Annals of Indian Academy of Neurology
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Year : 2007  |  Volume : 10  |  Issue : 5  |  Page : 7-18

Convulsive status epilepticus in children

Neurosciences Unit, UCL-Institute of Child Health, London; Epilepsy Unit, Great Ormond Street Hospital for Children NHS Trust, London; The National Center for Young People with Epilepsy, Lingfield, United Kingdom

Correspondence Address:
Rod C Scott
Neurosciences Unit, UCL - Institute of Child Health. The Wolfson Center, Mecklenburgh Square, London WC1N 2AP
United Kingdom
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Source of Support: None, Conflict of Interest: None

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Convulsive status epilepticus (CSE) is the most common neurological emergency in childhood. It differs from adult CSE in aspects of epidemiology, pathophysiology and clinical presentations, which justifies a separate analysis. The incidence is 18-20/100,000 children/year and distribution of aetiologies is markedly age-dependent: Febrile and acute symptomatic CSE are most common in children aged <2 years, whereas cryptogenic-idiopathic and remote symptomatic aetiologies are more common in older children.
Mortality is 3-5% and morbidity directly attributable to CSE is less than 15%. When compared to brief seizures, the incidence of subsequent epilepsy is increased only in symptomatic goups. Aetiology is the main determinant of outcome, while the separate effect on outcome of duration, age and treatment remains controversial. The risk of sequelae in unprovoked and febrile CSE is low. There is some evidence that CSE, especially febrile CSE, might cause hippocampal injury, although its role in the development of mesial temporal sclerosis remains uncertain. Prolonged seizures lasting over 5-10 minutes are unlikely to stop spontaneously and should be treated as CSE. Prehospital administration of benzodiazepines is safe and simplifies subsequent management of CSE in the hospital setting. Treatment includes resuscitation measures, identification and treatment of causal factors and early antiepileptic treatment following local guidelines that may be based on national guidelines.

Keywords: Children, epilepsy, outcome, status epilepticus, treatment

How to cite this article:
Raspall-Chaure M, Scott RC. Convulsive status epilepticus in children. Ann Indian Acad Neurol 2007;10, Suppl S1:7-18

How to cite this URL:
Raspall-Chaure M, Scott RC. Convulsive status epilepticus in children. Ann Indian Acad Neurol [serial online] 2007 [cited 2022 Jan 28];10, Suppl S1:7-18. Available from:

   Introduction Top

Status epilepticus (SE) is a common condition in acute medical care. Approximately 4.5 million SE events occur worldwide every year and, in the United States, the cost of care of SE has been estimated at $3-4 billion/year.[1] The number of studies that are annually published on SE has steadily increased during the last few years and >50% out of the over 5000 currently Medline-indexed studies on SE have been published during the last decade. But despite the socioeconomic burden of SE and the interest among the medical community, many questions concerning its pathogenesis, management and outcome remain unanswered.

While some features of SE are common to all age groups, there are specific epidemiological, pathophysiological and clinical presentations in childhood that differ from that in adult populations and thus will be emphasized during the current review. We will focus on pediatric convulsive SE (CSE) as nonconvulsive SE and neonatal SE are separate disorders with differing epidemiology, clinical presentation and prognosis and deserve study in their own right.

   Definition Top

The ILAE 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 baseline central nervous system function",[2],[3] but has not set a temporal criterion in its last revised proposal of terminology as has previously been the case. Most studies use the 30 min duration criteria, which may demarcate the transition point at which SE may become self-sustaining, pharmacoresistance may have developed and seizure-induced neuronal injury may take place.[4]

This 30 min definition is obviously inappropriate as a guide for treatment. Consequently, "operational" definitions with durations ranging from 5 to 20 minutes have been proposed, i.e., a time when the patient should be treated as having CSE, even if such patient is not in established CSE (see below).[5],[6] Operational definitions are necessary for research studies evaluating the efficacy of antiepileptic drugs (AEDs) and match the widely accepted practice of treating patients with prolonged seizures well before the seizure has lasted 30 min.

There are strong statistical arguments for using a shorter duration operational criterion i.e., five minutes. Mean duration of generalised tonic-clonic seizures in adults is 62 seconds[7] and mean duration of complex partial seizures in children is 97 seconds.[8] Seizure duration in children with new-onset seizures shows a biexponential distribution: 3.6 minutes in one group (76% of cases) versus 31 minutes in the other (24%).[9] Children who have seizures lasting more than five minutes are very likely to be in the latter group.


From a clinical point of view, SE can be classified into as many types as there are epileptic seizure categories.[10] In the most recent ILAE revision of the classification of seizures and epilepsy syndrome, a distinction between generalized and focal SE is made [Table - 1].[3]

From a practical viewpoint, it is classically separated into convulsive and nonconvulsive status epilepticus as a result of marked differences regarding aetiology, management and outcome.[11] However, the term "non-convulsive status epilepticus" is falling out of favour and is no longer included in the ILAE's revision of classification and terminology since it comprises dissimilar conditions (i.e ., focal limbic SE and generalised absence SE), which also differ in aetiology, management and outcome.[3]

According to aetiology, CSE can be grossly classified into provoked (including the febrile and the acute symptomatic aetiologies) and unprovoked CSE (including the idiopathic-cryptogenic, remote symptomatic and progressive aetiologies) [Table - 2].[12]

   Epidemiology Top

Most epidemiological studies of CSE have been primarily or exclusively based on adult populations and their results may not reflect a reliable characterisation of CSE in childhood.[13] To our knowledge, only one purely pediatric prospective population-based study addressing the epidemiology of CSE has been published.[14]

Overall estimated incidence is 18-20/100000 children/year. The incidence is highest during the first year of life (51/100000 children/year) and subsequently declines (2/100000 children/year in children 10-15 years-old).[14]

CSE in childhood is more commonly seen as the first manifestation of seizure disorders than later in life, especially in younger children[15] and when CSE does not occur in the first few years of the epilepsy, it is less likely to occur at a later date.[16] In a prospective study that followed children with a first unprovoked seizure, 12% of children were seen with CSE as their first unprovoked seizure. After a mean follow-up of 6.3 years, only 1% of the children with a recurrence following an initial brief seizure met criteria for CSE in the recurrent event.[17],[18]

The spectrum of aetiologies in childhood CSE differs markedly to that in adult populations. Febrile CSE occurs in about 5% of patients with febrile seizures[19],[20] and it is the most common form of CSE in childhood, accounting for 25-40% of all cases. Children with progressive disorders represent <10% of patients, with the remaining cases being approximately equally distributed among the idiopathic-cryptogenic, acute symptomatic and remote symptomatic categories. However, the distribution of aetiologies is markedly age-dependent: in children younger than two years, febrile CSE and acute symptomatic aetiologies are most common, whereas cryptogenic and remote symptomatic aetiologies are more common in the older children. The reported effect of age on outcome may, at least in part, be determined by this uneven distribution of aetiologies.[12],[14],[21],[22],[23],[24],[25]

Duration is commonly reported to be a function of aetiology, with >60% of acute symptomatic cases lasting >1 hour.[26],[27] However, a recent population-based study did not find significant differences in seizure duration between aetiological groups.[14]

Children with preexisting neurological abnormalities or prior episodes of CSE are at highest risk of experiencing an episode of CSE. Neurologically abnormal children are more susceptible to develop seizures in general and CSE in particular. In a general epilepsy population, 30% of children are expected to be neurologically abnormal although this proportion is lower in children with first unprovoked seizures. In contrast, >40% of children with CSE are neurologically abnormal prior to the episode.[15]

Finally, epidemiology of CSE may be influenced by genetic, ethnic and socioeconomic factors. The role of genetic factors is clear in some genetically determined epilepsy syndrome (i.e., Dravet syndrome and febrile CSE; ring chromosome 20 and non-convulsive status epilepticus)[28],[29],[30] and twin studies suggest that there might also be some still unrecognized genetic predisposition to CSE in many other individuals.[31] There is some evidence that incidence of CSE is higher in non-white ethnic groups.[32] Whether perceived ethnicitiy effects are influenced by socioeconomic factors is currently being investigated in a prospective pediatric population-based study in children with CSE (Chin et al. , personal communication).

