Case-based Learning – Pediatric Seizures

Objectives:
1. What are the components of a focused seizure history?
2. What is a simple vs. complex febrile seizure?
3. What are red flags on physical examination following a seizure?
4. When do you need to investigate a febrile seizure?
5. How and what do you counsel regarding simple febrile seizures?
6. How do you manage status epilepticus?
7. How do you counsel about seizure safety?

You’re the Pediatrician on-call for a community hospital. The ER doctor has called you in to see
David, a 20 month old boy who was brought in by his parents for a seizure. From what the ER
doctor told you over the phone, you know that the boy is previously healthy, but had been having
URTI symptoms for the past few days.

As you walk towards the ER, you think of what you will ask the parents on history, especially
your focused seizure history.

<Pause for discussion>

You walk into the room and introduce yourself. David’s parents are polite but are visibly anxious
and worried. David is standing happily in the hospital crib. He points at you and smiles at his
parents when you walk in. Pleased that he seems to be stable, you proceed with asking your
history.

David’s parents tell you that he started getting a runny nose and cough 3 days ago. Starting
yesterday, he developed a fever that they controlled with Tylenol. His appetite decreased, but his
drinking and urine output remained normal. There was no vomiting, diarrhea, or rash. There have
been no sick contacts or recent travel.

David awoke this morning with a fever of T 38.7°C axillary and was again treated with Tylenol.
However, as his parents were getting him dressed, David started having “full body shaking with
jerking of both his arms and legs”. The movements were rhythmic and he seemed “out of it”. His
eyes were stared straight ahead, and parents did not notice any facial or mouth movements. He
was still wearing his overnight diaper, so they are unsure of any bowel/bladder incontinence.
They did hear some grunting, but there was no change in his colour. The entire episode lasted
about 1 minute and David was sleepy afterwards for about 30 minutes, during which his parents
had brought him to the hospital. He is now back to his normal behaviour. This has never
happened before.

His pregnancy and birth history are unremarkable. He is previously healthy with no history of
seizures, head trauma, or meningitis. He is not on any regular medications, has no known drug
allergies, and his immunizations are up to date. He and his family did not get the flu shot this
year. He is developmentally normal for his age.
The family is not consanguineous. There is no family history of developmental delay or
metabolic disorders. David’s maternal uncle had febrile seizures as a child but “grew out of it”.
David currently attends full-time daycare while both parents are at work. There is no prior CAS
involvement, no financial concerns, and good social supports.

After obtaining your history, you proceed with the physical examination. Since David is an
active 20 month old, you know you must be both systematic and organized.

<Pause for discussion>

David is alert and looks well. Not dysmorphic. HR 110, RR 25, BP 85/55, O2 sat 99% in RA, T
38.5°C ax at triage, now T 36.3°C after Tylenol. He has some nasal congestion with an
erythematous throat and tympanic membranes bilaterally. Chest is clear. Pupils are equal 4mm
and reactive to light. He has normal tone and reflexes 2+ throughout. He is active and playful
with normal gait and no neurological deficits.

You determine based on your history and physical examination that David most likely had a
simple febrile seizure. You debate in your mind whether any investigations, such as bloodwork,
lumbar puncture, EEG, and/or head imaging is warranted.

<Pause for discussion>

Because you are a newly graduated Pediatrician, and therefore tend to be overly cautious, you
decide to order some basic blood work (CBC, electrolytes, extended lytes) knowing that they
will likely be of low yield. However, you will not investigate further with a LP, EEG, or head
imaging.

As anticipated, the blood work is entirely benign and David is practically climbing out of his
crib. He definitely looks well enough for you to send him home. His parents, however, are still
quite anxious about the whole event and have many questions.

“What’s the likelihood that this will happen again? What are the risk factors for recurrence?”
“What should we do if it happens again? Should we call 911 or bring him back here?”
“Is this epilepsy? Does he need anti-seizure medications?”

<Pause for discussion>

After reassurance and counselling, David and his parents head home. You have arranged follow-
up with his family doctor in 2 days.

You’re about to leave the ER when your pager goes off again. You turn around to see EMS
wheeling in a young girl on a stretcher. She has an oxygen mask over her face and she is actively
seizing. EMS tells you that Emily is a 7 year old girl with a known seizure disorder. Her
neurologist has been trying to wean her off her anti-epileptics, with her most recent dose
reduction occurring yesterday. She has already been seizing for at least 15 minutes. As your
medical team connects her to monitors, gets a set of vital signs, and obtains IV access, you
quickly run through the status epilepticus algorithm in your mind.

<Pause for discussion>

Thankfully, Emily’s generalized-tonic-clonic seizure stopped after 2 doses of IV lorazepam and

she did not require a loading dose of phenobarbital or phenytoin. You decide to admit her
overnight for further monitoring and will contact her neurologist in the morning. You remind
yourself that you should discuss seizure safety with Emily’s family prior to discharge. You head
to your call room hoping to catch some sleep, since you have a full day in the office tomorrow.
 Pediatric Seizures
Reet Sidhu, Kohilavani Velayudam and Gregory Barnes
Pediatrics in Review 2013;34;333
DOI: 10.1542/pir.34-8-333

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/34/8/333

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601.

