Afebrile Pediatric

S e i z u res
a,b c,
Ghazala Q. Sharieff, MD , Phyllis L. Hendry, MD *

KEYWORDS
 Absence seizures  Neonatal seizures  Infantile spasms
 Afebrile  Hyponatremia  Convulsions  Epilepsy

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Seizures in children can be anxiety provoking for both the parent and the medical care-
giver. By 14 years of age, approximately 1% of children will experience an afebrile seizure
with the highest incidence being in children younger than 3 years.1 Population-based
studies reveal that there are between 25,000 and 40,000 children per year in the United
States who sustain a first-time, unprovoked seizure, 70% of which are idiopathic.2,3
The overall recurrence rate in children with a first unprovoked afebrile seizure varies
from 14% to 65%4; however, up to 88% of seizure recurrences occur within the first 2
years of the initial event.5,6 Furthermore, Shinnar and colleagues7 found that children
who experience their first unprovoked seizure during sleep have approximately twice
the recurrence rate as children whose first seizure occurred while awake. The first priority
in a seizing patient is airway management and subsequent termination of the seizure.

SEIZURES THAT OCCUR IN CHILDHOOD

Absence Seizures
Simple (typical) absence seizures are uncommon before 5 years of age, and are typi-
cally characterized by a sudden cessation of motor activity with an accompanying

a
Department of Emergency Medicine, Palomar-Pomerado Health System/California Emer-
gency Physicians, 3020 Children’s Way, San Diego, CA 92011, USA
b
University of California, San Diego, CA, USA
c
Department of Emergency Medicine, University of Florida College of Medicine, 655 West
Eighth Street, Jacksonville, FL 32209, USA
* Corresponding author.
E-mail address: phyllis.hendry@jax.ufl.edu

Emerg Med Clin N Am 29 (2011) 95–108

doi:10.1016/j.emc.2010.08.009 emed.theclinics.com
0733-8627/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved.
96 Sharieff & Hendry

blank expression. Flickering of the eyelids may also be seen. The episodes last less
than 30 seconds and are not associated with a postictal period. Complex (atypical)
absence seizures are usually associated with myoclonic activity in the face or extrem-
ities, and are associated with an altered level of consciousness.
Lennox-Gastault
In this seizure disorder, patients experience a combination of tonic, absence, atonic,
or myoclonic seizures with seizure onset between 3 and 5 years of age. Most of these
children also have accompanying mental retardation and severe behavioral problems.
An electroencephalogram (EEG) shows an irregular, slow, high-voltage spike pattern.
While many drugs have been used to treat this condition, management is still very diffi-
cult. Valproic acid is the drug that is most commonly used; however, felbamate, top-
iramate, lamotrigine, and ethosuximide have also been used as add-on therapy.8,9 The
ketogenic diet (high fat, low protein, low carbohydrates) has been used with some
success for these children. A study by Hemingway and colleagues10 revealed that
13% of patients with intractable seizures who were treated with the ketogenic diet
were seizure free at 1 year. Furthermore, a decrease by up to 99% in the frequency
of seizures was noted in an additional 14% of patients who were started on the keto-
genic diet. It is important to remember that if glucose is given, increased seizure
activity may be seen.
Benign Rolandic Epilepsy
This syndrome typically involves children between 3 and 13 years of age who experi-
ence nighttime seizures. The initial phase of the seizure involves clonic activity of the
face, which can then secondarily generalize. The history is characteristic with the
seizures occurring during sleep. An EEG is important in the evaluation, as a character-
istic perisylvian spiking pattern can be seen. Unless these seizures are frequent, no
therapy is needed as patients will usually outgrow these episodes by early adulthood.
Carbamazepine and levetiracetam have been used with success in the treatment of
benign Rolandic seizures.
Juvenile Myoclonic Epilepsy of Janz
As the name implies, this disorder begins in early adolescence (peak age range is
12–15 years). Patients experience myoclonic jerks typically on awakening, but
may also have tonic-clonic (80%) or absence (25%) seizures. Typical inducing
factors include stress, alcohol, hormonal changes, or lack of sleep. The EEG is help-
ful in the diagnosis as a pattern of fast spike-and-wave discharges can be seen.
Valproic acid has traditionally been the drug of choice; however, levetiracetam
has shown effectiveness as both add-on and monotherapy for partial and general-
ized seizures.1
Infantile Spasms (West syndrome)
Children with this syndrome typically present between 4 and 18 months of age,
and males are more commonly affected than females. Up to 95% of these chil-
dren are mentally retarded and there is a 20% mortality rate. Patients experience
spasms, which are typically single jerking episodes in flexion or extension of the
involved muscle groups. The jerking is spasmodic, often occurring in clusters,
and the child often cries during the episode. Episodes rarely occur during sleep.
Up to 25% of patients have tuberous sclerosis. The EEG shows the classic
pattern of hypsarrhythmia (random high-voltage slow waves with multifocal
spikes). Treatment with adrenocorticotropic hormone (ACTH), prednisone
 Afebrile Pediatric Seizures 97

vigabatrin, and pyridoxine have been used with some success. Valproic acid,
lamotrigine, topiramate, zonisamide, levetiracetam, and benzodiazepines have
also shown some effectiveness.8,9,11,12

