MRI predictors of disease and disability progression in African Americans with multiple sclerosis

项目摘要 越来越多的证据表明，患有多发性硬化症（MS）的非洲裔美国人（AAs）表现出更多的 严重的疾病过程比白人美国人（CA）与MS。据报道，临床残疾， 结果更差，炎症和MRI生物标志物在AAs MS中明显更不利 患者比他们的CA同行。虽然遗传和环境风险因素可能会发挥作用， 目前还不清楚为什么AAs MS患者即使在控制了疾病后， 教育收入和保险状况之前的两项MRI研究表明， 病程与较高的白色（WM）病变积聚相关，而不是与较大的整体 脑萎缩然而，这些研究受到回顾性或横断面设计的限制， 缺乏对局部皮质和皮质下灰质（GM）体积的评估。此外，潜力 MS之间脑GM皮质病变（CL）计数和脊髓（SC）面积/体积的差异 迄今为止，尚未对AA和CA血统的患者进行研究。脑GM萎缩和CL以及 SC萎缩发生在MS的早期阶段，是身体残疾的独立预测因子， 认知功能障碍，表明它们在决定疾病的程度和速度方面发挥着重要作用 进展因此，我们建议对MS患者进行前瞻性、纵向脑和颈部SC MRI研究 AA和CA祖先的研究重点是评估战略解剖区域的萎缩，如 丘脑和SC，对胼胝体中弥漫性显微WM组织损伤的评估， SC和皮质GM局灶性炎症的评估。我们还将研究 基线和随访时的脑和SC MRI指标以及神经和认知功能障碍。本研究 是创新的，因为它提出了第一个前瞻性的临床和MRI研究的AA MS患者与 纵向设计，以研究AA血统MS患者的疾病病理生理学， 确定疾病和残疾进展的短期和中期预测因素。拟议的研究是 意义重大，因为它将促进我们对MS中神经变性的病理生理学的理解， 将提供准确的工具，以更好地（i）了解导致身体和认知能力更差的机制 （ii）确定MS患者中更具侵袭性疾病进展的预测因子， AA血统，和（iii）帮助定制治疗开发和临床干预的基础上，这方面的知识。

PROJECT SUMMARY There is ever-growing evidence that African Americans (AAs) with multiple sclerosis (MS) present with a more severe disease course than Caucasian-Americans (CAs) with MS. It has been reported that clinical disability outcomes are worse, and inflammatory and MRI biomarkers significantly more unfavourable in AAs MS patients than in their CAs counterparts. Although genetic and environmental risk factors are likely to play a role, it is unclear why AAs MS patients experience a more disabling effect of the disease even after controlling for education, income, and insurance status. Two previous MRI studies have suggested that the more severe course is associated with the higher white matter (WM) lesion accumulation rather than with greater whole brain atrophy. However, these studies were limited by the retrospective or cross-sectional design and by the lack of assessment of regional cortical and sub-cortical gray matter (GM) volume. Moreover, potential differences in brain GM cortical lesion (CL) count and in area/volume of the spinal cord (SC) between MS patients of AA and CA ancestry have not been investigated up to date. Brain GM atrophy and CLs as well as SC atrophy occur since the early stages of MS and are independent predictors of physical disability and cognitive impairment suggesting their prominent role in determining the extent and pace of disease progression. Therefore, we propose a prospective, longitudinal brain and cervical SC MRI study of MS patients of AA and CA ancestry focused on the assessment of atrophy of strategic anatomical regions such as the thalamus and SC, on the assessment of diffuse microscopic WM tissue damage in the corpus callosum and SC and the assessment of cortical GM focal inflammation. We will also investigate the relationship between brain and SC MRI metrics and neurological and cognitive impairment at baseline and follow-up. This research is innovative because it proposes the first prospective clinical and MRI study of AAs MS patients with a longitudinal design to investigate the pathophysiology of the disease in MS patients of AA ancestry and to identify short- and medium-term predictors of disease and disability progression. The proposed research is significant because it will advance our understanding of the pathophysiology of neurodegeneration in MS and will provide accurate tools to better (i) understand the mechanisms leading to worse physical and cognitive disability in AAs MS patients; (ii) identify predictors of more aggressive disease progression in MS patients of AA descent, and (iii) help tailor therapeutic development and clinical interventions based on this knowledge.