Relation of antiphospholipid antibodies to postmortem brain infarcts in older people.

BACKGROUND: There are few data on the relationship of antiphospholipid antibodies (aPLs) to pathologically proven brain infarcts. We tested the hypothesis that aPLs are associated with a higher odds of brain infarcts among older, community-dwelling individuals who came to autopsy. METHODS AND RESULTS: Specimens and clinical and pathological data were derived from 607 deceased subjects (mean age at death, 89 years; 66% women) who were participating in 1 of 2 cohort studies of aging (Rush Memory and Aging Project and Religious Orders Study) and had agreed to brain autopsy. Brain infarcts were identified on gross and microscopic examinations, and severity of cerebral vessel disease (atherosclerosis, arteriolosclerosis) was graded. Four clinically used aPLs were measured longitudinally: 3 in serum (anticardiolipin antibodies, ß2-glycoprotein I, and anti-phosphatidyl-serine) and 1 in plasma (lupus anticoagulant). A quarter of subjects (142 of 607, 23%) had at least 1 aPL present at baseline (median time interval from baseline to death, 4.6 years), and three quarters of these subjects had persistently positive measures over time. In a logistic regression analysis, baseline aPL positivity did not increase the odds of brain infarcts (odds ratio=1.08; 95% confidence interval, 0.74-1.58; P=0.19) or of gross or microscopic infarcts separately. Findings were essentially unchanged when considering number of baseline aPLs, aPLs proximate to death, and persistence of aPLs. Associations did not differ among subjects with increased severity of vessel disease. CONCLUSION: Overall, we did not find evidence that aPLs increase the odds of pathological brain infarcts in older people.

Risk of intracerebral hemorrhage in HIV/AIDS: a systematic review and meta-analysis.

Evidence for the association and the increased risk of stroke with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is growing. Recent studies have reported on HIV infection as a potent risk factor for intracerebral hemorrhage (ICH). We used the pooled results from case-control studies to conduct a systematic review and a meta-analysis in order to evaluate the risk of ICH with HIV/AIDS. Our systematic review and meta-analysis was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm of all available case-control studies that reported on the risk of ICH in patients with HIV/AIDS. Five eligible studies were identified, totaling 5,310,426 person-years studied over various periods that ranged from 1985 to 2010. There were a total of 724 cases of ICH, 138 with HIV/AIDS. HIV-infected ICH patients were in average younger. Pooled crude incidence rate ratio (IRR) for ICH in HIV/AIDS patients was 3.40 (95 % confidence intervals [CI] 1.44-8.04; p = 0.005, random-effects model). Clinical AIDS was associated with a higher IRR of ICH (11.99, 95 % CI 2.84-50.53; p = 0.0007) than HIV+ status without AIDS (1.73, 95 % CI 1.39-2.16; p < 0.0001). Patients with CD4+ lymphocyte count <200 cells/mm3 were similarly at a higher risk. Antiretroviral therapy did not seem to increase the risk of ICH. The available evidence suggests that HIV/AIDS is an important risk factor for ICH, particularly in younger HIV-infected patients and those with advanced disease.

Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio.

BACKGROUND: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. METHODS: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-ß2-glycoprotein-I (anti-ß2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. RESULTS: Persistent anti-ß2GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-ß2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-ß2GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. CONCLUSIONS: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-ß2GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.

Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy.

