Night-time unravelling of the brain web: impaired synaptic downscaling in ESES--the Penelope syndrome.

ESES (encephalopathy with status epilepticus during sleep) is an epileptic encephalopathy with heterogeneous clinical manifestations (cognitive, motor, and behavioral disturbances in different associations, and various seizure types) related to a peculiar electroencephalography (EEG) pattern characterized by paroxysmal activity significantly activated during slow sleep—that is, a condition of continuous spikes and waves, or status epilepticus, during sleep. The pathophysiologic mechanisms underlying this condition are still incompletely understood; since 2005 we suggested that the abnormal epileptic EEG activity occurring during sleep might cause the typical clinical symptoms by interfering with sleep-related physiologic functions, and possibly neuroplasticity processes mediating higher cortical functions such as learning and memory consolidation (the ‘Penelope syndrome’ hypothesis - Tassinari et al., 2005, 2009; Tassinari and Rubboli, 2006). In this Editorial we discussed the results of the first study demonstrating that physiological downscaling during NREM sleep is impaired in ESES (Bölsterli et al. 2011), confirming our previous hypothesis, and opening a new way for the understanding of the relevance of paroxysmal activities during sleep, not only for ESES but for a large population of children with significant activation of focal paroxysmal epileptiform activity during sleep.