A 44-year-old man is brought to the emergency department by a co-worker after he is noted to have a seizure. It was noted that he let out a moan, followed by intense muscular contractions involving arms and legs, followed in less than a minute by alternating muscular relaxation and contraction. He was turning blue. Finally, after a couple of minutes, the periods of muscuclar relaxation predominated until he became flaccid but still unresponsive. His breathing became regular and his colour returned. He was drooling, and his pants were wet with urine (which explained why only one of his friends volunteered to take him to the ED).

In the emergency department, he becomes responsive but does not remember the episode. After waiting 2 hours to see a physician, he has a headache and myalgias. On physical examination there are no abnormal findings. The neurologic examination is normal. Laboratory studies show Hct 44%, blood glucose 77 mg/dL, and serum creatinine 1.1 mg/dL.

Questions:

4.1 What is the most likely diagnosis?

He has had a generalized tonic-clonic (grand mal) seizure.

4.2 What should be done next?

An electroencephalogram (EEG) can help to document the findings more fully. An EEG shows an abnormal pattern of progressive increase in generalized low voltage fast activity followed by high amplitude poly spike discharges in the tonic phase. There is a spike-and-wave pattern in the clonic phase. There is diffuse slowing in the post-ictal phase.

Seizures in an adult may be due to underlying metabolic or CNS diseases. With new onset seizures, additional workup, including imaging studies, may be considered.

4.3 What pharmacologic therapy may be indicated for treatment?

Valproic acid or lamotrigine are first choice drugs for treatment. If these are not effective or not tolerated, then phenytoin or carbamazepine may be used. If a single drug does not control the seizures, then other drugs may be added (such as phenobarbital or primidone).

4.4 Explain the mechanism of action of the drug therapy.

Lamotrigine, carbamazepine, and phenytoin all block sodium channels and inhibit rapid, repetitive neuronal electrical discharge, preventing the spread of the abnormal electrical activity from the focus to normal neurons.

Valproic acid blocks NMDA receptor-mediated excitation and increases GABA; at high concentrations it acts on potassium channels to increase membrane conductance.

4.5 Why must phenytoin be monitored carefully?

It has a narrow therapeutic range, and the deactivation changes from first order to zero order with increasing dosage.

4.6 What is required of the physician to report regarding this incident?

A patient suffering a seizure must be reported to the Department of Motor Vehicles. Such a person should not be operating a motor vehicle.