Status Epilepticus in Children
Rani K. Singh, MD, and William D. Gaillard, MD
Corresponding author
William D. Gaillard, MD
Children’s National Medical Center, 111 Michigan Avenue NW,
Washington, DC 20010, USA.
E-mail: wgaillar@cnmc.org
Current Neurology and Neuroscience Reports 2009, 9:137–144
Current Medicine Group LLC ISSN 1528-4042
Copyright © 2009 by Current Medicine Group LLC
Status epilepticus is a common, life-threatening medi-
cal emergency in pediatric patients. Recent medical
literature has focused on identifying risks and treat-
ment options. This article highlights the epidemiology
of status epilepticus, both convulsive and nonconvul-
sive, in children. It also reviews the recommended
medications for first-line treatment of status epilep-
ticus and refractory status epilepticus. Emphasis is
placed on future pharmacotherapies and consideration
of neurosurgical intervention when indicated.
Introduction
The defi nition of status epilepticus (SE) has a long and
rich history. The fi rst known reference to status epilep-
ticus dates from 718–612 bc in the Sakikku cuneiform,
as follows: “If the possessing demon possesses him many
times during the middle watch of the night, and at the
time of his possession his hands and feet are cold, he is
much darkened, keeps opening and shutting his mouth, is
brown and yellow as to the eyes…It may go on for some
time, but he will die.”
In 1962, at the Xth Marseilles Colloquium (the tenth
European electroencephalography meeting), a more
contemporary definition was developed: “A condition char-
acterized by epileptic seizures that are sufficiently prolonged
or repeated at sufficiently brief intervals so as to produce an
unvarying and enduring epileptic condition” [1].
The most recent revision by the International League
Against Epilepsy defines SE as “a seizure that shows no
clinical signs of arresting after a duration encompassing
the great majority of seizures of that type in most patients
or recurrent seizures without interictal resumption of base-
line of CNS function” [2]. Although this definition does
not specify a temporal meaning, the traditional view of the
duration is greater than 30 minutes. As the molecular basis
for the advantages of early seizure cessation has begun to
be elucidated, more recent literature advocates that there
should be a revised definition of SE as lasting no longer than
10 minutes [3] or even 5 minutes [4]. However, determining
the duration of SE is not always possible because the onset
may not be observed. In the setting of convulsive SE (CSE),
the termination, which would be when all clinical signs of
tonic, tonic-clonic, or motor activity have stopped, may be
easier to recognize. Conversely, the termination of noncon-
vulsive SE (NCSE) may be less clear [5••]. It is likely that
the various definitions will persist until the pathophysiol-
ogy of CSE and NCSE is better understood.
Classification of Status Epilepticus
It is important to identify and classify the causes of CSE.
The International League Against Epilepsy classification
has been the standard for adult and pediatric SE and
separates the etiology into acute symptomatic, remote
symptomatic, idiopathic epilepsy-related, cryptogenic epi-
lepsy-related, and unclassified [2].
Recent epidemiologic studies have argued that febrile
convulsions should be a separate entity from acute CSE
because they have a more favorable prognosis overall.
Moreover, studies that do not separate febrile CSE from
acute symptomatic CSE are likely to overstate the severity
of outcome of febrile CSE, thus attenuating the severity
of acute neurologic insults [6,7••]. Pediatric studies have
also classified SE according to CSE, which can be further
divided into generalized CSE and partial CSE and also
NCSE (in which the primary symptom is the disturbance
of consciousness with or without subtle motor manifesta-
tions) [8•]. Because accurate categorization of individual
cases may depend on the degree of investigation, the
availability of ancillary tests, and clinical data, a revised
classification may still have its limitations [6].
Epidemiology
The annual incidence of pediatric SE ranges from 10 to
73 per 100,000. The highest incidence is in children less
than 2 years of age, where it ranges from 135 to 156 per
100,000, with the greatest peak in the fi rst year of life. If
febrile SE is excluded, the incidence is decreased by 25%
to 40% [7••,8•,9].
