Patients with NPSLE experience poorer HRQoL and more fatigue than SLE patients with no neuropsychiatric involvement, irrespective of neuropsychiatric activity.

OBJECTIVES: Substantial proportions of patients with SLE report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes. METHODS: We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968). The NPSLE group comprised individuals with NP-BILAG A/B/C/D or score in any descriptor of the NP-SLEDAI-2K at baseline (N = 350), while the non-NPSLE group consisted of patients with NP-BILAG E (N = 2618). HRQoL was assessed with the SF-36, EQ-5D-3L, and FACIT-F. Full health state (FHS) was defined as 'no problems' in all EQ-5D dimensions. RESULTS: NPSLE patients reported lower scores in the SF-36 physical and mental component summary compared with the non-NPSLE population [mean (s.d.): 35.7 (9.1) vs 39.6 (9.6); P < 0.001 and 37.3 (12.1) vs 41.4 (11.0); P < 0.001, respectively]. NPSLE patients also exhibited impaired HRQoL in all EQ-5D dimensions compared with non-NPSLE patients (P < 0.05 for all). A substantially lower proportion of NPSLE patients experienced FHS in comparison with the non-NPSLE group (3.3% vs 14.5%; P < 0.001). NPSLE was associated with severe fatigue [23.8 (12.2) vs 31.5 (11.6); P < 0.001]. Notably, our findings revealed no discernible distinctions between active and inactive NPSLE patients with regard to SF-36, EQ-5D, FHS or FACIT-F scores. CONCLUSION: NP in patients with SLE has a detrimental effect on HRQoL experience and is associated with severe fatigue, regardless of the degree of neuropsychiatric disease activity. Early intervention is warranted in NPSLE patients to enhance long-term HRQoL experience.

A rare case of lupus cerebritis presenting as ictal epileptic headache: A case report.

Ictal epileptic headache, characterized by headache as the sole symptom of a seizure attack, is a rare condition. In this case report, we present a 52-year-old female with a history of systemic lupus erythematosus who sought medical attention at the headache clinic due to a new type of headache. The headache was described as an intense painful wave followed by a dull headache, without autonomic symptoms or migrainous features. Magnetic resonance imaging revealed an enhancing lesion in the left hippocampus in addition to two other lesions in the corpus callosum and left parieto-occipital lobe. Electroencephalography during the headache episodes showed epileptic discharges originating from the left fronto-temporal region. The patient was initiated on levetiracetam, which resulted in the resolution of both the epileptic discharges and the headaches. This case underscores the significance of considering ictal epileptic headache as a potential secondary cause for headaches, particularly in patients with underlying conditions that may predispose them to epilepsy, such as systemic lupus erythematosus.

Update οn the diagnosis and management of systemic lupus erythematosus.

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

Quantitative MRI adds to neuropsychiatric lupus diagnostics.

OBJECTIVE: Attributing neuropsychiatric manifestations to SLE is often challenging. Brain white matter lesions are frequent in SLE at MRI, but their diagnostic role is unclear. Here, we assessed whether white matter lesions count, volume and distribution measurement can help in the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Brain dual-echo and 3D T1-weighted sequences were acquired from 32 patients with SLE and 32 healthy controls with a 3 T-scanner and employed to derive T2-hyperintense lesion volume (T2LV), number (T2LN) and probability maps (LPM) using a semi-automatic local thresholding segmentation technique. NPSLE was classified as per the ACR nomenclature, the Italian Society for Rheumatology algorithm and by clinical impression. Clinical descriptors including the SLE International Collaborating Clinics/ACR damage index (SDI) were also recorded. RESULTS: Higher T2LV were observed in SLE vs healthy controls (P < 0.001) and in NPSLE vs other SLE (P =0.006). Patients with NPSLE also had higher T2LN (P =0.003) compared with other SLE. In SLE, T2LPM revealed a high prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata. T2LV and T2LN correlated with SLE duration (rho = 0.606; P <0.001 and rho = 0.483; P =0.005, respectively) and age (rho = 0.478; P =0.006 and rho = 0.362; P = 0.042, respectively). T2LV also correlated with SDI (rho = 0.352; P =0.048). SLE patients with fatigue had lower T2LN (P =0.038) compared with patients without fatigue. Thresholds of T2LV ≥ 0.423 cm3 or of T2LN ≥ 12 were associated with definite NPSLE and improved the classification of patients with possible NPSLE per clinical impression. CONCLUSION: Brain white matter lesions (WML) quantitation adds to NPSLE diagnostics.

