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: 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
• 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; 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. 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）：慢性疲劳综合征（CFS）是一种令人衰弱的多症状障碍，其特征是无法解释和长时间疲劳，其诊断目前是基于相对较广泛的临床病例定义。因此，疾病临床研究中包括的CFS患者库非常异质 - 这一事实可能阻碍了迄今为止的研究进展。了解CFS的病理生理学迈出的主要一步将涉及通过识别一个或多个患有不同病理生理原因的患者的亚组，然后选择其中一个亚组以纳入研究研究。在过去的几年中，我们和其他人提供了大量数据，该数据支持了患有神经生物学原因的亚组，基于根据合并症轴I心理病理学（CFS-NO Psych或CFS-NO Psych或CFS-NP和CFS-NP和CFS-P Psyse-psych）的缺失或存在对样本进行分层的基础。与CFS-P患者相比，CFS-NP患者具有更大的认知功能障碍，脑脊液异常（CSF）的发现率较高，较低的区域脑血流（RCBF）和较高的心室CSF乳酸乳酸盐值。这些研究的进一步并发症和局限性是，每个研究都仅研究了一个与大脑相关的变量，将CFS患者分为亚组的效用受到限制。目前的探索/发展研究赠款（R21）提案的目的是严格评估并确认CFS -NP组的患者是否在几个不同的神经病理学变量之间是否存在一致的异常 - 如果实际上该组确实具有独特的神经生物学底膜，则可以预期的结果。具体而言，在同一主题中，我们将（a）使用客观神经心理学测试评估认知功能； （b）对通过腰穿点获得的脊柱流体样品进行生化分析； （c）在CFS-P和CFS-NP患者中，分别使用磁共振成像和光谱法测量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患者具有更多的异常。我们的第二个目标将在集群分析中使用第一个目标的结果来尝试将CFS受试者的数据驱动分类为亚型，然后根据成员资格比较CFS-NP或CFS-P组的结果亚组。该目标将检验以下假设：群集分析的结果将确定所研究的多个基于大脑的变量的组异常，并且该组将由CFS-NP患者明显高于其他组。 公共卫生相关性：慢性疲劳综合征（CFS）是一种医学上无法解释的使人衰弱的疾病，由于存在一组预定义症状而被诊断出来。由于没有对疾病进行验证的诊断测试，因此了解其原因的进展很慢。从我们小组和其他人的一系列研究中，出现了强有力的初步证据，这些证据支持存在疾病似乎是由于大脑特定生物学异常引起的CFS患者的存在。该探索性/发展赠款提案的目的是进行仔细控制的研究，以寻求确认存在这种CFS患者的存在。如果成功完成，这项研究可以验证一种方法，以在未来的研究中选择更均匀的CFS患者人群，以使他们能够更好地专注于理解CFS的确切原因并为疾病开发有效的治疗方法。