Introduction
A widely accepted definition of status epilepticus is more than 30 minutes of continuous seizure activ-ity or 2 or more sequential seizures without full recovery of consciousness between seizures. The incidence in the United States is about 125,000 cases annually. Each year 55,000 deaths occur that are associated with status epilepticus, which has the highest incidence in the first year of life and in the elderly, though the elderly have the highest mortality rate. Over 10% of adults with their first seizures present in status epilepticus. Table 15-4 lists the etiologies for status epilepticus.
Pathophysiology
Presumably the seizures are initiated by the same mechanism as with all seizures. However, status epilepticus involves a failure to terminate the
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Table 15-4 Etiologies of Status Epilepticus
Etiology Frequency
Low Anticonvulsant Level 34%
Cerebrovascular Accident 22%
Hypoxia/Anoxia 18%
Metabolic Cause 15%
Drug Overdose 13%
Alcohol Related 13%
Central Nervous System Infection 10%
Brain Tumor 7%
Other 5%
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seizure. Experimental studies find this failure can arise from abnormally persistent, excessive excita-tion or ineffective recruitment of inhibiexcita-tion. Stan-dard drugs used for status epilepticus are more effective if given in the first hour of status.
Status epilepticus can cause cerebral injury, especially in limbic structures such as the hip-pocampus. During the first 30 minutes of seizures, the brain is able to maintain homeostasis through increases in blood flow, blood glucose, and oxygen utilization. After 30 minutes, homeostatic failure begins and may contribute to brain damage.
Hyperthermia, rhabdomyolysis, hyperkalemia, and lactic acidosis develop from constant wide-spread muscle firing. After 30 minutes, other signs of decompensation may develop, including hypoxia, hypoglycemia, hypotension, leukocytosis, and poor cardiac output: However, seizure activity itself appears sufficient to cause brain damage.
One mechanism of damage is glutamate-mediated excitotoxicity, particularly in the hippocampus.
The normal concentration of calcium outside of neurons is at least 1,000 times greater than that inside of neurons. During seizures, the receptor-gated calcium channel is opened following stimu-lation of the N-methyl-D-aspartate (NMDA) receptor by glutamine. This enables intracellular calcium levels to rise potentially to cytotoxic levels.
Major Clinical Features
Initially patients are unresponsive and have clini-cally obvious seizures with tonic, clonic, or tonic–
clonic limb movements. With time the seizure activity is less obvious. Patients may show only small-amplitude twitching movements of the face, hands, and feet and nystagmoid jerking of the eyes.
If the seizure-induced movements stop, the patient remains unresponsive or very confused and the next seizure begins.
On neurologic exam the patient will not respond to verbal commands. He or she will have increased or decreased muscle tone, no purposeful limb movements, and will frequently demonstrate Babinski signs. In general, the neurologic signs will be symmetrical.
There are occasional patients who present with constant confusion, impaired awareness, and able to move limbs and walk that have a type of status epilepticus called nonconvulsive status epilepticus
(complex partial status epilepticus). In these patients, a persistently and specifically abnormal EEG establishes the diagnosis.
Major Laboratory Findings
A marked leukocytosis (WBC count >20,000/mm3) without an increase in bands occurs due to loss of margination of WBCs rather than production from bone marrow as seen in an infection. As a consequence of prolonged seizures, the patient develops elevated serum potassium, metabolic aci-dosis (pH <7.0), and varying degrees of hypoxia. A screen of toxins and anticonvulsant levels that are low or absent also may establish the cause.
The EEG is always severely abnormal, showing continuous or nearly continuous spike and wave complexes. The findings on neuroimaging depend on the etiology of the status epilepticus, as status epilepticus of unknown cause may have initially normal neuroimaging.
Principles of Management and Prognosis The goal is to stop the seizures from status epilep-ticus, identify and treat the cause, and prevent complications. The initial priority is to establish an airway and maintain circulation (“ABCs”). This is accomplished by administering oxygen by mask or cannula; monitoring heart rate, temperature, and blood pressure; following oxygen saturation by pulse oximetry; and establishing intravenous access with administration of thiamine and a bolus of 50% glucose (glucose will terminate seizures due to hypoglycemia).
The initial anticonvulsant given is usually lorazepam delivered intravenously as soon as pos-sible. This is soon followed by a full intravenous loading dose of fosphenytoin or phenytoin to maintain cessation of the seizures. Fosphenytoin is a water-soluble analogue of phenytoin that is con-verted to phenytoin in the body. Fosphenytoin can be given at a faster rate and is somewhat safer than phenytoin but is more expensive.
If fosphenytoin and lorazepam fail to control the seizures, the patient should be intubated and placed on a ventilator. Iatrogenic anesthetic coma is then induced with pentobarbital or occasionally midazolam until there is cessation of seizure activ-ity both clinically and on the EEG. Attempts should 162 FUNDAMENTALS OF NEUROLOGIC DISEASE
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be made to wean these drugs slowly under EEG control to ensure that the seizures do not return.
Patients, especially children, with epilepsy who experience repeated bouts of status epilepticus can begin early treatment at home by rectal adminis-tration of a special gel formulation of diazepam. In children, this rectal delivery often stops seizures within 15 minutes.
RECOMMENDED READING
Browne TR, Holmes GL. Epilepsy. N Eng J Med 2001;344:1145–1151. (Excellent review aimed at the primary care physician.)
Cascino GD. Complex partial seizures: clinical fea-tures and differential diagnosis. Psych Clin N Amer 1992;15:373–382. (Reviews clinical fea-tures, EEG findings, and anticonvulsants.) Lowenstein DH, Alldredge BK. Status epilepticus.
N Engl J Med 1998;338:970–976. (Reviews cur-rent management options in detail.)
Mikati MA, Lepejian GA, Holmes GL. Medical treatment of patients with infantile spasms.
Clin Neuropharmacol 2002;25:61–70. (Good review of syndrome and challenges to treatment.)
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