Symptoms Of Neuropsychiatric Systemic Lupus Erythematosus Research Articles

One-Year Outcomes for Depression and Anxiety in SLE Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe form of SLE involving the nervous system, resulting in neurological and psychiatric symptoms. Although research has shown that SLE patients often suffer from cognitive impairments, depression, and anxiety, there are no specialized guidelines for psychiatric assessment and treatment. This study aimed to investigate the progression of neuropsychiatric symptoms in SLE patients, explicitly focusing on anxiety and depression, over a year. It also aimed to identify potential biomarkers linked to NPSLE and explore the connection between NPSLE and the overall progression of SLE. Our research involved a longitudinal study with 65 adults diagnosed with SLE. Participants underwent various physical, biochemical, and serological tests and were assessed using disease activity indexes like BILAG-2004 and SLEDAI-2K. Participants also underwent psychological assessments using the Hamilton Anxiety and Depression Rating Scales. The study did not find any significant impact of antidepressant therapy on the evolution of anxiety and depression among participants. However, medications like Methotrexate and Plaquenil showed a substantial reduction in these symptoms. Moreover, anxiolytic therapy seems to influence depression in SLE patients. The study also noted that anxiety levels tend to increase over time but are not directly associated with SLE activity. This study concludes that although specific SLE medications can affect the level of anxiety and depression, the overall effectiveness of neuropsychiatric therapy in managing these symptoms is limited. The findings suggest that further research into the tailored management of NPSLE symptoms and a deeper understanding of the disease's psychiatric aspects are needed.

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.

Haloperidol's Cytogenetic Effect on T Lymphocytes of Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: An In Vitro Study.

Investigating haloperidol's cytogenetic behavior in cultured human T lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Four haloperidol solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides, and stained with the fluorescence plus Giemsa method, and sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope. Result analysis revealed: (a) a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE patients compared to healthy individuals; (b) a statistically significant (p=0.001) dose-dependent decrease of SCEs in RA patients for haloperidol concentrations 5, 10μg/mL; (c) a statistically significant (p=0.001) dose-dependent increase of SCEs in RA patients for haloperidol concentrations 20, 100μg/mL; and (d) a statistically significant (p=0.001) dose-dependent reduction of PRI and MI in both patient groups compared to healthy individuals. Furthermore, a correlation was observed between (a) SCE and PRI index variations, (b) MI and SCE index variations, and (c) PRI and MI index variations. Haloperidol affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures, DNA damage response, and ferroptosis. Considering the wide use of haloperidol in neuropsychiatric symptoms of SLE and RA patients, further studies with more immune cell subsets are needed to evaluate its effects on human genetic material.

An evaluation of neuropsychiatric manifestations in systemic lupus erythematosus patients in Saudi Arabia and their associated factors.

To establish the prevalence of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) symptoms in Saudi Arabia and the variables that are linked to it. This cross-sectional study was conducted in June 2021 among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26. Two hundred and eight SLE patients participated in the study (females 91.3% vs. males 8.7%). In addition, 13.5% of patients had a family history of SLE, and 26% had SLE for one to 3 years. The most common symptoms of NPSLE were alteration or loss of sensation (53.4%), followed by fear (52.4%), and headache (48.1%). The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE CONCLUSION: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.

Olanzapine’s Cytogenetic Effect on T Lymphocytes in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: In Vitro Study

This study will investigate olanzapine's cytogenetic behavior in cultured human T lymphocytes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Three olanzapine solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides and stained with the fluorescence plus Giemsa method. Sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope. There was a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE and RA patients compared to healthy individuals and a statistically significant (p=0.001) reduction of PRI and MI in the highest concentration in the SLE group. Moreover, Spearman's rank correlation coefficient was applied to calculate the correlation between SCEs, PRI, and MI. Negative significant correlations were noticed for both patient groups concerning SCEs-PRI alterations and SCEs-MI alterations. Conversely, positive correlations were noticed for both patient groups for PRI-MI alterations. Conclusions: Olanzapine affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures and DNA damage response. Considering the use of olanzapine in neuropsychiatric symptoms of SLE, further in vivo studies are necessary to evaluate its effect on human DNA.

Acute Confusional State in a Neuropsychiatric Systemic Lupus Erythematosus Patient: A Case Report

Systemic Lupus Erythematosus (SLE) affects various systems in human including central and peripheral nervous systems. The Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe complication of SLE which causes a formidable challenge in term of diagnosis and its management. Acute confusional state (delirium) is a rare entity of numerous symptoms of NPSLE which is being overlooked even though it is associated with increased mortality. The present case report describe about the presentation of SLE consisting of hyperpigmentation maculopapular rashes over face, neck regions, lower back and extremities in a 36-yearold female with abrupt onset and fluctuating course of psychotic symptoms, acute confusional state and oddities in behaviours. Treatment with low dose of antipsychotic (aripiprazole) resolve the symptom with due consideration taken to rule out steroid induced manifestation of above symptoms.

