STATUS EPILEPTICUS

DR. CHOK CHIN NAM

Status epilepticus

The most common medical neurologic emergency in childhood.

Serious and often life-threatening medical emergency

DEFINITION

Epileptic seizure:Paroxysmal stereotyped disturbance of consciousness, motor function, sensation, emotion, behaviour, or perception on clinical ground resulted from cortical neuronal discharge (Concensus guideline on management of epilepsy 2010. Epilepsy Council, Malaysian Society of Neurosciences)

Status Epilepticus:Continuous seizure activity or recurrent seizure activity without regaining of consciousness lasting for >30 min

Definition

Convulsive seizure lasting more than five minutes has a high risk of lasting 30 minutes or more.

Treatment delay is associated with delayed treatment response.

Increased of seizure associated with increase mortality&morbdity

(Shinnar S et al. How long do new-onset seizures in children last? Ann Neurol 2001; 49:659.)

(Erikson K et al. Treatment delay and the risk of prolonged status epilepticus. Neurology 2005; 65:1316.)

THEREFORE: Treatment of seizure should start if no spontaneous resolution after 5 minutes or if evidence of cardio-respiratory compromise

Refractory status epilepticus: Seizures lasting for >60 minutes or not responding to adequate doses of and second line medications.

Epidemiology

The incidence of status epilepticus (SE) is 10 to 60 per 100,000 person-years (BMJ best practice)

SE occurs equally in males and females. Although SE can occur at any age, its temporal distribution is bimodal, affecting extremes of age (1st years of life and above 60s) (BMJ best practice)

Febrile status epilepticus is the most common type of status epilepticus in children.

About 1/3 of patients presenting with status epilepticus are having their first seizure, 40% of these later develop epilepsy.

Another 1/3 patients have an established diagnosis of epilepsy, and the remaining 1/3 have no prior history of epilepsy.

10 to 20% of children with epilepsy has at least 1 episode of SE.

Aetiology

New onset of epilepsy of any type CNS infection(meningitis, encephalitis,

cerebral abscess) Cerebral tumours, posterior fossa tumours Trauma Hypoglycemia Electrolyte Imbalance(hypo Na/Ca/Mg) Febrile seizure Inborn error of metabolism(NK-

hyperglycinemia, MELAS, galactosaemia…)

Aetiology

Refractory epilepsy Cardiac arrest Stroke and cerebral haemorrhage Alcohol abuse/withdrawal Drug overdose and toxicity

More than 80 % of the younger children had SE of febrile or acute symptomatic etiology, whereas older children were more likely to be in the cryptogenic

Risk factor

Underlying epilepsyPartial epilepsy SE comes in cluster of attack History of prior SE Young age (one year or less) at onset Symptomatic etiology of epilepsy(epilepsy with known cause)

BEWARE OF NON EPILEPTIC SEIZURE

Reflex anoxic seizure Breathing holding attack Cardiac Syncope Psychogenic seizure

Infection related SE

Herpes simplex - complex partial and convulsive status)

Bartonella particularly non convulsive status

Epstein-Barr virus, mycoplasma (postinfections encephalomyelitis with any type of SE)

Pathophysiology

When neurons are depolarized, calcium enters and floor the neuron cell through NMDA channels and causes injury or death.

Basis:Persistent neuronal excitation, inadequate inhibition of abnormal neuronal discharge.

Failure of desensitization of AMPA glutamate receptors, and reduction of GABA-mediated inhibition.

Endocytosis of the GABA-A receptors might partly explain the failure of GABA-A inhibition and the progressive pharmacoresistance to benzodiazepines like diazepam, lorazepam

At the same time, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) and N-methyl D-aspartate (NMDA) receptor subunits move to the synaptic membrane where they form additional excitatory receptors

Nair P P, Kalita J, Misra U K. Status epilepticus: Why, what, and how. J Postgrad Med 2011;57:242-52

Types of Status Epilepticus

Generalized Status Epilepticus (Most common)Generalized tonic-clonic status epilepticusClonic status epilepticusAbsence status epilepticusTonic status epilepticusMyoclonic status epilepticus

Focal Status Epilepticus Epilepsia partialis continua of KojevnikovAura continuaLimbic status epilepticus (psychomotor status)Hemiconvulsive status with hemiparesis

Subclinical seizure (non convulsive)- diagnosed on EEG (esp. Comatose)

New-onset refractory status epilepticus (NORSE) a distinct entity that can be caused by almost any of the causes of status epilepticus in a patient without prior epilepsy.

often unknown etiology, presumed to be encephalitic or postencephalitic, can last several weeks or longer, and often has a poor prognosis.

