BRAIN CONNECTIONS: ADD-ON STUDY OF SERIAL BRAIN MRIS EVERY SIX MONTHS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 脑部疾病：每六个月进行一次连续脑部核磁共振检查的附加研究 摘要(年报12/01/2004-11/30/2005) 背景： 神经性系统性红斑狼疮(NPSLE)发生在50%-75%的SLE患者中，这取决于抽样程序和使用的诊断标准，是发病率和生活质量下降的主要来源。如果通过敏感的神经心理测试仔细评估认知功能，更多的患者可能会有与SLE相关的神经损害。与系统性红斑狼疮相关的神经病变包括广泛的神经和精神病学特征，从中风、癫痫、周围神经病变、舞蹈病、痴呆、焦虑和抑郁到更细微的认知异常，如注意力、记忆和视觉空间异常。 脑成像是无创性识别和区分NPSLE综合征的病理生理机制的有力工具。单独或联合应用解剖磁共振成像(MRI)和正电子发射断层扫描(PET)结合2-[18F]氟-2-脱氧-D-葡萄糖(FDG)是研究NPSLE综合征最广泛使用的脑成像技术。文献中关于这些技术的敏感性和特异性的不一致可能反映了由不同的潜在病理生理机制引起的具有不同临床表现的SLE患者。 Brain Contions是由美国国立卫生研究院资助的一项正在进行的、前瞻性的、观察性的多中心队列研究，旨在研究新诊断的系统性红斑狼疮患者的认知功能。脑部核磁共振和正电子发射计算机断层扫描是在第三年的基线上进行的，如果ANAM的认知功能有明显的下降，那么ANAM就是一组自动化的测试。 基本原理： 到目前为止，对脑部连接研究参与者进行的31次基线脑MRI扫描分析发现，脑萎缩的频率令人惊讶：26%的患者患有轻度脑萎缩，26%的患者患有中度脑萎缩。 脑部疾病研究的这一最新成像发现表明：1)新诊断的SLE患者有很高的解剖脑MRI异常频率，2)MRI异常与研究开始时持续注意力和反应时间的降低以及疾病活动性的增加有关。这表明，大脑的功能和结构损伤在疾病过程的早期就很明显，并强调了了解SLE大脑参与的潜在机制的迫切需要。 “大脑连接：每六个月进行一次连续大脑核磁共振成像的附加研究”允许每六个月进行一次大脑核磁共振成像，以找到大脑萎缩的关联和预测因素，而不考虑认知功能的重大变化。 研究问题和具体目标： 一：在基线和6个月的随访中确定脑萎缩的频率和潜在的可逆性或恶化。 第二：确定萎缩是否与临床活动性有关，通过临床疾病指数或包括低补体、高抗DNA和抗磷脂抗体的血清学分析来衡量。 第三：确定SLE治疗(由其他器官的活动决定)是否影响脑萎缩：泼尼松是否会加重脑萎缩？ 研究设计： 这是一项初步研究，旨在确定SLE患者的脑萎缩是进行性、稳定性还是可逆性的。此外，我们将探索可能与脑萎缩相关或预测脑萎缩的人口学和临床特征。 神经图像采集 解剖MRI图像扫描每六个月进行一次，时间为患者在脑连接研究中剩余的时间。由于萎缩的患病率在基线时如此之高，我们认为每隔六个月跟踪受试者以确定萎缩是否可逆以及是否与临床活动有关是很重要的。 解剖MRI扫描将包括T1加权、T2加权、质子密度加权和3D梯度回想采集。将对屏幕监视器上显示的图像执行图像读取。 所有的MRI图像都将是DICOM3格式。 控制总是以一种盲目的方式包括在德克萨斯大学圣安东尼奥分校的阅读课程中。有男性对照可用。Brey博士和Fox博士(神经科医生和神经放射科医生)是主要读者。对于病人，我们记录精神疾病。 对于定性分析，从脑部核磁共振扫描获得的图像将以盲目的方式使用计算机投影显示在屏幕上。图像将以随机顺序投射，并将由德克萨斯大学圣安东尼奥分校的神经学家一致阅读。MRI评分为：0=正常，1=轻度萎缩，2=中度萎缩，任意局灶性病变，3=重度萎缩，5局灶性病变。 研究人群： 所有进入霍普金斯大学的脑部疾病患者都有资格参加这项附加研究。 结果衡量标准： 主要结果是评级等级为0、1(轻度)、2(中度)和3(重度)。 目前招生人数(12/01/2004-11/30/2005)： 31例患者已经完成了附加研究的第一次脑MRI，其中18例患者还完成了6个月的随访MRI。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brain CONECTIONS: Add-on Study of Serial Brain MRIs Every Six Months ABSTRACT (Annual Report 12/01/2004 - 11/30/2005) Background: Neuropsychaitric SLE (NPSLE) occurs in 50-75% of SLE patients, depending on the sampling procedures and diagnostic criteria used and is a major source of morbidity and decreased quality of life. If cognitive function is carefully evaluated with sensitive neuropsychological testing, an even larger number of patients may have SLE-related neurologic involvement. SLE-related neurologic involvement encompasses a wide spectrum of overt neurologic and psychiatric features ranging from strokes, seizures, peripheral neuropathy, chorea, dementia, anxiety, and depression to more subtle cognitive abnormalities such as attention, memory, and visio-spatial abnormalities. Brain imaging is a powerful tool to noninvasively identify and differentiate the pathophysiological mechanisms responsible for NPSLE syndromes. Alone or in combination, anatomic Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) are the most widely used brain imaging techniques to study patients with NPSLE syndromes. Inconsistencies in the literature regarding the sensitivity and specificity of these techniques likely reflect inclusion of SLE patients with heterogeneous clinical presentations caused by different underlying pathophysiological mechanisms. Brain CONECTIONS is an NIH-funded ongoing, prospective, observational multi-center cohort study of cognitive function in newly-diagnosed patients with SLE. Brain MRI and PET are done at baseline, at year 3, and if there is an important decline in cognitive functioning on the ANAM, an