEMAX), qui reprend les correspondances de points, contraintes par la forme, de SPHARM, et sur lequel les courbures locales et les vecteurs de positions sont calculés. Notre méthode a été validée sur des formes synthétiques. 2) A l'aide des métriques développées en (1), nous avons étudié les motifs de pathologie mésiotemporale chez les patients ELT, en effectuant des comparaisons de groupes, point à point, entre des patients atteints d'une atrophie hippocampique (TLE-HA), ceux dont le volume hippocampique est normal (TLE-NV), et des contrôles sains. De plus, nous avons évalué la capacité de notre modélisation de formes surfacique 3D à latéraliser le foyer épileptogène et à prédire l'issue de la chirurgie. 3) Les sillons corticaux ont été automatiquement extraits et identifiés à partir d'images IRM grâce à un modèle utilisant une assemblée de réseaux neuronaux artificels. Nous avons inspecté visuellement en 3D les arrangements sulcaux de la face inférieure du lobe temporal, et les avons décrits en quatre classes de motifs. 4) Nous avons segmenté l'hippocampe des sujets contrôle et des patients ELT en utilisant SACHA, un algorithme de croissance de région contraint par des a priori anatomiques, et FreeSurfer, un logiciel libre se basant sur un atlas. Pour quantifier les malrotations, des modèles 3D ont été créés à partir des segmentations manuelles d'hippocampes et des sillons collatéraux extraits automatiquement.
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Bernasconi-Ladbon, Neda. "MRI of the parahippocampal region in temporal lobe epilepsy." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85081.
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Temporal lobe epilepsy (TLE) is among the most common chronic seizure disorders, accounting for approximately one-fourth of all cases of epilepsy. Although hippocampal sclerosis is the most common pattern of damage in TLE, there is electrophysiological and neuropathological evidence in both humans and animal models of this condition for the involvement of the parahippocampal region.In clinical practice, the investigation and treatment of patients with epilepsy has been revolutionized by the advent of MRI, which has been demonstrated to be a reliable and accurate indicator of pathologic findings underlying epilepsy. Advances in image acquisition and processing techniques combined with detailed descriptions of anatomy and cytoarchitectonic borders of parahippocampal structures on histologic sections have created the basis for precise determination of the boundaries of these cortical areas on MRI. This dissertation presents a series of MRI studies aimed at assessing volume changes in vivo of the parahippocampal region, and further elucidating its role in the pathogenesis of TLE.
To accomplish this we developed a standardized MRI protocol to measure the volume of the parahippocampal region structures in vivo. In agreement with previous neuropathological studies (Meencke and Veith, 1991), our results showed that damage to the mesial temporal lobe involves not only the hippocampus and the amygdala, but also the parahippocampal region structures in patients with intractable TLE. Within the parahippocampal region, the entorhinal cortex was the most affected structure. We observed that the atrophy was more severe in the anterior portion of the mesial temporal lobe involving mostly the hippocampal head and body as well as the EC. This pattern of atrophy, characterized by an antero-posterior gradient of pathology, may be explained by a disruption of entorhinal-hippocampal connections.
To evaluate the clinical role of entorhinal cortex volumetry we studied groups of TLE patients with hippocampal atrophy and those with normal hippocampal volumes as well as patients with extra-temporal lobe epilepsy.
Entorhinal cortex volumetry could provide correct lateralization of the seizure focus in 73% of TLE patients with hippocampal atrophy. Entorhinal cortex atrophy seems to be specific to TLE, since we found no atrophy in other forms of epilepsy, including frontal lobe and primary generalized epilepsy. We subsequently demonstrated that entorhinal cortex atrophy ipsilateral to the seizure focus can be the only MRI sign of mesial temporal damage in 64% of patients with normal hippocampal volumes.
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Bernhardt, Boris. "MRI - based cortical thickness analysis in temporal lobe epilepsy." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96974.
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Background. Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. TLE is typically associated with mesiotemporal atrophy on MRI, but ample data suggests further structural damage in neocortical regions and the thalamus. However, the underlying pathogenesis and relevance of these changes are poorly understood.Purpose. Our overall goal was to analyze the topography and progression of neocortical thinning, its clinical relevance, and its relationship to patterns of connectivity in drug-resistant TLE using MRI-based cortical thickness measurements.Methods. We carried out the following experiments: 1. Mapping the extent of neocortical thinning and assessing its relationship to mesiotemporal pathology. 2. Mapping progressive cortical thinning in TLE through cross-sectional and longitudinal analyses. 3. Assessing the clinical value of cortical thickness measurements in TLE by investigating their reproducibility and relationship to surgical outcome. 4. Assessing organizational disruptions in cortico-cortical networks in TLE through a graph-theoretical analysis of cortical thickness correlations. 5. Analyzing the relationship between cortical thinning and thalamo-cortical connectivity. Local patterns of thalamic changes were assessed using thalamic surface-shape analysis. 6. Analyzing the relationship between cortical thinning and disruptions of subcortical white matter quantified by diffusion tensor imaging tractography.Results. We observed marked and progressive cortical thinning in TLE in mainly temporo-limbic and fronto-central cortices. Patterns of thinning were reproducible across datasets and bootstrap simulations, and seen inpatients with and without hippocampal atrophy. The degree of fronto-central cortical thinning correlated to atrophy in medial thalamic divisions, as well as to microstructural derangements in underlying white matter tracts. In operated patients, local patterns of cortical thinning as well as patterns of large-scale disruptions in cortico-cortical network organization related to post-surgical seizure recurrence.Significance. TLE is associated with widespread cortical thinning and large-scale structural network disruptions, indicating a systemic nature of brain pathology in this disorder. Cortical thinning is progressive and correlates with the degree of pathology in thalamic divisions, likely indicating damage due to seizure spread from mesiotemporal to thalamo-cortical networks. Local cortical thickness measurements and data from cortical thickness correlation networks provided useful information for surgical outcome prediction, and may ultimately improve the presurgical assessment in individual TLE patients.Contexte. L'épilepsie du lobe temporal (ELT) est la forme la plus courante d'épilepsie pharmaco-résistante chez l'adulte. ELT est généralement associée à une atrophie mésiotemporale visible en IRM, mais de nombreuses données suggèrent l'existence de dommages structurels plus étendus dans des régions néocorticales et le thalamus. Cependant la pathogénèse sous-jacente et la pertinence de ces changements sont mal connus.Objectif. Notre but était d'analyser la topographie et la progression de l'amincissement néocortical, sa pertinence clinique et ses liens avec des profils de connectivité dans des cas de ELT pharmaco-résistantes, à l'aide de mesures d'épaisseur corticale basées sur l'IRM.Méthodes. Nous avons réalisé les expériences suivantes: 1. Cartographie de l'étendue de l'amincissement cortical et évaluation de ses liens avec des pathologies mésiotemporales. 