Main term 1 focuses on location and defines this as: Generalized (G); Lateralized (L); Bilateral independent (BI); or Multifocal (Mf).

Main term 2 focuses on pattern morphology and defines this as: Periodic; Rhythmic delta activity; and Spike-and-wave or Sharp-and-wave. The remaining options are modifiers.

Reference: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol 2013;30:1–27.

The EEG displayed shows generalized (main term 1) periodic (main term 2) discharges. When associated with cardiac arrest, the prognosis is poor (a, c). In refractory status, the presence of GPDs after seizure resolution has been associated with seizure recurrence. GPDs have not been associated with brain death (b). The association of GPDS and epilepsy is unclear and warrants further study (d). Note that the clinical context, including the underlying etiology, are essential when considering the prognostic significance of GPDs.

Reference: Akman CI, Khaled KJA, Segal E, et al. Generalized periodic epileptiform discharges in critically ill children: Clinical features, and outcome. Epilepsy Res 2013;106:378–385.

The EEG shows lateralized (main term 1) periodic (main term 2) discharges. They are located maximally at F3 (confirmed on an average referential montage) and are confined to the left hemisphere. LPDs have been associated with herpes simplex encephalitis when in the temporal lobe. However, structural etiologies and other infectious etiologies have also been associated with LPDs. In addition to these associations, LPDs (formerly PLEDS) are associated with seizures. A recent study in adults showed that 58% of patients with LPDs have seizures.

References: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1–27.

PeBenito R, Cracco JB. Periodic lateralized epileptiform discharges in infants and children. Ann Neurol. 1979;6:47–50.

Raroque HG Jr, Wagner W, Gonzales PC, et al. Reassessment of the clinical significance of periodic lateralized epileptiform discharges in pediatric patients. Epilepsia. 1993;34:275–278.

Ruiz AR, Vlachy J, Lee, JW, et al. Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients. JAMA Neurol. 2017;74:181–188.

The EEG shows generalized (main term 1), rhythmic delta activity (main term 2), which is maximal in the bifrontal regions. This pattern is nonspecific, and it is most commonly associated with encephalopathy. GRDA with a bifrontal predominance has been associated with increased ICP, however this is neither a sensitive or specific finding (d). There are no associations with refractory seizures or epilepsy (a, b).

Reference: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1–27.

The EEG shows lateralized (main term 1), periodic (main term 2) discharges. They are maximal over the midline at Cz with a field to Pz. This is confirmed on the average referential montage. The other choices do not describe the pattern. In light of a cardiac arrest, it is most likely that these are associated with a structural lesion, particularly an ischemic infarct given the mechanism being cardiac arrest and cannulation to ECMO. The other options have been associated with LPDs but would be much less likely given the clinical history.

References: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1–27.

PeBenito R, Cracco JB. Periodic lateralized epileptiform discharges in infants and children. Ann Neurol 1979;6:47–50.

Generalized rhythmic delta activity with a bifrontal predominance has been reported in association with increased intracranial pressure, not generalized rhythmic delta activity over the biparietal regions (d). Generalized rhythmic delta activity with a bifrontal predominance is typically seen in children who are awake but drowsy or mildly lethargic. It is characterized by rhythmic delta activity that recurs at irregular intervals on a background comprised of mild-to-moderate generalized theta slowing. It is typically bilaterally synchronous and attenuates with eye opening or alerting. It is most commonly seen over the frontal region and prior to the publication of the ACNS standardized critical care EEG terminology was referred to as FIRDA (frontal intermittent rhythmic delta activity) (c). In children, generalized rhythmic delta activity can, alternatively, have a bioccipital predominance, previously referred to as occipital intermittent rhythmic delta activity (OIRDA). Frontal intermittent rhythmic delta activity has also been reported in association with increased intracranial pressure and deep midline lesions, and occipital intermittent rhythmic delta activity can be seen in children with absence epilepsy (b). An additional form of intermittent rhythmic delta activity over the temporal region is seen in adults in association with temporal lobe epilepsy and is not commonly considered a marker of encephalopathy (a).

