Seizures in Childhood Kitesh Moodley January 2009

Introduction Convulsion associated with febrile disease –2-4% of all children before the age of 5 years Symptomatic seizures –0.5-1% Epilepsy: –Recurrent unprovoked seizures First year of life: –1,2/1 000 Childhood and adolescents: –0,5-1/10000

Aetiology of Epilepsy Specific aetiology –Identifiable in only 30% of cases Idiopathic67.6% Congenital20% –Trauma –HIE –Congenital brain anomalies Trauma4.7% Infection4.0% Vascular1.5% Neoplastic1.5%

Seizure type Partial (Only a portion of the brain) - Simple (Normal consciousness) - Complex (Impaired consciousness) Generalized (Both hemispheres are involved)

Epilepsy classification Clinical presentation is quite variable –age of onset –seizure type –interictal condition –EEG –Outcome Evaluate the: –the epileptic syndrome –Possible aetiology The seizure type and syndrome type determine the –Specific appropriate treatment –Further evaluation

ILAE.org 1.Partial seizures –Simple With motor symptoms Autonomic symptoms Psychic symptoms –Complex Simple then altered LOC Altered LOC from beginning –Simple or complex which become generalised

Generalised Seizures –Absence –Myoclonic –Clonic –Tonic –Atonic –Tonic-clonic

Epilepsy syndromes Seizures may occur as partial or generalised Further divided into –Idiopathic –Symptomatic –Cryptogenic Special situations i.e febrile seizures

Main Periods according to Age Neonates –Subtle, erratic, non-febrile Infancy and early childhood –3 months to 3 years –Febrile seizures –Infantile spasms –Lennox Gastaut –Myoclonic seizures –Status epilepticus –Partial complex

Main Periods according to Age Childhood to early adolescence –Cryptogenic –Absences –Benign rolandic epilepsy Nine years to adulthood –Primary generalized epilepsy –Focal epilepsy with brain injury

Stats from ILAE Primary tonic-clonic seizures 20% Simple partial 20% Absence seizures 10% (more in children) Other 10% 40% of Epilepsy in adults is Complex partial seizures

Neonatal seizures Subtle seizures –Deviation of the eyes –Eyelids are flickering –Swimming or pedaling movements –Apnoeic spells Tonic Clonic Myoclonic Seldom tonic clonic seizures

Aetiology of neonatal seizures Perinatal: –HIE Metabolic –Hypoglycemia, hypocalcemia –hypomagnesemia –Other Infections Structural abnormalities

Treatment of neonatal seizures Optimize ventilation, cardiac output, BP, glucose, electrolytes and pH. Treat the underlying disease Intravenous line is essential Treat the seizures promptly and vigorously Phenobarbitone Phenytoin

Febrile seizures Definition: –Seizure in children between the age of 6 months and 3-4(5) years in association with fever but without evidence of an intracranial infection Majority occurs before the age of 3 years Average age of onset: 18 months to 22 months Boys more than girls

Pathophysiology Seizure threshold is low in children Susceptible to infections i.e urti, LRTI Possible role of endogenous pyrogens IL1 –May increase neuronal activity Probable role of cytokines

2 Types Simple febrile seizures –Generalise –<15min duration –Do not recur within 24hrs Complex –Prolonged seizures –Usually more than one in a 24hr period –Or may be focal –Indicative of a more serious condition

Febrile seizures Recurrence –1/3 may have at least one recurrence –The younger the age of onset the greater the risk of recurrence –Low fever at first seizure –Family hx Risk of developing epilepsy –2% (vs 1% in gen pop) –Risk increases with: Complex Abnormal neurological state

Investigation of febrile seizures Lab investigations, although routine, usually unhelpful, in the evaluation of first time seizure – possible just a Na and Glucose CT is not warranted in the evaluation of simple febrile convulsions but considered for complex –Study of 71 patient with complex seizures None had an intracranial condition requiring treatement Routine EEG is seldom necessary ??LP –Simple febrile seizure probable not indicated Probable those with prolonged post-ictal phase –Current recommendation should be routine in the under 12 month group

Treatment of febrile convulsion Oxygen and supportive care Benzodiazapines Antipyretics –Do not appear to prvent recurrence Councel parents