2. Cartographie de la progression de l'amincissement cortical accompagnant ELT, par le biais d'analyses transversales et longitudinales. 3. Évaluation de la valeur clinique des mesures d'épaisseur corticale pour ELT, par l'étude de leur reproductibilité et leurs relations avec les résultats de chirurgie. 4. Évaluation des perturbations de l'organisation des réseaux cortico-corticaux chez des patients avec ELT, par une analyse de théorie des graphes des corrélations de l'épaisseur corticale. 5. Analyse des relations entre l'amincissement cortical et la connectivité thalamo-corticale. Les motifs locaux de modifications thalamiques ont été évalués à l'aide d'une analyse de formes de la surface du thalamus. 6. Analyse des liens entre l'amincissement cortical et les perturbations de la matière blanche sous-corticale, quantifiés par des techniques de tractographie à partir d'images du tenseur de diffusion.Résultats. Nous avons observé un amincissement progressif marqué dans ELT, principalement dans le cortex temporo-limbique et fronto-central. Les motifs d'amincissement étaient reproductibles à travers des jeux de données et des simulations "bootstrap", et observés chez des patients présentant ou non une atrophie hippocampique. Le degré d'amincissement du cortex fronto-central corrélait à l'atrophie des divisions thalamiques médiales, aussi bien qu'aux perturbations de la microstructure des faisceaux de la matière blanche. Chez les patients opérés, les motifs locaux de l'amincissement cortical, tout comme les perturbations à grande échelle de l'organisation des réseaux cortico-corticaux, étaient en rapport avec la récidive post-opératoire des crises d'épilepsies.Significativité. ELT est associée à un amincissement cortical général et à des perturbations à grande échelle des réseaux structurels, suggérant la nature systémique de la pathologie cérébrale. L'amincissement cortical est progressif et corrèle au degré de pathologie des divisions thalamiques, ce qui indique des dommages probablement dus à la propagation des crises d'épilepsie des réseaux mésiotemporaux aux réseaux thalamo-corticaux. Les mesures locales de l'épaisseur corticale, ainsi que les données provenant des réseaux de corrélation d'épaisseur corticale, ont apporté des informations utiles à la prédiction des résultats chirurgicaux, et pourraient contribuer à améliorer l'évaluation pré-chirurgicale des patients atteints de ELT.
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Howard, Charlotte Emma. "Memory and metamemory in patients with temporal lobe epilepsy." Thesis, University of Plymouth, 2009. http://hdl.handle.net/10026.1/2257.
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It is well established that patients with temporal lobe epilepsy (TLE) commonly report memory difficulties. The aim of this thesis was to use a novel approach adopting Nelson & Narens' (1990) theoretical framework to investigate whether metacognitive knowledge and memory performance were differentially disrupted in patients with TLE. More specifically, investigating to what extent poor memory in TLE could result from inadequate metamemory monitoring, inadequate metamemory control or both. Experiment I employed a combined Judgement-of-Learning and Feeling-of-Knowing task to investigate whether participants could monitor their memory successfully at both the item-by-item and global levels. The results revealed a dissociation between memory and metamemory in TLE patients. TLE patients presented with a clear episodic memory deficit compared with controls yet preserved metamemory abilities. Experiments 2 and 3 explored the sensitivity approach to examine metacognitive processes that operate during encoding in TLE patients and controls. Both these experiments demonstrated that TLE patients were sensitive to monitoring and control processes at encoding. The final experiment further investigated memory performance by examining the role of lateralisation of the seizure focus using material specific information and the 'Remember-Know' paradigm. The findings from the verbal task provided partial support to the material-specific hypothesis. The results from these experiments are discussed in terms of their association with executive functioning and memory deficits in TLE, and have important implications for future research examining memory and metamemory in TLE patients and other clinical populations.
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Egerton, Karen. "Social cognition and emotional intelligence in temporal lobe epilepsy." Thesis, University of Sheffield, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.575534.
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This thesis begins by reviewing the current literature regarding social cognition and Temporal Lobe Epilepsy (TLE) and proceeds to investigate Emotional Intelligence (El) in people with People with TLE before and after surgical resection of the temporal lobe. Psychosocial maladjustment is noted as a significant problem in people with temporal lobe epilepsy (TLE). Whether these difficulties are a consequence of living with a chronic seizure condition or whether the neuropathology associated with TLE may have a causal influence remains unclear. Recent literature in the field of social cognitive neuroscience regarding social cognition in TLE is reviewed. It is concluded that people with T1.E tend to have specific deficits in some aspects of social cognition, linked to the underlying neuropathology of the condition, and that this is likely to be a factor in the psychosocial difficulties often presented in this population. A research study is then reported in which emotional intelligence (El), a concept related to social cognition, is investigated in a TLE population. El in people with medically managed TLE was compared with people with TLE who had undergone resective surgery to control their seizures to further investigate whether impaired El in TLE is due to living with chronic seizures or a consequence of the underlying neuropathology. Results suggest that impaired ET of this population is likely a complex interaction of both these factors.
