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

描述(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，在SLE患者中，神经精神症状，包括神经(中枢或外周)、精神和认知障碍，从14%到75%不等。对中枢神经系统(CMS)参与的判断是基于各种表现，从明显的癫痫、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。后者更细微和弥漫的表现的发病机制尚不清楚，CMS受累的诊断仍然存在问题。最近，“CMS”系统性红斑狼疮仅用于描述那些有明显CMS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。不管用于确定神经精神和/或CMS参与SLE的分类标准如何，当包括轻度损害时，高达80%的SLE患者报告有认知障碍。最常见的缺陷是注意力、信息处理速度、学习和工作记忆(WM)方面的缺陷。这项建议的主要目的是研究CMS参与无明显中枢神经系统症状(例如中风、癫痫、精神病)的SLE患者认知障碍的潜在病理生理学。SLExT患者将使用：(1)事件相关脑电位(ERPs)获得脑功能指数；(2)常规和非常规定量磁共振成像(MRI)获得解剖病理指数；以及(3)神经心理学(NP)措施确定这些患者的认知障碍模式。NP电池将由多个测试组成，这些测试分为认知领域，特别强调注意力、工作记忆和处理速度。企业资源规划指标将从两个范例中获得，这两个范例对编码、维护、操作和匹配/响应选择等工作流管理组件很敏感。MRI测量的重点将是磁化转移率(MTR)，以量化组织丢失和微观组织损伤。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。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(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SLE患者认知障碍的敏感指标。能够更清楚地定义SLE中出现的信息处理缺陷以及这些缺陷的潜在解剖和功能基础，将进一步了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。

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.