A 30-year-old woman has experienced odd movements of her right hand for the past year. These episodes have occurred at various times during the day, about 3 or 4 times a month. An episode begins with what she describes as "twitching" of her fingers for about a minute, followed by "shaking" of her whole hand "as if I were beating a drum." Sometimes during one of these episodes she experiences an intense odor of burning toast (but she doesn't own a toaster). She does not lose consciousness. Episodes have never lasted more than 5 minutes. A friend once asked her why she was making faces during an episode.

Physical examination by her physician shows normal vital signs. There are no abnormal findings. The neurologic examination is normal.

Questions:

6.1 What are diagnostic possibilities?

A seizure disorder is suggested. The pattern fits best with simple partial seizure. If she had "lost contact" with her surroundings and was unable to recollect what happened during or soon after the episode, then she would have complex partial seizures. There are no generalized features, such as widespread tonic-clonic movements, that suggest partial seizures with secondary generalization.

6.2 What should be done next?

An electroencephalogram (EEG) can help to document the findings more fully. An EEG shows an abnormal pattern of discharges involving an area of the left posterior frontal lobe.

6.3 What pharmacologic therapy may be indicated for treatment?

Generally, the same therapies are employed for partial seizures and for grand mal seizures. Preferred drugs may include carbamazepine, valproic acid, lamotrigine, or phenytoin, but phenytoin is less frequently used. Carbamazepine is the first choice. Adjunctive agents such as phenobarbital or primidone are often required.

6.4 Explain the mechanism of action of the drug therapy.

Lamotrigine, carbamazepine, and phenytoin all block sodium channels and inhibit rapid, repetitive neuronal electrical discharge. Valproic acid blocks NMDA receptor-mediated excitation and increases GABA; at high concentrations it acts on potassium channels to increase membrane conductance. Phenobarbital and primidone both increase GABA or increase chloride ion influx.