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Van, Paesschen Wim. "Quantitative MRI and hippocampal neuropathology of temporal lobe epilepsy." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265249.
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Chandler, Kate Emma. "The role of GABAB receptors in temporal lobe epilepsy." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446842/.
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Temporal lobe epilepsy is the most common partial epilepsy syndrome seen in adult humans. The hippocampus is a key structure in the evolution of temporal lobe seizures. The axons of the dentate granule cells, the mossy fibres, constitute a major hippocampal excitatory input. Inhibitory phenomena at mossy fibre synapses may therefore prevent seizure propagation through the hippocampus. One such inhibitory phenomenon is heterosynaptic depression. In this thesis I studied the role of GABAB receptors in temporal lobe epilepsy. In particular I studied changes in GABAB receptor-mediated heterosynaptic depression at the mossy fibre synapse following status epilepticus. I have shown that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hours later by a loss of GABAB receptor-mediated heterosynaptic depression among populations of mossy fibres. This was accompanied by a decrease in the sensitivity of mossy fibre transmission to the exogenous GABAB receptor agonist baclofen. Autoradiography revealed a reduction in GABAB receptor binding in stratum lucidum after status epilepticus. I then addressed the question: what is the source of the GABA that mediates heterosynaptic depression I have also shown that the GABAB receptor agonist baclofen has antiepileptic properties. In addition, GABAB receptors do not appear to be involved in the function of the antiepileptic drug tiagabine. Failure of GABAB receptor-mediated modulation of mossy fibre transmission may contribute to the development of spontaneous seizures after status epilepticus. The GABAB receptor may be useful as a target for antiepileptic drugs.
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Bonner, Shawna N. "Social cognition and psychosocial functioning in temporal lobe epilepsy." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382373117.
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Powell, Howell William Robert. "Investigating brain structure and function in temporal lobe epilepsy." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1446099/.
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Background Anterior temporal lobe resection (ATLR) is increasingly used in the treatment of patients with refractory temporal lobe epilepsy (TLE). Complications of surgery include a decline in language and memory abilities, and visual field defects. The principal aim of this thesis was to use magnetic resonance imaging (MRI) techniques to improve the planning of effective surgical treatment for patients with TLE by using functional MRI to localise areas in the brain involved in language and memory function, and MR-tractography to investigate the structural connections of these areas and those involved in visual function. Methods Ten control subjects underwent tractography to study the connections of the medial temporal lobe (MTL). Two patients underwent tractography pre- and post-operatively to look at the trajectory of the optic radiation. For the memory studies we scanned 10 control subjects and 15 presurgical patients with refractory TLE. For the combined language fMRI and tractography study, 10 control subjects and 14 patients with hippocampal sclerosis underwent both fMRI and tractography. All scans were performed on a 1.5T GE Signa Horizon scanner. Findings The connections of the MTL were identified in a group of control subjects. The optic radiation was mapped preoperatively and shown to be disrupted following ATLR in a patient with a visual field defect. A material-specific lateralisation of memory encoding activation was demonstrated in control subjects with reduced ipsilateral activation in patients with TLE. Increased ipsilateral hippocampal activation correlated with better preoperative memory function and with greater postoperative memory decline. fMRI and tractography were combined to study the structural connections of functional language areas in controls and TLE patients, demonstrating reduced left sided and increased right hemisphere connections in left TLE patients, findings that reflected the pattern of functional activation.
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Barbosa, Patricia Horn 1980. "Associação entre alterações eletroencefalográficas interictais, ressonância magnética e resultado cirúrgico de pacientes com epilepsia de lobo temporal." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312639.
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Orientador: Fernando CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Epilepsia de lobo temporal resulta com freqüência em refratariedade ao tratamento medicamentoso. Alguns fatores prognósticos da epilepsia focal e seu tratamento já foram descritos, mas outros ainda estão por ser melhor conhecidos. Nosso objetivo foi investigar associação entre alterações no EEG pré e pós-operatório e na ressonância de crânio pré-operatória com o resultado cirúrgico de pacientes com epilepsia de lobo temporal. Pacientes com epilepsia focal refratária submetidos a cirurgia após investigação não invasiva foram reavaliados. Calculamos o período livre de crises até a recorrência. Realizamos análise visual da RM crânio pré-operatória buscando sinais de atrofia hipocampal e alterações sutis no hipocampo contralateral. Revisamos exames de EEG pré e pós-operatórios buscando inicialmente a presença ou ausência de descargas epileptiformes. Posteriormente, quantificamos atividade epileptiforme interictal e buscamos associação com recorrência de crises. Utilizamos os testes estatísticos qui-quadrado e Fisher, quando adequados, e construímos curvas de sobrevivência de Kaplan-Meier, considerando recorrência de crises como desfecho, com comparação pelo