Diagnosis Of Neuropsychiatric Systemic Lupus Erythematosus Research Articles

A neuropsychiatric systemic lupus erythematosus presenting with acute confusional state: a case report

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by variable clinical symptoms. It disproportionately affects African-American women and women from other ethnic groups. The complexity of SLE, stemming from its genetic and phenotypic diversity, poses challenges in diagnosis, treatment, and development of novel therapies. Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a spectrum of neurological syndromes involving the central, peripheral, and autonomic nervous systems, as well as psychiatric syndromes diagnosed in SLE patients after ruling out other causes. Neuropsychiatric manifestations typically emerge in the later stages of SLE (10–75%). The acute onset of neuropsychiatric symptoms as the primary presentation of NPSLE is exceptionally rare and can be diagnostically elusive when other organs are unaffected. In this article, we present the case of a 53-year-old woman who was admitted to the hospital due to disorientation and an acute confusional state. Following the diagnosis of NPSLE, she received treatment consisting of three doses of pulse corticosteroids and one dose of cyclophosphamide. She exhibited a favorable clinical response, leading to partial resolution of her symptoms and subsequent discharge from the hospital. Practical Implications. Due to the rarity and diverse clinical presentations of NPSLE, particularly with the sudden onset of neuropsychiatric symptoms, there is a significant risk of delayed or incorrect diagnosis, which can lead to ineffective treatment. Therefore, maintaining a high index of clinical suspicion is paramount for achieving early and accurate diagnosis, which is crucial for initiating timely and effective treatment strategies.

Recent advances in the diagnosis and management of neuropsychiatric lupus.

Neuropsychiatric manifestations of systemic lupus erythematosus (SLE) are common and frequently associated with a substantial negative impact on health outcomes. The pathogenesis of neuropsychiatric SLE (NPSLE) remains largely unknown, but a single pathogenic mechanism is unlikely to be responsible for the heterogeneous array of clinical manifestations, and a combination of inflammatory and ischaemic mechanistic pathways have been implicated. Currently, valid and reliable biomarkers for the diagnosis of NPSLE are lacking, and differentiating NPSLE from nervous system dysfunction not caused by SLE remains a major challenge for clinicians. However, correct attribution is essential to ensure timely institution of appropriate treatment. In the absence of randomized clinical trials on NPSLE, current treatment strategies are derived from clinical experience with different therapeutic modalities and their efficacy in the management of other manifestations of SLE or of neuropsychiatric disease in non-SLE populations. This Review describes recent advances in the understanding of NPSLE that can inform diagnosis and management, as well as unanswered questions that necessitate further research.

Comprehensive Insights into Neuropsychiatric Systemic Lupus Erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, often affecting women of childbearing age, with periods of exacerbations and remissions. SLE can impact multiple organs, causing a range of clinical symptoms. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes symptoms like headaches, seizures, anxiety disorders, cognitive dysfunctions, psychosis, and neuropathies. Its diagnosis is challenging, and treatment is complex. Purpose: This study aims to explain the pathophysiology of NPSLE, describe diagnostic methods, and summarize current treatment methods based on recent research. Methods: Databases such as PubMed, Medline, and ResearchGate were used. State of current knowledge: Early and accurate diagnosis of SLE is crucial for optimal patient management. The 2019 EULAR/ACR classification criteria have improved diagnostic precision with a weighted scoring system for diverse disease manifestations. Therapy of neuropsychiatric lupus focuses on symptom control and causal treatment, considering anti-inflammatory action or counteracting ischemic incidents. It involves immunosuppressive agents and antiplatelet or anticoagulant substances. Non-pharmacological interventions and lifestyle modifications are also important. The dynamic criteria reflect ongoing advancements in understanding SLE, emphasizing continuous research and collaboration. Conclusions: The diagnosis of NPSLE requires excluding other causes of neuropsychiatric symptoms, such as infections, endocrine disorders, or drug reactions. Diagnostic methods vary based on symptoms, including lumbar puncture, CSF analysis, EEG, cognitive function assessment, and MRI. The treatment of NPSLE focuses on symptom control and causal treatment, with therapy individualized based on symptom severity and patient burden.

