Definition

Status epilepticus (SE) is a life-threatening medical emergency. In children, SE often necessitates urgent treatment and monitoring in the pediatric intensive care unit (PICU) and requires that the pediatric intensivist be comfortable with the diagnosis and management of this common condition.

The International League Against Epilepsy defines SE as a seizure that persists for a sufficient length of time or is repeated enough to produce a fixed and enduring epileptic condition.¹ From the practical perspective of the treating physician, this definition is difficult to apply. A more commonly used clinical definition includes duration of seizure activity, specifying SE as seizures lasting 30 minutes or longer, which is based on the theory that neuronal damage may begin after 30 minutes of continuous seizures. No clinical data support the 30-minute rule, however, and more recent definitions of SE include a shorter duration of seizure activity. An operational definition has been proposed, in which generalized convulsive SE in adults and children older than 5 years is “greater than or equal to 5 minutes of continuous seizures or two or more discrete seizures between which there is incomplete recovery of consciousness.”² This definition has been supported by clinical studies showing that most secondarily generalized convulsive seizures in adults last less than 5 minutes³; these results suggest that seizures lasting more than 5 minutes should be regarded as more significant. Similar data in children have shown that new-onset seizures cluster by duration; most seizures (76%) last less than 5 minutes and 24% last longer, with a mean duration of 31 minutes.⁴ The shorter duration definition of SE remains controversial, however, because although it is less common for seizures to persist beyond 5 minutes, it also has been shown that seizures lasting 10 to 29 minutes that stop spontaneously are associated with a significantly lower mortality rate than seizures lasting beyond 30 minutes.⁵ Thus before the definition of SE includes a seizure duration of less than 30 minutes, further study and discussion are required.

Regardless of the definition of SE, there is a consensus in the medical community that continuous or prolonged seizures require urgent intervention. Children with prolonged seizures should receive prompt and aggressive treatment with the aim of stopping seizures as soon as possible.

Classification of Status Epilepticus

SE should be classified with the same terminology used for seizure classification. The International League Against Epilepsy Task Force on Classification and Terminology identifies two major categories that may be applied to both self-limited and continuous seizures.⁶ Generalized seizures refer to seizures involving both cerebral hemispheres, which are believed to originate within, and rapidly engage, bilaterally distributed neuronal networks. Consciousness is usually impaired. Generalized seizures include seizures with motor movements as well as absence seizures during which no convulsive signs may be present. Electroencephalography (EEG) indicates seizure activity involving both cerebral hemispheres. Focal seizures, previously referred to as partial seizures, are those in which the first clinical and EEG changes indicate seizures that originate within one cerebral hemisphere. Generalized seizures that begin as focal seizures are termed secondarily generalized seizures. Complex focal seizures are associated with an impairment of consciousness. Simple focal seizures have no impairment of consciousness. When simple focal seizures are prolonged and have a focal motor component, the term epilepsia partialis continua is used.⁷ These same terms are also used to describe continuous seizures and SE. SE also may be defined more specifically by seizure type, including myoclonic status, tonic status, and absence status.⁶ Although these distinctions are helpful to predict the cause and outcomes of SE, the differentiation may require EEG and has limited utility in the acute clinical situation.

A more clinically useful classification scheme involves categorizing SE by the presence of motor movements (Box 60-1). Convulsive SE (CSE) consists of continuous clonic or tonic motor activity with bilateral epileptiform discharges on the EEG. As CSE progresses, the motor movements are reduced and may be characterized only by subtle twitching of the limbs, face, or trunk. This condition is termed subtle CSE.

Nonconvulsive SE consists of continuous electrographic seizures with no motor movements. This type of seizure may occur after prolonged generalized CSE. Nonconvulsive SE also refers to SE consisting of absence seizures or focal onset seizures that do not produce motor movements.

In children, an additional category, febrile SE, may be considered. SE occurring in association with fever represents one form of complex febrile convulsions.

Finally, SE also may be classified with respect to cause. Symptomatic implies a known cause for SE and can be further divided into acute symptomatic and remote symptomatic on the basis of cause. Examples of acute symptomatic causes include toxins and acute infections. Remote symptomatic SE is most often associated with a long-standing history of epilepsy or remote central nervous system (CNS) insult. The term idiopathic SE is used when there is no known or suspected cause for the seizures.

Nonepileptic seizures, also known as nonepileptic events, also may present as SE. Patients with and without a prior history of epileptic seizures may have nonepileptic SE. In this situation, EEG may be necessary for diagnosis to confirm the absence of abnormal electrical discharges in the brain.

Epidemiology of Status Epilepticus

Outcome

Pathophysiology

The exact mechanism that permits a seizure to become sustained is not known. Theoretically, either a failure of physiologic neuronal inhibition or an excess of excitation is required. Much of the research in this area has focused on the failure of neuronal inhibition by the major inhibitory neurotransmitter in the CNS, γ-aminobutyric acid (GABA). Prolonged seizures have been associated with deficits in GABA-mediated neuronal inhibition because of the rapid internalization of synaptic GABAA receptors. Clinically this phenomenon may be demonstrated by the poor response of prolonged seizures to the GABA agonists benzodiazepines and barbiturates,²⁸ a phenomenon known as time-dependent pharmacoresistance.^29–31

SE causes neuronal injury by both hypoxic-ischemic and excitotoxic mechanisms. The pathophysiology of SE-induced hypoxic-ischemic injury is illustrated in Figure 60-1.³² Early in SE, an increase in neuronal metabolic demand occurs with a compensatory increase in cerebral blood flow (CBF) and brain oxygenation. Later in SE, these homeostatic mechanisms are unable to keep up with the sustained increase in cerebral metabolic demand. Autoregulation of CBF fails, and consequently a higher mean arterial pressure is required to maintain adequate brain perfusion. As systemic blood pressure falls, a subsequent reduction in brain parenchymal oxygenation occurs. In the face of increased neuronal metabolic demand, uncontrolled muscular contractions, hyperthermia, and impaired airway control, both impaired oxygenation and ventilation contribute to the mismatch between metabolic supply and demand. However, neuropathologic injury occurs even when these systemic factors are controlled and before CBF is reduced, presumably because of unmet neuronal metabolic demands alone.