método de Mantel. Na primeira parte do estudo foram incluídos 86 pacientes com atrofia hipocampal. EEG pré-operatório unilateral não se associou a resultado cirúrgico favorável; EEG pós-operatório com presença de atividade epileptiforme interictal não se associou a resultado cirúrgico desfavorável; RM cranio com hipocampo contralateral alterado se associou tanto a resultado cirúrgico desfavorável, quanto com bilateralidade nos EEGs pré-operatórios. Na segunda parte do estudo, com 129 pacientes incluídos, não encontramos associação significativa entre presença de atividade epileptiforme interictal no EEG pós-operatório e resultado cirúrgico. As curvas de sobrevivência dos grupos com descargas epileptiformes presentes versus ausentes não foram estatisticamente diferentes (p=0,09), porem observamos uma tendência, o que motivou a terceira parte. Desta forma, demonstramos, através da quantificação da atividade epileptiforme, associação entre descargas pouco frequentes no EEG pós-operatório com resultado cirúrgico favorável. Finalmente, na tentativa de estabelecer o EEG pós-operatório como preditor de recorrência de crises, não encontramos, com a amostra disponível, associação entre EEG pós-operatório com atividade epileptiforme pouco frequente e resultado cirúrgico favorável. Estes resultados demonstram que é importante valorizar alterações sutis no volume, conformação, eixo e sinal do hipocampo menos afetado na indicação de cirurgia de pacientes com epilepsia de lobo temporal e atrofia hipocampal. O resultado cirúrgico dos pacientes com hipocampo contralateral normal é mais favorável. Alteração eletrográfica bitemporal no EEG pré-operatório, em geral, está associada a alteração estrutural sutil no hipocampo contralateral, que muitas vezes não é valorizada. Tal achado corrobora evidências previamente descritas de que pacientes com EEG pré-operatório bitemporal tem prognóstico cirúrgico menos favorável. Os dados relacionados à análise quantitativa de descargas epileptiformes no EEG pós-operatório mostraram associação entre atividade epileptiforme e resultado cirúrgico. Tal achado sugere que o EEG pode ser uma ferramenta útil no seguimento clínico pós-operatório. Em conclusão, nossos resultados indicaram dois fatores importantes no prognóstico de controle de crises após cirurgia em ELT: presença de alteração hipocampal contralateral mesmo que sutil, e espículas em uma frequência maior que 4 por um período de 15 minutos
Abstract: Temporal lobe epilepsy is frequently linked to medical refractoriness. Many clinical prognostic data on focal epilepsy have repeatedly been described, while surgical outcome factors are yet to be fully known. We presently look into an association between interictal epileptiform discharges in pre and postoperative EEG, as well as preoperative brain magnetic resonance imaging, and surgical outcome of temporal lobe epilepsy. Patients with medically refractory focal epilepsy submitted to surgery following non invasive investigation were reassessed. We calculated time until seizure recurrence. We visually analysed preoperative MRI searching for signs of hipoccampal atrophy, as well as subtle contralateral hipoccampal changes. We reviewed pre and postoperative EEGs concerning presence or absence of interictal epileptiform discharges. Later on, we quantified interictal discharges and tested association with seizure freedom. We used chi square or Fisher¿s exact test, when most adequate. We also built Kaplan-Meier¿s survival curves setting seizure recurrence as endpoint, and compared curves by Mantel method. We initially included 86 patients with hipoccampal atrophy. Preoperative unilateral EEG was not associated with favorable surgical outcome; presence of IED in postoperative EEG was not associated with unfavorable outcome; contralateral hipoccampal changes on preoperative MRI was strongly associated with unfavorable surgical outcome, as well as with bilateral preoperative EEGs. We then studied postoperative EEGs of 129 individuals. There was not a significant association between postoperative EEG and surgical outcome. Survival curves of group of patients with interictal discharges present and absent were not statistically different (p=0.09), but we observed a tendency in that direction. Therefore, we were able to demonstrate through manual quantification of epileptiform discharges that postoperative EEG direct association with surgical outcome. Our ultimate goal was to establish postoperative EEG as predictor of seizure recurrence. Unfortunately we were not able to demonstrate it with data available on our sample. These results highlight importance of assessing subtle changes in volume, form, axis and signal intensity on contralateral hipoccampus prior to indication of surgery in patients with temporal lobe epilepsy with hipoccampal atrophy. Surgical outcome is more favorable when contralateral hipoccampus is normal. Bilateral discharges over temporal electrodes in pre-operative EEG are associated with subtle structural changes on contralateral hipoccampus, which may be underestimated. Such findings is in agreement with previously described evidence of bitemporal preoperative EEG associated with less favorable surgical outcome. Quantification data on postoperative EEG sets forth direct association with epileptiform discharges and surgical outcome. Such finding suggests EEG may be a useful tool in postoperative followup. In conclusion, our results indicate two important prognostic factors for seizure control in surgically treated temporal lobe epilepsy patients: presence of contralateral signs of hipoccampal sclerosis, even if subtle, and interictal epileptiform discharges occuring in a frequency higher than 4 at 15 minutes period
Doutorado
Neurociencias
Fisiopatologia Médica
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Monnerat, Bruno Zanotelli. "Uso do padrão ictal na epilepsia da região mesial do lobo temporal associada à esclerose hipocampal como marcador prognóstico pós-cirúrgico: uma coorte retrospectiva." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/17/17140/tde-31032012-090652/.