Diagnosis of neuropsychiatric systemic lupus erythematosus by label-free serum microsphere-coupled SERS fingerprints with machine learning

Surface-enhanced Raman spectroscopy (SERS) is a powerful optical technique for non-invasive and label-free bioanalysis of liquid biopsy, facilitating to diagnosis of potential diseases. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the subgroups of systemic lupus erythematosus (SLE) with serious manifestations for a high mortality rate. Unfortunately, lack of well-established gold standards results in the clinical diagnosis of NPSLE being a challenge so far. Here we develop a novel Raman fingerprinting machine learning (ML-) assisted diagnostic method. The microsphere-coupled SERS (McSERS) substrates are employed to acquire Raman spectra for analysis via convolutional neural network (CNN). The McSERS substrates demonstrate better performance to distinguish the Raman spectra from serums between SLE and NPSLE, attributed to the boosted signal-to-noise ratio of Raman intensities due to the multiple optical regulation in microspheres and AuNPs. Eight statistically-significant (p-value <0.05) Raman shifts are identified, for the first time, as the characteristic spectral markers. The classification model established by CNN algorithm demonstrates 95.0% in accuracy, 95.9% in sensitivity, and 93.5% in specificity for NPSLE diagnosis. The present work paves a new way achieving clinical label-free serum diagnosis of rheumatic diseases by enhanced Raman fingerprints with machine learning.

Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Correlation Between B-Cell Activating Factor of the Tumor Necrosis Factor Family Level in Serum and Immune Inflammation in Patients with Neuropsychiatric Systemic Lupus Erythematosus and its Clinical Value

ABSTRACT Objective Neuropsychiatric systemic lupus erythematosus (NPSLE) is a form of SLE associated with severe NP syndromes causing mortality and morbidity. Respecting the fundamental of BAFF in NPSLE pathophysiology, we investigated its clinical value. Methods Totally 105 NPSLE and 101 SLE cases without NPSLE (non-NPSLE, control) were included. Serum BAFF/TNF-α/IL-6/IL-10 levels were measured using ELISA kits. T lymphocytes were detected by flow cytometry. The independent influencing factors for NPSLE, and the auxiliary diagnostic efficacy and the ability of BAFF levels to predict adverse prognosis of NPSLE patients were analyzed by multiple factor logistic regression, and ROC curve and survival curve. Results In NPSLE patients, serum BAFF level was increased and positively correlated with SLEDAI-2k, serum proinflammatory cytokines, while negatively correlated with CD4+T/CD8+T cells, and anti-inflammatory cytokine. High serum BAFF protein level was associated with a higher risk of developing NPSLE. The AUC of serum BAFF > 301.7 assisting in NPSLE diagnosis was 0.8196. Furthermore, high levels of serum BAFF were associated with a higher risk of adverse outcomes in NPSLE patients. Conclusion Serum BAFF level in NPSLE patients was correlated with lymphocytes and high serum BAFF protein level could assist in diagnosis and to predict adverse outcomes in NPSLE patients.

Nutrition Status And Neuropsychiatric Disorders In Indonesian Childhood Lupus: Experience At A Single Tertiary Referral Center

NPSLE diagnosis is still challenging because of many SLE-related and non-SLE-related processes that can be presented in patient. The report of NPSLE in Indonesia is still limited. This study aim to describe the clinical features, nutrition status, and laboratory characteristics of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) and compared to non NPSLE case in Indonesian children. The study is a retrospective cohort study. Data were collected from the complete medical record of Juvenile Systemic lupus Erythematosus (jSLE) patients 2016 - 2020 at the Allergy Immunology Outpatient clinic at Dr. Soetomo General Academic Hospital. We include all patients with ages ranging from age 0-18 years old with a diagnosis of Systemic lupus Erythematosus (SLE). The diagnosis fo SLE based on American College of Rheumatology (ACR) criteria 1997 and Neuropsychiatric (NP) manifestations were classified using the standardized nomenclature and case definitions for the 19 NP manifestations linked to SLE developed in 1999 by the ACR ad hoc Committee. Disease activity SLE was defined according to the American Mexican-Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) criteria. Statistical analysis conducted in this study was descriptive analysis, paired T-test (NPSLE vs. non-NPSLE as the dependent variable), Fischer exact test, and Pearson Chi-square test using SPSS ver. 21. A total of 90 patients with juvenile SLE were enrolled, but only 71 patients were eligible as participants with complete medical records obtained. Mex-SLEDAI score was significantly higher on NPSLE compared to non-NPSLE (p=0.001).

