The Intersection of Autoimmunity and Neurology: Insights From a Case of Striatal Lupus Encephalitis.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder predominantly affecting women, characterized by the production of autoantibodies against various nuclear antigens, leading to widespread immune dysregulation and multisystem involvement. Among its complex manifestations, neuropsychiatric systemic lupus erythematosus (NPSLE) represents a particularly challenging aspect of the disease due to its wide spectrum of neurological and psychiatric symptoms. This case report presents a rare instance of striatal lupus encephalitis, a severe subtype of NPSLE, in a 32-year-old woman, highlighting its distinct clinical and radiological features. The patient initially developed bilateral ocular occlusive vasculitis and later presented with acute right-sided hemiparesis and facial asymmetry. Magnetic resonance imaging (MRI) revealed bilateral symmetrical T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintense signals in the basal ganglia, consistent with striatal lupus encephalitis. No white matter hyperintensity or vasculitis changes were seen. Cerebrospinal fluid analysis revealed markedly elevated protein levels, though no infectious organism was identified. The patient was treated with high-dose prednisolone, alongside empirical antibiotic and antiviral therapy to address potential meningoencephalitis. Remarkably, she made a full recovery from her stroke-like symptoms. Despite its rarity, the identification of striatal lupus encephalitis is critical due to the severe and potentially irreversible nature of the neurological damage. This case underscores the importance of a comprehensive diagnostic approach, integrating clinical, serological, and neuroimaging findings to differentiate striatal lupus encephalitis from other neuropsychiatric conditions associated with SLE. Its management typically involves aggressive immunosuppressive therapy, with intravenous methylprednisolone being the first-line treatment. The case also illustrates the potential for recovery with prompt and appropriate treatment, as evidenced by the complete resolution of neurological symptoms and MRI findings at follow-up.

Perfusion-weighted MRI patterns in neuropsychiatric systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a complex manifestation of Systemic Lupus Erythematosus (SLE) characterized by a wide range of neurological and psychiatric symptoms. This study aims to elucidate the patterns of Perfusion-Weighted MRI (PWI) in NPSLE patients compared to SLE patients without neuropsychiatric manifestations (non-NPSLE) and healthy controls (HCs). MATERIAL AND METHODS: A systematic search was conducted in PubMed/Medline, Embase, Web of Science, and Scopus for studies utilizing PWI in NPSLE patients published through April 14, 2024. Cerebral blood flow (CBF) data from NPSLE, non-NPSLE patients, and HCs were extracted for meta-analysis, using standardized mean difference (SMD) as an estimate measure. For studies lacking sufficient data for inclusion, CBF, cerebral blood volume (CBV), and mean transit time (MTT) were reviewed qualitatively. RESULTS: Our review included eight observational studies employing PWI techniques, including dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL). The meta-analysis of NPSLE compared to non-NPSLE incorporated four studies, encompassing 104 NPSLE patients and 90 non-NPSLE patients. The results revealed an SMD of -1.42 (95% CI: -2.85-0.00, I2: 94%) for CBF in NPSLE compared to non-NPSLE. CONCLUSION: PWI reveals informative patterns of cerebral perfusion, showing a significant reduction in mean CBF in NPSLE patients compared to non-NPSLE patients. Our qualitative synthesis highlights these changes, particularly in the frontal and temporal lobes. However, the existing data exhibits considerable heterogeneity and limitations.

Intermittent fasting attenuates cognitive dysfunction and systemic disease activity in mice with neuropsychiatric systemic lupus erythematosus.

AIMS: Cognitive dysfunction and systemic disease activity are common manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE), a condition that affects a patient's health and quality of life. Clinical and preclinical studies have demonstrated that intermittent fasting (IF) improves health conditions and quality of life. Therefore, we aimed to test whether IF improves cognitive dysfunction and systemic disease activities in mice with NPSLE and to examine the underlying mechanisms. MAIN METHODS: NPSLE-prone MRL/lpr mice underwent 8 weeks of alternate-day fasting or ad libitum feeding, followed by behavioral tests to assess cognitive manifestations and biochemical tests to evaluate systemic disease activities. KEY FINDINGS: IF significantly improved cognitive functionality, decreased blood-brain barrier permeability, and reduced the activation of astrocytes and microglia in the hippocampi of MRL/lpr mice. IF also improved systemic disease activities, including reduced kidney glomerular injury and interstitial inflammation, peripheral blood autoantibody titer, and splenic T lymphocyte contents. Mechanistic studies demonstrated that IF attenuates cognitive dysfunction by facilitating the microglial transition to the M2-like phenotype via the AMPK/PPARγ/NF-κB pathway. SIGNIFICANCE: Together, observations from this study suggest a potential therapeutic benefit of IF in the treatment of cognitive dysfunction in patients with NPSLE.