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Pacientes com epilepsia do lobo temporal farmacorresistente, frequentemente, possuem esclerose hipocampal como lesão epileptogênica. Muitas vezes, estes pacientes se beneficiam de lobectomia temporal para redução da ocorrência de crises epilépticas. Para que possam se submeter a este procedimento, é necessário o uso da videoeletroencefalografia prolongada para delimitação apurada da zona epileptogênica. Apesar dos avanços dos métodos diagnósticos nesta área, a busca por um instrumento que permita uma avaliação clara da chance de uma vida livre de crises após cirurgia permanece. No presente trabalho, a apresentação do padrão eletroencefalográfico ictal foi estudado, de forma a se pesquisar se existe relação entre a sua ocorrência e permanência em apenas um hemisfério cerebral com um melhor prognóstico pós-cirúrgico. Foram revisados os dados eletroencefalográficos ictais e os prontuários médicos de 284 pacientes. Procedeu-se à classificação de seus padrões eletroencefalográficos ictais em unilaterais ou bilaterais, e seu prognóstico após um, dois e cinco anos após cirurgia em livre de crise ou não livre de crise epiléptica. Apresentavam padrão unilateral 132 pacientes, e 152 apresentavam padrão bilateral. Estavam livres de crises 236 pacientes, e 48 ainda persistiam com crises epilépticas após cirurgia. Não houve associação entre padrões ictais unilaterais e uma vida livre de crises epilépticas após a cirurgia (diferença de 7,5%; p=0,092; chi-quadrado). Dessa forma, não se pode aplicar o padrão ictal eletroencefalográfico como ferramenta para predição de uma vida livre de crises após lobectomia temporal em pacientes com epilepsia da região mesial do lobo temporal associada à esclerose hipocampal.Patients with drug-resistant temporal lobe epilepsy usually have hippocampal sclerosis as an epileptogenic lesion. Most of the times, these patients are benefited from temporal lobectomy for seizure relief. For this procedure to occur, a long-term videoelectroencephalogram is necessary for the accurate delineation of the epileptogenic zone. Despite the developments in the diagnostic methods on this area, the quest continues for an instrument that allows a clear evaluation of the chance to obtain a seizure-free life after epilepsy surgery. In the present study, the electroencephalographic ictal patterns were evaluated, and the relationship between its occurrence and permanence in one cerebral hemisphere and the possibility of a seizure-free outcome after surgery were compared. The ictal electroencephalografic and medical records of 284 patients were analyzed. A classification of ictal patterns, whether unilateral or bilateral, was issued, and the seizure outcome after one, two, and five years after surgery annotated. Unilateral ictal patterns occurred in 132 patients, and bilateral ictal patterns in 152. Seizure-free status was obtained in 236 patients, and 48 still persisted with seizures. There was no association between a unilateral ictal status and a seizure-free outcome after surgery (difference of 7.5%, p=0.092; chi-square). So, the electroencephalographic ictal pattern is not a valuable tool for predictions regarding seizure outcome in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis that are submitted to temporal lobectomy.
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Trentin, Marine Meliksetyan. "Padrão alternante cíclico nas epilepsias do lobo temporal." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/11796.
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Introdução: O Padrão Alternante Cíclico (“CAP”, do inglês - Cyclic Alternating Pattern) é um ritmo fisiológico do sono NREM, que corresponde aos períodos de ativação cíclica expressos por eventos fásicos do sono. O aumento na expressão de taxa do CAP tem sido considerado uma medida de instabilidade e fragmentação do sono. O CAP representa uma condição favorável para a ocorrência de descargas interictais e/ou ictais. A modulação do CAP em pacientes com Epilepsia do Lobo Temporal (ELT) não está bem definida. Objetivos: Analisar a expressão do CAP em pacientes com ELT e comparar com o grupo de controle. Selecionar o grupo de pacientes sem distúrbios do sono que possam influenciar a organização do sono. Métodos: Foi realizado estudo transversal com grupo de controle de comparação. A seleção foi pareada em sexo e idade entre pacientes com ELT e o grupo de controle, obedecendo aos critérios de inclusão e exclusão. Os parâmetros do sono e CAP foram analisados em 13 pacientes com ELT (6 do sexo masculino e 7 do sexo feminino; idade média: 33,8 ± 8,5 anos) e 13 indivíduos sadios (8 do sexo masculino e 5 do sexo feminino; idade média: 26,1 ± 9,2 anos), os quais não apresentaram distúrbios do sono. A comparação dos dois grupos foi realizada através do “teste t” de Student e confirmada pelo “teste U” de Mann-Whitney. Resultados: Os pacientes com ELT apresentaram aumento na taxa de CAP (44,02 ± 5,23 % versus 31,83 ± 3 %; p<0,001) e maior duração do tempo de CAP (133,77 ± 15,56 min. versus 99,38 ± 9,6 min.; p<0,001) em relação aos indivíduos sadios. Não houve diferença na média da duração da fase A (9,27 ± 1,15 seg. versus 8,7 ± 0,61 seg.; p<0,131), e a média da duração da fase B não atingiu diferença significativa (22,92 ± 1,71 seg. versus 21,54 ± 1,78 seg.; p<0,054) entre os dois grupos. A comparação dos parâmetros de sono e de CAP dentro de cada grupo, mostrou não haver diferença entre os gêneros. A análise estatística dos parâmetros do sono em pacientes com ELT evidenciou uma diferença significativa das seguintes variáveis: menor latência ao sono (5,8 ± 2,4 min. versus 14,2 ± 7,6 min.; p=0,002); aumento do número da troca de estágios com média de 91,1 ± 25,7 versus 68,2 ± 12,8; p=0,008; menor duração de estágio IV (30,8 ± 14,8 min. versus 51,4 ± 12,5 min.; p=0,001); maior percentual do estágio III (7,7 ± 2,8% versus 5,7 ± 1,7%; p=0,035); menor percentual do estágio IV (7,9 ± 4% versus 12,9 ± 3,3%; p=0,002) em pacientes com ELT, comparando com o grupo de controle. A análise dos despertares breves demonstrou em pacientes com ELT: maior número de despertares breves em sono (66,5 ± 20 versus 41,8 ± 9; p=0,001); maior número de despertares breves em sono NREM (52,9 ± 19,6 versus 31 ± 9,5; p=0,002); maior duração total de despertares breves em sono (549,1 ± 170,3 