Status Epilepticus for Pediatricians - 2011

STATUS EPILEPTICUS in Children and Adolescents:

STATUS EPILEPTICUS in Children and Adolescents Jay E. Selman, MD 2011

Overview:

Overview Definition Epidemiology Seizure types Effects of Status Epilepticus (SE) Risk factors for SE Management of SE 5.4.2011 Status Epilepticus 2011 2

Seizure = convulsion = fit:

Seizure = convulsion = fit Abnormal electrical discharge in the brain Associated change in behavior “Negative” = absence spell, ?drop “Positive” = tonic, clonic, combined, drop, myoclonic

SE: Definition (ILAE):

SE: Definition (ILAE) A seizure that shows no clinical signs of arresting after a duration encompassing the great majority of seizures of that type in most patients OR recurrent seizures without interictal resumption of baseline of CNS function . Commission on Classification and Terminology, 1989 5.4.2011 Status Epilepticus 2011 4

Status Epilepticus: Definitions:

Status Epilepticus: Definitions Convulsive seizure lasting > 30 min Serial seizures between which incomplete restoration of consciousness (Seizure present on arrival in the ER) OLD: Not Now 5.4.2011 Status Epilepticus 2011 5

Status Epilepticus: Current Definitions:

Status Epilepticus: Current Definitions Threatened / impending / prodromal / incipient SE : 0 to 5-10 minutes Established: >/= ~ 30 minutes Refractory: >/= 60 minutes 5.4.2011 Status Epilepticus 2011 6

Epidemiology:

Epidemiology 10 – 73/100,000 < 2 yo: 135 – 156/100,000 Febrile Status: 25-40 % of cases 4 – 8/1000 by age 15 years 5.4.2011 Status Epilepticus 2011 7

Etiology of New Onset SE:

Etiology of New Onset SE Singh, RK et al. Neurology 2010

Convulsive vs. Non-convulsive status:

Convulsive vs. Non-convulsive status Convulsive ~ 85% Non-convulsive ~ 15% 5.4.2011 Status Epilepticus 2011 9

Classification of Seizure Type:

Classification of Seizure Type Localization – related Generalized Unclassifiable 5.4.2011 Status Epilepticus 2011 10

Epilepsy Etiology: Classification:

Epilepsy Etiology: Classification Symptomatic Acute (< 7 days to event) Remote (> 7 days from event Progressive Idiopathic Cryptogenic = presumed symptomatic but ? etiology 5.4.2011 Status Epilepticus 2011 11

“Symptomatic” Etiologies:

“Symptomatic” Etiologies Acute Systemic / metabolic / toxic insult Infectious / parainfectious Structural Trauma Vascular (AVM, aneurysm, stroke) Dysgenesis

Epilepsy Etiology: Classification:

Epilepsy Etiology: Classification Symptomatic Acute (< 7 days to event) Remote (> 7 days from event Progressive Idiopathic Cryptogenic = presumed symptomatic but ? etiology 5.4.2011 Status Epilepticus 2011 13

Risk Factors Morbidity Mortality:

Risk Factors Morbidity Mortality

Risk Factors for Status - 1:

Risk Factors for Status - 1 PRIOR episode of status epilepticus Non-compliance Prior seizures Younger age Symptomatic etiology (TBI, ABI, etc) 5.4.2011 Status Epilepticus 2011 15

Risk Factors for Status - 2:

Risk Factors for Status - 2 Epilepsy syndrome Epileptic encephalopathy Questionable episode of status Mental retardation Hydrocephalus 5.4.2011 Status Epilepticus 2011 16

Risk Factors for SE - 3:

Risk Factors for SE - 3 Post op Neurosurgery Cardiac surgery Post hypothermia Progressive neurological disorder Family history of epilepsy 5.4.2011 Status Epilepticus 2011 17

Morbidity of SE - 1 :

