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Title: Novel TMS and EEG markers of diagnosis and treatment response in epilepsy
Author: Pawley, Adam David
ISNI:       0000 0004 5917 8823
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Approximately 30% of epilepsy patients do not respond to treatment, whereas others attain seizure freedom with the same medication, the reasons remain unclear. Previous work utilised transcranial magnetic stimulation (TMS) to reveal predictive markers of treatment response in new-onset drug-naïve patients, distinguishing good responders from those who become intractable. I hypothesised that these markers should also be present in long-term treatment resistant epilepsy, allowing outcome prediction in patients commencing new medications. A central hypothesis in this thesis is that, interictal brain dynamics in epilepsy differ from the stable state of the healthy brain and are related to seizure frequency. I addressed this using TMS measures of excitation and inhibition, and electroencephalography (EEG) as a measure of the larger-scale electrophysiological dynamic system. Using existing TMS data I examined motor evoked potentials (MEPs) in Idiopathic generalised epilepsy (IGE). MEPs were more polyphasic in patients and their relatives than controls, which may represent an inherited endophenotype. TMS measures were also compared between patients with well and poorly controlled epilepsy. Findings broadly indicated that poorly controlled patients have reduced excitability vs well controlled, the reasons are unknown, although a protective homeostatic mechanism may be responsible. Furthermore, TMS parameters in well-controlled epilepsy were closer to healthy controls than poorly controlled patients. A longitudinal TMS study in chronic epilepsy with patients studied before and after treatment change, revealed a weak effect suggesting reduced excitability in poor responders, although a range of factors suggested that TMS would not have utility as a predictive marker clinically. A pilot study also investigated whether external trigeminal nerve stimulation (eTNS) has a measureable effect on brain excitability. There was a small effect which may associate with treatment outcome. Finally, EEG measures were compared in well and poorly-controlled epilepsy, with the profile of a well-controlled patient closer to that of the healthy brain. Future work focusing on EEG as a marker of response in newly diagnosed epilepsy, utilising TMS-EEG for revealing mechanisms underlying treatment response would be appropriate.
Supervisor: Richardson, Mark Philip ; Valentin, Antonio Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available