EMERGENCY DEPARTMENT EVALUATION OF THE FIRST AFEBRILE SEIZURE

History and Physical Examination
The history should focus on the events immediately before the onset of the episode,
a description of the seizure including seizure duration, cyanosis, loss of conscious-
ness, the presence of incontinence, length of the postictal period, any postictal neuro-
logic abnormalities, recent immunizations, change in diet or oral intake, and family
history of seizures. A detailed birth history is important in new-onset seizures in
neonates and infants. Home therapies and home remedies for any recent illnesses
should also be determined. If the patient has a known seizure disorder, then it is impor-
tant to ascertain if this seizure was different from previous seizures, the normal seizure
frequency for the patient, medications the patient is on, if the patient has been
compliant with the medication regimen, or if there have been any recent medication
changes. The history may often help to differentiate a true seizure from a seizure
mimic. Psychosocial history and recent family events are important in determining
psychogenic seizures versus neurologic seizures. Patients who experience true
seizures may describe an aura such as epigastric discomfort or a feeling of fear.
The patient’s positioning during the seizure, loss of sphincter control, duration of
seizure, and the length of the postictal state should also be noted.
The physical examination focuses on the neurologic examination. In infants,
measurement of head circumference may be helpful. A bulging fontanel indicates
increased intracranial pressure. The eyes should be examined for papilledema and
retinal hemorrhages. The presence of hepatosplenomegaly may indicate a metabolic
or glycogen storage disease. The skin should also be checked for lesions such as
café-au-lait spots (neurofibromatosis), vitiliginous lesions (tuberous sclerosis), and
port-wine stains (Sturge-Weber syndrome). The differential diagnosis of seizures in
children is listed in Box 1.

EMERGENCY DEPARTMENT MANAGEMENT

For the patient who is no longer seizing and whose airway is protected, little immediate
management is needed beyond supportive care and continued monitoring. A bedside
blood glucose reading should be obtained and hypoglycemia treated as follows: D10
solution (3–10 mL/kg) for newborns and D25 (2–4 mL/kg) solution for children. Dextrose
should not be empirically given to children on ketogenic diets, as this will break the
ketogenic state and may result in seizures. Any seizure that has lasted longer than 5
minutes should be treated with a benzodiazepine.13 Lorazepam is an excellent choice,
as it has an antiseizure duration of action of approximately 12 hours. Other options are
diazepam and midazolam (Table 1). If the patient is actively seizing and intravenous
(IV) access cannot be obtained, rectal diazepam, dosed at 0.3 to 0.5 mg/kg, can be
administered.15 Parents of known epileptics may have already administered this medi-
cation before paramedic arrival. Although diazepam has been the agent of choice in
the past, recent studies support the use of midazolam.16–18 The advantage of midazo-
lam is that it can be administered by many routes including IV, intramuscular (IM),
rectal, intranasal, and buccal.19,20 In one study, when compared with IV diazepam,
IM midazolam (0.2 mg/kg) resulted in faster seizure termination due to more rapid
administration rates.21
98 Sharieff & Hendry

Box 1
Differential diagnosis of seizures in children

Benign paroxysmal vertigo

Benign myoclonus of infancy
Benign sleep myoclonus
Breath-holding spellsa
Gastroesophageal reflux
Sandifer syndromeb
Migraine headaches
Night terrors, sleepwalking, somniloquy, narcolepsyc
Psychological
Attention-deficit disorder
Hyperventilation
Hysteria and rage attacks
Pseudoseizures
Panic attacks
Shuddering attacksd
Sleepwalking
Syncope
Tics-Tourette syndrome
Toxins
a
Breath-holding spells: Patients with cyanotic breath holding spells typically become angry,
stop breathing in end-exhalation, pass out, and may have a hypoxic seizure.
b
Gastrointestinal reflux: Infants with Sandifer syndrome present with crying, vomiting,
esophagitis, and writhing and arching movements of the neck and back that may be confused
with seizure activity.
c
Sleep disorders: Night terrors occur when the child sits up suddenly during sleep, cries,
screams, and is unresponsive to consoling attempts. The patient then returns to sleep and
has no recollection of the event the next morning.
d
Paroxysmal movement disorders: Shudder attacks are episodes of shivering activity that are
not associated with any change in mental status. Spasmus mutans typically occurs in infants
between 4 and 12 months of age, with the child experiencing head nodding, head tilt, and
nystagmus.

