Complex Neurodegenerative Disorders Clinic

神经退行性疾病的传统分类为离散的疾病已经挑战了科学发现显示重叠的临床症状，基因和病理。与细胞内错误折叠的TDP-43或微管相关tau蛋白聚集相关的神经退行性疾病的临床连续性尤为显著。患者可能同时出现认知、语言和运动症状。这些疾病的例子包括肌萎缩性侧索硬化症（ALS）、额颞叶痴呆（FTD）、皮质基底综合征（CBS）、进行性核上性麻痹（PSP）、原发性进行性失语症（PPA）和hd阴性亨廷顿舞蹈症。每种疾病都发现了一些致病基因，尽管大多数患者是散发性疾病。有趣的是，相同的基因突变可以产生不同的临床表型。基因突变与这些疾病的病理之间的联系可能在于受突变基因产物影响的分子和细胞过程。随着神经学领域越来越趋向于神经退行性疾病的分子表征，有必要在病理和遗传或表观遗传缺陷的背景下了解临床现象学，这些是疾病的驱动因素。鉴于这一疾病家族中广泛的神经系统症状，该诊所的目标是汇集一批具有广泛临床专业知识和科学方法的杰出而充满活力的医生和研究人员。目标是获得知识，为精准医疗奠定基础，精准医疗将根据每位患者疾病的根本原因量身定制治疗方案。

The traditional classification of neurodegenerative disorders into discrete diseases has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. A clinical continuum is particularly notable for neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins. Patients can have a mixture of cognitive, language, and motor symptoms. Examples of these disorders include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), primary progressive aphasia (PPA), and HD-negative Huntington. 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, the goal of this clinic is to bring together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. The objective is to gain knowledge that will set the stage for precision medicine in which therapy will be tailored to the underlying cause of each patient's disease. In FY19, a screening clinic has been held each month to evaluate patients with complex neurodegenerative disorders referred by neurologists, both from the local community and throughout the US. 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. Otherwise 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.