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Pediatric Seizures
Reet Sidhu, MD,*
Kohilavani Velayudam, MD,†
Gregory Barnes, MD, PhD†
Author Disclosure
Drs Sidhu, Velayudam,
and Barnes have
disclosed no financial
relationships relevant
to this article. This
commentary does
contain discussion of
unapproved/
investigative use of
a commercial product/
device.
The causes of epilepsy are varied. The most common causes of acute seizures are fevers,
Abbreviations
ADHD: attention-deficit/hyperactivity disorder
AED: antiepileptic drug
CAE: childhood absence epilepsy
CNS: central nervous system
EEG: electroencephalography
GTC: generalized tonic-clonic
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Article neurologic disorders
Educational Gap
The causes of seizures are many, and a number of other conditions can mimic seizures,
making careful evaluation of seizurelike episodes critical. Febrile seizures are the most
common type of seizure in children, and their management is usually the task of the gen-
eral pediatrician. Status epilepticus constitutes an emergency situation that can have
severe consequences and requires skilled therapy.
Objectives After completing this article, readers should be able to:
1. Identify the key elements in the evaluation of an individual who has seizures.
2. Know the main features of febrile seizures.
3. Understand the core principles in the treatment of status epilepticus.
4. Identify the salient clinical features of the main childhood epilepsy syndromes.
5. Be aware of common comorbidities in epilepsy syndromes.
6. Recognize the key differences between epileptic and nonepileptic seizures.
Definition and Pathophysiology of Epilepsy
Seizures (sometimes called epileptic seizures) are the stereotypical clinical manifestations
(signs and symptoms) of excessive synchronous, usually self-limited, abnormal electrical ac-
tivity of neurons situated in the cerebral cortex. Epilepsy is defined as 2 or more unpro-
voked afebrile seizures (International League Against Epilepsy). Although both children
who have normal development and children who have developmental delay can display un-
usual movements, the clinical signs (semiology) of epileptic seizures have specific stereo-
typical features.
At the cellular level, ordinarily the neurons of the cerebral cortex fire asynchronously,
albeit in patterns that facilitate learning, memory, sensory input, and behavioral output of
defined neural circuits. A zone of ictogenesis (an area of brain capable of generating sei-
zures) contains millions of neurons, all of which can fire synchronously. During electroen-
cephalography (EEG), the recording electrodes on the scalp detect the synchronous firing
of at least a 1-cm2 brain region as a spike and slow wave, the so-called epileptiform activity.
Causes of Acute Seizures and Mimics
infections, and head injury, which are detected through his-
tory and laboratory testing. These types of seizures are re-
ferred to as symptomatic seizures. In general, patients who
have focal seizures or focal neurologic signs should have neu-
roimaging on initial presentation.
The evaluation process begins with a careful history and
description of the spells. Parents may not always recognize
the symptoms of a seizure. Many epileptic seizures present
as a substantial but stereotypical episode in which children
demonstrate jerking of the limbs, drooling, and eye rolling,
during which consciousness is clearly impaired. After this
*Department of Neurology, Columbia University School of Medicine, New York, NY.
†
Departments of Neurology and Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
Pediatrics in Review Vol.34 No.8 August 2013 333
neurologic disorders seizures
type of seizure, most children are confused and tired and
may sleep for a prolonged period (postictal phase). How-
ever, not all seizures are easily recognized.
Signs can be subtle, with staring that resembles day-
dreaming or a vacant stare. During these types of sei-
zures, children will not respond to tactile stimulation.
Pertinent points in the history include the presence of
clonic movements or jerks, facial movements, eye and
head version, loss of bladder or bowel function, color
changes, unusual noises, breathing abnormalities, heart
rate changes, and other stereotypical movements. The
length of each spell, the presence of a postictal phase,
and how often the spell occurs should be determined.
Children often stare and do not respond to voice at
times. This behavior is commonly referred to as day-
dreaming or mind-wandering. These benign, nonepilep-
tic episodes may be characterized by the child quickly
reorienting to the parents or caregiver, and no other signs
or symptoms of a seizure are present. When a child ap-
pears to be daydreaming but has accompanying facial
movements (eye rolling, blinking, or fluttering) or a pause
in activity commonly referred to as behavioral arrest, one
should consider the possibility of a seizure.
Episodic movements with altered consciousness sug-
gest seizure activity when any of the following features
are present: (1) no response to tactile stimulation (touch
of the face or body), (2) unusual eye movements (rapid
eye fluttering or fixed eye deviation), (3) unusual head
movements (forced head version), (4) unusual mouth
movements (chewing or lip smacking), (5) unusual facial
movements (twitching of the face), (6) stereotyped hand
movements (repetitive reaching), (7) unusual posturing
of a limb (freezing of an arm or leg), or (8) unexpected
incontinence.
The environmental setting and time of the day are also
important to diagnose because nonepileptic spells may
have inciting events. Nonepileptic spells during the night
may be associated with sleep disorders, such as sleep ap-
nea or sleepwalking. Nocturnal seizures may present as
unexpected arousals with odd or repetitive hypermotor
behavior or complex behavioral automatisms, such as
lip smacking or other facial movements, stereotyped hand
movements, unusual posturing, unexpected inconti-
nence, or gelastic (laughing) spells. Nocturnal seizures
are not associated with difficulty falling asleep, early
morning or multiple awakenings, or prolonged periods
of wakefulness without altered consciousness or other
automatisms.
It is crucial to assess for other conditions that may
mimic seizures, including sleep disorders, gastroesopha-
geal reflux and other gastrointestinal disorders, and
334 Pediatrics in Review Vol.34 No.8 August 2013
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psychiatric disorders, including attention-deficit/hyperac-
tivity disorder (ADHD). Review of the child’s medica-
tions occasionally can reveal a medication that may
lower the seizure threshold, although buspirone is the
only psychotropic medication associated consistently
with unprovoked seizures in children. Other medica-
tions used in the pediatric population, including stimu-
lants and neuroleptics, rarely, if ever, lower the seizure
threshold in an individual patient.
A family history of epilepsy is a risk factor for epilepsy
in children and should be assessed. Parents should keep
a seizure diary describing the spells in detail and including
the time of day the spells occur, the length of the spells,
and whether there was a postictal phase. Videotape re-
cording of the spells is encouraged, especially when the
event is not clearly epileptic. One should note a previous
history of epilepsy; whether the child is taking antiepileptic
drugs (AEDs); presence of conditions associated with elec-
trolyte (magnesium, phosphate, or calcium) disturbances,
such as diarrhea or rickets; presence of acidosis associated
with hypoxia; and history of ingestion. Provoking factors,
such as sleep deprivation, fevers, and illness or infections,
should be noted.
A child who presents with a change in sensorium and
repetitive seizures, with or without fever, should be inves-
tigated for encephalitis. Focal neurologic signs may or
may not be present with encephalitis. Persistent focal
neurologic signs after seizures not associated with fever
should alert one to the possibility of an arterial stroke
or cerebral venous sinus thrombosis. Persistent focal neu-
rologic deficits usually warrant acute neurodiagnostic
testing with computed tomography of the head with
contrast.
Febrile Seizures
The most common type of seizures in the pediatric pop-
ulation is the febrile seizure. Febrile seizures are defined
as seizures occurring in childhood after age 1 month, as-
sociated with febrile illness but not caused by infection of
the central nervous system (CNS), unassociated with pre-
vious neonatal seizures or unprovoked seizures, and not
meeting criteria for other acute symptomatic seizures. Fe-
brile seizures usually occur in children ages 6 months to 5
years, with a peak age at onset of approximately 18
months. The incidence is 3% to 8% in children younger
than 5 years.
There are 2 types of febrile seizures: simple and com-
plex. Simple febrile seizures are the most common type
and are characterized by (1) generalized clinical features,
(2) duration less than 15 minutes, and (3) a single seizure
in a 24-hour period. In contrast, complex febrile seizures

are characterized by (1) focal clinical manifestation, (2)
duration longer than 15 minutes, and (3) more than
one in a 24-hour period. Approximately 25% to 40% of
children who have febrile seizures have a family history
of febrile seizures; 9% to 22% of children have a sibling
who has a history of febrile seizures.
A high incidence of sodium channel mutations is re-
ported in patients who have febrile seizures in childhood.
The most important risk factors that predispose children
to having febrile seizures include peak temperature dur-
ing the illness, history of febrile seizure in first-degree rel-
atives, neurodevelopmental delays, increased exposure to
human herpesvirus 6, and vaccinations with measles-
mumps-rubella, diphtheria-tetanus-pertussis, and influ-
enza vaccines. Almost 50% of the children who present
with febrile seizures will not have any identified risk
factors.
The main purpose of the evaluation of children who
have febrile seizures is to exclude underlying CNS infec-
tions. Lumbar puncture should be considered strongly in
infants younger than 12 months, those who have prolonged
complex febrile seizures or febrile status epilepticus, and
children who are partially treated with antibiotics. Rou-
tine EEG and neuroimaging are not indicated for simple
febrile seizures. Neuroimaging is recommended in pa-
tients who have complex febrile seizures, neurologic def-
icit on examination, prolonged postictal state, and signs
of raised intracranial pressure. Patients who have febrile
status epilepticus require EEG testing.
Reassurance and counseling are essential in the man-
agement of febrile seizures. Rectal diazepam can be used
in the short term in a child who has risk factors for re-
current febrile seizures, prolonged febrile seizures, or a
very low threshold for febrile seizures. Daily prophylactic
antiepileptic medication may reduce the recurrence of the
febrile seizures but will not reduce the risk of developing
epilepsy and is not recommended routinely. Recurrence
of a febrile seizure usually occurs within the initial 1 to 2
years after the initial seizure. (1) This association is im-
portant to note when counseling families, given the high
degree of anxiety surrounding seizures.
The risk of recurrence of a febrile seizure is approxi-
mately 60% after the initial febrile seizure. Risk factors
for recurrence include younger age of onset, having an
initial febrile seizure associated with a relatively low tem-
perature, family history of febrile seizures in a first-degree
relative, and brief duration between the onset of the fever
and seizure. Approximately 2% to 7% of children who
have a history of febrile seizures have a risk of developing
epilepsy. Risk factors for developing subsequent epilepsy
after febrile seizures include having a family history of
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neurologic disorders seizures
epilepsy, complex febrile seizure, and neurodevelopmen-
tal abnormalities.
Approximately 40% of adults who have a history of
complex febrile seizures and febrile status epilepticus in
childhood develop mesial temporal lobe epilepsy. Simple
febrile seizures have a benign prognosis. There is no sig-
nificant association between febrile seizures and later sig-
nificant cognitive developmental delay or with sudden
infant death syndrome.
Treatment of Seizures
In the pediatric population, treatment with AEDs is rec-
ommended after 2 or more recurrent afebrile seizures.
The characteristics of different types of seizures and drugs
of choice for treating them are presented in the Table.
Most children (approximately 60%) who experience a sin-
gle unprovoked seizure will not have another. As indi-
cated below, the choice of AEDs is dictated mainly by
the seizure type and interictal findings on EEG. How-
ever, the other factors should be considered, including
the need to control mood stability, the presence of co-
morbid conditions (obesity), and the simultaneous use
of other medications (long-term antibiotic therapy, such
as with macrolides).
The Food and Drug Administration has approved
a number of drugs, including levetiracetam and oxcarba-
mazepine, for use as therapy in pediatric seizures. Leve-
tiracetam can be used to treat partial or generalized
seizures, whereas oxcarbamazepine is indicated for partial
seizures. Initial doses of levetiracetam (20 mg/kg daily;
range, 20-60 mg/kg daily) and oxcarbamazepine (10
mg/kg daily; range, 10-40 mg/kg daily) can be increased
every week to a higher dose. Other AEDs are discussed
below and include valproic acid, used to treat juvenile
myoclonic epilepsy; ethosuximide-lamotrigine, used to
treat childhood absence epilepsy (CAE); and carbamaze-
pine-gabapentin, used to treat benign rolandic epilepsy.
Fast-metabolizing individuals between 6 and 60
months of age can be identified by measuring trough
AED levels before the initial morning dose. Oxcarbama-
zepine and carbamazepine levels can be elevated by mac-
rolide antibiotics. Levetiracetam can exacerbate known
neurobehavioral symptoms. A total of 100 mg/d of vita-
min B6 can mitigate this problem. Complete blood cell
counts and serum sodium levels are monitored in patients
taking oxcarbamazepine because this drug can depress
the white blood cell counts and sodium levels.
When doses of AEDs are missed, the medication
should be taken at the next opportunity (after the reali-
zation that the dose was missed). When patients are seen
Pediatrics in Review Vol.34 No.8 August 2013 335
neurologic disorders seizures
Table. Characteristics of Distinct Seizure Phenotypes
Seizure Type Interictal EEG Features
Partial complex Focal epileptiform or focal slowing
Generalized
Tonic-clonic Generalized epileptiform activity
Absence 3-Hz generalized spike wave
Atypical absence £2.5-Hz generalized spike wave
Myoclonic tonic 4- to 6-Hz spike/polyspike and 1.5- to
or atonic 2.5-Hz generalized spike wave
in the emergency department with frequent seizures after
missing doses, levetiracetam can be reloaded intrave-
nously at 20 to 30 mg/kg per dose.
In general, AED therapy is continued for at least 2
years of seizure freedom. AEDs should be weaned grad-
ually for months when possible. The risk of seizure recur-
rence (approximately 90%) is highest in the 2 years after
therapy discontinuation, with most recurrences in the
first year.
Children who have the highest risk of seizure recur-
rence are those having (1) a history in the distant past
of a disorder, such as viral encephalitis, that is known
to cause seizures; (2) abnormal EEG findings (epilepti-
form discharges or focal slowing); (3) nocturnal seizures;
(4) a history of febrile seizures; and (5) a history of Todd
paresis. (2)
Pediatric patients who have active epilepsy should not
participate in contact sports that can cause head injury,
such as football, and should never swim unsupervised
or alone or ride a bicycle without a helmet. In addition,
every family should be educated about seizure first aid,
when rescue medications should be administered, and
when to go to the emergency department for increased
seizure frequency.
Uncontrolled seizures put patients at risk for signifi-
cant morbidity and mortality. For instance, the risk of
death is elevated 8-fold for children who have autism
who also have epilepsy. Sudden unexplained death in ep-
ilepsy can occur in patients who have uncontrolled seiz-
ures. Current standard of care in these patients includes
conversations about the deadly consequences of seizures,
the implication on prognosis, and the impact on quality
of life.
Treatment of Status Epilepticus
Status epilepticus is defined commonly as repeated seiz-
ures without a return to consciousness lasting longer than
336 Pediatrics in Review Vol.34 No.8 August 2013
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Treatment of Choice
Oxcarbamazepine, levetiracetam
Lamotrigine, valproic acid topiramate
Ethosuximide, valproic acid, lamotrigine
Valproic acid
Valproic acid, levetiracetam
Lamotrigine, topiramate, clobazam, rufinamide,
felbamate
30 minutes. Most types of epileptic seizures can be man-
ifested as status epilepticus. The 2 major types of status
epilepticus, generalized convulsive status epilepticus (ma-
jor motor seizures and recurrent generalized tonic-clonic
[GTC] convulsions) and nonconvulsive status epilepticus
(recurrent nonconvulsive seizures, which include absence
status, partial complex status, and simple partial status),
are recognized clinically.
Convulsive status epilepticus is the most common
emergency associated with neurologic disease because
brain damage and death can result from the systemic con-
sequences of repeated GTC seizures. Most persons who
experience GTC status epilepticus have localized cerebral
disturbances as a cause and therefore have secondary gen-
eralized partial seizures.
Repeated cerebral epileptic activity can disrupt brain
structures or otherwise cause permanent neurologic or
intellectual deficits. Common causes of status epilepticus
include CNS infections, toxins, ingestions (including
AED ingestion), and drug withdrawal, such as from opi-
ates or benzodiazepines. The most common cause of
benzodiazepine withdrawal seizures is abrupt discontinu-
ation of clonazepam use in patients undergoing long-
term therapy for seizures or anxiety.
Therapy must be directed at suppressing all ictal (elec-
trical seizure) activity on EEG. Ictal EEG activity can
show the following progression: (1) discrete seizures,
(2) merging of seizures with waxing and waning of am-
plitude and frequency in variable locations, (3) continu-
ous ictal activity, (4) continuous ictal activity intermixed
with periods of isoelectric EEG, and (5) a periodic later-
alized or generalized epileptic discharge pattern.
Frequent repetitive GTC seizures create a life-threatening
systemic condition of hyperpyrexia, failure of cerebrovas-
cular autoregulation, acidosis, and severe hypoxia, caus-
ing hypotension, hypoperfusion of the brain, pulmonary
edema, electrolyte disturbances, and eventual circulatory
collapse. Even after cessation of status epilepticus and