BACKGROUND AND PURPOSE: Because of its association with atrial fibrillation and heart failure, we hypothesized that amino terminal pro-B-type natriuretic peptide (NT-proBNP) would identify a subgroup of patients from the Warfarin-Aspirin Recurrent Stroke Study, diagnosed with inferred noncardioembolic ischemic strokes, where anticoagulation would be more effective than antiplatelet agents in reducing risk of subsequent events. METHODS: NT-proBNP was measured in stored serum collected at baseline from participants enrolled in Warfarin-Aspirin Recurrent Stroke Study, a previously reported randomized trial. Relative effectiveness of warfarin and aspirin in preventing recurrent ischemic stroke or death over 2 years was compared based on NT-proBNP concentrations. RESULTS: About 95% of 1028 patients with assays had NT-proBNP below 750 pg/mL, and among them, no evidence for treatment effect modification was evident. For 49 patients with NT-proBNP >750 pg/mL, the 2-year rate of events per 100 person-years was 45.9 for the aspirin group and 16.6 for the warfarin group, whereas for 979 patients with NT-proBNP ≤750 pg/mL, rates were similar for both treatments. For those with NT-proBNP >750 pg/mL, the hazard ratio was 0.30 (95% confidence interval: 0.12-0.84; P=0.021) significantly favoring warfarin over aspirin. A formal test for interaction of NT-proBNP with treatment was significant (P=0.01). CONCLUSIONS: For secondary stroke prevention, elevated NT-proBNP concentrations may identify a subgroup of ischemic stroke patients without known atrial fibrillation, about 5% based on the current study, who may benefit more from anticoagulants than antiplatelet agents. Clinical Trial Registration- This trial was not registered because enrollment began before 2005.

Antiphospholipid antibodies, brain infarcts, and cognitive and motor decline in aging (ABICMA): design of a community-based, longitudinal, clinical-pathological study.

The overall goal of the Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging study is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically proven brain infarcts and are related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using antemortem magnetic resonance neuroimaging and postmortem neuropathology, as well as nonvascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of antemortem biological specimens (longitudinally collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 elderly, community-dwelling women and men who have agreed to brain autopsy at the time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project.

Neuroimaging evidence of white matter inflammation in newly diagnosed systemic lupus erythematosus.

OBJECTIVE: Central nervous system (CNS) involvement occurs frequently in systemic lupus erythematosus (SLE) and frequently results in morbidity. The primary pathophysiology of CNS involvement in SLE is thought to be inflammation secondary to autoantibody-mediated vasculitis. Neuroimaging studies have shown hypometabolism (representing impending cell failure) and atrophy (representing late-stage pathology), but not inflammation. The purpose of this study was to detect the presence and regional distribution of inflammation (hypermetabolism) and tissue failure, apoptosis, or atrophy (hypometabolism). METHODS: Eighty-five patients with newly diagnosed SLE, who had no focal neurologic symptoms, were studied. Disease activity was quantified using the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI), a validated index of SLE-related disease activity. 18Fluorodeoxyglucose (FDG) positron emission tomography (PET) images of glucose uptake were analyzed by visual inspection and as group statistical parametric images, using the SELENA-SLEDAI score as the analysis regressor. RESULTS: SELENA-SLEDAI-correlated increases in glucose uptake were found throughout the white matter, most markedly in heavily myelinated tracts. SELENA-SLEDAI-correlated decreases were found in the frontal and parietal cortex, in a pattern similar to that seen during visual inspection and presented in previous reports of hypometabolism. CONCLUSION: The SELENA-SLEDAI-correlated increases in glucose consumption are potential evidence of inflammation, consistent with prior reports of hypermetabolism in inflammatory disorders. To our knowledge, this is the first imaging-based evidence of SLE-induced CNS inflammation in an SLE inception cohort. The dissociation among 18FDG uptake characteristics, spatial distribution, and disease activity correlation is in accordance with the notion that glucose hypermetabolism and hypometabolism reflect fundamentally different aspects of the pathophysiology of SLE with CNS involvement.

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus.

BACKGROUND: Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. OBJECTIVE: We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. MATERIALS AND METHODS: We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. RESULTS: Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. CONCLUSION: MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults.

Patent foramen ovale, cardiac valve thickening, and antiphospholipid antibodies as risk factors for subsequent vascular events: the PICSS-APASS study.

