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: 7035480
• 负责人: JANET L SHUCARD
• 金额: $ 30.8万
• 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/7035480
• 关键词: attention; brain electrical activity; clinical research; cognition disorders; evoked potentials; human subject; magnetic resonance imaging; nervous system disorder; nervous system disorder diagnosis; neural information processing; neuropsychological tests; patient oriented research; short term memory; systemic lupus erythematosus

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患者的神经精神表现，包括神经（中枢或外周）、精神和认知障碍，占14%至75%。中枢神经系统（CMS）受累的确定基于表现，从明显的紊乱，如癫痫、中风或精神病，到弥漫性和更可疑的CMS紊乱，如轻度情绪障碍、头痛和微妙的认知缺陷。后者的发病机制更微妙和弥漫性的表现是未知的和诊断的CMS累及仍然有问题。最近，“CMS”SLE仅用于描述那些有明显CMS紊乱的患者，而其他所有患者都被归类为“非中枢神经系统”SLE。无论用于确定SLE中神经精神和/或CMS累及的分类标准如何，当包括轻度损害时，多达80%的SLE患者报告存在认知障碍。最常见的缺陷是在注意力、信息处理速度、学习和工作记忆（WM）方面。本提案的主要目的是研究CMS参与无明显中枢神经系统表现（如中风、癫痫、精神病）的SLE患者认知障碍的潜在病理生理学。slex患者将采用以下方法进行研究：(1)事件相关脑电位（event- relevant brain potentials, ERPs）获得脑功能指标；(2)常规与非常规定量磁共振成像（MRI）获取解剖病理指标；(3)采用神经心理学（NP）方法来确定这些患者的认知缺陷模式。NP测试将由多个认知领域的测试组成，特别强调注意力、WM和处理速度。ERP测量将从两个范式中获得，这两个范式对编码、维护、操作和匹配/响应选择的WM组件敏感。MRI测量将侧重于磁化传递比（MTR）来量化组织损失和显微组织损伤。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“非中枢神经系统”SLE患者中，MRI（特别是MTR）和ERP（振幅、潜伏期、与病情相关的头皮地形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中所见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可能的病理生理机制，并导致改进的分类和治疗。