Novel Multimodality Imaging in the Planning and Surgical Treatment of Epilepsy Mr Mark John Nowell Thesis submitted for the degree of Doctor of Philosophy Department of Clinical and Experimental Epilepsy Institute of Neurology University College London August 2015 Declaration I, Mark Nowell, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Signed: Date: 1 Abstract Over 50 million people worldwide are affected by epilepsy and in one third of these the condition is poorly controlled by medication. In these patients epilepsy surgery offers potentially curative treatment. The presurgical evaluation and surgical management of epilepsy is complex. Patients typically undergo a range of imaging modalities, and may also require intracranial EEG (ic- EEG) evaluation. Cortical resections are informed by these investigations, with the aim of removing the epileptogenic zone (EZ) without causing any functional deficits. I have investigated the use of 3D multimodality image integration (3DMMI) and it’s relevance in epilepsy surgery in adults. I have supported the use of 3DMMI in our busy epilepsy surgery unit, and demonstrated that disclosure of models changes and informs clinical decision making during presurgical evaluation and surgical planning. EpiNavTM is custom-designed software for use in epilepsy surgery, representing an image- guided solution to address the complexities of the pipeline. I have incorporated this software into our clinical workflow and demonstrated the potential benefits of computer-assistance in planning depth electrode implantations. 3DMMI and EpiNav have been crucial in the development of the stereoEEG (SEEG) service in our unit. I describe the implementation of frameless SEEG, which forms part of our simplified, image guided pipeline for epilepsy surgery. Finally, I have gained experience in the generation of optic radiation tractography using constrained spherical deconvolution techniques, which are increasingly used in clinical practice. In a pilot study I demonstrate an association between language lateralisation determined by functional MRI and asymmetry in the position of the anterior bundle of the optic radiation in patients with epilepsy. 2 Table of Contents Table of Figures ..................................................................................................................................... 11 Table of Tables ...................................................................................................................................... 14 Abbreviations ........................................................................................................................................ 16 Acknowledgements ............................................................................................................................... 19 Funding sources .................................................................................................................................... 21 Outline and statement of personal contribution .................................................................................. 22 Publications associated with this thesis ................................................................................................ 25 1 Principles of epilepsy surgery ....................................................................................................... 29 1.1 Historical perspective ............................................................................................................ 29 1.1.1 Early history .................................................................................................................. 29 1.1.2 Functional localisation .................................................................................................. 29 1.1.3 Early advances in temporal lobe surgery ...................................................................... 32 1.2 Temporal lobe surgery .......................................................................................................... 35 1.2.1 Surgical anatomy of the temporal lobe ........................................................................ 35 1.2.2 Standard anterior temporal lobe resection .................................................................. 38 1.2.3 Selective amygdalohippocampectomy ......................................................................... 39 1.3 Extra-temporal Surgery ......................................................................................................... 40 1.3.1 Lesionectomy ................................................................................................................ 40 1.3.2 Hemispherotomy .......................................................................................................... 41 1.4 Palliative Surgery ................................................................................................................... 42 1.4.1 Disconnection techniques ............................................................................................. 42 1.4.2 Vagus nerve stimulation ............................................................................................... 43 2 Outcomes of epilepsy surgery ...................................................................................................... 45 2.1 Risk benefit analysis .............................................................................................................. 45 2.2 Limitations with previous studies ......................................................................................... 46 2.2.1 Outcome classification scores ....................................................................................... 46 2.2.2 Temporal lobe surgery .................................................................................................. 48 2.2.3 Extratemporal surgery .................................................................................................. 51 2.2.4 Hemispherotomy .......................................................................................................... 51 2.2.5 Palliative ........................................................................................................................ 52 2.2.6 Summary ....................................................................................................................... 52 2.3 Surgical morbidity and mortality .......................................................................................... 53 2.3.1 Temporal lobe surgery .................................................................................................. 53 3 2.3.2 Extratemporal surgery .................................................................................................. 54 2.3.3 Hemispherotomy .......................................................................................................... 55 2.3.4 Palliative procedures ..................................................................................................... 56 2.4 Neuropsychological outcomes .............................................................................................. 56 2.4.1 Memory ......................................................................................................................... 57 2.4.2 Language ....................................................................................................................... 58 2.4.3 Cognition ....................................................................................................................... 58 2.4.4 Psychiatric ..................................................................................................................... 58 2.4.5 Social outcomes ............................................................................................................ 59 3 Presurgical evaluation of epilepsy ................................................................................................ 61 3.1 Aims of evaluation ................................................................................................................ 61 3.2 Patient selection ................................................................................................................... 62 3.3 General pathway for presurgical evaluation......................................................................... 63 3.4 Clinical evaluation ................................................................................................................. 65 3.5 Scalp EEG and video telemetry ............................................................................................. 66 3.5.1 Background ................................................................................................................... 66 3.5.2 Epileptiform discharges ................................................................................................ 67 3.5.3 Ictal EEG ........................................................................................................................ 68 3.5.4 Interictal EEG ................................................................................................................. 68 3.5.5 Quantitative EEG ........................................................................................................... 69 3.5.6 Seizure semiology ........................................................................................................