correction of systemic abnormalities, sepsis from aspira-
tion pneumonia can be a late but life-threatening
complication.
Treatment of status epilepticus consists of correction
of glucose, electrolyte, magnesium, and calcium distur-
bances; control of blood pressure and oxygenation; and
the administration of benzodiazepines and a series of rou-
tine anticonvulsants. At home, caregivers and parents can
administer rectal diazepam, which is absorbed rapidly
through blood vessels, while they call 911 to summon
emergency medical personnel.
Intravenous lorazepam (0.1 mg/kg per dose) usually
is administered first in treating status epilepticus. If the
seizures do not break, a second dose of intravenous lor-
azepam (0.1 mg./kg per dose) is followed by fospheny-
toin (20 mg/kg per dose). Next, a loading dose of
phenobarbital (20 mg/kg per dose) is considered if seiz-
ures continue. Intubation is a consideration if respiratory
depression is observed with either benzodiazepines or
phenobarbital. Seizures that are refractory to the treat-
ments described may necessitate the use of inhaled gases
or, more commonly, pentobarbital-induced medical co-
ma. During status epilepticus, transport to a facility
skilled in dealing with pediatric status epilepticus, pediat-
ric intensive care monitoring, and continuous video EEG
monitoring is essential.
Partial Complex Epilepsy
The most common type of seizure during childhood,
a partial seizure, is described in 2 categories. Simple par-
tial seizures are those in which the initial clinical signs and
EEG signatures begin focally in one area of the brain
without impairment of consciousness. Simple partial sei-
zures show focal neurologic signs, such as focal jerking of
one hand or arm, sensory change or pain in one limb, or
a unilateral contraction of the face.
Partial complex seizures (psychomotor seizures) are
the more common of the 2 types of partial seizures that
manifest as focal neurologic signs with impairment of
consciousness. Commonly, for instance, in temporal lobe
epilepsy, patients may experience a gustatory sensation,
rising epigastric feeling, or some other aura followed
by behavioral arrest. The child does not respond, often
staring off, then becomes lethargic. Sometimes children
develop jerking movements of limbs contralateral to
the seizure focus.
Secondary generalization of partial complex seizures
occurs when seizures spread to the opposite hemisphere
and are manifest clinically as GTC seizures. Thus, when
obtaining a clinical history in a patient who has had GTC
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neurologic disorders seizures
seizures, it is important to consider partial epilepsy. The
interictal epileptiform activity (between seizures) is uni-
lateral, focal, or multifocal epileptiform discharges. The
ictal manifestations on EEG usually include evolving
focal sharp waves or spike and slow wave discharges.
Levetiracetam or oxcarbazepine often are used as first-
line monotherapy for the treatment of pediatric partial
seizures.
As children become older, epileptiform discharges on
EEG are more frequent in the frontal or centrofrontal re-
gions. Adolescents can have multifocal epilepsy, in which
the predominant seizure type is a partial complex seizure.
However, most seizures in the adolescent are generalized
seizures. GTC seizures are the most common type of
generalized seizures.
The seizure may have a prodrome in which a change in
behavior is seen. However, most seizures begin without
warning when the patient falls to the floor and cries out,
the eyes roll toward the back of the head, and the limbs
exhibit a rhythmic, tonic-clonic-tonic pattern of jerking.
The individual may lose bowel or bladder function at the
end of the seizure (ictal phase). Cyanosis can develop but
usually is transient.
GTC seizures are typical of frontal lobe epilepsy, which
occurs in adolescents. The EEG correlate is a buildup of
low-voltage fast activity, which evolves into high-amplitude
spike/polyspike or polyspike and wave discharges. Patients
typically are sleepy or confused for a period after the sei-
zure (postictal phase).
Many broad-spectrum AEDs, including levetiracetam,
lamotrigine, topiramate, valproic acid, and zonisamide,
are used in the treatment of GTC seizures.
Idiopathic Generalized Epilepsies
The second most common type of epilepsy, CAE, ac-
counts for 8% of epilepsy cases in school-age children
and has an estimated incidence of 7 in 100,000 children
ages 1 to 15 years. The incidence peaks at age 5 years, and
girls constitute 60% to 70% of those who have CAE. Ab-
sence seizures are characterized by lapses in consciousness
in which one can see a motionless stare, usually lasting 10
to 15 seconds. During this brief event, eyelids may droop,
flutter, or briefly roll backwards. The children usually re-
sume their full activity after the seizure or may be briefly
confused (<30 seconds).
Absence seizures can be associated with other activity,
including automatisms, brief clonic movements of arms
or eyelids, or loss of postural tone. The onset of absence
seizures is associated with an EEG pattern of regular, bi-
laterally frontal-predominant generalized 3-Hz spike and
Pediatrics in Review Vol.34 No.8 August 2013 337
neurologic disorders seizures
wave discharges, which begin and end suddenly in the
setting of a normal EEG background.
With either absence or GTC seizures, children can
have fragments of interictal discharges, which include bi-
laterally frontal-predominant generalized spike and slow
wave discharges. In the clinical trial study of CAE, treat-
ment with ethosuximide, valproic acid, and lamotrigine
had the greatest efficacy. (3) Ethosuximide, which causes
gastric upset, is taken in capsules or liquid at a dose of 20
mg/kg daily divided twice a day. Lamotrigine had the
least efficacy but the best adverse effect profile in the trial.
With its black box warning regarding the risk of rash and
Stevens-Johnson syndrome, lamotrigine should be ad-
ministered cautiously, with dose changes every 10 to
14 days, until reaching a dose of 5 mg/kg daily divided
twice a daily. Valproic acid is discussed below. In general,
most children who have CAE have remission of absence
seizures by ages 12 to 16 years. Comorbidities are com-
mon and include subtle cognitive deficits, linguistic diffi-
culties, and psychiatric disorders, particularly ADHD and
anxiety.
Atypical absence seizures are lapses in consciousness in
which the patient can manifest a motionless stare, but
these spells are associated more with motor signs, partic-
ularly changes in tone, and can be more apparent than
typical absence seizures. These seizures can have focal or
lateralizing signs. The onset and cessation of these seizures
are less clear, and the duration is longer, typically 15 to 60
seconds, with variable postictal confusion. These children
are more likely to have absence status epilepticus.
The clinical onset is associated with similar generalized
spike-wave discharges but usually at a frequency of less
than 2.5 Hz. Although atypical absence seizures can be
seen in the setting of Lennox-Gastaut syndrome, these
seizures are not common in this population. These sei-
zures and typical childhood absence seizures often are re-
sponsive to valproic acid. Valproic acid usually is given at
10 to 15 mg/kg daily divided twice daily and should be
avoided in children younger than 2 years. Maintenance
doses usually are 25 to 30 mg/kg daily. Because of its
ability to depress platelet counts and elevate liver function
test results and pancreatic enzyme levels, routine blood
monitoring of valproic acid levels, blood cell counts,
and liver and pancreas function tests is recommended.
Juvenile myoclonic epilepsy is an epileptic syndrome
of the idiopathic generalized epilepsy type of CAE, which
begins at approximately ages 5 to 15 years. This epilepsy
is defined by (1) myoclonic jerks on awakening, (2) GTC
seizures in 90% of patients, and (3) development of ab-
sence seizures in one-third of all patients. Myoclonic seiz-
ures (epileptic myoclonus) are relatively rare outside the
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syndrome of juvenile myoclonic epilepsy and usually are
seen in the most profoundly affected epilepsy patients,
such as those who have Lennox-Gastaut syndrome.
The broader term myoclonus refers to quick, involuntary
muscle jerks that involve any part of the neuroaxis. Myo-
clonic seizures can be differentiated both by semiology
and neurophysiologically from movement disorders, hy-
perreflexia, and rare cases of spasticity. Myoclonic seiz-
ures usually are bilateral generalized jerks (although
they can be unifocal, multifocal, or unilateral), which
are either sporadic or rhythmic in nature.
Commonly, myoclonic seizures are rapid, rhythmic,
bilateral synchronous jerks (2-8 Hz) of the upper extrem-
ities with occasional lower-extremity or whole body
involvement. The ictal EEG is characterized by general-
ized 4- to 6-Hz polyspike and slow wave discharges asso-
ciated with the quick jerks. Most neuroimaging does not
detect abnormalities in classic juvenile myoclonic epilepsy.
Seizures usually are controlled easily with valproic acid
(20-40 mg/kg daily divided twice daily) or levetiracetam
(20-40 mg/kg daily divided twice daily).
Symptomatic Generalized Epilepsies
Tonic and atonic seizures are more common than, but
not necessarily always associated with, Lennox-Gastaut
syndrome. Those AEDs with Food and Drug Adminis-
tration indications for Lennox-Gastaut syndrome, includ-
ing lamotrigine, topiramate, rufinamide, clobazam, and
felbamate, are all effective for seizures that collectively
are causes of drops attacks (tonic, atonic, and myoclonic
seizures).
Tonic seizures are more common in childhood and
represent a continuum of the atonic-tonic seizures. These
seizures are characterized by tonic spasms of the face or
chest and trunk, with tonic flexion of the upper extrem-
ities and flexion or extension of the lower extremities.
Along with impairment of consciousness, patients can
have papillary dilation, tachycardia, apnea or cyanosis,
and urinary incontinence, followed by a period of postictal
confusion. Ictal EEG is low-amplitude, very fast activity.
Atonic seizures (usually called drop attacks) consist of
a sudden loss of postural tone. In some patients, the drop
attacks are preceded by one or more clonic jerks. In mild
forms, the child may have a brief head drop (forward flex-
ion of head and neck). In severe forms, the patient’s
whole body may drop to the floor and, if refractory to
medications, may require a seizure helmet. The atonic
seizure usually lasts only a few seconds and has little to
no postictal period. The ictal EEG of an atonic seizure
exhibits either generalized polyspike and wave discharges