Treatment of Epilepsy –Drug treatment should be regular –Simple as possible –Minimum of side effects –Monotherapy –Changes should be made gradually –High initial dosages increases side effects –Rapid withdrawal carries the risk of provoking status –Always calculate the dosage according to the weight

Treatment of Epilepsy Drugs commonly used –Carbamazepine –Sodium valproate –Clonazepam –Phenobarbitone –Phenytoin Newer drugs –Clobazam –Oxcarbazepine –Gabapentin –Vigabatrin –Lamotrigine

Treatment of Epilepsy Antiepileptics can cause convulsions –Benzodiazepines can induce TC seizures in LGS –Carbamazepine may exacerbate absence seizures What is used as first line treatment. –Absence: Sodium valproate –Focal and Generalized TC: Carbamazepine

Status epilepticus (SE) presents in a multitude of forms, dependent on aetiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.) Generalized, tonic-clonic SE (GCSE) is the most common form of SE

Definition Conventional “textbook” definition of status epilepticus: –Single seizure > 30 minutes –Series of seizures > 30 minutes without full recovery

Why 30 minutes ? Animal experiments in the 1970s and 1980s had shown that... … neuronal injury could be demonstrated after 30 min of seizure activity, even while maintaining respiration and circulation Nevander G. Ann Neurol 1985;18(3):

More practical: Mechanistic definition GCSE is a condition which most likely will not terminate rapidly and / or spontaneously GCSE is a condition which requires prompt intervention Lowenstein DH. Epilepsia 1999

The longer SE persists, –the lower is the likelihood of spontaneous cessation –the harder it is to control –the higher is the risk of morbidity and mortality Bleck TP. Epilepsia 1999;40(1):S64-6 The Status Epilepticus Working Party. Arch Dis Child 2000;83(5):415-9.

Typical seizure duration Children > 5 years: Typical, generalized tonic-clonic seizure lasts < 5 minutes Young children and infants: little data. latsts < minutes Reviewed in: Lowenstein DH. It's time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120-2.

Revised Definition Generalized, convulsive status epilepticus in older children (> 5 years) refers to > 5 minutes of continuous seizure or >2 discrete seizures with incomplete recovery of consciousness

Causes Fever Medication change Unknown Metabolic Congenital Anoxic Other (trauma, vascular, infection, tumor, drugs) 36% 20% 9% 8% 7% 5% 15% \

Mortality Adults Childre n 15 to 22% 3 to 15% Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23- 30

Mortality The primary determinant of mortality and morbidity of SE in children is its aetiology With the highest mortality rates caused by an acute neurological condition (infection, trauma, stroke) Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

Prolonged seizures Duration of seizure Lifethreateningsystemicchanges Death Temporarysystemicchanges

Respiratory Hypoxia and hypercarbia – Ventilation (chest rigidity from muscle spasm) –Hypermetabolism (  O 2 consumption,  CO 2 production) –Poor handling of secretions –Neurogenic pulmonary oedema

Hypoxia Hypoxia/anoxia markedly increase (triple?) the risk of mortality in SE Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Towne AR. Epilepsia 1994;35(1):27-34

Acidosis Respiratory Lactic –Impaired tissue oxygenation –Increased energy expenditure

Haemodynamics Sympathetic overdrive –Massive catecholamine / autonomic discharge –Hypertension –Tachycardia Exhaustion –Hypotension –Hypoperfusion Exhaustion –Hypotension –Hypoperfusion 0 min 60 min

Cerebral blood flow - Cerebral O 2 requirement Blood pressure Blood flow O 2 requirement Seizure duration Hyperdyna mic Exhaustion Lothman E. Neurology 1990;40(5 Suppl 2): Hyperdynamic phase –CBF meets CMRO 2 Exhaustion phase –CBF drops as hypotension sets in –Autoregulation exhausted –Neuronal damage ensues Hyperdynamic phase –CBF meets CMRO 2 Exhaustion phase –CBF drops as hypotension sets in –Autoregulation exhausted –Neuronal damage ensues

