Guideline source: American Academy of Neurology and the Child Neurology Society
Literature search described? Yes
Evidence rating system used? Yes
Published source: Neurology, November 14, 2006
Available at: http://www.neurology.org/content/vol67/issue9
Status epilepticus is a life-threatening condition that requires timely recognition and immediate treatment in children and adults. There are many definitions of status epilepticus, but the one most commonly accepted is 30 minutes of continuous seizures or two or more seizures in a row without full recovery of consciousness between seizures. Status epilepticus can be categorized based on the type and etiology of the seizure (Table 1), with type being determined by the origin of epileptic discharge (i.e., focal or generalized); however, if there is insufficient information available, the seizure is indeterminate or unclassifiable.
|Remote symptomatic (33%)||SE occurring without an acute provocation in a patient with a history of CNS insult (e.g., chronic encephalopathy)||CNS malformation, previous traumatic brain injury or insult, chromosomal disorder|
|Acute symptomatic (26%)||SE occurring during an acute illness (e.g., acute CNS insult, acute encephalopathy)||Meningitis, encephalitis, electrolyte disturbance, hypoxia, intoxication, sepsis, trauma|
|Febrile (22%)||SE occurring when the only provocation is a febrile illness, after excluding a direct CNS infection such as meningitis or encephalitis||Upper respiratory infection, sinusitis, sepsis|
|Cryptogenic† (15%)||SE occurring in the absence of an acute precipitating CNS insult, systemic metabolic disturbance, or both||No definable cause|
|Progressive encephalopathy (3%)||SE occurring with an underlying, progressive CNS disorder||Amino or organic acidopathies, CNS lipid storage diseases, mitochondrial disorders|
|Remote symptomatic with an acute precipitant (1%)||SE occurring with a chronic encephalopathy, but with an acute provocation||CNS malformation or previous CNS insult with concurrent infection, hypoglycemia, hypocalcemia, or intoxication|
Studies have shown that symptomatic status epilepticus is common in younger children and infants. In one study of almost 400 children one month to 16 years of age, more than 80 percent of those younger than two years had acute symptomatic or febrile status epilepticus or a progressive encephalopathy. The incidence of status epilepticus in children one to 19 years of age is 10 to 58 per 100,000 children per year. Infants younger than one year have a higher incidence, with approximately 135 to 156 per 100,000 infants affected per year. Status epilepticus is common in children with epilepsy (occurring at a rate of 9.1 to 27.0 percent), and it may be a presenting sign of epilepsy.
Children may develop status epilepticus for many different reasons. Infectious or inflammatory illnesses may cause seizures by affecting the brain or through involvement of the central nervous system (CNS). Drug abuse or ingestion of a toxin also could be to blame. If the child is taking antiepileptic drugs, a low drug level from inadequate dosing, noncompliance, or discontinuation of treatment may cause the status epilepticus. Inborn errors of metabolism (e.g., amino acid, ammonia, or organic acid disorders), as well as specific chromosomal and genetic disorders, can cause neurologic dysfunction and epilepsy. In some children, seizures may get worse because of metabolic stress or during an intercurrent illness.
Drug treatment guidelines for status epilepticus in children are already available; however, there are no guidelines on diagnostic evaluation that are specific to children or that are evidence based. The American Academy of Neurology (AAN) and the Child Neurology Society reviewed the available evidence on children with status epilepticus and created recommendations for diagnostic laboratory testing.
Evidence and Recommendations
In six studies (n = 357) that reported on sepsis, a minimal diagnostic yield of a positive blood culture was found in 2.5 percent of children with status epilepticus. This minimal diagnostic yield was based on the assumption that blood cultures were obtained in all patients in the studies, whether or not sepsis was suspected.
The evidence is insufficient to support or refute whether blood cultures should be obtained routinely in children with no clinical suspicion of infection. None of the studies indicated that blood cultures were obtained routinely in all children with status epilepticus; it was either stated or presumed that testing was done selectively.
Data from 18 studies (n = 1,859) showed that the diagnosed CNS infection rate was 12.8 percent. According to the results of one study involving 49 children with convulsive status epilepticus, 24 children (49 percent) had a fever, and 17 percent of those had bacterial meningitis; none of the children without fever had meningitis. In three studies involving 185 children, lumbar puncture was used to diagnose and confirm the following illnesses: meningitis (14 percent of children), encephalitis (11 percent), and leukemic meningitis (1 percent). Vasculitis and shunted hydrocephalus each occurred in less than 1 percent of the children.
The evidence is insufficient to support or refute whether lumbar puncture should be performed routinely in children with no clinical suspicion of CNS infection. As with blood culture, there was no indication to show that lumbar puncture was performed routinely in these studies.
ANTIEPILEPTIC DRUG LEVELS
Data on antiepileptic drug levels were available in nine studies (n = 528), with low levels reported in 32 percent of children. Reasons for the low drug levels included discontinuation of treatment (9 percent) and noncompliance (0.2 percent). However, it was not assumed that the low levels of antiepileptic drugs were the cause of status epilepticus in the children studied.
