P e d i a t r i c S e i z u re s

Maneesha Agarwal, MD, Sean M. Fox, MD*

KEYWORDS
 Seizures  Febrile seizures  New-onset seizures  Neonatal seizures  Pediatric
 Ketogenic diet  Status epilepticus

KEY POINTS
 Neonatal seizures may often be subtle but still have a high correlation with significant
pathologic conditions.
 Because patients who have had a simple febrile seizure are at no greater risk for having
meningitis than those who have a fever without a seizure, the evaluation of a simple febrile
seizure should focus on an age-appropriate evaluation of the fever, and the management
should include appropriate anticipatory guidance and education for the family.
 Complex febrile seizures include a vast spectrum of disease; therefore, the evaluation
should be tailored to the individual case but with greater suspicion for potential central
nervous system infection.
 Patients who have had a first-time afebrile seizure should have neuroimaging (with the
preferred modality being magnetic resonance imaging), which can be performed as an
outpatient if appropriate follow-up has been arranged.
 Emergent neuroimaging should be obtained in the emergency department after a new-
onset seizure for those patients who have specific risk factors (eg, bleeding disorder,
sickle cell disease, human immunodeficiency virus, head injury, ventriculoperitoneal
shunt, age less than 6 months, focal seizure, prolonged postictal period, status epilepti-
cus, and so forth).
 Status epilepticus becomes more refractory as seizure activity persists, so it should be
aggressively treated. Standard algorithms for the management are still applicable, but
new routes for administration of benzodiazepines and new second-line and third-line
medications may be considered for use.

INTRODUCTION

Seizures represent the most common neurologic emergency of childhood and can be
terrifying for patients and families. Although there are a variety of potential causes for
seizures, the common pathophysiology entails abnormal electrical discharge of neu-
rons; the extent of this aberrant electrical activity and subsequent manifestation of

Disclosures: None.
Department of Emergency Medicine, Carolinas Medical Center, 3rd Floor Medical Education
Building, 1000 Blythe Boulevard, Charlotte, NC 28203, USA
* Corresponding author.
E-mail address: [email protected]

Emerg Med Clin N Am 31 (2013) 733–754

http://dx.doi.org/10.1016/j.emc.2013.04.001 emed.theclinics.com
0733-8627/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved.
734 Agarwal & Fox

the seizure may range from subtle, nonconvulsive events to stereotypic movements to
dramatic generalized convulsions. Additionally, the severity of a seizure can be
varied, ranging from self-limited episodes without any hemodynamic compromise to
prolonged events that may ultimately prove to be fatal in as many as 3% to 4% of
patients.1,2
Seizures will affect 4% to 10% of children at some point during their lifetime, which
translates to approximately 150,000 children in the United States experiencing a
new-onset seizure annually.3 About 10% of these new-onset pediatric seizures may
present to the emergency department in status epilepticus.4 Fortunately, of patients
presenting with a new-onset seizure, only 30 000 will go on to develop epilepsy,3
whereas the remainder will have manifested seizures secondary to other causes,
such as fever, infection, or trauma. Those newly diagnosed with epilepsy will add to
the 326,000 children residing in the United States who already carry a diagnosis
of epilepsy undergoing various treatments ranging from medications to special diets
to surgical interventions.5 Given these numbers, it is critical for every emergency
physician to be adept in the acute management of pediatric seizures and possess
basic knowledge pertaining to pediatric epilepsy, its management, and potential
complications.

SEIZURE MIMICS

Appropriate diagnosis of a seizure is critical to management. However, it is important

to recognize that events that result in an altered level of consciousness or abnormal
movements may not actually represent a seizure. A detailed history of the event by
eyewitnesses (who may not always accompany patients to the emergency depart-
ment) and a thorough physical examination of patients may yield an alternative diag-
nosis from a seizure. The differential diagnosis of seizurelike activity is broad but must
be considered in all patients, even in those who carry a diagnosis of epilepsy (Box 1).
Infants and toddlers, who have developing nervous systems, may present with a
myriad of diagnoses unique to their age group that may be interpreted by the family
as a seizure. Parents can misinterpret the normal neonatal reflexes, particularly the
startle reflex, as seizure activity. Additionally, they may exhibit jitteriness, which is
characterized by symmetric tremor of the extremities with facial sparing; unlike seizure
activity, these common movements can be stopped with gentle restraint.6,7 During
sleep, migrating myoclonic movements that do not disturb or wake the child may
represent self-limited benign sleep myoclonus.8 Additionally, shuddering attacks
can cause concern with parents and consist of rapid shivering of the head, shoulder,
and trunk as if cold water were dripping down the child’s spine. These attacks may
also have start in infancy and can persist through early childhood.9 Severe gastro-
esophageal reflex may manifest as Sandifer syndrome, which has also been miscon-
strued as seizures because of its associated back arching, crying, and writhing.
In addition, some common childhood behaviors can also mimic seizure activity.
Breath-holding spells is a well-documented entity that can be seen in 5% of all chil-
dren between 6 months and 5 years of age. They can have varied presentations,
and some can seem to be associated with seizurelike activity. Breath-holding spells
are associated with emotional stimuli or minor trauma and are brief, self-resolving,
and without a postictal phase. They have an excellent prognosis with spontaneous
remission with age.10 In some children, families may also potentially interpret the
rhythmic movements of self-gratification or stimulation as seizure activity.11 Sleep dis-
turbances, such as pavor nocturnus (night terrors), represent another category of
seizure mimics in young children.
 Pediatric Seizures 735

Box 1
Differential diagnosis of seizures

 Arrhythmia
 Benign myoclonus of sleep
 Breath-holding spells
 Dystonic reaction
 Hyperekplexia
 Jitteriness
 Migrainous syndromes (confusional, basilar)
 Opsoclonus-myoclonus-ataxia syndrome (neuroblastoma)
 Paroxysmal movement disorders
 Psychiatric disorders (attention-deficit hyperactivity disorder, hysteria, rage attacks)
 Psychogenic nonepileptic seizures (pseudoseizures)
 Sandifer syndrome
 Self-gratification disorder
 Shuddering attacks
 Sleep disorders (pavor nocturnus/night terrors, somnambulism/sleepwalking, narcolepsy)
 Spasmus nutans
 Syncope
 Tics, stereotypies

