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Status Epilepticus in Children

Rani K. Singh, MD, and William D. Gaillard, MD

Corresponding author 10 minutes [3] or even 5 minutes [4]. However, determining

William D. Gaillard, MD the duration of SE is not always possible because the onset
Children’s National Medical Center, 111 Michigan Avenue NW, may not be observed. In the setting of convulsive SE (CSE),
Washington, DC 20010, USA.
the termination, which would be when all clinical signs of
tonic, tonic-clonic, or motor activity have stopped, may be
Current Neurology and Neuroscience Reports 2009, 9:137–144
Current Medicine Group LLC ISSN 1528-4042 easier to recognize. Conversely, the termination of noncon-
Copyright © 2009 by Current Medicine Group LLC 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.
Status epilepticus is a common, life-threatening medi-
cal emergency in pediatric patients. Recent medical
literature has focused on identifying risks and treat- Classification of Status Epilepticus
ment options. This article highlights the epidemiology It is important to identify and classify the causes of CSE.
of status epilepticus, both convulsive and nonconvul- The International League Against Epilepsy classification
sive, in children. It also reviews the recommended has been the standard for adult and pediatric SE and
medications for first-line treatment of status epilep- separates the etiology into acute symptomatic, remote
ticus and refractory status epilepticus. Emphasis is symptomatic, idiopathic epilepsy-related, cryptogenic epi-
placed on future pharmacotherapies and consideration lepsy-related, and unclassified [2].
of neurosurgical intervention when indicated. Recent epidemiologic studies have argued that febrile
convulsions should be a separate entity from acute CSE
because they have a more favorable prognosis overall.
Introduction Moreover, studies that do not separate febrile CSE from
The defi nition of status epilepticus (SE) has a long and acute symptomatic CSE are likely to overstate the severity
rich history. The fi rst known reference to status epilep- of outcome of febrile CSE, thus attenuating the severity
ticus dates from 718–612 bc in the Sakikku cuneiform, of acute neurologic insults [6,7••]. Pediatric studies have
as follows: “If the possessing demon possesses him many also classified SE according to CSE, which can be further
times during the middle watch of the night, and at the divided into generalized CSE and partial CSE and also
time of his possession his hands and feet are cold, he is NCSE (in which the primary symptom is the disturbance
much darkened, keeps opening and shutting his mouth, is of consciousness with or without subtle motor manifesta-
brown and yellow as to the eyes…It may go on for some tions) [8•]. Because accurate categorization of individual
time, but he will die.” cases may depend on the degree of investigation, the
In 1962, at the Xth Marseilles Colloquium (the tenth availability of ancillary tests, and clinical data, a revised
European electroencephalography meeting), a more classification may still have its limitations [6].
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 Epidemiology
unvarying and enduring epileptic condition” [1]. The annual incidence of pediatric SE ranges from 10 to
The most recent revision by the International League 73 per 100,000. The highest incidence is in children less
Against Epilepsy defines SE as “a seizure that shows no than 2 years of age, where it ranges from 135 to 156 per
clinical signs of arresting after a duration encompassing 100,000, with the greatest peak in the fi rst year of life. If
the great majority of seizures of that type in most patients febrile SE is excluded, the incidence is decreased by 25%
or recurrent seizures without interictal resumption of base- to 40% [7••,8•,9].
line of CNS function” [2]. Although this definition does Prospective population-based studies have stratified
not specify a temporal meaning, the traditional view of the the etiology of SE in children. Prolonged febrile convulsion
duration is greater than 30 minutes. As the molecular basis is the most common etiology (32%–46%), followed by
for the advantages of early seizure cessation has begun to acute symptomatic (17%–24%) and remote symptomatic
be elucidated, more recent literature advocates that there (11%–28%) SE. Less common are cryptogenic or idio-
should be a revised definition of SE as lasting no longer than pathic (11%–16%) SE [5••,7••,8•]. CSE is more common
I Pediatric Neurology

Table 1. Common etiologies of status epilepticus neurologic abnormality. A Finnish study included only
in children and incidences from population- patients with afebrile SE and found that more than half
based studies of those with SE experienced recurrent SE [12]. The risk
Acute for recurrent afebrile SE in this study was 13.1% at 1 year
and 16.9% at 2 years [12]. In a Minnesota population-
Acute symptomatic (17%–52%)
based study combining all ages, one-third of individuals
Acute CNS infection (bacterial meningitis, viral experienced a second episode of SE, with the risk doubled
meningitis, encephalitis)
for those with progressive symptomatic etiology and for
Metabolic derangement (hypoglycemia, hyperglycemia, female patients [15•].
