Phase-amplitude coupling of interictal fast activities modulated by slow waves on scalp EEG and its correlation with seizure outcomes of disconnection surgery in children with intractable nonlesional epileptic spasms

OBJECTIVE Epileptic spasms (ESs) are classified as focal, generalized, or unknown onset ESs. The classification of ESs and surgery in patients without lesions apparent on MRI is challenging. Total corpus callosotomy (TCC) is a surgi- cal option for diagnosis of the lateralization and possible treatment for ESs. This study investigated phase-amplitude coupling (PAC) of fast activity modulated by slow waves on scalp electroencephalography (EEG) to evaluate the strength of the modulation index (MI) before and after disconnection surgery in children with intractable nonlesional ESs. The authors hypothesize that a decreased MI due to surgery correlates with good seizure outcomes. METHODS The authors studied 10 children with ESs without lesions on MRI who underwent disconnection surgeries. Scalp EEG was obtained before and after surgery. The authors collected 20 epochs of 3 minutes each during non-rapid eye movement sleep. The MI of the gamma (30-70 Hz) amplitude and delta (0.5-4 Hz) phase was obtained in each electrode. MIs for each electrode were averaged in 4 brain areas (left/right, anterior/posterior quadrants) and evaluated to determine the correlation with seizure outcomes. RESULTS The median age at first surgery was 2.3 years (range 10 months-9.1 years). Two patients with focal onset ESs underwent anterior quadrant disconnection (AQD). TCC alone was performed in 5 patients with generalized or unknown onset ESs. Two patients achieved seizure freedom. Three patients had residual generalized onset ESs. Disconnection surgeries in addition to TCC consisted of TCC + posterior quadrant disconnection (PQD) (1 patient); TCC + AQD + PQD (1 patient); and TCC + AQD + hemispherotomy (1 patient). Seven patients became seizure free with a mean follow-up period of 28 months (range 5-54 months). After TCC, MIs in 4 quadrants were significantly lower in the 2 sei- zure-free patients than in the 6 patients with residual ESs (p < 0.001). After all 15 disconnection surgeries in 10 patients, MIs in the 13 target quadrants for each disconnection surgery that resulted in freedom from seizures were significantly lower than in the 26 target quadrants in patients with residual ESs (p < 0.001). CONCLUSIONS In children with nonlesional ESs, PAC for scalp EEG before and after disconnection surgery may be a surrogate marker for control of ESs. The MI may indicate epileptogenic neuronal modulation of the interhemispheric corpus callosum and intrahemispheric subcortical network for ESs. TCC may be a therapeutic option to disconnect the interhemispheric modulation of epileptic networks.