Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES). Issue 5 (May 2020)

• Record Type: Journal Article
• Authors: Bonardi, Claudia M.; Mignot, Cyril; Serratosa, Jose M.; Giraldez, Beatriz G.; Moretti, Raffaella; Rudolf, Gabrielle; Reale, Chiara; Gellert, Pia M.; Johannesen, Katrine M.; Lesca, Gaetan; Tassinari, Carlo A.; Gardella, Elena; Møller, Rikke S.; Rubboli, Guido
• Is Part Of: Clinical neurophysiology. Volume 131:Issue 5(2020:May)
• Page Start: 1030
• Page End: 1039
• Publication Date: 2020-05
• Subjects: CNKSR2 -- ESES -- Encephalopathy -- Speech/oro-motor dyspraxia -- X-linked intellectual disabilities -- Spike-wave-index (SWI); AED anti-epileptic drugs -- array-CGH array-comparative genomic hybridization -- EAS epilepsia aphasia spectrum disorders -- EEG electroencephalogram -- ESES encephalopathy with status epilepticus during slow sleep -- MRI magnetic resonance imaging -- NGS next generation sequencing -- NREM non-rapid eye movement -- REM rapid eye movement -- SWI spike wave index -- WES whole exome sequencing -- WISC-R Wechsler intelligence scale for children revised -- WPPSI Wechsler preschool and primary scale of intelligence; Neurophysiology -- Periodicals; Electroencephalography -- Periodicals; Electromyography -- Periodicals; Neurology -- Periodicals; 612.8
• DOI: 10.1016/j.clinph.2020.01.020
• Languages: English
• ISSNs: 1388-2457

Abstract

Highlights: Worsening of epilepsy associated with increment of awake spike-wave-index. A frontal topography of sleep EEG epileptic activity in the active phase of ESES. Language disorder due to speech/oro-motor dyspraxia. Abstract: Objective: To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. Methods: Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2 -related ESES. Results: Neurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2–6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60–96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood. Conclusions: Novel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia. Significance: Our findings expand the phenotypic spectrum of CNKSR2 -related ESES.