Predictive factors of psychiatric syndrome in patients with systemic lupus erythematosus.

Introduction: Early detection of neuropsychiatric systemic lupus erythematosus (NPSLE) remains a challenge in clinical settings. Previous studies have found different autoantibodies as markers for NPSLE. This study aimed to describe the distribution of psychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) and to investigate the association between psychiatric syndromes and specific autoantibodies. Methods: This retrospective study was conducted at a single medical center in China. We reviewed medical records of hospitalized patients with SLE who were consulted by psychiatrists due to potential mental disorders. Results of serum autoantibodies and general laboratory tests were collected. The correlation between clinical variables was examined. Binary logistic regression analyses were used to determine factors related to NPSLE and different psychiatric diagnoses. Results: Among the 171 psychiatric manifestations in 160 patients, 141 (82.4%) were attributed to SLE. Acute confusional state (ACS) had the highest prevalence (57.4%). Anti-cardiolipin (ACL) antibody (X2 = 142.261, p < 0.001) and anti-ß2 glycoprotein I (-ß2GP1) antibody (X2 = 139.818, p < 0.001) varied significantly between groups, with the highest positive rate found in patients with mood disorders (27.3% and 18.2%). SLE disease activity index - 2000 (SLEDAI-2K) score excluding item ACS and item psychosis was a predictor of NPSLE (OR 1.172 [95% CI 1.105 - 1.243]). Conclusions: Disease activity reflected by SLEDAI-2K score is a predictor for NPSLE. Antiphospholipid antibodies are associated with mood disorders in SLE. Further separate investigation of neuropsychiatric disorders is needed in order to better comprehend NPSLE's pathological mechanism.

Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.

BACKGROUND: Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE's pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice. METHODS: We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala. RESULTS: MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R2 = 0.58; p = 0.03), but not motivated behavior, in MRL/lpr mice. Compared to MRL/lpr IL-6 WT, IL-6 KO mice exhibited improved novelty preference on object placement (45.4% vs 60.2%, p < 0.0001) and object recognition (48.9% vs 67.9%, p = 0.002) but equivalent performance in tests for anxiety-like disease and depression-like behavior. IL-6 KO mice displayed decreased cortical expression of aif1 (microglia; p = 0.049) and gfap (astrocytes; p = 0.044). Correspondingly, IL-6 KO mice exhibited decreased density of GFAP + cells compared to IL-6 WT in the entorhinal cortex (89 vs 148 cells/mm2, p = 0.037), an area vital to memory. CONCLUSIONS: The inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.

Role of F-18 FDG PET-CT in neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major contributor to morbidity and mortality in systemic lupus erythematosus (SLE) patients. To date no single clinical, laboratory or imaging test has proven accurate for NPSLE diagnosis which is a testament to the intricate and multifactorial pathophysiological mechanisms suspected to exist. Functional imaging with FDG PET-CT has shown promise in NPSLE diagnosis, detecting abnormalities prior to changes evident on anatomical imaging. Research indicates that NPSLE may be more aggressive in people of African descent with higher mortality rates, making rapid and correct diagnosis even more important in the African context. METHODS: In this narrative review, we provide a thorough appraisal of the current literature on the role of FDG PET-CT in NPSLE. Large, well-known databases were searched using appropriate search terms. Manual searches of references of retrieved literature were also included. FINDINGS: A total of 73 article abstracts were assessed, yielding 26 papers that were directly relevant to the topic of FDG PET-CT in NPSLE. Results suggest that FDG PET-CT is a sensitive imaging test for NPSLE diagnosis and may play a role in assessing treatment response. It is complementary to routine anatomical imaging, particularly in diffuse manifestations of the disease. Newer quantitative analyses are commonly used for interpretation and can detect even subtle abnormalities, missed on visual inspection. Findings of group-wise analyses of FDG PET-CT scans in NPSLE patients are important in furthering our understanding of the complicated pathophysiological mechanisms involved. Limitations of FDG PET-CT include its lack of specificity, high cost and poor access. CONCLUSION: FDG PET-CT is a sensitive test for NPSLE diagnosis but is hampered by lack of specificity. It is a valuable tool for clinicians managing SLE patients, particularly when anatomical imaging is negative. Its exact application will depend on the local context and clinical scenario.

Microglia orchestrate synaptic and neuronal stripping: Implication in neuropsychiatric lupus.

Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia-mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1-like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety-like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.