Temporal and spatial changes in cerebral blood flow in neuropsychiatric systemic lupus erythematosus: a subtraction brain spect study

This study was addressed to evaluate the temporal and spatial changes in regional cerebral blood flow (rCBF) of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Our objective was to correlate the subtracted SPECT coregistered to MRI features (SISCOM) with demographic, clinical and laboratory findings to shed light upon the pathophysiological evolution of the NPSLE. Twenty-six NPSLE patients with MRI and pre- and post-treatment brain SPECT with [99mTc]Tc-ECD. SISCOM features were categorized as improvement, worsening, activation and/or deactivation of rCBF findings. Patients mean age of 43.19 years and 65.38% white were evaluated. The patients mean age at onset of SLE was 26.05 and 42.29 for NPSLE. The mean time between the onset of SLE and first NPSLE symptoms was 05.57 years. The disease has already been initiated as NPSLE in 4 patients. The SLEDAI average score was 31.69 and the SLICC/ACR-DI score was 06.96. The patients underwent an average of 09.23 cyclophosphamide. The SISCOM findings showed functional and pathological states on different brain regions. The rCBF changes were not associated with index scores. There was, however, a trend towards an association between lower SLEDAI scores with improvement and higher SLEDAI with worsening in SISCOM, Also a trend of association between lower SLICC score with improvement, and higher SLICC with worsening. The female gender was predictive of activation and worsening, separately, and deactivation and worsening in a set. Non-white patients were predictive of worsening. The seizure was predictive of deactivation separately, and deactivation and worsening in a set. Finally, normal C3 was a predictor of improvement. The present study showed dynamic brain changes in NPSLE patients. SISCOM technique showed improved rCBF in some brain areas, and worsening, activation and deactivation in others. There were associations between rCBF changes and gender, skin colour and complement C3 and association trends with SLEDAI and SLICC scores.

A Novel Microglia-Specific Transcriptional Signature Correlates With Behavioral Deficits in Neuropsychiatric Lupus

Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) affect over one-half of SLE patients, yet underlying mechanisms remain largely unknown. We demonstrate that SLE-prone mice (CReCOM) develop NP-SLE, including behavioral deficits prior to systemic autoimmunity, reduced brain volumes, decreased vascular integrity, and brain-infiltrating leukocytes. NP-SLE microglia exhibit numerical expansion, increased synaptic uptake, and a more metabolically active phenotype. Microglia from multiple SLE-prone models express a “NP-SLE signature” unrelated to type I interferon. Rather, the signature is associated with lipid metabolism, scavenger receptor activity and downregulation of inflammatory and chemotaxis processes, suggesting a more regulatory, anti-inflammatory profile. NP-SLE microglia also express genes associated with disease-associated microglia (DAM), a subset of microglia thought to be instrumental in neurodegenerative diseases. Further, expression of “NP-SLE” and “DAM” signatures correlate with the severity of behavioral deficits in young SLE-prone mice prior to overt systemic disease. Our data are the first to demonstrate the predictive value of our newly identified microglia-specific “NP-SLE” and “DAM” signatures as a surrogate for NP-SLE clinical outcomes and suggests that microglia-intrinsic defects precede contributions from systemic SLE for neuropsychiatric manifestations.

Epilepsy in systemic lupus erythematosus: prevalence and risk factors.

The aim was to study the prevalence of epilepsy in a hospital-based systemic lupus erythematosus (SLE) cohort and to investigate the relationship between epilepsy and other manifestations of neuropsychiatric SLE (NPSLE). The study population consisted of 440 SLE patients recruited from 1998 to 2012. An epilepsy-screening questionnaire was sent to all patients, where those screening positive were invited to a neurological examination with documentation of NPSLE symptoms according to the American College of Rheumatology nomenclature. Occurrences of autoantibodies (double stranded DNAantibody, antinuclear antibody, lupus anticoagulant, Sjögren's syndrome A, Sjögren's syndrome B) and the antiphospholipid syndrome (APS) were tabulated. Out of 440 patients, 14% were dead and 2.7% were lost to follow-up. The questionnaire was sent to 368 patients; 312 (85%) responded. Of these, 131 (42%) screened positive. Epilepsy was confirmed in 36 (11.5%), of whom 30 (83%) had focal onset. Ten (3.2%) patients had isolated or provoked seizures. Manifestations of NPSLE occurred in 50%. The rates of cerebrovascular disease and psychosis were elevated two- and three-fold in NPSLE patients with epilepsy versus NPSLE patients without epilepsy, respectively (P=0.001 and P=0.0006). APS was more common in patients with epilepsy compared to epilepsy-free SLE patients with or without NPSLE (P=0.02). In 50% of patients with epilepsy, no other etiology than SLE was detected. A high prevalence of epilepsy in SLE patients is reported, with association to concurrent cerebrovascular disease, APS and psychosis. Our findings support the notion of a multifactorial background for epilepsy in SLE including both vascular disease and features consistent with autoimmunity.