seg. versus 357,2 ± 88,5 seg.; p=0,002); maior duração total de despertares breves em sono NREM (436,8 ± 165,7 seg. versus 271,9 ± 95,2 seg.; p=0,006); aumento do índice de despertar breve em sono (10,2 ± 2,9 versus 6,3 ± 1,7; p=0,001); aumento do índice de despertar breve em sono NREM (10,3 ± 3,4 versus 6 ± 2; p=0,001). Não houve diferença significativa de número (13,6 ± 5,6 versus 10,8 ± 3,7; p=0,149), duração total (112,3 ± 48,3 seg. versus 85,3 ± 25,2 seg.; p=0,091) e índice de despertar breve (9,7 ± 3,8 versus 7,4 ± 2,4; p=0,075) em sono REM entre os dois grupos. Todos os pacientes comELT tiveram uma eficiência do sono normal e similar ao grupo de controle (90,4 ± 2,9 % versus 90,6 ± 2,9 %). Conclusões: Os pacientes com ELT apresentam aumento da taxa de CAP e da duração de tempo de CAP em relação ao grupo controle, demonstrando um aumento na instabilidade e fragmentação do sono. O aumento na expressão da taxa de CAP, alterações nos parâmetros de fragmentação e descontinuidade do sono, expressos pelo aumento de número, duração e índice de despertares breves em sono NREM e o número de mudanças de estágios, associados à eficiência normal do sono em nosso grupo de pacientes com ELT, podem sugerir que o CAP tem um papel na modulação do sono. A fragmentação e a instabilidade do sono em pacientes com ELT, provavelmente, ocorrem devido à própria epilepsia e podem refletir a interação do foco epiléptico com os sistemas responsáveis pela manutenção e estabilidade de sono.Introduction: Cyclic Alternating Pattern (“CAP”) is a NREM sleep physiological rhythm corresponding to periods of cyclical activation expressed by phasic events of sleep. The increase in the CAP rate expression has been considered a measure for sleep instability and fragmentation. CAP offers a favorable condition for interictal and/or ictal discharges. The CAP modulation in patients with Temporal Lobe Epilepsy (TLE) is not well defined. Objectives: Analyze the CAP expression in patients with TLE comparing it with a control group. Select the group of patients without sleep disorders which may interfere with sleep organization. Methods: A transversal study was conducted with a comparing control group. The selection was paired on gender and age between patients with TLE and the control group, in accordance with inclusion and exclusion criteria. The sleep parameters and CAP were analyzed in 13 patients (6 males and 7 females; mean age: 33,8 ± 8,5 years) and 13 healthy individuals (8 males and 5 females; mean age: 26,1 ± 9,2 years) who did not present sleep disorders. The comparison of the two groups was made through Student’s t-test and was confirmed by the Mann-Whitney U test. Results: Patients with TLE showed an increase in the CAP rate (44,02 ± 5,23% versus 31,83 ± 3%; p<0,001) and CAP time was longer (133,77 ± 15,56 min. versus 99,38 ± 9,6 min.; p<0,001) as compared to healthy individuals. There was no difference in the duration average of stage A (9,27 ± 1,15 sec. versus 8,7 ± 0,61 sec.; p<0,131), and the duration average of stage B did not show a significant difference (22,92 ± 1,71 sec. versus 21,54 ± 1,78 sec.; p<0,054) between both groups. The comparison of sleep parameters and CAP within the group showed that there is no difference between the genders. The statistical analysis of sleep parameters in patients with TLE showed a significant difference in the following variables: lower sleep latency (5,8 ± 2,4 min. versus 14,2 ± 7,6 min.; p=0,002); increase in the number of stage shifts with an average of (91,1 ± 25,7 versus 68,2 ± 12,8; p=0,008); lower duration of the stage IV (30,8 ± 14,8 min. versus 51,4 ± 12,5 min.; p=0,001); higher percentage of the stage III (7,7 ± 2,8% versus 5,7 ± 1,7%; p=0,035); lower percentage of the stage IV (7,9 ± 4% versus 12,9 ± 3,3%; p=0,002) in patients with TLE as compared to the control group. The analysis of arousals in patients with TLE showed: a higher number of arousals during sleep (66,5 ± 20 versus 41,8 ± 9; p=0,001); a higher number of arousals during NREM sleep (52,9 ± 19,6 versus 31 ± 9,5; p=0,002); a longer total duration of arousals during sleep (549,1 ± 170,3 sec. versus 357,2 ± 88,5 sec.; p=0,002); a longer total duration of arousals during NREM sleep (436,8 ± 165,7 sec. versus 271,9 ± 95,2 sec.; p=0,006); an increase of arousal index during sleep (10,2 ± 2,9 versus 6,3 ± 1,7; p=0,001); an increase of arousal index during NREM sleep (10,3 ± 3,4 versus 6 ± 2; p=0,001). There was not a significant difference in number (13,6 ± 5,6 versus 10,8 ± 3,7; p=0,149), total duration (112,3 ± 48,3 sec. versus 85,3 ± 25,2 sec.; p=0,091) and arousal index (9,7 ± 3,8 versus 7,4 ± 2,4; p=0,075) during REM sleep between the two groups. All patients with TLE showed a sleep efficiency that is normal and similar to the control group (90,4 ± 2,9% versus 90,6 ± 2,9%).Conclusions: Patients with TLE showed an increase in CAP rate and a longer CAP duration in relation to the control group, demonstrating an increase in the instability and fragmentation of sleep. The increase in the CAP rate expression, alterations in the parameters of sleep fragmentation and discontinuity that as expressed by increase in the number, duration, arousal index during NREM sleep and number of stage shifts, associated with normal sleep efficiency in our group of patients with TLE may suggest that CAP may have influence in the modulation of sleep. Sleep fragmentation and instability in patients with TLE may occur probably due to epilepsy itself, reflecting the interaction of the epileptic foci with the systems responsible for the maintenance and stability of sleep.
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Farrow, Tom F. D. "Hippocampus, cognitive function and epilepsy." Thesis, University of Sheffield, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322874.
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Pniewski, Krystne. "The assessment and treatment of concerns and anxiety in patients undergoing pre-surgical monitoring for epilepsy /." Connect to thesis, 2006. http://eprints.unimelb.edu.au/archive/00002908.
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Bonilha, Leonardo Fator Gouvea. "Dano neuronal em pacientes com epilepsia do lombo temporal medial refrataria a tratamento clinico : estudo quantitativo por ressonancia magnetica." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313569.