If benzodiazepines do not terminate the seizure, the next agent of choice is either
phenytoin or fosphenytoin because they do not cause central nervous system or
respiratory depression. Fosphenytoin can be given 3 times as quickly as phenytoin
(3 mg/kg/min vs 1 mg/kg/min) and reaches therapeutic serum concentrations within
15 minutes (phenytoin takes 25 minutes).22

LABORATORY TESTING

In patients who are on anticonvulsant medications, a drug level should be obtained.

The practice of obtaining an electrolyte panel, and calcium and magnesium levels
on every patient with a short seizure has been called into question in the child who
 Afebrile Pediatric Seizures 99

Table 1
Drugs used in the management of seizures

Diazepam 0.2–0.3 mg/kg IV, 0.5 mg/kg rectal

Lorazepam 0.05–0.1 mg/kg IV
Midazolam 0.1 mg/kg IV, 0.2 mg/kg IM
Phenytoin 15–20 mg/kg IV (no faster than 1 mg/kg/min)
Fosphenytoin 15–20 mg/kg IV or IM (can be given 3 mg/kg/min IV)
Phenobarbital 18–20 mg/kg IV, then 5–10 mg every 10 min (1 mg/kg/min)
(maximum 50–60 mg/kg)
Levetiracetam IV 50 mg/kg (maximum 2.5 g)
Oral treatment should be initiated with a daily dose of 20 mg/kg
in 2 divided doses (10 mg/kg bid). The daily dose should be increased
every 2 weeks by increments of 20 mg/kg to the recommended daily
dose of 60 mg/kg (30 mg/kg bid)14
Pyridoxine 50–100 mg IV
Lidocaine 1–2 mg/kg IV, then 4–6 mg/kg/h for refractory seizures

Abbreviations: bid, twice a day; IM, intramuscular; IV, intravenous.

is alert, interactive, and back to his or her baseline level of functioning. The Report of
the Quality Standards Subcommittee of the American Academy of Neurology, the
Child Neurology Society, and the American Epilepsy Society recommends that labo-
ratory testing only be ordered based on clinical circumstances such as vomiting, diar-
rhea, dehydration, or failure to return to baseline level of consciousness.23
Furthermore, a toxicology screen should be performed if there is any suspicion of
drug exposure or abuse.
Newborns and children younger than 6 months have been found to be at greater risk
for electrolyte abnormalities because of underlying metabolic abnormalities,24 specif-
ically hyponatremic seizures due to increased free water intake from formula overdilu-
tion. Farrar and colleagues25 studied 47 patients younger than 6 months with seizures,
and reported that the median seizure duration was longer (30 minutes vs 17 minutes,
P 5 .007) in patients with hyponatremia, with a greater incidence of status epilepticus,
73% versus 36% (P 5 .02). Furthermore, emergency intubation was performed more
often in hyponatremic patients than in normonatremic patients (P 5 .009). Median
temperature was lower in hyponatremic infants (35.5 C vs 37.2 C, P 5 .0001).
Temperature less than 36.5 C was the best predictor of hyponatremic seizures in
infants younger than 6 months.
In a retrospective review of 149 infants younger than 12 months, Scarfone and
colleagues26 studied 214 visits for seizures, 80 of which were classified as febrile
seizures. All laboratory results were reviewed: 19 of 80 febrile seizures were tested
and none had abnormal electrolytes or calcium or magnesium levels: 67 of 134 non-
febrile infants were tested, with 13% having abnormal chemistry results. However,
patients with abnormal laboratory results were more likely to be actively seizing in
the emergency department (ED), have hypothermia (temperature <36.5 C), or be
younger than 1 month.
Based on the results of these studies, it is reasonable to obtain laboratory studies on
pediatric patients with prolonged seizures, age less than 6 months, history of diabetes
or metabolic disorder, dehydration or history of excess free water intake, and with an
altered level of consciousness. Routine lumbar puncture in patients who are alert and
oriented after a first afebrile seizure is not indicated. However, a spinal tap should be
100 Sharieff & Hendry

performed in patients with altered mental status, signs of meningitis/encephalitis, pro-

longed postictal period, or immunocompromised state, or if there is any suspicion of
subarachnoid hemorrhage.

