Development of visual and neurologic outcome measures in pediatric MS

描述(由申请人提供)：这项申请提出了一个儿童神经学教师的职业发展奖，该教师对定义儿童多发性硬化症(MS)的视觉和神经学结果测量有科学兴趣。她的长期职业目标是进行独立的临床研究，定义、验证并将这些结果指标应用于儿科多发性硬化症试验。这项建议将为候选人提供额外的培训，以完善研究设计，执行动手测试，执行数据分析，并准备手稿和未来的赠款，以支持作为独立临床科学家的职业生涯。新的技能和进一步的知识将通过一个多学科的 这是一项横跨神经学、儿科、眼科和放射学领域的研究计划，采用三种互补的方法：1)密集的指导和与高级研究人员的合作，2)在生物统计学和生物医学成像和分析方面的额外教学培训，以及3)原创研究的表现。成人MS试验结果指标的发展导致了关于疾病发病机制的重要发现，建立了视力损失(通过低对比度字母视力测试捕获)与轴突和神经元损失(通过使用光学相干断层扫描[OCT]对视网膜神经纤维层[RNFL]和黄斑进行结构性非侵入性成像测量)之间的相关性。儿童的视觉和神经学测量还没有得到严格的研究，目前的研究表明，与成人相比，儿童疾病的发病机制存在差异。这项建议将实现以下目标：具体目标1-确定儿童多发性硬化症的视觉和神经功能概况，并确定哪些指标最好地区分疾病儿童和对照组。具体目标2-确定视觉和神经功能的测量如何反映OCT捕获的轴突和神经元丢失，并根据视神经炎病史进行调整。具体目标3-使用其他电生理学和MRI替代物验证OCT测量的轴突丢失的存在或不存在。这些研究将确定这些测量儿童视觉和神经功能和结构的潜在作用 MS临床试验。该提案中概述的机构、导师和合作者致力于研究和培养年轻的研究人员。提出了一项有严格指导的科学研究的结构化职业发展计划，以便在五年结束时将候选人置于独立调查的位置。

DESCRIPTION (provided by applicant): This application proposes a career development award for an Instructor in Child Neurology with scientific interest in defining visual and neurologic outcome measures in pediatric multiple sclerosis (MS). Her long-term career goal is to conduct independent clinical research that defines, validates, and applies these outcome measures to pediatric MS trials. This proposal will provide the Candidate with additional training for the refinement of study design, performance of hands-on testing, execution of data analysis, and preparation of manuscripts and future grants to support a career as an independent clinician scientist. New skills and further knowledge will be obtained through a multi-disciplinary research program that spans the fields of neurology, pediatrics, ophthalmology, radiology using three complementary approaches: 1) intensive mentorship and collaboration with senior investigators, 2) additional didactic training in biostatistics and biomedical imaging and analysis and 3) performance of original research. The development of outcome measures for adult MS trials has led to important discoveries about the pathogenesis of disease by establishing a correlation between visual loss (as captured by low-contrast letter acuity testing) and axonal and neuronal loss (as measured by structural non-invasive imaging of the retinal nerve fiber layer [RNFL] and macula using optical coherence tomography [OCT]). Visual and neurologic measures have not been rigorously studied in children, and current research has demonstrated differences in the pathogenesis of disease in children compared to adults. This proposal will accomplish the following aims: Specific Aim 1 - Define the profile of visual and neurologic function in pediatric MS and establish which measures best distinguish children with disease from controls. Specific Aim 2 - Determine how measures of visual and neurologic function reflect axonal and neuronal loss as captured by OCT, adjusting for a history of optic neuritis. Specific Aim 3 - Validate the presence or absence of axonal loss as measured by OCT using other electrophysiologic and MRI surrogates for axonal loss. These investigations will define the potential roles for these measures of visual and neurologic function and structure in pediatric MS clinical trials. The Institutions, Mentor, and Collaborators outlined in this proposal are dedicated to research and cultivating young investigators. A structured career development plan with a rigorously mentored scientific study is proposed to position the candidate for independent investigation at the end of five years.