Although some entities that mimic seizure activity can be caused by benign causes,
others are associated with more concerning causes. Hyperekplexia (when infants
have marked startling at sudden sounds or touch) may be so profound that it results
in total body stiffening and apnea. Spasmus nutans is another entity that presents in
children 4 to 12 months of age with pendular nystagmus, head nodding, and some
head tilt or unusual head positioning. The rare syndrome of opsoclonus-myoclonus-
ataxia that is associated with neuroblastoma may also be misconstrued as seizure
activity.8
As children age, the differential diagnosis of seizurelike activity becomes similar to
that of adults. New-onset narcolepsy, particular with regard to cataplexy, may raise
concern for atonic (drop) seizures. Syncope may also be confused with seizures; in
one study of patients with controlled initiation of ventricular arrhythmia, 65% of all
patients had convulsive movements without an electrographic correlate of seizure
activity.12 Arrhythmia must be considered in any patient presenting with a concern
for a new seizure.
One diagnosis that is difficult to differentiate from seizures is psychogenic nonepi-
leptic seizures (PNES). This disorder may begin to present in early adolescence. These
seizures are involuntary, physical expressions in response to psychological conflict
from emotional, physical, or social distress.13,14 Patients with PNES are overwhelm-
ingly female, typically with psychiatric comorbidities, such as posttraumatic stress
disorder, anxiety, or depression, and have had prior exposure to individuals with a
history of seizures that serve as a model for seizurelike activity. Characteristics that
are more suggestive of seizures include tongue biting, injury, bowel or bladder
736 Agarwal & Fox

incontinence, significant vital sign instability, cyanosis, altered pupillary responses,

and postictal state.15 Prolonged events in excess of 15 to 30 minutes; bizarre motor
activity along the lines of thrashing, arching, or flailing; occurrence of events only in
the presence of an audience; incorporation of verbal cues from bystanders; and brief
or odd postictal states with crying or baby talking are more likely to represent PNES.14
It can be particularly difficult to distinguish between PNES and true seizures because,
in part, many individuals may suffer from both PNES and epilepsy. In some popula-
tions, accurate diagnosis may be delayed by a mean of 7 years with patients receiving
aggressive antiepileptic therapy and other interventions for difficult-to-control epi-
lepsy or recurrent cases of “refractory status epilepticus.”13

NEONATAL SEIZURES

Although the previously mentioned entities and others can be inappropriately mis-
construed as seizure activity, true seizures that occur in neonates (28 days of
age) can often be misidentified as being benign. Neonatal seizures are not often
as dramatic and clinically evident as seizures in older children and adults. General-
ized tonic-clonic activity is rarely seen in neonates; instead, the neonate’s immature
nervous system and pattern of myelination generally leads to more subtle presenta-
tions of seizures.16,17 Ocular movements, lip smacking, bicycling movements, and
even apnea can be seizure presentations in neonates. Subtle seizure types account
for approximately 50% of all neonatal seizures.18 Other clonic or tonic seizure types
are possible but are seen less commonly. The myoclonic seizure type can be easily
perceived as representing a Moro reflex and can be of a benign origin or indicate a
more ominous sign of significant brain damage.16,18 Additionally, alterations in vital
signs (eg, hypertension, tachycardia) of an unclear cause can also represent neonatal
seizures.19
Although the presentations of neonatal seizures may be subtle, the cause is often
associated with significant morbidity and mortality. Ninety percent of seizures in full-
term newborns are caused by an identifiable cause.20 The immature nervous system
of neonates not only leads to a restricted repertoire from which patients can demon-
strate illness to their families and physicians but also makes it more susceptible to
having seizures because of any perturbation in its physiology. This circumstance
leads to a broad differential diagnosis list for neonatal seizures. From an emergency
medicine standpoint, one substantial cause to consider is infection. There should be
a low threshold to initiate the workup of possible meningoencephalitis in neonates
who are presenting with seizures. The commonly considered organisms (group B
streptococci, Escherichia coli, and Listeria) may be the culprits; but other entities
must also be considered, whether newly acquired or congenital, like toxoplasmosis,
rubella, cytomegalovirus, and herpes simplex virus.16
Fortunately, although infection is extremely important to consider on the differential
of neonatal seizures, it is not the most common cause. Hypoxic-ischemic encephalop-
athy (HIE) is the most common cause of neonatal seizures and usually manifests within
the first 48 hours of life.18 Intracranial hemorrhage should be considered also because
it accounts for 10% of neonatal seizures.16 Birth trauma can lead to subarachnoid or
subdural hemorrhage and, because of the subtle nature of the neonatal seizures, may
not be noticed until after hospital discharge. Premature infants are particularly at risk
for intracranial hemorrhage, and all children are at risk for sustaining injury caused by
nonaccidental trauma. Aside from hemorrhage, congenital intracranial anomalies,
such as tuberous sclerosis, pachygyria, or lissencephaly, can also lead to seizures
in neonates.19
 Pediatric Seizures 737

