Complex Neurodegenerative Disorders Clinic

尽管神经退行性疾病在历史上被认为是离散的疾病，但科学发现显示出重叠的临床症状、基因和病理，这一概念受到了挑战。与错误折叠的TDP-43或微管相关的tau蛋白在细胞内聚集相关的神经退行性疾病可能表现为认知、语言和运动症状的混合。患者可能被诊断为肌萎缩侧索硬化症(ALS)、额颞叶痴呆(FTD)、皮质-基底综合征(CBS)、进行性核上性麻痹(PSP)或原发性进行性失语(PPA)。尽管大多数患者都有零星疾病，但已经发现了每种疾病的一些致病基因。有趣的是，相同的基因突变可以产生不同的临床表型。这些疾病的基因突变和病理之间的联系可能存在于突变基因产物影响的分子和细胞过程中。随着神经学领域更多地向神经退行性疾病的分子特征发展，有必要在病理学和作为疾病驱动因素的遗传或表观遗传缺陷的背景下理解临床现象学。考虑到这一疾病家族中广泛的神经症状，该诊所汇集了一群杰出的、精力充沛的医生和研究人员，他们拥有广泛的临床专业知识和科学方法。患者接受临床和认知评估、成像和收集生物样品进行研究。其目的是获得知识，为精确医学奠定基础，在这种医学中，治疗是针对每个患者的根本原因量身定做的。 该诊所在2020财年运行顺利，直到3月份由于新冠肺炎大流行而减少了选择性入院人数。诊所的工作人员安排有助于确定诊断的临床研究，以及一系列标准的临床和认知测试。患者可以选择为了研究目的而给出生物检验剂。每个月，诊所都会与神经学家、神经心理学家和参与临床的卫生人员举行一次多学科会议，讨论个别患者及其诊断和研究方案的适用性。被发现有资格参加正在进行的研究的患者被转介到这些研究。患者可以注册注册，以接收未来NIH研究的信息和年度问卷，以更新他们的当前状态和对研究的持续兴趣。

Although neurodegenerative disorders were historically considered as discrete diseases, this concept has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. Neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins may present with a mixture of cognitive, language, and motor symptoms. Patients may be diagnosed with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), or primary progressive aphasia (PPA). Some causative genes have been found for each disorder, although most patients have sporadic disease. Interestingly, the same genetic mutation can produce different clinical phenotypes. The link between the gene mutations and pathology in these disorders may lie in the molecular and cellular processes affected by mutant gene products. As the field of neurology moves more towards the molecular characterization of neurodegenerative disorders, there is a need to understand clinical phenomenology in the context of pathology and genetic or epigenetic defects that are the drivers of disease. Given the broad spectrum of neurological symptoms in this family of disorders, this clinic brings together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. Patients undergo clinical and cognitive assessments, imaging, and collection of biospecimens for research studies. The objective is to gain knowledge that will set the stage for precision medicine in which therapy is tailored to the underlying cause of each patient's disease. The clinic operated smoothly in FY2020, up until the March reduction in elective admissions due to the COVID-19 pandemic. The staff of the clinic arrange clinical studies that help to establish the diagnosis, as well as a standard battery of clinical and cognitive testing. Patients have the option of giving biospecimens for research purposes. Each month, the clinic holds a multidisciplinary conference with neurologists, neuropsychologists, and health personnel involved in the clinic to discuss individual patients and their diagnosis and suitability for research protocols. Patients who are found to be eligible for ongoing research studies are referred to those studies. Patients may sign up for a registry for receiving information on future NIH studies and an annual questionnaire to update their current status and continued interest in research.