automated battery of tests. Rationale: Analyses of 31 baseline brain MRI scans done to date among the participants of Brain CONECTIONS study found a surprising frequency of brain atrophy: 26% of patients had mild brain atrophy and 26% had moderate brain atrophy. This recent imaging findings from the Brain CONECTIONS study suggest the following: 1) newly diagnosed SLE patients have a high frequency of anatomic brain MRI abnormalities, 2) MRI abnormalities are associated with decreased sustained attention and reaction time and higher disease activity at study entry. This suggests that both functional and structural damage to the brain is evident early in the disease process and underscores the critical need to understand the underlying mechanism of brain involvement in SLE. "Brain CONECTIONS: Add-on Study of Serial Brain MRIs Every Six Months" allows brain MRIs to be done every 6 months, to find associates and predictors of brain atrophy irrespective of major change in cognitive functioning. Study questions and Specific aim: One: Determine the frequency of and potential reversibility or worsening of brain atrophy at baseline AND at 6 monthly follow-up. Two: Determine if atrophy is associated with clinical activity, as measured by clinical disease indices or serologic assays including low complements, high anti-DNA, and antiphospholipid antibodies. Three: Determine whether SLE treatment (determined by activity in other organs) affects brain atrophy: does prednisone worsens brain atrophy? Study Design: This is a pilot study designed to ascertain whether brain atrophy in SLE patients is progressive, stable, or reversible. In addition, we will explore demographic and clinical characteristics that may be associated with or predictive of brain atrophy. Neuro Image Acquisition Anatomic MRI image scanning are done every six months for the time that the patient has remaining in the Brain CONECTIONS study. As the prevalence of atrophy was so high at baseline, we feel it is important to follow subjects at six month intervals to determine if the atrophy is reversible and if it is associated with clinical activity. Anatomical MRI scans will include a T1- weighted, a T2- weighted, a proton density-weighted, and a 3D Gradient Recalled Acquisitions. Image reading will be performed on images displayed on screen monitors. All MRI images will be in DICOM 3 format. Controls are always included, in a blinded fashion, in the reading sessions at the University of Texas, San Antonio. Male controls are available. Dr. Brey and Dr. Fox (neurologist and neuroradiologist) are the principal readers. For patients, we record psychiatric illness. For qualitative analyses, images obtained from the brain MRI scans will be displayed on a screen using computer projection in a blinded fashion. Images will be projected in random order and will be read by consensus by the neurologists at the University of Texas, San Antonio. The rating for the MRI are: 0 = Normal, 1 = Mild atrophy, 2 = Moderate atrophy, any focal lesion, 3 = Severe atrophy, >5 focal lesions. Study Population: All Brain CONECTIONS patients entered at Hopkins are eligible for this add-on study. Outcome Measures: The primary outcome is the rating scale of 0, 1 (Mild), 2 (Moderate), and 3 (Severe). Current enrollment (12/01/2004 - 11/30/2005): 31 patients already completed the 1st Brain MRI of the add-on study of which 18 patients also completed the 6 month follow-up MRI.