About one third of patients with newly diagnosed epilepsy do not achieve seizure control despite medical therapy and should be assessed in detail to confirm the diagnosis, to determine the epilepsy syndrome and to plan treatment strategy. Refractory epilepsy is established when there is inadequate seizure control despite using potentially effective antiepileptic drugs (AEDs) at tolerable levels for 1-2 years, and excluding nonepileptic events and poor compliance. An overview of patient management in everyday clinical practice is given. Risk factors for refractoriness include (1) generalized epilepsy with lesions; (2) focal epilepsy with hippocampal sclerosis, cortical dysplasia or hemorrhages; (3) early epilepsy onset; (4) high seizure frequency; (5) absence of response to the first 2 AEDs; (6) high frequency of interictal spikes, and (7) multifocal spikes. The efficacy of surgery ranges from curative (resection) to palliative (vagus nerve stimulation, callosotomy, multiple subpial transections) depending on the epilepsy syndrome and etiology. Using a new antiepileptic drug benefits about one third of patients. Refractoriness is constitutive in most patients and shows a progressive or remission-relapse course in others. As the transporter and target hypotheses do not entirely explain refractoriness, other hypotheses are emerging. New treatments under investigation are described.
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