NEUROIMAGING

Magnetic resonance imaging (MRI) has superior resolution and is more sensitive than
head computed tomography (CT) for the detection of low-grade tumors and heterotopic
gray matter. A recent study of MRI findings in children with a first recognized seizure
found at least one abnormality in 31% of children. Abnormalities defined as significant
or related to seizures occurred in only 14%.27 MRI is not readily available in all EDs and
may be best performed on an outpatient nonemergent basis. MRI also lacks the radia-
tion risks of CT scans.28 Children are at greater risk than adults from a given dose of radi-
ation because they are more radiosensitive and because they have more remaining
years of life during which a radiation-induced cancer could develop.29
Although many providers routinely perform CT scans on every patient with new-onset
seizures, this practice has been called into question. In 1997, Warden and colleagues30
recommended that emergent neuroimaging be reserved for patients with a prolonged
postictal period, status epilepticus, age less than 6 months, new-onset focal neurologic
defects, recent head injury, patients with ventriculoperitoneal shunts, or other neurocu-
taneous disorders. In 1998, Garvey and colleagues31 conducted a retrospective anal-
ysis of 107 neurologically normal patients who underwent neuroimaging in the ED for
“first seizure”: 8 of 107 had nonepileptic events (gastroesophageal reflux, syncope,
and rigor). Of the remaining 99 patients, 49 had provoked seizures and 50 had unpro-
voked seizures: 19 of 99 patients had CT abnormalities, and 9 of 49 with provoked
seizures had abnormalities on CT, but none required intervention (mild hydrocephalus,
angioma, asymmetry, periventricular leukomalacia). Ten of 50 patients with unpro-
voked seizures had CT abnormalities, with 7 receiving further investigation or interven-
tions: 2 had tumors, 3 had vascular abnormalities, 1 had cysticercosis, and 1 had
obstructive hydrocephalus. In this study, CT scan abnormalities requiring treatment
or monitoring were more often seen in children with unprovoked seizures (P<.01) and
in children with focal seizures or focal neurologic findings (P<.04).
Sharma and colleagues32 reviewed 500 patients with new-onset seizures, of whom
475 underwent neuroimaging. The mean patient age was 62 months (range 0–21
months). Focal seizures were present in 33% of patients. Risk factors for neuroimag-
ing abnormalities included the presence of a predisposing condition or a focal seizure
in children younger than 33 months. Predisposing conditions were sickle cell disease,
bleeding disorders, cerebral vascular disease, malignancy, human immunodeficiency
virus (HIV), hydrocephalus, travel to areas with cysticercosis, closed head injury, or
the presence of hemihypertrophy. Clinically significant findings were present in 8%
(38/475) of patients who underwent neuroimaging. Twenty-six percent (32/121) of
high-risk patients had abnormalities versus 2% (6/354) of the low-risk patients. The
investigators concluded that emergent imaging should be performed only in patients
with high-risk criteria. Furthermore, they advised that if follow-up can be obtained,
low-risk patients can be discharged without immediate ED imaging.
A practice guideline written jointly by the Quality Standards Subcommittee of the
American Academy of Neurology, the Child Neurology Society, and the American
Epilepsy Society concur that there is insufficient evidence to support the routine
performance of neuroimaging in children with a first unprovoked nonfebrile seizure.23
Bedside brain ultrasonography is often the imaging study of choice in neonatal
seizures, due to challenges of transporting critically ill neonates to CT or MRI. The
 Afebrile Pediatric Seizures 101

disadvantage of ultrasonography is the poor detection of cortical lesions and

subarachnoid blood.

ELECTROENCEPHALOGRAPHY

An EEG is rarely needed in the ED setting, except for patients with refractory seizures
or in patients in whom the diagnosis of nonconvulsive status epilepticus is being
considered. Well-appearing children who have experienced a first-time afebrile
seizure can be managed as outpatients, with an EEG arranged by the primary care
physician. In idiopathic and cryptogenic seizures, the EEG has been found to be the
most important predictor of recurrence, with a 2-year recurrence rate of 58% in
patients with an abnormal EEG compared with a 28% seizure recurrence rate in
patients with a normal EEG.33 Of note, a normal EEG does not rule out a seizure
disorder or other underlying neurologic disorder.
Portable EEG monitoring is now available in many EDs and pediatric intensive care
units, and can be used to determine treatment response.

ANTIEPILEPTIC AGENTS

In a critical review of the literature, the Quality Standards Subcommittee of the Amer-
ican Academy of Neurology and the Practice Committee of the Child Neurology
Society found that although anticonvulsant agents decrease the incidence of second
seizures, they do not decrease the long-term risk of developing epilepsy.23 Therefore,
they recommend that for stable, well-appearing children who have experienced
a single seizure that did not require emergent anticonvulsant therapy, maintenance
medications are not initiated. Patients who experience recurrent seizures should be
started on an antiepileptic medication. The decision to initiate long-term anticonvul-
sant therapy should be made in conjunction with a pediatric neurologist or the
patient’s primary care physician. The most common agents used to treat afebrile
seizures are listed in Table 2. Felbamate is not commonly used because of the avail-
ability of safer antiepileptic agents, and is indicated only for cases of severe refractory
seizures (Lennox-Gastault syndrome) where the benefit clearly outweighs the risk of
liver toxicity and aplastic anemia.