Prospective population-based studies have stratified
the etiology of SE in children. Prolonged febrile convulsion
is the most common etiology (32%–46%), followed by
acute symptomatic (17%–24%) and remote symptomatic
(11%–28%) SE. Less common are cryptogenic or idio-
pathic (11%–16%) SE [5••,7••,8•]. CSE is more common
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I Pediatric Neurology
Table 1. Common etiologies of status epilepticus
in children and incidences from population-
based studies
Acute
Acute symptomatic (17%–52%)
Acute CNS infection (bacterial meningitis, viral
meningitis, encephalitis)
Metabolic derangement (hypoglycemia, hyperglycemia,
hyponatremia, hypocalcemia, anoxic injury)
AED noncompliance or withdrawal
AED overdose
Non-AED/drug overdose
Prolonged febrile convulsion (23%–30%)
Influenza
Exanthem subicum
Remote (16%–39%)
Cerebral migrational disorders (lissencephaly, schizencephaly)
Cerebral dysgenesis
Perinatal hypoxic-ischemic encephalopathy
Progressive neurodegenerative disorders
Idiopathic/cryptogenic (5%–19%)
AED—antiepileptic drug; CNS—central nervous system.
than NCSE, occurring in as much as 86% of patients [8•].
Table 1 lists the common etiologies of SE in children that
should be considered in each case.
Between four and eight children per 1000 are expected
to experience CSE before age 15 years [5••]. The most
common risk factor for SE in children is a prior history
of SE [10,11]. Other common risk factors for pediatric SE
include a younger age, a symptomatic etiology, and a his-
tory of an epileptic encephalopathy or a specific epilepsy
syndrome. Common in the adult population, noncompli-
ance with antiepileptic drugs (AEDs) is not as common
a risk factor for children [11,12]. In children who have
no history of previous SE, the risk of SE decreased with
increasing age. In children who have a previous history
of SE, patients with symptomatic epilepsy have a higher
risk. Children who have had a questionable episode of SE
before the diagnosis of epilepsy are more likely to have SE
during the follow-up [11]. Karasalihoglu et al. [13] sug-
gested that SE is more likely to appear in children who
have had a partial seizure evolving to a secondarily gener-
alized seizure or in those with myoclonic seizures.
Morbidity and Mortality
The outcome of pediatric SE is based upon its morbidity
and mortality. Among children, the risk of recurrence of
SE at 1 year was 11% in one study [14] and 16% in another
[7••] and was 18% at 2 years [14]. Both studies included
children with a fi rst febrile episode of SE and reported an
increased risk for recurrence associated with a preexisting
neurologic abnormality. A Finnish study included only
patients with afebrile SE and found that more than half
of those with SE experienced recurrent SE [12]. The risk
for recurrent afebrile SE in this study was 13.1% at 1 year
and 16.9% at 2 years [12]. In a Minnesota population-
based study combining all ages, one-third of individuals
experienced a second episode of SE, with the risk doubled
for those with progressive symptomatic etiology and for
female patients [15•].
Future epilepsy, focal neurologic deficits, cognitive
impairment, and behavioral problems may be associated
with CSE. However, specific risk factors in the pediatric
population have not yet been reported [6]. In patients
with cryptogenic SE, a significant portion of infants went
on to develop West syndrome or mental deficiency, most
because of an underlying neurologic disorder [8•].
A devastating epileptic encephalopathy, which begins
with intractable SE evolving over days to weeks and per-
sists as bilateral temporal lobe pharmaco-resistant epilepsy,
has become increasingly recognized in children. The main
features include 1) onset in previously healthy school-aged
children; 2) an initial febrile context but no evidence of
intracranial infection; 3) onset with prolonged intractable
SE followed by intractable epilepsy without any latent period
in between; 4) clinical and electroencephalogram (EEG) fea-
tures of focal seizure onset during both SE and follow-up,
primarily in the perisylvian areas; 5) bilateral mesial tem-
poral dysfunction on neuropsychological tests with atrophy
and/or in hypersignal on MRI; and 6) frontal lobe involve-
ment in half of the cases. The morbidity of this devastating
encephalopathy, more commonly known as fever-induced
epileptic encephalopathy in school-aged children (FIRES),
consists of severe memory, language, and behavior troubles
with permanent cognitive sequelae [16••].
