A Study of Interactions Between Memory Disorders and Epilepsy: Epileptic Seizures in Dementia, Contrasted with Transient Epileptic Amnesia
Date: 10 February 2020
University of Exeter
PhD in Medical Studies
The term dementia refers to a group of progressive neurodegenerative diseases in which patients experience a range of cognitive symptoms, with memory impairment the most common. These patients are also at risk of experiencing epileptic seizures. Transient Epileptic Amnesia (TEA) is a syndrome of temporal lobe epilepsy in which the ...
The term dementia refers to a group of progressive neurodegenerative diseases in which patients experience a range of cognitive symptoms, with memory impairment the most common. These patients are also at risk of experiencing epileptic seizures. Transient Epileptic Amnesia (TEA) is a syndrome of temporal lobe epilepsy in which the principal manifestation of a seizure is a brief episode of amnesia during which other mental functions are predominantly or entirely preserved. Patients with TEA describe persistent memory impairments which are distinct from their seizures. In this thesis two studies are described which look in detail at each of these conditions separately. The demographic features, seizure presentations and cognitive profiles of these two groups are then compared in order to improve our understanding of these under-recognised conditions, and to assist clinicians tasked with their diagnosis. It has been known for over a century that patients with Alzheimer’s disease (AD) can experience epileptic seizures. However, the degree to which the risk of epilepsy is increased in these patients remains unclear. Seizures were long thought of as a feature of advanced disease in these patients, only occurring several years after the onset of symptoms. However, more recent evidence has suggested that seizures can occur at an early stage of the disease, maybe even prior to the onset of memory symptoms. This suggests that seizures in this population may be a cause of decline, rather than purely a marker of severe disease. The aim of the work reported in this thesis is to investigate a cohort of patients with dementia and Mild Cognitive Impairment (MCI), recruited from a regional memory clinic in order to determine the prevalence, clinical features and prognosis of epileptic seizures in patients with MCI and all forms of dementia. A UK-based, prospective study of this nature has not been conducted before 144 patients with MCI and dementia were recruited from the Exeter memory clinic. Diagnoses were confirmed using established diagnostic criteria, together with a group of 80 age- and gender- matched healthy control subjects. Participants underwent a clinical interview and cognitive testing, in the company of a reliable informant, who also completed further questionnaires. Cognitive testing and informant questionnaires were repeated following a 12-month interval. A prevalence of epilepsy of between 12.5 and 25.7% is identified in this population. Patients in whom a clinical suspicion of epilepsy was suspected were no different to those in whom there was no clinical evidence of epilepsy in terms of age of onset or cognitive performance at their initial study assessment. However epilepsy patients scored higher on the informant questionnaires, suggesting a greater impairment and increased care requirements. At the time of their 12-month assessment, the patients in whom epilepsy had been identified performed significantly worse on cognitive testing, suggesting that the presence of seizures was associated with a more rapid decline in this group. The concept of TEA has been established for over 25 years. These patients describe amnesic episodes which are brief and frequently occur upon waking. Seizures may be associated with olfactory hallucinations. Studies have shown that they respond well to anti-epileptic medications. An initial cohort of 50 patients with TEA was described in 2007. In this thesis a further cohort of 65 patients is described and combined with the original 50 patients in order to clarify and more fully describe the demographic, clinical and neuropsychological features of this condition. Through this largest ever cohort of TEA patients it is shown that the mean age of onset of TEA is 61.7 years, and that men are more commonly diagnosed than women. Seizures in TEA typically last from 15 to 30 minutes and frequently occur on a monthly basis. 93% of patients in this study reported cessation of seizures following the initiation of medication. Despite this, interictal memory concerns are common: including autobiographical amnesia, accelerated long-term forgetting and topographical amnesia. In comparing these two groups it is shown that patients who experience TEA are younger than those who experience epileptic seizures as a feature of MCI or dementia. They perform better on cognitive testing and neuroradiological investigations are more likely to be normal. In TEA, ictal amnesia is more likely to be the sole feature of a seizure, and olfactory hallucinations are more common. Patients with dementia are more likely to experience periods of unresponsiveness. Patients who develop epileptic seizures as a feature of MCI or dementia demonstrate significant cognitive decline over time, whereas cognitive performance is typically stable in patients with TEA.
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