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Children with generalized seizures are often excluded as epilepsy surgery candidates. This prospective study was conducted to evaluate the utility of magnetoencephalography (MEG) to refine the location of the “irritative zone” in children with single lesions on magnetic resonance imaging (MRI) but with generalized ictal electroencephalographic (EEG) findings.Patients admitted with refractory epilepsy with imaging studies showing focal or hemispheric abnormalities but scalp video EEG showing generalized or multiregional epileptiform abnormalities were included. Patients were encouraged into natural sleep, and simultaneous whole-head MEG/EEG was recorded. Source localization of epileptic spikes on MEG was carried out while blinded to other results. Acceptable dipoles were classified into 3 groups: focal, hemispheric clusters, and single focal cluster with additional widespread dipoles.Nine patients (4 female, 5 males; ages 10 months to 15 years) were included. Two had focal features on clinical semiology, whereas all had generalized or multiregional interictal and ictal EEG. Etiologies included tuberous sclerosis complex (2), postencephalitic sequelae (1), focal cortical dysplasia (1), and unknown (2). Five patients had clear focal lesions on brain MRI whereas the other 2 had focal positron emission tomography (PET) abnormalities. An average of 38 spikes were accepted (average goodness of fit = 85.3%). A single tight cluster of dipoles was identified in 5 patients, 1 had dipoles with propagation from left occipital to right temporal. One patient had 2 distinct dipole clusters. MEG demonstrated focal findings 9 times more often than the simultaneously recorded scalp EEG, and 3 times more often than the associated multiday video EEG recordings.This study shows that neurophysiologic evidence of focal epileptiform abnormalities in patients with focal brain lesions and generalized EEG findings can be strengthened using MEG. Further feasibility of surgical candidacy should be evaluated in these patients.