Longitudinal Course of MSA

MSA的纵向路线

• 批准号: 7990740
• 负责人: SID GILMAN
• 金额: $ 25.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990740
• 关键词: Adult; Affect; Age; Age Distribution; Age of Onset; Ataxia; Atrophic; Autonomic Denervation; Autonomic Dysfunction; Autonomic nervous system; Autonomic nervous system disorders; Autopsy; Babinski Reflex; Bladder; Blood Pressure; Bradykinesia; Brain Stem; Cardiac; Case Study; Cerebellar Ataxia; Cerebellar Diseases; Cerebellar Gait; Cerebellum; Cervical; Cessation of life; Classification; Clinic; Clinical; Clinical Trials; Consensus; Consent; Controlled Clinical Trials; Data; Databases; Deglutition Disorders; Denervation; Deposition; Deterioration; Diagnosis; Diagnostic; Disease; Disease Progression; Documentation; Double-Blind Method; Dysarthria; Dyskinetic syndrome; Endowment; Enrollment; Erectile dysfunction; Evolution; Failure; Fiber; Frequencies; Functional disorder; Funding; Future; Gait Ataxia; Gender; Grant; Grouping; Hyperreflexia; Infarction; Investigation; Left ventricular structure; Levodopa; Lewy Bodies; Life; Limb Ataxia; Magnetic Resonance Imaging; Measures; Medical center; Methods; Michigan; Microscopic; Motor; Multiple System Atrophy; Muscle Rigidity; Natural History; Nerve; Nerve Fibers; Nervous System Physiology; Neuraxis; Neurodegenerative Disorders; Neurologic; Onset of illness; Orthostatic Hypotension; Outcome; Parkinsonian Disorders; Pathology; Patients; Perfusion; Peripheral; Pilot Projects; Placebo Control; Pontine structure; Positron-Emission Tomography; Procedures; Prospective Studies; Recruitment Activity; Rifampin; Scanning; Sensitivity and Specificity; Severities; Site; Sleep Apnea Syndromes; Specific qualifier value; Staging; Stridor; Study Subject; Subgroup; Sympathectomy; Sympathetic Ganglia; Symptoms; Testing; Time; Tremor; Tyrosine 3-Monooxygenase; Universities; Urinary Incontinence; Variant; Vascular Diseases; alpha synuclein; base; cohort; disability; experience; follow-up; heart innervation; immunoreactivity; improved; longitudinal course; male; meetings; micturition urgency; nerve supply; novel; oculomotor; presynaptic; programs; prospective; putamen; research clinical testing; response; single photon emission computed tomography

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.

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分类可预测疾病的病程。(2)在亚组中，随着疾病进展发生节后交感神经心脏去神经支配 无论帕金森病或小脑症状的变化率如何，快速进行性自主神经功能障碍的患者中均存在;和（3）由于利福平能够抑制α-突触核蛋白原纤维的形成并分解已经形成的原纤维，因此利福平将延迟MSA的进展或逆转MSA中的神经和自主神经异常。在上一个资助周期中，在美国12个不同研究中心启动的175例可能患有MSA的患者的前瞻性自然史研究将继续进行，并增加100例受试者 在可能的MSA的早期阶段招募，并且从密歇根大学和马约医学中心站点招募相同数量的人。定期、详细的临床评估，包括自主神经和神经功能，将通过对受试者进行尸检来验证诊断。节后 每2年在20名新招募的可能患有MSA的受试者和20名年龄和性别分布大致相等的正常对照受试者中评价交感神经心脏神经支配。研究将利用临床评价，[13 NJNH 3]和[11 C]羟麻黄碱与正电子发射断层扫描（PET）， 评估心脏灌注和神经支配。将前瞻性随访所有受试者直至尸检。 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患者神经系统和自主神经功能障碍的进展。初步研究表明，结果将是稳健的，因为目前的数据已经表明：（1）在尸检时研究的29例病例中，有28例诊断准确;（2）临床观察结果表明表型分类与随后的病程密切相关;（3）在相当大比例的晚期MSA受试者中，心脏去神经支配。 这些研究将产生关于MSA自然史的新信息，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进行病例选择。