EPILEPSY RELATED DEATH IN CHILDREN Chris Rittey - Sheffield Children's Hospital.

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Presentation transcript:

EPILEPSY RELATED DEATH IN CHILDREN Chris Rittey - Sheffield Children's Hospital

Definitions Definite SUDEP Patient suffered from epilepsy Patient died unexpectedly in reasonable health Death occurred suddenly (where known) An obvious medical cause of death was not found Death was not the direct result of seizure or SE Probable SUDEP As above but no PM Possible SUDEP SUDEP cannot be ruled out but insufficient information Nashef et al, 1997

Epidemiology Risk factors Mechanisms Management strategies Providing information Checklist

EPIDEMIOLOGY Incidence much lower in reported series in children Rates fairly consistent across studies in UK, Europe and USA Main issue remains ascertainment

Incidence Epilepsy related deaths Harvey et al /10000 patient years Donner et al /10000 (SUDEP) Callenbach et al /1000 (all deaths) Camfield & Camfield /1000 Weber et al /10000 (SUDEP) McGregor et al over 12 years (11 <19 years) – 7 def, 9 prob Nickels et al /10000 (SUDEP 2.2)

Camfield & Camfield Population based cohort study All children who developed epilepsy in Nova Scotia ( ) – population children – 26 deaths Only 4 unexpected deaths – 2 epilepsy related, 1 SUDEP (21 year old woman) Lancet 2002, 359:

Callenbach et al Dutch epilepsy study group – all children with epilepsy (< 16 years) – 494 children (22 excluded) 5 year follow-up or to death 9 deaths – no SUDEP Pediatrics 2001; 107:

Nesbitt et al Retrospective UK review from tertiary paediatric neurology service (97 deaths)/CEMACH (168 deaths) Neurology cohort - 66% deaths unrelated to seizure disorder, 7 unexplained deaths (7.3%) CEMACH cohort – 79% unrelated to seizure disorder, 25 unexplained (9.7%) Dev Med Child Neurol 2012; 54:

Risk factors for SUDEP Majority of cases of SUDEP in adults had childhood onset epilepsy Most deaths occur in sleep Risks for childhood SUDEP include Male sex Symptomatic epilepsy GTCS Prone sleep posture (?) Risks not identified Low AED levels, polypharmacy, specific AEDs

SUDEP in adults Risks identified: GTCS Polypharmacy Duration of epilepsy Young age at onset of epilepsy Male gender Symptomatic epilepsy Lamotrigine therapy Lack of terminal remission Hesdorfer et al, Epilepsia 2011; 52:

Idiopathic epilepsy Extremely low risk of epilepsy related death and SUDEP in children with idiopathic epilepsy Very rare reports of epilepsy related deaths in children with idiopathic epilepsy Nesbitt et al suggest risk of 65/ (cf diabetes 45/100000)

Causes of death In childhood majority of deaths unrelated to seizure disorder (i.e. due to underlying condition or co-morbidities)

Sillanpaa & Shinnar Long term follow-up of childhood onset epilepsy children, 40 years, 60 deaths 33/60 epilepsy related deaths 23/60 SUDEP (8 < 19 years) 4/60 status epilepticus (2 < 19 years) 6/60 drowning (3 < 19 years) Epilepsy & Behaviour 2013; 28:

Mechanisms of SUDEP SUDEP is likely to be the consequence of a variety of processes Likely mechanisms – respiratory – cardiac – ‘electrocerebral shutdown’

Respiratory mechanisms Most witnessed cases occur with GTCS Most reported cases had difficulty with breathing Apnoea a frequent finding in VT recorded seizures Likely that central and obstructive apnoea plays a role

Respiratory mechanisms Several postulated mechanisms – Respiratory arrest – Neurogenic pulmonary oedema – Asphyxiation Recent interest in 5HT defects in SUDEP (Richerson and Buchanan, Epilepsia 2011) – mouse models – 5HT role in control of breathing – common pathway with SIDS

Cardiac mechanisms Most important mechanism likely to be cardiac dysrhythmia caused by seizure – bradyarrhythmia – ventricular tachyarrhythmias – role of long QT syndromes Right hemispheric control of sympathetic cardiac control – cardiovascular dysregulation common in children with right temporal lobe seizures

Cardiac mechanisms Possible role of stress induced release of catecholamines Potential role of environmental stress  possible therapeutic interventions SUDEP reported in people with VNS but evidence suggests slight reduction of SUDEP risk in this population

Management I Almost all witnessed cases of SUDEP are associated with a seizure Reduced SUDEP rate in people undergoing successful epilepsy surgery Phase II trials in adults suggest increased mortality and SUDEP in those randomised to placebo Suggests causal relationship between seizure and SUDEP

Management II Aim for seizure freedom Suggestion that where this cannot be achieved aggressive attempts at seizure control can reduce but not eliminate risk of SUDEP Careful attention to basic safety precautions (bathing, swimming) Pet ownership (?) – see Terra et al, Seizure 2012; 21:

What do we tell our patients? SUDEP is a risk for patients with epilepsy not in remission In neurologically normal children risk is not significant until adolescence/adulthood ? Need to discuss at all with families of children with idiopathic epilepsy likely to remit in childhood (e.g. BCECTS)

Gayatri et al Questionnaires to parents attending regional paediatric neurology service and to 71 UK paediatric neurologists Parental questionnaire – repeated after 3 months 100 children (57 focal/epileptic encephalopathy) 1/3 had heard of SUDEP before the study 91% wanted to be told about SUDEP (74% at diagnosis, 16% when seizures poorly controlled)

Gayatri et al Majority of parents reported no adverse effects of being given SUDEP information Approx 50% said they would alter care for their child following information Neurologist questionnaire – 46 responses 43/46 (93%) provided SUDEP information 20% - to all patients 63% - to patients with intractable seizure 46% - to parents and children (> 12 years)

SUDEP checklist Several risk factors for SUDEP are potentially modifiable Shankar et al suggest use of evidence based checklist may allow clinicians and patients to identify and act on these Potential benefit in improving discussion about epilepsy related death Seizure 2013 – in press

Conclusions Children with epilepsy have a 3-4 x increase risk of death than the general population Most deaths in children with epilepsy are not related to the seizure disorder Death may occur as a result of SE, accident and SUDEP

Conclusions SUDEP risks are extremely low in children but finite risk in those with poorly controlled symptomatic epilepsies Strategies directed towards optimal seizure control likely to be most useful in reducing SUDEP rate Parents want to be told about SUDEP Checklist may be of value but will probably need modification in childhood