Temporal lobe epilepsy (TLE) is a common form of intractable epilepsy that can be treated with surgical resection of the epileptogenic medial temporal lobe tissue, specifically the hippocampus. This resection can lead to a variable degree of memory deficit and considerable research has been directed at identifying predictors of these deficits. This thesis explores the relationship between structural predictors and functional predictors in TLE. I looked at fMRI activation asymmetry produced by a scene encoding task as well as volume asymmetry ratios within the hippocampus and the relationship of these predictors to memory performance in patients with TLE. Mediation analysis was performed according to Baron and Kenny (1986) and showed that fMRI activation asymmetry mediated the relationship between volume asymmetry and memory asymmetry in patients with TLE. This suggests that activation asymmetry may be a preferred variable for assessing functional adequacy in the medial temporal region.

Underling neuronal loss and subsequent hippocampal sclerosis, as reflected by hippocampal atrophy on structural magnetic resonance (MR) imaging, are the dominant findings in the patient with mesial temporal lobe epilepsy (MTLE). Yet, prolongation of T2 relaxation time has also been reported as an early marker for MTLE, but it is a rather insensitive marker. Typical age-related atrophy often constitutes a significant confounding factor, and atrophy often represents a late sign in hippocampal sclerosis. In this connection, there is an urge for a sensitive independent predictor for the early detection of MTLE. T1rho MR imaging provides a distinct contrast mechanism in tissue characteristics. It is sensitive to physio-chemical processes and has been tested successfully in Alzheimer’s disease, Parkinson’s disease and certain brain tumors. Therefore, it is possible to depict early biochemical change in patients with MTLE by means of measuring the changes in T1rho relaxation time. T1rho relaxation time is not affected by age-related atrophic changes and thus can be used as an independent marker. In this preliminary study, we aimed to assess the feasibility of T2 relaxometry and T1rho MR imaging in identification of the atrophied zones in patients with MTLE. Seven patients with unilateral MTLE and fourteen normal subjects were recruited. Three-dimensional T1-weighted imaging, axial T2 relaxometry and T1rho imaging were performed on a 3T MR scanner. Hippocampal head, hippocampal body, hippocampal tail and amygdala were contoured on the axial T2-weighted images and then co-registered onto T2 relaxometry and T1rho images. A combination of visual and quantitative volumetric assessment was used as the primary end outcome. For T2 relaxometry and T1rho imaging, their respective relaxation times together with the corresponding right-left asymmetric ratios were calculated for subsequent analysis. Abnormal right-left asymmetric ratio is defined as a deviation of 2SD from the mean of the Z-score. In the lateralizing epileptogenic zones, T1rho yielded an overall accuracy of 92.9% (sensitivity 100%, specificity 60%), while T2 relaxometry yielded an overall accuracy of 71.4% (sensitivity 65.2%, specificity 100%) only. T1rho imaging is thus superior to T2 relaxometry (P = 0.036, by chi-square test). To conclude, the present study indicated that T1rho is feasible and potentially useful to serve as a non-invasive imaging tool in the detection of lateralization of the epileptogenic zone in patients with MTLE. It can also facilitate prompt diagnosis and longitudinal disease monitoring. In addition, the generation of associated color-coded parametric map can provide an easy mean for direct visual analysis. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

Through the use of chronic experimental animal models, the majority of in vitro investigations of temporal lobe epilepsy have demonstrated enhanced network activity within the subdivisions of the hippocampal formation. However, clinical evidence in combination with in vivo and in vitro studies indicates that structures external to the hippocampus contribute to the genesis of seizure activity. To address the effects of limbic network excitation, I have utilized combined hippocampal---entorhinal cortex brain slices from pilocarpine-treated rats that display chronic seizures. / My investigations have focused upon three structures, the subiculum, entorhinal cortex and the insular cortex. The experiments in the pilocarpine-treated subiculum demonstrated increased network excitability that was attributed to a more positive GABAA receptor mediated inhibitory post-synaptic potential (IPSP) reversal point coupled with a reduced IPSP peak conductance. Utilizing RT-PCR analysis and immunohistochemical staining we observed a decline in K+-Cl- cotransporter mRNA expression and a reduced number of parvalbumin-positive, presumptive inhibitory interneurons. My second project assessed the network hyperexcitability in layer V of the lateral entorhinal cortex. This is the first study to report spontaneous bursting, in the absence of epileptogenic agents, in the epileptic entorhinal cortex. We attributed this level of network excitation to reduced GABAA receptor mediated inhibition and increased synaptic sprouting. In the final project, we extended our slice preparation to include the insular cortex, a structure external to the temporal lobe. Our investigations identified a mechanism of NMDA receptor dependent synaptic bursting that masked GABA A receptor mediated conductances.