References: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1–27.

Ruiz AR, Vlachy J, Lee JW, et al. Association of periodic and rhythmic electroencephalographic patterns with seizures in critically ill patients. JAMA Neurol. 2017;74:181–188.

In a multicenter retrospective cohort study of pediatric ICU patients, 30% of patients undergoing video EEG monitoring were found to have electrographic seizures (ES). ES were more likely to occur in younger children (median age of 23 months in those with seizure compared to 42 months in those without seizure), suggesting younger age as a risk factor for seizure occurrence (a). In a study of 719 critically ill children with acute encephalopathy undergoing cEEG in the pediatric intensive care unit, variables associated with increased ES risk included age (a), etiology of encephalopathy, clinical seizures prior to cEEG initiation, EEG background category, and the presence of epileptiform discharges. In a study of 98 children presenting with convulsive status epilepticus, risk factors for electrographic seizures after convulsive status epilepticus included a prior diagnosis of epilepsy (d) and the presence of interictal epileptiform discharges. Other background features found to correlate with development of ES include lateralized periodic discharges (c) and absence of background reactivity (b).

References: Abend NS, Arndt DH, Carpenter JL, et al. Electrographic seizures in pediatric ICU patients: Cohort study of risk factors and mortality. Neurology. 2013;81:383–391.

Fung FW, Jacobwitz M, Parikh DS, et al. Development of a model to predict electroencephalographic seizures in critically ill children. Epilepsia. 2020;61:498–508.

Jette N, Claassen J, Emerson RG, et al. Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children. Arch Neurol. 2006;63:1750–1755.

Sánchez Fernández I, Abend NS, Arndt DH, et al. Electrographic seizures after convulsive status epilepticus in children and young adults: A retrospective multicenter study. J Pediatr. 2014;164:339–346.

The Neurocritical Care Society suggests that cEEG be initiated within 1 hour of the onset of status epilepticus if continued seizure activity is present. This patient is at risk for ongoing nonconvulsive seizure activity and, therefore, warrants continuous EEG monitoring. The American Clinical Neurophysiology Society recommends continuous EEG monitoring to identify nonconvulsive seizures and nonconvulsive status epilepticus in critically ill children with persistently abnormal mental status following generalized convulsive status epilepticus or other clinically evident seizures if there is any impairment of consciousness for greater than 30 minutes after cessation of clinically evident seizure activity (a).

References: Brophy GM, Bell R, Claassen J. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3–23.

Herman ST, Abend NS, Bleck TP, et al. Consensus statement on continuous EEG in critically ill adults and children, part I: Indications. J Clin Neurophysiol. 2015;32:87–95.

The American Clinical Neurophysiology Society and the Neurocritical Care Society recommend that EEG be continued for a minimum of 24 hours after the last seizure.

References: Brophy GM, Bell R, Claassen J. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17:3–23.

Herman ST, Abend NS, Bleck TP, et al. Consensus statement on continuous EEG in critically ill adults and children, part I: Indications. J Clin Neurophysiol. 2015;32:87–95.

Continuous EEG (cEEG) can be used in the assessment of paroxysmal events (a), prognostication (c), and identification of subclinical seizures or nonconvulsive status epilepticus (NCSE) (d). cEEG is also used, primarily in adults, for the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (e). The gold standard for intracranial pressure measurement relies on invasive techniques. To date, there are no validated noninvasive techniques for intracranial pressure monitoring.

References: Herman ST, Abend NS, Bleck TP, et al. Consensus statement on continuous EEG in critically ill adults and children, part I: Indications. J Clin Neurophysiol. 2015;32:87–95.

Patients on ECMO are at risk for electrographic seizures. The initial study in 2013 focused on this population noted that 21% of children being treated with ECMO had seizures on continuous EEG monitoring, with half having nonconvulsive status epilepticus. Subsequent studies have shown that 18 to 23% of patients on ECMO have electrographic seizures; these studies have additionally shown an association between seizures and mortality in this population.

