Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.798538
Title: The heart of epilepsy : cardiac comorbidity and sudden death
Author: Shmuely, Sharon
ISNI:       0000 0004 8507 6855
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
The research described in this thesis aims to increase understanding of cardiac comorbidities and sudden unexpected death in epilepsy (SUDEP). People with epilepsy have a three-fold increased risk of dying prematurely compared to the general population. Common contributors to this are cardiovascular comorbidities, of which I provide an overview. Cardiovascular conditions and epilepsy can both lead to transient loss of consciousness (TLOC) with overlapping semiology. Particularly, myoclonic jerks which are commonly observed during syncope can be mistaken for signs of epilepsy. A misdiagnosis with detrimental consequences. I provide evidence that a careful analysis of motor phenomena can distinguish the two conditions. SUDEP is the commonest direct epilepsy-related premature death (UK > 500 people/year). It typically occurs following convulsive seizures (CS). Most victims are found prone and some suggested people should sleep supine. I assessed video-EEG recordings of 180 CS and demonstrated peri-ictal positions often change, and most ending prone turned during CS. Sleeping supine is thus unlikely to prevent a postictal prone position and reduce risk of SUDEP. Pathomechanisms underlying SUDEP are likely a combination of interacting cardiorespiratory and autonomic factors. People with Dravet syndrome (DS) have a particular high SUDEP risk. I show that 49% of reported deaths in DS are SUDEP cases, most < 10 years (78%). In DS, SCN1A mutations are mostly found, encoding a sodium channel expressed in brain and heart. DS mouse models suggest a key role for peri-ictal cardiac arrhythmias in SUDEP. I conducted a multicentre observational study and recorded 547 seizures in 45 DS participants. No major peri-ictal arrhythmias were found. Peri-ictal QTc-lengthening was, however, more common in DS than controls. This may reflect unstable repolarisation and increased propensity for arrhythmias. Prospective data to determine whether these peri-ictal variables can predict SUDEP risk is warranted.
Supervisor: Sander, J. W. ; Thijs, R. ; Sisodiya, S. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.798538  DOI: Not available
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