Epileptic spasms with terror during sleep in CDKL5 encephalopathy

Study objectives to describe early diagnostic clues in Cyclin-dependent kinase-like 5 (CDKL5) refractory encephalopathy, to improve treatment strategies. Methods we retrospectively studied 35 patients (25 females, 10 males) with CDKL5 gene mutations or deletion, focusing on their early seizure semiology, the electroencephalogram pattern, the effect of treatment and developmental outcome. Results the first seizures were recognizable and consisted of tonic, then clonic and spasms phases, occurring in sleep at a median age of 6 weeks. Clusters of spasms were observed in quiet sleep (QS) or slow wave sleep (SWS), with screaming, staring and arms’ extension that mimicked sleep terror in 28 of 35 patients (80%). Programmed awakening prevented these spasms in nine of 16 patients and small doses of clonazepam given at night improved epilepsy in 14 of 23 patients. Conclusion peculiar seizures with spasms starting in SWS are an early diagnostic clue in infants with CDKL5 encephalopathy. Sleep video-EEG polygraphy is an easy tool to disclose these early seizures and epileptic spasms in infants during first months of life while polysomnography is unlikely to give contribution at that early age. While conventional antiepileptic treatment and corticosteroids are poorly, transiently or not efficient, therapeutic strategy used for sleep terror could help, although the mechanism of spasms generation in SWS needs to be elucidated.