hyponatremia, hypocalcemia, anoxic injury) Future epilepsy, focal neurologic deficits, cognitive
AED noncompliance or withdrawal impairment, and behavioral problems may be associated
AED overdose with CSE. However, specific risk factors in the pediatric
Non-AED/drug overdose population have not yet been reported [6]. In patients
with cryptogenic SE, a significant portion of infants went
Prolonged febrile convulsion (23%–30%)
on to develop West syndrome or mental deficiency, most
Influenza because of an underlying neurologic disorder [8•].
Exanthem subicum A devastating epileptic encephalopathy, which begins
Remote (16%–39%) with intractable SE evolving over days to weeks and per-
sists as bilateral temporal lobe pharmaco-resistant epilepsy,
Cerebral migrational disorders (lissencephaly, schizencephaly)
has become increasingly recognized in children. The main
Cerebral dysgenesis features include 1) onset in previously healthy school-aged
Perinatal hypoxic-ischemic encephalopathy children; 2) an initial febrile context but no evidence of
Progressive neurodegenerative disorders intracranial infection; 3) onset with prolonged intractable
SE followed by intractable epilepsy without any latent period
Idiopathic/cryptogenic (5%–19%)
in between; 4) clinical and electroencephalogram (EEG) fea-
AED—antiepileptic drug; CNS—central nervous system.
tures of focal seizure onset during both SE and follow-up,
primarily in the perisylvian areas; 5) bilateral mesial tem-
than NCSE, occurring in as much as 86% of patients [8•]. poral dysfunction on neuropsychological tests with atrophy
Table 1 lists the common etiologies of SE in children that and/or in hypersignal on MRI; and 6) frontal lobe involve-
should be considered in each case. ment in half of the cases. The morbidity of this devastating
Between four and eight children per 1000 are expected encephalopathy, more commonly known as fever-induced
to experience CSE before age 15 years [5••]. The most epileptic encephalopathy in school-aged children (FIRES),
common risk factor for SE in children is a prior history consists of severe memory, language, and behavior troubles
of SE [10,11]. Other common risk factors for pediatric SE with permanent cognitive sequelae [16••].
include a younger age, a symptomatic etiology, and a his- In a population-based study of adults and children, the
tory of an epileptic encephalopathy or a specific epilepsy rate of fatalities ranged from 7.6% to 22% and showed
syndrome. Common in the adult population, noncompli- a bimodal distribution, with young children and elderly
ance with antiepileptic drugs (AEDs) is not as common patients experiencing the greatest mortality from CSE. Age
a risk factor for children [11,12]. In children who have was the only significant predictor of in-hospital death fol-
no history of previous SE, the risk of SE decreased with lowing generalized CSE [9]. The mortality rate in pediatric
increasing age. In children who have a previous history SE ranges from 0% to 7% [5••,7••,12]. Children with acute
of SE, patients with symptomatic epilepsy have a higher or remote symptomatic CSE are associated with the high-
risk. Children who have had a questionable episode of SE est mortality during hospitalization [7••]. Death due to SE
before the diagnosis of epilepsy are more likely to have SE is most often due to the underlying cause, such as central
during the follow-up [11]. Karasalihoglu et al. [13] sug- nervous system infection or severe neurologic disabilities.
gested that SE is more likely to appear in children who Some have associated SE as a direct cause of death, regard-
have had a partial seizure evolving to a secondarily gener- less of the underlying etiology [12,15•]. The relatively low
alized seizure or in those with myoclonic seizures. 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-
Morbidity and Mortality agement, and evolving AED therapy [5••].