A Conscious Resting State fMRI Study in SLE Patients Without Major Neuropsychiatric Manifestations.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the main causes of death in patients with systemic lupus erythematosus (SLE). Signs and symptoms of NPSLE are heterogeneous, and it is hard to diagnose, and treat NPSLE patients in the early stage. We conducted this study to explore the possible brain activity changes using resting state functional magnetic resonance imaging (rs-fMRI) in SLE patients without major neuropsychiatric manifestations (non-NPSLE patients). We also tried to investigate the possible associations among brain activity, disease activity, depression, and anxiety. In our study, 118 non-NPSLE patients and 81 healthy controls (HC) were recruited. Rs-fMRI data were used to calculate the regional homogeneity (ReHo) in all participants. We found decreased ReHo values in the fusiform gyrus and thalamus and increased ReHo values in the parahippocampal gyrus and uncus. The disease activity was positively correlated with ReHo values of the cerebellum and negatively correlated with values in the frontal gyrus. Several brain areas showed correlations with depressive and anxiety statuses. These results suggested that abnormal brain activities might occur before NPSLE and might be the foundation of anxiety and depression symptoms. Early detection and proper treatment of brain dysfunction might prevent the progression to NPSLE. More studies are needed to understand the complicated underlying mechanisms.

Acute hypomania in systemic lupus erythematosus, differential diagnosis. A case report

IntroductionIt is well known that seizures and psychosis are diagnostic criteria for systemic lupus erythematosus (SLE), however, there could be many other neuropsychiatric symptoms. The American College of Rheumatology Nomenclature provides case definitions for 19 neuropsychiatric syndromes seen in SLE (NPSLE), including cognitive impairment, psychosis, mood and anxiety disorders. Lack of specific manifestations difficult diagnosis and treatment.ObjectivesTo address the diagnostic difficulties that involve the appearance of hypomanic symptoms in the course of SLE treated with high doses of corticoids in a patient with a depressive episode history.MethodDescription of case report and literature revision. We report the case of a 22-year-old woman who presented irritable mood, sexual disinhibition, insomnia and inflated self-esteem. The patient was recently diagnosed with SLE and was on treatment with 50 mg/d prednisone. She had familiar history for bipolar disorder and was taking 20 mg/d paroxetine since the last 6 months after being diagnosed with major depressive episode.ResultsWe proposed differential diagnosis between psychiatric symptoms secondary to central nervous system SLE involvement, a comorbid bipolar disorder or prednisone-induced mood symptoms. Fluctuation of hypomanic symptoms during hospitalization, poor relationship with variation in corticosteroid doses, findings on brain MRI compatible with vasculitis and positive antibodies, oriented this case to a neuropsychiatric manifestation of LES.ConclusionsWe should keep in mind that symptoms of neuropsychiatric SLE may vary from more established manifestations of NPSLE to mild diffuses ones. More studies are needed to expand knowledge in the relationship between mood disorders and neuropsychiatric SLE.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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

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

Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers.

Systemic lupus erythematosus (SLE) is a complex clinical syndrome, elements of which remain poorly understood. Although recognized over 140 years ago when Kaposi recorded the systemic nature and manifestations of the disease, CNS involvement represents one of the least understood aspects of SLE. This knowledge gap remains despite the fact that up to 75% of adults and children with SLE will, at some point over the course of the disease and to different extents, experience the various disabling effects of neuropsychiatric SLE (NPSLE). Indeed, after decades of research, our understanding of the underlying pathophysiology of NPSLE, in particular, remains limited. Numerous factors contribute to the immune dysfunction that occurs in SLE, including genetic, environmental and hormonal influences, and the contributory or predisposing components that lead to neurological tropism of disease in some patients have not been clearly demonstrated. Features of NPSLE pathogenesis that might be directly linked to clinical manifestations have been identified; however, the complexity and variety of NPSLE symptoms and the clinical overlap with other psychiatric disorders continue to make accurate diagnosis difficult and time-consuming. Thus, efforts to define biomarkers of NPSLE are needed to improve prediction of disease outcomes and guide treatment. In this article, we review the manifestation and pathogenesis of NPSLE, focusing on the features that might aid identification of potential biomarkers.