Autoimmune and neuropsychiatric phenotypes in a Mecp2 transgenic mouse model on C57BL/6 background.

Introduction: Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable. Methods: C57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting. Results: B6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3. Discussion: Collectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.

Animal models of neuropsychiatric systemic lupus erythematosus: deciphering the complexity and guiding therapeutic development.

Systemic lupus erythematosus (SLE) poses formidable challenges due to its multifaceted etiology while impacting multiple tissues and organs and displaying diverse clinical manifestations. Genetic and environmental factors contribute to SLE complexity, with relatively limited approved therapeutic options. Murine models offer insights into SLE pathogenesis but do not always replicate the nuances of human disease. This review critically evaluates spontaneous and induced animal models, emphasizing their validity and relevance to neuropsychiatric SLE (NPSLE). While these models undoubtedly contribute to understanding disease pathophysiology, discrepancies persist in mimicking some NPSLE intricacies. The lack of literature addressing this issue impedes therapeutic progress. We underscore the urgent need for refining models that truly reflect NPSLE complexities to enhance translational fidelity. We encourage a comprehensive, creative translational approach for targeted SLE interventions, balancing scientific progress with ethical considerations to eventually improve the management of NPSLE patients. A thorough grasp of these issues informs researchers in designing experiments, interpreting results, and exploring alternatives to advance NPSLE research.

Ectopic CD4+ T cells in choroid plexus mediate neuropsychiatric lupus symptoms in mice via interferon-γ induced microglia activation.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a disabling and potentially life-threatening complication of SLE. This study aims to investigate whether ectopic CD4+ T cells in the choroid plexus mediate NPSLE in mice. Intracerebroventricular (ICV) injection of anti-CD4 antibody effectively depleted CP-resident CD4+ T cells and alleviated NPSLE-like symptoms in MRL/lpr mice. Following ICV injection, the majority of isolated lupus CD4+ T cells from donor MRL/lpr mice predominantly stayed in the CP for at least 28 days in recipient C57BL/6 mice, while nearly all isolated CD4+ T cells from MRL/MpJ mice disappeared within 7 days. ICV injection of lupus CD4+ T cells resulted in NPSLE-like symptoms, including impaired behavioral performances, increased microglial activation, and abnormal microstructure changes. Flow cytometry analysis revealed that the majority of isolated lupus CD4+ T cells were positive for IFN-γ. Neutralizing intracerebral IFN-γ alleviated NPSLE-like symptoms in MRL/lpr mice. Moreover, ICV injection of anti-IFN-γ antibody or microglial depletion by PLX3397 benefited most NPSLE-like symptoms in lupus CD4+ T-treated mice, while ICV injection of IFN-γ mimicked most NPSLE-like symptoms. In conclusion, CP-resident lupus CD4+ T cells contribute to NPSLE-like symptoms in mice via Interferon-γ induced microglia activation. Depleting CP-resident lupus CD4+ T cells, interferon-γ, or activated microglia may be potential therapeutic targets for NPSLE.

Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment.

Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple factors, such as environmental (infections), genetic (many HLA alleles including DR2 and DR3, and genes including C4), and immunological influences on self-antigens, such as nuclear antigens, lead to the formation of multiple autoantibodies that cause deleterious damage to bodily tissues and organs. The production of autoantibodies, such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of this disease. This autoimmune disease results from a failure of the mechanisms responsible for maintaining self-tolerance in T cells, B cells, or both. Immune complexes, circulating antibodies, cytokines, and autoreactive T lymphocytes are responsible for tissue injury in this autoimmune disease. The diagnosis of SLE is a rheumatological challenge despite the availability of clinical criteria. NPSLE was previously referred to as lupus cerebritis or lupus sclerosis. However, these terms are no longer recommended because there is no definitive pathological cause for the neuropsychiatric manifestations of SLE. Currently, the treatment options are primarily based on symptomatic presentations. These include the use of antipsychotics, antidepressants, and anxiolytic medications for the treatment of psychiatric and mood disorders. Antiepileptic drugs to treat seizures, and immunosuppressants (e.g., corticosteroids, azathioprine, and mycophenolate mofetil), are directed against inflammatory responses along with non-pharmacological interventions.

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score.

OBJECTIVE: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. METHODS: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. RESULTS: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. CONCLUSION: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

Correlation between the changes of brain amplitude of low-frequency fluctuation and cognitive impairment in patients with neuropsychiatric lupus.