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 Nonconvulsive Status Epilepticus
[7••] and was 18% at 2 years [14]. Both studies included NCSE is an important subtype of SE, but it is difficult
children with a fi rst febrile episode of SE and reported an to identify and treat. It is defi ned as an EEG-recorded
increased risk for recurrence associated with a preexisting ictal episode, continuous or recurrent, for greater than
Status Epilepticus in Children
I Singh and Gaillard
I 139

30 minutes without improvement in clinical state or EEG fi ndings in NCSE are more variable, including
return to a preictal EEG pattern between seizures. In 49 typical and atypical spike and wave, multiple or polyspike
admissions of 43 patients in a neurointensive care unit, discharges, and a rhythmic sharp delta pattern [19•].
23 patients were found to be in NCSE [17]. Seventy-six Abnormal EEG patterns such as periodic lateralized epi-
percent of patients had a history of a clinical seizure pre- leptiform discharges, generalized periodic epileptiform
ceding NCSE, and 25% were de novo [17]. Mortality of discharges, and burst suppression patterns were seen in
NCSE in this combined adult–pediatric study was 57% those patients with NCSE who required prolonged EEG
and was strongly linked to duration of NCSE and delay monitoring [18]. In a recent pediatric study, most ictal
of diagnosis of NCSE [17]. In a large hospital-based EEGs showed a focal distribution of discharges [19•].
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 Treatment of Status Epilepticus
state on neurologic examination, age younger than 18 Acute status epilepticus
years, a past medical history of epilepsy, and a convul- Benzodiazepines are recommended as the initial drug of
sive seizure prior to monitoring [18]. choice for treating SE. Intravenous (IV) diazepam was
The incidence of NCSE in pediatric patients undergoing developed first, followed by IV lorazepam. IV diazepam
long-term monitoring in the intensive care setting ranges has a more rapid onset of activity, whereas IV lorazepam
from 16% to 32% [19•,20,21••]. Tay et al. [19•] found has a longer duration of antiseizure effect. In the past, when
that half of these children had preexisting epilepsy, with IV diazepam was administered as the first-line medication,
common causes including an exacerbation of the underly- a second AED was often required because breakthrough
ing metabolic disorder or an acute infection. The overall seizures would develop. With the development of rectal
mortality rate of NCSE was 26% [19•]. Median duration diazepam, there seems to be less risk of breakthrough
lasted from 48 to 56 hours. More than one-fourth of the seizures. However, there are no published pediatric head-
pediatric patients were less than 1 year of age [19•,21••]. to-head comparison trials of the benzodiazepines.
Most studies in adults have shown that NCSE is often Most studies for the acute treatment of SE have been
due to an acute or remote central nervous system insult in the adult population. The Veterans Affairs Status Epi-
(eg, stroke, anoxic-ischemic encephalopathy, intracere- lepticus Cooperative Study [24], a multicentered adult
bral hemorrhage). However, most children with NCSE trial, evaluated four different treatment modalities for
are previously healthy and have no preexisting disease SE: 1) diazepam then phenytoin, 2) lorazepam, 3) phe-
[19•,21••]. The availability of prolonged EEG monitoring nobarbital, or 4) phenytoin. Of the 570 patients who
has allowed increased recognition of this condition. Rec- met inclusion criteria, 395 (69%) were in SE. In a pair-
ommendations for monitoring include any patient with wise comparison, lorazepam was significantly superior
unexplained or protracted impairment of consciousness, to phenytoin but not to the combination of diazepam
comatose state on neurologic examination, or altered then phenytoin or phenobarbital alone. Among the 134
behavior after a recognized seizure [17]. patients with a verified diagnosis of NCSE, there were
no significant differences among the treatments [24].
