The Radiologically Isolated Syndrome in Children

项目总结/摘要 Makhani博士是一名儿科神经学家，其长期目标是实施预防多发性硬化的策略。 有患硬化症风险的儿童。建议的培训和指导研究经验将使她能够 发展进行纵向队列研究和使用MRI作为临床和研究工具的专业知识。 博士Makhani已经组建了一个专家团队，由导师和顾问组成，致力于帮助她。尤金博士 夏皮罗，她的主要导师，是一个公认的领导人在临床流行病学研究和博士丹尼尔佩尔蒂埃 他是一位世界级的专家，擅长利用核磁共振成像研究多发性硬化症的生物学。马哈尼医生会 课程在耶鲁大学的理论和应用成像技术在神经学研究中的使用，并将 我花了六个月的时间在Pelletier博士的多发性硬化症高级成像实验室接受实践培训 在南加州大学。她还将参加耶鲁大学遗传学高级课程，以及 成像数据、纵向数据、事件发生时间数据和临床试验的分析。 儿童多发性硬化症是中枢神经系统最常见的自身免疫性疾病， 复发率高，可能在年轻时发展为残疾，但治疗可能会改善两者。的 在没有任何多发性硬化症症状的人群中发现了多发性硬化症的典型MRI表现 因其他原因接受脑部MRI扫描的患者（例如，头部创伤）。这种临床情况一直是 放射学孤立综合征（RIS）。在患有RIS的成年人中，34%的人发展为临床神经系统疾病， 在最初MRI异常的五年内出现与多发性硬化症一致的症状。在患有RIS的成人中， 年龄<37岁、男性和MRI上的脊髓病变与临床神经系统疾病的发生相关 症状我们不知道风险或什么因素与临床诊断有关 多发性硬化症的发病率 我们将进行一项混合的历史和前瞻性纵向队列研究，以确定 可能性和相关因素（临床、人口统计学、MRI、实验室和遗传） RIS儿童多发性硬化症的临床诊断。这项研究将有助于确定 哪些患有RIS的儿童患临床多发性硬化症的风险最大，并将为干预奠定基础 在这些儿童中进行预防或延迟临床多发性硬化症发作的试验。在完成这项奖励后， 博士Makhani将是世界上唯一一位在儿科多学科领域接受过正式奖学金培训的儿科神经学家。 在儿童多发性硬化症的研究中使用神经成像技术的正规培训。她 将与她合作，对患有RIS的儿童进行第一次也是唯一一次纵向队列研究。 儿科RIS联盟，这将为未来的研究提供必要的基础设施，她会很好 准备申请资金成为一名独立的临床科学家。

PROJECT SUMMARY / ABSTRACT Dr. Makhani is a pediatric neurologist whose long-term goal is to implement strategies to prevent multiple sclerosis in children at risk. The training and mentored research experience proposed will enable her to develop expertise in conducting longitudinal cohort studies and in using MRI as a clinical and research tool. Dr. Makhani has assembled an expert and committed team of mentors and advisors to help her. Dr. Eugene Shapiro, her primary mentor, is a recognized leader in clinical epidemiological research and Dr. Daniel Pelletier (co-mentor) is a world expert in using MRI to study the biology of multiple sclerosis. Dr. Makhani will take courses at Yale on the theory and application of use of imaging techniques in neurological research and will spend six months with Dr. Pelletier getting hands-on training in his Advanced Imaging in Multiple Sclerosis lab at the University of Southern California. She will also take advanced courses at Yale in genetics, as well as in the analysis of imaging data, of longitudinal data, of time-to-event data and of clinical trials. Children with multiple sclerosis, the most common autoimmune disease of the central nervous system, have high relapse rates and may develop disability at a young age, but treatment may improve both. The typical MRI findings of multiple sclerosis have been found in people without any symptoms of multiple sclerosis who underwent MRI scans of the brain for other reasons (e.g., head trauma). This clinical scenario has been termed the radiologically isolated syndrome (RIS). Among adults with RIS, 34% developed clinical neurological symptoms consistent with multiple sclerosis within five years of the initial abnormal MRI. In adults with RIS, age <37 years, male sex and spinal cord lesions on MRI were associated with developing clinical neurological symptoms. We do not know either the risk of or what factors are associated with developing a clinical diagnosis of multiple sclerosis in children with RIS. We will conduct a mixed historical and prospective longitudinal cohort study to determine both the likelihood of and the factors (clinical, demographic, MRI, laboratory and genetic) associated with the development of a clinical diagnosis of multiple sclerosis in children with RIS. This study will help determine which children with RIS are at greatest risk of a clinical multiple sclerosis and will set the stage for intervention trials to prevent or to delay onset of clinical multiple sclerosis in these children. Upon completion of this award, Dr. Makhani will be the only pediatric neurologist in the world with formal fellowship training in pediatric multiple sclerosis and formal training in using neuroimaging techniques for research in pediatric multiple sclerosis. She will have conducted the first and only longitudinal cohort study of children with RIS in collaboration with her Pediatric RIS Consortium, that will provide the necessary infrastructure for future studies, and she will be well poised to apply for funding to become an independent clinician-scientist.