Electroconvulsive Therapy for Severe Neuropsychiatric Lupus With Psychosis

Systemic lupus erythematosus (SLE) is an autoimmune disorder that requires long-term management and can have a profound impact on the quality of life of patients. Among patients with SLE, neuropsychiatric manifestations are fairly common, occurring in up to 75% of patients with SLE. Neuropsychiatric symptoms of SLE (NPSLE) presenting with psychosis, however, is less common, with a prevalence of up to 11%. Treatment of psychosis in NPSLE has largely involved antipsychotics and immunosuppressants, with not much in the literature about the use of electroconvulsive therapy (ECT) as a method of treatment. We report 3 cases of patients who presented with psychosis during a lupus relapse, who were treated successfully with ECT after their symptoms did not improve on medical treatment. Although all 3 patients were treated with antipsychotics and immunosuppressants simultaneously with the ECT sessions, the time scale of these 3 case studies suggests that ECT played a role in the resolution of these patients' symptoms. Our 3 cases highlight that ECT can be safely and effectively used in patients with NPSLE with prominent psychotic symptoms.

The MRL/lpr mouse strain as a model for neuropsychiatric systemic lupus erythematosus.

To date, CNS disease and neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. In this review, we focus on a specific mouse model of lupus and the ways in which this model reflects some of the most common manifestations and potential mechanisms of human NP-SLE. The mouse MRL lymphoproliferation strain (a.k.a. MRL/lpr) spontaneously develops the hallmark serological markers and peripheral pathologies typifying lupus in addition to displaying the cognitive and affective dysfunction characteristic of NP-SLE, which may be among the earliest symptoms of lupus. We suggest that although NP-SLE may share common mechanisms with peripheral organ pathology in lupus, especially in the latter stages of the disease, the immunologically privileged nature of the CNS indicates that early manifestations of particularly mood disorders maybe derived from some unique mechanisms. These include altered cytokine profiles that can activate astrocytes, microglia, and alter neuronal function before dysregulation of the blood-brain barrier and development of clinical autoantibody titres.

Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus

Objectives. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious but potentially treatable disease. However, biological markers such as IgG index or IL-6 do not always reflect the severity of the psychotic symptoms of NPSLE. We hypothesized that serum BDNF levels may be a biological marker for reflecting the severity of the psychiatric symptoms of NPSLE. Methods. The participants enrolled in this study were 28 healthy volunteers and 54 Japanese SLE inpatients at the University Hospital of Occupational and Environmental Health, all of whom fulfilled the criteria for the classification of SLE. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms including an acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis (NP group); NPSLE without psychiatric symptoms (NN group); and SLE without neuropsychiatric symptoms (S group). The serum BDNF levels were measured by ELISA. Results. Serum BDNF levels were significantly increased in the NP group (mean ± SE = 37.0 ± 5.46 ng/ml) compared with those in the other three groups (NN group; mean ± SE=9.1 ± 2.44 ng/ml, P < 0.0001, S group; mean ± SE=10.4 ± 2.51 ng/ml, P < 0.0001, healthy control; mean ± SE= 11.44 ± 0.69, P < 0.0001). Subsequently, serum BDNF levels were decreased in parallel with the improvement of psychiatric symptoms in the NP group. Conclusion. These results suggest that serum BDNF is a biological marker for the severity of psychiatric symptoms in NPSLE patients.

Intramural platelet deposition in cerebral vasculopathy of systemic lupus erythematosus.

To test the hypothesis that fragments of platelet thrombi and vascular endothelium are incorporated into the walls of small cerebral vessels in systemic lupus erythematosus (SLE). Six varied necropsy cases of central nervous system (CNS) SLE and 15 controls were studied. The controls were selected to represent a wide range of diseases in which the cerebral circulation is compromised. Tissue sections were stained by standard histochemical and immunocytochemical methods, the latter using antibodies to platelet membrane glycoprotein IIIa (CD61), and vascular endothelium (CD31). In four of six cases of CNS SLE characterised by small vessel hyalinization and thickening, fragments of platelet membrane were found in the walls of small cortical and meningeal vessels. Similar findings were not evident in two other SLE cases that were characterised by relatively short clinical histories and an acute vasculitis. One control case of severe polyarteritis nodosa showed platelet fragment deposition in arteries larger than the vessels so affected in SLE. Previous studies have suggested that neuropsychiatric symptoms in SLE may be related to repeated episodes of vasculitis in small cerebral vessels that are triggered by antiphospholipid antibodies. Concurrent thrombus formation might facilitate the incorporation of platelet fragments into small vessel walls. This process contributes to the thickening and irregularity of small vessels, a major feature of longstanding cases of CNS SLE.