References: Lin JJ, Banwell BL, Berg RA, et al. Electrographic seizures in children and neonates undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2017;18:249–257.

Okochi S, Shakoor A, Barton S, et al. Prevalence of seizures in pediatric extracorporeal membrane oxygenation patients as measured by continuous electroencephalography. Pediatr Crit Care Med 2018;19:1162–1167.

Piantino JA, Wainwright MS, Grimason M, et al. Nonconvulsive seizures are common in children treated with extracorporeal cardiac life support. Pediatr Crit Care Med. 2013;14:601–609.

Timing of seizure onset from the start of cEEG is similar across pediatric subpopulations with a few notable exceptions. In patients with acute encephalopathy monitored on video EEG and found to have seizures, 97% had their first electrographic seizure within the first 24 hours of recording. Similarly, in a cohort of children with nonconvulsive status epilepticus, 100% were detected within the first 24 hours of continuous EEG monitoring. When including all indications for EEG monitoring in the neonatal and pediatric ICU, 80% of seizures occur within the first 24 hours and 87% within the first 48 hours of the initiation of cEEG monitoring. The first electrographic seizures have been reported to occur between 10 and 36 hours postoperatively in children with congenital heart disease with a mean time of onset of 21 hours +/− 6 hours. This suggests that strict adherence to the ACNS guideline for a minimum duration of 24 hours of cEEG to identify seizures may not be sufficient in this population. The initial study of electrographic seizures in patients on ECMO found that all seizures were captured within the first 24 hours of cEEG initiation, with 50% of those being captured within the first hour of recording. In contrast, Lin et al. found that the median time to first seizure was 15 hours (IQR 6-24), while Okochi et al. found that only 50% of seizures were captured in the first 24 hours, suggesting that this population may also benefit from 48 hours of cEEG to identify seizures. This patient’s presentation is concerning for abusive head trauma. The incidence of acute seizures in the aftermath of abusive head trauma ranges from 33 to 77.3% (a). According to the Brain Trauma Foundation Guidelines for the Management of Severe Traumatic Brain Injury, 3rd edition, “at the present time, there is insufficient evidence to recommend levetiracetam over phenytoin based on either efficacy in preventing early [post-traumatic seizures] or toxicity” (c). The incidence of posttraumatic epilepsy in children has been less well-studied than the incidence of acute seizures (d). A survey of caregivers of 191 children with mild traumatic brain injury a mean of 7.4 years after the TBI revealed a self-reported incidence of epilepsy (defined as two or more unprovoked seizures) of 3%. A similar study in children with moderate to severe TBI revealed an incidence of posttraumatic epilepsy of 9%. In a cohort of patients with traumatic brain injury referred to a child neurologist at a tertiary pediatric hospital, the incidence of posttraumatic epilepsy was 15%. The highest rates of posttraumatic epilepsy were seen in patients with severe TBI, with 83% of patients with severe TBI developing posttraumatic epilepsy. All patients with nonaccidental trauma in this cohort had severe TBI. In an additional cohort of 44 children with nonaccidental trauma, 22% developed posttraumatic epilepsy. Similar rates of posttraumatic epilepsy, 9% and 21.4%, were seen in children admitted to an inpatient rehabilitation hospital after severe TBI and in children with substantial head trauma, respectively. In the subset of children with abusive head trauma, posttraumatic epilepsy risk was as high as 43%.

References: Appleton RE, Demellweek C. Post-traumatic epilepsy in children requiring inpatient rehabilitation following head injury. J Neurol Neurosurg Psychiatry. 2002;72:669–672.

Arndt DH, Goodkin HP, Giza CC. Early posttraumatic seizures in the pediatric population. J Child Neurol. 2016;31:46–56.

Arndt DH, Lerner JT, Matsumoto JH, et al. Subclinical early posttraumatic seizures detected by continuous EEG monitoring in a consecutive pediatric cohort. Epilepsia. 2013;54:1780–1788.

Barlow KM, Spowart JJ, Minns RA. Early posttraumatic seizures in non-accidental head injury: Relation to outcome. Dev Med Child Neurol. 2000;42:591–594.