Adult studies have also evaluated out-of-hospital
EEG Findings in Status Epilepticus treatment for SE. In a randomized double-blinded trial,
Treiman et al. [22] initially described five identifiable EEG patients were given either 5 mg of diazepam repeated to
patterns that occurred in a predictable sequence during a maximum of 10 mg, 2 mg of lorazepam repeated to a
the course of secondarily generalized CSE in adults. The maximum of 4 mg, or placebo. Primary outcome was ter-
stages were 1) EEG changes of discrete seizures with inter- mination of SE by the time of arrival to the emergency
ictal slowing; 2) merging seizures with waxing and waning department. Secondary outcome measures included
ictal discharges; 3) continuous ictal discharges; 4) contin- out-of-hospital complications, complications during treat-
uous ictal discharges with “flat” periods; and 5) periodic ment, duration of SE prior to arrival at the hospital, and
epileptiform discharges on a “flat” background [22]. In a neurologic outcome at discharge. The study found IV
primarily adult retrospective review, focal interictal epi- benzodiazepines to be safe and effective when adminis-
leptiform discharges were most common during routine tered by paramedics. Lorazepam and diazepam were both
and digital video EEG, with the latter more commonly more effective than placebo, with a trend favoring loraz-
detecting electrographic seizures. Other patterns included epam over diazepam. However, between 41% and 57% of
periodic lateralized epileptiform discharges, burst sup- patients who received active therapy were still in SE upon
pression, and generalized spike-and-wave discharges [23]. arrival to the hospital [25]. In 45 episodes of generalized
Generalized background abnormalities were also com- CSE in 38 children, prehospital treatment with diaz-
mon in patients with CSE [13]. After the resolution of SE, epam was associated with a shorter duration of SE (32
epileptiform discharges were significantly more common minutes vs 60 minutes) compared with lorazepam, with
in the remote symptomatic and cryptogenic groups than a decreased risk of recurrent seizures in the emergency
in the acute symptomatic group [8•]. department (58% vs 85%) [26].
I Pediatric Neurology

In a retrospective pediatric study in the United Kingdom with acute repetitive seizures, only one had further seizures
evaluating pre–intensive care unit treatment of SE, either after valproic acid infusion, with transient tremor as an
diazepam or lorazepam was the most commonly adminis- adverse effect in one patient [32]. In a relatively large study
tered first-line AED, but the dose was frequently lower than of intravenous valproic acid in children in SE, 78% of the
that recommended. Children who had prehospital treatment patients who were refractory to initial standard therapy
were more likely to receive more than two doses of benzodi- responded to valproic acid, and in most cases the response
azepine, and those who had prehospital treatment were also was very rapid [33]. Sixty-five percent of these patients
more likely to have respiratory depression [27]. responded immediately (within 2–6 minutes). The remain-
Traditionally, based on long-term clinical experience ing 10% responded within 3 to 10 minutes. Loading doses
and case-control studies, IV phenytoin has been used as ranged from 20 to 40 mg/kg, with the highest success rate
the second-line drug for SE [28••]. A dose of 18 mg/kg of being from 30 to 40 mg/kg [33]. Valproic acid, along with
phenytoin given over 20 minutes through an IV peripheral the newer anticonvulsants discussed in the following text,
line is recommended, with additional bolus to maximize may eventually move to replace phenytoin as second-line
the total dose to 25 mg/kg [24]. Fosphenytoin is a prodrug therapy for SE. Table 2 summarizes suggested medications
of phenytoin (150 mg of fosphenytoin is equivalent to 10 for acute and refractory SE.
mg of phenytoin) with 100% bioavailability. Although
there are limited adult and pediatric efficacy data on the Refractory status epilepticus
use of fosphenytoin, the drug’s practical benefits include a More than 90% of all convulsive seizures end spontane-
reduced risk and incidence of serious extravasation reac- ously within the first 5 minutes. As the time of initiation of
tions, hypotension, and cardiac dysrhythmias. Although therapy for SE with benzodiazepines increases, the efficacy
it is more expensive and not routinely available in most of these medications decreases [12]. The most accepted def-
hospitals worldwide, it may eventually replace phenytoin inition of refractory SE is when a seizure continues despite
as the long-acting anticonvulsant of choice [29]. the administration of two or more first-line medications
Phenobarbital may also be used as a second-line agent [5••]. Others have characterized the duration to refractory
or as an alternative to phenytoin when a benzodiazepine SE (RSE) as lasting greater than 60 minutes [34,35••,36•].