or a sudden electrodecrement (suppression) of the EEG.
Because synchronization of discharges between hemi-
spheres is important for these seizure types to develop,
a corpus callosotomy can be an effective surgical treat-
ment to abolish these seizures.
Benign Rolandic Epilepsy
Benign rolandic epilepsy, also referred to as benign child-
hood epilepsy with centrotemporal spikes, is the most
common type of partial epilepsy in childhood, with onset
usually between the ages of 5 and 10 years. On the basis
of its neuroanatomical location, most of these seizures in-
volve unilateral facial sensory-motor and oropharyngo-
gutteral symptoms, hypersalivation, and speech arrest.
This partial seizure is the hallmark of benign rolandic ep-
ilepsy. The child is awake, fully aware but unable to speak,
drooling, and experiencing unilateral face and arm
twitching. GTC seizures also occur, and approximately
75% of children have these seizures only during sleep
and have 5 or fewer seizures in their lifetime. Seizures
can happen during the day and with more frequency in
some patients.
Most child neurologists will prescribe medications only
after 3 or more seizures, and, even then, the interval be-
tween seizures plus parental concern and anxiety are con-
sidered when initiating treatment with AEDs. Almost all of
these seizures usually remit by age 16 years. However, ap-
proximately 20% have a medication-resistant epilepsy with
several seizures or clusters of seizures during the day.
The hallmark of the EEG is biphasic, focal centrotem-
poral spikes and slow waves. The centrotemporal spikes
are a clinical biomarker, with a strong genetic influence
and linked clinical phenotype. Some patients who have
centrotemporal spikes have a chromosome 11p13 auto-
somal dominant inheritance pattern with variants of the
ELP4 gene, a gene important in cortical maturation. Half
of the children who demonstrate centrotemporal spikes
might not show any clinical presentation of this EEG
trait. According to 2006 International League Against
Epilepsy guidelines, no AED has level A or level B evi-
dence for efficacy and effectiveness. Carbamazepine, lev-
etiracetam, valproic acid, phenobarbital, phenytoin, and
clonazepam have equivalent efficacy in this syndrome.
If AEDs are prescribed, they may be slowly tapered in pa-
tients who are seizure free for 2 years or more. Most seiz-
ures remit by age 16 years.
Infantile Spasms
Infantile spasms (West syndrome) are a specific type of
seizure occurring in infancy that often is classified as an
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neurologic disorders seizures
epileptic encephalopathy. This condition is considered
among the most severe developmental epilepsies of in-
fancy and childhood. With more than 200 known causes,
infantile spasms has a diverse set of causes, including hyp-
oxic ischemic encephalopathy; tuberous sclerosis; brain
malformations; central nervous system infections, includ-
ing TORCH (toxoplasmosis, other [syphilis, varicella-
zoster, parvovirus B19], rubella, cytomegalovirus, herpes)
infections and encephalitis with herpes simplex virus;
metabolic disorders; and genetic causes, such as Down
syndrome.
Gene mutations that affect synapse development, ion
transport, protein phosphorylation, gene transcription,
and other cellular functions are novel genetic causes asso-
ciated with infantile spasms.
The clinical presentation of infants ages 3 to 9 months
includes spasmlike seizures that involve flexion, exten-
sion, or mixed flexion-extension of the arms, legs, and
trunk. The spasms occur in clusters associated with elec-
trodecremental response on EEG. The background or in-
terictal EEG is chaotic, with a characteristic pattern called
hypsarrhythmia.
High-dose adrenocorticotropic hormone therapy
(150 IU/m2 body surface area per day) for 2 weeks, fol-
lowed by a taper, is considered by the American Academy
of Neurology and the Child Neurology Society to be the
treatment of choice for infantile spasms. Adrenocortico-
tropic hormone therapy remains the gold standard for the
termination of spasms and resolution of hypsarrhythmia
on EEG. Both goals are considered important to maxi-
mize neurodevelopmental outcome. Thus, it is consid-
ered important to identify and begin therapy as soon as
possible in patients who are having infantile spasms.
Vigabatrin (100-150 mg/kg daily divided twice daily)
usually is the treatment of choice for children who have tu-
berous sclerosis who have infantile spasms. Treatment with
vigabatrin typically is for 6 months, during which time for-
mal eye examinations should be monitored for retinal toxic
effects. The overall neurologic outcome is poor in patients
who have symptomatic causes of infantile spasms, whereas
those who have cryptogenic infantile spasms can have better
outcomes. Children who have Down syndrome, however,
respond well to treatment of infantile spasms. Recurrence
of other seizure types after treatment of infantile spasms is
common. Patients who experience cessation of infantile
spasms should be considered for long-term AED therapy
for at least 1 year after treatment.
Cognitive and Behavioral Issues in Epilepsy
Many epileptic syndromes, such as benign rolandic epi-
lepsy and CAE, demonstrate that pediatric epilepsies
Pediatrics in Review Vol.34 No.8 August 2013 339
neurologic disorders seizures
can have significant potential comorbidities that involve
behavior and cognition. (4) Recent studies in children
who have new-onset epilepsy suggest that the mecha-
nisms responsible for seizures in childhood rather than
the epilepsy itself may be responsible for cognitive diffi-
culties. Children who have new-onset seizures have
a higher occurrence of depressive disorders (22.6%), anx-
iety disorder (35.8%), and ADHD (26.4%) compared
with controls (P<.01), but no difference was found in
children who have focal vs generalized seizures. In 45%
of the children who have epilepsy, psychiatric comorbid-
ity antedated epilepsy. (5)
In a similar group of patients who have new-onset
seizures, ADHD, inattentive type, was seen in 31% of pa-
tients vs 6% of controls (P<.001). The onset of ADHD
antedated the diagnosis of epilepsy in 82% of patients,
with 65% of patients having been referred for educational
support services. Again, no difference was seen in gener-
alized vs focal epilepsy.
Data on cognitive ability, language skills, and presence
of psychopathology in 69 children who have CAE and
103 age- and sex-matched healthy children suggested
a similar theme. Patients and their parents had semistruc-
tured psychiatric interviews, cognitive evaluation, and
language testing. Twenty-five percent and 43% of the
children who had absence epilepsy had subtle cognitive
and linguistic deficits, respectively. Interestingly, a surpris-
ing 61% of children who have absence epilepsy satisfied
Diagnostic and Statistical Manual of Mental Disorders
(Fourth Edition) criteria for a psychiatric illness, particu-
larly ADHD and anxiety. Parents reported significant
scores on the Child Behavioral Checklist in the areas of
attention, somatic symptoms, and social and thought
problems. (3)
The relation of these symptoms to the overall duration
and frequency of absence seizures and to AED treatments
suggests that the electrographic signature of 3-Hz spike
and wave, even after disappearance of clinical seizures
with AED treatment, may herald continuing neuronal
dysfunction in multiple cortical-thalamic circuits.
Pediatric Pseudoseizures
Psychogenic nonepileptic seizures, also referred to as
pseudoseizures, are relatively rare in the pediatric popu-
lations. (6) The prevalence is rare in adults (2-30 per
100,000 population), without similar data existing for
pediatric populations. Approximately 5% of all events
seen in the pediatric epilepsy monitoring of a children’s
hospital are psychogenic nonepileptic seizures. Most of
these episodes occur in patients who have no history of
340 Pediatrics in Review Vol.34 No.8 August 2013
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epilepsy (67%), although one-third may occur in children
who have epilepsy.
Psychogenic nonepileptic seizures are paroxysmal
events that often resemble epileptic seizures but are psy-
chological in origin. The major causes are stressors, usu-
ally associated with family, school, or friends. Less than
5% are due to physical or sexual abuse, but nonetheless
it is important to screen for this important potential
cause.
In younger patients, prolonged unresponsiveness with
subtle motor changes tends to be the norm without any
electrical changes on the EEG. Overall, children who
have nonepileptic seizures typically are older, in the age
range of 11 to 14 years. The mean duration of nonepilep-
tic seizures (‡3-4 minutes) is much longer than the typ-
ical pediatric epileptic seizure duration of 1 to 2 minutes.
Tremors, either synchronous or asynchronous, in the up-
per extremity are the most common motor signs. Trem-
ors confined to one limb are observed commonly in the
setting of at least some responsiveness.
Unresponsiveness with expression of mostly negative
emotion (weeping, crying, painful facial expression, or
fear) or laughing was observed more in the older patients.
More complex motor movements, often asynchronous
and involving multiple limbs, often are associated with
disturbed consciousness. Memories of these events and
a short apparent postevent period with quick return to
normal activity should increase the suspicion of a nonepi-
leptic seizure.
Treatment of nonepileptic seizure begins immediately
after video EEG monitoring with a consultation with
a child psychiatrist. Before the consultation, a conversa-
tion with the child’s caregivers regarding the nature of
the spells and video EEG findings is of paramount im-
portance. Nonepileptic seizures do not have an organic
cause but require a search for psychogenic factors. The
loss of consciousness that can occur during nonepileptic
seizures is puzzling but should be discussed with the
family.
Typical conversations center around the reactions of
the body, comparing nonepileptic seizures to other stress
reactions. It is important to point out that although the
cause is psychological in origin, the condition is no less
important and also very amenable to treatment if insti-
tuted promptly. It is important to emphasize to parents
that undergoing further unnecessary medical diagnostic
testing only delays treatment and should be avoided.
Treatment of psychological factors with medications
for anxiety or depression with or without cognitive be-
havioral therapy usually results in a lessening and then
complete disappearance of the nonepileptic seizures.
 neurologic disorders seizures

