Neurological Indices of CNS Involvement in "Non-CNS" SLE

“非 CNS”SLE 中 CNS 受累的神经学指标

• 批准号: 7345396
• 负责人: JANET L SHUCARD
• 金额: $ 29.73万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7345396
• 关键词: Accounting; Activities of Daily Living; Address; Adrenal Cortex Hormones; Anatomy; Anterior; Appendix; Area; Attention; Attentional deficit; Auditory; Autoimmune Diseases; Back; Brain; Brain Pathology; Chronic; Classification; Cognitive; Cognitive deficits; Computer information processing; Condition; Control Groups; Data; Depth; Detection; Diagnosis; Diffuse; Disease; EP300 gene; Electrodes; Evaluation; Event; Event-Related Potentials; Exhibits; Fatigue; Functional disorder; Goals; Headache; Image; Impaired cognition; Impairment; Individual; Injury; Lead; Learning; Length; Literature; Lupus Erythematosus; Magnetic Resonance Imaging; Maintenance; Measures; Memory impairment; Mental Depression; Methodology; Methods; Microscopic; Mitochondrial Carnitine Palmitoyltransferase Pathway; Modeling; Mood Disorders; Neuraxis; Neurobiology; Neurocognitive Deficit; Neurologic; Neuropsychological Tests; Numbers; Organ; Parietal; Participant; Pathogenesis; Pathology; Patients; Pattern; Performance; Peripheral; Pharmaceutical Preparations; Procedures; Process; Psychological Factors; Psychotic Disorders; Range; Recording of previous events; Reporting; Response Latencies; Response to stimulus physiology; Role; Scalp structure; Score; Seizures; Short-Term Memory; Site; Speed; Staging; Standards of Weights and Measures; Steroids; Stimulus; Stroke; System; Systemic Lupus Erythematosus; Task Performances; Techniques; Testing; Time; Tissues; base; brain tissue; design; frontal lobe; illness length; improved; indexing; interest; memory process; neuropathology; neuropsychiatry; neuropsychological; novel; processing speed; relating to nervous system; response; tool

Systemic Lupus Erythematosus (SLE) is a chronic, multi-organ autoimmune disease. Neuropsychiatric manifestations, including neurologic (central or peripheral), psychiatric, and cognitive disturbances, have been reported to range from 14 to 75% in SLE patients. The determination of central nervous system (CMS) involvement has been based on manifestations ranging from overt disturbances such as seizure, stroke,or psychosis, to diffuse and more questionable CMSdisturbances, such as mild mood disorder, headache,and subtle cognitive deficits. The pathogenesis of these latter more subtle and diffuse manifestations is unknown and the diagnosis of CMS involvement remains problematic. More recently, "CMS" SLE has been used to describe only those patients with overt CMSdisturbances, while all others are categorized as "Non-CNS" SLE. Regardless of the classification criteria used to determine neuropsychiatric and/or CMS involvement in SLE, cognitive disturbances have been reported in up to 80% of patients with SLE when mild impairment is included. The most frequently reported deficits are in the areas of attention, speed of information processing, learning, and working memory (WM). The primary objective of this proposal is to examine the underlying pathophysiology of CMS involvement in the cognitive disturbances seen in SLE patients without overt CNS manifestations (e.g. stroke, seizure, psychosis). SLExpatientswill be studied using: (1) event-related brain potentials (ERPs) to obtain indices of brain function; (2) conventional and unconventional quantitative magnetic resonance imaging (MRI) to obtain indices of anatomic pathology; and (3) neuropsychological(NP) measures to determine the pattern of cognitive deficits in these patients. The NP battery will be composed of multiple tests grouped into cognitive domains, with particular emphasis on attention, WM, andprocessing speed. The ERP measures will be obtained from two paradigms that are sensitive to the WM components of encoding, maintenance, manipulation, and matching/response selection. MRI measures will focus on magnetization transfer ratio (MTR) to quantify tissue loss and microscopic tissue injury. The roles of active and inactive disease, medication use, and psychological factors will be carefully considered. Healthy control participants will also be studied. It is hypothesized that in patients with "Non-CNS" SLE, MRI (particularly MTR), and ERP (amplitude, latency, condition-related scalp topography, and single trial latency variability) will be sensitive indices of the cognitive deficits seen in SLE. The ability to define more clearly the information processing deficits seen in SLE and the underlying anatomical and functional basis of these deficits, will further the understanding of possible pathophysiological mechanisms of this disorder and lead to improved classification and treatment.

系统性红斑狼疮(SLE)是一种慢性、多器官自身免疫性疾病。神经精神病学 表现，包括神经系统(中枢或外周)、精神和认知障碍，有 据报道，在系统性红斑狼疮患者中，这一比例从14%到75%不等。中枢神经系统(CMS)测定 参与的基础是各种表现，从癫痫、中风或 精神病，以弥漫性和更可疑的CMS障碍，如轻度情绪障碍，头痛，和 微妙的认知缺陷。后者更细微和弥漫的表现的发病机制尚不清楚。 而CMS受累的诊断仍然存在问题。最近，“CMS”SLE已被用于 只描述那些有明显中枢神经系统障碍的患者，而所有其他患者都被归类为“非中枢神经系统” SLE。无论用于确定神经精神疾病和/或CMS参与的分类标准如何 据报道，80%的SLE患者在轻度损害时出现认知障碍。 包括在内。最常报告的缺陷是在注意力、信息处理速度、 学习和工作记忆(WM)。这项建议的主要目标是检查潜在的 CMS参与无明显中枢神经系统的SLE患者认知障碍的病理生理学研究 症状(如中风、癫痫、精神病)。SLE患者将使用以下方法进行研究：(1)事件相关脑 (2)常规定量和非常规定量 磁共振成像(MRI)以获得解剖病理指标；以及(3)神经心理学(NP) 确定这些患者认知缺陷模式的措施。NP电池将由以下组件组成 多项测试分成认知领域，特别强调注意力、工作记忆和加工 速度。企业资源计划的衡量标准将从两个范例中获得，这两个范例对工作流管理的组成部分很敏感 编码、维护、操作和匹配/响应选择。核磁共振措施将重点放在 磁化转移率(MTR)用于量化组织丢失和微观组织损伤。主动者的角色 不活跃的疾病、用药和心理因素将被仔细考虑。健康对照 参与者也将被研究。据推测，在“非中枢神经系统”SLE患者中，MRI(特别是 MTR)和ERP(幅度、潜伏期、与条件相关的头皮地形图和单次试验潜伏期变异性) 将是系统性红斑狼疮患者认知缺陷的敏感指标。能够更清楚地定义 系统性红斑狼疮患者的信息处理缺陷及其潜在的解剖学和功能基础 缺陷，将进一步了解这种疾病的可能病理生理机制，并导致 改进了分类和治疗。