NEONATAL SEIZURES

It is often difficult in the newborn to differentiate between a seizure from other condi-
tions, especially because newborn seizures can present in a variety of different ways
including apnea, subtle eye deviations, or abnormal chewing movements. In addition,
associated autonomic system findings seen with older patients with seizures may not
be seen. Useful tips in differentiating between a newborn with seizures and a “jittery
baby” are that true seizures cannot be suppressed by passive restraint and seizures
cannot be elicited by motion or startling.
The most common cause of a seizure in the first 3 days of life is perinatal hypoxia or
anoxia. Approximately 50% to 65% of newborn seizures are due to hypoxic-ischemic
encephalopathy.34 Intraventricular, subdural, and subarachnoid hemorrhages
account for 15% of newborn seizures, and an additional 10% are caused by inborn
errors of metabolism, sepsis, metabolic disorders, and toxins (Box 2).35 Pyridoxine
deficiency is an autosomal recessive disorder that is a rare cause of seizures, and
usually presents in the first 1 to 2 days of life.36
Benign familial neonatal convulsions and benign idiopathic neonatal convulsions
are 2 types of neonatal seizures that are benign and carry a favorable prognosis.
 102
Sharieff & Hendry
Table 2
Common anticonvulsant agents

Drug Type of Seizure Side Effects Maintenance

Carbamazepine (Tegretol) Generalized tonic-clonic, partial, Rash, liver disease, diplopia, 10–40 mg/kg divided bid or tid
benign Rolandic seizures aplastic anemia, leukopenia
Clonazepam (Rivotril, Klonopin) Myoclonic, akinetic, infantile Fatigue, behavioral issues, 0.05–0.3 mg/kg/d divided bid or tid
spasms, partial, Lennox-Gastault salivation
Ethosuximide (Zarontin) Absence GI upset, weight gain, lethargy, 20–40 mg/kg/d divided qd or bid
SLE, rash
Gabapentin (Neurontin) Partial and secondarily Fatigue, dizziness, diarrhea, ataxia 20–70 mg/kg/d
generalized seizures
Lamotrigine (Lamictal) Complex partial (atypical Headache, nausea, rash, Stevens- 10–12 mg/kg/d if given as
absence), Lennox-Gastaut, Johnson syndrome, monotherapy, 2–5 mg/kg/d
myoclonic, absence, tonic-clonic lymphadenopathy, diplopia, GI if given with valproic acid
upset
Levetiracetam (Keppra) Partial-onset seizures in children Dizziness, somnolence, headache 20 mg/kg/d divided bid. Daily dose
>4 y, generalized tonic-clonic increased every 2 wk by
seizures in children >6 y, juvenile increments of 20 mg/kg to the
myoclonic seizures in children recommended daily dose of 60
>12 y mg/kg (30 mg/kg bid)
Phenobarbital (Luminol) Generalized tonic-clonic, partial Sedation, behavioral issues 2–6 mg/kg/d divided qd or bid
Phenytoin (Dilantin) Generalized tonic-clonic, partial Gingival hyperplasia, hirsutism, 4–8 mg/kg/d divided bid, tid, or
rash, Stevens-Johnson qhs
syndrome, lymphoma
 Primidone (Mysoline) Generalized tonic-clonic, partial Rash, ataxia, behavioral issues, 10–25 mg/kg/d divided bid, tid, or
sedation, anemia qid
Topiramate (Topamax) Refractory complex partial Fatigue, nephrolithiasis, ataxia, 1–9 mg/kg/d
seizures, infantile spasms, headache, tremor, GI upset
adjunctive therapy for temporal
lobe epilepsy
Tiagabine (Gabitril) Adjunctive therapy for refractory Decreased attention span, tremor, Average dose 6 mg/d
complex partial (focal) seizures dizziness, anorexia
Valproic acid (Epicene, Epical) Generalized tonic-clonic, absence, GI upset, liver involvement, 10–60 mg/kg/d divided tid or qid
myoclonic, partial, akinetic, alopecia, sedation
juvenile myoclonic epilepsy of
Janz, infantile spasms
Vigabatrin (Sabril) Infantile spasms, adjunctive Weight gain, agitation, 30–100 mg/kg/d divided qd or bid
therapy for refractory seizures depression, behavioral changes,
visual field constriction, optic
neuritis
Oxcarbazepine (Trileptal) Partial/focal seizures Hyponatremia, hepatic or 20–40 mg/kg/d
blood dyscrasias
Zonis amide (zonegran) Adjunctive therapy for partial Rash, renal calculi, Begin with 1–2 mg/kg/d
or general seizures photosensitivity

Abbreviations: bid, twice a day; GI, gastrointestinal; SLE, systemic lupus erythematosus; tid, 3 times a day; qd, every day; qhs, every bedtime; qid, 4 times a day.