has failed. The initial dose for SE may range from 15 to High-dose pentobarbital, or pentobarbital coma,
20 mg/kg in children, with a maintenance dosage of 3 to has commonly been used in the intensive care unit for
4 mg/kg per day. However, the dose of phenobarbital to RSE, and this requires continuous EEG for monitoring
be recommended is not as precisely determined as other burst suppression. It is generally given as a bolus dose
AEDs. Very high-dose phenobarbital, without reference of 5 to 15 mg/kg followed by a maintenance infusion
to a predetermined maximum dose or serum level, has of 1 to 5 mg/kg per hour. Although it is effective in
also been used to treat refractory SE. Adverse effects of terminating seizures, pentobarbital administration is
the higher dose include a marked and prolonged sedative associated with hypotension, myocardial depression,
effect, with depression of respiratory drive and hypoten- and low cardiac output. It is also a potent respiratory
sion at higher doses [30]. depressant, often requiring endotracheal intubation
Combined adult and pediatric randomized trials have and mechanical ventilation [35••].
suggested the favorability of valproic acid over phenytoin. More recently, midazolam has been suggested as a
In a randomized trial of age- and sex-matched groups fi rst-line therapy in RSE. In a retrospective multicenter
comparing IV valproic acid with IV phenytoin, IV valproic study, 76% of patients treated with midazolam achieved
acid was found to be as effective as IV phenytoin and was clinical seizure control within 30 minutes of treatment
more tolerable [28••]. Similarly, Misra et al. [31•] looked at initiation [35••]. Midazolam was eventually success-
seizure control with either loading phenytoin at 18 mg/kg ful in treating 15 seizure episodes (88%). Relapse after
at an infusion rate of 50 mg/min or valproic acid at 30 discontinuation of therapy occurred in one patient (6%),
mg/kg over 15 minutes. Valproic acid was more effective and there were no significant adverse effects [35••].
than phenytoin in controlling CSE, both as the first (66% Morrison et al. [36•] recently developed a high-dose
vs 42%) and as the second choice (79% vs 25%). VPA as a midazolam algorithm with an emphasis on rapid seizure
second choice terminated SE more frequently (79%) than control. The bolus dose was 0.5 mg/kg followed by an
phenytoin (25%) [31•]. However, this study did not com- infusion of 2 μg/kg per minute up to 24 μg/kg per min-
pare the maximum dose of valproic acid to the maximum ute and reaching as high as 32 μg/kg per minute. Of 17
equivalent dose of phenytoin (25 mg/kg). patients admitted to the pediatric intensive care unit who
Valproic acid has also been effective in pediatric ret- followed this algorithm, 15 patients were controlled and
rospective studies. In a retrospective review of 40 patients remained seizure free for 12 to 24 hours on midazolam
loaded with valproic acid, 20 of whom had SE, rapid load- prior to weaning. The remaining two patients could not
ing at 25 mg/kg at a rate of 3 mg/kg per minute stopped be controlled with midazolam therapy and required the
seizures in 18 (90%) patients with SE within 20 minutes administration of sodium thiopentone [36•].