   Pathophysiology Top

Most of our understanding of the pathophysiology of CSE is from animal models rather than from observations in humans. Seizures are usually pharmacologically or electrically induced in adult animals and therefore we must be cautious about extrapolating these experimental findings to spontaneous and prolonged seizures in childhood.

CSE initiation requires neurons with intrinsic burst generation, failure or loss of inhibition surrounding the abnormally firing neurons and then spread, synchronization and maintenance of a discharge. It is likely that seizure initiation is caused by an imbalance between excitatory and inhibitory neurotransmission. The extracellular concentration of the excitatory neurotransmitter glutamate increases at the site of the seizure focus at the beginning of seizure activity.[33] With increasing seizure length, inhibitory GABAA receptors are internalized from synaptic membranes to endosomes, where they are inactive, leading to the failure of the inhibitory systems.[34] At the same time, N-methyl-D-aspartate (NMDA) and a-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors are recruited to synaptic membranes were they form functional receptors. These mechanisms may underlie the observed refractoriness to treatment with GABA-acting medications observed during refractory CSE and, in some animal models, improved responsiveness to NMDA antagonists with increasing duration of CSE.[35],[36] Both excessive excitatory neurotransmission and failure of inhibition are closely related, i.e., decreased GABAA receptor function has been observed to be dependent on NMDA receptor activation.

The initial systemic effects of a generalized tonic clonic seizure are dominated by the body's attempt to maintain homeostasis and include increase in cerebral blood flow, blood glucose and oxygen utilization. After 30-60 minutes homeostatic failure begins, as cerebral blood flow and thus brain glucose supply and parenchymal oxygenation, all decrease. Respiratory and metabolic acidosis, cardiac arryhthmias, electrolyte imbalance, hyperthermia and rhabdomyolysis may all occur.[37],[38] Furthermore, many of the AEDs used in CSE have depressant cardiorespiratory side effects and may worsen the systemic effects of CSE. However, neuronal damage associated with CSE has been reported in the absence of systemic complications such as hypotension, hypoxemia or hypoglycemia.[39]

   CSE and Brain Damage Top

CSE can result in permanent brain damage. There is pathological evidence of acute changes in the hippocampus, amygdala, thalamus, basal ganglia, cerebellum and neocortex, although pathological descriptions in humans are limited to case reports.[39],[40] Two recent series using diffusion weighted images have also shown prominent white matter abnormalities in children with febrile CSE who subsequently develop neurological sequelae.[41],[42] The knowledge of the basic mechanisms underlying brain damage and acquired epilepsy associated with CSE is essential for developing novel strategies to prevent neuronal injury (i.e., neuroprotective therapies) and the development of epilepsy following CSE (i.e., antiepileptogenic therapies).

The hypothesis that cell damage is mediated by glutamate excitotoxicity is the most widely accepted.[43] Excessive activation of NMDA glutamate receptors leads to an increase of intracellular calcium,[44] which underlies the basis for calcium second-messenger effects on both cell death and neuronal plasticity in survival neurons.[45] A high level of intracellular calcium generates reactive oxygen species, uncouples oxidative phosphorylation and activates a wide range of enzymes that collectively have adverse consequences for cell function.

Although seizures can induce changes in multiple brain regions, the hippocampus seems particularly vulnerable to seizure-induced damage. In animal models, CSE causes neuronal loss in hippocampal fields CA1 and CA3, the dentate granule cell layer and the dentate hilus, as well as sprouting of mossy fibers.[46] In humans, it has long been hypothesized that CSE (and in particular febrile CSE) can cause mesial temporal sclerosis (MTS) and associated temporal lobe epilepsy. Retrospective studies from tertiary epilepsy centres highlight this association, with a history of febrile CSE being present in 35-63% of patients with MTS.[47],[48],[49],[50] However, neither population-based nor prospective hospital-based studies report a significant association between CSE in childhood and subsequent MTS.[51],[52],[53] Although febrile CSE has been associated with increased incidence of subsequent partial seizures, the structural basis for these seizures has not been characterized.[20],[23]

Prospective MRI-based studies have tried to further characterize the relationship between febrile CSE and MTS. Hippocampal asymmetry consistent with hippocampal oedema, identified using hippocampal volumetry, was first reported in 4/15 children following a prolonged and lateralized febrile seizure.[54] Subsequently, another group found symmetrical large hippocampal volumes and prolongation of hippocampal T 2 relaxation times in patients investigated within 48h of febrile CSE, also consistent with hippocampal oedema.[55] Follow-up investigations on the latter patient population after four to eight months demonstrated a reduction both in hippocampal volumes and in T 2 relaxation times, with significant increase in hippocampal volume asymmetry when compared with the initial data supporting the view that febrile CSE can cause hippocampal damage. Length of follow-up was insufficient to detect if any of the patients developed temporal lobe epilepsy.[56]

Genetic factors may also play a role on the pathogenesis of CSE-related MTS. A higher frequency of interleukin-1β-511T allele occurrence in patients with temporal lobe epilepsy associated with MTS has been reported, with the maximum increase in the allele frequency being observed in patients with a previous episode of febrile CSE.[57],[58] Additionally, homozygosity for a low expression allele for dynorphin was shown to be strongly associated with CSE, while heterozygosity was associated with familial temporal lobe epilepsy, implying a common genetic link between the allele, CSE and temporal lobe epilepsy.[59]

   CSE and the Immature Brain Top

The seizure threshold appears to be lower in the immature brain although the mechanisms that underlie this increased susceptibility remain unclear. Several developmental factors might be responsible for the higher frequency of CSE in childhood: 1) Excitatory synapses mature earlier than inhibitory synapses and this, coupled with an increase in the susceptibility of excitatory neurotransmitter receptors, increases the likelihood that an excitation-inhibition imbalance may occur, 2) Stimulation of GABAA receptors in the immature brain results in depolarization rather than hyperpolarization, as occurs in the adult brain and 3) The immature cerebral cortex has a high synaptic density at around two months of age and this may contribute to the development of hypersynchrony of neural groups.[60]

Current evidence suggest that seizures can damage the developing brain.[61],[62],[63],[64] However, while experimental studies show that the immature brain is more prone to develop seizures and CSE, they also show that the developing brain may be more resistant to the toxic effects of glutamate and to CSE-induced damage, at least in terms of MTS-like pathology.[64] Despite the experimental evidence, clinical evidence is sparse.[46]

   Clinical Characteristics Top

Generalized CSE is the most frequent, dramatic and life-threatening form of SE. It may present either as a series of generalized tonic clonic seizures without intervening recovery (i.e., intermittent CSE) or as a continuous seizure, which is usually clonic in nature (i.e., continuous CSE). The latter type is especially common in children and it is noted in 40-80% of cases.[11] In children with intermittent CSE, generalized tonic clonic seizures usually last from one to three minutes. They tend to become briefer as time elapses and the clonic phase may disappear. Other forms of CSE (i.e. myoclonic, tonic, etc) are much less frequent.

