Shortman, Rob; (2025) The Impact of Brain Metabolism as Assessed using 18F-FDG PET in Patients with Temporal Lobe Epilepsy on Cognitive Function and Post Operative Seizure Outcomes. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text Shortman_10205272_thesis.pdf Download (10MB) | Preview

Abstract

Rationale: The focus of epilepsy research on brain metabolism, particularly in white matter regions, has indicated a potentially crucial role in the development and progression of the condition (Imamura et al., 2016). The current thesis examines cerebral glucose metabolism in patients with suspected temporal lobe epilepsy (TLE) for whom structural imaging did not convincingly determine a potential location/target for resective surgery to identify; regions of hypometabolism in patients vs normal controls; differences in metabolic pattern between patients with a positive/negative post-operative seizure status; the effects of reduced cerebral glucose metabolism on pre-morbid cognitive function; and presurgical and post-surgical verbal and visual recall. Study 1: Group Differences in Cortical and Subcortical Metabolism in Patients with Temporal Lobe Compared with Age- and Sex-Matched Controls Neurological sex differences in structure, as well metabolic differences, may interact with changes caused by the progression of focal epilepsy, but as yet these remain undefined. This study aims to compare uptake of 18F-fluorodeoxyglucose (18F-FDG) in the brains of a large sample of control participants compared with that of TLE patients to untie the effects of sex, and confirm if differences in TLE are independent of age-related changes.// Study 2: Pre-Operative Cerebral Glucose Metabolism in Patients and its Relationship to Post-Operative Seizure Status Correlation of unilobar cortical hypometabolism, with results from electroencephalogram (EEG) or structural magnetic resonance imaging, was related to positive post-surgical outcomes (Tomás et al., 2019). Recently, results of diffusion tensor imaging studies have revealed that white matter changes, also predictive of surgical outcome, are associated with reduced metabolism. This study aims to identify if there are patterns of cortical/subcortical hypometabolism related to post-operative seizure status. Study 3: The Effect of Reduced Cerebral Metabolism on Premorbid Cognitive Function and Pre and Post-Operative Verbal and Visual Recall in Temporal Lobe Epilepsy The aim of resective surgery for refractory TLE is the amelioration of the debilitating effects of seizures while maintaining cognitive function. Numerous risk factors have been identified for post-operative cognitive decline, including preserved pre-operative functioning and the identification of unilateral structural or metabolic disruptions concordant with results from neurophysiological investigations. Recent studies have identified the influence of metabolic disruptions in Alzheimers and Huntingtons disease, while white matter integrity has been associated with cognition in patients with human immunodeficiency virus (HIV). This study aims to identify whether white and grey matter metabolism is associated with cognitive decline in patients with TLE, and the relationship between cerebral metabolism and pre and post operative memory function.// Methods: FDG positron emission tomography (PET) data were pre-processed, normalizing PET data to a template, and analysed using Statistical Parametric Mapping software (SPM12, Welcome Trust Centre for Neuroimaging, London, UK; https://www.fil.ion.ucl.ac.uk/spm/) from within MATLAB (version 2022b, The Mathworks, Inc., USA, 2022).// Study 1: Cerebral glucose metabolism was analysed using SPM12 in groups of TLE patients divided by the hemisphere of presumed seizure onset as assessed using EEG and sex with age as a covariate. Further analysis was undertaken with patients divided by hemisphere of seizure onset zone, with age and sex as covariates. Study 2: Cerebral glucose metabolism was analysed using SPM12 in groups of TLE patients subsequent to resective temporal lobe surgery, divided by their post-operative surgical status as defined by the Engel classification (A1/<A1). The FDG PET Brain PET data acquired from the RTLE patients was mirrored in order that the presumed seizure focus was aligned to the Left hemisphere. // Study 3: Cerebral glucose metabolism was analysed using VBM in groups of TLE patients subsequent to resective temporal lobe surgery, divided by whether or not they suffered from pre-morbid cognitive decline (DECLINE/STABLE). For the DECLINE/STABLE comparison FDG PET Brain PET data acquired from the RTLE patients was mirrored in order that the presumed seizure focus was aligned to the Left hemisphere. Subsequent analysis was performed to identify cortical and subcortical regions in which variance in metabolism is negatively associated with decreased pre- and post-operative verbal and visual memory performance. For the analysis of post operative memory data FDG PET Brain PET data acquired from the RTLE patients was mirrored in order that the presumed seizure focus was aligned to the Left hemisphere.// Results: Study 1: Group Differences in Cortical and Subcortical Metabolism in Patients with Temporal Lobe Compared with Age- and Sex-Matched Controls Whilst correcting multiple comparisons the effects of potential family wise error (FWE), significant differences were identified in left and right TLE (LTLE and RTLE) female groups with female controls (FWE p=0.05), and significant differences were also identified between LTLE male groups with male controls (FWE p=0.05). Differences between male RTLE groups and controls were identified at the trend level (p=0.001 uncorrected). When male and female LTLE and RTLE groups were combined with sex as a covariate, there was extensive significant hypometabolism in both TLE groups compared with controls in bilateral thalamic, cerebral white matter, orbitofrontal regions and the brain stem. In the LTLE group significant hypometabolism was identified in the piriform cortex. There was a significant effect of hippocampal hypometabolism, but this was restricted to the ipsilateral hemisphere. Study 2: Pre-Operative FDG Uptake in Patients and its Relationship to Post-Operative Seizure Status When pre-operative uptake of FDG as assessed using Positron Emission Tomography/Computed Tomography (PET/CT) was compared between participants, those who continued to experience seizures post operatively demonstrated significantly reduced metabolism in thalamic, cerebral white matter and brain stem regions compared with TLE patients that experienced an optimal post-operative recovery (Engel A1) (p=0.001 uncorrected). Study 3: The Effect of Reduced Cerebral Metabolism on Premorbid Cognitive Function and Pre and Post-Operative Verbal and Visual Recall in Temporal Lobe Epilepsy In patients with TLE that remained cognitively stable, subsequent to the onset of seizures was associated patients with decreased metabolism in cerebral white matter, brain stem, bilateral thalamus and left entorhinal cortex compared with the group that experienced cognitive decline. Pre-operative verbal recall was associated with small regions of reduced cortical metabolism, whereas reduced post-operative memory performance was associated small regions of reduced white matter metabolism bilaterally.// Conclusion: The present thesis has identified regions of reduced metabolism in the brain stem, piriform cortex, as well as bilateral thalamic, orbitofrontal and white matter metabolism in patients with TLE. It has also been demonstrated that while reduced subcortical metabolism is evident in patients with poor post operative outcomes, it is also associated with cognitive stability subsequent to the effects of seizures. Results point toward a dichotomy between pre operative cognitive stability and post operative memory decline, that would benefit from a larger sample size to confirm. These results have important implications in the identification of TLE patients for resective surgery, as well as FDG PET/CT image interpretation and reporting.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item