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 tonic-clonic seizure 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, electroencephalography (EEG) showed rare right temporal sharp waves. Magnetic resonance imaging (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 tonic-clonic seizure 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 (focal impaired awareness seizure, formerly complex partial seizure). A repeat EEG showed occasional right temporal spikes. What is one possible strategy for controlling her present symptoms?
Epilepsy is a chronic disorder of brain function characterized by the recurrent and unpredictable occurrence of seizures. Approximately 1% of the world’s population has epilepsy, which is the fourth most common neurologic disorder after migraine, stroke, and Alzheimer’s disease. Seizures that occur in people with epilepsy are transitory alterations in behavior, sensation, or consciousness caused by an abnormal, synchronized electrical discharge in the brain. Many cases of epilepsy are the result of damage to the brain, as occurs in traumatic brain injury, stroke, or infections, whereas in other cases, the epilepsy is caused by a brain tumor or developmental lesion such as a cortical or vascular malformation; these epilepsies are referred to as “symptomatic.” In other cases, genetic factors are believed to be the root cause. Genetic epilepsies are often called idiopathic. In most cases, the inheritance is complex (polygenic). Rarely, a single gene defect can be identified. A wide diversity of genes may be affected, including (1) those encoding voltage-gated ion channels and synaptic receptors such as GABAA receptors, (2) components of the neurotransmitter release machinery including syntaxin binding protein (STXBP1), (3) neural adhesion molecules such as PCDH19, and (4) proteins involved in synapse development such as leucine-rich glioma inactivated-1 (LGI1).
The antiseizure drugs described in this chapter are usually used chronically to prevent the occurrence of seizures in people with epilepsy. These drugs are also, on occasion, used in people who do not have epilepsy—to prevent seizures that may occur as part of an acute illness such as meningitis or in the early period following either neurosurgery or traumatic brain injury. In addition, certain antiseizure drugs are used to terminate ongoing seizures such as in status epilepticus or prolonged febrile seizures or following exposure to seizure-inducing nerve toxins. Seizures are occasionally caused by an acute underlying toxic or metabolic disorder, such as hypocalcemia, in which case appropriate therapy should be directed toward correcting ...