Performance of eye sign combined with increased interleukin-6 in cerebrospinal fluid in patients with neuropsychiatric lupus erythematosus.

To ascertain whether microvascular alterations of eye sign combined with intrathecal concentrations of interleukin-6 (IL-6) can predict the development of neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) and serum samples of IL-6 were collected and measured at the same time for patients with SLE who were consecutively enrolled. Patients with a diagnosis of NPSLE were identified. Eye sign examinations according to our criteria were performed and scored for all SLE patients. Demographic and clinical parameters were compared between groups to identify potential predictors for NPSLE using multivariable logistic regression analysis. The performance of potential predictors from eye sign along with IL-6 in the CSF was assessed. A total of 120 patients with SLE were enrolled; 30 with NPSLE and 90 with non-NPSLE. No significant positive correlation was observed between CSF level and serum level of IL-6. CSF IL-6 was significant higher in the NPSLE group than the non-NPSLE (P < 0.001) group. Multivariable logistic analysis revealed that total score, ramified loops, and microangioma of eye sign were predictors for NPSLE after adjusting for SLE Disease Activity Index (SLEDAI) and antiphospholipid antibody (APL). Total score, ramified loops, microangioma of eye sign, and SLEDAI remain significant predictors for NPSLE after adjusting for CSF IL-6. Using receiver operating characteristics curve analysis, the cut-off point of potential predictors was applied in multivariable logistic analysis; APL, total score, ramified loops, and microangioma of eye sign remain significant predictors for NPSLE after adjusting for CSF IL-6. Specific microvascular alterations of eye sign are predictors for the development of NPSLE in addition to increased IL-6 in the CSF.

The conundrum of neuropsychiatric systemic lupus erythematosus: Current and novel approaches to diagnosis.

Recognising neuropsychiatric involvement by systemic lupus erythematosus (SLE) is of growing importance, however many barriers to this exist at multiple levels of our currently available diagnostic algorithms that may ultimately delay its diagnosis and subsequent treatment. The heterogeneous and non-specific clinical syndromes, serological and cerebrospinal fluid (CSF) markers and neuroimaging findings that often do not mirror disease activity, highlight important research gaps in the diagnosis of neuropsychiatric SLE (NPSLE). Formal neuropsychological assessments or the more accessible screening metrics may also help improve objective recognition of cognitive or mood disorders. Novel serum and CSF markers, including autoantibodies, cytokines and chemokines have also shown increasing utility as part of diagnosis and monitoring, as well as in distinguishing NPSLE from SLE patients without SLE-related neuropsychiatric manifestations. Novel neuroimaging studies also expand upon our existing strategy by quantifying parameters that indicate microarchitectural integrity or provide an assessment of neuronal function. Some of these novel markers have shown associations with specific neuropsychiatric syndromes, suggesting that future research move away from considering NPSLE as a single entity but rather into its individually recognized neuropsychiatric manifestations. Nevertheless, it is likely that a composite panel of these investigations will be needed to better address the gaps impeding recognition of neuropsychiatric involvement by SLE.

Noise-Immune Extreme Ensemble Learning for Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus.

Early diagnosis is currently the most effective way of saving the life of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). However, it is rather difficult to detect this terrible disease at the early stage, due to the subtle and elusive symptomatic signals. Recent studies show that the 1H-MRS (proton magnetic resonance spectroscopy) imaging technique can capture more information reflecting the early appearance of this disease than conventional magnetic resonance imaging techniques. 1H-MRS data, however, also presents more noises that can bring serious diagnosis bias. We hence proposed a noise-immune extreme ensemble learning technique for effectively leveraging 1H-MRS data for advancing the early diagnosis of NPSLE. Our main results are that 1) by developing generalized maximum correntropy criterion in the kernel extreme learning setting, many types of non-Gaussian noises can be distinguished, and 2) weighted recursive feature elimination, using maximal information coefficient to weight feature's importance, helps to further alleviate the bad impact of noises on the diagnosis performance. The proposed method is assessed on a publicly available dataset with 97.5% accuracy, 95.8% sensitivity and 99.9% specificity, which well demonstrates its efficacy.