BACKGROUND AND PURPOSE: We sought to estimate risk of recurrent stroke/TIA/death in the subgroup of the Patent Foramen Ovale in the Cryptogenic Stroke Study (PICSS) cohort with patent foramen ovale (PFO) and antiphospholipid antibodies (aPL) and to estimate risk of recurrent stroke/TIA/death in aPL-positive patients who have thickened left-side heart valves (VaT). PFO is associated with cryptogenic ischemic stroke. Also, the presence of aPL is associated with ischemic cerebrovascular disease. METHODS: Combined data from 2 major substudies of the Warfarin Aspirin Recurrent Stroke Trial (WARSS) were evaluated. PICSS subjects were included if they were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and underwent a baseline aPL test (lupus anticoagulant, anticardiolipin antibodies, or both) within 1 month of the stroke. All patients in PICSS underwent transesophageal echocardiography for PFO as well as VaT, which was performed blinded to aPL status and treatment arm (325 mg/day aspirin or adjusted dose warfarin; target international normalized ratio, 1.4-2.8). The primary outcome event was the 2-year risk of recurrent stroke/TIA/death and was evaluated using Cox proportional hazards model. Because there was no treatment effect, warfarin and aspirin groups were combined to increase power. For the combined end point, power to detect HR of 2 was 47.8% for the PFO and aPL-positive group, and 75.3% for the valve thickening and aPL-positive group, assuming 2-sided type I error of 0.05. RESULTS: Five hundred twenty-five subjects were tested for the combined presence of PFO and aPL and were available for evaluation. The primary outcome event rate was 23.9% (HR, 1.39; 95% CI, 0.75-2.59) in the PFO-positive/aPL-positive group, compared to 13.9% (HR, 0.83; 95% CI, 0.44-1.56) in the PFO-positive/aPL-negative group, and 19.9% (HR, 1.16; 95% CI, 0.68-1.90) in the PFO-negative/aPL-positive group. Five hundred forty-five subjects tested for combined presence of aPL and left-side cardiac VaT were available for evaluation. The primary event rate was 22.6% (HR, 1.65; 95% CI, 0.88-3.09) in the VaT-positive/aPL-positive group, compared to 19.4% (HR, 1.50; 95% CI, 0.82-2.75) in the VaT-positive/aPL-negative group, and 20.2% (HR, 1.63; 95% CI, 0.81-3.25) in the VaT-negative/aPL-positive group. CONCLUSIONS: The combined presence of aPL either with a PFO or with left-side cardiac VaT did not significantly increase risk of subsequent cerebrovascular events in this PICCS/APASS cohort of patients.

Neurologic manifestations of the antiphospholipid syndrome: integrating molecular and clinical lessons.

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by autoantibody production and thrombosis or pregnancy morbidity. The most prevalent neurologic manifestation of APS is cerebrovascular ischemic events due to arterial thromboses. Antiphospholipid antibodies can also cause neurologic impairments unrelated to thrombosis, through antibody-cellular interactions, possibly because of a disrupted blood-brain barrier. Antiplatelet or anticoagulant therapies are currently indicated for APS-related ischemic strokes, but they remain controversial for non-thrombotic neurologic manifestations. Scant literature exists on neurologic manifestations and treatment regimens in childhood APS. Modifiable cardiac risk factors and valvular heart disease may worsen APS cerebrovascular outcomes. Adjunctive therapies (eg, statins, antimalarials, and angiotensin-converting enzyme inhibitors) warrant clinical trials.

Antiphospholipid antibodies and stroke in young women.