In a population-based study of adults and children, the
rate of fatalities ranged from 7.6% to 22% and showed
a bimodal distribution, with young children and elderly
patients experiencing the greatest mortality from CSE. Age
was the only significant predictor of in-hospital death fol-
lowing generalized CSE [9]. The mortality rate in pediatric
SE ranges from 0% to 7% [5••,7••,12]. Children with acute
or remote symptomatic CSE are associated with the high-
est mortality during hospitalization [7••]. Death due to SE
is most often due to the underlying cause, such as central
nervous system infection or severe neurologic disabilities.
Some have associated SE as a direct cause of death, regard-
less of the underlying etiology [12,15•]. The relatively low
morbidity and mortality in pediatric SE is likely multifacto-
rial, being helped by advances in childhood medical and
nursing practices with acute life support, critical care man-
agement, and evolving AED therapy [5••].
Nonconvulsive Status Epilepticus
NCSE is an important subtype of SE, but it is difficult
to identify and treat. It is defi ned as an EEG-recorded
ictal episode, continuous or recurrent, for greater than

30 minutes without improvement in clinical state or
return to a preictal EEG pattern between seizures. In 49
admissions of 43 patients in a neurointensive care unit,
23 patients were found to be in NCSE [17]. Seventy-six
percent of patients had a history of a clinical seizure pre-
ceding NCSE, and 25% were de novo [17]. Mortality of
NCSE in this combined adult–pediatric study was 57%
and was strongly linked to duration of NCSE and delay
of diagnosis of NCSE [17]. In a large hospital-based
series, 92% of patients with nonconvulsive seizures were
in NCSE (for an overall incidence of 17% in those moni-
tored) [18]. Risk factors in this study included comatose
state on neurologic examination, age younger than 18
years, a past medical history of epilepsy, and a convul-
sive seizure prior to monitoring [18].
The incidence of NCSE in pediatric patients undergoing
long-term monitoring in the intensive care setting ranges
from 16% to 32% [19•,20,21••]. Tay et al. [19•] found
that half of these children had preexisting epilepsy, with
common causes including an exacerbation of the underly-
ing metabolic disorder or an acute infection. The overall
mortality rate of NCSE was 26% [19•]. Median duration
lasted from 48 to 56 hours. More than one-fourth of the
pediatric patients were less than 1 year of age [19•,21••].
Most studies in adults have shown that NCSE is often
due to an acute or remote central nervous system insult
(eg, stroke, anoxic-ischemic encephalopathy, intracere-
bral hemorrhage). However, most children with NCSE
are previously healthy and have no preexisting disease
[19•,21••]. The availability of prolonged EEG monitoring
has allowed increased recognition of this condition. Rec-
ommendations for monitoring include any patient with
unexplained or protracted impairment of consciousness,
comatose state on neurologic examination, or altered
behavior after a recognized seizure [17].
EEG Findings in Status Epilepticus
Treiman et al. [22] initially described five identifiable EEG
patterns that occurred in a predictable sequence during
the course of secondarily generalized CSE in adults. The
stages were 1) EEG changes of discrete seizures with inter-
ictal slowing; 2) merging seizures with waxing and waning
ictal discharges; 3) continuous ictal discharges; 4) contin-
uous ictal discharges with “flat” periods; and 5) periodic
epileptiform discharges on a “flat” background [22]. In a
primarily adult retrospective review, focal interictal epi-
leptiform discharges were most common during routine
and digital video EEG, with the latter more commonly
detecting electrographic seizures. Other patterns included
periodic lateralized epileptiform discharges, burst sup-
pression, and generalized spike-and-wave discharges [23].
Generalized background abnormalities were also com-
mon in patients with CSE [13]. After the resolution of SE,
epileptiform discharges were significantly more common
in the remote symptomatic and cryptogenic groups than
in the acute symptomatic group [8•].
Status Epilepticus in Children
I Singh and Gaillard
I 139
EEG fi ndings in NCSE are more variable, including
typical and atypical spike and wave, multiple or polyspike
discharges, and a rhythmic sharp delta pattern [19•].
Abnormal EEG patterns such as periodic lateralized epi-
leptiform discharges, generalized periodic epileptiform
discharges, and burst suppression patterns were seen in
those patients with NCSE who required prolonged EEG
monitoring [18]. In a recent pediatric study, most ictal
EEGs showed a focal distribution of discharges [19•].
