From the Departments of Psychiatry and Neurology (S.S.J.), and Department of Psychiatry (J.K., B.M., C.S.), UCLA Semel Institute of Neuroscience and Human Behavior, Los Angeles, CA; Division of Pediatric Neurology (J.Y.W.), Mattel Children's Hospital, UCLA, Los Angeles; Department of Biostatistics (D.S.), School of Public Health, UCLA, Los Angeles; and Laboratories of Cognitive Neuroscience (K.V., V.V.-F., C.A.N.), Division of Developmental Medicine, Department of Neurology (K.D.), F.M. Kirby Neurobiology Center (M.S.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Neurology. 2014 Jul 8;83(2):160-8. doi: 10.1212/WNL.0000000000000568. Epub 2014 Jun 11.
We performed a longitudinal cohort study of infants with tuberous sclerosis complex (TSC), with the overarching goal of defining early clinical, behavioral, and biological markers of autism spectrum disorder (ASD) in this high-risk population.
Infants with TSC and typically developing controls were recruited as early as 3 months of age and followed longitudinally until 36 months of age. Data gathered at each time point included detailed seizure history, developmental testing using the Mullen Scales of Early Learning, and social-communication assessments using the Autism Observation Scale for Infants. At 18 to 36 months, a diagnostic evaluation for ASD was performed using the Autism Diagnostic Observation Schedule.
Infants with TSC demonstrated delays confined to nonverbal abilities, particularly in the visual domain, which then generalized to more global delays by age 9 months. Twenty-two of 40 infants with TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental trajectories over the second and third years of life differentiated the groups. By 12 months of age, the ASD group demonstrated significantly greater cognitive delays and a significant decline in nonverbal IQ from 12 to 36 months.
This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.
我们对结节性硬化症 (TSC) 患儿进行了一项纵向队列研究，其首要目标是在这一高危人群中确定自闭症谱系障碍 (ASD) 的早期临床、行为和生物学标志物。
从 3 个月大开始招募患有 TSC 和发育正常的对照组婴儿，并进行纵向随访至 36 个月。在每个时间点收集的数据包括详细的癫痫发作史、使用 Mullen 早期学习量表进行的发育测试以及使用婴儿自闭症观察量表进行的社交沟通评估。在 18 至 36 个月时，使用自闭症诊断观察量表进行 ASD 的诊断评估。
患有 TSC 的婴儿表现出仅限于非语言能力的延迟，特别是在视觉领域，到 9 个月大时则扩展到更广泛的延迟。40 名患有 TSC 的婴儿中有 22 名被诊断为 ASD。12 个月时的认知能力和第二年和第三年的发育轨迹都能区分这两组。到 12 个月大时，ASD 组表现出明显更大的认知延迟和从 12 到 36 个月非言语智商的显著下降。
这项前瞻性研究描述了 TSC 婴儿 ASD 的早期发育标志物。TSC 组整体上视觉接收和精细运动能力的早期延迟，加上 ASD 患儿的非语言能力下降，表明 ASD 存在特定领域的途径，可以为这些高危婴儿提供更有针对性的干预措施。