A noise-immune reinforcement learning method for early diagnosis of neuropsychiatric systemic lupus erythematosus.

The neuropsychiatric systemic lupus erythematosus (NPSLE), a severe disease that can damage the heart, liver, kidney, and other vital organs, often involves the central nervous system and even leads to death. Magnetic resonance spectroscopy (MRS) is a brain functional imaging technology that can detect the concentration of metabolites in organs and tissues non-invasively. However, the performance of early diagnosis of NPSLE through conventional MRS analysis is still unsatisfactory. In this paper, we propose a novel method based on genetic algorithm (GA) and multi-agent reinforcement learning (MARL) to improve the performance of the NPSLE diagnosis model. Firstly, the proton magnetic resonance spectroscopy (1H-MRS) data from 23 NPSLE patients and 16 age-matched healthy controls (HC) were standardized before training. Secondly, we adopt MARL by assigning an agent to each feature to select the optimal feature subset. Thirdly, the parameter of SVM is optimized by GA. Our experiment shows that the SVM classifier optimized by feature selection and parameter optimization achieves 94.9% accuracy, 91.3% sensitivity, 100% specificity and 0.87 cross-validation score, which is the best score compared with other state-of-the-art machine learning algorithms. Furthermore, our method is even better than other dimension reduction ones, such as SVM based on principal component analysis (PCA) and variational autoencoder (VAE). By analyzing the metabolites obtained by MRS, we believe that this method can provide a reliable classification result for doctors and can be effectively used for the early diagnosis of this disease.

Neuropsychiatric Systemic Lupus Erythematosus in Older Adults: Diagnosis and Management.

Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease with variable clinical manifestations. Neuropsychiatric systemic lupus erythematosus (NPSLE) includes the neurologic syndromes of the central, peripheral and autonomic nervous system and the psychiatric syndromes observed in patients with SLE. Neuropsychiatric systemic lupus erythematosus events may present as an initial manifestation of SLE or may be diagnosed later in the course of the disease. Older adults with NPLSE include those who are ageing with known SLE and those with late-onset SLE. The diagnosis of NPSLE across the lifespan continues to be hampered by the lack of sensitive and specific laboratory and imaging biomarkers. In this review, we discuss the particular complexity of NPSLE diagnosis and management in older adults. We first discuss the epidemiology of late-onset NPSLE, then review principles of diagnosis of NPSLE, highlighting issues that are pertinent to older adults and that make diagnosis and attribution more challenging, such as atypical disease presentation, higher medical comorbidity, and differences in neuroimaging and autoantibody investigations. We also discuss clinical issues that are of particular relevance to older adults that have a high degree of overlap with SLE, including drug-induced lupus, cerebrovascular disease and neurocognitive disorders. Finally, we review the management of NPSLE, mainly moderate to high- dose glucocorticoids and immunosuppressants, again highlighting considerations for older adults, such as increased medication (especially glucocorticoids) adverse effects, ageing-related pharmacokinetic changes that can affect SLE medication management, medication dosing and attention to medical comorbidities affecting brain health.

Utility of autoantibody against an UCH-L1 epitope as a serum diagnostic marker for neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most serious complications of systemic lupus erythematosus (SLE), lacking efficient diagnostic biomarkers. Previous studies have shown that anti-ubiquitin carboxyl hydrolase L1(UCH-L1) autoantibody is a promising cerebrospinal fluid (CSF) biomarker for NPSLE diagnosis. The purpose of this study is to explore the serum autoantibodies against different UCH-L1 epitopes and investigate the potential diagnostic value of serum autoantibodies against different UCH-L1 epitopes in NPSLE. The epitopes of UCH-L1 protein were predicted in DNAStar software. The serum levels of different UCH-L1 epitope autoantibodies in 40 NPSLE patients, 32 SLE patients without neuropsychiatric symptoms and 21 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Data were analysed using Pearson correlation analysis, ROC curve analysis, nonparametric Mann-Whitney test, t-test and χ2 test. We screened three candidate epitopes of UCH-L1 protein. The autoantibody against amino acid 58 to 69 of UCH-L1 (UCH58-69) showed highest diagnostic power in distinguishing NPSLE patients from SLE patients without neuro-psychiatric symptoms (p=0.0038). The ROC analysis showed that the specificity and sensitivity of anti-UCH58-69 were 92.3% and 37.5%, respectively. In addition, increased serum anti-UCH58-69 levels were associated with increased SLEDAI, CSF microprotein, CSF leukocyte count, ESR, AnuA, anti-dsDNA, IgG and IgM but with decrease of C3 in SLE patients. The serum levels of anti-UCH58-69 significantly increased in NPSLE patients compared with SLE patients without neuropsychiatric symptoms and were correlated with disease severity. Anti-UCH58-69 autoantibody may become a novel serum biomarker for NPSLE non-invasive diagnosis, which might be applicable for NPSLE early screening and diagnosis.