Glucose Seizure duration 30 min SE SE + hypoxia Lothman E. Neurology 1990;40(5 Suppl 2): Hyperdynamic phase –Hyperglycemia Exhaustion phase –Hypoglycemia develops –Hypoglycemia appears earlier in presence of hypoxia –Neuronal damage ensues Hyperdynamic phase –Hyperglycemia Exhaustion phase –Hypoglycemia develops –Hypoglycemia appears earlier in presence of hypoxia –Neuronal damage ensues

Hyperpyrexia Hyperpyrexia may develop during protracted SE which impairs substrate delivery while increasing metabolic demand Treat hyperpyrexia aggressively –Antipyretics, external cooling –Ensure normal temperatures

Other alterations Increase WCC (50% of children) Spinal fluid leukocytosis (15% of children)  K +  creatine kinase Myoglobinuria

Oxygen, oral airway. Suction. Avoid hypoxia! Consider bag-valve mask ventilation. Consider intubation IV/IO access. Treat hypotension, but NOT hypertension A A B B C C

Treatment Intubate? –It may be difficult to intubate a child with active seizures –Stop or slow seizures first, give O 2, consider BVM ventilation –If using paralytic agent to intubate, assume that SE continues

Initial investigations Labs –Na, Ca, Mg, PO 4, glucose –WCC –Liver function tests, ammonia –Anticonvulsant drug level –Toxicology

Initial investigations Lumbar puncture –Always defer LP in unstable patients, but never delay antibiotic/antiviral treatment if indicated CT scan –Indicated for focal seizures or focal deficit or focal EEG, history of trauma or bleeding disorder Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA 1993;270(7):

Treatment Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless normo- or hyperglycemic Hyperglycemia has no negative effect in SE

Treatment The longer you wait to administer anticonvulsants, the more anticonvulsants you will need to stop SE Most common mistake is ineffective dose

Anticonvulsants Rapid acting plus Long acting

Anticonvulsants - Rapid acting Benzodiazepines –Lorazepam 0.1 mg/kg i.v. over 1-2 minutes –Diazepam 0.2 mg/kg i.v. over 1-2 minutes –If SE persists, repeat every 5-10 minutes

Benzodiazepines Diazepam –High lipid solubility –Thus very rapid onset –Redistributes rapidly –Thus rapid loss of anticonvulsant effect –Adverse effects are persistent: Hypotension Respiratory depression Lorazepam –Low lipid solubility –Action delayed 2 minutes –Anticonvulsant effect 6-12 hrs –Less respiratory depression than diazepam Midazolam –May be given i.m.

Benzodiazepine - Intramuscular Intramuscular midazolam –0.2 mg/kg i.m. –Aqueous solution is rapidly absorbed, anticonvulsant effect begins after 2 minutes Intramuscular lorazepam –Can be given, but lacks water solubility, thus later onset than midazolam Chamberlain JM. Pediatr Emerg Care 1997;13(2):92-4. Towne AR. J Emerg Med 1999;17(2):323-8.

Anticonvulsants - Long acting Phenytoin –20 mg/kg i.v. over 20 min –pH 12 Extravasation causes severe tissue injury –Onset min –May cause hypotension, dysrhythmia

Anticonvulsants - Long acting Phenobarbital –20 mg/kg i.v. over min –Onset min –May cause hypotension, respiratory depression –Neurology RXH : no upper limit to phenobarb High dose phenobarb for SE will prob need icu admission

If SE persists Propofol infusion 5-10 mg/kg/hr after bolus 2 mg/kg Midazolam infusion mcg/kg/min after bolus 0.15 mg/kg Isoflurane

Non - convulsive status epilepticus How do you tell that patient’s seizures have stopped?

Non - convulsive SE ? Neurologic signs after termination of SE are common: –Pupillary changes –Abnormal tone –Abnormal Babinski reflex –Posturing –Clonus –May be asymmetrical

Non - convulsive SE ? Up to 20% of children with SE have non - convulsive SE after tonic - clonic SE Particularly common in infants < 2 months Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

Non - convulsive SE ? If child does not begin to respond to painful stimuli within minutes after tonic - clonic SE stops, suspect non - convulsive SE –Urgent EEG

And Remember Airway Breathing Circulation Don’t Ever Forget Glucose