Treatment of Status Epilepticus
Acute status epilepticus
Benzodiazepines are recommended as the initial drug of
choice for treating SE. Intravenous (IV) diazepam was
developed first, followed by IV lorazepam. IV diazepam
has a more rapid onset of activity, whereas IV lorazepam
has a longer duration of antiseizure effect. In the past, when
IV diazepam was administered as the first-line medication,
a second AED was often required because breakthrough
seizures would develop. With the development of rectal
diazepam, there seems to be less risk of breakthrough
seizures. However, there are no published pediatric head-
to-head comparison trials of the benzodiazepines.
Most studies for the acute treatment of SE have been
in the adult population. The Veterans Affairs Status Epi-
lepticus Cooperative Study [24], a multicentered adult
trial, evaluated four different treatment modalities for
SE: 1) diazepam then phenytoin, 2) lorazepam, 3) phe-
nobarbital, or 4) phenytoin. Of the 570 patients who
met inclusion criteria, 395 (69%) were in SE. In a pair-
wise comparison, lorazepam was significantly superior
to phenytoin but not to the combination of diazepam
then phenytoin or phenobarbital alone. Among the 134
patients with a verified diagnosis of NCSE, there were
no significant differences among the treatments [24].
Adult studies have also evaluated out-of-hospital
treatment for SE. In a randomized double-blinded trial,
patients were given either 5 mg of diazepam repeated to
a maximum of 10 mg, 2 mg of lorazepam repeated to a
maximum of 4 mg, or placebo. Primary outcome was ter-
mination of SE by the time of arrival to the emergency
department. Secondary outcome measures included
out-of-hospital complications, complications during treat-
ment, duration of SE prior to arrival at the hospital, and
neurologic outcome at discharge. The study found IV
benzodiazepines to be safe and effective when adminis-
tered by paramedics. Lorazepam and diazepam were both
more effective than placebo, with a trend favoring loraz-
epam over diazepam. However, between 41% and 57% of
patients who received active therapy were still in SE upon
arrival to the hospital [25]. In 45 episodes of generalized
CSE in 38 children, prehospital treatment with diaz-
epam was associated with a shorter duration of SE (32
minutes vs 60 minutes) compared with lorazepam, with
a decreased risk of recurrent seizures in the emergency
department (58% vs 85%) [26].
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I Pediatric Neurology
In a retrospective pediatric study in the United Kingdom
evaluating pre–intensive care unit treatment of SE, either
diazepam or lorazepam was the most commonly adminis-
tered first-line AED, but the dose was frequently lower than
that recommended. Children who had prehospital treatment
were more likely to receive more than two doses of benzodi-
azepine, and those who had prehospital treatment were also
more likely to have respiratory depression [27].
Traditionally, based on long-term clinical experience
and case-control studies, IV phenytoin has been used as
the second-line drug for SE [28••]. A dose of 18 mg/kg of
phenytoin given over 20 minutes through an IV peripheral
line is recommended, with additional bolus to maximize
the total dose to 25 mg/kg [24]. Fosphenytoin is a prodrug
of phenytoin (150 mg of fosphenytoin is equivalent to 10
mg of phenytoin) with 100% bioavailability. Although
there are limited adult and pediatric efficacy data on the
use of fosphenytoin, the drug’s practical benefits include a
reduced risk and incidence of serious extravasation reac-
tions, hypotension, and cardiac dysrhythmias. Although
it is more expensive and not routinely available in most
hospitals worldwide, it may eventually replace phenytoin
as the long-acting anticonvulsant of choice [29].
Phenobarbital may also be used as a second-line agent
or as an alternative to phenytoin when a benzodiazepine
has failed. The initial dose for SE may range from 15 to
20 mg/kg in children, with a maintenance dosage of 3 to
4 mg/kg per day. However, the dose of phenobarbital to
be recommended is not as precisely determined as other
AEDs. Very high-dose phenobarbital, without reference
to a predetermined maximum dose or serum level, has
also been used to treat refractory SE. Adverse effects of
the higher dose include a marked and prolonged sedative
effect, with depression of respiratory drive and hypoten-
sion at higher doses [30].
Combined adult and pediatric randomized trials have
suggested the favorability of valproic acid over phenytoin.
