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Epilepsy is a common neurological disorder characterized by the recurrence of provoked seizures. Investigating the cellular and molecular events following a zure leads to a greater understanding in the mechanisms that potentiate subsequent seizures. Nitric oxide (NO) regulates the excitatory neurotransmitter, glutamate, through N-methyl-D-aspaitate (NMDA) receptors suggesting a role for NO in regulating neuronal excitability.

Background: Patients with Temporal Lobe epilepsy (TLE) commonly report difficulties with their memory but might not always exhibit impairment on standard memory tests. Recent research in TLE has suggested that extending published memory tests to assess recall over an extended period of several hours-weeks might reveal a pattern of accelerated long-term forgetting (ALF) that cannot be observed within the standard 30-40 minute (re)assessment period. This clinically-driven study aimed to examine memory in TLE using tests that included a sufficient delay to identify ALF but that were also ecologically-valid and clinically-practical; issues that have rarely been discussed in the existing literature. Method: Three participant groups were recruited to the study: n=14 people with TLE, n=16 control participants, and n=13 people with idiopathic generalized epilepsy (IGE). Memory performance was assessed by asking participants to recall or recognize material immediately after stimulus presentation (T1) and again following delays of 40-minutes (T2) and twoweeks (T3). As well as published word-list and story recall tasks, a novel news test was developed that examined memory with greater face-validity by using stimuli drawn from real television broadcasts. Further, procedures commonly employed in previous studies to artificially match groups' initial learning rates were avoided to prevent potentially compromising ecological-validity. Instead, the inclusion of the IGE clinical comparison group permitted the analysis of forgetting rate in TLE in the context of incidentally matched learning. The clinical practicality of including an extended delay period in assessment was addressed by conducting the two-week delayed assessment over the telephone. Results: The TLE group typically remembered less information than control participants at all delay periods; the discrepancy between their scores did not Page 58 of 225 Thesis Abstract Background: People with Temporal Lobe Epilepsy (TLE) commonly report memory difficulties. Confusingly, however, some of these patients perform within the normal range on standard memory tests that assess retention following a 30-40 minute delay. One interpretation of this discrepancy could be that mood disturbance causes over-reporting of memory difficulties. Alternatively, standard memory tests might lack the specificity required to assess the particular memory disturbance experienced in TLE. Concordant with the latter of these hypotheses, recent research has suggested that patients with TLE do exhibit objective memory disturbance provided that standard tests are adapted to examine recall after an extended delay of several hours-weeks; a phenomenon known as Accelerated Long-term Forgetting (ALF). Although there has been a steady increase in the number of group studies demonstrating ALF in TLE, relatively little is known about the clinical relevance of these findings in terms of their correspondence with patients' , everyday memory difficulties. This is particularly concerning given that studies reporting ALF have typically paid relatively little attention to the ecological validity of the assessments used. Aims: The primary aim of the present study was to increase the clinical salience of ALF research by examining whether this pattern of impairment would be observed in typical TLE when more ecologically-valid assessment materials and methods were employed. Further, we examined the relationship between patients' performance on objective memory tests and their subjective memory disturbances. The clinically-driven nature of the study meant that a secondary aim was to assess long-term memory in a way that would be practical to replicate in a clinical context. Method: Fourteen people with TLE were recruited. Their ability to retain neWly-learned information was assessed immediately after stimulus presentation (T1), following a delay of 40-minutes (T2) and again after an Page 2 of 225 extended period of two-weeks (+/- two days; T3). Clinical practicality was addressed by conducting the extended-delay assessment over the telephone. The rate at which participants with TLE lost information from memory was examined by comparing their performance to that of 16 control participants and 13 people with Idiopathic Generalised Epilepsy (IGE). Ecological -validity was addressed in three ways. Firstly, in addition to published word-list and story recall tests, a novel news story task was developed to assess participants' memory using stimuli drawn from real television broadcasts. Secondly, the inclusion of the IGE group meant that it was possible to compare forgetting rates between groups without matching initial learning levels through artificial experimental procedures used in most previous studies. Finally, we examined the relationship between participants' objective memory performance and their subjective views of memory disturbance gathered through self- and informant-based questionnaires as well as a self-report measure of mood. , Results: Group-level analyses indicated that patients with TLE experienced significant difficulties with their memory but the pattern of impairment was not indicative of ALF. Relative to the control participants, the TLE exhibited impaired memory within the standard 40-minute delay period that did not become exaggerated over the extended delay period. Compared to the IGE group, participants with TLE performed comparably for most memory tasks at most delay-points. Although there.was some indication that TLE participants' two-week delayed performance on the novel news story recall task was lower than expected, the contrast did not survive mUltiple-comparisons correction. Concordant with the group-level analyses, an individual case-series approach indicated ALF in only a small number of people and this was typically only evident for one memory task. Subjective and objective memory measures were not well correlated with each other or with mood. Unlike the other participant groups, however, informant-rated memory was associated with mood for the TLE group. Page 3 of 225 t Conclusion: ALF might not represent a clinically significant phenomenon amongst the typical TLE population. Page

Myoclonic epilepsy with ragged red fibres (MERRF) is a mitochondrial encephalopathy that results due to a single base change within the mitochondrial genome (m.8344A>G). Patients with MERRF present with disabling neurological symptoms such as myoclonus, epilepsy, ataxia and myopathy. Approximately 80% of MERRF patients carrying the m.8344A>G mutation also develop large tumours of adipose tissue known as lipomas within the dorsal, cervical and interscapular regions. Not only are these lipomas extremely disfiguring, they cause physical discomfort within patients restricting their movement.

Some people with epilepsy experience problems at work, putting them at risk of job loss. Work Instability [WI] is a state arising from a mismatch between an individual's functional abilities and the demands of the job, the consequences of which could threaten continuing employment. Currently there is no reliable way of screening for people with epilepsy who may have WI. This research aimed to develop a scale that can predict the risk of job loss for those in work and ascertain the relevance of the scale in clinical practice.

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