Suicidal and homicidal thoughts or delusions should be
treated aggressively in conjunction with a child psychia-
trist. Success with these treatment modalities is high in
children up to age 18 years, with more than 80% of pa-
tients experiencing significant reductions or cessation of
their nonepileptic seizures.
Summary
• On the basis of strong evidence, treatment is highly
dependent on the seizure semiology results,
electroencephalography (EEG) findings, and origin.
• On the basis of moderate evidence and consensus,
vigorous use of video EEG recordings and home video
cameras should be used to delineate the epileptic
syndromes.
• On the basis of strong evidence, pediatric epilepsy
syndromes have common comorbidities. As
a consensus, some pediatric epilepsy centers consider
referral to a neuropsychologist to be first-line care in
these patients.
• On the basis of strong evidence and consensus,
antiepileptic drug therapy has its own complications
and should be discontinued after an appropriate
treatment course.
• On the basis of moderate evidence and consensus,
uncontrolled seizures put patients at risk for
significant morbidity and mortality.
References
1. American Academy of Pediatrics Subcommittee on Febrile
Seizures. Neurodiagnostic evaluation of the child with a simple
febrile seizure. Pediatrics. 2011;127(2):389–394
2. 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):216–225
3. Glauser TA, Cnaan A, Shinnar S, et al, for the Childhood
Absence Epilepsy Study Team. Ethosuximide, valproic acid, and
lamotrigine in childhood absence epilepsy: initial monotherapy
outcomes at 12 months. Epilepsia. 2013;54(1):1–15
4. Jones JE, Austin JK, Caplan R, Dunn D, Plioplys S, Salpekar JA.
Psychiatric disorders in children and adolescents who have epilepsy.
Pediatr Rev. 2008;29(2):e9–e14
5. Kerr MP, Mensah S, Besag F, et al; International League of
Epilepsy (ILAE) Commission on the Neuropsychiatric Aspects of
Epilepsy. International consensus clinical practice statements for the
treatment of neuropsychiatric conditions associated with epilepsy.
Epilepsia. 2011;52(11):2133–2138
6. Szabó L, Siegler Z, Zubek L, et al. A detailed semiologic analysis
of childhood psychogenic nonepileptic seizures. Epilepsia. 2012;53
(3):565–570
Suggested Reading
Costello DJ, Cole AJ. Treatment of acute seizures and status
epilepticus. J Intensive Care Med. 2007;22(6):319–347
Gaillard WD, Chiron C, Cross JH, et al; ILAE, Committee for
Neuroimaging, Subcommittee for Pediatric. Guidelines for
imaging infants and children with recent-onset epilepsy. Epi-
lepsia. 2009;50(9):2147–2153
Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE treatment
guidelines: evidence-based analysis of antiepileptic drug efficacy
and effectiveness as initial monotherapy for epileptic seizures
and syndromes. Epilepsia. 2006;47(7):1094–1120
Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline
update: medical treatment of infantile spasms: report of the
Guideline Development Subcommittee of the American Acad-
emy of Neurology and the Practice Committee of the Child
Neurology Society. Neurology. 2012;78(24):1974–1980
Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment
of pediatric epilepsy: European expert opinion, 2007. Epileptic
Disord. 2007;9(4):353–412

Parent Resources From the AAP at HealthyChildren.org

The reader is likely to find material relevant to this article to share with parents by visiting these links:
• http://www.healthychildren.org/English/health-issues/injuries-emergencies/Pages/Seizures.aspx
• http://www.healthychildren.org/English/health-issues/conditions/head-neck-nervous-system/Pages/Difference-Between-
Seizure-and-Convulsion.aspx
• http://www.healthychildren.org/English/health-issues/conditions/head-neck-nervous-system/Pages/Seizures-Convulsions-
and-Epilepsy.aspx

Pediatrics in Review Vol.34 No.8 August 2013 341

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neurologic disorders seizures

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1. A 2-year-old has febrile seizures. Which of the following factors will increase her risk of subsequently
developing epilepsy?
A. An initial febrile seizure with a relatively low temperature.
B. Brief duration between onset of the fever and seizure.
C. Complex febrile seizure.
D. Family history of febrile seizures in a first-degree relative.
E. Younger age at onset of febrile seizures.