Systemic Complication of SE Hypoxaemiaimpaired ventilationincreased oxygen consumptionexcessive salivation tracheobronchial secretions

Haemodynamic DisturbanceRaised HR, BP Initially(catecholamine & sympathetic)Raised cerebral blood flow, to accommodate increased cerebral metabolic need.Eventually BP fall if prolonged.

Systemic Complication of SE Blood glucoseInitially high due to sympathetic discharge,Later decreased at 15-30mins after prolonged increased metabolic needs.

AcidaemiaLactic acidosis and/or respiratory acidosis

Prolonged muscle contractionHyperkalaemia, raised muscle enzyme, myoglobinuria(cause renal failure)

Systemic Complication of SE

Increased ICP Due to metabolic acidosis, hypoxemia, and carbon dioxide retention causing compensatory cerebral vasodilatation and increased cerebral blood flow.

Increase ICP Reduce oxygen and substrate delivery cerebral odema increase ICP (VICIOUS CYCLE)

Systemic Complication of SE CSF PleocytosisIncreased WBC in CSF

General approached to status epilepticus

Airway Breathing, oxygen high flow mask, spO2 monitoring Circulation, venous access BP, HR, cardiac

monitoring Rapid neurological deficits assessment

Rapidly rule out and correct hypoglycemia <2.6mmol.Suppository paracetamol if feverLoose clothing, remove patient from dangerous area, left lateral positioning

Initial Investigation

FBC BUSE Ca/Mg/Po4 Blood Glucose Blood Gas Liver function test Urine and blood toxicology (if applicable) Anti epileptic drug level (if applicable)

Status epilepticus algorithmn Available in Paediatric Protocol for

Malayian Hospital (3rd edition)

First line AED

Benzodiazepine Enhances GABA receptor mediated neuroinhibition.First line AED, 1st dose given at 5 mins, 2nd dose at 10 mins.

PR diazepam commonly given first 0.2-0.5mg/kg.IV lorazepam 0.1mg/kgIV diazepam 0.2mg/kg IM/buccal midazolam 0.1mg/kg

Rectal diazepam

Second line AED

PhenytoinVoltage gated Na+ channel blocker Second line AED, longer acting, preventing recurrence of SE for extended periods of time Loading dose: 20mg/kg, given over half to 1

hour. Repeated dose of 5-10mg/kg can be given if unresponsive.

SE: hypotension, cardiac arrthymia Less effective in seizure cause by drug or

toxins.

Alternate second line AED

Phenobarbitone/phenobarbitalLongest acting, loading 20mg/kg, infused at 25mg-50mg/min. Direct blockade of glutamate, GABA

mediated influx of chloride into neuron. Use phenobarbitone if patient already on

regular phenytoin. Prolonged sedation and respiratory depression, likely require intubation.

Alternate second line AED

Sodium ValproateLoading Bolus 20mg/kg, follow by infusion 1-5mg/kg/min.

IV midazolamBolus 0.2mg/kg, then infusion at 3-5mcg/kg/min.

Refractory seizure

Pentobarbital — bolus infusion of 5 to 15 mg/kg IV then continuous infusion of 0.5 to 5.0 mg/kg/Hour

side effects : respiratory depression, hypotension, myocardial depression, and reduced cardiac output. Thus, intubation and mechanical ventilation with intravascular pressure monitoring are required prior to treatment, and inotropic agents frequently are needed.

Midazolam — bolus infusion of 0.2 mg/kg IV followed by a continuous infusion of 0.05 to 2 mg/kg/hour; for breakthrough seizures, additional 0.1 to 0.2 mg/kg boluses can be given and the continuous infusion rate increased by 0.05 to 0.1 mg/kg/hr every 3 to 4 hours. Minimal cardiovascular side effects

Propofol — Propintravenous anesthetic with rapid onset and short duration of action.

Side effects include hypotension(if fast infusion), apnea and bradycardia. However, adverse cardiovascular effects occur less often with propofol than with pentobarbital. Hypertriglyceridemia and pulmonary edema. Maintenance infusions associated with fatal acidosis and rhabdomyolysis of the skeletal and cardiac muscles

Refractory seizure

Intubation require if unable to sustain oxygen saturation, unable to maintain airway.

Intubation needed if convulsive status epilepticus >30 minutes.