Both clinical and EEG progression during CSE has been observed. Proposed clinical stages include:[65]

  1. Premonitory (prodromal). This usually manifests as confusion, myoclonus or increasing seizure frequency (i.e., serial seizures).
  2. Incipient (0 to 5 minutes)
  3. Early stage (5 to 30 minutes)
  4. Late or Established stage (30 to 60 minutes)
  5. Refractory stage (60 to 90 minutes). Definitions of refractory CSE vary in terms of the number of AEDs (2 or 3) that must be employed before CSE is considered refractory;[66],[67] others define refractory CSE on the basis of its duration (usually 60 minutes).[68],[69] Refractory CSE may only manifest as "subtle" generalized CSE. 14% of adults treated for generalized CSE will continue to have electroencephalographic seizure activity after cessation of clinical signs of convulsive activity.[70] The proportion of children with clinically controlled CSE but persisting electrical seizure activity is unknown.
  6. Postictal stage. Postictal (and interictal) neurological signs may include unilateral or bilateral Babinski responses, hyperreflexia and hemiplegia. Hemiconvulsion-Hemiplegia syndrome was reported in 11-19% of children with febrile CSE in older studies.[22],[71] It's incidence has considerably declined over the past 20 years in developed countries, probably due to improvement in treatment. A minimum duration of hemiplegia is arbitrarily set at seven days to separate it from the more common postictal or Todd paralysis.[72]

Treiman et al. has also distinguished five successive EEG stages in adults[73] and animal models, which are more or less correlated with the clinical stages: 1) discrete seizures with interictal slowing, 2) waxing and waning of ictal discharges, 3) continuous ictal discharges, 4) continuous ictal discharges punctuated by flat periods and 5) periodic epileptiform discharges on a flat background.

   Outcome Top

CSE is associated with significant mortality and morbidity. Aetiology is the main determinant of outcome and there is still much controversy as to which other factors such as age, duration, treatment or CSE itself, modify the outcome. Much of the controversy arises from the methodological differences of the studies that have addressed this topic.[74],[75],[76] The impact of these non-biological variables on reported outcomes of pediatric CSE was recently investigated in a systematic review. According to its results, prospective design and overall better methodological quality were associated with better outcome.[77]


Short-term mortality following CSE, i.e., that occurring during hospital admission or during the first 30-60 days from seizure onset, is 2.7-5.2%. Most deaths occur in children with acute symptomatic or progressive aetiologies and may not be attributable to the CSE itself.[12],[25],[68],[78],[79],[80] Mortality directly attributable to CSE, as that observed with unprovoked CSE or febrile CSE, is 0-2%, compared to 12.5-16% in children with acute symptomatic CSE.[12],[81],[82],[83] Particularly high mortality is seen with some acute symptomatic aetiologies such as anoxia[84] or meningoencephalitis.[25]

A correlation between younger age at CSE and higher mortality has been reported,[22],[81],[85] with studies on CSE occurring in the first one to two years of life, reporting mortality rates of 3-22.5%.[81],[86],[87],[88] However, this relationship may only reflect the higher incidence of acute symptomatic CSE in this age group. Similarly, a direct relationship between longer duration of CSE and higher mortality is also frequently reported[32],[89],[89],[90],[91] although the effect of duration is difficult to separate form aetiology.[92] One meta-analysis concluded that the overall mortality in children treated for refractory generalized CSE was 16%,[93] but it was not possible to rule out the contribution of potential selection bias, i.e most studies were retrospective and hospital-based. Additionally, the studies included for review did not correct for the severity of the underlying aetiology (which is acute symptomatic CSE in >60% cases of refractory CSE).[94]

Long-term mortality data after a first-ever episode of CSE range from 5.4% to 17% and is significantly increased only among children with symptomatic aetiologies.[16],[23],[95],[96]

Subsequent epilepsy

The overall risk of subsequent unprovoked seizures two years following a first-ever unprovoked episode of CSE is 25-40%,[12],[24] which is similar to the 37% reported risk following a brief first unprovoked seizure.[18],[97] However, this effect is dominated by children with acute symptomatic aetiologies or previous neurological abnormalities in whom more than 50% will develop epilepsy.[12],[23],[85],[98]

Data on epilepsy following febrile CSE are controversial and much of the variability of estimates arises from differences in inclusion criteria. Those studies that include children with prior neurological abnormalites reveal that, when compared to brief febrile seizures, the risk following febrile CSE is not different in neurologically normal children but it is significantly increased (38%) in those with prior neurological abnormalities.[53],[83] Nelson et al. reported that 4.1% of children with first febrile seizure as febrile CSE developed epilepsy, which is significantly higher than in the normal population, but did not reach statistical significance when compared to children who had brief febrile seizures.[19] In contrast, Verity et al found a significantly greater risk of developing afebrile seizures in children with febrile CSE compared with children with brief febrile seizures (21% vs 3.4%; x 2 9.77; P <0.005).[23]

The risk of seizure recurrence is highest during the first year following CSE and tends to decrease with increasing interval from the index seizure.[18],[99] The impact of early treatment on the prevention or course of epilepsy remains largely unknown and the current recommendation of not starting long-term treatment after a first unprovoked CSE is based on the reported low impact of CSE on the risk of recurrence.[12]

   Recurrence Top

Overall recurrence of CSE is 20% at four years and 70% of recurrences occur within one to two years of the initial episode of CSE.[16],[100] Recurrence is low in febrile CSE and idiopathic CSE (<4%) and increases in the acute symptomatic, remote symptomatic and progressive groups (11%, 44% and 67% respectively). Children with pre-existing neurological abnormalities and prior history of CSE are at highest risk of recurrent CSE. Most neurologically abnormal children are receiving AEDs at the time of recurrence.[12],[79],[95],[100],[101]

Association with neurological, developmental, cognitive and behavioral impairments

In addition to epilepsy, focal neurological deficits, cognitive impairment and behavioural problems can be associated with CSE although consistent specific risk factors for each of these complications are not reported.

The poorest outcome is observed in acute symptomatic CSE, which is followed by new neurological dysfunction in >20% of cases.[12],[24],[98] In the absence of an acute or progressive neurological disorder, morbidity of CSE is low and <15% of children with febrile CSE and unprovoked CSE develop new neurological deficits attributable to CSE.[12],[24],[27],[98],[102] However, low power and lack of detailed neurocognitive assessment might have underestimated the incidence of minor sequelae in most of the studies.

Other factors that are reported to influence the outcome are longer duration and younger age at onset. As mentioned above, the poorer outcome observed in refractory CSE and in young children might be only explained by the greater incidence of acute symptomatic CSE in these groups.[103]

   Management Top

General principles

Most generalized tonic clonic seizures will stop spontaneously, often within five min, before the child arrives in the emergency department. Children that present to an emergency department with a generalized tonic clonic seizure are likely to be having a seizure that it is unlikely to stop spontaneously and which will ultimately meet the definition of CSE. Therefore, for practical (or operational) purposes, the approach in these circumstances should be the same as that with the child who is in established CSE.

CSE is an emergency and the fact that aetiology emerges as the most powerful predictor of outcome should not be read as meaning that interventions may not alter that outcome. The main objectives of treatment, which should be addressed simultaneously, are:

a) Support of vital functions.

b) Termination of seizure .

c) Identification and treatment of causal or precipitating factors.

a) Support of vital functions

Treatment should follow the ABC principles of resuscitation in order to maintain airway, ventilation-oxygenation and blood pressure. High flow oxygen should be given and continuous monitoring of vital signs, EKG and pulse oximetry are recommended.