Although intracranial abnormalities is intuitively linked to seizures, there are other

important entities to consider in neonates who are seizing. Metabolic disturbances
and derangements should be considered in neonates with seizures. Hypoglycemia,
hypocalcemia, hypomagnesemia, hypernatremia, and hyponatremia are all known
to cause seizures and can result from a variety of conditions, from errors in mixing
formula to inborn errors of metabolism.16 Although the indiscriminant investigation
of electrolytes is often unnecessary in older patients, chemistry panels can prove
to be useful in this at-risk neonatal population,21 particularly in those who are
actively seizing. Seizures caused by inborn errors of metabolism are poorly respon-
sive to conventional therapies for seizures.20 The specific inborn errors of meta-
bolism that can lead to neonatal seizures are beyond the scope of this review but
do warrant consideration as a whole when evaluating a child with neonatal seizures
because additional blood, cerebrospinal fluid (CSF), and urine should ideally be
obtained and held to assist with making the definitive diagnosis during the
hospitalization.
The evaluation and management of neonates with seizures should initially focus on
the life-threatening and treatable causes while keeping a perspective about what is
common as well as rare. A thorough history and physical examination may help
direct the evaluation (eg, fevers, bulging fontanelle, dysmorphic features, hepatos-
plenomegaly, bruising), but a normal examination does not eliminate the need for
concern. After airway, breathing, and circulation issues have been addressed,
obtaining a glucose level is imperative. Although infection is not the most common
cause of neonatal seizures, the authors think that its potential existence should be
addressed rapidly and appropriate cultures obtained and antimicrobials initiated.
Metabolic laboratory investigation is also warranted, and the consideration of
possible inborn errors of metabolism before the initiation of therapies can aid in mak-
ing the diagnosis. Emergent neurologic imaging should also be considered to inves-
tigate for intracranial pathologies like hemorrhage or congenital anomalies. In
neonates, although ultrasound may provide valuable information regarding interven-
tricular or parenchymal hemorrhage, computed tomography (CT) imaging is superior
in identifying the extent of intracranial hemorrhage, cortical lesions, subarachnoid
blood, and other pathologies and is generally viewed as the preferred imaging
modality.18,22 If patients are clinically stable and there is rapid availability, however,
magnetic resonance imaging (MRI) will typically reveal even more detailed and useful
information.23
Therapeutic medication options for actively seizing neonates still start with benzo-
diazepines; however, should seizures persist beyond benzodiazepine therapy, pheno-
barbital is generally favored over phenytoin in neonates.16,24 Weight-based doses for
these medicines are the same as for older children (Table 1). Obvious electrolyte
abnormalities, such as hyponatremia, should also be promptly corrected. For status
epilepticus that is resistant to traditional therapies, pyridoxine dependency may be
the culprit, and empiric pyridoxine administration of 50 to 100 mg intravenously may
prove to be useful.16,19

FEBRILE SEIZURES

Febrile seizures represent an entity unique to pediatric populations that requires

special discussion. They are estimated to occur in approximately 2% to 5% of the
US pediatric population, with a peak incidence at 18 months.25 Given the dramatic
presentation, often in a previously well child, these patients are almost universally
brought to the emergency department for evaluation; thus, it is critical that every
738 Agarwal & Fox

Table 1
Medications to treat status epilepticus

First-Line Medications: Benzodiazepines

Lorazepam IV/IM 0.05–0.1 mg/kg (max: 4 mg per dose)
Diazepam IV 0.2–0.3 mg/kg (max: 10 mg per dose)
PR 0.5–1.0 mg/kg
Midazolam IV 0.05–0.1 mg/kg (max: 6 mg per dose less than 6 y; 10 mg per dose 6 y
and older)
IM 0.1–0.2 mg/kg (max: 5 mg per dose)
IN 0.2–0.3 mg/kg (max: 7.5 mg per dose)
Buccal 0.15–0.3 mg/kg (max: 20 mg per dose)
Second-Line Medications
Phenytoin IV 15–20 mg/kg (no faster than 1 mg/kg/min)
Fosphenytoin IV/IM 15–20 PE/kg (no faster than 3 PE/kg/min)
Phenobarbital IV 15–20 mg/kg (no faster than 1 mg/kg/min)
Valproate IV 20–40 mg/kg load; can follow with 3–6 mg/kg/min infusion
Levetiracetam IV 20–30 mg/kg load
Dextrose IV 2–4 mL/kg of 25% dextrose
Pyridoxine IV 50–100 mg per dose
Infusions for Refractory Status Epilepticus
Midazolam IV 0.1–0.3 mg/kg load followed by 0.05–0.4 mg/kg/h
Propofol IV 2.0–3.5 mg/kg load followed by 125–300 mg/kg/min
Pentobarbital IV 0.5–1.0 mg/kg load followed by 1–6 mg/kg/h
Ketamine IV 1–2 mg/kg load followed by 5–20 mg/kg/min
Lidocaine IV 1–2 mg/kg load followed by 4–6 mg/kg/h

Abbreviations: IM, intramuscular; IN, intranasal; IV, intravenous; max, maximum; PE, phenytoin
equivalents; PR, rectally.
Data from Refs.10,22,111,138

practicing emergency medicine physician be well versed in the diagnosis, evaluation,

management, and anticipated outcomes in this condition.
The generally accepted definition of febrile seizures in the United States set forth by
the American Academy of Pediatrics (AAP) “is a seizure accompanied by a fever (tem-
perature 100.4 F or 38 C by any method), without central nervous system infection,
that occurs in infants and children 6 through 60 months of age.”26 Febrile seizures are
further defined as either simple or complex; this classification helps better delineate
workup and outcomes. Simple febrile seizures consist of primary generalized tonic-
clonic seizures lasting for less than 15 minutes. The postictal period is generally brief,
often resolving by the time of evaluation in the emergency department and the child
returns to his or her neurologic baseline. Evidence of focality, duration of 15 minutes
or more, or recurrence within 24 hours characterize complex febrile seizures (AAP
2011)27; about 35% of febrile seizures are thought to be complex and 5% may actually
present in febrile status epilepticus.25 In fact, febrile status epilepticus is thought to
account for about one-third of all instances of pediatric status epilepticus cases and
is by far the most common cause of status epilepticus in this age group.1,4
The exact pathophysiology of febrile seizures remains unclear, with competing the-
ories pertaining to the rate of increase of fever versus the peak temperature. There is
also new data suggesting a possible correlation with iron deficiency anemia.27,28
Evidence does exist that there is a genetic predisposition, with a positive family history
 Pediatric Seizures 739

