1. Tackling Epilepsy Mortality
EpiGen-UK0261
Date of Preparation: June 2018
Tackling Epilepsy Mortality
Making waves in epilepsy meeting
18th May 2018
Dr Rebecca Liu
Royal Free London NHS Foundation Trust
This meeting has been initiated and funded by Eisai

2. I have received a speaker’s fee from Eisai for this presentation

3. agenda Epidemiology and common causes Case reports SUDEP
Indirect causes of death in epilepsy

5. Causes of death in epilepsy (adapted from Devinsky et al
Causes of death in epilepsy (adapted from Devinsky et al. Neurology 2016)
Deaths directly due to epilepsy (34%) *
SUDEP
Status epilepticus
Drowning
Trauma / Motor accidents
Falls, burns, asphyxiation
Aspiration pneumonia
Treatment-related deaths
Idiosyncratic drug reactions
Medication adverse events
Deaths related to underlying disease
Brain tumour
Stroke
Cerebral infection
Inherited disorders
Deaths indirectly or unrelated to epilepsy
Pneumonia
Suicide
Cardiovascular / cerebrovascular disease
Neoplasms outside the CNS
*National Sentinel Clinical Audit of Epilepsy Related Deaths

6. Case Studies have been omitted at the request of the speaker

7. Learning points Extend safety advice to travel on public transport
Avoid travelling alone following a seizure
Advise on safety at home, risk assessment
Treat seizures aggressively - Even minor seizures can be life threatening

8. Psychiatric comorbidity
75% of people with epilepsy who died from suicide, assault, accident, had lifetime history of psychiatric disorder cf. 41% for the overall epilepsy cohort (Fazel et al. Lancet 2013)
Screen for and treat comorbid depression
Risk for suicidality and drug adherence

9. LEARNING POINTS:
Recognition that SE can cause DIC, multiorgan failure and death even in low risk individuals

10. SUDEP Sudden and Unexpected death in person with epilepsy
Witnessed or unwitnessed
May or may not have been related to a recent seizure
Not related to trauma, drowning or status epilepticus
Definite SUDEP – autopsy shows no structural / toxicological cause
Near SUDEP – death likely if resuscitation not applied.
Nashef and Brown. Epilepsia 1997

11. SUDEP
Accounts for 50% of epilepsy related deaths in refractory epilepsy (Lhatoo & Sander 2005)
Young PWE are 24X more likely to die of sudden death
Commonest in age years

12. MORTEMUS study
Retrospective survey of EMU in Europe, Israel, Australia and New Zealand
147 Units participated
16 SUDEP - ½ definite, ½ probable
Ryvlin et al. Lancet Neurol 2013; 12: 966–77

14. Postictal generalised EEG suppression
Reported in all observed EMU SUDEP cases
Absence of EEG activity >10mcV amplitude postictally
Postictal generalised EEG suppression (PGES)- 65% adults with convulsive seizures. Rare following CPS
More common at night and following drug withdrawal
Leads to failure of protective arousal mechanisms
Often motionless post-ictally reflecting deeper postictal coma

16. Ameliorating risk
Encourage patients to use EpSMon (Epilepsy Self Monitor)
Based on SUDEP and Seizure Safety Checklist

17. Ameliorating risk Achieving best seizure control possible. Positioning
Stimulation, supervision
Consider seizure detection device
Discuss SUDEP risk with patients

18. Are we discussing SUDEP?
ABN Survey of UK Neurologists Morton et al. JNNP 2006
2/13 (15%) RFH neurologists (2015) discuss with all patients

19. Findings 72% PWE felt that SUDEP should be discussed with all patients
44% felt SUDEP information should be given at the point of diagnosis
68% wanted information to be given by their specialist face to face (+/- info sheet)
75% wanted their family members informed about SUDEP
2-7% patients and caregivers wished they had not been told
Keddie, Liu JRSM Open 7(9) 1–7

20. An approach to SUDEP discussions
To drive discussions on: treatment initiation, lifestyle, independent living, compliance, drug withdrawal, referral for surgery / VNS.
Discuss early rather than later
Discussing SUDEP in context of avoiding seizure-related accidents may be more palatable
Put risk into perspective

21. Causes of death in epilepsy (adapted from Devinsky et al
Causes of death in epilepsy (adapted from Devinsky et al. Neurology 2016)
Deaths directly due to epilepsy (34%) *
SUDEP
Status epilepticus
Drowning
Trauma / Motor accidents
Falls, burns, asphyxiation
Aspiration pneumonia
Treatment-related deaths
Idiosyncratic drug reactions
Medication adverse events
Deaths related to underlying disease
Brain tumour
Stroke
Cerebral infection
Inherited disorders
Deaths indirectly or unrelated to epilepsy
Pneumonia
Suicide
Cardiovascular / cerebrovascular disease
Neoplasms outside the CNS
*National Sentinel Clinical Audit of Epilepsy Related Deaths

22. Epilepsy and non-CNS cancer risk
Conflicting findings
Potential mechanisms:
AEDs
Lifestyles
Genetic predisposition
Possible reduced cancer survival–enzyme inducing AEDs and cytotoxic drugs

23. Epilepsy and vascular disease
Epilepsy associated with increased mortality from CVD - Annegers 1984, Nilsson, 1997
Increased carotid intima media thickness – positively correlated with AED duration (Tan 2009)
WHY might there be an increased cardiovascular risk?
Lifestyle factors – exercise less, dietary habits, smoke more
Enzyme inducers increase total serum cholesterol, TG, LDL fractions and range of surrogate markers of vascular risk
Valproate – obesity (70%), sedation, metabolic syndrome (40% females)

24. action Discuss lifestyle measures, address vascular risk factors
Consider choice of AEDs if pre-existing metabolic / vascular risk factors
High dose statins +/- Ezetimibe

25. Take home messages All patients with epilepsy are at risk
Encourage use of EpsMon app / Sudep and Seizure Safety Checklists
Counsel about SUDEP risk early
Other causes of epilepsy related mortality also warrant discussion
Screen for psychiatric comorbidity
Discuss vascular risk factors and lifestyle in high risk patients