Antiepileptic drug levels should be considered when a child with epilepsy on antiepileptic prophylaxis develops status epilepticus.
In 11 studies (n = 1,221), toxic ingestion was found in 3.6 percent of children. Specific toxins included theophylline, lindane, carbamazepine (Tegretol), and chemotherapy. It is unknown whether toxicology testing was performed on the patients based on history or physical examination findings, or because initial laboratory studies were unable to find other causes of the children's status epilepticus.
Because ingestion was found to be the cause of status epilepticus in 3.6 percent of children, toxicology testing can be considered if no apparent cause is immediately found. A specific serum toxicology test is required when identifying specific ingestion, which may be suspected because of the patient's clinical history.
METABOLIC AND GENETIC TESTING
Nine studies (n = 735) showed that an inborn error of metabolism was the diagnosis in 4.2 percent of children. More specifically, pyridoxine (vitamin B6) dependency, Leigh disease, neuronal ceroid-lipofuscinosis, and mitochondrial disorders were each found in 0.3 percent of the children, and Alper's disease, methylmalonicacidemia, and carnitine deficiency were each found in 0.2 percent. Separate information on genetic or chromosomal disorders was unavailable.
Studies for inborn errors of metabolism can be considered if initial evaluation finds no etiology, especially if the patient has a history suggestive of a metabolic disorder. The type of study that should be done depends on the patient history and clinical examination; however, there are insufficient data to support or refute their routine use. There also are insufficient data to support or refute routine use of genetic testing (e.g., chromosomal, molecular).
Six studies that included 413 electroencephalography (EEG) findings in 358 children found that 89 percent of the findings could be categorized as abnormal. Generalized or focal epileptiform activity was observed in 43.1 percent of the children. One study (n = 407) that looked at the prognosis of those with a first unprovoked seizure reviewed the EEG findings in 46 of the children with status epilepticus. Sixty-two percent of the EEG findings in children with status epilepticus were considered abnormal compared with 41 percent in children who only had seizures lasting less than 30 minutes.
Nonconvulsive status epilepticus and pseudostatus epilepticus (a nonepileptic event that imitates status epilepticus) also may occur. One study (n = 29) of children with convulsive status epilepticus found that 21 percent had pseudoseizures. No data are available on the prevalence of nonconvulsive status epilepticus in children after convulsive status epilepticus is controlled; however, one study showed that among adults, nonconvulsive status epilepticus is present in 14 percent of patients in whom impaired consciousness remains after convulsive status epilepticus is controlled.
EEG may be considered in children presenting with new-onset status epilepticus because it can help to determine whether there are focal or generalized abnormalities, which can influence diagnosis and treatment (Table 2). Although nonconvulsive status epilepticus does occur, the evidence is insufficient to support or refute recommendations regarding the use of EEG to confirm this diagnosis. EEG may be considered if a diagnosis of pseudostatus epilepticus is suspected.
|EEG findings||Number of patients||Percentage||Range (%)|
|Electrocerebral inactivity||8||1.9||0 to 3.9|
|Focal only||66||16.0||0 to 47|
|Generalized only||33||8.0||0 to 19|
|Generalized and focal||79||19.1||0 to 42|
|Focal slowing||26||6.3||0 to 23|
|Generalized slowing||169||41.0||26 to 93|
|Normal||32||7.7||0 to 34|
Information from 20 studies (n = 1,951) found that lesions were detected by neuroimaging in 7.8 percent of patients. Specific lesions included CNS malformation in 1.7 percent, trauma in 1.6 percent, stroke/hemorrhage in 0.9 percent, tumor in 0.8 percent, infarction in 0.6 percent, hemorrhage in 0.4 percent, and abscess/cerebritis in 0.4 percent.
In five studies reporting on computed tomography (CT) results, a mean of 49 percent of CT findings were categorized as abnormal (e.g., presence of cerebral edema, atrophy, infection). In one small study, magnetic resonance imaging was performed in nine of 24 children. The findings were classified as normal in two of the children and abnormal in seven.
Neuroimaging may be considered if clinically indicated or if the etiology of status epilepticus is unknown. It should be used only after the seizures are under control and the patient is stabilized. The data are insufficient to support or refute routine use of neuroimaging. Neuroimaging can identify structural causes of status epilepticus and eliminate the need for neurosurgical interventions in children with new-onset status epilepticus and no history of epilepsy, or in those in whom status epilepticus persists despite treatment.
Research is still needed to help define what precipitates status epilepticus in children, as well as to determine the frequency, etiology, and prognostic significance of nonconvulsive status epilepticus in children whose convulsive status epilepticus has already been adequately controlled. Controlled prospective trials should be conducted to determine the role of routine or selective laboratory testing, to define the setting and timing of EEG, and to examine the yield of routine or selective neuroimaging in the evaluation of children with status epilepticus.