Evaluation of pupillary light reflex as biomarker of neurodevelopmental disorder

瞳孔对光反射作为神经发育障碍生物标志物的评估

• 批准号: 8487938
• 负责人: GANG YAO
• 金额: $ 22.63万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-08 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487938
• 关键词: 17 year old; 6 year old; 8 year old; Academy; Address; Adult; Age; American; Biological Markers; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinical; Data; Development; Diagnosis; Early identification; Economics; Ensure; Evaluation; Functional disorder; Funding Opportunities; Gender; Head; Image; Infant; Light; Literature; Measurement; Measures; Medical; Monitor; Nervous System Physiology; Neurodevelopmental Disability; Neurodevelopmental Disorder; Neurologic; Outcome; Parents; Pediatrics; Positioning Attribute; Procedures; Pupil; Pupil light reflex; Reporting; Services; System; Testing; Therapeutic; Therapeutic Intervention; Time; Toddler; United States National Institutes of Health; age related; autism spectrum disorder; behavior observation; constriction; empowered; improved; instrumentation; meetings; nervous system disorder; novel; public health relevance; remediation; response; tool; trend

DESCRIPTION (provided by applicant): Every one in eight children in the USA is born with a neurodevelopmental disability that will require medical, educational and special services remediation. Autism spectrum disorder (ASD) alone develops in 1 in 88 children in the US (CDC data). Early therapeutic intervention is the only available treatment and has been clinically proven effective in improving these children's outcomes. However, current practice for early identification of neurodevelopmental disorders relies on parent reporting plus behavioral observation that suffers from poor accuracy and sensitivity. Therefore, there is a clinical need for an objective measure ("biomarker") that can track normal neurodevelopmental progress in infants and toddlers. Pupillary light reflex (PLR) is a simple functional neurological test that measures the pupil size changes in response to a short light flash. Our recent studies revealed that children with ASD had significantly longer PLR latency, lesser constriction amplitude, and shorter constriction and redilation times than typically developing children. Moreover, the PLR latency decreased significantly from 6 to 8 years of age in typically developing children. This age trend did not occur in children with ASD. These results suggest that PLR may have the potential to meet this aforementioned clinical need of an objective biomarker for the early identification of neurodevelopmental disorders. Unfortunately there is a lack of PLR data in children younger than 6 years old in the literature because existing PLR instrumentation cannot be reliably used in young children. To address this deficiency, we have developed a novel remote imaging system that can measure PLR in children without the need to hold their head still. We propose here to measure PLR in fifty 2 to 6 years old children with ASD (10 children at each age) and equal number of demographically matched (age and gender) typical controls. Specifically, we will test the hypothesis that atypical PLR parameters observed in older children with ASD also exist in younger children from 2 to 6 years old. In addition, we will test the hypothesis that PLR latency decreases with age in typically developing children younger than 6 years old and such age trend fails to occur in young children with ASD. This R21 project will produce data that are currently missing from literature, yet are critical to determining whether PLR can be used as a biomarker for neurodevelopmental disability in children younger than 6 years. If successful, such a simple physical biomarker will improve tremendously the current practice of early identification of neurodevelopmental disorders in children and ensure prompt diagnosis and therapeutic intervention.

描述（由申请人提供）：美国八分之一的孩子天生患有神经发育残疾，需要医疗，教育和特殊服务修复。仅在美国，有88名儿童中有1个单独出现自闭症谱系障碍（ASD）（CDC数据）。早期的治疗干预是唯一可用的治疗方法，并且在临床上证明有效地改善了这些儿童的结果。但是，当前对神经发育障碍的早期鉴定的实践取决于父母的报告以及行为观察，其准确性和敏感性差。因此，临床需要进行客观度量（“生物标志物”），该测量可以跟踪婴儿和幼儿的正常神经发育进展。瞳孔光反射（PLR）是一种简单的功能性神经测试，可测量瞳孔大小的变化，以响应短闪光。我们最近的研究表明，与典型的儿童相比，ASD儿童的PLR潜伏期明显更长，收缩幅度较小，收缩时间较短和降级时间。此外，PLR潜伏期在典型发展的儿童中从6岁到8岁显着下降。 ASD儿童没有发生这种年龄趋势。这些结果表明，PLR可能有可能满足上述临床需求，这是对神经发育障碍的早期鉴定的客观生物标志物。不幸的是，文献中6岁以下儿童缺乏PLR数据，因为现有的PLR仪器无法可靠地用于幼儿。为了解决这种缺陷，我们开发了一种新颖的远程成像系统，该系统可以在儿童中衡量PLR，而无需保持头脑。我们在这里提议在五十2至6岁的ASD儿童（每个年龄段10个儿童）和相等数量的人口统计学匹配（年龄和性别）典型控制中测量PLR。具体而言，我们将测试以下假设：在2至6岁的年幼儿童中，ASD的大儿童中观察到的非典型PLR参数也存在。此外，我们将检验以下假设：PLR潜伏期随着年龄的增长而在6岁以下的典型儿童中随着年龄的增长而降低，而这种年龄趋势未能发生在ASD的幼儿中。这个R21项目将产生目前文献中缺少的数据，但对于确定PLR是否可以用作6岁以下儿童神经发育残疾的生物标志物至关重要。如果成功的话，如此简单的物理生物标志物将极大地改善当前对儿童神经发育障碍的早期鉴定的实践，并确保迅速的诊断和治疗干预。