Simultaneous electroencephalography-transcranial magnetic stimulation (EEG-TMS) investigates cortical reactivity to external perturbations. TMS evoked potentials (TEPs) have been described in normals during sleep and wake but not after sleep deprivation or in pathologically enhanced excitability, i.e., epilepsy. The aim of our study was to identify TEPs and their modifications via EEG-TMS co-registration in healthy controls and patients with juvenile myoclonic epilepsy (JME) during wake, sleep deprivation and sleep conditions. Focal TMS was administered to the primary motor cortex in 12 healthy controls and 10 patients with JME. At least 150 TMS were delivered randomly every 8-15s during wake, sleep deprivation and sleep conditions. EEG was simultaneously acquired from 32 scalp electrodes. A significant increase in late peak amplitudes (P100 and N190) was observed in all subjects during the sleep-deprived condition, with a marked anterior increase and overall higher amplitude potentials in the JME patients. We demonstrated an overall higher cortical excitability in the JME patients, particularly over the anterior cortex after sleep deprivation and rebound sleep. This phenomenon could be related to the cortico-thalamic circuit dysfunctions believed to cause myoclonic epilepsy and a higher susceptibility of the frontal and prefrontal areas to the effects of sleep deprivation.