The underlying aetiology, the seizure itself or the treatment can all contribute to complications from CSE. Careful diagnosis and management of such complications, i.e., hypotension, hypoxemia, hyperthermia or hypoglycemia, is essential throughout the course of CSE. Maintaining cerebral blood flow and thereby adequate supply of oxygen and glucose to the brain are as important as reducing cerebral metabolic needs by restricting seizures and hyperthermia.

b) Termination of seizure

The deleterious effects of seizure duration remain controversial and there is no documented clinical evidence that early seizure control prevents neurologic sequelae or improves outcome. However, experimental evidence suggests that this should be true. It is believed that early pharmacological intervention leads to termination of seizures with smaller doses than would be required if seizures were allowed to progress.[104] As previously discussed, experimental data show time-dependent loss of synaptic GABAA receptors and thus of GABA-mediated inhibition, which correlates with the progressive pharmacological resistance to GABAergic medication observed in refractory CSE.[34],[36]

The feasibility of early treatment with transmucosal benzodiazepines, i.e., rectal diazepam and buccal or nasal midazolam or lorazepam, has been addressed in several randomized controlled studies both in the pre-hospital and hospital settings.[105],[106],[107],[108],[109],[110],[111],[112],[113],[114],[115],[116],[117] Most have provided positive results regarding both efficacy (i.e., shortening the duration of CSE and simplified subsequent management in the emergency department) and safety (i.e., lack of respiratory depression) in both settings.[118] However, the risk of respiratory depression is higher when more than two doses of benzodiazepines are administered and prehospital benzodiazepine administration should be taken into account during further treatment.[119] Early administration of transmucosal benzodiazepines is especially advisable in that population of patients with a tendency to have prolonged seizures.

The risk-benefit ratio for antiepileptic treatments is one of the biggest challenges in seizure management. As a general rule, the intensity of the treatment should reflect the risk to the patient from CSE. The ideal AED should be available for intravenous administration, efficacious, with a rapid and long-lasting effect and lack of major side effects. Clearly none of the current AEDs meets all these characteristics [Table - 3].

The optimum pharmacological therapeutic scheme for CSE needs to be further defined by controlled trials. Published studies are typically observational, describing the efficacy of single agents. Only a few controlled, double-blind, clinical studies of treatment of CSE have been published and none has been conducted in children.[120],[121],[122] Because of the paucity of randomized controlled trials, treatment protocols vary enormously from hospital to hospital. Implementation of institutional treatment protocols based on national guidelines is recommended as this helps avoid unnecessary delays in starting treatment. Simply adopting a protocol (irrespective of the detail within the protocol) has itself been shown to reduce mortality and morbidity.[123] Although there is evidence about the individual efficacy of most of the drugs included, none of the recommended protocols has been shown to be better than any other. Thus, the treatment protocol suggested in the [Figure - 1] should be simply read as a proposal that may be modified locally.

Initial AED treatment should start within the first 5-10 minutes of seizure onset with a benzodiazepine, which can be repeated after five to ten min if seizure persists. In the hospital setting the intravenous route is the first choice and rectal or buccal medications should only be administered where there is failure to secure an intravenous access. Lorazepam is the preferred agent, as its duration is longer than for diazepam or midazolam, which minimizes the risk of relapse.[124] However, the superiority of lorazepam over other benzodiazepines in children has not yet been demonstrated.[125]

If a seizure fails to respond to two doses of benzodiazepines, most protocols will recommend administration of phenytoin, which is usually preferred to phenobarbitone at this stage as it causes less respiratory and central nervous system depression. Some authors advice the administration of a long-acting AED even when seizures cease following benzodiazepine administration so as to avoid seizure recurrence when the benzodiazepine is eliminated. Phenytoin infusion can only be made up in 0.9% saline and at a maximum concentration of 10 mg/mL. It should be infused at no more than 1 mg/kg/min because of the risk of hypotension and cardiac arrythmias associated with faster administration.[126] Such complications are in part attributable to its 40% propylene glycol diluent. Fosphenytoin is a prodrug of phenytoin, which is rapidly converted to phenytoin after either intravenous or intramuscular injection. Fosphenytoin is freely soluble in aqueous solutions, does not require organic solvents and does not precipitate in commonly used intravenous diluents. It can be infused up to three times more rapidly than phenytoin (i.e., 3 mg/kg/min), although the time to peak brain concentration is almost identical.[127] Potential benefits of fosphenytoin include reduced local and systemic adverse effects.[128],[129]

Sodium valproate is a nonsedating AED that does not cause respiratory depression or hypotension even if administered to critically ill patients.[130],[131] Although it is being increasingly included into therapeutic protocols, its efficacy in CSE is yet to be formally characterized. Lidocaine is another nonsedating agent which has been shown effective in CSE and in particular in infantile convulsions with mild diarrhea.[132] The antiepileptic action of the drug is transient and a continuous infusion is usually necessary to avoid seizure recurrence.[133] Paraldehyde is included in some protocols although there are limited published data on its efficacy. Intramuscular paraldehyde stopped 61% of seizures in a recent open randomized trial in children and was not associated with clinically important cardiorespiratory events.[113] Although the efficacy of rectal paraldehyde is not supported by any randomized trial, it is still included in some pediatric guidelines, mainly in the United Kingdom.[126]

Intravenous pyridoxine 100 mg should be administered to all children below two years with cryptogenic CSE as soon as possible during the course of CSE if the rare diagnosis of pyridoxine-dependent seizures is not to be missed.[11],[134]

If seizure persists following phenytoin (or any of the proposed alternatives), rapid sequence induction of anesthesia with either thiopentone or pentobarbital is commonly recommended. Propofol and midazolam infusions have been proposed as alternative AED in this situation based on a more favorable side effects profile.[69],[135],[136],[137] However, some studies reporting fatal cases of propofol infusion syndrome (i.e., metabolic acidosis, rhabdomyolysis and bradycardia) have limited the use of propofol in children.[138] Additionally, a systematic review of studies involving only adult populations found pentobarbital superior to propofol or midazolam in seizure control.[139] Other agents that have been used include clonazepam, lorazepam, ketamine or inhalation anesthetics. Exceptionally, children with focal abnormalities might be amenable to surgical treatment if CSE persists or recurs when treatment is withdrawn. At experienced centers, these children might be at lower risk of morbidity than by having prolonged high-dose suppressive therapy.[140] Furthemore, seizure outcome after surgery in children presenting with CSE may not be altered when compared with other epilepsy surgery patients.[141]

It is suggested that aiming for background suppression, as opposed to simply seizure termination, is associated with less breakthrough seizures (4% vs 53%) and better control of refractory CSE.[139] Reported optimal interburst intervals ranging from 5 to 30 seconds are proposed as an endpoint of titration.[36],[65] If neuromuscular paralysis is used this should be short acting so as not to mask the clinical signs of the convulsion. Treatment is usually withdrawn after 24h of seizure control and resumed if CSE recurs.

At this stage, the endpoint of treatment should be individualized. In previously normal children with refractory idiopathic or febrile CSE, it should aim to achieve complete seizure control and return to baseline status. However, this may not be a reasonable objective in children with acute symptomatic or progressive aetiologies with breakthrough seizures on every attempt to withdraw the high-dose suppressive therapy, in whom subsequent epilepsy and significant morbidity is almost the rule. In these cases, the realization that a seizure-free state is unlikely can lead to a shorter duration of suppressive therapy with eventually the same outcome but fewer complications.