Diagnostic Challenges in Neuro-Psychiatric Systemic Lupus Erythematosus: A Case of a Patient With Psychosis Secondary to Lupus Cerebritis in the Setting of a Steroid Taper.

Systemic lupus erythematosus (SLE) is an autoimmune condition whereby autoantibodies target systemic tissues, causing manifestations of inflammation and tissue damage. Neurologic inflammation in SLE can cause an array of neuropsychiatric (NP) symptoms, including headaches, depression, seizures, demyelinating conditions, mania, and psychosis. Patients treated for SLE are often on anti-inflammatory regimens, including high-dose steroids, which can independently precipitate psychosis. Steroid-induced psychosis (SIP) and lupus cerebritis (LC) are two distinct conditions that patients with SLE may have but often have overlapping presentations, which present a challenge for clinicians. Accurately differentiating between SIP and LC in an emergency setting is crucial for directing appropriate management and preventing potential complications. A clear timeline of the history of symptoms can help narrow down the cause. Diagnostic tools, mainly MRI patterns, can further clarify and indicate the presence of LC. We present a case of a 19-year-old African American female with a history of one steroid-induced psychotic episode five months prior in the setting of SLE who developed subsequent psychosis while on a steroid taper. MRI imaging elucidated a diagnosis of LC rather than a second SIP episode. There are few, if any, case reports that describe a patient with past SIP with a subsequent flare of cerebritis with psychotic symptoms. Strategic approaches to differentiating SIP from LC in the setting of SLE can lead to improved patient outcomes, follow-up care, and an overall understanding of the neuropsychiatric complexities of SLE.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): A Case Report and an Overview of the Diagnosis, Treatment Modalities, and Prognosis.

Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem autoimmune disease with a broad spectrum of clinical presentations. Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to neurological and psychiatric symptoms involving the central and peripheral nervous systems.  A 23-year-old African American female with a history of undifferentiated connective tissue disease on hydroxychloroquine and poor medication adherence presented to the emergency department with an altered mental status and generalized headache. In addition, she had a fever, associated tachycardia (104 BPM), and hypotension (90/63 mmHg). She was given fluids and started on broad-spectrum antibiotics and antivirals, suspecting bacterial or viral meningitis. However, a broad infectious workup, including cerebral spinal fluid (CSF) culture, was unrevealing. Given the lack of improvement of antibiotics, an immunological workup for SLE was initiated, which showed low CH50, C3, and C4; anti-nucleic acid antibody (ANA) was 1:1280, anti-double-stranded (anti-DS) DNA antibody not detected, and fluorescent ANA was positive. For severe NPSLE, rituximab is the most commonly utilized immunosuppressant; it was not utilized in this case due to the patient's insurance. The patient was placed on methylprednisolone and cyclophosphamide (CYC) infusion per ACR guidelines. Due to the toxic effects of CYC on the gonads, we offered ovarian preservation; however, the patient opted to refuse. The patient's mental status started to improve after three days of pulse steroids. The patient was advised to follow up with rheumatology for CYC therapy and a gradual taper of her steroids. NPSLE is a diagnosis of exclusion primarily based on expert opinion due to the absence of a gold standard diagnostic procedure. Disease-specific therapy, symptomatic therapy, nonpharmacological approaches, and correction of aggravating variables are all used to treat individuals with NPSLE.  This paper aims to contribute to the existing literature on NPSLE, with the intention to educate and strive for early detection and treatment. We hereby present an interesting case of SLE in a 23-year-old female who would not have responded to one treatment. Instead, she needed multidisciplinary management, along with poor compliance.

Longitudinally Extensive Transverse Myelitis in a Patient With Systemic Lupus Erythematosus, Recent Influenza Infection, and Nutritional Deficiencies in the Setting of Chronic Alcohol Use.

Longitudinally extensive transverse myelitis (LETM) is traditionally classified as an inflammatory disorder of the spinal cord spanning three or more vertebral segments. The differential diagnosis for TM is vast and can include infectious, nutritional, and can even be idiopathic in some reported cases. However, autoimmune etiologies such as systemic lupus erythematosus (SLE) can rarely present with neurological manifestations such as LETM. In this case report, we present a 33-year-old female with a prior history of SLE who developed an LETM in the setting of possible provoking factors such as nutritional deficiencies and a recent viral illness. In this case report, we highlight her clinical course, recovery, and working differential diagnosis after laboratory testing and neurological imaging. Finally, we discuss the different treatments that ultimately lead to her successful recovery after her prolonged clinical course.

Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review.

Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to the neurological and psychiatric manifestations of systemic lupus erythematosus (SLE), which remain poorly understood yet often have a profound effect on the lives of afflicted patients. The aim of this study is to synthesize the available information on the pathogenesis, diagnostics, management, and prognosis of this disease. Our hope is to increase awareness and call for further investigations that may optimize NPSLE patient outcomes and quality of life. We performed a literature review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, resulting in 11 studies of inclusion. Within each study, we extracted data on epidemiologic factors, diagnostics, therapeutic modalities, and prognosis for each neuropsychiatric condition. The most widely discussed neuropsychiatric manifestations of SLE based on the American College of Rheumatology (ACR) classifications included status epilepticus (SE) and seizures, transverse myelitis (TM), and cognitive dysfunction. SE and TM had a prevalence of 1-2%, while cognitive dysfunction was nearly 38%. Diagnostics varied depending on symptom presentation but often included brain magnetic resonance imaging (MRI) and antibody testing. Treatment for NPSLE is still widely understudied, but concurrent treatment with immunosuppressants and anti-inflammatories for symptom control and more targeted immunotherapies based on the specific condition is often effective. Prognosis is highly symptom dependent, ranging from a 12.5% one-year mortality in SE and seizure patients to near resolution of symptoms in certain presentations including idiopathic intracranial hypertension and cerebellar ataxia. Further studies are needed to better understand the pathophysiology, diagnostics, and effective therapeutic measures for NPSLE. The severity of these manifestations and generally poor prognosis highlight the need for more research to accurately diagnose and treat this disease. While there is still little data available, this literature review serves to provide updated context on this condition.

Correlation between neuropsychiatric systemic lupus erythematosus and immunological markers: a real-world retrospective study.

OBJECTIVES: This study aimed to investigate disparities in clinical profiles and autoantibody patterns between patients with and without neuropsychiatric systemic lupus erythematosus (NPSLE) in a cohort and to identify risk factors associated with NPSLE in the Chinese population. METHODS: SLE patients were retrospectively reviewed from two tertiary hospitals. The relationships between NPSLE and immunological biomarkers were explored. RESULTS: Among the 945 SLE patients, 75 (7.94%) were diagnosed with NPSLE. The most prevalent NP manifestations involved cognitive disorder (30.67%), headache (26.67%), seizure disorder (26.67%), and psychosis (26.67%).We observed significant associations between psychosis and anti-ß2GPI antibodies (F = 6.092, p = 0.015), polyneuropathy and anti-Scl70 antibodies (F = 20.161, p < 0.001), demyelinating syndrome and anti-cardiolipin antibodies (F = 6.637, p = 0.011), myasthenia gravis and anti-RNP (F = 5.864, p = 0.017), and anti-Smith antibodies (F = 5.096, p = 0.026). Multivariate logistics analysis showed that anti-prothrombin (aPT) IgM antibodies (OR = 10.985, CI 1.279-94.343, p = 0.029), age (OR = 1.169, CI 1.032-1.325, p = 0.014), and serum creatinine (SCr) (OR = 1.014, CI 1.003-1.025, p = 0.009) were independent risk factors of NPSLE, while anti-Sjogren syndrome antigen B (SSB) antibodies (OR 0.023, CI 0.002-0.622, p = 0.023) and high complement C3 (OR = 0.001, CI 0-0.045, p < 0.001) indicated reduced risk of NPSLE. CONCLUSION: Various neuropsychiatric manifestations in SLE were found to be correlated with specific autoantibodies. Independent risk factors for NPSLE included aPT IgM antibodies, age, and elevated serum creatinine, while the absence of anti-SSB antibodies and low complement C3 levels were associated with increased risk. KEY POINTS: •Significant associations were found between specific autoantibodies and neuropsychiatric symptoms, shedding light on potential biomarkers for predicting and understanding NPSLE. •The study identifies independent risk factors for NPSLE in the Chinese population, including the presence of anti-prothrombin IgM antibodies, older age, elevated serum creatinine, and lower complement C3 levels.

Locked-In Syndrome: A Rare Manifestation of Neuropsychiatric Lupus.