[32]. All 18 patients regained baseline mental status within Brevoord et al. [37] retrospectively reviewed four dif-
1 hour of seizure cessation. Among the other 22 patients ferent treatment modalities in the cessation of generalized
Status Epilepticus in Children
I Singh and Gaillard
I 141

Table 2. Potential options for pharmacologic treatment of status epilepticus

Medication Dose Rate Adverse effects
Acute status epilepticus
Lorazepam 0.1–0.15 mg/kg IV < 2 mg/min Hypotension, respiratory depression,
depressed level of consciousness
Diazepam 0.3 mg/kg IV, IV over 2–5 min to Hypotension, respiratory depression,
0.5–0.7 mg/kg rectal prevent apnea depressed level of consciousness
Phenytoin 20 mg/kg up to 25 mg/kg IV 50 mg/min Hypotension, cardiac arrhythmias
Fosphenytoin 15–20 mg/kg up to 150 mg PE/min Hypotension, cardiac arrhythmias
25 mg/kg PE IV
Phenobarbital 15–20 mg/kg up to 1 mg/kg/min (maximum Hypotension, respiratory depression,
30 mg/kg or serum 2 mg/kg/min in child, depressed level of consciousness
concentration 15–45 mg/L 100 mg/min in adult)
Valproate (remains 20 mg/kg IV then 6 mg/kg/min Hypotension, fatal hepatoxicity
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 Hypotension, respiratory depression,
or to effect depressed level of consciousness
Midazolam 0.15–0.3 mg/kg load, Respiratory depression
1–18 μg/kg/h or to effect (less common)
Phenobarbital (high Dosing twice daily Respiratory depression but
dose) to achieve increased develop tolerance
serum concentration
(up to 70 mg/L)
Pentobarbital 2–10 mg/kg load* Cardiac suppression, hyoptension,
up to 20 mg/kg† then poor cardiac output, immune
0.5–5 mg/kg/h or to effect suppression, respiratory depression
Propofol 3–5 mg/kg load then Propofol infusion syndrome in children
1–15 mg/kg/h or to effect
Levetiracetam 20 mg/kg load then Sedation, irritability
(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 Metabolic acidosis
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, Anesthetic treatment of refractory status epilepticus
2) phenytoin bolus, 3) phenytoin bolus followed by a versed Various anesthetics have been administered in adult and
continuous infusion, or 4) phenobarbital/pentobarbital pediatric SE. Propofol has been administered for RSE and
bolus and infusion. Most of the patients (68%) had initially has been shown to terminate clinical seizures, but the qual-
received rectal diazepam. Cessation of epileptic activity ity of burst suppression has been variable [38•]. However,
was achieved with midazolam only in 58 patients (48%); case reports of propofol infusion syndrome in children,
with midazolam and phenytoin in 19 patients (15%); with characterized by metabolic acidosis, lipemic serum, and
midazolam, phenytoin, and continuous midazolam in 32 bradyarrhythmia leading to progressive myocardial failure,
patients (26%); and with additional barbiturates in 13 make this a less desirable option [39]. Within minutes of
patients (11%) [37]. initiating therapy, the inhalational anesthetic isoflurane,
I Pediatric Neurology

accompanied by desflurane when necessary, stops epilep- to control the seizures and prevent the progressive cognitive
tic discharges with sustained burst suppression [40]. In a decline that accompanies the disease. Neurosurgical inter-
pediatric retrospective study, propofol was more safe and vention may also be considered in the rare case of medically
effective than thiopental in controlling RSE (64% vs 55%, refractory SE. Emergent epilepsy surgery in 10 children
respectively) [41]. In the past and in certain cases, other with focal epileptogenesis successfully stopped SE, and all
anesthetics, including paraldehyde and lidocaine, along patients showed significant improvement during follow-up
with the ketogenic diet, have been used in treating RSE. [49]. In a retrospective analysis of patients receiving epi-
lepsy surgery, 20% were in continuous SE or intermittent
Emerging pharmacotherapy SE. All of these patients had extratemporal localization of
Newer studies suggest that both levetiracetam and the epilepsy, and most (86%) of these patients underwent
topiramate may have promise in RSE in the future. hemispherectomy [50]. In a 4-year period at two tertiary
Since 1999, levetiracetam has been prescribed world- referral epilepsy centers, five pediatric patients were treated
wide as adjunctive therapy for partial-onset seizures in successfully with neurosurgery for SE. The seizures were
adults and in children older than 4 years of age. Most fully controlled in four patients, and in the fifth patient the
analyses have been in the adult population. Patel et al. seizure frequency was reduced by more than 90% [51••].
[42•] found that in six patients (including children and
adolescents) with SE refractory to at least two AEDs,
adjunctive levetiracetam proved effective in several Conclusions
types of SE, including generalized, focal, and NCSE. SE is a common medical emergency in pediatrics.