In a randomized trial of age- and sex-matched groups
comparing IV valproic acid with IV phenytoin, IV valproic
acid was found to be as effective as IV phenytoin and was
more tolerable [28••]. Similarly, Misra et al. [31•] looked at
seizure control with either loading phenytoin at 18 mg/kg
at an infusion rate of 50 mg/min or valproic acid at 30
mg/kg over 15 minutes. Valproic acid was more effective
than phenytoin in controlling CSE, both as the first (66%
vs 42%) and as the second choice (79% vs 25%). VPA as a
second choice terminated SE more frequently (79%) than
phenytoin (25%) [31•]. However, this study did not com-
pare the maximum dose of valproic acid to the maximum
equivalent dose of phenytoin (25 mg/kg).
Valproic acid has also been effective in pediatric ret-
rospective studies. In a retrospective review of 40 patients
loaded with valproic acid, 20 of whom had SE, rapid load-
ing at 25 mg/kg at a rate of 3 mg/kg per minute stopped
seizures in 18 (90%) patients with SE within 20 minutes
[32]. All 18 patients regained baseline mental status within
1 hour of seizure cessation. Among the other 22 patients
with acute repetitive seizures, only one had further seizures
after valproic acid infusion, with transient tremor as an
adverse effect in one patient [32]. In a relatively large study
of intravenous valproic acid in children in SE, 78% of the
patients who were refractory to initial standard therapy
responded to valproic acid, and in most cases the response
was very rapid [33]. Sixty-five percent of these patients
responded immediately (within 2–6 minutes). The remain-
ing 10% responded within 3 to 10 minutes. Loading doses
ranged from 20 to 40 mg/kg, with the highest success rate
being from 30 to 40 mg/kg [33]. Valproic acid, along with
the newer anticonvulsants discussed in the following text,
may eventually move to replace phenytoin as second-line
therapy for SE. Table 2 summarizes suggested medications
for acute and refractory SE.
Refractory status epilepticus
More than 90% of all convulsive seizures end spontane-
ously within the first 5 minutes. As the time of initiation of
therapy for SE with benzodiazepines increases, the efficacy
of these medications decreases [12]. The most accepted def-
inition of refractory SE is when a seizure continues despite
the administration of two or more first-line medications
[5••]. Others have characterized the duration to refractory
SE (RSE) as lasting greater than 60 minutes [34,35••,36•].
High-dose pentobarbital, or pentobarbital coma,
has commonly been used in the intensive care unit for
RSE, and this requires continuous EEG for monitoring
burst suppression. It is generally given as a bolus dose
of 5 to 15 mg/kg followed by a maintenance infusion
of 1 to 5 mg/kg per hour. Although it is effective in
terminating seizures, pentobarbital administration is
associated with hypotension, myocardial depression,
and low cardiac output. It is also a potent respiratory
depressant, often requiring endotracheal intubation
and mechanical ventilation [35••].
More recently, midazolam has been suggested as a
fi rst-line therapy in RSE. In a retrospective multicenter
study, 76% of patients treated with midazolam achieved
clinical seizure control within 30 minutes of treatment
initiation [35••]. Midazolam was eventually success-
ful in treating 15 seizure episodes (88%). Relapse after
discontinuation of therapy occurred in one patient (6%),
and there were no significant adverse effects [35••].
Morrison et al. [36•] recently developed a high-dose
midazolam algorithm with an emphasis on rapid seizure
control. The bolus dose was 0.5 mg/kg followed by an
infusion of 2 μg/kg per minute up to 24 μg/kg per min-
ute and reaching as high as 32 μg/kg per minute. Of 17
patients admitted to the pediatric intensive care unit who
followed this algorithm, 15 patients were controlled and
remained seizure free for 12 to 24 hours on midazolam
prior to weaning. The remaining two patients could not
be controlled with midazolam therapy and required the
administration of sodium thiopentone [36•].