Figure 60–1 Pathophysiology of hypoxic-ischemic brain injury in status epilepticus.

(Modified from Lothman E: The biochemical basis and pathophysiology of status epilepticus, Neurology 40(5 suppl 2):13-23, 1990.)

Excitotoxicity is the second major mechanism for neuronal injury in SE. Glutamate is the major excitatory neurotransmitter in the CNS, and glutamate agonists are used to induce seizures in experimental animal models of SE. Studies have implicated both the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptors in the pathophysiology of SE.³³ The NMDA receptor may have a dual function in the pathophysiology of SE. Magnesium blocks the NMDA channel when it is in its normal state. With depolarization, magnesium no longer blocks the channel, and calcium, which is allowed to flow into the cell, produces further depolarization. Thus the NMDA receptor is activated when the cell is depolarized and responds by further depolarizing the cell, sustaining the excitation. This process also has been implicated in SE-induced neuronal injury, as the accumulation of intracellular calcium activates pathologic processes resulting in both necrotic and apoptotic cell death.^34,35

Diagnosis

The clinical presentation of SE is variable, depending on seizure type and the baseline developmental and medical status of the child. Diagnosis depends on the identification of continuous or repetitive seizures, which is usually straightforward in the presence of convulsive seizures. However, after prolonged convulsive seizures the motor manifestations often diminish, and the seizures may become subtle or even nonconvulsive. Differentiating between such nonconvulsive seizures and a postictal state can be challenging. Patients with nonconvulsive SE, including absence SE, may be difficult to identify by history and physical examination alone. These patients can have intermittent altered awareness and continuous lethargy or unresponsiveness with or without subtle myoclonic jerks of the face or limbs. In such cases, continuous EEG monitoring is critical for diagnosis. EEG monitoring also can be used to identify nonepileptic (psychogenic) SE. Although uncommon, prolonged delays in the EEG-based diagnosis of nonepileptic SE can lead to unnecessary medical intervention.³⁶

EEG measures extracellular electrical activity generated by cortical neurons. Data are collected with a standard array of scalp electrodes and presented for visual display onto a paper or digital record.

Because EEG provides real-time information regarding brain activity, it is invaluable in the evaluation of patients with SE, permitting direct correlation between patient behavior and neuronal activity. EEG interpretation should be performed with the assistance of a trained neurologist or neurophysiologist to reduce the potential for both over- and under-identification of seizures.

Recent advances in computing and networking technology have facilitated the remote interpretation of continuous EEG recordings. Regular communication between ICU staff and the neurology team remains essential to optimizing the care of SE patients. Quantitative EEG trending tools such as amplitude-integrated EEG and color density spectral array are increasingly being incorporated into portable EEG systems and bedside monitors (Figure 60-2). These tools may be applied to visualize single or multiple channels of EEG, providing a time-compressed overview of cerebral function that is simpler to interpret than conventional EEG. However, because these displays are generally less sensitive and specific for the identification of seizures, they should be used judiciously, with corroboration by careful analysis of the underlying raw EEG tracing.

Figure 60–2 Examplesof 8-channel quantitative electroencephalographic (EEG) displays depicting 4 hours of raw EEG containing several generalized seizures. The timing of seizures is indicated at the top of each display. A, On an amplitude-integrated EEG display, seizures are characterized by elevations in the upper and lower margins of the tracing. B, On a color density spectral array display, seizures are characterized by bright bands of color.

Abnormal waveforms on EEG can be divided into two categories: epileptiform abnormalities and nonepileptiform abnormalities. Epileptiform abnormalities are abnormal discharges associated with an increased risk of seizures, including sharp waves, spikes, polyspikes, and spike and slow wave discharges (Figure 60-3). When present between seizures, these waveforms are termed “interictal” abnormalities. Seizures are defined electrographically by the presence of “ictal” EEG abnormalities, whose hallmark is their rhythmicity and their evolution in frequency or distribution over the course of a seizure. Generalized seizures are characterized by widespread bilateral rhythmic epileptiform discharges (Figure 60-4, A). Focal seizures are characterized by rhythmic epileptiform discharges that are confined to one brain region (Figure 60-4, B). Focal seizures may spread to involve both cerebral hemispheres, a process termed secondary generalization.

Figure 60–3 Examples of normal electroencephalographic (EEG) background and interictal epileptiform discharges. A, Normal 3- to 4-Hz awake background rhythm in a 7-month-old boy. B, Normal 9-Hz awake background rhythm in a 4-year-old girl, with a right temporo-occipital spike-wave discharge highlighted in blue. C, Normal sleep background in an 8-year-old girl, with a vertex sleep wave highlighted in red and a generalized polyspike discharge highlighted in blue.