Development of visual and neurologic outcome measures in pediatric MS

儿科多发性硬化症视觉和神经系统结果测量的发展

• 批准号: 9085475
• 负责人: Amy Tara Waldman
• 金额: $ 18.44万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9085475
• 关键词: Accounting; Adolescence; Adult; Age; Anterior; Auditory; Biometry; Blindness; Brain; Child; Childhood; Clinical Research; Clinical Trials; Collaborations; Conduct Clinical Trials; Data; Data Analyses; Demyelinations; Development; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Enhancing Lesion; Eye; Foundations; Functional disorder; Future; Goals; Grant; Health; Image; Image Analysis; Institution; Investigation; K-Series Research Career Programs; Knowledge; Letters; MRI Scans; Magnetic Resonance Imaging; Manuscripts; Measures; Mentors; Mentorship; Methods; Modeling; Motor; Multiple Sclerosis; Nervous System Physiology; Neurologic; Neurological outcome; Onset of illness; Ophthalmology; Optic Neuritis; Optical Coherence Tomography; Optics; Outcome; Outcome Assessment; Outcome Measure; Pathogenesis; Patients; Pattern; Pediatric Neurology; Performance; Positioning Attribute; Preparation; Radiation; Radiology Specialty; Receiver Operating Characteristics; Recording of previous events; Recruitment Activity; Relapse; Research; Research Design; Research Personnel; Research Support; Resolution; Role; Scientist; Structure; Testing; Thick; Time; Training; Vision; Visual; Visual Acuity; Visual Pathways; Visual evoked cortical potential; Walking; Work; age group; bioimaging; burden of illness; career; career development; disability; disorder control; follow-up; foot; gray matter; imaging modality; improved outcome; indexing; insight; instructor; interest; macula; middle age; monocular; multiple sclerosis patient; neuron loss; non-invasive imaging; programs; quantitative imaging; research study; retinal nerve fiber layer; skills; vision development; white matter

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.

描述（由申请人提供）：本申请为儿童神经病学讲师提出职业发展奖，该讲师对定义小儿多发性硬化症 (MS) 的视觉和神经系统结果测量具有科学兴趣。她的长期职业目标是进行独立的临床研究，定义、验证这些结果指标并将其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、进行实践测试、执行数据分析以及准备手稿和未来的资助，以支持独立临床科学家的职业生涯。新技能和更多知识将通过多学科获得 研究计划涵盖神经病学、儿科、眼科、放射学领域，采用三种互补方法：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方面的额外教学培训，3）原创研究的表现。 成人多发性硬化症试验结果测量的发展通过建立视力丧失（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，获得了关于疾病发病机制的重要发现。尚未对儿童进行严格的视觉和神经学测量研究，目前的研究已证明儿童与成人相比，疾病发病机制存在差异。该提案将实现以下目标： 具体目标 1 - 定义儿科多发性硬化症的视觉和神经功能概况，并确定哪些措施最能区分患有疾病的儿童和对照儿童。 具体目标 2 - 确定视觉和神经功能测量如何反映 OCT 捕获的轴突和神经元损失，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 替代轴突损失的 OCT 测量结果，验证是否存在轴突损失。 这些研究将确定这些视觉和神经功能和结构测量在儿科中的潜在作用 多发性硬化症临床试验。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研究人员。建议制定一个结构化的职业发展计划，并进行严格指导的科学研究，以便候选人在五年后接受独立调查。

项目成果

International Pediatric MS Study Group Global Members Symposium report.

国际儿科多发性硬化症研究组全球成员研讨会报告。

• DOI: 10.1212/wnl.0000000000002880
• 发表时间: 2016
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Wassmer,Evangeline;Chitnis,Tanuja;Pohl,Daniela;Amato,MariaPia;Banwell,Brenda;Ghezzi,Angelo;Hintzen,RogierQ;Krupp,LaurenB;Makhani,Naila;Rostásy,Kevin;Tardieu,Marc;Tenembaum,Silvia;Waldman,Amy;Waubant,Emmanuelle;Kornberg,Andr
• 通讯作者: Kornberg,Andr

Optical coherence tomography and visual evoked potentials in pediatric MS.

• DOI: 10.1212/nxi.0000000000000356
• 发表时间: 2017-07
• 期刊: Neurology(R) neuroimmunology & neuroinflammation
• 作者: Waldman AT;Liu GT;Lavery AM;Liu G;Gaetz W;Aleman TS;Banwell BL
• 通讯作者: Banwell BL

Leukodystrophies.

脑白质营养不良。

• DOI: 10.1212/con.0000000000000560
• 发表时间: 2018
• 期刊: Continuum (Minneapolis, Minn.)
• 作者: Waldman,AmyT

Structural correlates of atypical visual and motor cortical oscillations in pediatric-onset multiple sclerosis.

• DOI: 10.1002/hbm.25126
• 发表时间: 2020-10-15
• 期刊: Human brain mapping
• 影响因子: 4.8
• 作者: Waldman AT;Sollee JR;Datta R;Lavery AM;Liu G;Aleman TS;Banwell BL;Gaetz WC
• 通讯作者: Gaetz WC

Correction to: Impact of an electronic monitoring device and behavioural feedback on adherence to multiple sclerosis therapies in youth: results of a randomized trial.

更正：电子监测设备和行为反馈对青少年多发性硬化症治疗依从性的影响：随机试验的结果。

• DOI: 10.1007/s11136-017-1773-4
• 发表时间: 2018
• 期刊: Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
• 作者: Yeh,EAnn;Grover,StephanieA;Powell,VictoriaE;Alper,Gulay;Banwell,BrendaL;Edwards,Kim;Gorman,Mark;Graves,Jennifer;Lotze,TimothyE;Mah,JeanK;Mednick,Lauren;Ness,Jayne;Obadia,Maya;Slater,Ruth;Waldman,Amy;Waubant,Emmanuelle