Pope, RA; (2014) Neurosurgery for Temporal Lobe Epilepsy: Psychiatric Outcome and Relationship to Cognitive Function. Doctoral thesis , UCL (University College London).

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Abstract

Temporal lobe epilepsy (TLE) is a chronic neurological disorder characterised by recurrent seizures arising from temporal lobe structures. Medical treatment is effective for the majority but for the remainder, seizure control remains difficult to achieve. Epilepsy surgery, however, has proved an effective treatment. Following TLE surgery psychiatric symptoms can develop for the first time (de novo), and pre-existing symptoms may worsen; having a detrimental impact on patients’ quality of life. Yet, research data on psychiatric complications following TLE surgery is limited, in sharp contrast to the continuing emphasis on neuropsychological and neurological sequelae. The central aims of this thesis were to increase our understanding of the psychiatric status of patients with intractable TLE pre- and postoperatively, and to identify risk factors associated with poorer postoperative outcomes. This thesis is divided into 2 main sections. Section 1 (Chapters 1-5) provide a literature review that demonstrates pre- and postoperative psychopathology in TLE is common, unrecognised, and under-treated. Emerging evidence suggests that pre-surgical psychiatric morbidity is associated with more widespread cerebral pathology, but striking, is the lack of attention to its relationship to cognitive variables. The central hypothesis formulated and explored here is that TLE patients with less localised cerebral dysfunction, as supported by electrophysiological, neuro-radiological and cognitive indicators will be at risk for psychiatric disturbance preoperatively and have poorer outcomes following TLE surgery. Section 2 consists of 5 interlinked studies incorporating retrospective and prospective methodologies. In Study 1 (Chapter 7), the medical records of 280 TLE surgical cases were reviewed, and more than a third presented with significant psychiatric morbidity within 4 years following surgery. Fifty-one patients (18%) developed de novo psychopathology, half within 6 months of surgery and for the majority, persisted for more than 6 months. A preoperative history of secondary generalised tonic-clonic seizures (SGTCS) was an independent predictor of de novo psychopathology, but cognitive variables were not. Patients with a history of SGTCS and those with a preoperative psychiatric diagnosis were significantly less likely to remain seizure free. Using voxel based morphometry (VBM), Study 2 (Chapter 8) explored the preoperative neural correlates of de novo depression in a sub-group of patients (n=43) presented in Study 1. Grey matter (GM) reductions in the orbitofrontal cortices (OFC), ipsilateral cingulate gyrus and ipsilateral thalamus were associated with the development of de novo depression within 4 years postoperatively. In Study 3 (Chapter 9), a sub-group of patients from Study 1, with a diagnosis of post-ictal psychosis (TLE+PIP), were compared to age-matched TLE patients without any psychiatric history (TLE-only; n=60), with respect to pre-surgical clinical and cognitive variables. TLE+PIP patients were significantly less likely to have localised ictal epileptiform activity and more likely to have a positive family psychiatric history than TLE controls. Other clinical and cognitive variables did not distinguish between the groups. Patients with two or more PIP episodes had significantly increased odds of developing de novo psychopathology within 4 years of surgery, after controlling for comorbid pre-surgical psychiatric status and a history of SGTCS. A history of PIP was not a predictor of seizure status or cognitive outcome. Study 4 (Chapter 11) investigated the relationship between executive function and concurrent depression in TLE patients undergoing surgical evaluation. Depressed mood in TLE patients was associated with clinical, cognitive and behavioural indicators of more diffuse cerebral dysfunction. Using multilevel modelling, Study 5 (Chapter 12) provides clinically relevant data confirming that psychiatric disturbance is a significant complication following TLE surgery, and is predicted by the presence of pre-surgical executive dysfunction. The final chapter provides an overall summary of the findings, their implications, methodological limitations and directions for future research. It is argued that these studies have provided clinically relevant data that will aid the surgical decision-making process, and hopefully guide and improve post-surgical care and support.

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