BACKGROUND AND PURPOSE: Antiphospholipid antibodies have been associated with ischemic stroke in some but not all studies. METHODS: We performed a population-based case-control study examining antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants) using stored frozen sera and plasma in 160 cases and 340 controls enrolled in the Stroke Prevention in Young Women study. We evaluated for the presence of anticardiolipin antibody (IgG, IgM, and IgA isotypes) by an enzyme-linked immunosorbent assay and for the lupus anticoagulant using several phospholipid-dependent coagulation tests (activated partial thromboplastin time, dilute Russell's viper venom time) with mixing studies. If mixing studies were prolonged, confirmatory tests were performed. RESULTS: A positive anticardiolipin antibody level of any isotype was seen in 43 cases (26.9%) and 62 controls (18.2%) (P=0.03), lupus anticoagulant in 29 cases (20.9%) and 38 controls (12.8%) (P=0.03), and either anticardiolipin antibody or lupus anticoagulant in 61 cases (42.1%) and 86 controls (27.9%) (P=0.003). After adjustment for age, current cigarette smoking, hypertension, diabetes, angina, ethnicity, body mass index, and high-density lipoprotein levels, the relative odds of stroke for women with anticardiolipin antibody immunoreactivity of any isotype or a lupus anticoagulant was 1.87 (95% confidence interval, 1.24 to 2.83; P=0.0027). CONCLUSIONS: The results from this study support the importance of antiphospholipid antibodies as an independent risk factor for stroke in young women.

Soluble adhesion molecule levels, neuropsychiatric lupus and lupus-related damage.

Nervous system dysfunction may occur in as many as 80% of patients with Systemic Lupus Erythematous (SLE) at some point in their disease course. Upregulation of adhesion molecules has been linked to acute SLE-related disease activity and chronic damage. We evaluated the relationship between soluble adhesion molecule levels and neuropsychiatric lupus (NPSLE) manifestations using the American College of Rheumatology (ACR) case definitions to investigate for evidence of a link between upregulation of adhesion molecules and NPSLE manifestations. Sera from the initial study visit of 133 SLE patients enrolled in the San Antonio Lupus Study of Neuropsychiatric Disease (SALUD) and 40 controls were evaluated for soluble adhesion molecule levels (VCAM-1, ICAM-1 and E-selectin) and antiphospholipid antibodies. A subset of 57 SLE patients were evaluated for soluble adhesion molecule levels and antiphospholipid antibodies on two subsequent study visits, as well. NPSLE manifestations at the time of sera ascertainment were recorded using ACR case definitions and SLE-related acute activity and damage were measured. Elevated levels of all three soluble adhesion molecules were seen in SLE patients compared to normal control values. Soluble VCAM-1 levels correlated with measures of current disease activity, NPSLE manifestations and deep venous thrombosis. Persistently positive levels of ICAM-1 and VCAM-1, but not E-selectin were association with increased SLE-related damage. Elevated levels of all soluble adhesion molecule levels correlated with abnormal levels of antiphospholipid antibodies, which are associated with some NPSLE manifestations and have been shown to upregulate adhesion molecule expression.

Management of the neurological manifestations of APS--what do the trials tell us?

PURPOSE: To systematically review evidence from clinical trials about the management of neurological manifestations of Antiphospholipid Syndrome (APS). METHODS: Articles reporting case-control, cohort and prospective studies and treatment trials of primary or secondary stroke prevention in patients with aPL were identified in an OVID literature search from 1966 to 2004, using the keywords: APS, aPL and cerebrovascular disease. Articles were evaluated according to the standard system for assessing medical evidence to answer the following questions: (1) What is the role of aPL and recurrent stroke risk in both primary and secondary APS populations? (2) What is the evidence to support specific treatment strategies for secondary prevention of aPL-associated stroke? (3) What is the evidence to support specific treatment strategies for primary prevention of aPL-associated stroke? CONCLUSIONS: (1) aPL are a risk factor for incident stroke (Grade A, established as useful for the given condition in the specified population). (2) The evidence to support the role of aPL in recurrent stroke is conflicting and, therefore, inconclusive. (3) Warfarin at moderate-intensity doses is equally effective in preventing a recurrent thrombotic event as warfarin at high-intensity doses in patients with APS (Grade A evidence, established as useful for the given condition in the specified population). (4) Warfarin, at moderate-intensity doses is as effective as aspirin (at a dose of 325 mg/day) in preventing recurrent thrombotic events in patients who are aPL-positive at the time of an initial stroke (Grade B evidence, probably useful for the given condition in the given population). (5) Currently there are no data to support the use of any prophylactic therapy in patients with aPL and no clinical manifestations for the purposes of preventing an incident stroke.

Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE).

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of focal and diffuse central and peripheral nervous system disorders and affects up to 75% of SLE patients. NPSLE can occur any time in the course of SLE, even during periods in which no SLE disease activity is detected, and is likely to be caused by multiple factors, including autoantibody production, microvasculopathy and pro-inflammatory cytokines. Central to the diagnosis of NPSLE is the question of whether the presenting neuropsychiatric symptoms are due to SLE-mediated organ dysfunction, infection, medication side-effects or metabolic abnormalities (e.g. uraemia), or are due to an unrelated condition. The diagnostic inference of NPSLE can be made only after these secondary causes have been excluded. There is no one single diagnostic tool specific to NPSLE, and clinical diagnostic impressions must be based on the combined use of immunoserological testing, functional and/or structural neuroimaging and standardized neurological, rheumatological, psychiatric and neuropsychological assessments. The management of NPSLE includes symptomatic and/or immunosuppressive treatment strategies depending on the specific presenting neuropsychiatric symptoms and whether these occur in the setting of an SLE disease activity flare.

Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke.

CONTEXT: The presence of antiphospholipid antibodies (aPL) has been associated with vascular occlusive events. However, the role of aPL in predicting ischemic events, particularly recurrent ischemic stroke, is controversial. OBJECTIVE: To evaluate the effect of baseline aPL positivity (ie, positivity for anticardiolipin antibodies [aCL], lupus anticoagulant antibodies [LA], or both) on subsequent thrombo-occlusive events, including recurrent stroke. DESIGN, SETTING, AND PARTICIPANTS: The Antiphospholipid Antibodies and Stroke Study (APASS), a prospective cohort study within the Warfarin vs Aspirin Recurrent Stroke Study (WARSS), a randomized double-blind trial (N = 2206) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin (target international normalized ratio, 1.4-2.8) and aspirin (325 mg/d) for prevention of recurrent stroke or death. APASS participants were 1770 (80%) WARSS participants who consented to enroll in the APASS, with usable baseline blood samples drawn prior to randomization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory. Quality assurance was performed on approximately 10% of samples by a second independent laboratory. MAIN OUTCOME MEASURE: Two-year rate of the composite end point of death from any cause, ischemic stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, and other systemic thrombo-occlusive events. The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately, after risk-factor adjustment (since these aPL-positive vs aPL-negative comparisons were not randomized). RESULTS: Of the 1770 APASS patients, 720 (41%) were classified as aPL-positive and 1050 (59%) as aPL-negative. There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin (relative risk [RR], 0.99; 95% confidence interval [CI], 0.75-1.31; P =.94), or aspirin (RR, 0.94; 95% CI, 0.70-1.28; P =.71). The overall event rate was 22.2% among aPL-positive and 21.8% among aPL-negative patients. There was no treatment x aPL interaction (P =.91). Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate (31.7%) than did patients who tested negative for both antibodies (24.0%) (unadjusted RR, 1.36; 95% CI, 0.97-1.92; P =.07). Classification and regression tree analyses did not identify a specific LA test or aCL isotype or titer that was associated with increased risk of thrombo-occlusive event. CONCLUSIONS: The presence of aPL (either LA or aCL) among patients with ischemic stroke does not predict either increased risk for subsequent vascular occlusive events over 2 years or a differential response to aspirin or warfarin therapy. Routine screening for aPL in patients with ischemic stroke does not appear warranted.

Neurologic manifestations of systemic lupus erythematosus in children and adults.

