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

“非 CNS”SLE 中 CNS 受累的神经学指标

基本信息

批准号：
7560404
负责人：
JANET L SHUCARD
金额：
$ 29.91万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7560404
关键词：
Accounting Activities of Daily Living Address Adrenal Cortex Hormones Anatomy Anterior Area Attention Attentional deficit Auditory Autoimmune Diseases Back Brain Brain Pathology Chronic Classification Cognitive Cognitive deficits Control Groups Data 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 Magnetic Resonance Imaging Maintenance Measures Memory impairment Methodology Methods Microscopic Modeling Mood Disorders Neuraxis Neurobiology Neurocognitive Deficit Neurologic Neuropsychological Tests Organ Parietal Participant Pathogenesis Pathology Patients Pattern Performance Peripheral Pharmaceutical Preparations Procedures Process Psychological Factors Psychotic Disorders Recording of previous events Reporting Response Latencies Response to stimulus physiology Role Scalp structure Seizures Short-Term Memory Site Speed Staging Steroids Stimulus Stroke System Systemic Lupus Erythematosus Task Performances Techniques Testing Time Tissues base brain tissue depression design frontal lobe illness length improved indexing information processing interest memory process neuropathology neuropsychiatry neuropsychological novel processing speed relating to nervous system response tool

项目摘要

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。神经精神临床表现，包括神经系统（中枢或外周），精神和认知障碍，据报道，SLE患者的发病率为14%至75%。中枢神经系统（CMS）的测定涉及的表现范围从明显的障碍，如癫痫发作，中风，精神病，弥漫性和更可疑的CMS障碍，如轻度情绪障碍，头痛，微妙的认知缺陷后者的发病机制更微妙和弥漫性的表现是未知的并且CMS参与的诊断仍然存在问题。最近，“CMS”SLE已被用于仅描述那些有明显CMS障碍的患者，而所有其他患者均被归类为“非CNS” SLE。无论用于确定神经精神和/或CMS参与的分类标准如何，在SLE患者中，当轻度损害时，包括.最常被报道的缺陷是在注意力、信息处理速度、工作记忆（Working Memory，WM）本建议的主要目的是审查 CMS参与无明显CNS的SLE患者认知障碍的病理生理学临床表现（如中风、癫痫、精神病）。SLExs患者将使用：（1）事件相关脑电位（ERPs），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标;（3）神经心理学（NP）测量以确定这些患者的认知缺陷模式。NP电池将由将多个测试分为认知领域，特别强调注意力、工作记忆和处理速度ERP测量将从两个范式中获得，这两个范式对WM组件敏感，编码、维护、操作和匹配/响应选择。MRI措施将侧重于磁化传递率（MTR）来量化组织损失和微观组织损伤。积极的角色并且将仔细考虑非活动性疾病、药物使用和心理因素。健康对照参与者也将被研究。假设在“非CNS”SLE患者中，MRI（特别是 MTR）和ERP（振幅、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SLE认知缺陷的敏感指标。能够更清楚地定义 SLE中的信息处理缺陷及其潜在的解剖和功能基础缺陷，将进一步了解这种疾病的可能病理生理机制，并导致改善分类和治疗。