2. Treatment with antiepileptic drugs is recommended after 2 or more recurrent afebrile seizures. A common
question from parents in response to this treatment parameter is, “What percentage of children who
experience a single unprovoked seizure will not have another?”
A. 10%.
B. 20%.
C. 40%.
D. 60%.
E. 80%.

3. An 8-year-old child with a long history of recurrent generalized tonic-clonic seizures develops generalized
convulsive status epilepticus. Which of the following is the first treatment of choice on encountering trained
medical personnel?
A. Diazepam.
B. Fosphenytoin.
C. Lorazepam.
D. Pentobarbital.
E. Phenobarbital.

4. A 7-year-old boy develops spells that consist of a unilateral contraction of the left side of his face without
impairment of consciousness or speech arrest. Which of the following is the most likely diagnosis?
A. Absence seizures.
B. Benign rolandic epilepsy.
C. Juvenile myoclonic epilepsy.
D. Psychomotor seizures.
E. Simple partial seizures.

5. Generalized tonic-clonic seizures in adolescents are typical of which epileptic region of the brain?
A. Centrofrontal lobe region.
B. Corpus callosum region.
C. Frontal lobe region.
D. Parietal lobe region.
E. Temporal lobe region.

342 Pediatrics in Review Vol.34 No.8 August 2013

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 Pediatric Seizures
Reet Sidhu, Kohilavani Velayudam and Gregory Barnes
Pediatrics in Review 2013;34;333
DOI: 10.1542/pir.34-8-333

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Services http://pedsinreview.aappublications.org/content/34/8/333
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http://pedsinreview.aappublications.org/content/34/8/333#BIBL
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Emergency management of the
paediatric patient with generalized convulsive
status epilepticus
JN Friedman; Canadian Paediatric Society
Acute Care Committee
Paediatr Child Health 2011;16(2):91-7

all morbidity (mainly newly diagnosed neurological disorders)

Abstract
The present guideline paper addresses the emergency
management of generalized convulsive status epilepticus
(CSE) in children and infants older than one month of
age. It replaces the previous statement from 1996, and in-
cludes a new treatment algorithm and table of recom-
mended medications, reflecting new evidence and the
evolution of clinical practice over the past 15 years. The
document focuses on the acute pharmacological manage-
ment of CSE, but some issues regarding supportive care,
diagnostic approach and treatment of refractory CSE are
discussed.
Key Words: Convulsions; Emergency management; Pae-
diatrics; Seizures; Status epilepticus
of between 10% and 20% [2].
TABLE 1
Common etiologies of convulsive status epilepticus in children and inci-
dences from population-based studies
Acute
• Acute symptomatic (17% to 52%)
– Acute CNS infection (bacterial meningitis, viral meningitis or en-
cephalitis)
– Metabolic derangement (hypoglycemia, hyperglycemia, hyponatrem-
ia, hypocalcemia or anoxic injury)
– Antiepileptic drug noncompliance or withdrawal

– Antiepileptic drug overdose

– Non-antiepileptic drug overdose

Background and epidemiology • Prolonged febrile convulsion (23% to 30%)

Remote (16% to 39%)

The conventional definition of convulsive status epilepticus
(CSE) is continuous generalized tonic-clonic seizure activity • Cerebral migrational disorders (lissencephaly or schizencephaly)
with loss of consciousness for longer than 30 min, or two or
more discrete seizures without a return to baseline mental sta- • Cerebral dysgenesis
tus [1]. More recently, the terms ‘early’ or ‘impending’ status • Perinatal hypoxic-ischemic encephalopathy
epilepticus have been based on a definition of continuous or
intermittent seizures lasting longer than 5 min without full • Progressive neurodegenerative disorders
recovery of consciousness between seizures. It has been
shown that early treatment is more effective in stopping the Idiopathic/cryptogenic (5% to 19%)
seizure, and treatment delay results in increased morbidity
and mortality [2]. CNS Central nervous system. Adapted from reference [3]

The annual incidence of CSE in children is reported as 10 to

73 episodes/100,000 children and is highest (135/100,000 to The present guideline paper addresses CSE in children and
156/100,000 children) in children younger than two years of infants older than one month of age. It replaces the state-
age [3]. Common etiologies are listed in Table 1 [3]. Mortality ment published in 1996 [4].
has been reported to be between 2.7% and 8%, with an over-

ACUTE CARE COMMITTEE, CANADIAN PAEDIATRIC SOCIETY | 1


Protocols and guidelines
There is limited evidence in paediatrics on which to base a
‘gold standard’ protocol for the management of CSE. There
are many different variations of guidelines, protocols and al-
gorithms endorsed by organizations and institutions around
the world, based on a combination of evidence, consensus
opinion, local experience and drug availability [2]-[10]. Despite
the minor variations in detail, in many ways they are quite
similar.
In the highly stressed setting of this type of medical emer-
gency, a familiar standardized protocol of recommended
management saves time, prevents errors and facilitates care.
Although the outcome is mainly determined by its cause, the
duration of CSE is very important. A timely approach may be
more important than the exact individual pharmacological in-
terventions. Particular local expertise or resource limitations
may provide legitimate reasons to adapt or adjust the recom-
mended protocol. For individual children, who are known to
respond well to specific medications, a more tailored ap-
proach may be more appropriate.
The objectives for the acute management of CSE are as fol-
lows:
1. Maintenance of adequate airway, breathing and circula-
tion (ABCs).
2. Termination of the seizure and prevention of recur-
rence.
3. Diagnosis and initial therapy of life-threatening causes
of CSE (eg, hypoglycemia, meningitis and cerebral space-
occupying lesions).
4. Arrangement of appropriate referral for ongoing care or
transport to a secondary or tertiary care centre.
5. Management of refractory status epilepticus (RSE).
1. Maintenance of adequate ABCS
Inability to maintain the airway is the most important imme-
diate risk to the patient with CSE. Factors responsible for the
2 | EMERGENCY MANAGEMENT OF THE PAEDIATRIC PATIENT WITH GENERALIZED CONVULSIVE STATUS EPILEPTICUS
airway and ventilation being at risk include a clenched jaw,
poorly coordinated respirations, and production of secretions
and vomitus. Hypoxia is frequently present. Management of
the airway includes positioning the child on his/her side and
suctioning the easily accessible secretions. The teeth should
not be pried apart. After suctioning, the patient should be
repositioned on his/her back and a chin lift or jaw thrust
should be applied, if necessary, to help open the airway. Oxy-
gen (100%) should be given by face mask, and cardiorespira-
tory and oxygen saturation monitors should be used. Breath-
ing should be carefully monitored. Assisted ventilation
should be considered if the child shows signs of respiratory
depression or if oxygen saturations remain low despite receiv-
ing 100% oxygen by face mask.
Increased heart rate and blood pressure (BP) are usually ob-
served in the convulsing patient. They should return to nor-
mal when the seizure stops. Bradycardia, hypotension and
poor perfusion are ominous signs. They imply severe hypoxia
and an immediate need to establish the airway and ventilate
the patient, either by bag-valve mask ventilation or intuba-
tion. Intravenous (IV) access should be obtained immediately
(two large-bore IV lines if possible) and the bedside blood glu-
cose level should be checked. Further testing should be con-
sidered once the ABCs have been stabilized.
2. Termination of the seizure and
prevention of recurrence
Principles of treatment and monitoring
The major goal of treatment is to stop the seizure and, in do-
ing so, prevent brain injury. In animal models, ischemic and
excitotoxic neuronal cell loss starts to occur after 30 min of
seizure activity. Seizures that last longer than 5 min to 10 min
are at high risk of continuing for at least 30 min, so early
treatment is associated with the best outcome. This is the ra-
tionale behind assuming that any child who arrives in the
emergency department with acute tonic-clonic generalized
convulsions is in early CSE, which should immediately trig-
ger the first-line treatment with benzodiazepines as per the
management protocol (Figure 1)
ACUTE CARE COMMITTEE, CANADIAN PAEDIATRIC SOCIETY | 3
 TABLE 2
Anticonvulsant drug therapies for convulsive status epilepticus

Drug and route Dose Maximum Rate Repeat Risks Comments

First-line treatments

Lorazepam 0.1 mg/kg 4 mg <2 mg/min Every 5 Hypotension, respiratory Use sublingual tablets for buccal
(IV, IO, buccal, PR) (IV over 0.5–1 min) min ×2 depression, sedation route.
For PR route, dilute injection to 2 mg/
mL in D5W or NS