Afebrile Pediatric Seizures

103
104 Sharieff & Hendry

Box 2
Etiology of newborn seizures

First day of life

Anoxia
Hypoxia
Trauma
Intracranial hemorrhage
Drugs
Infection
Hypoglycemia/hyperglycemia
Pyridoxine deficiency
Second and third day of life
Sepsis
Inborn errors of metabolism
Trauma
Hypocalcemia
Hypoglycemia
Hypomagnesemia
Hyperphosphatemia
Hyponatremia/hypernatremia
Drug withdrawal
Congenital anomalies
Developmental brain disorders
Benign familial neonatal seizures
Hypertension
Day 4 of life to 6 months of age
Hypocalcemia
Hyponatremia/hypernatremia
Infection
Drug withdrawal
Inborn errors of metabolism
Hyperphosphatemia
Hypertension
Congenital anomalies
Developmental brain disorders
Benign idiopathic neonatal seizures

The etiology is unknown. Benign familial neonatal convulsions typically present in

the first 3 days of life, and there is a strong family history of epilepsy or neonatal
seizures. These seizures resolve by 1 to 6 months of age. Benign idiopathic
neonatal convulsions, also known as “fifth-day fits,” occur on the fifth day of life
 Afebrile Pediatric Seizures 105

and cease on day 15 of life.36 These diagnoses should be ones of exclusion. The
workup should be tailored to the patient but may include cranial ultrasonography,
a head CT or MRI scan, electrolytes, glucose, calcium, magnesium, toxicology
screen, urinalysis and culture, complete blood count and culture, and cerebrospinal
fluid (CSF) studies. If an inborn error of metabolism is suspected, then blood for
amino acids, lactate, pyruvate and ammonia levels should be obtained, as well
as urine for organic acids.
In neonates who are actively seizing, treatment includes attention to the airway,
breathing, and circulation. Benzodiazepines are often given as the first line of treat-
ment, followed by phenobarbital, fosphenytoin, or phenytoin, all of which have risks
and benefits.34 Benzodiazepines have been associated with serious adverse effects
such as hypotension and respiratory depression in preterm and term infants, and
therefore should be used with caution.37 Phenytoin is not the preferred initial agent,
as it has a depressive effect on the newborn myocardium and has an unpredictable
rate of metabolism due to immature hepatic function.33 Pyridoxine (50–100 mg IV)
or lidocaine may be used if refractory seizures are present (see Table 1).36 If the
seizure is a result of an electrolyte abnormality such as hyponatremia, hypocalcemia,
or hypomagnesemia, these abnormalities should be rapidly identified and treated. In
patients who are actively seizing, hyponatremia can be treated with normal saline
(0.9%) boluses or alternatively with 5 to 10 mL/kg IV of 3% saline (this can be
administered as a bolus given over 10 minutes). If the patient has hypocalcemia
(plasma calcium <7.0 mg/dL), then 100 to 300 mg/kg of IV 10% calcium gluconate
should be infused. In cases of hypomagnesemia (serum magnesium <1 mEq/L), 0.1
to 0.3 mL/kg of 50% magnesium sulfate should be given IV IV or IM. Ampicillin and
cefotaxime should be initiated in any patient considered to have sepsis. Acyclovir
(20 mg/kg every 8 h IV) should also be administered if there is a positive maternal
history of herpes, if the patient has a vesicular rash, focal neurologic findings, or
a CSF pleocytosis or elevated CSF protein without organisms on Gram stain.38
Patients should be admitted to a monitored bed for further observation and evaluation.

FUTURE DIRECTIONS

Future research needs must focus on:

 Neuroimaging safety and guidelines for imaging
 Safe antiepileptic drugs for children
 Improved access to pediatric neurologic evaluation for the subset of children
with difficult to manage and refractory afebrile seizures.