Neuropsychiatric systemic lupus erythematosus (SLE) is a rare condition that has a multitude of mechanisms resulting in the emergence of variable clinical presentations. We describe a peculiar case of a 33-year-old female with a history of SLE presented with two weeks of fever, headache, and vomiting. On admission, she became obtunded and was emergently intubated. Initial lumbar puncture revealed pleocytosis (46% neutrophils, 320 corrected nucleated cells/µL), elevated protein (244 mg/dL; normal, 15-40 mg/dL), normal glucose (63 mg/dL), and negative cultures. Empiric acyclovir, ampicillin, ceftriaxone, and vancomycin were initiated without clinical improvement. Neurological examination was notable for limited ability to follow commands, vertical nystagmus, horizontal gaze palsy, diffuse hyperreflexia, and quadriparesis. Electroencephalogram (EEG) was consistent with diffuse encephalopathy. Brain magnetic resonance imaging demonstrated restricted diffusion and contrast enhancement in the posterior and central pons with edema. A cerebral angiogram showed no signs of vasculitis. Treatment with intravenous (IV) methylprednisolone 1 g and IV immunoglobulin 2 g/kg was initiated for five days. Despite these interventions, no discernible clinical improvement was observed, prompting the commencement of 500 mg/m2 cyclophosphamide and daily maintenance of IV methylprednisolone at 2 mg/kg. A repeat MRI three weeks later revealed a marked reduction in the size of the lesion involving the pons. The patient also improved clinically over the month with successful extubation, complete return in mental capabilities, and the ability to ambulate short distances with assistance.

Serotonin Syndrome-Mimicking Manifestations in a Patient with Systemic Lupus Erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of systemic lupus erythematosus with diverse clinical presentations sharing common features with variable neurologic disorders. Magnetic resonance imaging (MRI) may provide imaging evidence of structural brain abnormalities associated with symptoms of NPSLE. Serotonin syndrome is a toxidrome characterized by altered mental status, autonomic hyperactivity, and neuromuscular abnormalities. It is mostly caused by medications that increase serotonin and is rarely reported as a manifestation of neuropsychiatric lupus. We presented the case of a 24-year-old Taiwanese woman with a history of systemic lupus erythematosus diagnosed at 21 years of age. The initial clinical and laboratory presentations upon diagnosis included fever, arthritis, hypocomplementemia, positive antinuclear antibody, anti-double-stranded DNA antibody, and anti-ribosomal P antibody. Her condition once remained stable under oral glucocorticoids and immunosuppressants, but she developed sudden-onset consciousness disturbance, incoherent speech, and unsteady gait ten days before our assessment. A high fever of up to 39 °C with tremor and clonus occurred at the intensive care unit. Brain MRI revealed symmetric T2 hyperintensity without diffusion restriction over the bilateral globus pallidus. High-dose pulse glucocorticoid and rituximab were prescribed during her admission and the neuropsychiatric symptoms diminished upon treatment. No alternation in mental status or involuntary movements were noted at follow-up. Our patient was diagnosed with neuropsychiatric lupus, with clinical symptoms and image findings mimicking those of serotonin syndrome. Neuroimaging, such as MRI, detects various structural brain abnormalities and may provide pathophysiological evidence of clinical manifestations.

Neuropsychiatric Systemic Lupus Erythematosus in a Patient with Pancytopenia and Chronic Schizophrenia Requiring Hospitalisation.

We herein report a patient with systemic lupus erythematosus (SLE) and neuropsychiatric SLE (NPSLE), who had been misdiagnosed with schizophrenia for a long time and presented with pancytopenia. Brain magnetic resonance imaging revealed sporadic punctate hyperintense areas in the cerebral white matter. Single-photon emission computed tomography revealed a clear decrease in blood flow from the parietotemporal association area to the temporal lobe. NPSLE is a serious organ complication that significantly worsens the SLE prognosis. NPSLE symptoms are diverse and difficult to diagnose and differentiate from those of other neuropsychiatric disorders, especially in an early onset.

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.

Brain 18 F-FDG PET reveals cortico-subcortical hypermetabolic dysfunction in juvenile neuropsychiatric systemic lupus erythematosus.

