The Radiologically Isolated Syndrome in Children

项目摘要/摘要 马克哈尼博士是一名儿科神经科医生，他的长期目标是实施预防多发性多发性硬化的策略。 高危儿童的硬化症。建议的培训和有指导的研究经验将使她能够 发展在进行纵向队列研究以及将核磁共振用作临床和研究工具方面的专业知识。 马克哈尼博士召集了一支专业的、尽职尽责的导师和顾问团队来帮助她。尤金博士 夏皮罗是她的主要导师，是临床流行病学研究的公认领导者，丹尼尔·佩尔蒂埃博士 (共同导师)是使用核磁共振研究多发性硬化症生物学的世界专家。马克哈尼博士将带着 耶鲁大学在神经学研究中使用成像技术的理论和应用的课程 与Pelletier博士在多发性硬化症实验室接受高级成像实践培训6个月 在南加州大学。她还将在耶鲁大学参加遗传学高级课程，以及 影像数据、纵向数据、事件发生时间数据和临床试验的分析。 患有多发性硬化症的儿童，是最常见的中枢神经系统自身免疫性疾病， 复发率高，并可能在年轻时发展为残疾，但治疗可能会改善两者。这个 在没有任何多发性硬化症症状的人中发现了多发性硬化症的典型MRI表现 他们因其他原因(如头部创伤)接受了脑部核磁共振扫描。这一临床情景一直是 称为放射隔离综合征(RIS)。在患有RIS的成年人中，34%的人发展为临床神经系统疾病 症状与多发性硬化症一致，在最初的MRI异常的五年内。在患有RIS的成年人中， 年龄37岁、男性和MRI上的脊髓病变与临床神经功能的发展有关 症状。我们既不知道发生临床诊断的风险，也不知道哪些因素与临床诊断有关。 患有RIS的儿童的多发性硬化症。 我们将进行混合的历史和前瞻性纵向队列研究，以确定 发病的可能性及其相关因素(临床、人口学、核磁共振、实验室和遗传学) RIS儿童多发性硬化症的临床诊断进展。这项研究将有助于确定 哪些患有RIS的儿童临床上多发性硬化症的风险最高，并将为干预奠定基础 预防或延缓这些儿童临床多发性硬化症发病的试验。在完成本奖项后， Makhani博士将是世界上唯一一位接受过儿科多学科正式团契培训的儿科神经科医生。 在儿科多发性硬化症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，将为未来的研究提供必要的基础设施，她会很好的 准备申请资金成为一名独立的临床医生-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.