Exertional Exhaustion in CFS

CFS 中的劳力衰竭

• 批准号: 8896084
• 负责人: JAMES N BARANIUK
• 金额: $ 34.02万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8896084
• 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; Health; 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; cognitive testing; drug development; exhaustion; insight; meetings; morphometry; neurocognitive test; neuromechanism; neuropathology; neurophysiology; novel; novel diagnostics; relating to nervous system; response; sedentary; somatosensory; stressor; white matter

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：疲劳、广泛疼痛和触痛是慢性疲劳综合症（CFS）以及海湾战争病（GWI）和纤维肌痛（FM）等相关疾病的常见表现。此外，他们共享睡眠改变，不同的伤害性投诉，偏头痛和全身痛觉过敏。这种重叠表明这些综合征具有共同的神经病理生理学特定机制。中枢致敏是他们疼痛的合理解释，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“劳力性衰竭”。运动、认知或其他应激源会诱发症状复发，可能是立即的，也可能延迟至24小时。尽管研究发现CFS患者的变化与运动有关，但大脑与运动异常反应之间的因果关系尚不清楚。此外，预测过渡到劳力性衰竭的变化尚未确定。我们开发了一种新的运动负荷试验，功能磁共振成像，神经认知测试策略，以研究这一现象的GWI受试者谁符合1994年CFS标准。我们相信这些结果可以推广到CFS，并形成对这种疾病的新认识的基础。假设：运动引起认知、躯体感觉和自主神经功能障碍，这些是CFS、GWI和FM的共同特征。轴突改变可能是神经病理学的原因（特异性目的1）。运动应激破坏脆弱的补偿神经机制，通过功能磁共振成像（特定目的2）揭示两个自主和认知表型。FM中的轴突功能障碍可以从与大脑特定失调的神经递质相关的功能连接研究中确定（特定目的3）。推论：CFS神经病理学可以基于GWI受试者的运动诱导的结果来建模。我们的综合运动和功能磁共振成像方案确定了新的发现，显着增加轴向扩散（AD）在特定的白色物质束的扩散张量成像（DTI）是预测GWI状态相比，控制。GWI组也符合CFS标准。接下来，我们发现运动扰乱神经生理学脑网络，导致2种GWI表型，其与运动诱导的自主控制、白色物质完整性、皮质和脑干萎缩以及脑血流动力学的变化相关。基线研究表明，有限的横截面“静态”的差异，但运动应激揭示了因果关系和显着的“动态”的神经过程的改变。我们建议，CFS的主题将显示一个可比较的二分法的客观结果。CFS亚群的确定将开始确定CFS客观神经病理机制的过程。这些客观结果可能定义特定的CFS表型，并有助于解释这种疾病的异质性表现。相反，其他相干模式的识别可能会提供新的客观定义的标准CFS。这些机制可以导致客观的诊断测试和识别新的治疗目标。