Different patterns of cerebral perfusion in SLE patients with and without neuropsychiatric manifestations.

To investigate brain perfusion patterns in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE and non-NPSLE, respectively) and to identify biomarkers for the diagnosis of NPSLE using noninvasive three-dimensional (3D) arterial spin labeling (ASL). Thirty-one NPSLE and 24 non-NPSLE patients and 32 age- and sex-matched normal controls (NCs) were recruited. Three-dimensional ASL-MRI was applied to quantify cerebral perfusion. Whole brain, gray (GM) and white matter (WM), and voxel-based analysis (VBA) were performed to explore perfusion characteristics. Correlation analysis was performed to find the relationship between the perfusion measures, lesion volumes, and clinical variables. Receiver operating characteristic (ROC) analysis and support vector machine (SVM) classification were applied to differentiate NPSLE patients from non-NPSLE patients and healthy controls. Compared to NCs, NPSLE patients showed increased cerebral blood flow (CBF) within WM but decreased CBF within GM, while non-NPSLE patients showed increased CBF within both GM and WM. Compared to non-NPSLE patients, NPSLE patients showed significantly reduced CBF in the frontal gyrus, cerebellum, and corpus callosum. CBF within several brain regions such as cingulate and corpus callosum showed significant correlations with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index scores. ROC analysis showed moderate performance in distinguishing NPSLE from non-NPSLE patients with AUCs > 0.7, while SVM analysis demonstrated that CBF within the corpus callosum achieved an accuracy of 83.6% in distinguishing NPSLE from non-NPSLE patients. Different brain perfusion patterns were observed between NPSLE and non-NPSLE patients. CBF measured by noninvasive 3D ASL could be a useful biomarker for the diagnosis and disease monitoring of NPSLE and non-NPSLE patients.

Mortality in patients with systemic lupus erythematosus and neuropsychiatric involvement: A retrospective analysis from a tertiary referral center in the Netherlands.

OBJECTIVE: We aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018. METHODS: Patients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE. RESULTS: 351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI: 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI: 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR: 1.0 (95% CI: 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients. CONCLUSION: Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.

Analysis of brain metabolites by gas chromatography-mass spectrometry reveals the risk-benefit concerns of prednisone in MRL/lpr lupus mice.

OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice. METHODS: Metabolic changes were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease of N-acetyl-L-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus. CONCLUSION: These results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk-benefit balance of prednisone for SLE or NPSLE remains to be further evaluated.

Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus.

Involvement of the central nervous system (CNS) is an uncommon feature in systemic lupus erythematosus (SLE), making diagnosis rather difficult and challenging due to the poor specificity of neuropathic symptoms and neurological symptoms. In this work, we used human-induced pluripotent stem cells (hiPSCs) derived from CNS-SLE patient, with the aim to dissect the molecular insights underlying the disease by gene expression analysis and modulation of implicated pathways. CNS-SLE-derived hiPSCs allowed us to provide evidence of Erk and Akt pathways involvement and to identify a novel cohort of potential biomarkers, namely CHCHD2, IDO1, S100A10, EPHA4 and LEFTY1, never reported so far. We further extended the study analysing a panel of oxidative stress-related miRNAs and demonstrated, under normal or stress conditions, a strong dysregulation of several miRNAs in CNS-SLE-derived compared to control hiPSCs. In conclusion, we provide evidence that iPSCs reprogrammed from CNS-SLE patient are a powerful useful tool to investigate the molecular mechanisms underlying the disease and to eventually develop innovative therapeutic approaches.

Cerebral blood flow abnormalities in neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To investigate the clinical characteristics, imaging changes and early diagnostic methods of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty-five SLE patients, of which 16 had overt neuropsychiatric symptoms, underwent examination for multiple autoantibodies, including anti-double-stranded DNA (anti-dsDNA) antibody, anti-nucleosome antibody, anti-cardiac-phospholipid antibody (aCL)-IgG, aCL-IgM, anti-ß2-glycoprotein I antibody and anti-ribosomal P antibody, and the SLEDAI score of every patient was recorded. All patients further received neuropsychological tests, including the Mini-Mental State Examination, the Self-Rating Anxiety Scale and the Self-Rating Depression Scale. Imaging examination using 3D arterial spin labeling was performed on 3.0 T MRI scanners. After processing the 3D arterial spin labeling image, the cerebral blood flow map was obtained and the cerebral blood flow value was calculated. RESULTS: The values of anti-dsDNA, anti-nucleosome antibody, aCL-IgG and anti-ß2-glycoprotein I antibodies were significantly higher in the NPSLE group than those in the SLE group. The SLEDAI scores of the NPSLE group were significantly higher than those of the SLE group. There were no significant differences between the NPSLE group and the SLE group in the directional ability, memory, attention, numeracy, recall ability or language ability scores on the Mini-Mental State Examination scale. Furthermore, there were no symptoms of anxiety or depression in any of the patients, according to the Self-Rating Anxiety Scale and Self-Rating Depression Scale. In the 35 patients with SLE, decreases in blood perfusion were seen in some areas, and were unilateral and asymmetrically distributed. There was obvious asymmetry between sides in areas including the frontal lobe, temporal lobe, parietal lobe and occipital lobe. The incidence of perfusion decreases in frontal lobe in the NPSLE group was significantly higher than in the SLE group. CONCLUSION: Neurological lesions in SLE patients can be detected by arterial spin labeling. Cerebral blood flow abnormalities may be helpful for the early diagnosis of neurological lesions in NPSLE.