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Orientadores: Li Li Min, Fernando CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A esclerose hipocampal (EH) é a alteração histológica mais comum em pacientes com epilepsia do lobo temporal medial (ELTM). A Ressonância Magnética (RM) de crânio possibilita a detecção in vivo de sinais associados à EH, permitindo que pacientes com EL TM reftatária à medicação sejam submetidos à ressecção cirúrgica do hipocampo para tratamento de crises epilépticas. As causas de reftatariedade à medicação e ao tratamento cirúrgico ainda são desconhecidas, porém supõe-se que um dos motivos seja a presença de lesão neuronal acometendo outras áreas cerebrais além do hipocampo. O uso da morfometria por RM permite avaliação do dano neuronal tanto no hipocampo como em outras estruturas cerebrais através da avaliação e quantificação da atrofia presente nestas estruturas. Para avaliação pormenorizada das estruturas cerebrais foi realizada a implementação e validação de um protocolo anatômico para mensuração da região mesial do lobo temporal, com uso de RM tridimensional de alta definição. Foi também definido um protocolo para volumetria automatizada baseada em voxel de todo o cérebro. Foi observado que o dano neuronal em pacientes com EL TM se estende além do hipocampo e acomete regiões que se conectam funcionalmente e anatomicamente ao hipocampo. Tál achado sugere que exista lesão abrangendo uma rede neuronal, o que pode ser responsável em conjunto pelas manifestações clínicas observadas nesses pacientes
Abstract: Hippocampal sclerosis (HS) is the most common histological finding in patients with media! temporal lobe epilepsy (MTLE). Magnetic resonance imaging (MRl) permits in vivo detection of signs that are associated to HS, permitting the surgical treatment for these patients. The causes of medical and surgical reftactoriness observed in patients with MTLE are still unknown. One possible explanation is the fact that the neuronalloss encountered in these patients spans over other brain areas beyond the hippocampus. The use of morphometric quantification of brain structures through MRI is a powerful tool to investigate the neuronalloss in the hippocampus and in other areas of the brain. In order to assess the neuronal damage in brain structures of patients with MTLE, we developed a protocol for manual MRI morphometry of the media! temporallobe structures. We also developed an automatic protocol to assess the concentration of gray matter in the whole brain of these patients through the use of Voxel Based Morphometry. We observed that patients with MTLE exhibit neuronal loss that is not restricted to the hippocampus, but affects di:fferent areas throughout the brain that are functionally and anatomica1ly connected to the hippocampus. These findings suggest that a lesion of a network of neural structures may be responsible for the clinical symptomatology exhibited by patients with MTLE
Doutorado
Neurologia
Doutor em Ciências Médicas
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Ferreira, Ana Erika Dias 1988. "Expressão hipocampal de fatores de crescimento de fibroblastos em pacientes com epilepsia do lobo temporal = Hippocampal expression of fibroblast growth factors in temporal lobe epilepsy patients." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310407.
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Orientadores: Lília Freire Rodrigues de Souza Li, Marcelo Ananias TeocchiDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Epilepsia do lobo temporal (ELT) é a forma mais comum de epilepsia em adultos. O processo de epileptogênese inclui a morte neuronal, brotamento axonal, inflamação, neurogênese, estresse oxidativo e gliose. No entanto, os mecanismos moleculares subjacentes não são totalmente compreendidos. Os fatores de crescimento de fibroblastos (FGFs) são uma família de proteínas com várias funções no organismo, especialmente no sistema nervoso central. No entanto, o funcionamento dos FGFs no cérebro humano não é totalmente compreendido. O FGF2 é o membro mais estudado dessa família e seu papel na fisiopatologia da epilepsia é controversa. Na tentativa de esclarecer o envolvimento da via de FGF na ELT, nós quantificamos a expressão hipocampal dos seguintes genes: FGF2, FGF8, FGF22, FGFR1, FGFR2, FGFR3, ITPR3, PIK3R3 e PIK3R5 em 10 pacientes resistentes a fármacos e quatro controles post mortem. Além disso, avaliamos a expressão da proteína de FGF2 por imunofluorescência indireta. Apenas para o FGF2, houve aumento do RNAm no hipocampo dos pacientes para os dois genes de referência testados, HPRT1 e ENO2 + TBP em combinação (P = 0,002 e P = 0,036; respectivamente). A porcentagem de células imunomarcadas para FGF2 no giro dentado foi maior nos pacientes do que nos controles (P <0,05), mas nenhuma alteração significativa foi encontrada no Corno de Ammon. O FGF2 pode preservar os neurônios após lesão e atua como um poderoso fator para a proliferação de células-tronco neurais. Assim, o FGF2 poderia aliviar os danos induzidos pelas crises, intensificar a reparação e reduzir a epileptogênese no hipocampo. Por outro lado, evidências têm demonstrado o envolvimento do FGF2 em mecanismos epileptogênicos, como brotamento de fibras musgosas e neurogênese. Nossos resultados sugerem a participação do FGF2 na fisiopatologia da ELT e o indica como um importante alvo para estudos farmacológicos
Abstract: Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. The process of epileptogenesis includes neuronal death, axonal sprouting, inflammation, neurogenesis, oxidative stress and gliosis. However, the molecular mechanisms behind them are not fully understood. Fibroblast growth factor (FGF) gene family encodes proteins with several functions in the organism, especially in the central nervous system. FGF family member functions in the human brain are unclear. To shed light on the involvement of the FGF pathway in TLE, we quantified the hippocampal expression of the following genes: FGF2, FGF8, FGF22, FGFR1, FGFR2, FGFR3, ITPR3, PIK3R3 and PIK3R5 in 10 pharmacoresistant patients and four post mortem controls. We also assessed the FGF2 protein expression by indirect immunofluorescence. Only for FGF2, was the mRNA level markedly increased in patients¿ hippocampi for the two reference genes tested, HPRT1 and ENO2+TBP in combination (P = 0.002 and P = 0.036, respectively). The percentage of FGF2 immunostained cells in the dentate gyrus was higher in patients than in the controls (P <0.05), but no significant alteration was found in the Ammon¿s horn. FGF2 preserves neurons from ongoing injury and acts as a powerful proliferation factor for neural stem cells. It could potentially alleviate seizure-induced damage and intensify repair and reduce epileptogenesis in the hippocampus. On the other hand, evidence has shown FGF2¿s involvement in epileptogenic mechanisms, such as axonal sprouting and neurogenesis. Our results clearly suggest the FGF2 participation in TLE physiopathology and point it out as an important target for pharmacological studies
Mestrado
Saude da Criança e do Adolescente
Mestra em Ciências
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O'Dwyer, Rebecca. "Quantitative Analysis of Ictal Head Movements in Temporal Lobe Epilepsy." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-82320.