The neuroprotective and antiepileptogenic role of several AEDs has been investigated in animals but none has been found to completely protect against neuronal injury nor to prevent the development of spontaneous recurrent seizures.[142],[143],[144],[145],[146]

c) Identification and treatment of causal or precipitating factors

Management of CSE includes identification and treatment of the underlying cause. In the absence of an obvious aetiology, blood glucose, blood gases and electrolytes (including sodium, calcium and magnesium) should be tested and any metabolic derangement should be corrected. However, the diagnostic assessment should not delay treatment and clinicians should be able to diagnose CSE on clinical grounds alone.

In general, an EEG, neuroimaging or other laboratory studies are not needed before the initiation of anticonvulsant therapy. If available, indications for emergency EEG include:[147]

  • Clinical impression of pseudoseizures presenting as CSE
  • Unexplained altered awareness or no improvement or return to baseline of mental status after controlling overt convulsive movements (to exclude ongoing seizure electroencephalographic activity).
  • Neuromuscular paralysis.
  • High-dose suppressive therapy for refractory CSE.

The incidence of bacterial meningitis among young children with CSE and fever is reported to be 12-17%, which is siginificantly higher than the 1.2% incidence in those with short seizures and fever.[14] However, central nervous system infections are an overlooked cause of CSE in infants and young children with fever, as the classical symptoms and signs of bacterial meningitis may be absent in this age group. Therefore, a high index of suspicion for meningitis in the child with CSE with fever is paramount and lumbar puncture and early parenteral antibiotics are advisable.[148] Conversely, the possibility of cerebrospinal fluid pleocytosis as a direct consequence of CSE has been reported both in adults[149],[150] and children.[151]

Finally, clinicians should be familiar with the causes of intractable seizures or CSE in their geographic setting (i.e. tuberculous meningitis, malaria or neurocysticercosis are important causes of CSE in some parts of the world).[147]

Thus, CSE is a common and potentially dangerous disorder that deserves appropriate treatment following a guideline. Recent advances in functional neuroimaging, genomic investigation and prospective human data are likely to increase our knowledge of seizure induced injury, which will hopefully lead to improved algorithms for prevention and treatment of CSE.

