Redefining Chiari Type I Malformation through Genetically, Radiologically, and Clinically-Derived Endophenotypes that are Predictive of Long-Term Neurological Outcome

通过遗传、放射学和临床衍生的可预测长期神经系统结果的内表型重新定义 Chiari I 型畸形

基本信息

  • 批准号:
    10629124
  • 负责人:
  • 金额:
    $ 18.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-07-01 至 2028-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Project 4: Redefining CM Using Multidimensional Endophenotypes Predictive of Long-Term Outcome Chiari type 1 malformation (CM) is a common and potentially debilitating disease typically defined by caudal displacement of the cerebellar tonsils below the foramen magnum. While radiographic CM may be found in 1% or more of the population, this population is extremely heterogeneous. Patients with classically defined CM may be clinically asymptomatic or present with severe symptoms such as debilitating headaches or signs of brainstem or spinal cord malfunction. Furthermore, patients with similar clinical presentations may have distinct genetic profiles and comorbid diagnoses that suggest differing etiologies contributing to superficially similar disease. Increasing recognition of this heterogeneity has emphasized the need for a data-driven approach to reclassifying traditionally-defined “CM.” Furthermore, advances in contemporary methods in imaging, genomics, and patient-centered clinical measures have substantially expanded opportunities for phenotyping complex diseases, such as CM. Leveraging Washington University’s unique strengths in these areas, the overall objective of Project 4 is to derive clinically relevant, multidimensional endophenotypes within traditionally- defined “CM” to inform clinical management and optimize long-term patient outcomes. In particular, we expect these multidimensional endophenotypes will both aid in outcome prediction and also provide new biological insights regarding disease pathogenesis, thereby supporting personalized treatment strategies. We intend to pursue this objective through three specific aims. In Aim 1, we will apply well-established unsupervised and semi- supervised clustering methods to multidimensional clinical and radiological data to derive novel clusters in a large, multicenter dataset. We will then externally validate those multidimensional endophenotypes in three external, multicenter datasets. In Aim 2 we will compare differences in disease presentation across clusters and also use state-of-the-art genetics and advanced imaging techniques to obtain new insights into biological differences underlying CM heterogeneity and pathogenesis. In Aim 3 we will examine the association between these clusters and important CM outcomes (e.g., change in quality of life, postoperative complications). We will then use prediction modeling to examine how both cluster identity and other characteristics impact these outcomes. Finally, we will use a Modified Delphi Approach to create a novel treatment framework based on this Project’s findings along with structured feedback from experts in the research and clinical management of CM. Taken together, this Project’s results will offer a fundamentally new data-driven approach for classifying CM. We expect these findings will have an immediate impact on clinical management practices and will guide future research in this field.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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David Delmar Limbrick其他文献

David Delmar Limbrick的其他文献

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{{ truncateString('David Delmar Limbrick', 18)}}的其他基金

Redefining Chiari Type I Malformation and its Impact on Brain Development
重新定义 Chiari I 型畸形及其对大脑发育的影响
  • 批准号:
    10629116
  • 财政年份:
    2023
  • 资助金额:
    $ 18.69万
  • 项目类别:
Admin Core
管理核心
  • 批准号:
    10629117
  • 财政年份:
    2023
  • 资助金额:
    $ 18.69万
  • 项目类别:
Clinical Core
临床核心
  • 批准号:
    10629119
  • 财政年份:
    2023
  • 资助金额:
    $ 18.69万
  • 项目类别:
Effects of ventricular volume and cerebral connectivity on neurological outcomes in preterm intraventricular hemorrhage
心室容量和脑连通性对早产脑室内出血神经系统结局的影响
  • 批准号:
    10581476
  • 财政年份:
    2022
  • 资助金额:
    $ 18.69万
  • 项目类别:
Effects of ventricular volume and cerebral connectivity on neurological outcomes in preterm intraventricular hemorrhage
心室容量和脑连通性对早产脑室内出血神经系统结局的影响
  • 批准号:
    10345013
  • 财政年份:
    2022
  • 资助金额:
    $ 18.69万
  • 项目类别:
Experimental Studies of Endoscopic Third Ventriculostomy and Choroid Plexus Cauterization in Hydrocephalus
内镜下第三脑室造口术和脉络丛烧灼术治疗脑积水的实验研究
  • 批准号:
    10710213
  • 财政年份:
    2022
  • 资助金额:
    $ 18.69万
  • 项目类别:
Experimental Studies of Endoscopic Third Ventriculostomy and Choroid Plexus Cauterization in Hydrocephalus
内镜下第三脑室造口术和脉络丛烧灼术治疗脑积水的实验研究
  • 批准号:
    10568647
  • 财政年份:
    2022
  • 资助金额:
    $ 18.69万
  • 项目类别:
Experimental endoscopic third ventriculostomy with choroid plexus cauterization and its effects on brain development
实验性内镜第三脑室造口术结合脉络丛烧灼及其对大脑发育的影响
  • 批准号:
    9896631
  • 财政年份:
    2020
  • 资助金额:
    $ 18.69万
  • 项目类别:
CSF LEVELS OF L1CAM AND AMYLOID PRECURSOR PROTEIN IN POST-HEMORRHAGIC HYDROCEPHAL
出血后脑积水脑脊液中 L1CAM 和淀粉样前体蛋白的水平
  • 批准号:
    8300378
  • 财政年份:
    2012
  • 资助金额:
    $ 18.69万
  • 项目类别:
CSF LEVELS OF L1CAM AND AMYLOID PRECURSOR PROTEIN IN POST-HEMORRHAGIC HYDROCEPHAL
出血后脑积水脑脊液中 L1CAM 和淀粉样前体蛋白的水平
  • 批准号:
    8460508
  • 财政年份:
    2012
  • 资助金额:
    $ 18.69万
  • 项目类别:

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机构外的生活:1900 - 1960 年心理健康善后护理的历史
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