Patients with juvenile myoclonic epilepsy, even those with long seizure-free periods, should probably continue medication life-long, but there have been no thorough studies to support this dictum. In young women with this disorder who plan or a likely to become pregnant, changing from valproate to levetiracetam may be sensible. The appropriate duration of treatment for postinfarction epilepsy has not been studied, and most neurologists continue to use one drug indefinitely. Interestingly, epilepsy caused by military brain wounds tends to wane in frequency or to disappear in 20 to 30 years, thereafter no longer requiring treatment (Caveness). In contrast, childhood uncomplicated absence seizures do not require lifelong treatment.
A curious and unexplained lesion in the splenium of the corpus callosum has been detected in patients who have had their antiepileptic drug(s) withdrawn in the previous few days. A review of 16 patients by Gürtler and colleagues did not find a clinical correlate for this change. A broad range of drugs was implicated and the lesion was most prominent on FLAIR MRI. Various metabolic derangements cause similar lesions but the mechanism in all these instances has not been established as discussed Doherty and colleagues.
Specific Drugs in the Treatment of Seizures
The putative mechanisms of action of the most commonly used drugs are reasonably well known but gaps remain. A review by Bialer and White contains a schematic depiction of putative drug actions at excitatory and inhibitory synapses, as adopted in Fig. 15-6 and as summarized in Table 15-5. There it is apparent that for each of these two physiologic classes of neurons, some medications have their main effect on voltage-gated ion channels and others, on membrane receptors or intracellular vesicular activity.
Phenytoin, carbamazepine, levetiracetam, and valproate are representative antiepileptic drugs that may be considered “broad spectrum” and are more or less equally effective in the treatment of both generalized and focal seizures (see Table 15-6 for typical initial dosages). The first two of these drugs act by blocking sodium channels, thus preventing abnormal neuronal firing and seizure spread. Lamotrigine has become an alternative for treating focal seizures with a different side effect profile from the other three (see also Schmidt).
Because carbamazepine (or the related oxcarbazepine) and levetiracetam have somewhat fewer side effects, one or the other is preferred as the initial drug by many neurologists, though phenytoin and valproate have very similar therapeutic and side-effect profiles. In many cases, levetiracetam, phenytoin or carbamazepine alone will control seizures. If not, the use of valproate (which facilitates GABA activity) alone, or the combined use of two medications, produces better control. Levetiracetam has attained popularity largely because of its lack of interactions with other antiepileptic and other medications. Carbamazepine, levetiracetam, and valproate are probably preferable to phenytoin for children because they do not coarsen facial features and do not produce gum hypertrophy or breast enlargement. Because of the high incidence of myoclonic epilepsy in adolescence, it has been the practice of many neurologists to use valproate as the first drug in this age group. Weight gain, menstrual irregularities (see below) during the period of initiation of valproate, and its teratogenic effects also must be accounted for in the choice of initial drug for otherwise uncomplicated seizures in young women.