Status Epilepticus

Overview of Status Epilepticus

Status epilepticus has been reported to account for 1–8% of all hospital admissions for epilepsy, 3.5% of admissions to neurological intensive care, and 0.13% of all visits to a university hospital emergency department (ED).

SE is more common at the extremes of age, with over 50% of all cases occurring in children and a disproportionately high incidence in those over 60 years of age. SE is also more frequent in the mentally handicapped Opens in new window and in those with structural cerebral pathology, especially of the frontal lobes. Four to 16% of adults and 10–25% of children with known epilepsy will have at least one episode of SE. However, SE occurs most commonly in patients with no previous history of epilepsy.

Many compensatory physiological changes accompany seizures. As the duration is increased these mechanisms begin to fail, with an increased risk of permanent damage. Brain damage resulting from prolonged SE is believed to be caused by excitatory amino acid neurotransmitters such as glutamate and aspartate. These lead to an influx of calcium into neuronal cytoplasm and an osmotolysis with cell destruction.

Continuing seizure activity itself contributes substantially to neuronal damage, which is further exacerbated by hypoxia, hypoglycaemia, lactic acidosis and hyperpyrexia. When seizures continue for over 60 minutes, the risk of neuronal injury increases despite optimal delivery of oxygen and glucose. The longer an episode of SE continues, the more refractory to treatment it becomes, and the more likely it is to result in permanent neuronal damage. Mortality increases from 2.7% with seizure duration under 1 hour, to 32% with duration beyond this. Generalized convulsive SE is therefore a medical emergency.

Treatment of SE is along the same lines as the resuscitation of all seriously ill patients. Management is in a resuscitation area with attention to four specific factors:

• Rapid stabilization of airway, breathing and circulation.
• Termination of seizure activity (clinical and electrical).
• Identification and treatment of precipitating and perpetuating factors.
• Identification and treatment of complications.

Each stage of resuscitation is made more difficult by the presence of active convulsions. No attempt should be made to prise clenched teeth apart to insert an oral airway: a soft nasal airway will suffice. Oxygen should be given by tight-fitting mask and the patient positioned in the left lateral position to minimize the risk of aspiration.

Intravenous access is important for drug treatment and fluid resuscitation, but may be difficult in actively seizing patients. Although SE cannot be diagnosed until seizures have persisted for 30 minutes, patients still seizing on arrival at the emergency department (ED) should be treated with anticonvulsants immediately.

The principal pharmacological agents used are benzodiazepines and phenytoin. The benzodiazepines used vary between countries, with little clinical evidence to support any particular one. In Australasian centers midazolam is preferred, in increments of 1–2 mg i.v. If i.v. access cannot be rapidly secured, midazolam i.m. at a dose of 0.2 mg/kg will terminate most seizures. Alternatives to midazolam are diazepam and clonazepam. Diazepam can be administered rectally if necessary, and this technique can be taught to parents with high-risk children. However, onset of action by this route in adults is slow and unpredictable. All benzodiazepines share the disadvantages of respiratory depression, hypotension, and a short duration of clinical effect.

Phenytoin is usually used as a second line agent in a dose of 15–20 mg/kg at a rate of no more than 50 mg/min. Rapid administration is associated with bradyarrhythmias and hypotension. The common practice of administering 1 g is inadequate for most adults. The effect of phenytoin does not commence until 40% of the dose has been administered; for this reason it should be commenced at the same time that i.v. benzodiazepines are given. Most people on anticonvulsants who present in SE have negligible drug levels, and the side effects from a full loading dose on top of a therapeutic level are minimal. The full loading dose should therefore be given even when the patient is known to be on therapy.

The most common causes of failure to control seizures are:

• Inadequate antiepileptic drug therapy.
• Failure to initiate maintenance antiepileptic drug therapy.
• Hypoxia, hypotension, cardiorespiratory failure, metabolic disturbance, e.g. hypoglycaemia.
• Failure to identify an underlying cause.
• Failure to recognize medical complications, e.g. hyperpyrexia, hypoglycaemia.
• Misdiagnosis of pseudoseizures   Opens in new window.

Causes of failure to regain consciousness following treatment of seizures include the medical consequences of SE (hypoxia, hypoglycaemia, cerebral oedema, hypotension, hyperpyrexia), sedation from antiepileptic medication, progression of the underlying disease process, non-convulsive SE and subtle generalized SE.

When benzodiazepines and phenytoin are ineffective, expert advice should be sought. Management in an intensive care unit is mandatory.

For all patients with SE, early consultation with intensive care and neurology services is essential in planning definitive management and disposition.

Non-convulsive Seizures

Not all seizures are associated with convulsive activity. Convulsive seizures are generally easy to recognize, whereas non-convulsive seizures are more subtle and often require a high index of suspicion. These types of seizure are an important cause of alterations in behavior and conscious level, and may precede or follow convulsive episodes. Seizures can involve any of the sensory modalities, vertiginous episodes, automatism, autonomic dysfunction or psychic disturbances, including déjà vu and jamais vu experiences. Non-convulsive seizures can easily be confused with migraine, cerebrovascular events or psychiatric conditions. The definitive diagnosis can only be made by EEG during the event.

Non-convulsive seizures may be partial (focal) or generalized. Complex partial seizures and focal seizures account for approximately one-third of all seizures, whereas primary generalized non-convulsive seizures (absence seizures) account for 6%.

Non-convulsive status epilepticus (NCS) accounts for at least 25% of all cases of SE and is diagnosed more frequently when actively considered. Absence seizures rarely result in complete unresponsiveness, and patients may appear relatively normal to unfamiliar observers. NCS may precede or follow convulsive seizures and may easily create the perception of a cerebral vascular or psychiatric event. The longest reported episode of absence status is 60 days, and that of complex partial status 28 days.

Treatment of non-convulsive seizures in the acute setting is the same as for convulsive seizures. The event is terminated with benzodiazepines in most instances, and should be followed by a search for precipitating causes. An estimated 50% of patients with simple partial seizures have abnormal CT scans. Long-term seizures control uses different agents from those used for convulsive seizures, highlighting the importance of involving a neurological service when planning follow-up.