Carpe Cerebrum: Seize the Brain

Do you have a plan for your little patient when he just won’t stop seizing?

What do you do when your typical treatment is not enough?

Definition of status epilepticus:

Continuous seizure activity of 5 minutes or greater

– OR –

Recurrent activity without recovery between intervals. (This definition includes clinically apparent seizures as well as those seen only on EEG.)

During a seizure, GABA receptors in the neuron’s membrane are internalized and destroyed. Seizure activity itself starts this self-defeating process – this is the first reason we need to act as quickly as possible and take advantage of the GABA receptors that are still recruitable.

Excitatory receptors – the NMDA receptors – are acutely upregulated and mobilize to the neuron’s surface. This is the second reason to act quickly and avoid this kindling effect.

In other words – time is brain.

Or… is it something else as well?

Pediatric status epilepticus is analogous to the multi-organ dysfunction syndrome in severe sepsis. Status epilepticus affects almost every organ system.

Cardiac – dysrhythmias, high output failure, and autonomic dysregulation resulting in hypotension or hypertension.

Respiratory – apnea and hypoxia, ARDS, and potentially aspiration pneumonia.

Renal – rhabdomyolysis, myoglobinuria, and acute renal failure.

Metabolic – lactic acidosis, hypercapnia, hyperglycemia, sometimes hypoglycemia, hyperkalemia, and leukocytosis.

Autonomic – hyperpyrexia and breakdown of cerebral circulation.

DeLorenzo et al.: Mortality correlated with time seizing. Once the seizure has met the 30 min mark, Delorenzo reported a jump from 4.4% mortality to 22%! If the seizure lasts greater than 2 hours, 45%. Time spent seizing is a vicious cycle: it’s harder to break the longer it goes on, and the longer it goes on, the higher the mortality.

Think about treatment of pediatric status epilepticus in terms of time: prehospital care, status epilepticus (greater than 5 min), initial refractory status epilepticus (greater than 10 min), later refractory status (at 20 min), and coma induction (at 25 minutes).

Pediatric Status Epilepticus Protocol

Case 1: Hyponatremic Status Epilepticus

Give 3 mL/kg of 3% saline over 30 min.

Stop the infusion as soon as the seizure stops.

Case 2: INH toxicity

Empiric treatment — you are the test. If we know the amount of ingestion in adults or children, we give a gram-for-gram replacement, up to 5 grams.

If a child under 2 years of age arrives to you in status epilepticus, give 100 mg of IV pyridoxime for potentially undiagnosed congenital deficiency.

Case 3: Headache and Arteriovenous Malformation

Unlike in adults, stroke in children is divided evenly between hemorrhagic and ischemic etiologies. The differential is vast: cardiac, hematologic, infectious, vascular, syndromic, metabolic, oncologic, traumatic, toxic.

Treatment: stabilization, embolization by interventional radiology, elective extirpation when more stable. Other options for stable patients include an endovascular flow-directed microcatheter using cyanoacrylate. Radiosurgery is an options for others.

Non-convulsive Status Epilepticus

Risk factors include age < 18, especially age < 1, no prior history of seizures, and traumatic brain injury. This would prompt you to ask for continuous EEG monitoring for non-convulsive status epilepticus, especially when there is a change in mental status for no other reason.

Also, a prolonged post-ictal state or prolonged altered mental status. Other considerations are those who had a seizure and cardiac arrest – ROSC without RONF, those with traumatic brain injury, and those needing ECMO – all within the context of seizures.

Summary

The longer the seizure lasts, the harder it is to break – act quickly
Have a plan for normal escalation of care, and search for an underlying cause
Recognize when the routine treatment is not enough.

Selected References

Abend NS et al. Nonconvulsive seizures are common in critically ill children. Neurology. 2011; 76(12):1071-7

Baren J. Pediatric Seizures and Strokes: Beyond Benzos and Brain Scans. ACEP Scientific Assembly. October 8th, 2009. Boston, MA.

Brophy et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocrit Care. 2012; DOI 10.1007/s12028-012-9695-z

Capovilla G et al. Treatment of convulsive status epilepticus in childhood: Recommendations of the Italian League Against Epilepsy. Epilepsia. 2013; 54 Suppl 7:23-34

Chin RFM et al., for the NLSTEPSS Collaborative Group. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006; 368: 222–29.

Chen JW, Chamberlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006; 5:246-256.

DeLorenzo RJ. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia. 1999 Feb;40(2):164-9.

LaRoche SM, Helmers SL. The New Antiepileptic Drugs: Scientific Review. JAMA. 2004;291:605-614.

Minns AB, Ghafouri N, Clark RF. Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy. Pediatr Emerg Care. 2010; 26(5):380-1.

Ogilvy CS et al. Recommendations for the Management of Intracranial Arteriovenous Malformations: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Stroke Council. Stroke. 2001; 32: 1458-1471

Rosati A et al. Efficacy and safety of ketamine in refractory status epilepticus in children. Neurology. 2012; 79:2355-2358.

Schwartz ID. Hyponatremic seizure in a child using desmopressin for nocturnal enuresis. Arch Pediatr Adolesc Med. 1998 Oct;152(10):1037-8.

Trommer BL, Pasternak JF. NMDA receptor antagonists inhibit kindling epileptogenesis and seizure expression in developing rats. Brain Res Dev Brain Res. 1990 May 1;53(2):248-52.

Waterhouse EJ et al. Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia. 1999 Jun;40(6).

Pediatric Seizures and Status Epilepticus on WikEM

This episode and post are dedicated to Sean Fox, MD and Michelle Lin, MD. Your love for your patients and passion for your work are an inspiration to us all.

A special acknowledgement and deep thanks to Michelle Johnston, MBBS, FACEM for her Cartesian acumen coupled with her ardent humanity. Medicine is a more meaningful journey for all of us with you along.

Powered by #FOAMed — Tim Horeczko, MD, MSCR, FACEP, FAAP

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