SUMMARY

Afebrile seizures in children are common and often recur. Fortunately, most children
with childhood epilepsy have a favorable long-term prognosis. In particular, patients
with idiopathic etiology usually reach remission.39 There are specific types of
afebrile seizure disorders that emergency physicians should be aware of, with
absence seizures being the most common. Newborn seizures are often difficult to
diagnose, and are evaluated and treated more aggressively than afebrile seizures
in older infants and children. Children that present to the ED often have a known
seizure disorder, are taking medications for their disorder, and usually are in a pos-
tictal state on arrival. Seizures lasting longer than 5 minutes should be treated
initially with a benzodiazepine and standard advanced life support protocols. Labo-
ratory studies are needed only in children younger than 6 months, in patients with
106 Sharieff & Hendry

prolonged seizures or altered level of consciousness, or in patients with history of

a metabolic disorder or dehydration. Routine neuroimaging is not recommended
in children with a first unprovoked afebrile seizure, although imaging studies should
be considered in children younger than 3 years with a predisposing condition or
focal seizures. Most well-appearing children can be managed as outpatients after
a first afebrile seizure, with instructions for an outpatient EEG and follow-up by
the primary care physician. Anticonvulsant drugs do not decrease the long-term
incidence of epilepsy and are therefore not usually recommended after a first
afebrile seizure. New anticonvulsant drugs continue to be investigated, but it is
important to recognize that no anticonvulsive agents decrease the long-term inci-
dence of epilepsy and are therefore not usually recommended after a first afebrile
seizure. Adjunct nonpharmacologic therapies such as vagal nerve stimulation are
also being used in patients with severe epilepsy. Intermittent electrical stimulation
is delivered to the cervical vagus nerve. The lead is usually located on the left
side of the neck, and the generator is implanted in the chest wall. The emergency
provider should keep abreast of new technologies and emerging trends in pharma-
cologic antiepileptic management.

KEY CONCEPTS

 An EEG should be performed as soon as possible on patients with an apparent first

unprovoked seizure.
 Electrolyte testing is not routinely necessary on well-appearing children older than 6 months.
 Emergent neuroimaging of children with first-time seizures should be performed on patients
with the following risk factors: focal seizures, prolonged postictal period, status epilepticus,
sickle cell disease, immunocompromise, head injury, age less than 6 months to 1 year,
ventriculoperitoneal shunts, recent travel to an area endemic for cysticercosis, bleeding
disorders, cerebral vascular disease, neurocutaneous disorders, malignancy, HIV, or
hydrocephalus.
 Well-appearing children who have experienced a first unprovoked seizure and are in the
low-risk category do not need emergent neuroimaging if they have close outpatient follow-
up.
 Children on ketogenic diets should not be given dextrose empirically.

REFERENCES

1. Verrotti A, D’Adamo E, Parisi P, et al. Levetiracetam in childhood epilepsy.

Paediatr Drugs 2010;12(3):177–86.
2. Camfield CS, Camfield PR, Gordon K, et al. Incidence of epilepsy in childhood
and adolescence: a population-based study in Nova Scotia from 1977 to 1985.
Epilepsia 1996;37(1):19–23.
3. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked
seizures in Rochester, Minnesota: 1935–1984. Epilepsia 1993;34(3):453–68.
4. Hirtz D, Berg A, Bettis D, et al. Practice parameter: treatment of the child with
a first unprovoked seizure: report of the quality standards subcommittee of the
American Academy of Neurology and the Practice Committee of the Child
Neurology Society. Neurology 2003;60(2):166–75.
5. Shinnar S, Berg AT, O’Dell C, et al. Predictors of multiple seizures in a cohort of
children prospectively followed from the time of their first unprovoked seizure.
Ann Neurol 2000;48(2):140–7.
 Afebrile Pediatric Seizures 107