Bennett KS, DeWitt PE, Harlaar N, et al. Seizures in children with severe traumatic brain injury. Pediatr Crit Care Med. 2017;18:54–63.

Clancy RR, Sharif U, Ichord R, et al. Electrographic neonatal seizures after infant heart surgery. Epilepsia. 2005;46:84–90.

Dingman AL, Stence NV, O’Neill BR, et al. Seizure severity is correlated with severity of hypoxic-ischemic injury in abusive head trauma. Pediatr Neurol. 2018;82:29–35.

Goldstein JL, Leonhardt D, Kmytyuk N, et al. Abnormal neuroimaging is associated with early in-hospital seizures in pediatric abusive head trauma. Neurocrit Care. 2011;15:63–69.

Jette N, Claassen J, Emerson RG, et al. Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children. Arch Neurol. 2006;63:1750–1755.

Keret A, Bennett-Back O, Rosenthal G, et al. Posttraumatic epilepsy: Long-term follow-up of children with mild traumatic brain injury. J Neurosurg Pediatr. 2017;20:64–70.

Keret A, Shweiki M, Bennett-Back O, et al. The clinical characteristics of posttraumatic epilepsy following moderate-to-severe traumatic brain injury in children. Seizure. 2018;58:29–34.

Kieslich M, Jacobi G. Incidence and risk factors of post-traumatic epilepsy in childhood. Lancet. 1995;345:187.

Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: Update of the Brain Trauma Foundation guidelines, executive summary. Pediatr Crit Care Med. 2019;20:280–289.

Lin JJ, Banwell BL, Berg RA, et al. Electrographic seizures in children and neonates undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2017;18:249–257.

McCoy B, Sharma R, Ochi A, et al. Predictors of nonconvulsive seizures among critically ill children. Epilepsia. 2011;52:1973–1978.

Oh A, Olson LD, Chern JJ, et al. Clinical characteristics and nonconvulsive seizures in young children with abusive head trauma. J Child Neurol. 2019;34:713–719.

Okochi S, Shakoor A, Barton S, et al. Prevalence of seizures in pediatric extracorporeal membrane oxygenation patients as measured by continuous electroencephalography. Pediatr Crit Care Med. 2018;19:1162–1167.

O’Neill BR, Handler MH, Tong S, et al. Incidence of seizures on continuous EEG monitoring following traumatic brain injury in children. J Neurosurg Pediatr. 2015;16:167–176.

Park JT, Chugani HT. Post-traumatic epilepsy in children-experience from a tertiary referral center. Pediatr Neurol. 2015;52:174–181.

Piantino JA, Wainwright MS, Grimason M, et al. Nonconvulsive seizures are common in children treated with extracorporeal cardiac life support. Pediatr Crit Care Med. 2013;14:601–609.

Schreiber JM, Zelleke T, Gaillard WD, et al. Continuous video EEG for patients with acute encephalopathy in a pediatric intensive care unit. Neurocrit Care. 2012;17:31–38.

There is no evidence to suggest that early treatment of electrographic seizures (ES) improves outcome. The remaining choices are true. One study examining ES and outcome found that in 200 patients with acute encephalopathy monitored by continuous EEG, ES alone were not associated with in-hospital mortality or worsening of Pediatric Cerebral Performance Category (PCPC) score (the PCPC is a measure of overall neurologic function). However, electrographic status epilepticus had a clear association with in-hospital mortality and PCPC worsening. In contrast, electrographic seizures in the ECMO population have been associated with in-hospital mortality. A prospective observational study assessing the relationship between electrographic seizure burden and short-term neurologic outcome found that patients with posthospitalization neurologic decline were found to have a mean seizure burden of 15.7% per hour compared to only 1.8% per hour for those without a decline in neurologic function. Seizure burden was calculated from the one-hour epoch of EEG with maximum seizure duration, and neurologic outcome was based on PCPC scores. The probability and severity of neurologic decline rose sharply above a maximum seizure burden of 20% (12 minutes/hour), suggesting that seizure burden, or maximum percentage per hour of seizure activity, was independently associated with poor short-term neurologic outcome.