Among the collagen vascular diseases neurologic manifestations have been most commonly recognized and well-studied in systemic lupus erythematosus (SLE, lupus). Neurologic manifestations are less prevalent in other systemic inflammatory and autoimmune disorders. This review focuses on the clinical presentation, pathophysiology, and treatment strategies of neuropsychiatric lupus (NPSLE) in children and adults.

Cerebral and cerebellar volume loss in children and adolescents with systemic lupus erythematosus: a review of clinically acquired brain magnetic resonance imaging.

OBJECTIVE: Cerebral atrophy is a prominent feature in adults with systemic lupus erythematosus (SLE). We assessed cerebral and cerebellar volume loss on clinically acquired brain magnetic resonance imaging (MRI) scans of children and adolescents with SLE. METHODS: We abstracted information on disease course for patients who underwent clinical brain MRI during the period 2002-2008. We completed qualitative assessments of volume loss and measured corpus callosum thickness and ventricular enlargement for patients with lupus and controls. RESULTS: Forty-nine children underwent brain MRI during the review period due to clinical indications. The lupus cohort was predominantly female and ethnically diverse. Mean age at imaging was 15.3 +/- 2.6 years and mean disease duration was 30.6 +/- 33.3 months. Findings suggestive of cerebral and cerebellar volume loss were seen respectively in 89.8% and 91.8% of lupus patients. Cerebral volume loss was moderate or severe in 26.5% of children. Cerebellar volume loss was moderate in 20.4% of these patients. Linear measurement means reflected corpus callosum thinning and ventricular enlargement in lupus patients. Volume loss was observed in newly diagnosed patients prior to corticosteroid use. Disease duration and corticosteroid use did not predict the severity of volume loss. There were statistically significant differences in linear imaging measurements comparing lupus patients to 14 similar-age controls. CONCLUSION: Regional volume loss was observed in most adolescents with lupus undergoing clinical brain MRI scans. As in other pediatric conditions with inflammatory or vascular etiologies, these findings may be reflecting disease-associated neuronal loss and not solely the effects of corticosteroid.

Depression and cognitive impairment in newly diagnosed systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is present in 80% of patients with systemic lupus erythematosus (SLE) 10 years after diagnosis. The natural history of cognitive dysfunction in newly diagnosed SLE is unknown. We examined the association of depression and cognitive performance in newly diagnosed SLE. METHODS: A multicenter cohort of 111 patients newly diagnosed (within 9 months) with SLE underwent cognitive function testing using an automated battery [Automated Neuropsychological Assessment Metrics (ANAM)] with 9 subtests. Depression was measured using the Calgary Depression Scale (CDS). RESULTS: The patient cohort was 97.3% female, 55.9% white, 15.3% African American, 20.7% Hispanic, mean age 37.8 years, mean education 15.2 years. CDS score ranged from 0 to 18 (mean 5.0 ± 4.6). CDS score did not differ by age, sex, ethnicity, or prednisone dose. Higher Krupp Fatigue Severity Scale scores and presence of fibromyalgia were significantly associated with higher CDS score (p < 0.001; p = 0.006, respectively). Depressed patients, defined by a CDS score > 6, had significantly poorer performance on 5 ANAM throughput measures: code substitution (p = 0.03), continuous performance (p = 0.02), matching-to-sample (p = 0.04), simple reaction time (p = 0.02), and the Sternberg memory test (p = 0.04). Adjusting for age, sex, ethnicity, education, and prednisone dose, a higher CDS score remained significantly associated with poorer performance on 3 measures, but the association was slightly attenuated for code substitution and matching-to-sample. Depression was not associated with mathematical or spatial processing. CONCLUSION: Depression, a modifiable risk factor, is associated with significantly poorer function in several cognitive domains in patients newly diagnosed with SLE. Treatment of depression when the CDS score is greater than 6 may improve cognitive functioning and should be further studied.