of febrile seizures in about 25% to 40% of patients.10,25 Additionally, febrile seizures

have been associated with specific causes, such as human herpesvirus 6,29,30
influenza A,31 and even some routine childhood immunizations.32–34
The appropriate management of a child with a febrile seizure focuses on 3 key prin-
ciples: acute management if the child is still seizing, diagnosis and management of the
source of the fever, and anticipatory guidance to parents. It is in the last 2 principles
that defining the febrile seizure as simple or complex impacts the care and messages
delivered.
As with any seizing patient, acute management of a child with a febrile seizure
focuses on the initial management of the airway, breathing, and circulation. Further
management of ongoing seizure activity is discussed later; treatment is similar to
afebrile seizures, with the addition of antipyretic therapy to control the fever.
From an emergency medicine perspective, the combination of fever and seizure
provokes a concern for meningitis. Fortunately, it is known that if the child fits the defi-
nition of a simple febrile seizure, then he or she is not at any increased risk for menin-
gitis.35,36 Comprehensive review of the extensive medical literature on febrile seizures
has been used to generate a clinical practice guideline by the AAP.26 Research, both
before and after the release of the newer immunizations for Haemophilus influenzae
type b and Streptococcus pneumoniae, document that the risk of bacteremia, urinary
tract infection, and meningitis are similar between children presenting with a simple
febrile seizure versus those who present with a fever without seizure.36–40 Thus, it is
recommended that the evaluation of simple febrile seizures essentially become the
evaluation of fever alone. Even with aggressive evaluation for a source, approximately
30% of children with a febrile seizure will have no focal illness or specific viral or bac-
terial cause identified.38 There is no role or evidence to support routine neuroimaging,
specific blood work, or obtaining an electroencephalogram (EEG).36 It is important,
however, to ensure that patients are appropriately diagnosed as having a simple
febrile seizure before relying on this information.
While evaluating a child who has presented with a seizure and does fit the definition
of simple febrile seizure, often the parental concern will still focus on meningitis. It is
important and useful to convey that bacterial meningitis does not typically present
with seizure as its sole manifestation.41 Additionally, in a large study of more than
700 children aged 6 to 18 months with simple febrile seizures, no child had bacterial
meningitis.35 Thus, in the child with a simple febrile seizure, empiric antibiotics are
not advantageous and the lumbar puncture is not mandatory. Lumbar puncture is
worth consideration if patients are younger than 12 months with a less reliable physical
examination, incompletely immunized, or pretreated with antibiotics that might mask
the signs and symptoms of meningitis. Certainly, any child with symptoms concerning
for meningitis (such as nuchal rigidity, persistent postictal period, altered mental
status, or bulging fontanelle) warrants a lumbar puncture for CSF analysis. If CSF is
obtained, recent studies suggest pleocytosis should not be attributed to the seizure
and instead managed appropriately.42,43
In contrast to the well-supported guidelines for the evaluation and management of
simple febrile seizure, complex febrile seizures do not have any definitive management
guidelines because of the significant clinical heterogeneity within the definition of com-
plex febrile seizures. For example, the febrile 3-year-old child with clear herpangina
who has had 2 seizures within a 24-hour period as well as the 18-month-old child
who presents with febrile status epilepticus both are classified as complex febrile sei-
zures. Certainly though, these 2 cases represent extremely different clinical scenarios.
With each case of complex febrile seizures, a strategy for obtaining laboratory values,
cultures, neuroimaging, neurology consultation, and admission needs to be tailored
740 Agarwal & Fox

for the individual based on the available history and physical examination and at the
discretion of the treating physicians.
Despite the lack of clear, definitive guidelines for complex febrile seizures, there is
some evidence pertaining to the risk of meningitis and the potential benefit of neuro-
imaging. In a recent study of more than 500 patients presenting with a complex
febrile seizure, 3 patients were ultimately diagnosed with bacterial meningitis; 2 pa-
tients had abnormal findings on examination, and 1 patient was presumptively
treated for bacterial meningitis based on a lack of CSF but positive blood culture.44
In the instance of febrile status epilepticus, which is included within the broader cate-
gory of complex febrile seizures, there is a definite increased risk of meningitis
compared with those with simple febrile seizures, with an estimated risk of bacterial
meningitis of 12% to 18%.1,45 Thus, in the case of complex febrile seizures, a lumbar
puncture should be strongly considered and any pleocytosis should be appropriately
interpreted.
Again, with the complex febrile seizure cohort including a diverse set of conditions,
the utility of neuroimaging needs to be addressed on an individual case basis. The
child with clinical herpangina and 2 simple febrile seizures in a 24-hour period may
not benefit greatly from a CT scan of the brain, whereas the child in febrile status epi-
lepticus may. Routine imaging should not be performed for patients with complex
febrile seizures, but rather the clinical scenario should help determine who is at greater
risk of having an intracranial abnormality. Abnormalities are generally noted only in
patients with an abnormal physical examination.46,47
Parental concern surrounding this event will often be appropriately high; thus, it is
imperative that for every child who meets criteria for discharge after suffering a febrile
seizure, the emergency physician provides appropriate anticipatory guidance to the
parents. Guidance should be provided on the risk of recurrence, appropriate precau-
tions in the event of another seizure, subsequent risk of epilepsy, and the generally
excellent prognosis for children who suffer febrile seizures despite the lack of thera-
pies to prevent further seizure activity. The risk of recurrence of a febrile seizure is
about 33%, with about 10% having multiple seizures.25 Specific risk factors that in-
crease the risk of recurrence include age less than 18 months, a family history of febrile
seizures, a shorter duration of fever before seizing, and lower temperature at onset of
seizing. The presence of multiple risk factors increases the likelihood of seizure recur-
rence further.25,48,49 Although seizure recurrence is not uncommon, the risk of epi-
lepsy after a child suffers a febrile seizure is the same as the general population at
1%.50 The risk may increase to 10% in some studies, especially in the context of a pre-
existing neurodevelopmental abnormality, family history of epilepsy, patient history of
complex febrile seizure, multiple complex features to the seizure, and brief duration of
fever.25,51
Unfortunately, extensive research on preventing the recurrence of febrile seizures or
the subsequent development of epilepsy has been unfruitful. Routine antipyretic ther-
apy during febrile illnesses has not demonstrated any benefit in prevention.52–54
Intermittent and routine antiepileptic therapy with benzodiazepines, phenytoin, pheno-
barbital, valproate, and other agents have varying levels of efficacy; however, the
range of adverse side effects outweigh any potential benefit.49,55–57 Fortunately,
research also indicates that febrile seizures, even when prolonged, are not associated
with any negative impact on cognitive function.58,59 Thus, the AAP does not recom-
mend routine use of antipyretics or antiepileptics in patients with from febrile sei-
zures.50 Under extenuating circumstances (eg, febrile status epilepticus, distance
from emergency health care, severe parental anxiety), one could consider discharging
patients home with a prescription for rectal diazepam for use in case of a prolonged
 Pediatric Seizures 741