Anti-IFNAR treatment does not reverse neuropsychiatric disease in MRL/lpr lupus mice.

OBJECTIVE: Many systemic lupus erythematosus patients display a type I interferon (IFN) signature, and IFNα levels positively correlate with disease severity. Previous studies blocking the type I IFN pathway systemically in lupus models showed some beneficial effects. However, its effects on neuropsychiatric manifestations have yet to be carefully assessed, even though IFNα has been associated with induction of depression. Our aim was to investigate whether disrupting the type I IFN pathway would attenuate the development of murine neuropsychiatric lupus. METHODS: Female MRL/lpr mice were administered an antitype I IFN receptor (IFNAR) antibody or a control antibody intraperitoneally three times weekly for 12 weeks starting at age 4-5 weeks. Behavior was assessed during and at the end of the treatment schedule. RESULTS: No significant differences were seen between the anti-IFNAR- and control-treated mice when assessing for depression-like behavior or cognitive dysfunction, although anti-IFNAR antibody-treated mice displayed significant decreases in levels of IFN-stimulated genes. Anti-IFNAR treatment also did not significantly improve brain histology, cellular infiltration, or blood-brain barrier integrity. CONCLUSIONS: Surprisingly, our results showed no improvement in neuropsychiatric disease and suggest that the role of IFNAR signaling in the pathogenesis of neuropsychiatric lupus continues to need to be carefully assessed.

Anti-N-Methyl-D-Aspartic Acid Receptor 2 (Anti-NR2) Antibody in Neuropsychiatric Lupus Serum Damages the Blood-Brain Barrier and Enters the Brain.

BACKGROUND Brain microvessel endothelial cells constitute an important component in the blood-brain barrier. Cell-culture-based models of the blood-brain barrier (BBB) have been extensively applied in pharmacology, pathology and physiology. This study investigated effects of anti-N-methyl-D-aspartic acid receptor 2 (anti-NR2), N-methyl-D-aspartic acid (NMDA) receptor antibodies, NMDA receptor antagonists, and NMDA receptor agonists on brain microvessel endothelial cell models, and verified the effect of anti-NR2 antibody on the BBB as a receptor agonist. MATERIAL AND METHODS The primary brain microvessel endothelial cells were isolated and cultured, and an in vitro BBB model was established based on microvessel endothelial cells. Anti-NR2 antibody, glutamic acid, ifenprodil, and memantine were added in the BBB model to analyze changes in transepithelial electrical resistance (TEER) and to examine the permeability of the brain microvessel endothelial cell model. RESULTS The results showed that TEER values were significantly decreased by the addition of anti-NR2 antibody and glutamate, but were significantly increased by the addition of ifenprodil and memantine. TEER values showed no changes when treated by anti-NR2 antibody and ifenprodil, as well as anti-NR2 antibody and memantine. When dexamethasone was added, the TEER values increased by 23.8%, 39.4%, and 29.6% by treating with anti-NR2 antibody, positive cerebrospinal fluid, and positive serum, respectively. CONCLUSIONS Our findings show that anti-NR2 antibody in neuropsychiatric lupus serum can damage the BBB and enter the brain.

Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its most prevalent manifestation is neuropsychiatric SLE (NP-SLE), which is characterized by increased involvement of the nervous system, with relevant symptoms, such as marked cognitive deficits, which are directly involved in subsequent functional disability. The objective of this study is to identify and compare the profile of cognitive deficits in patients with NP-SLE and patients with non-neuropsychiatric SLE (nonNP-SLE) by means of a systematic review and meta-analysis. METHODS: We performed a systematic literature search based on the key words "cogn* OR neurocogn* AND lupus AND neuropsychiatry*" and included articles published between April 1999 and December 2016. A total of 244 articles were retrieved. We excluded reviews and meta-analyses, experiments not performed in humans, and single case reports. We included studies that used standardized cognitive measures and had included at least the subgroups NP-SLE and non NP-SLE. RESULTS: The meta-analysis was finally based on six studies, and 10 neuropsychological variables were examined. Significant differences were observed between the groups for six variables. In the remaining four variables, we observed marked heterogeneity between the groups or a low number of studies. CONCLUSIONS: The data obtained indicate greater cognitive impairment among NP-SLE patients than among nonNP-SLE patients, at least for the cognitive domains of visuomotor coordination, attention, executive function, visual learning and memory, and phonetic fluency. The identification and definition of cognitive deficits in SLE patients is necessary to develop adequate cognitive remediation programs to improve functional outcomes. (JINS, 2018, 24, 629-639).

Diagnosing and attributing neuropsychiatric events to systemic lupus erythematosus: time to untie the Gordian knot?

Neurological and psychiatric syndromes, collectively referred to as NPSLE, occur frequently in SLE. The frequency of NPSLE varies from 21 to 95%; however, only 13-38% of neuropsychiatric (NP) events could be attributable to SLE in the NPSLE SLICC inception cohort. This variability in the frequency of NPSLE is attributable to the low specificity of the ACR case definitions for SLE-attributed NP syndromes, inclusion of minor NP events in the ACR nomenclature, difficulty in ascertainment of NP events and diverse experience of rheumatologists in the clinical assessment of NP events. Making the correct and early attribution of NP events to SLE is important to institute appropriate immunosuppressive treatment for favourable outcomes. Various attribution models using composite decision rules have been developed and used to ascribe NP events to SLE. This review will focus on the various clinical presentations, diagnostic work-up and attributions of the common NPSLE syndromes, including other NP events not included in the ACR nomenclature but which have come to attention in recent years.

Brain morphology and cortical thickness variations in systemic lupus erythematosus patients: Differences among neurological, psychiatric, and nonneuropsychiatric manifestations.

PURPOSE: To determine whether systemic lupus erythematosus (SLE) affecting subcortical white matter volumes, deep gray matter volumes, and cortical thickness differ between groups of SLE patients with psychiatric (P-SLE), neurological (N-SLE), or nonneuropsychiatric (non-NPSLE) presentations. MATERIALS AND METHODS: Sixty-seven participants were divided into three groups (P-SLE [n = 19], N-SLE [n = 12], and non-NPSLE [n = 36]) and examined with a 1.5T MRI scanner. The images were segmented in FreeSurfer software into volumetric and cortical thickness measures using T1 3D magnetization prepared rapid gradient echo-weighted imaging. For comparative analyses of volume, multivariate analyses of covariance (MANCOVA) were applied followed by Bonferroni post-hoc tests, with age as a covariate. For cortical thickness analyses, the groups were compared with the Query Design Estimate Contrast tool adjusted for age. RESULTS: Globus pallidus volumes in both left (P ≤ 0.01) and right (P ≤ 0.05) hemispheres were larger in the N-SLE group than in the non-NPSLE group, and the left GP volume was greater in the N-SLE group than in the P-SLE group (P ≤ 0.05) (MANCOVA, post-hoc Bonferroni). The P-SLE group presented with thinning of cortical areas relative to the N-SLE (predominantly in the left parietal and right frontal and parietal regions) (P ≤ 0.05) and non-NPSLE (predominantly in parietal and occipital regions) (P ≤ 0.05) groups, whereas the N-SLE group presented with thickening of cortical areas (mostly right frontal and left parietal regions) relative to the non-NPSLE (P ≤ 0.05) and P-SLE groups. CONCLUSION: N-SLE patients had greater local volumes and cortical thicknesses than the other two groups, whereas P-SLE patients presented with decreased volumes and cortical thinning. These findings provide evidence of distinct neuroanatomical abnormalities in neurological versus psychiatric manifestations of SLE. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:150-158.

Neuropsychiatric symptoms in systemic lupus erythematosus: impact on quality of life.

Objective Assess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE). Methods Quality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases. Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role ( p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health ( p = 0.014) and mental component score ( p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE. Conclusion Quality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.

A comparison of patients' and physicians' assessments of disease activity using the Swedish version of the Systemic Lupus Activity Questionnaire.