Postpartum Psychosis Masking the Diagnosis of Neuropsychiatric Lupus

Systemic Lupus Erythematosus (SLE) is a chronic, relapsing, and remitting systemic disease. Autoimmunity and protean clinical manifestations affecting almost all the systems are the hallmarks of SLE. Systemic lupus can affect the central nervous system. The severity of CNS manifestations varies from less severe subclinical neurocognitive dysfunction affecting memory, intellect, and learning to more severe manifestations such as seizure, stroke, or transverse myelitis [1]. The psychotic features of primary psychiatric disorders overlap with Neuropsychiatric SLE (NPSLE) and often mask and delay the diagnosis of NPSLE.

Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus by Deep Learning Enhanced Magnetic Resonance Spectroscopy

The neuropsychiatric systemic lupus erythematosus (NPSLE) has higher disability and mortality rates, which is one of the main causes of death in systemic lupus erythematosus (SLE) patients. Magnetic resonance spectroscopy (MRS) can detect the changes of metabolites in different intracranial areas in vivo in patients with SLE, so as to provide evidence for the early diagnosis of NPSLE. Different from the conventional single-voxel MRS, which can only screen one brain region with one metabolic change, we simultaneously detect 13 kinds of intracranial metabolic changes in nine brain regions by multivoxel proton MRS (MVS). We use a recursive feature elimination algorithm to select the most related metabolites for better identifying NPSLE. To accurately diagnosis NPSLE by these intracranial metabolites, we train a support vector machine deep stacked network (SVM-DSN) for quantitative analysis of these metabolites. Comparing with the conventional statistic method, which is about 70% of accuracy, the proposed model achieves 97.5% of accuracy for NPSLE diagnosis. We conclude the trained SVM-DSN can effectively analyze the metabolites obtained by multivoxel proton MRS for NPSLE diagnosis, which may help to early diagnosis and intervention of NPSLE, and alleviate the bias of manual screening.

Broad Learning Enhanced 1H-MRS for Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus.

In this paper, we explore the potential of using the multivoxel proton magnetic resonance spectroscopy (1H-MRS) to diagnose neuropsychiatric systemic lupus erythematosus (NPSLE) with the assistance of a support vector machine broad learning system (BL-SVM). We retrospectively analysed 23 confirmed patients and 16 healthy controls, who underwent a 3.0 T magnetic resonance imaging (MRI) sequence with multivoxel 1H-MRS in our hospitals. One hundred and seventeen metabolic features were extracted from the multivoxel 1H-MRS image. Thirty-three metabolic features selected by the Mann-Whitney U test were considered to have a statistically significant difference (p < 0.05). However, the best accuracy achieved by conventional statistical methods using these 33 metabolic features was only 77%. We turned to develop a support vector machine broad learning system (BL-SVM) to quantitatively analyse the metabolic features from 1H-MRS. Although not all the individual features manifested statistics significantly, the BL-SVM could still learn to distinguish the NPSLE from the healthy controls. The area under the receiver operating characteristic curve (AUC), the sensitivity, and the specificity of our BL-SVM in predicting NPSLE were 95%, 95.8%, and 93%, respectively, by 3-fold cross-validation. We consequently conclude that the proposed system effectively and efficiently working on limited and noisy samples may brighten a noinvasive in vivo instrument for early diagnosis of NPSLE.