Brevoord et al. [37] retrospectively reviewed four dif-
ferent treatment modalities in the cessation of generalized

Table 2. Potential options for pharmacologic treatment of status epilepticus
Medication Dose
Acute status epilepticus
Lorazepam 0.1–0.15 mg/kg IV
Diazepam 0.3 mg/kg IV,
0.5–0.7 mg/kg rectal
Phenytoin 20 mg/kg up to 25 mg/kg IV
Fosphenytoin 15–20 mg/kg up to
25 mg/kg PE IV
Phenobarbital 15–20 mg/kg up to
30 mg/kg or serum
concentration 15–45 mg/L
Valproate (remains 20 mg/kg IV then
experimental) 1 mg/kg/h or 24 mg/kg
divided every 8 h (maintain
serum concentration at
75 mg/L, or > 100 mg/d
when dosing every 4 h)
Refratory status epilepticus
Diazepam 0.01–0.1 mg/kg/min
or to effect
Midazolam 0.15–0.3 mg/kg load,
1–18 μg/kg/h or to effect
Phenobarbital (high Dosing twice daily
dose) to achieve increased
serum concentration
(up to 70 mg/L)
Pentobarbital 2–10 mg/kg load*
up to 20 mg/kg† then
0.5–5 mg/kg/h or to effect
Propofol 3–5 mg/kg load then
1–15 mg/kg/h or to effect
Levetiracetam 20 mg/kg load then
(remains additional 20 mg/kg
experimental) to effect or maximum
of 80 mg/kg/d
(500–3000 mg/d in adults)
Topiramate (remains 2–5 mg/kg bolus NG
experimental) to maximum of
20 mg/kg/d or to effect
(300–1600 mg/d in adults)
*Rate is over 1 hour.
†
Rate is over 2 hours.
IV—intravenous; NG—nasogastric; PE—phenytoin equivalent.
CSE in children: 1) midazolam bolus and infusion,
2) phenytoin bolus, 3) phenytoin bolus followed by a versed
continuous infusion, or 4) phenobarbital/pentobarbital
bolus and infusion. Most of the patients (68%) had initially
received rectal diazepam. Cessation of epileptic activity
was achieved with midazolam only in 58 patients (48%);
with midazolam and phenytoin in 19 patients (15%); with
midazolam, phenytoin, and continuous midazolam in 32
patients (26%); and with additional barbiturates in 13
patients (11%) [37].
Status Epilepticus in Children
I Singh and Gaillard
I 141
Rate Adverse effects
< 2 mg/min Hypotension, respiratory depression,
depressed level of consciousness
IV over 2–5 min to Hypotension, respiratory depression,
prevent apnea depressed level of consciousness
50 mg/min Hypotension, cardiac arrhythmias
150 mg PE/min Hypotension, cardiac arrhythmias
1 mg/kg/min (maximum Hypotension, respiratory depression,
2 mg/kg/min in child, depressed level of consciousness
100 mg/min in adult)
6 mg/kg/min Hypotension, fatal hepatoxicity
Hypotension, respiratory depression,
depressed level of consciousness
Respiratory depression
(less common)
Respiratory depression but
develop tolerance
Cardiac suppression, hyoptension,
poor cardiac output, immune
suppression, respiratory depression
Propofol infusion syndrome in children
Sedation, irritability
Metabolic acidosis
Anesthetic treatment of refractory status epilepticus
Various anesthetics have been administered in adult and
pediatric SE. Propofol has been administered for RSE and
has been shown to terminate clinical seizures, but the qual-
ity of burst suppression has been variable [38•]. However,
case reports of propofol infusion syndrome in children,
characterized by metabolic acidosis, lipemic serum, and
bradyarrhythmia leading to progressive myocardial failure,
make this a less desirable option [39]. Within minutes of
initiating therapy, the inhalational anesthetic isoflurane,
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I Pediatric Neurology
accompanied by desflurane when necessary, stops epilep-
tic discharges with sustained burst suppression [40]. In a
pediatric retrospective study, propofol was more safe and
effective than thiopental in controlling RSE (64% vs 55%,
respectively) [41]. In the past and in certain cases, other
anesthetics, including paraldehyde and lidocaine, along
with the ketogenic diet, have been used in treating RSE.
Emerging pharmacotherapy
Newer studies suggest that both levetiracetam and
topiramate may have promise in RSE in the future.
Since 1999, levetiracetam has been prescribed world-
wide as adjunctive therapy for partial-onset seizures in
adults and in children older than 4 years of age. Most
analyses have been in the adult population. Patel et al.
[42•] found that in six patients (including children and
adolescents) with SE refractory to at least two AEDs,
adjunctive levetiracetam proved effective in several
types of SE, including generalized, focal, and NCSE.