   References Top

1.DeLorenzo RJ. Epidemiology and clinical presentation of status epilepticus. Adv Neurol 2006;97:199-215.  Back to cited text no. 1  [PUBMED]  
2.Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde BW, Engel J, Jr. Glossary of descriptive terminology for ictal semiology: Report of the ILAE task force on classification and terminology. Epilepsia 2001;42:1212-8.  Back to cited text no. 2    
3.Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42:796-803.  Back to cited text no. 3    
4.Chen JW, Wasterlain CG. Status epilepticus: Pathophysiology and management in adults. Lancet Neurol 2006;5:246-56.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Lowenstein DH. Status epilepticus: An overview of the clinical problem. Epilepsia 1999;40:S3-8.  Back to cited text no. 5    
6.Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia 1999;40:120-2.  Back to cited text no. 6  [PUBMED]  
7.Theodore WH, Porter RJ, Albert P, Kelley K, Bromfield E, Devinsky O, et al . The secondarily generalized tonic-clonic seizure: A videotape analysis. Neurology 1994;44:1403-7.  Back to cited text no. 7  [PUBMED]  
8.Holmes GL. Partial complex seizures in children: An analysis of 69 seizures in 24 patients using EEG FM radiotelemetry and videotape recording. Electroencephalogr Clin Neurophysiol 1984;57:13-20.  Back to cited text no. 8  [PUBMED]  
9.Shinnar S, Berg AT, Moshe SL, Shinnar R. How long do new-onset seizures in children last? Ann Neurol 2001;49:659-64.  Back to cited text no. 9  [PUBMED]  
10.Gastaut H. Clinical and electroencephalographical classification of epileptic seizures. Epilepsia 1970;11:102-13.  Back to cited text no. 10  [PUBMED]  
11.Arzimanoglou A, Guerrini R, Aicardi J. Status epilepticus. Aicardi's epilepsy in children. 3rd ed. Lippincot Williams and Williams: Philadelphia; 2004. p. 241-61.  Back to cited text no. 11    
12.Maytal J, Shinnar S, Moshe SL, Alvarez LA. Low morbidity and mortality of status epilepticus in children. Pediatrics 1989;83:323-31.  Back to cited text no. 12    
13.Chin RF, Neville BG, Scott RC. A systematic review of the epidemiology of status epilepticus. Eur J Neurol 2004;11:800-10.  Back to cited text no. 13    
14.Chin RF, Neville BG, Peckham C, Bedford H, Wade A, Scott RC, et al. Incidence, cause and short-term outcome of convulsive status epilepticus in childhood: Prospective population-based study. Lancet 2006;368:222-9.  Back to cited text no. 14    
15.Shinnar S, Pellock JM, Moshe SL, Maytal J, O'Dell C, Driscoll SM, et al . In whom does status epilepticus occur: Age-related differences in children. Epilepsia 1997;38:907-14.  Back to cited text no. 15    
16.Sillanpaa M, Shinnar S. Status epilepticus in a population-based cohort with childhood-onset epilepsy in Finland. Ann Neurol 2002;52:303-10.  Back to cited text no. 16    
17.Shinnar S, Berg AT, Moshe SL, Petix M, Maytal J, Kang H, et al . Risk of seizure recurrence following a first unprovoked seizure in childhood: A prospective study. Pediatrics 1990;85:1076-85.  Back to cited text no. 17    
18.Shinnar S, Berg AT, Moshe SL, O'Dell C, Alemany M, Newstein D, et al . The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: An extended follow-up. Pediatrics 1996;98:216-25.  Back to cited text no. 18    
19.Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978;61:720-7.  Back to cited text no. 19    
20.Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med 1987;316:493-8.  Back to cited text no. 20    
21.Phillips SA, Shanahan RJ. Etiology and mortality of status epilepticus in children: A recent update. Arch Neurol 1989;46:74-6.  Back to cited text no. 21    
22.Aicardi J, Chevrie JJ. Convulsive status epilepticus in infants and children. A study of 239 cases. Epilepsia 1970;11:187-97.  Back to cited text no. 22    
23.Verity CM, Ross EM, Golding J. Outcome of childhood status epilepticus and lengthy febrile convulsions: Findings of national cohort study. BMJ 1993;307:225-8.  Back to cited text no. 23    
24.Eriksson KJ, Koivikko MJ. Status epilepticus in children: Aetiology, treatment and outcome. Dev Med Child Neurol 1997;39:652-8.  Back to cited text no. 24    
25.Lacroix J, Deal C, Gauthier M, Rousseau E, Farrell CA. Admissions to a pediatric intensive care unit for status epilepticus: A 10-year experience. Crit Care Med 1994;22:827-32.  Back to cited text no. 25    
26.Yager JY, Cheang M, Seshia SS. Status epilepticus in children. Can J Neurol Sci 1988;15:402-5.  Back to cited text no. 26    
27.Dunn DW. Status epilepticus in children: Etiology, clinical features and outcome. J Child Neurol 1988;3:167-73.  Back to cited text no. 27    
28.Augustijn PB, Parra J, Wouters CH, Joosten P, Lindhout D, van Emde Boas W. Ring chromosome 20 epilepsy syndrome in children: Electroclinical features. Neurology 2001;57:1108-11.  Back to cited text no. 28    
29.Inoue Y, Fujiwara T, Matsuda K, Kubota H, Tanaka M, Yagi K, et al . Ring chromosome 20 and nonconvulsive status epilepticus. A new epileptic syndrome. Brain 1997;120:939-53.  Back to cited text no. 29    
30.Nabbout R, Dulac O. Epileptic encephalopathies: A brief overview. J Clin Neurophysiol 2003;20:393-7.  Back to cited text no. 30    
31.Corey LA, Pellock JM, Boggs JG, Miller LL, DeLorenzo RJ. Evidence for a genetic predisposition for status epilepticus. Neurology 1998;50:558-60.  Back to cited text no. 31    
32.DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, et al . A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996;46:1029-35.  Back to cited text no. 32    
33.During MJ, Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 1993;341:1607-10.  Back to cited text no. 33    
34.Kapur J, Stringer JL, Lothman EW. Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition. J Neurophysiol 1989;61:417-26.  Back to cited text no. 34    
35.Mazarati AM, Wasterlain CG. N-methyl-D-asparate receptor antagonists abolish the maintenance phase of self-sustaining status epilepticus in rat. Neurosci Lett 1999;265:187-90.  Back to cited text no. 35    
36.Dhar R, Mirsattari SM. Current approach to the diagnosis and treatment of refractory status epilepticus. Adv Neurol 2006;97:245-54.  Back to cited text no. 36    
37.Fountain NB, Lothman EW. Pathophysiology of status epilepticus. J Clin Neurophysiol 1995;12:326-42.  Back to cited text no. 37    
38.Lothman E. The biochemical basis and pathophysiology of status epilepticus. Neurology 1990;40:13-23.  Back to cited text no. 38    
39.Fujikawa DG, Itabashi HH, Wu A, Shinmei SS. Status epilepticus-induced neuronal loss in humans without systemic complications or epilepsy. Epilepsia 2000;41:981-91.  Back to cited text no. 39    
40.Nixon J, Bateman D, Moss T. An MRI and neuropathological study of a case of fatal status epilepticus. Seizure 2001;10:588-91.  Back to cited text no. 40    
41.Okamoto R, Fujii S, Inoue T, Lei K, Kondo A, Hirata T, et al . Biphasic clinical course and early white matter abnormalities may be indicators of neurological sequelae after status epilepticus in children. Neuropediatrics 2006;37:32-41.  Back to cited text no. 41    
42.Takanashi J, Oba H, Barkovich AJ, Tada H, Tanabe Y, Yamanouchi H, et al . Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy. Neurology 2006;66:1304-9.  Back to cited text no. 42    
43.Holmes GL. Seizure-induced neuronal injury: Animal data. Neurology 2002;59:S3-6.  Back to cited text no. 43    
44.Pal S, Sombati S, Limbrick DD Jr, DeLorenzo RJ. In vitro status epilepticus causes sustained elevation of intracellular calcium levels in hippocampal neurons. Brain Res 1999;851:20-31.  Back to cited text no. 44    
45.DeLorenzo RJ, Sun DA, Deshpande LS. Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintainance of epilepsy. Pharmacol Ther 2005;105:229-66.  Back to cited text no. 45    
46.Haut SR, Veliskova J, Moshe SL. Susceptibility of immature and adult brains to seizure effects. Lancet Neurol 2004;3:608-17.  Back to cited text no. 46    
47.Cendes F. Febrile seizures and mesial temporal sclerosis. Curr Opin Neurol 2004;17:161-4.  Back to cited text no. 47    
48.Cendes F, Andermann F, Dubeau F, Gloor P, Evans A, Jones-Gotman M, et al . Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures and temporal lobe epilepsy: An MRI volumetric study. Neurology 1993;43:1083-7.  Back to cited text no. 48    
49.Murakami N, Ohno S, Oka E, Tanaka A. Mesial temporal lobe epilepsy in childhood. Epilepsia 1996;37:52-6.  Back to cited text no. 49    
50.Trinka E, Unterrainer J, Haberlandt E, Luef G, Unterberger I, Niedermuller U, et al . Childhood febrile convulsions-which factors determine the subsequent epilepsy syndrome? A retrospective study. Epilepsy Res 2002;50:283-92.  Back to cited text no. 50    
51.Tarkka R, Paakko E, Pyhtinen J, Uhari M, Rantala H. Febrile seizures and mesial temporal sclerosis: No association in a long-term follow-up study. Neurology 2003;60:215-8.  Back to cited text no. 51    
