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: 7166039
• 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/7166039
• 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

DESCRIPTION (provided by applicant): 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 CMS disturbances, 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 CMS disturbances, 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). SLExpatients will 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, and processing 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.

描述（由申请人提供）：系统性红斑狼疮（SLE）是一种慢性、多器官自身免疫性疾病。据报道，SLE患者中的神经精神表现，包括神经系统（中枢或外周）、精神和认知障碍，范围为14%至75%。中枢神经系统（CMS）受累的确定是基于从明显的障碍（如癫痫发作、中风或精神病）到弥漫性和更可疑的CMS障碍（如轻度情绪障碍、头痛和微妙的认知缺陷）的表现。这些后者更微妙和弥漫性的表现的发病机制是未知的，CMS参与的诊断仍然存在问题。最近，“CMS”SLE仅用于描述那些有明显CMS紊乱的患者，而所有其他患者均被归类为“非CNS”SLE。无论用于确定SLE中神经精神和/或CMS参与的分类标准如何，当包括轻度损害时，高达80%的SLE患者报告了认知障碍。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）领域。本提案的主要目的是研究CMS参与无明显CNS表现（如卒中、癫痫发作、精神病）的SLE患者认知障碍的潜在病理生理学。SLEx患者将使用以下方法进行研究：（1）事件相关脑电位（ERP），以获得脑功能指数;（2）常规和非常规定量磁共振成像（MRI），以获得解剖病理学指数;（3）神经心理学（NP）测量，以确定这些患者的认知缺陷模式。NP成套测验将由分为认知领域的多个测验组成，特别强调注意力、WM和处理速度。ERP措施将从两个范式，是敏感的WM组件的编码，维护，操作，匹配/响应选择。MRI测量将侧重于磁化传递率（MTR），以量化组织损失和微观组织损伤。将仔细考虑活动性和非活动性疾病、药物使用和心理因素的作用。还将研究健康对照受试者。假设在“非CNS”SLE患者中，MRI（特别是MTR）和ERP（振幅、潜伏期、条件相关头皮地形图和单次试验潜伏期变异性）将是SLE中观察到的认知缺陷的敏感指标。更清楚地定义SLE中所见的信息处理缺陷以及这些缺陷的潜在解剖学和功能基础的能力，将进一步理解这种疾病的可能病理生理机制，并导致改进的分类和治疗。