Focal epilepsies refractory to AEDs: Algorithms to identify treatable causes

Abstract

Epilepsy can be due to CNS diseases or lesions, or systemic disorders. Patients with presumed focal epilepsy refractory to antiepileptic drugs need comprehensive revaluation. It is important to establish a patient is truly drug refractory. Current guidelines suggest that using two AEDs either sequentially or, preferably, in combination can establish drug failure, as long as drugs are given in adequate doses for enough time. Video-EEG recording can confirm a patient has focal rather than primary generalized epilepsy, and support focus localization. Family members may give clues to etiology such as a history of complex or prolonged febrile seizures, implying potential mesial temporal sclerosis. Family history may suggest heritable syndromes, such as Autosomal Dominant Partial Epilepsy with Auditory Features. History and physical examination may lead to appropriate studies to detect a systemic disorder. Limbic encephalitis is now recognized as a cause of refractory epilepsy, particularly if patients have subacute onset, and cognitive or psychiatric symptoms. MRI is increasingly sensitive for detecting drug-refractory focal epilepsy structural etiologies. MRI techniques such as magnetization transfer as well as novel approaches to post-processing may detect lesions such as focal cortical dysplasia not seen on standard scans. FDG-PET can detect focal hypometabolism, and subtraction ictal SPECT increased blood flow, in some patients with normal MRI, suggesting reasonable focal resection prognosis, or guiding intracranial EEG studies. Their value when MRI shows a lesion is less clear. Other PET ligands can image neurotransmitter receptor binding, serotonin precursor uptake or neuroinflammation with valuable research results but limited clinical application.