Exertional Exhaustion in CFS

CFS 中的劳力衰竭

• 批准号: 8614577
• 负责人: JAMES N BARANIUK
• 金额: $ 33.53万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614577
• 关键词: Accounting; Ally; Atrophic; Autonomic Dysfunction; Back; Bicycling; Bilateral; Blood flow; Brain; Brain Stem; Cerebellar vermis structure; Cerebrum; Chronic; Chronic Fatigue Syndrome; Clinical; Cognitive; Diagnostic tests; Diastolic Hypertension; Diffusion Magnetic Resonance Imaging; Disease; Exercise; Exercise stress test; Fatigue; Fibromyalgia; Functional Magnetic Resonance Imaging; Functional disorder; Gulf War; Hour; Hyperalgesia; Inferior; Insula of Reil; Lead; Left; Link; Measures; Migraine; Modeling; Molecular; Neurobiology; Neurocognitive; Neurons; Neurotransmitters; Nociception; Outcome; Pain; Pattern; Perception; Phenotype; Process; Protocols documentation; Relapse; Short-Term Memory; Signal Transduction; Sleep; Spectrum Analysis; Stress Tests; Subgroup; Symptoms; Syndrome; Tachycardia; Testing; base; blood oxygen level dependent; brain tract; central sensitization; cerebral atrophy; drug development; exhaustion; insight; meetings; morphometry; neurocognitive test; neuromechanism; neuropathology; neurophysiology; novel; novel diagnostics; relating to nervous system; response; sedentary; somatosensory; stressor; white matter

Fatigue, widespread pain and tenderness are common findings in Chronic Fatigue Syndrome (CFS) and allied disorders such as Gulf War Illness (GWI) and Fibromyalgia (FM). In addition, they share sleep alterations, diverse nociceptive complaints, migraine, and systemic hyperalgesia. This overlap suggests that these syndromes share specific mechanisms of neural pathophysiology. Central sensitization is a logical explanation for their pain complaints but has been difficult to explain at the neuronal level. One of the cardinal clinical features of FM, GWI and CFS is "exertional exhaustion". Exercise, cognitive or other stressors induce a relapse of symptoms that may be immediate or can be delayed up to 24 hours. Although studies have found changes associated with exercise in CFS, the causal relationship between the brain and the aberrant response to exercise are unknown. Furthermore, changes that predict the transition to exertional exhaustion have not yet been identified. We developed a novel exercise stress test, fMRI, neurocognitive testing strategy to study this phenomenon in GWI subjects who met 1994 CFS criteria. We believe the outcomes can be generalized to CFS, and form the basis for a new understanding of this disease. Hypothesis: Exercise induces cognitive, somatosensory and autonomic dysfunction that are common features of CFS, GWI, & FM. Axonal alterations may be responsible for the neuropathology (SPECIFIC AIM 1). The exercise stressor disrupts vulnerable compensatory neural mechanisms to reveal two autonomic and cognitive phenotypes via fMRI (SPECIFIC AIM 2). Axonal dysfunction in FM can be identified from functional connectivity studies linked to specific dysregulated neurotransmitters of the brain (SPECIFIC AIM 3). Corollary: CFS neuropathology can be modeled based on exercise-induced outcomes of GWI subjects. Our integrated exercise & fMRI protocol identified the novel finding of significantly increased axial diffusivity (AD) in specific white matter tracts by diffusion tensor imaging (DTI) that was predictive of GWI status compared to controls. GWI groups also met CFS criteria. Next, we found that exercise perturbs neurophysiological brain networks that led to 2 GWI phenotypes that were associated with exercise induced changes in autonomic control, white matter integrity, cortical and brainstem atrophy, and brain blood flow dynamics. Baseline studies showed limited cross-sectional "static" differences, but the exercise stressor revealed causal and significant "dynamic" alterations of neural processes. We propose that CFS subjects will display a comparable dichotomy of objective findings. Identification of CFS subgroups would begin the process of defining objective neuropathological mechanisms in CFS. These objective outcomes may define specific CFS phenotypes and help explain the heterogeneous presentation of this illness. Conversely, identification of other coherent patterns may provide new objectively defined criteria for CFS. These mechanisms can lead to objective diagnostic tests and identification of new targets for treatment.

疲劳，广泛的疼痛和压痛是慢性疲劳综合征（CFS）以及诸如海湾战争疾病（GWI）和纤维肌痛（FM）等盟友的常见发现。此外，他们共享睡眠改变，各种伤害性抱怨，偏头痛和全身性痛觉过敏。这种重叠表明这些综合征具有神经病理生理学的特定机制。中央敏化是对疼痛抱怨的逻辑解释，但在神经元水平上很难解释。 FM，GWI和CFS的主要临床特征之一是“劳累疲劳”。运动，认知或其他压力源会导致症状复发，或者可能立即延迟24小时。尽管研究发现与CFS运动有关的变化，但大脑与运动异常反应之间的因果关系尚不清楚。此外，尚未确定预测过渡到劳累疲劳的变化。我们开发了一种新型的运动压力测试，fMRI，神经认知测试策略，以研究符合1994 CFS标准的GWI受试者中的这种现象。我们认为，结果可以推广到CFS，并构成了对该疾病的新理解的基础。假设：运动引起认知，体感和自主神经功能障碍，这是CFS，GWI和FM的常见特征。轴突改变可能是神经病理学的原因（特定目标1）。运动压力源破坏了脆弱的补偿性神经机制，通过fMRI揭示了两种自主神经和认知表型（特定目标2）。 FM中的轴突功能障碍可以从与大脑的特定功能失调的神经递质相关的功能连通性研究中鉴定出来（特定的目标3）。推论：CFS神经病理学可以根据运动引起的GWI受试者的结局进行建模。我们的综合运动和FMRI方案通过扩散量张量成像（DTI）在特定的白质区域的轴向扩散率（AD）显着增加，这与对照组相比是GWI状态。 GWI组也符合CFS标准。接下来，我们发现锻炼会导致神经生理学脑网络导致2种与运动诱导的自主控制，白质完整性，皮质和脑干萎缩以及脑血流流动动态变化相关的GWI表型。基线研究显示横截面“静态”差异有限，但是运动压力源显示神经过程的因果关系和重要的“动态”改变。我们建议CFS受试者将显示客观发现的可比二分法。 CFS亚组的识别将开始定义CFS中客观神经病理学机制的过程。这些客观结果可能会定义特定的CFS表型，并有助于解释该疾病的异质表现。相反，对其他相干模式的识别可能会为CFS提供新的客观定义标准。这些机制可以导致客观的诊断测试并确定新的治疗靶标。