The clinical, MRI, and EEG findings in 54 patients (35 female, 19 male; aged 1 to 64 years) with periventricular nodular heterotopia (PNH) were analyzed in relation to epileptic outcome and genesis of epileptic discharges, in a study at the Neurological Institute and Epilepsy Surgery Center, Niguarda General Hospital, Milan, Italy. Five PNH groups were defined based on imaging and clinical findings: Group 1) bilateral and symmetrical (9 patients); 2) bilateral single-nodule (9); 3) bilateral asymmetrical (9); 4) unilateral (14); and 5) unilateral with neocortical extension (13). Focal interictal EEG abnormalities were related to PNH location and were frequently multifocal, except in group 2 patients. Ictal EEG and stereo-EEG recordings suggest that epileptic discharges and seizures originate from abnormal circuitries located close to or involving the PNH. Group 1 patients showed a female preponderance (8:1), normal neurologic and mental findings, and epilepsy preceded by febrile seizures; while group 2 showed male preponderance (7:2), large ventricles, and mental retardation, with a benign course of epilepsy. Groups 3, 4 and 5 had a worse epileptic outcome than groups 1 and 2. The outcome of groups 4 and 5 unilateral cases was similar, regardless of cortical involvement. Genetic factors are important in etiology of bilateral PNH cases, with mutations involving FLN1 and other novel genes. Acquired prenatal factors are important in unilateral heterotopias, with co-occurrence of genetic and environmental factors in some. [1]

COMMENT. Most PNH are associated with refractory epilepsy. Epileptiform activity is generated in the nodules or in the adjacent neocortex. The heterotopia are part of an abnormal circuitry involving surrounding cortex.

EEG-fMRI studies of grey matter heterotopia at the Montreal Neurological Institute showed metabolic responses in the heterotopia while spikes were generated in the neocortex [2]. Activation responses reflected excitation involving the heterotopia and surrounding cortex, and deactivation also reflected a distant, extra-lesional inhibition. EEG-fMRI is a non-invasive procedure that may explain the epileptogenicity of neuronal migration disorders and the involvement of areas of the brain distant from the heterotopia.