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

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

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

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

Case Studies have been omitted at the request of the speaker

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

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

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

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

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 20-40 years

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

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

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

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

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

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 2016 JRSM Open 7(9) 1–7

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

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

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

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)

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

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