Libman-Sacks Endocarditis as a Cause of Neuropsychiatric Systemic Lupus Erythematosus

The purpose of this study is to determine whether Libman-Sacks endocarditis (inflammation of the heart valves) is the cause of neuropsychiatric manifestations (stroke, transient ischemic attacks, cognitive dysfunction, seizures, acute confusional state, or psychosis) in patients with systemic lupus erythematosus.

Hypothesis of the study: Libman-Sacks endocarditis (especially valve vegetations or "small valve growths") generate macro (large) and micro (tiny) emboli that occlude the medium and small cerebral vessels resulting in altered perfusion, ischemic brain injury, and major NPSLE (stroke, TIA, seizures, cognitive dysfunction, acute confusional state, or psychosis).

Specific Aim 1: To determine cross-sectionally in SLE subjects the effects of valve vegetations detected by TEE on the presence of active cerebral microemboli, altered perfusion, ischemic brain lesions, and NPSLE. Findings in SLE patients will be compared to those in controls.

Specific Aim 2: To determine longitudinally in patients with new or recurrent NPSLE and during remission whether valve vegetations, active cerebral microemboli, and abnormal cerebral perfusion improve, or normalize when compared to baseline data in patients without NPSLE or matched controls.

Specific Aim 3: To determine cross-sectionally in SLE subjects the presence of active cerebral microemboli, altered brain perfusion, brain injury, and NPSLE in relation to other valve abnormalities, such as valve thickening or valve regurgitation, in addition to or independently of valve vegetations; and to determine longitudinally these relationships in patients with NPSLE. Findings in SLE patients will be compared to baseline data in patients without NPSLE or matched controls.

Our SLE/NPSLE cohort of \>400 subjects and our extensive cardiac and neuroimaging experience with TEE and MR-based techniques are essential resources for this study. We will integrate inflammatory and hemostatic parameters with multiple imaging modalities to investigate the causal connection between valve vegetations and the generation of microemboli and perfusion abnormalities, which then result in brain injury and NPSLE. A causal connection of valve vegetations to brain injury and NPSLE would result in a fundamental shift in the understanding of the pathogenesis, diagnosis, and therapy of Libman-Sacks endocarditis and NPSLE. These findings may extend to other inflammatory diseases associated with valve disease and complicated with central nervous system disease.

Eligibility Criteria:
Inclusion Criteria:

* Patients with diagnosis of SLE according to the American Rheumatology Association independent of gender or ethnicity and recruited from the Rheumatology Clinics at the University of New Mexico Health Sciences Center
* Patients (\> 18 and \< 60 years old) with new or recurrent major NPSLE
* Healthy volunteers based on history and physical examination
* Because of conscious sedation and the MR aspects of the study, women of childbearing potential who agree to participate will require to be on contraception therapy, had undergone an sterilization procedure, or have a negative pregnancy test for their inclusion in the study.

Exclusion Criteria:

* Children (as defined by NIH) will be excluded because the neurocognitive tests are standardized for individuals 18 or older. In New Mexico, adulthood is legally defined as 18 years old. Therefore, inclusion of subjects \<18 years old would invalidate the results of neurocognitive testing. Moreover, the number of children below 18 with SLE is so low in our population as to not provide a statistically viable result.
* Subjects older than 60 years will also be excluded because their high prevalence and incidence of aging related valve and brain pathology and neurocognitive dysfunction.
* Pregnant women will not be studied because of the need of conscious sedation during TEE and the MR aspects of the study. Women of childbearing potential who agree to participate and are not on contraception therapy or have not undergone an sterilization procedure will require a negative pregnancy test before their inclusion in the study.
* Patients with known or suspected valve or cardiac disease unrelated to SLE such as rheumatic valve disease, active or healed infective endocarditis, congenital bicuspid aortic valves, myxomatous mitral valves with prolapse, and those with prosthetic valves and/or sustained atrial fibrillation or flutter will be excluded.
* Patients with a known cardiac substrate for embolism (LV or LA thrombi, LV aneurysm, LV ejection fraction \<40% will be excluded on enrollment, but the development of these complications during the study will be noted and considered as a separate variable.
* Patients with non-SLE related cardiovascular or CNS disease such as congenital hypercoagulability syndromes, hypertensive encephalopathy, CNS infection, metabolic disturbances, hepatic failure, uncontrolled diabetes, or patients who are medicated with neuroleptic drugs.
* Patients with serious medical illness unsuitable for undergoing TEE and MRI scanning.
* Patients with thrombotic thrombocytopenic purpura (TTP).
* Patients with contraindications to esophageal intubation (i.e. esophageal stricture or esophageal varices).
* Patients at risk for hazard due to magnetic fields will be excluded. In critically ill patients TEE will be postponed until medically stable. Patients with supratherapeutic INR (\>3.5) will not undergo TEE until INR \<3.5. 11)
* Patients without NPSLE on warfarin at the entry phase of the study.
* History of head trauma in the form of concussion or contusion.