Effective doses of levetiracetam ranged from 500 to Advances in prolonged EEG monitoring have allowed
3000 mg/d, and seizure control was achieved within for increased recognition of NCSE in children. Because
12 to 96 hours [42•]. Rosetti and Bromfi eld [43] found there is increasing evidence that SE may be treated better
that levetiracetam administered together with other with earlier intervention, the defi nition of SE is evolving,
AEDs represented 10% of the cohort of patients with with an emphasis on shortening the duration of seizure
SE. As its pharmacokinetic profi le is very promising, activity. A significant percentage of patients who present
levetiracetam may represent a valuable alternative to with their fi rst seizure may present in SE. In the pediatric
the existing treatment of SE [43]. In 2007 the paren- population, the prolonged febrile convulsion should be
teral form of administration became available, allowing identified distinctly from the acute symptomatic group
earlier administration. The injectable formulation because of the distinct differences in prognosis and neu-
of levetiracetam has proven to be well tolerated and rologic outcomes. Patients at greatest risk, especially
exhibits similar pharmacokinetics to oral formulations, those with a history of prior SE, should be identified
broadening its clinical application [44]. early. Rectal diazepam should be made available to
Topiramate, a sulfamate-substituted monosaccha- caregivers for out-of-hospital treatment of SE. Benzodi-
ride, is a broad-coverage antiepileptic drug available azepines are still viewed as a fi rst-line medication, with
only in the parenteral form. Topiramate administered phenytoin, fosphenytoin, and phenobarbital following as
via nasogastric tube at doses between 300 and 1600 second-line medications. Valproic acid and midazolam
mg/d in six adults effectively terminated RSE in gen- loading and maintenance doses may be tolerable and
eralized CSE and NCSE [45]. In the case of infantile more efficacious at higher concentrations. Newer phar-
spasms, topiramate may be rapidly titrated or loaded macotherapies, including topiramate and levetiracetam,
without severe adverse effects [46]. Kahriman et al. [47] may prove more advantageous for acute and refractory
retrospectively reported on three children with pediat- SE in the future. Although neurosurgical treatment is
ric RSE who responded to rapidly titrated nasogastric never viewed as a fi rst- or second-line therapy, it should
topiramate at a daily dose of 5 to 6 mg/kg. Topiramate be considered in patients with RSE, but only in those
was initiated at 2 to 5 mg/kg per day and titrated up with focal epileptogenesis or epilepsia partialis conti-
to 22 to 25 mg/kg per day in children with partial nua. The future of successful SE treatment lies within
SE refractory to phenobarbital, phenytoin, and mid- evidence-based guidelines derived from out-of-hospital
azolam. Rapid titration to a very high total daily dose and in-hospital therapies, along with controlled studies
via nasogastric tube was well tolerated and allowed for in pediatric populations that target specifi c etiologies.
the successful taper to other AEDs [48]. Future studies should focus on the need to standardize
the treatment of convulsive emergencies to shorten the
Neurosurgical interventions for status epilepticus duration of in-hospital or intensive care unit stay, which
Rasmussen’s encephalitis is a rare childhood disease char- will ultimately decrease morbidity and mortality.
acterized by the triad of the development of intractable
focal seizures with epilepsia partialis continua, progressive
hemiparesis, and increasing intellectual impairment with Disclosures
inflammation of the brain and progressive atrophy of one No potential confl icts of interest relevant to this article
cerebral hemisphere. Hemispherectomy is often considered were reported.
Status Epilepticus in Children
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I 143

References and Recommended Reading 19.• Tay SK, Hirsch LJ, Leary L, et al.: Nonconvulsive status
epilepticus in children: clinical and EEG characteristics.
Papers of particular interest, published recently, Epilepsia 2006, 47:1503–1509.
have been highlighted as: This study shows that nonconvulsive SE in children occurs in previ-
• Of importance ously healthy children with EEG characteristic of focal discharges.
20. Abend NS, Dlugos DJ: Nonconvulsive status epilepticus
•• Of major importance in a pediatric intensive care unit. Pediatr Neurol 2007,
1. Shorvon S: The concept of status epilepticus and its history. 21.•• Saengpattrachai M, Sharma R, Hunjan A, et al.: Nonconvul-
In Status Epilepticus: Its Clinical Features and Treatment sive seizures in the pediatric intensive care unit: etiology, EEG,
in Children and Adults. Cambridge: Cambridge University and brain imaging findings. Epilepsia 2006, 47:1510–1518.
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I Pediatric Neurology

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