References: Lin JJ, Banwell BL, Berg RA, et al. Electrographic seizures in children and neonates undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2017;18:249–257.

Okochi S, Shakoor A, Barton S, et al. Prevalence of seizures in pediatric extracorporeal membrane oxygenation patients as measured by continuous electroencephalography. Pediatr Crit Care Med. 2018;19:1162–1167.

Payne ET, Zhao XY, Frndova H, et al. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014;37:1429–1438.

Topjian A, Gutierrez-Colina AM, Sanchez SM, et al. Electrographic status epilepticus is associated with mortality and worse short-term outcome in critically ill children. Crit Care Med. 2013;41:215–223.

The EEG above shows ~1 Hz epileptiform discharges maximal over the bilateral anterior quadrants. Nonconvulsive status epilepticus is defined as uninterrupted electrographic seizure activity lasting at least 30 minutes or repeated electrographic seizures totaling more than 30 minutes in any 1-hour period meeting the following criteria: (1) epileptiform discharges >2.5 Hz; or (2) epileptiform discharges ≤2.5 Hz or rhythmic delta/theta activity >0.5 Hz AND one of: (a) EEG and clinical improvement after intravenous antiseizure medication (ASM); (b) subtle clinical ictal phenomena during the EEG patterns mentioned above; or (c) typical spatiotemporal evolution (increase in voltage and change in frequency, or change in frequency >1 Hz, or change in location, or decrementing termination in voltage or frequency). A trial of lorazepam may help determine whether the above pattern represents nonconvulsive status epilepticus. Given that it is unclear whether the above pattern represents status epilepticus or not, a benzodiazepine trial is warranted prior to treatment with a nonbenzodiazepine ASM (a). An ammonia level should also be checked (c), and a lumbar puncture is likely warranted depending on the full clinical history (d).

Reference: Leitinger M, Beniczky S, Rohracher A, et al. Salzburg consensus criteria for non-convulsive status epilepticus—approach to clinical application. Epilepsy Behav. 2015;49:158–163.

In children outside of the neonatal period (>48 weeks postmenstrual age), unequivocal electrographic seizures are defined as generalized spike-wave discharges at 3/s or faster and clearly evolving discharges of any type that reach a frequency >4/s whether focal or generalized. Nonconvulsive status epilepticus is defined as uninterrupted electrographic seizure activity lasting at least 30 minutes or repeated electrographic seizures totaling more than 30 minutes in any 1-hour period meeting the following criteria: (1) epileptiform discharges >2.5 Hz; or (2) epileptiform discharges ≤2.5 Hz or rhythmic delta/theta activity >0.5 Hz AND one of: (a) EEG and clinical improvement after intravenous antiseizure medication; (b) subtle clinical ictal phenomena during the EEG patterns mentioned above; or (c) typical spatiotemporal evolution (increase in voltage and change in frequency, or change in frequency >1 Hz, or change in location, or decrementing termination in voltage or frequency).

References: Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society’s standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1–27.

Leitinger M, Beniczky S, Rohracher A, et al. Salzburg consensus criteria for non-convulsive status epilepticus—approach to clinical application. Epilepsy Behav. 2015;49:158–163.

Neonates and infants who undergo repair of congenital heart disease are at risk for electrographic seizures (ES). The incidence of postoperative clinical seizure activity varied widely among early studies, ranging from 5% to 19%. An early prospective study using both clinical and EEG criteria for seizure diagnosis found that among patients who underwent surgery for D-transposition of the great arteries, 6% had clinical seizures and 20% had ES in the postoperative period. Seizures were more common in patients who underwent deep hypothermic circulatory arrest as compared to low flow bypass. A later prospective study using EEG criteria for seizure diagnosis identified seizures in the postoperative period in 11% of patients with single ventricle physiology and 18% of patients with hypoplastic left heart syndrome. This study also showed that deep hypothermic circulatory arrest for greater than 40 minutes was associated with both clinical and electrographic seizures. Similarly, a prospective study using cEEG criteria for the diagnosis of seizure in patients with all types of congenital heart disease during the first 48 hours after surgery identified seizures in 12% of patients. A study focused on neonates found that 8% of patients monitored using cEEG had ES after congenital heart disease surgery, with the majority being electrographic-only; there was also a high rate of electrographic status epilepticus in this study.