febrile seizure with appropriate instruction in its use. Fortunately, for most cases of
simple febrile seizures, education and reassurance will be all that is required.

NEW-ONSET AFEBRILE SEIZURES

Every year, between 25,000 and 40,000 children in the United States will have an initial
afebrile seizure60; thus, it is also critical for emergency physicians to understand the
basic evaluation of a new-onset afebrile seizure. It is important for one to remember
that a seizure does not always equal epilepsy and instead signifies some sort of brain
dysfunction that has resulted in abnormal electrical activity in the brain61; thus, a broad
differential diagnosis beyond epilepsy is required when considering the child who has
suffered an afebrile seizure. Naturally, after acute stabilization of patients, a thorough
history and physical examination are critical initial steps in the evaluation. A detailed
description of the event is critical to categorizing the event as a seizure and further
delineation into categories, such as simple, partial, or partial with secondary general-
ization. A history of focality to the seizure, prior abnormal neurodevelopment, altered
fluid intake, recent immigration after years in a developing country, and possible sub-
stance exposure or the findings of abnormal skin lesions, hepatosplenomegaly, or
retinal hemorrhages all help delineate whether the seizure represents a de novo pre-
sentation of epilepsy versus a symptom of another process, such as a brain tumor,
hyponatremia, intracranial infection, ingestion, neurocutaneous syndrome (eg, tuber-
ous sclerosis), inborn error of metabolism, or nonaccidental trauma.
Just as the differential diagnosis list for afebrile seizure is diverse, the potential eval-
uation is vast. There is no standardized laboratory panel for children presenting with an
initial afebrile seizure that can be recommended. As documented in the American
Academy of Neurology practice parameter on the evaluation of afebrile seizures in
children, the yield of routine laboratory studies is abysmally low.60 Instead, laboratory
investigation should be tailored to the individual case as suggested by the patients’
history and physical examination. It is prudent to have a low threshold to obtain a
bedside glucose because hypoglycemia represents an easily correctable cause of
seizure. A basic electrolyte panel may be particularly useful in younger patients
because electrolyte abnormalities have been noted more frequently in this popula-
tion.21,62 Other studies that may warrant consideration based on the individual pa-
tient’s history and physical examination include complete blood counts, toxicology
screens, ammonia levels, serum organic acids, and urine amino acids. Lumbar punc-
ture may also be considered if there is clinical concern for meningoencephalitis,
although the yield of routine CSF studies is extremely low in patients with a normal
mental status and physical examination.
Potential structural anomalies and abnormalities also need to be contemplated
during the initial evaluation of patients with a new-onset afebrile seizure. There
are clear recommendations for neuroimaging in most cases of new-onset afebrile
seizures,63 and emergent CT imaging is available in most emergency departments.
However, there is growing concern about the detrimental effects of radiation on the
pediatric brain.64,65 Additionally, it has been found that the information gleaned from
the head CT performed after an afebrile seizure seldom results in a change in manage-
ment or in any acute intervention.60,66 Studies are also suggestive of the superiority of
MRI regarding identifying lesions compared with CT; in one study, 33% of patients
with an initially normal CT scan had abnormal findings identified on MRI.23 Thus,
MRI is the preferred modality for definitive neuroimaging.60,63 Unfortunately, MRI is
less readily available on an emergency basis and may require additional resources
for sedation in younger patients. Given the risks and benefits of various modalities
742 Agarwal & Fox

of neuroimaging, a uniform approach cannot be recommended. It is thought best to

discuss the risks, benefits, and limitations of the imaging modalities against the risk
for emergent intracranial pathologic conditions with patients’ families and the neurol-
ogist on an individual basis.
The desire to obtain the most prudent studies must be balanced with the physician’s
suspicion for important, emergent pathologic conditions. There are factors that may
heighten suspicion for pathologic conditions that might require immediate interven-
tion, such as a stroke or increased intracranial pressure, and, thus, lower the threshold
for obtaining emergent neuroimaging (Box 2). Unfortunately, the very young (less than
6 months of age) are more difficult to obtain a reliable neurologic examination on;
some advocate for obtaining emergent neuroimaging in these patients after a new-
onset afebrile seizure.67 Additionally, a prolonged seizure (>15 minutes), persistent
postictal focal deficit, or aberration from neurologic baseline should increase concern
for focal disease processes.60,67 Additionally, patients with a predisposing condition
like sickle cell disease, bleeding disorder, cerebrovascular disease, neurocutaneous
disorder, malignancy, human immunodeficiency virus, hemihypertrophy, hydrocepha-
lus, travel to an area endemic for cysticercosis, or a closed-head injury should in-
crease suspicion for significant abnormalities.67,68 Focal seizures in children
younger than 33 months should also lower the threshold for obtaining emergent neu-
roimaging.68 Otherwise, in the absence of the aforementioned concerning factors,
children with a reassuring neurologic examination and an appropriate, established

