Status Epilepticus

Definition

• Defined by International League Against Epilepsy as "seizure that persists for sufficient length of time or is repeated enough to produce a fixed and enduring epileptic condition"

• More commonly defined as seizures lasting 30 minutes or longer (or without significant cessation of seizures during that time period where the patient does not regain consciousness)

• Generally thought that seizures lasting more than 5 minutes are more significant as most (~75%) last less than 5 minutes in children

• Generalized vs focal: Generalized involves both cerebral hemispheres and involves impairment of consciousness. Focal (previously referred to as partial) seizures originate within one hemisphere and can have impairment of consciousness as well (called complex focal seizures)

• Convulsive vs non-convulsive status epilepticus

• Various causes: Non-CNS infection, low antiepileptic drug (AED) level, cerebrovascular disease, metabolic, hypoxia, CNS infection, drug overdose, idiopathic

• 12% of first seizures in children present with status epilepticus (Shinnar, Pediatrics 1996)

• Mortality risk fairly low at ~3% and depends on underlying etiology

• Risk of subsequent epilepsy after status epilepticus is 26-36% (Barnard, J child Neurol 1999 and Eriksson, Develop Med Child Neurol 1997)

Convulsive status epilepticus (CSE)

Generalised CSE

• • Can be tonic-clonic, tonic or clonic

  • May start with a series of seizures in known epileptics

  • Coma, dysautonomia, cyanosis and hypotension can be seen in between seizures.

Clonic SE

• • • These seizures may continue for a number of hours and they are usually unilateral however they can alternate between sides.

    • Post-ictal hemiplegia can occur and also loss of consciousness may not occur.

Tonic SE

• • • Seen in children with known epilepsy, although less common than tonic-clonic or clonic SE

    • Tonic SE may be longer than other forms of CSE

Focal Motor SE

• • May be seen in children with a diagnosis of epilepsy or an acute brain injury

Myoclonic SE

• • Commonly seen in children with hypoxic-ischaemic injury, but can also be seen in hypoglycaemia, hepatorenal failure or heavy metal intoxication

  • It is classified as repeated myoclonic jerks

Non convulsive status epilepticus (CSE)

• Need to consider NCSE in children with prolonged post-ictal state or unexplained alterations in consciousness.

• Features include:

  • Alteration in level of consciousness > 30 minutes

  • Complex partial seizures without full recovery of consciousness

  • clinical EEG responses to IV anticonvulsants

Refractory status epilepticus (RSE)

• Definitions:

  • Seizures that are unresponsive to adequate first line AED's

  • Seizures that are unresponsive to 2 doses of diazepam in succession followed by Phenytoin or Phenobarbitone (20mg/kg) given over 30 mins as an infusion

  • seizures that continue 60-90mins post initiation of seizure activity

Pathophysiology

• Imbalance between excitation and inhibition, with overall excitation

• Deficits in GABA with downregulation of GABA receptors

• Neurotoxicity due to excitotoxicity (via excess stimuation from glutamate on NMDA and AMPA receptors) as well as hypoxic-ischemic injury (imbalance between increased metabolic demand and cerebral blood flow/oxygenation)

From "Status Epilepticus," Franzon D, Stanford University

Diagnosis

• Convulsive status epilepticus usually fairly obvious but nonconvulsive subclinical status epilepticus can occur and can be confused with a postictal state

• Continuous EEG monitoring critical

• Other diagnostic measures aimed primarily at identifying underlying etiology including: Head CT, Brain MRI, lumbar puncture, metabolic panel, blood glucose, blood gas, cultures, etc

Treatment

• Major goal is to terminate the seizure prior to irreversible neuronal injury

• Irreversible neuronal injury thought to occur after ~20 min-1hr of continuous seizure activity

• Status epilepticus becomes more difficult to treat as the duration of seizure increases

• ABC's:

  • Secure airway as needed (Consider NP or oral airway, intubation as needed)

  • If intubation needed, better to utilize short acting agents to avoid confounding neurological exam

  • Ensure adequate oxygenation/ventilation

  • Careful monitoring and treatment of blood pressure and perfusion

• Abort Seizures: (In conjunction with Paediatric Neurology recommendations)

  • 1st line: Short acting benzodiazepenes (midazolam 0.5mg/kg buccal or if IV/IO access lorazepam 0.1mg/kg or Rectal Diazepam can also be used 0.5mg/kg )

  • 2nd line: Phenytoin (20 mg/kg IV). Note: Paraldehyde can be considered but should not delay phenytoin.

  • 3rd line: Phenobarbital (20 mg/kg IV)

  • 4th line: Continuous midazolam infusion, propofol infusion, or pentobarbital infusion (after initial loading dose of 5-10 mg/kg) often to achieve burst suppression. Done with continuous EEG monitoring and can be thought of as "resetting" the brain with 24-48 hours of burst suppression prior to weaning AED's

Figure 1: An Example of Burst Supression (4-5 seconds of suppression in between bursts) (via Medscape)

• Prolonged high dose barbituate infusions are immunosupressive and so patients need to be monitored closely for infection

• Consider pyridoxine in unusually refractory cases in young children <3 years old (required for metabolism and synthesis of GABA and deficiency can rarely lead to refractory seizures)

APLS Status Epilepticus Algorithm

• Treatment of Drug Refractory Epilepsy: Surgery has been advocated for drug resistant epilepsy with one single center RCT demonstrating improved rate of freedom from seizures, quality of life, and behavior for those that underwent surgery compared to the medical management group (Dwivedi, NEJM 2017)

References

1) K.J. Eriksson, M.J. Koivikko: Status epilepticus in children: aetiology, treatment, and outcome. Develop Med Child Neurol.39:652 1997

2) E. Lothman: The biochemical basis and pathophysiology of status epilepticus.Neurology. 40 (5 suppl 2):13-23 1990

3) Status epilepticus guidelines, drug handbook and formulary. 2009 The Hospital for Sick Children Toronto, Canada