Advances in the diagnosis, pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus

Diagnosing and treating neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging as the pathogenesis is still being debated. In this review, we discuss studies evaluating recent advances in diagnostic methods, pathogenic mediators and potential treatments. Screening tools used for neurodegenerative diseases were found to be both sensitive and moderately specific for cognitive dysfunction in NPSLE. Neuroimaging can be used to distinguish systemic lupus erythematosus (SLE) patients from healthy controls, but further refinement is needed to differentiate between lupus patients with and without neuropsychiatric manifestations. Elevated levels of specific molecules in the cerebrospinal fluid and/or serum, as well as the presence of certain autoantibodies, have been identified as potential biomarkers in attempts to facilitate a more accurate and objective diagnosis. Among such autoantibodies, anti-NR2 and anti-ribosomal P autoantibodies also have a pathogenic role, although newer studies demonstrate that blood-brain barrier damage may not always be required as previously believed. These and other observations, together with new evidence for disease attenuation after microglial modulation, suggest direct involvement of the central nervous system in NPSLE pathogenesis. Neuropsychiatric involvement of SLE includes a variety of symptoms that impact quality of life and patient prognosis. There have been recent advances in improving the diagnosis of NPSLE as well as in dissecting the underlying pathogenesis. The attenuation of neuropsychiatric disease in mouse models demonstrates the potential for targeted therapies, which are based on a clearer understanding of the pathogenesis of NPSLE. Further assessment of these treatments is required in NPSLE patients, as well as the potential use of neuroimaging to distinguish between SLE patients with or without neuropsychiatric manifestations.

Autoantibodies associated with neuropsychiatric systemic lupus erythematosus: the quest for symptom-specific biomarkers.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs, including the central nervous system. Neuropsychiatric SLE (NPSLE) is a severe and potentially fatal condition. Several factors including autoantibodies have been implicated in the pathogenesis of NPSLE. However, definitive biomarkers of NPSLE are yet to be identified owing to the complexity of this disease. This is a major barrier to accurate and timely diagnosis of NPSLE. Studies have identified several autoantibodies associated with NPSLE;some of these autoantibodies are well investigated and regarded as symptom-specific. In this review, we discuss recent advances in our understanding of the manifestations and pathogenesis of NPSLE. In addition, we describe representative symptom-specific autoantibodies that are considered to be closely associated with the pathogenesis of NPSLE.

Management of Psychosis in Neuropsychiatric Lupus

Manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Acute psychosis is an uncommon but well-recognized manifestation of NPSLE. With no specific biomarkers to date, the diagnosis of NPSLE relies on clinical acumen for circumstantial evidence and exclusion of important differential diagnoses. The attribution of psychosis to NPSLE is facilitated by the application attribution models. In particular, the American College of Rheumatology nomenclature, Systemic Lupus International Collaborating Clinics attribution models and Italian algorithm for the attribution of psychosis to NPSLE are revisited. The mainstay of treatment for psychosis attributable to NPSLE is immunosuppression and symptomatic control. In refractory cases, immunomodulatory and emerging biological agents may be considered. This article reviews the diagnostic dilemma, pathogenic mechanisms and treatment of psychosis in SLE patients.

Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus.

The whole protein of osteopontin (OPN full) and its cleaved form (OPN N-half) are involved in the immune response and the migration of immune cells to an inflammatory lesion. We have reported that serum OPN full and urine OPN N-half are elevated in lupus nephritis (LN). Neuropsychiatric systemic lupus erythematosus (NPSLE) is a refractory complication of SLE. To investigate whether OPN full and OPN N-half could serve as diagnostic markers for NPSLE, and to elucidate their role in NPSLE pathogenesis, the concentrations of OPN full and OPN N-half in cerebrospinal fluid (CSF) were measured in NPSLE and non-NPSLE patients. We found that the concentration of OPN full in the CSF was significantly higher in NPSLE than in non-NPSLE, and it decreased after treatment. When the cutoff value of OPN full in CSF was set to 963.4 ng/ml, the sensitivity and specificity for the diagnosis of NPSLE were 70% and 100%, respectively. The correlation analysis of OPN full, OPN N-half and various cytokines/chemokines suggested that the cytokines/chemokines could be divided into two clusters: cluster A, which contains OPN full and cluster B, which contains interleukin-6. OPN full in CSF could be a novel diagnostic marker for NPSLE.