Box 2
Factors lower threshold to obtain emergent neuroimaging for first-time afebrile seizure

Findings
 Less than 6 months of age
 Abnormal physical examination
 Prolonged seizure (>15 minutes)
 Persistent postictal period
 Altered mental status
 Persistent focal neurologic deficit
 Focal seizure in child less than 33 months of age
 Closed-head injury
 Travel to endemic area for cysticercosis
Concurrent medical conditions
 Bleeding disorder
 Cerebrovascular disease
 Hemihypertrophy
 Human immunodeficiency virus
 Hydrocephalus/ventriculoperitoneal shunt
 Malignancy
 Neurocutaneous disorder
 Sickle cell disease

Data from Refs.60,67,68

 Pediatric Seizures 743

outpatient follow-up plan may be appropriate for out-patient MRI rather than CT
before discharge from the emergency department.67
Before discharge, the family should be informed that the outpatient evaluation
would likely also include additionally studies. An EEG is indicated in all children with
an afebrile seizure, although the best time to obtain this study remains unclear.60
Nonspecific abnormalities secondary to the seizure are commonly seen in the few
days after a seizure; thus, there is no role for routine EEG before discharge for patients
with an initial afebrile seizure who have returned completely to neurologic baseline.
However, it is critical that these patients have appropriate outpatient follow-up for
EEG within a timely fashion because EEG abnormalities may in fact be the best pre-
dictor of seizure recurrence.69
Generally speaking, the outcomes of children with a new-onset afebrile seizure are
quite good. The overall recurrence rate of seizures is about 54%, with most recur-
rences occurring within 2 years of the initial seizure; thus, almost half of all children
with an initial afebrile seizure will not develop epilepsy. The risk of subsequent epilepsy
is increased in patients with an abnormal EEG and history of abnormal neurodevelop-
ment.70,71 Unfortunately, there are no known therapies that alter a patient’s potential
progression to epilepsy after an initial afebrile seizure. Because there have been no
detrimental effects noted in delaying seizure therapy until after a second seizure,
the initiation of antiepileptic medication is not recommended after an initial afebrile
seizure, with possible exceptions as discussed earlier in febrile seizures for prescrib-
ing rectal diazepam.72 Antiepileptic medication initiation is best left to the physician
who will follow patients long-term and monitor for potential complications. Even
among patients who go on to develop epilepsy, outcomes are not completely unfavor-
able. In one longitudinal cohort of children with epilepsy, around 70% of children were
able to achieve remission from seizures and 60% were able to discontinue antiepi-
leptic treatment, whereas only 10% had intractable epilepsy.73

STATUS EPILEPTICUS

Most patients who present to the emergency department for evaluation of a seizure
are no longer seizing. However, patients who are actively seizing will generate imme-
diate attention; seizure activity may easily recur or develop in any emergency
department patient. The annual incidence of pediatric status epilepticus is more
than 80,000.74 This entity accounts for approximately 10% of all patients with
new-onset pediatric seizures presenting to the emergency department4 and is
most common in children less than 2 years of age.75,76 Although there are many po-
tential precipitants of status epilepticus ranging from central nervous system infec-
tion to trauma to congenital anomalies to toxins, febrile seizures are the most
common cause of status epilepticus in children, accounting for approximately
one-third of all episodes1,77,78; this is in contrast to adults whereby cerebrovascular
accidents represent the most common cause of status epilepticus.79 Fortunately,
the quoted mortality rate for pediatric status epilepticus is quite low, ranging from
3% to 5%.80,81
Historically, status epilepticus has been defined as continuous seizure activity for
30 minutes or 2 or more seizures occurring without full recovery of consciousness
between episodes.77 However, there has been a recent trend to categorize seizures
lasting longer than 5 to 10 minutes as status epilepticus because there is evidence
that seizures are less likely to spontaneously cease after this time frame.82 From an
emergency medicine perspective, the categorization is less vital because it is the pa-
tients’ clinical condition that mandates the management of the patients.
744 Agarwal & Fox

Although the exact categorical label may still be debated, resolving the seizures as
expeditiously as possible is beneficial. With short-duration seizures, the increased
metabolic demands of the brain are met with increased cerebral blood flow; how-
ever, as the seizure continues, autoregulation can fail and the blood flow to tenuous
areas can be compromised, potentially leading to irreversible cerebral damage.77
Persistent neuronal excitation may also mediate neuronal injury.83 Furthermore, pro-
longed seizures can be associated with hyperthermia, myoglobinuria, hyperuricemia,
renal impairment, multiple metabolic derangements, aspiration, respiratory failure,
hepatic failure, and persistent neurodevelopmental abnormalities.77,84,85 Finally,
there is excellent evidence suggesting that seizures become more refractory to
therapy the longer they persist.75,86,87 In an effort to minimize the chance that the
seizure will progress to a refractory state, aggressive therapy should be initiated
as soon as possible.
As with all efforts to stabilize patients during emergent conditions, the initial steps
should focus on maintaining a patent airway, ensuring there is adequate ventilation,
and assessing patients for appropriate circulation. Actively seizing patients can
have derangements in one or all of these important systems. Although more aggres-
sive maneuvers may be necessary, often a simple jaw thrust will be adequate to help
maintain a patent airway. Supplemental oxygen is advisable if respirations become
compromised, and suctioning should be readied in case of emesis. The use of bite
blocks to protect the tongue has fallen out of favor given the risk of aspiration.
Although it is reasonable to observe patients briefly before administering medicines
in case the seizure spontaneously ceases, there is good evidence that seizures that
persist beyond 5 minutes are unlikely to stop82; thus, at this point, it is beneficial to
administer medications to halt the seizure. Benzodiazepines are considered first line
therapy for essentially all seizure disorders; they work by modulating the gamma-
aminobutyric acid (GABA) receptor.88 All medicines in this class carry the risk of
respiratory depression and hypotension, necessitating close monitoring for these
complications, especially when multiple doses or other medications are given. Each
benzodiazepine has unique characteristics and dosing (see Table 1). Diazepam is
commonly used given its rapid onset secondary to its highly lipophilic properties
enabling rapid penetration across the blood-brain barrier. It is also frequently pre-
scribed to patients with known seizure disorders for home administration rectally; it
can also be used in this manner in the emergency department if intravenous access
has not been established.89 More recently, midazolam has started to gain favor in
the prehospital and emergency department environments because of its ease of
use and efficacy via intranasal, intramuscular, and buccal routes.90–99 Because
vascular access is often difficult in pediatric patients (particularly ones who are ill),
intramuscular, intranasal, or buccal routes should be considered early in the manage-
ment. However, when intravenous access is established, lorazepam is the most
commonly used benzodiazepine because of its efficacy and duration of action of
6 to 12 hours.77
Continued seizure activity despite successive doses of benzodiazepine should lead
to the administration of medications that work by a different mechanism (see Table 1).
Phenytoin and fosphenytoin have traditionally been selected as second-line agents
and affect voltage-gated sodium channels. Unfortunately, phenytoin cannot be
administered rapidly because of the associated hypotension, widening of the QT in-
terval, and dysrhythmias owing to its diluents. There is also the risk of purple glove
syndrome.77,100,101 Unlike phenytoin, fosphenytoin can be administered more rapidly,
safely, and even given intramuscularly; however, it is a prodrug of phenytoin and takes
longer to have an effect.77,102
 Pediatric Seizures 745