6. Stroink H, Brouwer OF, Arts WF, et al. The first unprovoked, untreated seizure in
childhood: a hospital based study of the accuracy of the diagnosis, rate of recur-
rence, and long term outcome after recurrence. Dutch study of epilepsy in child-
hood. J Neurol Neurosurg Psychiatry 1998;64(5):595–600.
7. Shinnar S, Berg AT, Ptachewich Y, et al. Sleep state and the risk of seizure recurrence
following a first unprovoked seizure in childhood. Neurology 1993;43(4):701–6.
8. Trevathan E. Infantile spasms and Lennox-Gastaut syndrome. J Child Neurol
2002;17(Suppl 2):2S9–22.
9. Hancodk EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane
Database Syst Rev 2008;4:CD001770.
10. Hemingway C, Freeman JM, Pillas DJ. The ketogenic diet: a 3- to 6-year
follow-up of 150 children enrolled prospectively. Pediatrics 2001;108(4):
898–905.
11. Cossette P, Riviello JJ, Carmant L. ACTH versus vigabatrin therapy in infantile
spasms: a retrospective study. Neurology 1999;52(8):1691–4.
12. Elterman RD, Shields WD, Mansfield KA, et al. Randomized trial of vigabatrin in
patients with infantile spasms. Neurology 2001;57(8):1416–21.
13. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998;338(14):
970–6.
14. Ng YT, Hastriter EV, Cardenas JF, et al. Intravenous levetiracetam in children with
seizures: a prospective safety study. J Child Neurol 2010;25(5):551–5.
15. Fitzgerald BJ, Okos AJ, Miller JW. Treatment of out-of-hospital status epilepticus
with diazepam rectal gel. Seizure 2003;12(1):52–5.
16. Rainbow J, Browne GJ, Lam LT. Controlling seizures in the prehospital setting:
diazepam or midazolam? J Paediatr Child Health 2002;38(6):582–6.
17. Chamberlain JM, Altieri MA, Futterman C, et al. A prospective, randomized study
comparing intramuscular midazolam with intravenous diazepam for the treatment
of seizures in children. Pediatr Emerg Care 1997;13(2):92–4.
18. Vilke GM, Sharieff GQ, Marino A, et al. Midazolam for the treatment of out-of-
hospital pediatric seizures. Prehosp Emerg Care 2002;6(2):215–7.
19. Ashrafi MR, Khosroshahi N, Karimi P. Efficacy and usability of buccal midazolam
in controlling acute prolonged convulsive seizures in children. Eur J Paediatr
Neurol 2010;14(5):434–8.
20. Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for
treatment of prolonged seizures in childhood and adolescence: a randomised
trial. Lancet 1999;353(9153):623–6.
21. Gottwald MD, Akers LC, Liu PK, et al. Prehospital stability of diazepam and lora-
zepam. Am J Emerg Med 1999;17(4):333–7.
22. Fischer JH, Patel TV, Fischer PA. Fosphenytoin: clinical pharmacokinetics and
comparative advantages in the acute treatment of seizures. Clin Pharmacokinet
2003;42(1):33–58.
23. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile
seizure in children: report of the quality standards subcommittee of the American
Academy of Neurology, The Child Neurology Society, and The American Epilepsy
Society. Neurology 2000;55(5):616–23.
24. Bui TT, Delgado CA, Simon HK. Infant seizures not so infantile: first-time seizures
in children under six months of age presenting to the ED. Am J Emerg Med 2002;
20(6):518–20.
25. Farrar HC, Chande VT, Fitzpatrick DF, et al. Hyponatremia as the cause of
seizures in infants: a retrospective analysis of incidence, severity, and clinical
predictors. Ann Emerg Med 1995;26(1):42–8.
108 Sharieff & Hendry

26. Scarfone RJ, Pond K, Thompson K, et al. Utility of laboratory testing for infants
with seizures. Pediatr Emerg Care 2000;16(5):309–12.
27. Kalnin AJ, Fastenau PS, deGrauw TJ, et al. Magnetic resonance imaging
findings in children with a first recognized seizure. Pediatr Neurol 2008;39:
404–14.
28. Gaillard WD, Chiron C, Cross JH, et al. Guidelines for imaging infants and
children with recent-onset epilepsy. Epilepsia 2009;50:2147–53.
29. Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation
exposure. N Engl J Med 2007;357(22):2277–84.
30. Warden CR, Brownstein DR, Del Beccaro MA. Predictors of abnormal findings of
computed tomography of the head in pediatric patients presenting with seizures.
Ann Emerg Med 1997;29(4):518–23.
31. Garvey MA, Gaillard WD, Rusin JA, et al. Emergency brain computed tomog-
raphy in children with seizures: who is most likely to benefit? J Pediatr 1998;
133(5):664–9.
32. Sharma S, Riviello JJ, Harper MB, et al. The role of emergent neuroimaging in
children with new-onset afebrile seizures. Pediatrics 2003;111(1):1–5.
33. Shinnar S, Berg AT, Moshe SL, et al. The risk of seizure recurrence after a first
unprovoked afebrile seizure in childhood: an extended follow-up. Pediatrics
1996;98(2 Pt 1):216–25.
34. Stafstrom CE. Neonatal seizures. Pediatr Rev 1995;16(7):248–55.
35. Bernes SM, Kaplan AM. Evolution of neonatal seizures. Pediatr Clin North Am
1994;41(5):1069–104.
36. Evans D, Levene M. Neonatal seizures. Arch Dis Child Fetal Neonatal Ed 1998;
78(1):F70–5.
37. Ng E, Klinger G, Shah V, et al. Safety of benzodiazepines in newborns. Ann
Pharmacother 2002;36(7–8):1150–5.
38. Riley LE. Herpes simplex virus. Semin Perinatol 1998;22(4):284–92.
39. Geerts A, Arts WF, Stroink H, et al. Course and outcome of childhood epilepsy:
a 15-year follow-up of the Dutch study of epilepsy in childhood. Epilepsia
2010;51:1189–97.