Danish Epilepsy Centre, Dianalund, Denmark; Department of Woman's and Child's Health, University Hospital of Padua, Italy.
APHP, Groupe Hospitalier Pitié Salpêtrière, Unité Fonctionnelle de Génétique Médicale, Paris, France; Centre de Référence Déficiences Intellectuelles de Causes Rares, Paris, France; INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France.
Clin Neurophysiol. 2020 May;131(5):1030-1039. doi: 10.1016/j.clinph.2020.01.020. Epub 2020 Feb 13.
To investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants.
Detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES.
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.
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.
Our findings expand the phenotypic spectrum of CNKSR2-related ESES.
研究与 CNKSR2 致病性变异相关的慢波睡眠期癫痫持续状态（ESES）伴脑病的临床和脑电图特征。
收集了 5 例 CNKSR2 相关性 ESES 患者的详细临床病史、多次清醒/整夜睡眠脑电图和脑 MRI。
2 例患者婴儿期神经发育正常，3 例患者神经发育延迟。癫痫发作（年龄范围：2-6 岁）与认知障碍、语言退化和/或行为障碍的出现或加重有关。癫痫和认知/行为障碍的恶化与非快速眼动（NREM）睡眠相关的额区为主的脑电图癫痫放电增强（棘波指数（SWI）：60-96%）相一致，提示 ESES。3 例患者出现失神持续状态发作或非典型失神发作加重，后者伴有清醒 SWI 显著增加。4 例患者被诊断为言语/口运动性构音障碍。2 例患者长期随访显示癫痫缓解，轻度/中度认知障碍和行为障碍持续到成年。
本研究的新发现为女性也会发生该病，癫痫发作前神经发育正常，癫痫加重与清醒时 SWI 增强有关，成年后轻度/中度进展，以及言语/口运动性构音障碍导致的语言障碍。
我们的发现扩展了 CNKSR2 相关性 ESES 的表型谱。