Also need especially if respiratory depression from repeated benzodiazepine, phenobarbitone, propofol, thiopentone.

Additional consideration

Previous response — knows which AED was effective in arresting previous status epilepticus. If the child did not respond to phenytoin another drug like sodium valproate would be preferable.

Missed medication — If on long-term AED must ask any missed dose, (i.e child is known to missed one or more doses of VPA, intravenous VPA, rather than phenytoin, should be given. Low AED levels may contribute to SE in up to one third of patients

Paradoxical effects — AEDs can paradoxically trigger SE●AEDs, including phenytoin, carbamazepine, gabapentin, tiagabine, and vigabatrin, can precipitate generalized convulsive SE, particularly the myoclonic type, nonconvulsive (absence) SE.●Carbamazepine, phenytoin, and lamotrigine may worsen myoclonic seizures.●Carbamazepine and phenytoin may worsen complex partial seizures and increase generalized tonic-clonic seizures at high serum levels.●Carbamazepine is known to precipitate drop attacks, often with atypical absence seizures.●Benzodiazepines can rarely worsen seizures and precipitate tonic status epilepticus, particularly in children with Lennox-Gastaut syndrome

Additional consideration

Focal or brief seizures — Children with focal seizures or brief generalized motor seizures with relatively preserved interictal consciousness may require less emergent intervention

Repeated bolus infusions of benzodiazepines and barbiturates often lead to respiratory depression, endotracheal intubation, and hospitalization

Post ictal recovery

Most children begin to recover responsiveness within 20 to 30 minutes after generalized convulsions

Reason for delay recover : sedation from medications and ongoing non-convulsive seizures.

If do not return to a normal level of consciousness within a few hours after initial treatment, shoulde be monitored with EEG

Post ictal recovery

Full neurological examination

Additional investigation

Blood c&s , lumbar puncture if systemic or CNS infection is suspected

CT brain if suspected space occupying lesion or focal neurological abnomalities.

EEG once stabilized, or suspected subclinical seizure.

Recommendation by American Academy of Neurology; Child Neurology Society (2006, 2013)

There are insufficient data to support or refute whether blood cultures or a lumbar puncture should be done on a routine basis when there’s no clinical suspicion of systemic or CNS infection.

Anticonvulsant levels should be considered when a child with epilepsy on anticonvulsant prophylaxis.

Toxicology testing is considered when no apparent aetiology is immediately identified.

J. J. Riviello Jr et al. Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review). Neurology November 14, 2006 vol. 67 no. 9 1542-1550

Recommendation by American Academy of Neurology; Child Neurology Society (2006, 2013)

Metabolic studies for inborn errors of metabolism may be considered when there are clinical indicators.

EEG is considered in a child presenting with new-onset SE or if the diagnosis of non-convulsive SE or pseudostatus epilepticus is suspected.

Neuroimaging is considered if there are clinical indications or if the aetiology is unknown. it should only be done after the child is appropriately stabilised and the seizure activity controlled.

J. J. Riviello Jr et al. Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review). Neurology November 14, 2006 vol. 67 no. 9 1542-1550

Outcome

Mortality rates of SE in children varies between 3 to 9%.

The underlying etiology is the main predictor of mortality.

SE has14% risk of new neurologic deficits( focal motor deficits, mental retardation, behavioral disorders, and chronic epilepsy), most of this (12.5%) secondary to the underlying pathology.

Outcome

If SE is the first seizure, 50% will develop further seizure in the future. 20% of them became epilepsy.

21% will have recurrent status epilepticus

Conclusion

Status epilepsy is a serious medical emergency with mortality and associated neurological morbidity

Pharmacological treatment should commenced if seizure is established more than 5 to 10 minutes in view of delayed treatment causing delay response and pharmacoresistance.

reference

Angus Wilfong et al. UpToDate: Clinical features and complications of status epilepticus in children. Apr 28, 2015

Concensus guideline on management of epilepsy 2010. Epilepsy Council, Malaysian Society of Neurosciences

Shinnar S et al. How long do new-onset seizures in children last? Ann Neurol 2001; 49:659.

Erikson K et al. Treatment delay and the risk of prolonged status epilepticus. Neurology 2005; 65:1316.

Nair P P, Kalita J, Misra U K. Status epilepticus: Why, what, and how. J Postgrad Med 2011;57:242-52

J. J. Riviello Jr et al. Practice Parameter: Diagnostic assessment of the child with status epilepticus (an evidence-based review). Neurology November 14, 2006 vol. 67 no. 9 1542-1550