52.Berg AT, Shinnar S, Levy SR, Testa FM. Childhood-onset epilepsy with and without preceding febrile seizures. Neurology 1999;53:1742-8.  Back to cited text no. 52    
53.Camfield P, Camfield C, Gordon K, Dooley J. What types of epilepsy are preceded by febrile seizures? A population-based study of children. Dev Med Child Neurol 1994;36:887-92.  Back to cited text no. 53    
54.VanLandingham KE, Heinz ER, Cavazos JE, Lewis DV. Magnetic resonance imaging evidence of hippocampal injury after prolonged focal febrile convulsions. Ann Neurol 1998;43:413-26.  Back to cited text no. 54    
55.Scott RC, Gadian DG, King MD, Chong WK, Cox TC, Neville BG, et al . Magnetic resonance imaging findings within 5 days of status epilepticus in childhood. Brain 2002;125:1951-9.  Back to cited text no. 55    
56.Scott RC, King MD, Gadian DG, Neville BG, Connelly A. Hippocampal abnormalities after prolonged febrile convulsion: A longitudinal MRI study. Brain 2003;126:2551-7.  Back to cited text no. 56    
57.Kanemoto K, Kawasaki J, Miyamoto T, Obayashi H, Nishimura M. Interleukin (IL)1beta, IL-1alpha and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy. Ann Neurol 2000;47:571-4.  Back to cited text no. 57    
58.Kanemoto K, Kawasaki J, Yuasa S, Kumaki T, Tomohiro O, Kaji R, et al . Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis and prolonged febrile convulsion. Epilepsia 2003;44:796-9.  Back to cited text no. 58    
59.Stogmann E, Zimprich A, Baumgartner C, ull-Watschinger S, Hollt V, Zimprich F. A functional polymorphism in the prodynorphin gene promotor is associated with temporal lobe epilepsy. Ann Neurol 2002;51:260-3.  Back to cited text no. 59    
60.Schwartzkroin P. Epilepsy: Models, mechanisms and concepts. Cambridge University Press: Cambridge; 1993.  Back to cited text no. 60    
61.Miller SP, Weiss J, Barnwell A, Ferriero DM, Latal-Hajnal B, Ferrer-Rogers A, et al . Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology 2002;58:542-8.  Back to cited text no. 61    
62.Cherubini E, Ben-Ari Y, Krnjevic K. Anoxia produces smaller changes in synaptic transmission, membrane potential and input resistance in immature rat hippocampus. J Neurophysiol 1989;62:882-95.  Back to cited text no. 62    
63.Holmes GL, Khazipov R, Ben-Ari Y. Seizure-induced damage in the developing human: Relevance of experimental models. Prog Brain Res 2002;135:321-34.  Back to cited text no. 63    
64.Liu Z, Stafstrom CE, Sarkisian M, Tandon P, Yang Y, Hori A, et al . Age-dependent effects of glutamate toxicity in the hippocampus. Brain Res Dev Brain Res 1996;97:178-84.  Back to cited text no. 64    
65.Riviello JJ Jr, Holmes GL. The treatment of status epilepticus. Semin Pediatr Neurol 2004;11:129-38.  Back to cited text no. 65    
66.Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001;57:1036-42.  Back to cited text no. 66    
67.Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998;338:970-6.  Back to cited text no. 67    
68.Ozdemir D, Gulez P, Uran N, Yendur G, Kavakli T, Aydin A. Efficacy of continuous midazolam infusion and mortality in childhood refractory generalized convulsive status epilepticus. Seizure 2005;14:129-32.  Back to cited text no. 68    
69.van Gestel JP, Blusse van Oud-Alblas HJ, Malingre M, Ververs FF, Braun KP, van NO. Propofol and thiopental for refractory status epilepticus in children. Neurology 2005;65:591-2.  Back to cited text no. 69    
70.DeLorenzo RJ, Waterhouse EJ, Towne AR, Boggs JG, Ko D, DeLorenzo GA, et al . Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998;39:833-40.  Back to cited text no. 70    
71.Viani F, Beghi E, Romeo A, van Lierde A. Infantile febrile status epilepticus: Risk factors and outcome. Dev Med Child Neurol 1987;29:495-501.  Back to cited text no. 71    
72.Arzimanoglou A, Guerrini R, Aicardi J. Aicardi's epilepsy in children. 3rd ed. Lippincot Williams and Williams: Philadelphia; 2004.  Back to cited text no. 72    
73.Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res 1990;5:49-60.  Back to cited text no. 73    
74.Logroscino G, Hesdorffer DC. Methodologic issues in studies of mortality following epilepsy: Measures, types of studies, sources of cases, cohort effects and competing risks. Epilepsia 2005;46:3-7.  Back to cited text no. 74    
75.Hauser WA. Status epilepticus: Frequency, etiology and neurological sequelae. Adv Neurol 1983;34:3-14.  Back to cited text no. 75    
76.Drislane FW. Who's afraid of status epilepticus? Epilepsia 2006;47:7-9.  Back to cited text no. 76    
77.Raspall-Chaure M, Chin RF, Neville BG, Scott RC. Outcome of paediatric convulsive status epilepticus: A systematic review. Lancet Neurol 2006;5:769-79.  Back to cited text no. 77    
78.Brevoord JC, Joosten KF, Arts WF, van Rooij RW, de Hoog M. Status epilepticus: Clinical analysis of a treatment protocol based on midazolam and phenytoin. J Child Neurol 2005;20:476-81.  Back to cited text no. 78    
79.Kwong KL, Lee SL, Yung A, Wong VC. Status epilepticus in 37 Chinese children: Aetiology and outcome. J Paediatr Child Health 1995;31:395-8.  Back to cited text no. 79    
80.Mah JK, Mah MW. Pediatric status epilepticus: A perspective from Saudi Arabia. Pediatr Neurol 1999;20:364-9.  Back to cited text no. 80    
81.Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA. Short-term mortality after a first episode of status epilepticus. Epilepsia 1997;38:1344-9.  Back to cited text no. 81    
82.Maegaki Y, Kurozawa Y, Hanaki K, Ohno K. Risk factors for fatality and neurological sequelae after status epilepticus in children. Neuropediatrics 2005;36:186-92.  Back to cited text no. 82    
83.Maytal J, Shinnar S. Febrile status epilepticus. Pediatrics 1990;86:611-6.  Back to cited text no. 83    
84.Scholtes FB, Renier WO, Meinardi H. Status epilepticus in children. Seizure 1996;5:177-84.  Back to cited text no. 84    
85.Kwong KL, Chang K, Lam SY. Features predicting adverse outcomes of status epilepticus in childhood. Hong Kong Med J 2004;10:156-9.  Back to cited text no. 85    
86.Cavazzuti GB, Ferrari P, Lalla M. Follow-up study of 482 cases with convulsive disorders in the first year of life. Dev Med Child Neurol 1984;26:425-37.  Back to cited text no. 86    
87.Chevrie JJ, Aicardi J. Convulsive disorders in the first year of life: Neurological and mental outcome and mortality. Epilepsia 1978;19:67-74.  Back to cited text no. 87    
88.Tabarki B, Yacoub M, Selmi H, Oubich F, Barsaoui S, Essoussi AS. Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects. Seizure 2001;10:365-9.  Back to cited text no. 88    
89.DeLorenzo RJ, Garnett LK, Towne AR, Waterhouse EJ, Boggs JG, Morton L, et al . Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia 1999;40:164-9.  Back to cited text no. 89    
90.Gulati S, Kalra V, Sridhar MR. Status epilepticus in Indian children in a tertiary care center. Indian J Pediatr 2005;72:105-8.  Back to cited text no. 90    
91.Waterhouse EJ, Garnett LK, Towne AR, Morton LD, Barnes T, Ko D, et al . Prospective population-based study of intermittent and continuous convulsive status epilepticus in Richmond, Virginia. Epilepsia 1999;40:752-8.  Back to cited text no. 91    
92.Waterhouse EJ, Vaughan JK, Barnes TY, Boggs JG, Towne AR, Kopec-Garnett L, et al . Synergistic effect of status epilepticus and ischemic brain injury on mortality. Epilepsy Res 1998;29:175-83.  Back to cited text no. 92    
93.Gilbert DL, Gartside PS, Glauser TA. Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: A meta-analysis. J Child Neurol 1999;14:602-9.  Back to cited text no. 93    
94.Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Risk of unprovoked seizure after acute symptomatic seizure: Effect of status epilepticus. Ann Neurol 1998;44:908-12.  Back to cited text no. 94    
95.Berg AT, Shinnar S, Testa FM, Levy SR, Frobish D, Smith SN, et al . Status epilepticus after the initial diagnosis of epilepsy in children. Neurology 2004;63:1027-34.  Back to cited text no. 95    
96.Logroscino G, Hesdorffer DC, Cascino GD, Annegers JF, Bagiella E, Hauser WA. Long-term mortality after a first episode of status epilepticus. Neurology 2002;58:537-41.  Back to cited text no. 96    
97.Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: A quantitative review. Neurology 1991;41:965-72.  Back to cited text no. 97    
98.Barnard C, Wirrell E. Does status epilepticus in children cause developmental deterioration and exacerbation of epilepsy? J Child Neurol 1999;14:787-94.  Back to cited text no. 98    
99.Hauser WA anderson VE, Loewenson RB, McRoberts SM. Seizure recurrence after a first unprovoked seizure. N Engl J Med 1982;307:522-8.  Back to cited text no. 99    
100.Shinnar S, Maytal J, Krasnoff L, Moshe SL. Recurrent status epilepticus in children. Ann Neurol 1992;31:598-604.  Back to cited text no. 100    
