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

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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.