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

项目总结 越来越多的证据表明，患有多发性硬化症(MS)的非裔美国人(AA)存在更多的 病程比高加索美国人(CA)严重的MS有临床残疾的报道 AAS MS的预后更差，炎症和MRI生物标记物明显更不利 患者比他们的CA对应者更多。尽管遗传和环境风险因素可能会对 作用，目前尚不清楚为什么AAS MS患者即使在控制后也会经历更多的疾病致残效应 教育、收入和保险地位。之前的两项核磁共振研究表明，病情越严重 病程与更高的白质(WM)病变堆积有关，而不是与更大的整体相关 脑部萎缩。然而，这些研究受限于回溯性或横断面设计以及 缺乏对区域皮质和皮质下灰质(GM)体积的评估。此外，潜力 多发性硬化症患者脑GM皮质病变(CL)计数和脊髓面积/体积的差异 到目前为止，尚未对AA和CA血统患者进行调查。脑GM萎缩与CLS以及 SC萎缩始于MS的早期阶段，是身体残疾和 认知障碍提示它们在决定疾病的程度和速度方面起着重要作用 进步。因此，我们建议对MS患者进行前瞻性的、纵向的脑和颈椎SCMRI研究。 AA和CA血统的研究集中于对战略解剖区域萎缩的评估，例如 丘脑和SC对散在显微的WM组织损伤的评估 SC和皮质GM局灶性炎症的评估。我们还将调查两国之间的关系 基线和随访时的脑和SC MRI指标以及神经和认知功能障碍。这项研究 具有创新性，因为它提出了对AAS MS患者进行的第一项前瞻性临床和MRI研究 纵向设计研究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 因为它将促进我们对多发性硬化症和多发性硬化神经退行性变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状况恶化的机制 AAS多发性硬化患者的残疾；(Ii)确定多发性硬化患者更具侵袭性的疾病进展的预测因素 AA下降，以及(Iii)帮助根据这一知识制定治疗发展和临床干预措施。

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.