Phenobarbital has long held position as a third-line medication in the treatment of

status epilepticus. Although it also works on GABA receptors, it does so via a different
mechanism from benzodiazepines. It takes longer to terminate seizure activity but has
a prolonged therapeutic effect. Although there is no definitive evidence, it is a
commonly held belief that phenobarbital is more strongly associated with respiratory
depression, potential need for intubation, and hypotension compared with phenytoin.
Interestingly, phenobarbital is commonly favored over benzodiazepines as a first-line
or second-line therapy for the treatment of neonatal seizures and should be potentially
considered for use earlier when managing younger patients.24,103
Newer medications have recently demonstrated promise and potential value in the
acute management of status epilepticus. Valproate has shown benefit as a second-
line medication, with particular utility in patients already maintained on this medication
or who have nonconvulsive or partial status epilepticus.104–110 It also lacks adverse
effects on the cardiovascular or respiratory systems but does have potential risks of
hepatic dysfunction, parkinsonism, pancreatitis, and thrombocytopenia.102,111 Leve-
tiracetam has been shown to be safe in children as young as 6 months of age; it is
generally well tolerated, and side effects are reversible with cessation of the medica-
tion.112 Levetiracetam also offers the advantage of being able to be converted easily
over to oral medications later in the patients’ management. Preliminary evidence
suggests that levetiracetam may be safely administered intravenously as therapy for
status epilepticus, although further research is necessary to recommend routine use
of this medication.110,113–115
Unfortunately, refractory status epilepticus occurs in 25% of patients with status
epilepticus.116 If patients have continued to seize despite the previous interventions,
the seizure is considered to be refractory117 and patients are at an increased risk
for adverse events. Before this period, patients may or may not have required intuba-
tion to protect airway patency; however, the management of refractory status epilep-
ticus will require intubation because most therapies will essentially induce general
anesthesia and coma. In this scenario, emergent EEG monitoring is of vital importance
to guide further therapy because paralytics will mask potential continued convulsions.
There are no clear guidelines on what is the most advantageous therapy, but standard
options include continuous infusions of midazolam, propofol, pentobarbital, ketamine,
and lidocaine. Additional therapies that have growing evidence and may eventually
have a standardized role in the management of status epilepticus include lacosamide,
magnesium, topiramate, isoflurane, steroids, therapeutic hypothermia, electroconvul-
sive therapy, vagal nerve stimulation, and emergent surgery.116,118–122
Any discussion of status epilepticus would be incomplete without the consideration
of nonconvulsive status epilepticus. This entity is thought to account for approximately
25% of all cases of status epilepticus and is more common in patients with certain ep-
ilepsy syndromes.123 The classic subtypes include absence status epilepticus and
complex partial status epilepticus. About a quarter of cases of nonconvulsive status
epilepticus follow convulsive status epilepticus and represent burnt out or subtle
generalized status epilepticus.123,124 These patients may have a range of altered
mental status ranging from mild confusion to psychosis to coma with subtle physical
movements, such as twitches or automatisms.124 Nonconvulsive status epilepticus
should be considered in patients with an inexplicable, sudden change in mental status
or behavior, clinical concern for encephalopathy, unexplained coma, or delayed re-
covery of mental status after a seizure.123–125 EEG monitoring is paramount to be
able to make the appropriate diagnosis and management of this entity. Treatment is
the same as for convulsive status epilepticus with the possible consideration of val-
proate as a second-line medication.124
746 Agarwal & Fox