BACKGROUND: In juvenile systemic lupus erythematosus (j-SLE) with neuropsychiatric (NP) symptoms, there is a lack of diagnostic biomarkers. Thus, we study whether PET-FDG may identify any metabolic dysfunction in j-NPSLE. METHODS: A total of 19 18FDG-PET exams were consecutively performed using PET-MRI system in 11 non-sedated patients presenting with j-NPSLE (11-18y) for less than 18 months (m) and without any significant lesion at MRI. Psychiatric symptoms were scored from 0 (none) to 3 (severe) at PET time. PET images were visually analyzed and voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (spm) with an age-matched control group, at threshold set > 50 voxels using both p < 0.001 uncorrected (unc.) and p < 0.05 corrected family wise error (FWE). RESULTS: Patients exhibited mainly psychiatric symptoms, with diffuse inflammatory j-NPSLE. First PET (n = 11) was performed at a mean of 15y of age, second/third PET (n = 7/n = 1) 6 to 19 m later. PET individual analysis detected focal bilateral anomalies in 13/19 exams visually but 19/19 using spm (unc.), mostly hypermetabolic areas (18/19). A total of 15% of hypermetabolic areas identified by spm had been missed visually. PET group analysis (n = 19) did not identify any hypometabolic area, but a large bilateral cortico-subcortical hypermetabolic pattern including, by statistical decreasing order (unc.), thalamus, subthalamic brainstem, cerebellum (vermis and cortex), basal ganglia, visual, temporal and frontal cortices. Mostly the subcortical hypermetabolism survived to FWE analysis, being most intense and extensive (51% of total volume) in thalamus and subthalamus brainstem. Hypermetabolism was strictly subcortical in the most severe NP subgroup (n = 8, scores 2-3) whereas it also extended to cerebral cortex, mostly visual, in the less severe subgroup (n = 11, scores 0-1), but difference was not significant. Longitudinal visual analysis was inconclusive due to clinical heterogeneity. CONCLUSIONS: j-NPSLE patients showed a robust bilateral cortico-subcortical hypermetabolic network, focused subcortically, particularly in thalamus, proportionally to psychiatric features severity. Further studies with larger, but homogeneous, cohorts are needed to determine the sensitivity and specificity of this dysfunctional pattern as a potential biomarker in diffuse inflammatory j-NPSLE with normal brain MRI.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

OBJECTIVE: This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. METHODS: A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. RESULTS: Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. CONCLUSION: The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

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.

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.

Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.

Background: Diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to nonspecific biomarkers. High serum levels of neurofilament protein light subunit (NFL), high mobility group box 1 (HMGB1), Matrix metalloproteinase-9 (MMP-9) and have been reported in several autoimmune diseases. The aim of this study was to examine whether their plasma levels could serve as a diagnostic or prognostic biomarker for NPSLE. Methods: There were 90 SLE patients enrolled in this cross-sectional study (87.8% women and 12.2% men with a mean age of 41.67±11.05 years). We assessed the mental status of patients, also we measured the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ACR (SLICC/ ACR) Damage Index or SDI scores. Serum levels of NFL, HMGB1, MMP9, and ds-DNA were investigated to find a role in the pathophysiology of NPSLE. Results: Among the 90 patients with SLE, 63 (70%) met the criteria of NPSLE syndrome. Our results have shown a notable difference concerning SEDIAC-2k score, SDI score, PANS, MoCA, and Beck anxiety depression, between the two groups (p < 0.05). Although serum level of all measured serum biomarkers (NFL, MMP-9, HMGB1, dsDNA) were higher in patients with NPSLE, the difference was not statistically significant. Interestingly, our results showed that the serum level of NFL was correlated with the serum level of HMGB-1 and MMP-9. (r: 0.411, P=0.003). Conclusion: Serum level of NFL, HMGB-1 and MMP-9 may be used to detect abnormal mental status in patients with SLE.

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.

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.

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.

Biomarkers for systemic lupus erythematosus - a focus on organ damage.

INTRODUCTION: Systemic lupus erythematosus (SLE) is complex autoimmune disease with heterogenous manifestations, unpredictable disease course and response to treatment. One of the critical needs in SLE management is the identification of reliable biomarkers that can aid in early diagnosis, accurate monitoring of disease activity, and assessment of treatment response. AREAS COVERED: In the current review, we focus on the commonly affected organs (skin, kidney, and nervous system) in SLE to summarize the emerging biomarkers that show promise in disease diagnosis, monitoring and treatment response assessment. The subtitles within each organ domain were determined based on the most relevant and promising biomarkers for that specific organ damage. EXPERT OPINION: Biomarkers have the potential to significantly benefit the management of SLE by aiding in diagnosis, disease activity monitoring, prognosis, and treatment response assessment. However, despite decades of research, none has been validated and implemented for routine clinical use. Novel biomarkers could lead to the development of precision medicine for SLE, guide personalized treatment, and improve patient outcomes. Challenges in biomarker research in SLE include defining clear and clinically relevant questions, accounting for the heterogeneity of SLE, and confirming initial findings in larger, multi-center, multi-ethnic, independent cohorts that reflect real-world clinical scenarios.