Midazolam

4 | EMERGENCY MANAGEMENT OF THE PAEDIATRIC PATIENT WITH GENERALIZED CONVULSIVE STATUS EPILEPTICUS
Buccal 0.5 mg/kg 10 mg Every 5 Hypotension, respiratory
min ×2 depression, sedation

Intranasal 0.2 mg/kg 5 mg/nostril

IM 0.2 mg/kg

IV 0.1 mg/kg

Diazepam

IV 0.3 mg/kg 5 mg <2 mg/min Every 5 Hypotension, respiratory

(<5 yrs) (IV over 2 min) min ×2 depression, sedation

10 mg
(≥5 yrs)

PR 0.5 mg/kg 20 mg

Second-line treatments

Fosphenytoin 20 mg/kg 1000 mg IV over 5–10 Decreased risks com- Expensive

(IV, IM) phenytoin min pared with phenytoin
equivalents (in NS or D5W)

Phenytoin* (IV) 20 mg/kg 1000 mg 1 mg/kg/min Hypotension, bradycardia, Must be given in nonglucose-con-
(over 20 min in arrhythmia taining solution
NS)

Phenobarbital† 20 mg/kg 1000 mg 1 mg/kg/min Respiratory depression First choice in neonates, or if on

(IV, IO) (over 20 min in (especially if benzodi- phenytoin maintenance
NS or D5W) azepine has been used),
hypotension, sedation

Paraldehyde‡ (PR) 400 mg 10 g Mucosal irritation Dilute 1/1 in oil in glass syringe
(0.4 mL/kg/ (10 mL/dose)
dose)

*If a patient is already receiving phenytoin, a partial loading dose of 5 mg/kg may be given. Subsequent doses may be given based on anticonvulsant levels; †If a
patient is already on phenobarbital, a dose of 5 mg/kg may be given. Subsequent doses may be given based on anticonvulsant levels; ‡Paraldehyde is available
through Health Canada's Special Access Programme but, currently, is only used in certain regions of Canada. D5W 5% dextrose water; IM Intramuscular; IO In-
traosseous; IV Intravenous; NS Normal saline; PR Per rectum; yrs Years

Anticonvulsant drug therapies for CSE are listed in Table 2
and Figure 1. If IV access is unavailable, then other routes
(eg, buccal, intranasal and rectal) should be used while efforts
to establish access continue. Consideration should be given
to starting an intraosseous (IO) line if IV access is not possi-
ble and the seizure is prolonged or the patient is decompen-
sating.
Because of the time required to administer many of the sec-
ond-line treatments (eg, phenytoin and phenobarbital), prepa-
rations to give these should start at the same time as adminis-
tering the first dose of benzodiazepine. Regardless of the par-
ticular institutional protocol being followed, some of the fre-
quent problems encountered include the following [5]:
• Inadequate doses of benzodiazepines.

