Development of visual and neurologic outcome measures in pediatric MS

描述（由申请人提供）：本申请为儿童神经病学讲师提供职业发展奖，该讲师对定义儿童多发性硬化症（MS）的视觉和神经系统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、验证并将这些结果测量应用于儿科多发性硬化症试验。该提案将为候选人提供额外的培训，以完善研究设计，进行实际测试，执行数据分析，准备手稿和未来的资助，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获得通过多学科

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.