Morbidity of SE - 1 Brain / systemic hypoglycemia Lactic acidosis Neuronal death 5.4.2011 Status Epilepticus 2011 18

Morbidity of SE - 2 :

Morbidity of SE - 2 Hyperthermia Rhabdomyolysis Increased ICP Disruption of cerebral autoregulation 5.4.2011 Status Epilepticus 2011 19

Morbidity of SE - 3 :

Morbidity of SE - 3 Ictal bradycardia Stress cardiomyopathy Neurogenic pulmonary edema Renal failure Fractures 5.4.2011 Status Epilepticus 2011 20

Recurrence of Status Epilepticus:

Recurrence of Status Epilepticus 11 – 16% at 1 year (including febrile status) 18% at 2 years (including febrile status) Recurrence – w/o febrile status 13% at 1 year 17% at 2 years 50% total Sillanpaa, M et al, 2002 5.4.2011 Status Epilepticus 2011 21

Mortality:

Mortality 0 – 7 % Risk factors Acute Remote symptomatic Etiologies CNS infection Severe neurological disabilities 5.4.2011 Status Epilepticus 2011 22

Nonconvulsive Status Epilepticus:

Nonconvulsive Status Epilepticus EEG recorded ictal event > 30 minutes without improvement or resolution Characteristics 75% - pre-existing clinical seizures 25% - de novo 5.4.2011 Status Epilepticus 2011 23

Nonconvulsive Status Epilepticus:

Nonconvulsive Status Epilepticus Risk factors Comatose on examination < 18 years old, esp. < 1 year old Prior seizures Metabolic disorders Duration – mean 50 hours Prolonged monitoring necessary 5.4.2011 Status Epilepticus 2011 24

MANAGEMENT OF CONVULSIVE STATUS:

MANAGEMENT OF CONVULSIVE STATUS 5.4.2011 Status Epilepticus 2011 25

General Principles:

General Principles Treat early and aggressively Identification of etiological and aggravating factors Written plan Call Neurologist 5.4.2011 Status Epilepticus 2011 26

Time Periods:

Time Periods Pre-hospitalization Home EMT Emergency Department In-patient 5.4.2011 Status Epilepticus 2011 27

Time Periods at BCH:

Time Periods at BCH Identification of seizure Initial treatment Disposition decision Stabilization 5.4.2011 Status Epilepticus 2011 28

Timetable for Treatment:

Timetable for Treatment Time Goal (min) Rx 1 Rx 2 Comment 0 Order BZD Seizure onset 5 BZD 1 st dose Draw labs 10 LVT or PHT 10 BZD 2 nd dose If still seizing 15 BZD 3 rd dose Prepare for transfer if still seizing 20 TRANSFER 5.4.2011 Status Epilepticus 2011 29

Decision Point (DP) 1:

Decision Point (DP) 1 Is this a seizure? 5.4.2011 Status Epilepticus 2011 30

DP 1: Differential Dx:

DP 1: Differential Dx Syncope Hypertonic spell Pain episode Behavioral 5.4.2011 Status Epilepticus 2011 31

DP 2: A B C D:

DP 2: A B C D A irway B reathing C ardiac D extrostick 5.4.2011 Status Epilepticus 2011 32

DP 2.1: Labs:

DP 2.1: Labs BMP with glucose Blood levels of anticonvulsants CBC / ESR / culture – IF fever 5.4.2011 Status Epilepticus 2011 33

DP 3: Initial Management:

DP 3: Initial Management IV access Thiamine 100 mg if at risk IV D 25 W 2-4 mL/Kg Anticonvulsant (AED)

DP 3.1: Initial Anticonvulsant Rx:

DP 3.1: Initial Anticonvulsant Rx Rapid onset High efficacy Multiple delivery routes Rx available on floor at all times 5.4.2011 Status Epilepticus 2011 35

DP 3: Initial Rx Route:

