Neuropathologic Abnormalities Define A Subgroup of Patients with CFS

神经病理学异常定义了 CFS 患者的一个亚组

基本信息

批准号：
8175829
负责人：
Benjamin Natelson
金额：
$ 37.88万
依托单位：
BETH ISRAEL MEDICAL CTR (NEW YORK)
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8175829
关键词：
Accounting Address Adopted Applications Grants Base of the Brain Biochemical Biological Brain Centers for Disease Control and Prevention (U.S.)Cerebrospinal Fluid Cerebrovascular Circulation Chronic Fatigue Syndrome Classification Clinical Clinical Research Cluster Analysis Cognitive Complication Control Groups Controlled Study Data Development Diagnosis Diagnostic tests Disease Etiology Exclusion Exploratory/Developmental Grant Fatigue Functional disorder Grouping Heterogeneity Impaired cognition Laboratories Lead Learning Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Medical Neurobiology Neurologic Neuropsychological Tests Outcome Outcome Measure Patient Selection Patients Physiological Pilot Projects Population Protons Psychopathology Recommendation Reporting Research Research Project Grants Sampling Selection Criteria Series Shapes Spectrum Analysis Spin Labels Spinal Puncture Stratification Subgroup Symptoms System Techniques Testing Time Ventricular Work base cognitive function cohort disorder subtype effective therapy neuropsychiatry neuropsychological patient population research study stable plasma protein solution treatment strategy working group

项目摘要

DESCRIPTION (provided by applicant): Chronic fatigue syndrome (CFS) is a debilitating multi-symptom disorder characterized by unexplained and prolonged fatigue, whose diagnosis is currently based on a relatively broad clinical case definition. Consequently, the pool of CFS patients included in clinical studies of the illness is greatly heterogeneous - a fact that might have impeded research progress to date. A major step forward in understanding the pathophysiology of CFS would involve reducing this heterogeneity by identifying one or more subgroups of patients with different pathophysiological causes of their illness, and then selecting one of these subgroups for inclusion into research studies. Over the past few years, we and others have provided substantial data supporting the existence of a subgroup of patients with a neurobiological cause for their illness, based on stratifying the sample according to the absence or presence of comorbid Axis I psychopathology (CFS-no psych or CFS-NP and CFS-psych or CFS-P, respectively). Compared to CFS-P patients, the CFS-NP patients had more cognitive dysfunction, a higher rate of abnormal cerebrospinal fluid (CSF) findings, lower regional cerebral blood flow (rCBF), and higher ventricular CSF lactate values. A further complication and limitation of these studies is that each had investigated only one brain-related variable, whose utility in separating CFS patients into subgroups was limited. The purpose of the present Exploratory/Developmental Research Grant (R21) proposal is to rigorously assess and confirm whether patients in the CFS- NP group have consistent abnormalities across several different neuropathological variables - an outcome that would be expected if this group, in fact, does have distinct neurobiological underpinnings. Specifically, in the same subjects, we will (a) assess cognitive function using objective neuropsychological testing; (b) conduct biochemical analysis of spinal fluid samples obtained by lumbar puncture; and (c) measure rCBF and ventricular lactate using magnetic resonance imaging and spectroscopy, respectively, in CFS-P and CFS-NP patients. This will allow us to test the hypothesis that CFS-NP patients have more abnormalities in these outcome variables than CFS-P patients. Our second Aim will use the results from the first Aim in a cluster analysis to attempt objective, data-driven classification of the CFS subjects into subtypes, and then compare the resulting subgroups based on membership into CFS-NP or CFS-P groups. This aim will test the hypothesis that the results of the cluster analysis will identify a group with abnormalities across the multiple brain-based variables studied, and this group will be constituted of significantly more CFS-NP patients than in other groups. PUBLIC HEALTH RELEVANCE: Chronic fatigue syndrome (CFS) is a medically unexplained debilitating disease that is diagnosed by the presence of a set of predefined symptoms. Because there are no validated diagnostic tests for the illness, progress in understanding its causes has been slow. From a series of studies by our group and others there has emerged strong preliminary evidence that supports the existence of a subgroup of CFS patients whose illness appears to be due to specific biological abnormalities in the brain. The purpose of this Exploratory/Developmental grant proposal is to conduct carefully controlled studies that will seek to confirm the existence of such a subgroup of CFS patients. If successfully completed, this study could validate an approach for selecting more homogeneous CFS patient populations in future research studies to enable them to focus better on understanding the exact cause of CFS and developing effective treatments for the illness.

描述（由申请人提供）：慢性疲劳综合症（CFS）是一种使人衰弱的多症状疾病，其特征是无法解释的长期疲劳，其诊断目前基于相对广泛的临床病例定义。因此，参与该疾病临床研究的 CFS 患者群体存在很大差异，这一事实可能阻碍了迄今为止的研究进展。理解 CFS 病理生理学的一个重要步骤是通过识别一个或多个具有不同疾病病理生理原因的患者亚组，然后选择其中一个亚组纳入研究，来减少这种异质性。在过去的几年里，我们和其他人提供了大量数据，支持存在由神经生物学原因导致疾病的患者亚组的存在，这些数据基于根据是否存在共病 Axis I 精神病理学（CFS-no psych）对样本进行分层。或分别为 CFS-NP 和 CFS-psych 或 CFS-P）。与CFS-P患者相比，CFS-NP患者认知功能障碍更多，脑脊液（CSF）异常发生率更高，局部脑血流量（rCBF）更低，脑室CSF乳酸值更高。这些研究的另一个复杂性和局限性是，每项研究仅研究了一个与大脑相关的变量，其在将 CFS 患者分为亚组方面的效用有限。目前的探索性/发展性研究补助金 (R21) 提案的目的是严格评估和确认 CFS-NP 组患者在几个不同的神经病理学变量中是否具有一致的异常 - 如果该组事实上，则这是预期的结果确实具有独特的神经生物学基础。具体来说，在相同的受试者中，我们将（a）使用客观的神经心理学测试来评估认知功能； (b) 对腰椎穿刺获得的脊髓液样本进行生化分析； (c) 分别使用磁共振成像和光谱学测量 CFS-P 和 CFS-NP 患者的 rCBF 和心室乳酸。这将使我们能够检验以下假设：CFS-NP 患者在这些结果变量中比 CFS-P 患者有更多异常。我们的第二个目标将在聚类分析中使用第一个目标的结果，尝试对 CFS 受试者进行客观的、数据驱动的亚型分类，然后根据 CFS-NP 或 CFS-P 组的成员资格对所得亚组进行比较。这一目标将检验这样的假设：聚类分析的结果将识别出在所研究的多个基于大脑的变量中存在异常的一组，并且该组中的 CFS-NP 患者将明显多于其他组。公共卫生相关性：慢性疲劳综合症 (CFS) 是一种医学上无法解释的使人衰弱的疾病，通过出现一系列预先确定的症状来诊断。由于没有针对这种疾病的有效诊断测试，因此了解其原因的进展缓慢。从我们小组和其他人进行的一系列研究中，出现了强有力的初步证据，支持慢性疲劳综合症患者亚组的存在，这些患者的疾病似乎是由于大脑中特定的生物学异常造成的。本探索性/开发性拨款提案的目的是进行仔细对照的研究，以寻求确认此类慢性疲劳综合症患者亚组的存在。如果成功完成，这项研究可以验证在未来的研究中选择更多同质 CFS 患者群体的方法，使他们能够更好地专注于了解 CFS 的确切原因并开发针对该疾病的有效治疗方法。