Jeste Shafali S, Varcin Kandice J, Hellemann Gerhard S, Gulsrud Amanda C, Bhatt Rujuta, Kasari Connie, Wu Joyce Y, Sahin Mustafa, Nelson Charles A
From the UCLA Semel Institute of Neuroscience and Human Behavior (S.S.J., G.S.H., A.C.G., R.B., C.K.) and Division of Pediatric Neurology, Mattel Children's Hospital UCLA (R.B., J.Y.W.), David Geffen School of Medicine, Los Angeles, CA; Laboratories of Cognitive Neuroscience, Division of Developmental Medicine (K.J.V., C.A.N.), and F.M. Kirby Neurobiology Center, Translational Neuroscience Center, Department of Neurology (M.S.), Boston Children's Hospital/Harvard Medical School; and Harvard Graduate School of Education (C.A.N.), Harvard University, Cambridge, MA.
Neurology. 2016 Aug 23;87(8):766-72. doi: 10.1212/WNL.0000000000003002. Epub 2016 Jul 20.
To determine the extent to which deficits associated with autism spectrum disorder (ASD) in toddlers with tuberous sclerosis complex (TSC) overlap with those in toddlers with nonsyndromic ASD (nsASD) and to examine cognitive function and epilepsy severity in toddlers with TSC and comorbid ASD. This is the endpoint analysis from a longitudinal investigation of ASD risk factors in children with TSC.
Measures included the Autism Diagnostic Observation Schedule (ADOS), the Mullen Scales of Early Learning, and clinical epilepsy variables. A repeated-measures analysis of variance was performed with between-subjects factor of group (typically developing, TSC/no ASD, TSC/ASD, nsASD) and within-subjects factors of individual ADOS item scores in the social communication and repetitive behavior/restricted interest domains. Within the TSC group, comparisons of epilepsy characteristics and cognitive domains were performed using independent-samples t tests.
Children with TSC/ASD demonstrated a profile of social communication impairment that had complete convergence with nsASD. Measured social communication impairments included gestures, pointing, eye contact, responsive social smile, and shared enjoyment. This convergence was observed despite the high comorbidity between ASD and cognitive impairment in TSC.
This study supports the clinical diagnosis of ASD in young children with TSC and demonstrates remarkable convergence of autism symptoms between TSC/ASD and nsASD. Our results strongly suggest the need for early intervention in toddlers with TSC, with treatment strategies targeting social communication function as well as broader developmental domains, before the onset of autism symptoms.
确定结节性硬化症（TSC）幼儿中与自闭症谱系障碍（ASD）相关的缺陷与非综合征性ASD（nsASD）幼儿中缺陷的重叠程度，并检查患有TSC和共病ASD的幼儿的认知功能和癫痫严重程度。这是对TSC儿童ASD危险因素进行纵向调查的终点分析。
测量指标包括自闭症诊断观察量表（ADOS）、马伦早期学习量表以及临床癫痫变量。进行重复测量方差分析，组间因素为组别（发育正常、TSC/无ASD、TSC/ASD、nsASD），组内因素为社交沟通和重复行为/受限兴趣领域中各个ADOS项目得分。在TSC组内，使用独立样本t检验对癫痫特征和认知领域进行比较。
TSC/ASD儿童表现出与nsASD完全一致的社交沟通障碍特征。测量的社交沟通障碍包括手势、指物、眼神接触、有反应的社交微笑和共同乐趣。尽管TSC中ASD与认知障碍共病率很高，但仍观察到这种一致性。
本研究支持对TSC幼儿进行ASD的临床诊断，并证明TSC/ASD和nsASD之间自闭症症状有显著一致性。我们的结果强烈表明，需要对TSC幼儿进行早期干预，在自闭症症状出现之前，采用针对社交沟通功能以及更广泛发育领域的治疗策略。
