A 10-year-old boy is brought to the family physician because the child is having problems at school. In a parent-teacher conference, the teacher complained that this child is inattentive, rude to others, and a poor student. The teacher indicates that the child does not listen, does not always respond to others or acknowledge them, and doesn't care about remembering anything. The child complains that other children treat him badly, making him the brunt of jokes, talking about him, and picking on him in physical education classes. For example, when playing volleyball, the ball is always spiked or served in his direction, often striking him before he can move. His father recounts many episodes during the past 6 months in which he remarked to the boy, "What did I just tell you?" Before this year in a new school, the child was doing well with no problems.

A physical examination reveals no abnormalities. The neurologic examination is normal.

Questions:

1.1 What is the likely diagnosis?

He may be having lapses that are abrupt, short, and frequent. These findings are typical for generalized absence (petit mal) seizures.

1.2 What should be done next?

An electroencephalogram (EEG) can help to document the findings more fully. An EEG shows an abnormal pattern of generalized, symmetric, 3 Hz spike-and-wave discharges brought on by hyperventilation. These discharges begin and end abruptly after a few seconds. Otherwise, the EEG is normal.

1.3 What pharmacologic therapy may be indicated for treatment?

Drugs of choice include ethosuximide or valproic acid. The former is the drug of choice for "classic" or simple absence seizures. The latter is preferred for atypical absence seizures, either "complicated" or "variant" type (myoclonic, atonic, etc.). If neither of these is effective or tolerated, then clonazepam may be used.

1.4 Explain the mechanism of action of the drug therapy.

Ethosuximide alters calcium ion (low threshhold) currents by reducing calcium ion influx to reduce firing of nerve cells, particularly in the thalamus where the abnormal electrical discharges are thought to arise.

Valproic acid acts by multiple mechanisms. It blocks NMDA receptor-mediated excitation and increases GABA; it decreases sodium ion and calcium ion influx; at high concentrations it acts on potassium channels to increase membrane conductance.

Clonazepam, like other benzodiazepines, potentiates GABAergic inhibition by binding to GABA-a receptors of neuronal membranes. GABA is the major inhibitory neurotransmitter in the CNS.

1.5 What is the prognosis?

Some cases may be "atypical" with longer episodes, or episodes may be accompanied by tonic-clonic seizures. About 2/3 of cases may remit following adolescence.