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Jack, Roisin. "Memory functioning and quality of life in temporal lobe epilepsy." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/24736.
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The principal aim of this research was to explore whether individuals with temporal lobe epilepsy and significant memory impairment experience lower quality of life. Executive functioning and locus of control issues in temporal lobe epilepsy were also considered. A within subject design was used to explore these issues. Twenty-two participants with temporal lobe epilepsy underwent a neuropsychological assessment and completed 3 questionnaires; the Quality of Life in Epilepsy-31 item questionnaire, the Multidimensional Health Locus of Control questionnaire and the Hospital Anxiety and Depression Scale. Pearson correlations were used to investigate relationships between variables. A significant positive relationship between memory impairment and quality of life in temporal lobe epilepsy was revealed. Executive functioning was also shown to be an important factor influencing memory and quality of life. The influence of locus of control on memory and quality of life was less than anticipated. The results were discussed in relation to current literature. The implications of these findings for clinical practice and treatment were also considered.
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Carter, Georgina Maria. "Very long term memory in people with temporal lobe epilepsy." Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268653.
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Mickley, Nicole C. "Subtypes of Memory Impairment in Patients with Temporal Lobe Epilepsy." Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/psych_diss/64.
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Memory impairments are common in individuals with temporal lobe epilepsy (TLE). This is understandable given that temporal lobe brain structures involved in TLE play a central role in encoding memories. It is widely accepted that individuals whose seizure focus is in the left temporal lobe (LTLE) tend to have verbal memory impairments, whereas individuals whose seizure focus is in the right temporal lobe (RTLE) tend to have visuospatial memory impairments. However, evidence of functional subdivisions within the left and right temporal lobes in both the animal and human literature suggest that more specific subtypes of memory impairment may exist in TLE based on differences in seizure foci. The aim of this study was to identify more specific subtypes of memory-impairments in patients with intractable TLE using several measures of memory functioning and cluster analysis. Identification of more specific memory subtypes in TLE could have prognostic significance for patients and contribute to our knowledge about the organization of memory systems of the human brain. Four memory subtypes were identified in this sample: 1) patients with mild to moderate figural memory deficits; 2) patients with moderate to severe figural memory deficits, mild facial recognition deficits, and mild attention/concentration deficits; 3) patients with severe figural memory deficits and mild verbal episodic memory deficits; and 4) patients with no episodic or semantic memory deficits. Unexpectedly, the subtypes found did not exhibit the expected pattern of verbal memory impairments with left temporal lobe damage/dysfunction or visuospatial memory impairments with right temporal lobe damage/dysfunction. However, consistent with the literature, there was a trend towards some clusters with better verbal memory having higher left hippocampal volumes; and a trend towards one cluster with facial recognition deficits having lower anterior temporal lobe volumes. Small sample sizes in this study limited the ability to clearly validate many of the cluster differences, particularly differences in brain volumes. Nevertheless, the results of this study support the hypothesis that subtypes of memory impairment do exist in patients with TLE. With larger sample sizes, it is plausible that additional subtypes may be found, or the characteristics of the subtypes found may become clearer.
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Duchesne, Simon. "Computer aided diagnosis in temporal lobe epilepsy and Alzheimer's dementia." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=100354.
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Computer aided diagnosis within neuroimaging must rely on advanced image processing techniques to detect and quantify subtle signal changes that may be surrogate indicators of disease state. This thesis proposes two such novel methodologies that are both based on large volumes of interest, are data driven, and use cross-sectional scans: appearance-based classification (ABC) and voxel-based classification (VBC).The concept of appearance in ABC represents the union of intensity and shape information extracted from magnetic resonance images (MRI). The classification method relies on a linear modeling of appearance features via principal components analysis, and comparison of the distribution of projection coordinates for the populations under study within a reference multidimensional appearance eigenspace. Classification is achieved using forward, stepwise linear discriminant analyses, in multiple cross-validated trials. In this work, the ABC methodology is shown to accurately lateralize the seizure focus in temporal lobe epilepsy (TLE), differentiate normal aging individuals from patients with either Alzheimer's dementia (AD) or Mild Cognitive Impairment (MCI), and finally predict the progression of MCI patients to AD. These applications demonstrated that the ABC technique is robust to different signal changes due to two distinct pathologies, to low resolution data and motion artifacts, and to possible differences inherent to multi-site acquisition.
The VBC technique relies on voxel-based morphometry to identify regions of grey and white matter concentration differences between co-registered cohorts of individuals, and then on linear modeling of variables extracted from these regions. Classification is achieved using linear discriminant analyses within a multivariate space composed of voxel-based morphometry measures related to grey and white matter concentration, along with clinical variables of interest. VBC is shown to increase the accuracy of prediction of one-year clinical status from three to four out of five TLE patients having undergone selective amygdalo-hippocampectomy. These two techniques are shown to have the necessary potential to solve current problems in neurological research, assist clinical physicians with their decision-making process and influence positively patient management.
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Voets, Natalie L. "Pre-surgical fMRI evaluation of patients with temporal lobe epilepsy." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427657.
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Hawkins, C. A. "Some studies on an animal model of temporal lobe epilepsy." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375246.
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Anderson, Elizabeth. "Epilepsy of the temporal lobe origin : cognitive and psychosocial sequelae." Thesis, University of York, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261087.
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