De Ridder Jessie, Lavanga Mario, Verhelle Birgit, Vervisch Jan, Lemmens Katrien, Kotulska Katarzyna, Moavero Romina, Curatolo Paolo, Weschke Bernhard, Riney Kate, Feucht Martha, Krsek Pavel, Nabbout Rima, Jansen Anna C, Wojdan Konrad, Domanska-Pakieła Dorota, Kaczorowska-Frontczak Magdalena, Hertzberg Christoph, Ferrier Cyrille H, Samueli Sharon, Benova Barbora, Aronica Eleonora, Kwiatkowski David J, Jansen Floor E, Jóźwiak Sergiusz, Van Huffel Sabine, Lagae Lieven
Pediatric Neurology, Department of Development and Regeneration, University of Leuven KU Leuven, Leuven, Belgium.
Department of Electrical Engineering (ESAT), STADIUS Centre for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium.
Front Neurol. 2020 Oct 16;11:582891. doi: 10.3389/fneur.2020.582891. eCollection 2020.
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder with a high risk of early-onset epilepsy and a high prevalence of neurodevelopmental comorbidities, including intellectual disability and autism spectrum disorder (ASD). Therefore, TSC is an interesting disease model to investigate early biomarkers of neurodevelopmental comorbidities when interventions are favourable. We investigated whether early EEG characteristics can be used to predict neurodevelopment in infants with TSC. The first recorded EEG of 64 infants with TSC, enrolled in the international prospective EPISTOP trial (recorded at a median gestational age 42 4/7 weeks) was first visually assessed. EEG characteristics were correlated with ASD risk based on the ADOS-2 score, and cognitive, language, and motor developmental quotients (Bayley Scales of Infant and Toddler Development III) at the age of 24 months. Quantitative EEG analysis was used to validate the relationship between EEG background abnormalities and ASD risk. An abnormal first EEG (OR = 4.1, -value = 0.027) and more specifically a dysmature EEG background (OR = 4.6, -value = 0.017) was associated with a higher probability of ASD traits at the age of 24 months. This association between an early abnormal EEG and ASD risk remained significant in a multivariable model, adjusting for mutation and treatment (adjusted OR = 4.2, -value = 0.029). A dysmature EEG background was also associated with lower cognitive (-value = 0.029), language (-value = 0.001), and motor (-value = 0.017) developmental quotients at the age of 24 months. Our findings suggest that early EEG characteristics in newborns and infants with TSC can be used to predict neurodevelopmental comorbidities.
结节性硬化症(TSC)是一种多系统遗传性疾病,具有早发性癫痫的高风险以及神经发育合并症的高患病率,包括智力残疾和自闭症谱系障碍(ASD)。因此,当干预措施有利时,TSC是研究神经发育合并症早期生物标志物的一个有趣的疾病模型。我们研究了早期脑电图特征是否可用于预测TSC婴儿的神经发育情况。对纳入国际前瞻性EPISTOP试验的64例TSC婴儿(记录的中位胎龄为42又4/7周)的首次脑电图记录进行了初步视觉评估。根据ADOS-2评分以及24个月龄时的认知、语言和运动发育商(贝利婴幼儿发育量表第三版),将脑电图特征与ASD风险相关联。采用定量脑电图分析来验证脑电图背景异常与ASD风险之间的关系。首次脑电图异常(OR = 4.1,P值 = 0.027),更具体地说,脑电图背景发育不成熟(OR = 4.6,P值 = 0.017)与24个月龄时出现ASD特征的可能性较高相关。在调整了突变和治疗因素的多变量模型中,早期脑电图异常与ASD风险之间的这种关联仍然显著(调整后的OR = 4.2,P值 = 0.029)。脑电图背景发育不成熟还与24个月龄时较低的认知(P值 = 0.029)、语言(P值 = 0.001)和运动(P值 = 0.017)发育商相关。我们的研究结果表明,TSC新生儿和婴儿的早期脑电图特征可用于预测神经发育合并症。