Chapter 24

A 23-year-old woman presents to the office for consultation regarding her antiseizure medications. Seven years ago, this otherwise healthy young woman had a generalized tonic-clonic seizure (GTCS) at home. She was rushed to the emergency department, at which time she was alert but complained of headache. A consulting neurologist placed her on levetiracetam, 500 mg bid. Four days later, EEG showed rare right temporal sharp waves. MRI was normal. One year after this episode, a repeat EEG was unchanged, and levetiracetam was gradually increased to 1000 mg bid. The patient had no significant adverse effects from this dosage. At age 21, she had a second GTCS while in college; further discussion with her roommate at that time revealed a history of two recent episodes of 1–2 minutes of altered consciousness with lip smacking (complex partial seizures). A repeat EEG showed occasional right temporal spikes. Lamotrigine was gradually added to the regimen to a dosage of 200 mg bid. Since then, the patient has been seizure-free for almost 2 years but now comes to the office for a medication review. Gradual discontinuation of levetiracetam is planned if the patient continues to do well for another year, although risk of recurrent seizures is always present when medications are withdrawn.

*This case description includes the answers to implied questions regarding therapy.

Approximately 1% of the world's population has epilepsy, the second most common neurologic disorder after stroke. Although standard therapy permits control of seizures in 80% of these patients, millions (500,000 people in the USA alone) have uncontrolled epilepsy. Epilepsy is a heterogeneous symptom complex—a chronic disorder characterized by recurrent seizures. Seizures are finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons. The causes of seizures are many and include the full range of neurologic diseases—from infection to neoplasm and head injury. In some subgroups, heredity has proved to be a predominant factor. Single gene defects, usually of an autosomal dominant nature involving genes coding voltage-gated ion channels or GABAA receptors, have been shown to account for a small number of familial generalized epilepsies. Commonly, one family shows multiple epilepsy syndromes including, for example, febrile seizures, absence attacks, and juvenile myoclonic epilepsy.

The antiseizure drugs described in this chapter are also used in patients with febrile seizures or with seizures occurring as part of an acute illness such as meningitis. The term "epilepsy" is not usually applied to such patients unless chronic seizures develop later. Seizures are occasionally caused by an acute underlying toxic or metabolic disorder, in which case appropriate therapy should be directed toward the specific abnormality, eg, hypocalcemia. In most cases of epilepsy, however, the choice of medication depends on the empiric seizure classification.

### Drug Development for Epilepsy

For a long time it was assumed that a single antiepileptic drug (AED) could be developed for the treatment of all forms of epilepsy. However, the ...

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