ACUTE CARE COMMITTEE, CANADIAN PAEDIATRIC SOCIETY | 5

 • Treating with more than two doses of benzodiazepines
and a delay in initiating second-line treatment (usually
fosphenytoin/phenytoin or phenobarbital).
• Delay in initiating the RSE treatments (usually rapid se-
quence induction/intubation and initiation of midazo-
lam infusion).
It is important to obtain a brief history including any history
of seizure disorder, other symptoms (eg, fever), medication us-
age and allergies to medications. This can be completed by a
designated person not immediately involved in the acute re-
suscitation. This history will allow a simultaneous search for
cause (Table 1) and focused physical examination to be com-
pleted while termination of the seizure is undertaken.
A bedside glucose determination will establish the need for a
bolus of dextrose. If the blood glucose level is 2.6 mmol/L or
lower, then the recommended management is 2 mL/kg to 4
mL/kg of 25% dextrose water or 5 mL/kg of 10% dextrose
water (0.5 g/kg) by IV. If the patient is hypoglycemic, the bed-
side glucose level should be rechecked 3 min to 5 min postbo-
lus, and a repeat bolus should be given as necessary. In-
creased intracranial pressure (ICP) or sepsis should be sus-
pected and treated as needed.
During the administration of medications, pulse rate, respira-
tory rate, BP, cardiac monitoring and oxygen saturation via
pulse oximeter should be followed on a regular basis. Anti-
convulsant medications may cause loss of airway reflexes, res-
piratory depression, hypotension and cardiac arrhythmias.
Monitor the child’s temperature and aim for normothermia
using acetaminophen and ibuprofen as appropriate.
First-line treatment
First-line treatment usually begins outside the hospital. It has
been shown that prehospital treatment of children reduces
seizure length but often is not utilized [11]. Benzodiazepines
are the first-line drugs of choice in the treatment of CSE. If
used within the first 20 min of seizure onset, termination
rates of seizures can be as high as 70% to 85% [5]. Because IV
administration results in more rapid onset of action and im-
proved bioavailability and efficacy, IV access should be ob-
tained as soon as possible.
Prehospital: Treatment varies depending on local practices
and availability, but options include the following: buccal or
rectal lorazepam; buccal or intranasal midazolam; and rectal
diazepam (for dosing details see Table 2). Buccal midazolam
has been shown to control seizures in 56% of children com-
pared with rectal diazepam (27%) [12]. Two further studies [13]
[14] showed a 70% to 75% response to buccal midazolam com-
pared with a 57% to 59% response to rectal diazepam. In one
trial [15], intranasal midazolam (88%) was shown to be as ef-
fective as IV lorazepam (92%) in the treatment of prolonged
febrile convulsions of at least 10 min. If available, some
6 | EMERGENCY MANAGEMENT OF THE PAEDIATRIC PATIENT WITH GENERALIZED CONVULSIVE STATUS EPILEPTICUS
would consider buccal [16] or intranasal midazolam [2] to be
the first-line management in children without IV access.
In hospital: IV lorazepam is usually the first-line treatment.
It has a longer-lasting anticonvulsant activity and causes less
respiratory depression than diazepam [17]. It has been shown
to be more effective than diazepam or phenytoin in stopping
seizures [18]. Note that repeat doses are much less likely to be
effective (17% versus 85% for the first dose [12]). If children
have received benzodiazepines in the prehospital setting, one
repeat IV dose may be adequate [5] before moving to second-
line treatments if necessary. Because timing is critically impor-
tant, if no IV access is available, a second dose of benzodi-
azepine (lorazepam, midazolam or diazepam) should be given
through the buccal, intranasal, rectal or intramuscular (IM)
route while IV access is being obtained. Treatment with more
than two doses of benzodiazepines is associated with respira-
tory depression [11].
Second-line treatment
Fosphenytoin/phenytoin is generally preferred over pheno-
barbital because it is less likely to cause respiratory depression
and alter the level of consciousness of the child [3], which can
complicate the assessment. If no IV access is available, then
IM fosphenytoin, IO phenytoin or rectal paraldehyde are al-
ternative options. Note that evidence for the safety and effica-
cy of IO phenytoin or phenobarbital is scant.
Phenytoin and fosphenytoin: Phenytoin has been shown to
control 60% to 80% of seizures with a 20 mg/kg dose [19]. It
must be administered in normal saline (NS) because it precip-
itates in glucose-containing solutions. It is infused over ap-
proximately 20 min. Because of its high pH, extravasation of
phenytoin can result in severe subcutaneous irritation (‘pur-
ple glove syndrome’) characterized by edema, discolouration
and pain distal to the site of administration. This side effect
does not occur with fosphenytoin (20 mg/kg/dose), which is
a water-soluble prodrug of phenytoin. In addition to more
rapid IV infusion, fosphenytoin may be given by IM injec-
tion, but it is more expensive and is not universally available
[5]. Side effects of both phenytoin and fosphenytoin include
cardiac arrhythmias, bradycardia and hypotension, so contin-
uous BP and electrocardiogram monitoring is recommended
during infusion.
Phenobarbital: Early trials suggest that phenobarbital has
similar anticonvulsant activity to phenytoin, but a greater in-
cidence of respiratory depression, especially when used in
conjunction with benzodiazepines. The mechanism of action
is similar to benzodiazepines, so it may be less effective in
treating seizures refractory to these drugs [5]. It is still routine-
ly used for the treatment of neonatal seizures, as well as for
children who are already on phenytoin maintenance. The
loading dose is 20 mg/kg in NS or 5% dextrose water over 20
min. Side effects include sedation, respiratory depression and
hypotension, especially if a benzodiazepine has already been
given.
Paraldehyde: The mechanism of action is unknown. In the
only published randomized controlled trial [20] to date, IM
paraldehyde was found to be inferior to intranasal lorazepam
as a first-line treatment in sub-Saharan Africa. In a prospec-
tive observational study [11], children who received IV pheny-
toin were nine times more likely to stop seizing than those
who received rectal paraldehyde. There are, however, case se-
ries showing benefit in a minority of cases for which other an-
ticonvulsant drugs have failed. Because of side effects report-
ed with IV and IM use (eg, cyanosis, cough, hypotension and
pulmonary edema), only the rectal route with dilution in oil
is recommended. A dose of 0.4 mL/kg is mixed in an equal
amount of oil to a maximum total volume of 20 mL [5]. Par-
aldehyde is available through Health Canada’s Special Access
Programme but, currently, is only used in certain regions of
Canada. Many authorities no longer recommend paraldehyde
use, while others incorporate it only in cases for which there
is no IV access.
Sodium valproate: There is increasing interest in the use of
IV sodium valproate as a second- or third-line treatment. Ini-
tial open-label randomized trials look promising, with similar
efficacy to phenytoin, fewer adverse effects and, specifically,
no respiratory or cardiovascular compromise [3]. The IV load-
ing dose is 30 mg/kg over 5 min, followed by a 10 mg/kg bo-
lus if needed. The maintenance dose is 10 mg/kg by IV every
8 h [9]. Its role as a second-line treatment requires further in-
vestigation in well-controlled paediatric trials.
Pyridoxine: For children younger than 18 months of age in
whom seizures may be caused by an undiagnosed metabolic
disorder such as pyridoxine-dependent epilepsy, a trial of pyri-
doxine (vitamin B6) 100 mg by IV initially and then 50 mg IV
or by mouth twice a day, should be considered [9].
3. Diagnosis and initial therapy of life-
threatening causes of CSE
Investigations should be individualized according to the clini-
cal scenario (Table 1). The most common cause of CSE is a
prolonged febrile seizure. Children experiencing this type of
seizure may not require an extensive workup. The same may
apply to children with a known seizure disorder who are al-
ready on anticonvulsant therapy. However, a full clinical as-
sessment should involve a search for precipitating causes, fo-
cusing on signs of infection, meningeal irritation, trauma, fo-
cal neurological deficits and intoxication. It is important not
to mistake decorticate or decerebrate posturing for seizures.
When the etiology of the seizure is unclear, the following in-
vestigations should be considered [1]: blood for electrolytes,
glucose (to verify earlier bedside determination), complete
blood count and differential, cultures (if sepsis is suspected),
and capillary or arterial gas (perfusion must be adequate for
capillary gas). Anticonvulsant levels should be measured for
patients on long-term anticonvulsant therapy. Urine and
blood can be sent for toxicology screening. Serum calcium,
blood urea nitrogen, magnesium, liver enzymes, lactate and
ammonia may be required in selected cases. A decision re-
garding the need for lumbar puncture (LP) should be de-
ferred until the patient’s vital signs are stable, there is no sus-
picion of increased ICP and the convulsion has stopped. If
sepsis is believed to be likely, IV antibiotics may be given im-
mediately after blood cultures without waiting to perform the
LP. Prolonged attempts at obtaining cultures should not de-
lay treatment.
A history of trauma, evidence of increased ICP, focal neuro-
logical signs, unexplained loss of consciousness or suspicion
of cerebral herniation are some of the indications for a com-
puted tomography (CT) scan of the head. Head CT may be
performed after the ABCs have been stabilized and the con-
vulsion has terminated [1].
If there are clinical indications of raised intracranial pressure
or herniation, these must be treated immediately before fur-
ther investigation. A normal CT scan does not exclude signif-
icantly increased ICP. LP must be deferred if clinical or radio-
logical signs of increased ICP are present.
Intoxication should always be considered as a possibility. If
intoxication is proven or strongly suspected, and the convul-
sive activity has stopped, the use of activated charcoal may be
considered once the airway is protected, either through intu-
bation or after the child has woken up sufficiently to protect
his own airway.
Non-CSE
If the child’s level of consciousness does not recover as ex-
pected after the convulsion has stopped, or if neuromuscular
paralysis is being used, then an electroencephalogram (EEG)
should be performed to exclude non-CSE. If an EEG cannot
be obtained, then empirical treatment for non-CSE may be
indicated [10].
4. Arrangement of appropriate referral
for ongoing care or transport to a
secondary or tertiary care centre
Children without a previous history of epilepsy or febrile
seizures who present with CSE should be referred to either a
secondary or tertiary care hospital for further treatment and
investigation. Unstable vital signs or continuing CSE require
transport to a paediatric intensive care unit. Stabilization of
ACUTE CARE COMMITTEE, CANADIAN PAEDIATRIC SOCIETY | 7
 the child before transport must be discussed with a physician
skilled in paediatric emergency medicine or critical care.
5. Management of RSE
CSE that is unresponsive to two different antiepileptic med-
ications (eg, a benzodiazepine and phenytoin) is considered
to be refractory, although some authorities have added a du-
ration criterion such as longer than 30 min or longer than 60
min [3][21]. Studies in children have indicated that CSE lasts
longer than 1 h in 26% to 45% of patients [21]. These chil-
dren are unlikely to respond to other second-line anticonvul-
sants. Therefore, escalation to anesthetic support with sub-
specialist and intensive care consultation and initiation of a
midazolam infusion should be considered within 20 min to
30 min of starting the CSE algorithm (Figure 1).
It is recognized that paralysis may aid ventilation and prevent
the motor manifestations of seizures, but it does not termi-
nate the seizure activity in the brain. At this point, the
patient’s care is beyond the scope of the usual emergency de-
partment setting, and transfer to a paediatric intensive care
unit with neurological consultation for further management
will be necessary. Management will depend on the previous
experience in the individual centre involved, and may include
intermittent or constant EEG monitoring.
Pharmacotherapy in RSE
(Figure 1)
There are currently no published controlled trials examining
different treatment options for RSE in children. A number of
Canadian hospital guidelines have incorporated a continuous
infusion of midazolam as the first step. If this fails, then anes-
thetizing doses of barbiturates should be considered. Most re-
cently, the use of topiramate and levetiracetam has been sug-
gested, but the role of these drugs remains unclear at the
present time.
Midazolam: Midazolam is a fast-acting benzodiazepine with a
short half-life. It is believed to be effective in the management
of RSE and is administered by IV access with a bolus dose fol-
lowed by continuous infusion. A loading dose of 0.15 mg/kg
(maximum 8 mg) is followed by an infusion rate of 2 µg/kg/
min. This can be titrated up by increasing by 2 µg/kg/min
every 5 min until seizure control is achieved or a maximum of
24 µg/kg/min is reached [9][10]. Side effects include hypoten-
sion [21]. Therefore, BP should be monitored judiciously, and
low BP should be treated by giving 20 mL/kg IV boluses of
NS.
Barbiturates (thiopental and pentobarbital): Thiopental is
dosed at 2 mg/kg to 4 mg/kg bolus followed by 2 mg/kg/h to
4 mg/kg/h. Increases of 1 mg/kg/h can be used every 30 min
as needed, with a 2 mg/kg bolus with each increase in the in-
8 | EMERGENCY MANAGEMENT OF THE PAEDIATRIC PATIENT WITH GENERALIZED CONVULSIVE STATUS EPILEPTICUS
fusion rate to a maximum of 6 mg/kg/h. If midazolam and
phenobarbital are currently being used, they should be dis-
continued, whereas phenytoin should be maintained at thera-
peutic serum levels. Once seizures are controlled for 48 h, the
infusion rate of thiopental is decreased by 25% every 3 h;
phenobarbital is restarted while tapering [9].
If pentobarbital is used, it can be administered as a 10 mg/kg
bolus, followed by a continuous infusion at 0.5 mg/kg/h to 1
mg/kg/h [10]. Studies in children reported an efficacy for pen-
tobarbital of 74% to 100% and a high incidence of hypoten-
sion [21].
Other pharmacotherapy: Other options include propofol
[10], topiramate [9] and levetiracetam [3][21]. These drugs may be
useful in the management of RSE, but should be used by spe-
cialists with experience in their use.
Conclusion
There have been a number of changes in the emergency man-
agement of CSE over the past 15 years based on the emer-
gence of new evidence and medications. It is important for all
those involved in the acute medical management of children
to have an up-to-date, evidence-based approach to the emer-
gency management of children with CSE.
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ACUTE CARE COMMITTEE
Members: Adam Cheng MD; Catherine Farrell MD; Jeremy
N Friedman MD; Marie Gauthier MD (board representative);
Angelo Mikrogianakis MD (chair); Oliva Ortiz-Alvarez MD
Liaisons: Claudette Bardin MD, Hospital Paediatrics Sec-
tion, Canadian Paediatric Society; Laurel Chauvin-Kimoff
MD, Paediatric Emergency Medicine Section, Canadian Pae-
diatric Society; Dawn Hartfield MD, Hospital Paediatrics Sec-
tion, Canadian Paediatric Society
Principal author: Jeremy N Friedman MD
Also available at www.cps.ca/en
© Canadian Paediatric Society 2014
Disclaimer: The recommendations in this position statement do not indicate an
ACUTE CARE COMMITTEE, CANADIAN
exclusive course PAEDIATRIC
of treatment or procedureSOCIETY | Variations,
to be followed. 9 taking in-
to account individual circumstances, may be appropriate. Internet addresses
are current at time of publication.