DP 3: Initial Rx Route 5.4.2011 Status Epilepticus 2011 36

Routes of Administration:

Routes of Administration IN – intranasal B - buccal IM – intramuscular PR – per rectum 5.4.2011 Status Epilepticus 2011 37

DP 3: Initial Rx Route:

DP 3: Initial Rx Route 5.4.2011 Status Epilepticus 2011 38

DP 3.1: Initial Rx W/O IV:

DP 3.1: Initial Rx W/O IV Rx Generic Rx Brand IM Buccal Nasal Per Rectum Midazolam Versed X X X (x) Lorazepam Ativan X Diazepam Valium X Clonazepam Klonopin X 5.4.2011 Status Epilepticus 2011 39

DP 3.1: Initial Rx W/O IV:

DP 3.1: Initial Rx W/O IV Rx Generic Rx Brand IM Buccal Nasal Per Rectum Midazolam Versed 0.2 0.5 0.2 (x) Lorazepam Ativan 0.1 Diazepam Valium 0.2 – 0.5 Clonazepam ODT Klonopin 0.02 Doses are mg/kg/dose Give - then start IV 5.4.2011 Status Epilepticus 2011 40

DP 3.1: Initial Rx W/O IV Recommendations:

DP 3.1: Initial Rx W/O IV Recommendations Rx Generic IM Buccal Nasal Per Rectum Midazolam 0.2 0.5 0.2 Lorazepam 0.1 Diazepam 0.2 – 0.5 Doses are mg/kg/dose Give - then start IV 5.4.2011 Status Epilepticus 2011 41

LZP vs. DZP + PHT:

LZP vs. DZP + PHT N = 178 LZP at 0.1 mg/kg/dose x 1 or 2 = 100% DZP + PHT 18 mg/kg/dose = 100% 5.4.2011 Status Epilepticus 2011 42 Sreenath TG 2009

LZP vs. DZP + PHT:

LZP vs. DZP + PHT Sreenath TG 2009

DP 3: Initial Rx Route:

DP 3: Initial Rx Route 5.4.2011 Status Epilepticus 2011 44

DP 3.2: Initial Rx With IV:

DP 3.2: Initial Rx With IV Rx Generic Rx Brand IM Buccal Nasal Per Rectum Midazolam Versed X X X (x) Lorazepam Ativan X Diazepam Valium X Clonazepam Klonopin X 5.4.2011 Status Epilepticus 2011 45

DP 3.2: Initial Rx With IV:

DP 3.2: Initial Rx With IV Rx Generic Rx Brand IV Midazolam Versed 0.2 Lorazepam Ativan 0.2 Diazepam Valium 0.2 Doses are mg/kg/dose 5.4.2011 Status Epilepticus 2011 46

DP 4: Seizure CONTINUES:

DP 4: Seizure CONTINUES At 5 minutes after first dose REPEAT same IV dose if IV in place OR REPEAT same non-IV dose by same route 5.4.2011 Status Epilepticus 2011 47

DP 5: Next Rx:

DP 5: Next Rx 5.4.2011 Status Epilepticus 2011 48

IV AED - Anticonvulsants:

IV AED - Anticonvulsants Fosphenytoin (from Dilantin) Levetiracetam (Keppra) Valproic acid (Depacon) Benzodiazepines (LZP, DZP, MDZ) Phenobarbital Lacosamide (Vimpat) 5.4.2011 Status Epilepticus 2011 49

IV Medications:

IV Medications RX Mg/Kg Infusion rate Comment Levetiracetam (Keppra) 30 15 min Fosphenytoin (Cerebyx) 20 mg PE 3 mg/kg/min Valproic acid (Depacon) 30 15 min Phenobarbital 20 10 min ** Respiratory depression w BZD ** 5.4.2011 Status Epilepticus 2011 50

If not on AED in IV form, start de novo IV AED:

