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

• 批准号: 8318596
• 负责人: Benjamin Natelson
• 金额: $ 13.3万
• 依托单位: BETH ISRAEL MEDICAL CTR (NEW YORK)
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8318596
• 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

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.

描述（由申请人提供）：慢性疲劳综合征（CFS）是一种以不明原因和长期疲劳为特征的衰弱性多症状疾病，其诊断目前基于相对广泛的临床病例定义。因此，包括在疾病的临床研究中的CFS患者的池是非常异质性的-这一事实可能阻碍了迄今为止的研究进展。理解CFS的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病理生理学病因的患者亚组来减少这种异质性，然后选择其中一个亚组纳入研究。在过去的几年里，我们和其他人提供了大量的数据支持存在一个亚组的患者与神经生物学原因为他们的疾病，根据分层的样本根据共病轴I精神病理学（CFS-无精神或CFS-NP和CFS-精神或CFS-P，分别）。与CFS-P患者相比，CFS-NP患者有更多的认知功能障碍，更高的异常脑脊液（CSF）的结果，较低的局部脑血流量（rCBF），和较高的脑室CSF乳酸值。这些研究的另一个复杂性和局限性是，每项研究都只研究了一个脑相关变量，其在将CFS患者分成亚组方面的效用有限。目前探索性/发展性研究补助金（R21）提案的目的是严格评估和确认CFS- NP组的患者是否在几个不同的神经病理学变量中具有一致的异常-如果该组实际上确实具有不同的神经生物学基础，则预期会出现这种结果。具体而言，在相同的受试者中，我们将（a）使用客观神经心理学测试评估认知功能;（B）对通过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法测量CFS-P和CFS-NP患者的rCBF和心室乳酸。这将使我们能够检验CFS-NP患者在这些结果变量中比CFS-P患者有更多异常的假设。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，以尝试将CFS受试者客观地、数据驱动地分类为亚型，然后根据CFS-NP或CFS-P组的成员资格比较所得到的亚组。这一目的将检验以下假设：聚类分析的结果将确定一组在所研究的多个基于大脑的变量中存在异常，并且该组将由比其他组显著更多的CFS-NP患者组成。