Longitudinal Course of MSA

这项对多系统萎缩(MSA)患者的研究将检验以下假设：(1)前瞻性纵向研究将证明发病时的表型类别预测疾病的进程；(2)在一个亚组中，随着疾病的进展，节后交感神经节后心脏去神经发生。 对于患有快速进行性自主神经功能障碍的患者，无论帕金森氏症或小脑症状的改变率如何；以及(3)由于其抑制a-突触核蛋白纤维的形成和分解已经形成的纤维的能力，利福平将延缓MSA的进展或逆转神经和自主神经异常。在前一个资助周期启动的对美国12个不同地点的175名可能患有MSA的患者进行的前瞻性自然史研究将继续进行，并将增加100名受试者 在可能的MSA的早期阶段招募，并从密歇根大学和梅奥医学中心网站招募同等数量的人员。定期的、详细的临床评估，包括自主神经和神经功能，将通过对受试者的尸检来验证诊断。后神经节节段 交感神经支配将在20名可能患有MSA的新招募的受试者和20名年龄和性别分布大致相等的正常受试者中每两年进行一次评估。研究将利用正电子发射断层扫描(PET)的临床评估，[13NJNH3和[11C]羟麻黄 评估心脏灌注和神经支配情况。所有受试者都将被前瞻性地跟踪到尸检。 项目1和4将进行一项双盲安慰剂对照临床试验，以确定利福平是否会延缓或逆转MSA的神经和自主神经障碍的进展。初步研究表明，结果将是可靠的，因为目前的数据已经表明：(1)在尸检研究的29例病例中，有28例得到了准确的诊断；(2)临床观察表明，表型类型与后续病程有很强的相关性；以及(3)相当大比例的晚期MSA受试者出现心脏去神经支配。 这些研究将产生有关MSA自然病史的新信息，并揭示预测进展差异的方法，这些方法需要在未来的临床试验中了解病例选择。

This study of patients with multiple system atrophy (MSA) will test the following hypotheses: (1) prospective longitudinal investigation will demonstrate that the phenotypic class at onset predicts the course of the disease.; (2) postganglionic sympathetic cardiac denervation occurs with disease progression in a subgroup of patients who have rapidly progressive autonomic dysfunction irrespective of the rate of change in parkinsonian or cerebellar symptoms; and (3) owing to its ability to inhibit formation of a-synuclein fibrils and disaggregate fibrils already formed, Rifampicin will delay progression or reverse neurological and autonomic abnormalities in MSA. Prospective natural history studies of 175 patients with probable MSA in 12 different sites in the US initiated during the previous funding cycle will be continued and augmented by 100 subjects recruited at the earlier stage of possible MSA, and in equal numbers from the University of Michigan and the Mayo Medical Center sites. Regular, detailed clinical appraisals, including autonomic and neurologic function, will be augmented by postmortem examination of subjects to verify diagnosis. Post-ganglionic sympathetic cardiac innervation will be evaluated every 2 years in 20 newly recruited subjects with possible MSA and 20 normal control subjects with approximately equal distributions of age and gender. Studies will utilize clinical evaluation, [13NJNH3 and [11C]hydroxylephedrlne with positron emission tomography (PET) to evaluate cardiac perfusion and innervation. All subjects will be followed prospectively to postmortem. Projects 1 and 4 will undertake a double-blind placebo controlled clinical trial to determine whether Rifampicin will retard or reverse the progression of neurologic and autonomic disorders in MSA. Preliminary studies suggest that results will robust, as current data already indicate: (1) accurate diagnosis in 28 of 29 cases studied at autopsy; (2) clinical observations suggesting a strong association of phenotypic class with subsequent course; and (3) cardiac denervation In a substantial proportion of late-stage MSA subjects. These studies will generate novel information about the natural history of MSA and reveal methods of predicting differences in progression that need to be understood for case selection in future clinical trials.