References: Clancy RR, McGuarn S, Wernovsky G, et al. Risk of seizures in survivors of newborn heart surgery using deep hypothermic circulatory arrest. Pediatrics. 2003;111:592–601.

Clancy RR, Sharif U, Ichord R, et al. Electrographic neonatal seizures after infant heart surgery. Epilepsia. 2005;46:84–90.

Du Plessis AJ, Jonas R, Wypij D, et al. Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg. 1997;114:991–1000.

Gaynor JW, Nicolson SC, Jarvik GP, et al. Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures. J Thorac Cardiovasc Surg. 2005;130:1278–1286.

Helmers SL, Wypij D, Constantinou JE, et al. Perioperative electroencephalographic seizures in infants undergoing repair of complex congenital cardiac defects. Electroencephalogr Clin Neurophysiol. 1997;102:27–36.

Naim MY, Gaynor JW, Chen J, et al. Subclinical seizure identified by postoperative electroencephalopgraphic monitoring are common after neonatal cardiac surgery. J Thorac Cardiovasc Surg. 2015;150:169–178.

A retrospective review of 141 pediatric patients who were admitted or transferred to the PICU of a tertiary children’s hospital with an unexplained decrease in level of consciousness, no overt clinical seizures, and EEG recordings performed within 24 hours of onset of altered consciousness showed a mean duration of seizures of 159 seconds with a range of 10 seconds to 11 minutes. Electrographic seizures have been defined as paroxysmal events different from the EEG background, lasting longer than 10 seconds (or shorter if associated with a clinical change) with temporo-spatial evolution in morphology, frequency, and amplitude, and with a plausible electrographic field (a). Electrographic status epilepticus refers to a single seizure lasting 30 minutes or electrographic seizure activity that when summated occupies more than 50% of a one-hour epoch (d).

References: Abend NS, Arndt DH, Carpenter JL, et al. Electrographic seizures in pediatric ICU patients: Cohort study of risk factors and mortality. Neurology. 2013;81:383–391.

Kaplan PW. The clinical features, diagnosis, and prognosis of nonconvulsive status epilepticus. Neurologist. 2005;11:348–361.

Saengpattrachai M, Sharma R, Hunjan A, et al. Nonconvulsive seizures in the pediatric intensive care unit: Etiology, EEG, and brain imaging findings. Epilepsia. 2006;47:1510–1518.

Benzodiazepines are positive allosteric modulators of the GABA_A receptor, not GABA_A receptor inhibitors (a). During sustained seizure activity, there is a progressive internalization of GABA_A receptors (b) and a progressive increase in the concentration of NMDA receptors in the neuronal membrane (c). In animal models, the longer a seizure lasts, the more refractory to benzodiazepine treatment the animal becomes. In clinical studies, a similar tendency towards progressive resistance to benzodiazepines is seen in the setting of ongoing seizure activity. The use of fosphenytoin has not been shown to impact the efficacy of benzodiazepines (d).

References: Goodkin HP, Yeh JL, Kapur J. Status epilepticus increases the intracellular accumulation of GABAA receptors. J Neurosci. 2005;25:5511–5520.

Jones DM, Esmaeil N, Maren S, et al. Characterization of pharmacoresistance to benzodiazepines in the rat Li-pilocarpine model of status epilepticus. Epilepsy Res. 2002;50:301–312.

Kapur J, Macdonald RL. Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci. 1997;17:7532–7540.

Naylor DE, Liu H, Niquet J, et al. Rapid surface accumulation of NMDA receptors increases glutamatergic excitation during status epilepticus. Neurobiol Dis. 2013;54:225–238.

Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 2005;25:7724–7733.

