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）：在美国，每八名儿童中就有一人患有神经发育障碍，需要医疗、教育和特殊服务的补救。在美国，每 88 名儿童中就有 1 人患有自闭症谱系障碍 (ASD)（CDC 数据）。早期治疗干预是唯一可用的治疗方法，并且已被临床证明可以有效改善这些儿童的预后。然而，目前早期识别神经发育障碍的做法依赖于家长报告加上行为观察，但准确性和敏感性较差。因此，临床需要一种能够跟踪婴儿和幼儿正常神经发育进展的客观测量（“生物标志物”）。瞳孔光反射 (PLR) 是一种简单的功能性神经学测试，可测量瞳孔大小因短暂闪光而发生的变化。我们最近的研究表明，与正常发育的儿童相比，自闭症儿童的 PLR 潜伏期明显更长，收缩幅度更小，收缩和再扩张时间更短。此外，在正常发育的儿童中，PLR 潜伏期从 6 岁到 8 岁显着下降。自闭症谱系障碍儿童中并未出现这种年龄趋势。这些结果表明，PLR 可能有潜力满足上述临床需求，即早期识别神经发育障碍的客观生物标志物。遗憾的是，文献中缺乏 6 岁以下儿童的 PLR 数据，因为现有的 PLR 仪器无法可靠地用于幼儿。为了解决这一缺陷，我们开发了一种新型远程成像系统，可以测量儿童的 PLR，而无需保持头部静止。我们在此建议测量 50 名 2 至 6 岁 ASD 儿童（每个年龄 10 名儿童）和同等数量的人口统计匹配（年龄和性别）典型对照的 PLR。具体来说，我们将检验以下假设：在年龄较大的 ASD 儿童中观察到的非典型 PLR 参数也存在于 2 至 6 岁的年幼儿童中。此外，我们将检验以下假设：在 6 岁以下的典型发育儿童中，PLR 潜伏期随着年龄的增长而减少，而这种年龄趋势不会出现在患有自闭症谱系障碍 (ASD) 的幼儿中。该 R21 项目将产生目前文献中缺失的数据，但对于确定 PLR 是否可以用作 6 岁以下儿童神经发育障碍的生物标志物至关重要。如果成功，这样一个简单的物理生物标志物将极大地改善目前儿童神经发育障碍早期识别的实践，并确保及时诊断和治疗干预。