Development of visual and neurologic outcome measures in pediatric MS

描述（由申请人提供）：本申请提出了一个职业发展奖的教师在儿童神经学与科学的兴趣，在定义视觉和神经功能的结果措施在小儿多发性硬化症（MS）。她的长期职业目标是进行独立的临床研究，定义，验证，并将这些结果的措施应用于儿科MS试验。该提案将为候选人提供额外的培训，以完善研究设计，进行实践测试，执行数据分析，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多学科获得 该研究计划涵盖神经病学，儿科学，眼科学，放射学领域，采用三种互补的方法：1）与高级研究人员的强化指导和合作，2）生物统计学和生物医学成像和分析的额外教学培训，3）原创研究的表现。 成人MS试验结局指标的开发通过建立视力丧失（通过低对比度字母敏锐度测试捕获）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]和黄斑进行结构非侵入性成像测量）之间的相关性，导致了有关疾病发病机制的重要发现。视觉和神经功能的措施还没有严格的研究儿童，目前的研究表明，在疾病的发病机制在儿童相比，成人的差异。该提案将实现以下目标：具体目标1 -定义儿童MS的视觉和神经功能特征，并确定最佳区分疾病儿童和对照儿童的措施。 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损失，调整视神经炎病史。 具体目标3 -确定是否存在轴突损失，通过OCT使用轴突损失的其他电生理和MRI替代物测量。 这些研究将确定这些视觉和神经功能和结构的措施在儿童中的潜在作用。 MS临床试验。本提案中概述的机构，导师和合作者致力于研究和培养年轻的研究人员。提出了一个结构化的职业发展计划，其中包括一项严格指导的科学研究，以便在五年结束时将候选人定位为独立调查。

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.