101.Novak G, Maytal J, Alshansky A, Ascher C. Risk factors for status epilepticus in children with symptomatic epilepsy. Neurology 1997;49:533-7.  Back to cited text no. 101    
102.Shinnar S, Pellock JM, Berg AT, O'Dell C, Driscoll SM, Maytal J, et al . Short-term outcomes of children with febrile status epilepticus. Epilepsia 2001;42:47-53.  Back to cited text no. 102    
103.Kim SJ, Lee DY, Kim JS. Neurologic outcomes of pediatric epileptic patients with pentobarbital coma. Pediatr Neurol 2001;25:217-20.  Back to cited text no. 103    
104.Mazarati AM, Baldwin RA, Sankar R, Wasterlain CG. Time-dependent decrease in the effectiveness of antiepileptic drugs during the course of self-sustaining status epilepticus. Brain Res 1998;814:179-85.  Back to cited text no. 104    
105.Alldredge BK, Wall DB, Ferriero DM. Effect of prehospital treatment on the outcome of status epilepticus in children. Pediatr Neurol 1995;12:213-6.  Back to cited text no. 105    
106.Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: A randomised trial. Lancet 1999;353:623-6.  Back to cited text no. 106    
107.Dieckmann RA. Rectal diazepam for prehospital pediatric status epilepticus. Ann Emerg Med 1994;23:216-24.  Back to cited text no. 107    
108.Kapur J. Prehospital treatment of status epilepticus with benzodiazepines is effective and safe. Epilepsy Curr 2002;2:121-4.  Back to cited text no. 108    
109.Wiznitzer M. Buccal midazolam for seizures. Lancet 2005;366:182-3.  Back to cited text no. 109    
110.Camfield PR. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: A randomized trial. J Pediatr 1999;135:398-9.  Back to cited text no. 110    
111.Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs Rectal diazepam in acute childhood seizures. Pediatr Neurol 2006;34:355-9.  Back to cited text no. 111    
112.McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al . Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: A randomized controlled trial. Lancet 2005;366:205-10.  Back to cited text no. 112    
113.Ahmad S, Ellis JC, Kamwendo H, Molyneux E. Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: An open randomised trial. Lancet 2006;367:1591-7.  Back to cited text no. 113    
114.Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, et al . Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: Prospective randomized study. J Child Neurol 2002;17:123-6.  Back to cited text no. 114    
115.Dreifuss FE, Rosman NP, Cloyd JC, Pellock JM, Kuzniecky RI, Lo WD, et al . A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med 1998;338:1869-75.  Back to cited text no. 115    
116.Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav 2004;5:253-5.  Back to cited text no. 116    
117.Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: Prospective randomised study. BMJ 2000;321:83-6.  Back to cited text no. 117    
118.Scott RC. Buccal midazolam as rescue therapy for acute seizures. Lancet Neurol 2005;4:592-3.  Back to cited text no. 118    
119.Chin RF, Verhulst L, Neville BG, Peters MJ, Scott RC. Inappropriate emergency management of status epilepticus in children contributes to need for intensive care. J Neurol Neurosurg Psychiatry 2004;75:1584-8.  Back to cited text no. 119    
120.Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, et al . A comparison of lorazepam, diazepam and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001;345:631-7.  Back to cited text no. 120    
121.Leppik IE, Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983;249:1452-4.  Back to cited text no. 121    
122.Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al . A comparison of four treatments for generalized convulsive status epilepticus. Veterans affairs status epilepticus cooperative study group. N Engl J Med 1998;339:792-8.  Back to cited text no. 122    
123.Shepherd SM. Management of status epilepticus. Emerg Med Clin North Am 1994;12:941-61.  Back to cited text no. 123    
124.Prasad K, Al-Roomi K, Krishnan PR, Sequeira R. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev 2005;CD003723.  Back to cited text no. 124    
125.Appleton R, Martland T, Phillips B. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev 2002;CD001905.  Back to cited text no. 125    
126.Appleton R, Choonara I, Martland T, Phillips B, Scott R, Whitehouse W. The treatment of convulsive status epilepticus in children. The Status Epilepticus Working Party, Members of the Status Epilepticus Working Party. Arch Dis Child 2000;83:415-9.  Back to cited text no. 126    
127.Wang X, Patsalos PN. A comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin. Seizure 2003;12:330-6.  Back to cited text no. 127    
128.Pellock JM. Fosphenytoin use in children. Neurology 1996;46:S14-6.  Back to cited text no. 128    
129.Ramsay RE, DeToledo J. Intravenous administration of fosphenytoin: Options for the management of seizures. Neurology 1996;46:S17-9.  Back to cited text no. 129    
130.Uberall MA, Trollmann R, Wunsiedler U, Wenzel D. Intravenous valproate in pediatric epilepsy patients with refractory status epilepticus. Neurology 2000;54:2188-9.  Back to cited text no. 130    
131.Yu KT, Mills S, Thompson N, Cunanan C. Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures. Epilepsia 2003;44:724-6.  Back to cited text no. 131    
132.Okumura A, Uemura N, Negoro T, Watanabe K. Efficacy of antiepileptic drugs in patients with benign convulsions with mild gastroenteritis. Brain Dev 2004;26:164-7.  Back to cited text no. 132    
133.Hamano S, Sugiyama N, Yamashita S, Tanaka M, Hayakawa M, Minamitani M, et al . Intravenous lidocaine for status epilepticus during childhood. Dev Med Child Neurol 2006;48:220-2.  Back to cited text no. 133    
134.Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child 1999;81:431-3.  Back to cited text no. 134    
135.Holmes GL, Riviello JJ Jr. Midazolam and pentobarbital for refractory status epilepticus. Pediatr Neurol 1999;20:259-64.  Back to cited text no. 135    
136.Pellock JM. Use of midazolam for refractory status epilepticus in pediatric patients. J Child Neurol 1998;13:581-7.  Back to cited text no. 136    
137.Singhi S, Murthy A, Singhi P, Jayashree M. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol 2002;17:106-10.  Back to cited text no. 137    
138.Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med 2003;29:1417-25.  Back to cited text no. 138    
139.Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol or midazolam: A systematic review. Epilepsia 2002;43:146-53.  Back to cited text no. 139    
140.Alexopoulos A, Lachhwani DK, Gupta A, Kotagal P, Harrison AM, Bingaman W, et al . Resective surgery to treat refractory status epilepticus in children with focal epileptogenesis. Neurology 2005;64:567-70.  Back to cited text no. 140    
141.Koh S, Mathern GW, Glasser G, Wu JY, Shields WD, Jonas R, et al . Status epilepticus and frequent seizures: Incidence and clinical characteristics in pediatric epilepsy surgery patients. Epilepsia 2005;46:1950-4.  Back to cited text no. 141    
142.Brandt C, Potschka H, Loscher W, Ebert U. N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy. Neuroscience 2003;118:727-40.  Back to cited text no. 142    
143.Holmes GL, Yang Y, Liu Z, Cermak JM, Sarkisian MR, Stafstrom CE, et al . Seizure-induced memory impairment is reduced by choline supplementation before or after status epilepticus. Epilepsy Res 2002;48:3-13.  Back to cited text no. 143    
144.Prasad A, Williamson JM, Bertram EH. Phenobarbital and MK-801, but not phenytoin, improve the long-term outcome of status epilepticus. Ann Neurol 2002;51:175-81.  Back to cited text no. 144    
145.Rigoulot MA, Leroy C, Koning E, Ferrandon A, Nehlig A. Prolonged low-dose caffeine exposure protects against hippocampal damage but not against the occurrence of epilepsy in the lithium-pilocarpine model in the rat. Epilepsia 2003;44:529-35.  Back to cited text no. 145    
146.Rigoulot MA, Koning E, Ferrandon A, Nehlig A. Neuroprotective properties of topiramate in the lithium-pilocarpine model of epilepsy. J Pharmacol Exp Ther 2004;308:787-95.  Back to cited text no. 146    
147.Prasad AN, Seshia SS. Status epilepticus in pediatric practice: Neonate to adolescent. Adv Neurol 2006;97:229-43.  Back to cited text no. 147    
148.Chin RF, Neville BG, Scott RC. Meningitis is a common cause of convulsive status epilepticus with fever. Arch Dis Child 2005;90:66-9.  Back to cited text no. 148    
149.Edwards R, Schmidley JW, Simon RP. How often does a CSF pleocytosis follow generalized convulsions? Ann Neurol 1983;13:460-2.  Back to cited text no. 149    
150.Schmidley JW, Simon RP. Postictal pleocytosis. Ann Neurol 1981;9:81-4.  Back to cited text no. 150    
151.Woody RC, Yamauchi T, Bolyard K. Cerebrospinal fluid cell counts in childhood idiopathic status epilepticus. Pediatr Infect Dis J 1988;7:298-9.  Back to cited text no. 151    


  [Figure - 1]

  [Table - 1], [Table - 2], [Table - 3]


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