ADDITIONAL PEDIATRIC SEIZURE SYNDROMES AND UNIQUE THERAPIES

Although the authors have already discussed febrile seizures, which constitute the
largest category of seizures unique to the pediatric population, there are many other
seizure syndromes unique to pediatric patients. It is useful for the emergency medicine
physician to possess a basic knowledge about a few of these particular syndromes.
These entities range from benign, self-limited conditions to neurologically devastating
diseases and are further discussed in Table 2.
Despite the recent advent of new antiepileptic drugs and generally good prognosis
for patients with epilepsy, about 10% of children will have intractable epilepsy.73,126
Poorly controlled seizures are the primary risk factor for sudden unexpected death
in epilepsy, increasing the risk of this event from 1 in 1000 to 1 in 150.2,127–129 In these
cases, novel therapies, including implantable devices, specific diets, and surgery, may
be required. Rudimentary knowledge of some of these more aggressive therapies is
warranted.
The only implantable device currently approved for use in the United States is the
vagal nerve stimulator (VNS). This device consists of an implanted device in a sub-
cutaneous pocket, either under the clavicle or in abdominal tissue in smaller patients;
a microprocessor and battery are attached to the left vagus nerve via leads. The VNS
is typically set to deliver a stimulus designed to terminate seizures when a small
handheld magnet is held directly over the device for a few seconds; thus, activation
of a VNS may be useful in the management of seizures in patients who possess this
technology. If mandated, MRI generally can be completed regardless of VNS place-
ment; but this is best coordinated between neurosurgery and radiology. There is a
3% to 5% risk of infection of the VNS, and lead fractures may occur after direct
trauma to the neck. Patients may also present with complaints of twitching, cough-
ing, dysphagia, or other sensations secondary to VNS firing. Continual device activa-
tion may occur rarely, and taping the magnet over the patients’ VNS should turn it off
until neurosurgical evaluation can be obtained. Otherwise VNS are generally helpful
in reducing seizure frequency by about half in 50% of all patients.130,131
Another therapy that patients with intractable epilepsy may use is the ketogenic diet.
Essentially a starvation state is used to induce ketosis, generally resulting in up to a
30% to 40% reduction in seizures in numerous types of epilepsies, with even better
results in some individual patients.132 Within a few weeks of initiation, patients may
present with complications, such as dehydration, hypoglycemia, and other metabolic
derangements. However, long-term complications are typically limited to osteopenia,
nephrolithiasis, and cardiomyopathy. Occasionally, these patients will present to the
emergency department with ongoing seizure activity, potentially with hypoglycemia.
In this situation, correcting hypoglycemia may actually be harmful and worsen seizure
activity by breaking the patients’ ketotic state. Thus, dextrose infusion must be
reserved for patients with severe hypoglycemia, and other typical seizure therapies
should be maximized. Additionally, in cases of refractory status epilepticus, it may
be wise to avoid propofol because these patients are at a higher risk of propofol infu-
sion syndrome.22,133,134
Occasionally, patients will have seizures of such severity that they may require
experimental therapies or even surgery. At present, there are numerous devices,135
medications, alternative diets, and other therapies under investigation. Surgeries
may be particularly beneficial in focal epilepsies and the most intractable diseases.
These surgeries, such as hemispherectomy, corpus callosotomy, and anterior tem-
poral lobe resection, may be associated with delayed complications, such as
bleeding, hematoma formation, and obstructive hydrocephalus136; however, they
 Pediatric Seizures 747

Table 2
Seizure syndromes unique to pediatric patients

Benign Convulsions 6–60 mo Afebrile, brief, generalized seizures

Associated with Peaks 13–24 mo accompanying symptoms of gastroenteritis
Gastroenteritis without metabolic derangement, fever, or
Shigella infection; associated strongly with
rotavirus, although seen with other viral
causes; seizures may cluster, be difficult to
treat; spontaneously remits at conclusion of
illness139–141
Benign Familial Initial days of life Presentation may include behavioral arrest,
Neonatal Remits within 1 y eye deviation, tonic stiffening, myoclonic
Convulsions jerks; associated with positive family history;
some may develop subsequent epilepsy16
Benign Idiopathic Initial days of life Also called “fifth day fits”; presentation may
Neonatal Remits within 15 d include clonic movements, apnea; associated
Convulsions with positive family history; may account for
up to 5% of all seizures in term infants16
Absence Seizures 5–10 y Associated with sudden cessation of activity,
Remits by 14 y possible eye fluttering, brief duration (about
30 s), and no postictal period; seizures may
be triggered by hyperventilation; 70% of
patients spontaneously remit; 40% of
patients may have associated generalized
tonic-clonic seizures22,142
Benign Rolandic 3–13 y Typically associated with nighttime clonus
Epilepsy Remits by early (especially facial) while sleeping, which may
adulthood secondarily generalize; associated with
autosomal dominant inheritance22,143
Juvenile Myoclonic 12–15 y Typically associated with myoclonic jerks on
Epilepsy of Janz awaking, although also many have
generalized tonic-clonic or absence seizures;
triggered by stress, lack of sleep, alcohol;
associated with autosomal dominant
inheritance; generally requires ongoing
treatment22,143
Infantile Spasms 4–18 mo Sudden jerking of extremities, head, neck, and
Peaks 4–6 mo trunk, occasionally with associated cry,
typically occurring in clusters; associated
with other neurologic conditions (such as
tuberous sclerosis, HIE, congenital
infections); 95% of patients also have mental
retardation; treated with steroids,
vigabatrin; spasms typically spontaneously
remit, but most patients develop new
seizures143–145
Lennox-Gastaut 3–5 y Patients suffer from multiple seizure types
Syndrome including tonic, absence, atonic, myoclonic,
and status epilepticus; associated with static
encephalopathy, mental retardation,
intractability despite multiple medications
or use of rare therapies, such as surgery,
special diets22,145

Data from Refs.16,22,139–145

748 Agarwal & Fox

may ultimately be the most effective measure in providing relief to patients with
intractable epilepsy.137

SUMMARY

Pediatric seizures are common and have many characteristics that distinguish them
from seizures in adults. Appropriate diagnosis of seizures may be challenging given
numerous seizure mimics and the subtle presentation of neonatal seizures. Making
an appropriate diagnosis as to the presence of a seizure and any potential cause is
critical to delivering appropriate care. Although some entities may be relatively
benign, such as febrile seizures, status epilepticus and refractory seizure syndromes
can produce significant morbidity and mortality. Fortunately, the outcomes of sei-
zures in pediatric patients are generally excellent; there has been ongoing develop-
ment of additional therapies, including medications, diets, devices, and surgeries.

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