An impression which has dominated both the clinical setting and research literature is that patients with temporal lobe epilepsy (TLE) not infrequently issue "bitter" complaints about their memory function. This observation has rarely been subjected to investigation, based as it is, on the implicit assumption that TLE subjects are "entitled" to a memory disturbance given the involvement of a critical memory structure (i.e, hippocampus) in the pathogenesis of the disorder. While it is almost axiomatic that clinicians become aware of memory difficulties because of the subjective complaints issued by patients, there is growing awareness that the relationship between complaint and objective memory disturbance is a complex and often counterintuitive one. This is particularly true of many patients with TLE who while complaining about their memory function often do so in the presence of objectively normal interictal memory function. / This thesis addressed the question: Why do patients with TLE complain about their memory? It was premised on the notion that memory self-report is not a unidimensional construct explicable in terms of an underlying memory dysfunction alone, but the perception and expression of memory may arise from seemingly disparate sources. The principal objective of the thesis was to systematically and comprehensively investigate the complaint in TLE, and to derive an understanding of the variables which contribute to the perception and expression of poor memory in members of this population. The variables selected for investigation emerged from a detailed review of the literature and can be grouped into five broad conceptual domains: demographic, epileptological, psychological, cognitive, and metacognitive. (For complete abstract open document)

Thesis (M.Sc.)(Psych.)--University of Melbourne, Dept. of Behavioural Sciences, 2006. / Typescript. Includes bibliographical references (leaves 132-148).

Thesis (Ph. D.)--Cornell University, August, 2008. / Vita. Includes bibliographical references (leaves 126-141).

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 99-114).

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 95-104).

Orientadores: Fernando Cendes, Elba Cristina Sa de Camargo Etchebehere / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-08T16:14:13Z (GMT). No. of bitstreams: 1 Amorim_BarbaraJuarez_D.pdf: 19998647 bytes, checksum: 077344d8015d725dd9cde43d2987f38d (MD5) Previous issue date: 2007 / 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

M.A. / Himmehoch (1984, 1987) in discussion of major mood disorders related to epilepsy, describes an affective condition termed subictal mood disorder. Patients with subictal mood disorder are divided into manic-depressive and dysthymic subtypes, the former resembling an atypical, usually rapid-cycling bipolar mood disorder. The latter dysthymic group, are characterised by a baseline dysthymia, severe recurrent depressive episodes, and transient euphorias. In addition, these dysthymic patients are described as being especially prone to impulsive suicide attempts, extreme irritability, rage outbursts and deliberate self-harm. Himmelhoch (1984, 1987) postulates temporolimbic dysfunction with both ictal and subictal (subclinical) changes as the underlying aetiology. Temporolimbic phenomena such as anamnesic, dissociative and perceptive distortions are important aspects of neuropsychiatric phenomenology. Clinical evidence, however, suggests that these occurrences are not routinely sought for or uncovered during the clinical evaluation of patients and their relevance for atypical affective presentations not clearly understood. The aim of this clinical survey was to evaluate the presence and nature of both temporolimbic dysfunction and subictal mood disorder among a subpopulation of private psychiatric patients. Furthermore in order to explicate a possible association between the above, the electroencephalographic records of these patients were examined. Records of 761 patients who attended a private practice over a two-year period were retrospectively reviewed. 546 patients had been questioned in sufficient detail and were deemed reliable in their responses. Of the 546 patients reviewed 128 (23,4%) were found to have experienced significant temporolimbic phenomena. The most common features were dissociative states, deja vu, premonitions, jamais vu and tactile hallucinations. 150 (27,5%) patients met Himmelhoch's criteria for the presence of subictal mood disorder. Of those 150, 100 (66,7%) demonstrated significant temporolimbic phenomena. EEG results, with the exclusion of 16 patients (the appropriate records not being available), highlighted 64 iY (76,2%) ofthe probands as having met the criteria for significant temporolimbic phenomena and subictal mood disorder and demonstrating unequivocal abnormality onEEG. Taking into account the sample bias of this particular private practice, and the obvious flaws of a retrospective, naturalistic survey of this nature, the concept of sub ictal mood disorder is discussed. Case vignettes are used to illustrate the phenomenological presentation ofthese patients and the potential benefits of the addition of anticonvulsants in their management.