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The management of refractory idiopathic epilepsies.

Idiopathic epilepsies comprise a wide variety of partial and generalized syndromes that have in common a known or presumed genetic etiology and the lack of overt abnormalities other than the epilepsy itself. Most of these epilepsies have a benign natural history and/or show a favorable response to antiepileptic drug (AED) therapy, but pharmacoresistance does occur in some patients. In general, therapeutic algorithms in idiopathic partial epilepsies (IPEs) are similar to those used for symptomatic partial epilepsies, but aggressive pharmacologic therapy is rarely indicated in these patients. In self-limited conditions such as benign epilepsy of childhood with centrotemporal spikes or some forms of benign epilepsy with occipital paroxysms, AED treatment may not even be indicated unless seizures interfere significantly with quality of life. Valproate (VPA) is usually regarded as the drug of choice in idiopathic generalized epilepsies (IGEs). Most patients become rapidly seizure free, and poor compliance or prescription of an inappropriate AED because of misdiagnosis are the most common causes of treatment failure in IGEs. In those patients who did not respond well to VPA (or in whom VPA is considered contraindicated), the choice of alternative AEDs is guided by syndromic diagnosis and associated possible coexistence of multiple seizure types. Lamotrigine is establishing itself as a useful agent for many refractory IGEs, and might be considered for first-line use in selected patients. Topiramate (TPM) is another promising new agent in the management of refractory tonic-clonic seizures of nonfocal onset, but its potential efficacy against other primarily generalized seizure types has not been clearly established. Some of the older drugs, particularly ethosuximide (ESM), barbiturates, and benzodiazepines (BZDs), still have an important role in the management of refractory IGEs, especially in combination with VPA. Because carbamazepine (CBZ), phenytoin (PHT), tiagabine (TGB), vigabatrin (VGB), and gabapentin (GBP) may precipitate or aggravate absence and/or myoclonic jerks, their role in IGE syndromes associated with multiple seizure types is limited mostly to adjunctive use in patients unresponsive to first-line therapy.

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