Rajasekaran K, Todorovic M, Kapur J. Calcium-permeable AMPA receptors are expressed in a rodent model of status epilepticus. Ann Neurol. 2012;72:91–102.

Although guidelines recommend a timely stepwise administration of medications for status epilepticus every 5 to 10 minutes (a), significant and widespread delays exist (b, c). These delays are independently associated with poorer short-term outcomes (e).

References: Sánchez Fernández I, Gaínza-Lein M, Abend NS, et al. Factors associated with treatment delays in pediatric refractory convulsive status epilepticus. Neurology. 2018;90:e1692–e1701.

Sanchez Fernandez I, Jackson MC, Abend NS, et al. Refractory status epilepticus in children with and without prior epilepsy or status epilepticus. Neurology. 2017;88:386–394.

Electrographic-only seizures without accompanying convulsions cause brain damage in animal models. Convulsive status epilepticus is typically associated with hyperthermia and acidosis (b), not hypothermia and alkalosis. At the beginning of status epilepticus, perfusion to the brain and muscles is prioritized to meet metabolic demands (c). The main cause of death in primate models of status epilepticus is homeostatic decompensation, not a primary brain lesion (d).

References: Jones DM, Esmaeil N, Maren S, Macdonald RL. Characterization of pharmacoresistance to benzodiazepines in the rat Li-pilocarpine model of status epilepticus. Epilepsy Res. 2002;50:301–312.

Mazarati AM, Wasterlain CG. N-methyl-D-asparate receptor antagonists abolish the maintenance phase of self-sustaining status epilepticus in rat. Neurosci Lett. 1999;265:187–190.

Rajasekaran K, Todorovic M, Kapur J. Calcium-permeable AMPA receptors are expressed in a rodent model of status epilepticus. Ann Neurol. 2012;72:91–102.

The current ILAE definition of status epilepticus defines t1 as the time when seizures are likely to continue if not treated (c) and t2 as the time when there is likely irreversible brain damage (a). For generalized convulsive seizures, t1 is 5 minutes and t2 is 30 minutes. For focal status epilepticus with impairment of consciousness, t1 is 10 minutes and t2 is 60 minutes (b, e). For absence status, t1 is 10 to 15 minutes and t2 is unknown.

Reference: Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus—Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56:1515–1523.

During sustained seizure activity, there is a progressive internalization of GABA_A receptors and a progressive increase in the concentration of NMDA receptors at the synapse. Ketamine, a noncompetitive antagonist of the NMDA receptor, may theoretically work better than GABA_A agonists once a seizure has become prolonged. As an NMDA antagonist, it may also help minimize excitotoxicity, which results from the downstream effects of calcium influx through NMDA receptors and thereby provide a neuroprotective effect. Ketamine tends to have a better cardiorespiratory profile than midazolam, pentobarbital, and propofol (b). While early work suggested a risk of increased intracranial pressure with ketamine use, this is no longer felt to be a concern (c). Ketamine is used for the treatment of refractory and super-refractory status epilepticus, typically once more commonly used agents like midazolam, pentobarbital, and propofol (in adults) have failed (d).

References: Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: A critical review of available therapies and a clinical treatment protocol. Brain. 2011;134:2802–2818.

Vasquez A, Farias-Moeller R, Tatum W. Pediatric refractory and super-refractory status epilepticus. Seizure 2019;68:62–71.

Zeiler FA, Teitelbaum J, West M, et al. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014;21:163–173.

The above clinical presentation and EEG findings are consistent with complex partial status epilepticus (6-b).

The EEG shows rhythmic discharges over the left posterior quadrant. A trial of lorazepam should be the next step (7-a). This can be followed by a levetiracetam bolus as needed for ongoing seizure activity after treatment with lorazepam (7-c). A midazolam infusion would likely require intubation, an approach too aggressive in a patient who is clinically stable and in whom other treatments of status epilepticus have not yet been tried. The cause of this patient’s mental state has been identified (7-d).

Reference: Wakai S, Ito N, Sueoka H, et al. Complex partial status epilepticus in childhood. Pediatr Neurol. 1995;13:137–141.