Effective doses of levetiracetam ranged from 500 to
3000 mg/d, and seizure control was achieved within
12 to 96 hours [42•]. Rosetti and Bromfi eld [43] found
that levetiracetam administered together with other
AEDs represented 10% of the cohort of patients with
SE. As its pharmacokinetic profi le is very promising,
levetiracetam may represent a valuable alternative to
the existing treatment of SE [43]. In 2007 the paren-
teral form of administration became available, allowing
earlier administration. The injectable formulation
of levetiracetam has proven to be well tolerated and
exhibits similar pharmacokinetics to oral formulations,
broadening its clinical application [44].
Topiramate, a sulfamate-substituted monosaccha-
ride, is a broad-coverage antiepileptic drug available
only in the parenteral form. Topiramate administered
via nasogastric tube at doses between 300 and 1600
mg/d in six adults effectively terminated RSE in gen-
eralized CSE and NCSE [45]. In the case of infantile
spasms, topiramate may be rapidly titrated or loaded
without severe adverse effects [46]. Kahriman et al. [47]
retrospectively reported on three children with pediat-
ric RSE who responded to rapidly titrated nasogastric
topiramate at a daily dose of 5 to 6 mg/kg. Topiramate
was initiated at 2 to 5 mg/kg per day and titrated up
to 22 to 25 mg/kg per day in children with partial
SE refractory to phenobarbital, phenytoin, and mid-
azolam. Rapid titration to a very high total daily dose
via nasogastric tube was well tolerated and allowed for
the successful taper to other AEDs [48].
Neurosurgical interventions for status epilepticus
Rasmussen’s encephalitis is a rare childhood disease char-
acterized by the triad of the development of intractable
focal seizures with epilepsia partialis continua, progressive
hemiparesis, and increasing intellectual impairment with
inflammation of the brain and progressive atrophy of one
cerebral hemisphere. Hemispherectomy is often considered
to control the seizures and prevent the progressive cognitive
decline that accompanies the disease. Neurosurgical inter-
vention may also be considered in the rare case of medically
refractory SE. Emergent epilepsy surgery in 10 children
with focal epileptogenesis successfully stopped SE, and all
patients showed significant improvement during follow-up
[49]. In a retrospective analysis of patients receiving epi-
lepsy surgery, 20% were in continuous SE or intermittent
SE. All of these patients had extratemporal localization of
the epilepsy, and most (86%) of these patients underwent
hemispherectomy [50]. In a 4-year period at two tertiary
referral epilepsy centers, five pediatric patients were treated
successfully with neurosurgery for SE. The seizures were
fully controlled in four patients, and in the fifth patient the
seizure frequency was reduced by more than 90% [51••].
Conclusions
SE is a common medical emergency in pediatrics.
Advances in prolonged EEG monitoring have allowed
for increased recognition of NCSE in children. Because
there is increasing evidence that SE may be treated better
with earlier intervention, the defi nition of SE is evolving,
with an emphasis on shortening the duration of seizure
activity. A significant percentage of patients who present
with their fi rst seizure may present in SE. In the pediatric
population, the prolonged febrile convulsion should be
identified distinctly from the acute symptomatic group
because of the distinct differences in prognosis and neu-
rologic outcomes. Patients at greatest risk, especially
those with a history of prior SE, should be identified
early. Rectal diazepam should be made available to
caregivers for out-of-hospital treatment of SE. Benzodi-
azepines are still viewed as a fi rst-line medication, with
phenytoin, fosphenytoin, and phenobarbital following as
second-line medications. Valproic acid and midazolam
loading and maintenance doses may be tolerable and
more efficacious at higher concentrations. Newer phar-
macotherapies, including topiramate and levetiracetam,
may prove more advantageous for acute and refractory
SE in the future. Although neurosurgical treatment is
never viewed as a fi rst- or second-line therapy, it should
be considered in patients with RSE, but only in those
with focal epileptogenesis or epilepsia partialis conti-
nua. The future of successful SE treatment lies within
evidence-based guidelines derived from out-of-hospital
and in-hospital therapies, along with controlled studies
in pediatric populations that target specifi c etiologies.
Future studies should focus on the need to standardize
the treatment of convulsive emergencies to shorten the
duration of in-hospital or intensive care unit stay, which
will ultimately decrease morbidity and mortality.
Disclosures
No potential confl icts of interest relevant to this article
were reported.

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