TY - JOUR
T1 - Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES)
AU - Bonardi, Claudia M.
AU - Mignot, Cyril
AU - Serratosa, Jose M.
AU - Giraldez, Beatriz G.
AU - Moretti, Raffaella
AU - Rudolf, Gabrielle
AU - Reale, Chiara
AU - Gellert, Pia M.
AU - Johannesen, Katrine M.
AU - Lesca, Gaetan
AU - Tassinari, Carlo A.
AU - Gardella, Elena
AU - Møller, Rikke S.
AU - Rubboli, Guido
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - CNKSR2
KW - Encephalopathy
KW - ESES
KW - Speech/oro-motor dyspraxia
KW - Spike-wave-index (SWI)
KW - X-linked intellectual disabilities
U2 - 10.1016/j.clinph.2020.01.020
DO - 10.1016/j.clinph.2020.01.020
M3 - Journal article
C2 - 32197126
AN - SCOPUS:85082131787
VL - 131
SP - 1030
EP - 1039
JO - Clinical Neurophysiology
JF - Clinical Neurophysiology
SN - 1388-2457
IS - 5
ER -