If not on AED in IV form, start de novo IV AED Levetiracetam (Keppra) at 30 mg/kg/dose IV over 10 minutes OR Fosphenytoin 20 mg PE equiv at 20 PE /kg at a max rate of 3 mg PE/kg/min 5.4.2011 Status Epilepticus 2011 51

Timetable for Treatment:

Timetable for Treatment Time (min) Rx 1 Rx 2 Comment 0 Order BZD Seizure onset 5 BZD 1 st dose Draw labs 10 LVT or PHT 10 BZD 2 nd dose If still seizing 15 BZD 3 rd dose Prepare for transfer if still seizing 20 TRANSFER 5.4.2011 Status Epilepticus 2011 52

SUMMARY:

SUMMARY 5.4.2011 Status Epilepticus 2011 53

Key Points:

Key Points Early recognition Treatment plan available Treat aggressively Uncontrolled status causes neurological damage 5.4.2011 Status Epilepticus 2011 54

Bibliography:

Bibliography Abend, N et al Medical treatment of pediatric status epilepticus. Semin Pediatr Neurol 2010;17:169. Ahmad, S et al. Febrile status epilepticus: current state of clinical and basic research. Semin Pediatr Neurol 2010; 17:150. Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989, 30:389-99. Freilich, E et al Identification and evaluation of the child in status epilepticus Semin Pediatr Neurol 2010;17:144. Goldstein, J Status epilepticus in the pediatric emergency department. Clin Pediatr Emerg Med 2008;9:96. Lawrence, R et al. Neonatal status epilepticus Semin Pediatr Neurol 2010;17:163. McMullan, J et al Midazolam vs. DZP for the treatment of status epilepticus in children and young adults: a meta analysis. Acad Emerg Med 2010;17:575. Mikaeloff, Y et al. Devastating epileptic encephalopathy in school aged children (DESC): a pseudo encephalitis. Epilepsy Res 2006; 69:67-69. Lawrence, R et al. Neonatal status epilepticus. Semin Pediatr Neurol 2010;17:163. Ostrowsky, K et al. Outcome and prognosis of status epilepticus in children. Semin Pediatr Neurol 2010;17:195. Rajasekaran, K et al. Lessons from the laboratory: the pathophysiology and consequences of status epilepticus. Semin Pediatr Neurol 2010; 17:136. Rivello, JJ et al. Practice Parameter: diagnostic assessment of the child with status epilepticus (EBM); AAN;CNS. Neurology 2006;67:1542. Scott, RC. Status epilepticus in the developing brain: long term effects seen in humans. Epilepsia 50(suppl 12)2009:32. Sillanpaa, M, Shinnar, S. Status epilepticus in a population based cohort with childhood onset epilepsy in Finland. Ann Neurol 2002;52:303-310. Singh, R Gaillard, W. Status Epilepticus in Children. Current Neurology and Neurosciences Reports 2009, 9:137-144. Singh, RK et al. A prospective study of new onset seizures presenting as status epilepticus in childhood. Neurology 2010;74:636-642 Sreenath, TG et al. Lorazepam vs. diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: A randomized controlled trial. Eur J Paediatr Neurol 2009; 14:162-8. 5.4.2011 Status Epilepticus 2011 55

Etiology: Epidemiology:

Etiology: Epidemiology FC – status: 32 – 46% Acute symptomatic: 17 – 24% Remote symptomatic: 11 – 16% Cryptogenic / idiopathic:11 – 16% 5.4.2011 Status Epilepticus 2011 57

Epileptic Encephalopathy:

Epileptic Encephalopathy Childhood onset Premorbid status: normal Initial febrile illness w/o CNS infection Prolonged status epilepticus Evolution into intractable epilepsy Focal seizure onset, esp. in the perisylvian areas Abnormalities in hippocampi on MRI Frontal lobe involvement (50%) Permanent cognitive sequelae Mikaeloff, Y et al. 2006 5.4.2011 Status Epilepticus 2011 58