PURPOSE: To explore the relationship between brain function changes and clinical serological indicators and behavioral cognitive assessment in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), and understand the pathogenesis of NPSLE from the perspective of imaging. METHODS: The resting-state functional imaging data, clinical serological, and behavioral cognitive assessment scores of 28 patients with NPSLE and 22 healthy controls (HC) were prospectively collected. The resting-state amplitude of low-frequency fluctuation (ALFF) values obtained from the analysis and processing were correlated with the serological data and behavioral cognitive assessment scores to determine the relationship between these data. RESULTS: The average age of the patients of the NPSLE group was older than that of the HC group; significant differences in education level, Auditory Verbal Learning Test Hua Shan Version (AVLT-H), and Trail Making Test scores were observed between the two groups. The NPSLE group demonstrated increased brain activity in the insula, precentral gyrus, and superior temporal gyrus, and decreased brain activity in the superior parietal gyrus. The ALFF value of the insula positively correlated with the Anti-ß2gp1 antibody and negatively correlated with the anti-nucleosome antibody and the AVL-recall (RC) score. The ALFF of the precentral gyrus negatively correlated with the AVL-immediate recall (I). The ALFF value of the superior temporal gyrus negatively correlated with the AVL-RC score. The left superior parietal gyrus positively correlated with the c-reactive protein. The right superior parietal gyrus positively correlated with the System Lupus Erythematosus Disease Activity Index and negatively correlated with the AVL-I score. CONCLUSION: Patients with NPSLE show different brain activity changes in different brain regions, and the abnormal brain regions are correlated with certain lupus antibodies, inflammatory factors, and cognitive assessment, thereby suggesting that the correlation between the three could provide novel insights into the pathogenesis of NPSLE.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Impaired serotonin synthesis in hippocampus of murine lupus represents an early neuropsychiatric event.

BACKGROUND: Despite significant progress in understanding the mechanisms underlying hippocampal involvement in neuropsychiatric systemic lupus erythematosus (NPSLE), our understanding of how neuroinflammation affects the brain neurotransmitter systems is limited. To date, few studies have investigated the role of neurotransmitters in pathogenesis of NPSLE with contradictory results. METHODS: Hippocampal tissue from NZB/W-F1 lupus-prone mice and age-matched control strains were dissected in both pre-nephritic (3-month-old) and nephritic (6-month-old) stages. High-Performance Liquid Chromatography (HPLC) was used to evaluate the level of serotonin (5-HT), dopamine (DA), and their metabolites 5-HIAA and DOPAC, respectively, in mouse hippocampi. RESULTS: Lupus mice exhibit decreased levels of serotonin at the early stages of the disease, along with intact levels of its metabolite 5-HIAA. The 5-HT turnover ratio (5-HIAA/5-HT ratio) was increased in the hippocampus of lupus mice at pre-nephritic stage suggesting that low hippocampal serotonin levels in lupus are attributed to decreased serotonin synthesis. Both DA and DOPAC levels remained unaffected in lupus hippocampus at both early and late stages. CONCLUSION: Impaired hippocampal serotonin synthesis in the hippocampus of lupus-prone mice represents an early neuropsychiatric event. These findings may have important implications for the use of symptomatic therapy in diffuse NPSLE.

Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.

OBJECTIVES: Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. METHODS: A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics. RESULTS: A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). CONCLUSION: Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group.

Efficacy of Intrathecal Isoniazid and Steroid Therapy in Refractory Tuberculous Meningitis.

Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a case of refractory tuberculous meningitis in a 52-year-old woman with underlying neuropsychiatric systemic lupus erythematosus. Despite systemic treatment with anti-tuberculosis drugs and dexamethasone, her meningeal irritation deteriorated. Intrathecal isoniazid and prednisolone administration was therefore initiated, and the symptoms of severe meningeal irritation improved along with head magnetic resonance imaging and cerebrospinal fluid findings. This case report highlights the efficacy of intrathecal isoniazid and steroid injections for refractory tuberculous meningitis, particularly in patients with severe meningeal irritation.

A Case of Cerebral Large-Vessel Vasculitis Concomitant Fahr Syndrome in Systemic Lupus Erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus. CASE REPORT: We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome. CONCLUSIONS: The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis.

[Systemic lupus erythematosus associated macrophage activation syndrome with neuropsychiatric symptoms: A report of 2 cases].

Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.