OBJECTIVES: We compared patients' assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians' assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (< 1 year) versus long (≥ 1 year) disease duration. METHOD: Patients filled out the SLAQ before physicians' assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearman's ρ. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests. RESULTS: We included 203 patients (79% women), with a median age of 45 years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians' SLAM without laboratory items (SLAM-nolab) and patients' assessments were: SLAQ total, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 0.24). Patients' and physicians' assessments were notably more discordant for patients with short disease durations. CONCLUSION: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients' and physicians' assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.

Cyclophosphamide in combination with glucocorticoids for severe neuropsychiatric systemic lupus erythematosus: a retrospective, observational two-centre study.

Cyclophosphamide (CYC) is used in severe neuropsychiatric systemic lupus erythematosus (NPSLE), but long-term data regarding its efficacy and safety are lacking. We identified NPSLE cases who received CYC from two centres during the period 1999-2013 and had regular follow-up. General and neuropsychiatric outcome at last follow-up visit were determined, and major complications were documented. CYC was administered in 50 neuropsychiatric events. Median age was 45.0 years and 46% of patients were positive for antiphospholipid antibodies. Most frequent indications were psychosis (11 cases), polyneuropathy (six cases), and cerebrovascular disease, seizure disorder and cranial neuropathy (five cases). CYC was mainly administered as monthly pulses (median number: 8.0 (range 3-26), median cumulative dose: 7.2 g (range 2.4-33.8)). Cases were followed for a median of 46.5 months (range 5-408). At last follow-up, partial or complete response of NPSLE was observed in 84% of events; 10% had stable disease, whereas the remaining 6% failed to improve or worsened and were rescued with rituximab. In events that responded to CYC, maintenance therapy consisted of azathioprine in 31 events (65.9%), bimonthly or quarterly pulses of intravenous CYC in nine (19.1%), and mycophenolate mofetil in five (10.6%). Relapses were observed in six events (12%) at median eight months after initial response. No malignancies were observed, yet there were three cases of severe infections. Amenorrhea was recorded in three patients, who had not received gonadal protection. In conclusion, cyclophosphamide was efficacious and led to sustained response of severe NPSLE in a cohort with long follow-up.

Subclinical right ventricle systolic dysfunction in childhood-onset systemic lupus erythematosus: insights from two-dimensional speckle-tracking echocardiography.

OBJECTIVE: The objective of this article is to evaluate right ventricle strain imaging by two-dimensional speckle-tracking (2DST) in childhood-onset systemic lupus erythematosus (c-SLE). METHODS: Thirty-five c-SLE patients with no signs or symptoms of heart failure and 33 healthy volunteers were evaluated by standard echocardiogram and 2DST. Conventional parameters included tricuspid annular plane systolic excursion (TAPSE), RV tissue-Doppler-derived Tei index and systolic pulmonary artery pressure. Global peak longitudinal systolic strain (PLSS) and strain rate (PLSSR) of RV were obtained by 2DST. Demographic/clinical features, SLEDAI-2K/SLICC/ACR-DI and treatment were also assessed. RESULTS: The median current age was similar in patients and controls (14.75 vs. 14.88 years, p = 0.62). RV PLSS was significantly reduced in c-SLE (-24.5 ± 5.09 vs. -27.62 ± 3.02%, p = 0.003). Similar findings were observed after excluding patients with pulmonary hypertension (-24.62 ± 4.87% vs. -27.62 ± 3.02%, p = 0.0041). RV PLSS was positively correlated with TAPSE (r = +0.49, p = 0.0027) and negatively correlated with Tei index (r = -0.34, p = 0.04) in c-SLE. RV PLSSR was not different comparing patients and controls (-0.65 s(-1 )± 0.47 vs. -1.87 ± 0.49 s(-1), p = 0.07). Further analysis of c-SLE patients revealed higher frequencies of neuropsychiatric manifestations (39% vs. 0%, p = 0.007) and antiphospholipid antibodies (55% vs. 18%, p = 0.035) in those with RV PLSS ≤ -23.7% vs >-23.7%. No differences were evidenced in demographic data, disease activity/damage or treatments (p > 0.05). CONCLUSIONS: The present study, using a new and more sensitive technique, revealed subclinical RV systolic dysfunction in c-SLE patients that may have future prognostic implications. The novel association of asymptomatic RV dysfunction with neuropsychiatric manifestations and antiphospholipid antibodies may suggest common physiopathological pathways.

Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India.

Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients.

Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE).

Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10), interferon γ-inducible protein 10 (IP-10/CXCL10), lymphotactin, macrophage inhibitory protein 3ß (MIP-3ß/CCL19), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon γ (IFN-γ)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3-hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid). Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism.