Neuropsychiatric Manifestations Of Systemic Lupus Erythematosus Research Articles

Invasive candida infection as the cause of seizure in a patient with systemic lupus erythematosus: a report of unusual case

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of SLE involving the nervous and psychiatric systems with clinical manifestations including seizures, strokes, myelopathy, neuritis, meningitis, and psychosis. Seizures in NPSLE might be caused by intracranial infection, with bacteria as the most common pathogens. This study reported a rare case of seizure in a SLE patient due to invasive Candida infection. Case Presentation: A 26-year-old female presented in the emergency department of Dr. Soetomo Hospital Surabaya, Indonesia with seizure, which she has experienced in the last 2 days prior to hospital admission. She experienced a convulsion that lasted 5-10 minutes followed by loss of consciousness. The patient also complained of severe headaches two days before hospital admission. She was diagnosed with SLE in November 2022 and was currently taking methylprednisolone. Physical examination showed Glasgow Coma Scale (GCS) of E3V4M5, fever, dyspnea, and rough rhonchi on the right lung. Chest X-ray indicated pneumonia, while brain computed tomography (CT) suggested subacute to chronic thromboembolism. The patient was diagnosed with NPSLE due to intracranial infection, and hospital-acquired pneumonia (HAP), and was given Levofloxacin. On the 3rd day, a reddish lesion with central healing was found on the cheeks, and the patient had dyspnea, suggesting fungi infection. Methylprednisolone was stopped while fluconazole and urine cultures were initiated. Urine culture suggested Fluconazole-sensitive Candida and consultation with a dermato-venerologist confirmed Candida, thus, Fluconazole was continued along with dexamethasone, and Levofloxacin. The patient showed clinical improvement and was discharged after 12 days. Conclusion: Seizure is one of the most common manifestations of NPSLE, due to intracranial infection. Although rare, we cannot rule out the possibility of fungal infection in NPSLE patients with intracranial infection. Early diagnosis and prompt treatment are critical for better prognosis, as shown in this patient.

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.

Evaluation of Neurological Manifestations of Systemic Lupus Erythematosus

Abstract Background: Neuropsychiatric symptoms are typical consequences in patients with systemic lupus erythematosus (SLE). There is no apparent link between the clinical parameters of SLE patients and the development of neuropsychiatric symptoms. Objectives: to determine the incidence of neurological manifestations and the risks associated with them in SLE patients. Patients and Methods: This is a case-series study comprised 65 patients who visited the rheumatology Department at Baghdad Teaching Hospital/Medical City between January 2022 and February 2023. All patients' demographic and clinical data, including age, gender, disease duration, type and duration of treatment, general signs of the disease, and neurological and psychiatric manifestations of SLE, were collected. Laboratory data comprised plasma anti-phospholipid antibodies (aPL), anti-double stranded DNA (anti-dsDNA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The cognitive dysfunction was assessed using the six-item cognitive impairment test (6CIT). Results: Out of 65 patients, 34 (52.3%) were found to have at least one neuropsychiatric SLE (NPSLE) manifestation. Headache and depression were the most common NPSLE manifestation encountered in 36 patients (55.4%) followed by psychosis (21.5%), neuropathy (16.9%) and stroke and seizure (13.5%). In multivariate analysis, each of age >35 years (OR= 2.92, 95%CI= 1.12-34.2, p= 0.10), disease duration >5 years (4.45, 95%CI=1.23-28.43, p= 0.001), anti-phospholipid Abs (OR= 4.22, 95%CI= 1.17-89.38, p= 0.036), lupus nephritis (OR= 6.34, 95%CI= 1.27- 64.98, p= 0.029) and 6CIT>3 (OR= 5.83, 95%CI= 1.55- 21.87, p= 0.009) are independent predictors for NPSLE in patients with SLE. Conclusions: Neuropsychiatric manifestations developed in more than half of the SLE cases studied within up to six-year of disease duration. Headache and depression, psychosis and neuropathy are the most common NPSLE manifestations. Older age and longer disease duration are risk factors for development of NPSLE. Clinically, anti-phospholipid antibodies, lupus nephritis and a high score of the six-item cognitive impairment test (>8) are predictors for NPSLE. Received: May, 2023 Accepted: Sept., 2023 Published: Jan., 2024

Association between Inflammation and Thrombotic Pathway Link with Pathogenesis of Depression and Anxiety in SLE Patients.

As a complication of systemic lupus erythematosus (SLE), the neuropsychiatric form may manifest with neurological and psychiatric symptoms. Diagnosing neuropsychiatric SLE can be challenging due to the heterogeneity of this disease manifestation and the possibilities of investigation. This research aims to identify the possible associations between inflammation and thrombotic biomarkers alongside anxiety and/or depression manifestations in SLE patients. A group of 65 outpatients were investigated regarding the levels of depression, anxiety, disability, quality of life and other specific serum biomarkers linked with inflammation or coagulopathies. The results showed severe depression in eight participants, moderate depression in 22 (33.85%), and 26 (40%) subjects with mild depression. Anxiety was more prevalent within 64 participants (98.46%), while a degree of disability was reported by 52 participants (80%). Quality of life evaluated by EQ5D revealed a medium value of 1.57, and EQ5D VAS health medium value was 57.95 and was correlated with anxiety. A strong positive correlation between depression, anxiety and antibodies associated with anti-cardiolipin and anti beta2 glycoprotein I antibodies, lupus anticoagulant, ICAM-1, low C4 a and anti-ribosomal P antibodies were identified. These data results suggest that autoimmune/inflammatory and ischemic/thrombotic pathways could contribute to depression and anxiety as neuropsychiatric SLE manifestations.

Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice

The neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) present significant morbidity and mortality due to frequent non-response or adverse effects of the current clinical drugs. The disruption of the blood–brain barrier (BBB) contributes to inflammatory NPSLE disease progression. K-7174, a highly piperazine-derived compound, inhibits leukocyte adhesion and inflammatory factor expression. The present study aimed to comprehensively assess the treatment effect of neurobehavioral deficits in MRL/lpr mice, a validated neuropsychiatric lupus model. The intraperitoneal injection of K-7174 alleviated lupus-like symptoms and improved cognitive dysfunction in MRL/lpr mice. Also, it significantly attenuated neuronal degeneration and decreased serum albumin deposition in the hippocampus. Furthermore, K-7174 acted directly on the brain microvascular endothelial bEnd.3 cells and reduced the BBB permeability, manifested by inhibiting the activation of brain microvascular endothelial cells and increasing the expression of tight junctions (TJs). Notably, in vitro experiments showed that K-7174 alleviates the decreased ZO1 and Occludin expression in bEnd.3 cells caused by lactate increase, improving cell permeability via the MCT4/NKAP/CREB signaling pathway. These findings suggested that K-7174 mediates the attenuation of NPSLE in MRL/lpr mice, indicating a promising therapeutic strategy for NPSLE.

Anti-Ribosomal-P Antibody Association with Neuropsychiatric Lupus in Sudanese Patients Attending Rheumatology Clinic in Omdurman Military Hospital.

To assess and establish the relationship between neuropsychiatric systemic lupus erythematosus (NPSLE) involvement and serological biomarkers like antiribosomal-P antibodies. This is an analytical cross-sectional hospital-based study conducted on patients attending Omdurman Military Hospital from July 2019 to December 2019. A total of 90 patients were enrolled, 30 of whom had NPSLE compared with 60 SLE patients without NPSLE. SLE diagnosis was established based on the revised SLICC criteria (presence of at least 4 criteria) for SLE classification, with neuropsychiatric manifestations defined based on the ACR nomenclature. The immunological examination results have been performed by (ELISA immune-enzymatic method, immunofluorescence, and Western immunoblotting test). SPSS v 21.0 software was utilised for data analysis. NPSLE patients exhibited +ve ANA in 96.7% vs 75% in non-NPSLE (P-value = 0.008), antiribosomal-P antibodies (46.7% vs 20%; P-value = 0.0001), anti-nucleosome antibodies (26.7% vs 5%; P-value = 0.005), and anti-histones antibodies (40% vs 20%; P-value = 0.04). ANA antibodies were significantly associated with neurological manifestations as ANA antibodies were common in epilepsy (n = 9; 91%) and stroke (n = 8; 27.6%) (P-value < 0.001). Neuropsychiatric manifestation of systemic lupus erythematosus exhibits variable clinical manifestations. Neuropsychiatric manifestations of SLE are strongly associated with the anti-ribosomal P antibody presence and can be employed as a powerful diagnostic tool.

Pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus: A review

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.

Neuropsychiatric manifestations and their attribution to systemic lupus erythematosus: a retrospective single-center study in a Polish population.

Neuropsychiatric (NP) manifestations occur in patients with systemic lupus erythematosus (SLE), and it is challenging to distinguish these manifestations from other neuropsychiatric conditions. We aimed to assess the prevalence of primary neuropsychiatric SLE (NPSLE) in a Polish cohort of SLE patients. This retrospective, cross‑sectional study evaluated 164 patients with SLE. NP manifestations were attributed to SLE using the Italian model. Demographic and clinical data, including disease activity (measured by the Systemic Lupus Erythematosus Disease Activity Index version 2000 [SLEDAI‑2K] and the Physician Global Assessment) and organ damage (measured by the Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index), were obtained in patients with and without NP manifestations attributed to SLE. The final analysis set included 143 patients, 34 of whom (23.8%) had NP manifestations attributed to SLE. The age of the patients with NPSLE and the age of disease onset were significantly lower in comparison with those without NP symptoms attributed to SLE (median [interquartile range], 38 [29-45] vs 45 [32-55] years; P = 0.009, and 35 [24-38] vs 40 [25-48] years; P = 0.03, respectively). The disease activity and proportion of patients with active disease (SLEDAI‑2K ≥6) was significantly higher in the NPSLE patients than in those without NP symptoms attributed to SLE (P <0.005; 100% vs 85.3%; P = 0.01, respectively). NP manifestations in the central nervous system were the most frequent (91.5%). In the patients with NPSLE, cerebrovascular disease, seizures, cognitive dysfunction, psychosis, and cranial neuropathy occurred most often. NP manifestations occurred mainly in young patients with high disease activity. Cerebrovascular disease, seizures, psychosis, cognitive dysfunction, and cranial neuropathy were the most frequent manifestations of NPSLE.

Efficacy and safety of belimumab/low-dose cyclophosphamide therapy in moderate-to-severe systemic lupus erythematosus

ObjectivesWe have reported previously that Belimumab, a human monoclonal antibody that inhibits B-cell activating factor(BAFF) could be an effective and safe option to treat Neuropsychiatric manifestations of SLE (NPSLE). To avoid inadequate efficacy of Belimumab and significant adverse events of often-used dose of cyclophosphamide (CYC) for SLE, we evaluated the efficacy, safety, and possible immune mechanisms of Belimumab treatment in combination with intermittent low-dose intravenous CYC for moderate-to-severe SLE.MethodsIn this non blinded and parallel-group trial, we collected 82 cases of moderate-to-severe SLE patients, 40 received Belimumab treatment and 42 received conventional treatments as historical controls for 24 weeks. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups or subsets were compared before and after the treatments.ResultsCompared with the baseline, 6 months post Belimumab group treatment, disease activity score SLEDAI (13.78 to 3.82, P<0.05) and BILAG scores (16.40 to 5.48, P<0.05) were reduced; C3 (0.19 to 1.14, P<0.05) and C4 (0.04 to 0.22, P<0.05) increased; the absolute numbers of B and T cells were the first decreased and then significantly increased, tended to balance. Moreover, Belimumab group treatment significantly reduced the serum levels of IL-6, the ratio of B and T cells, and the proportion of infections and menstrual disorders.ConclusionCompared with conventional treatment, Belimumab with low-dose intravenous CYC significantly reduced disease activity scores and maintained the B/T cell balance for SLE patients at 24 weeks. It was more efficacy and safe (adverse events such as infection were significantly lower). It should be the mechanism that Belimumab combined with low-dose intravenous CYC therapy restores the balance of T and B cells, which proposes a potential treatment strategyfor SLE.

Diplopia as the Initial Manifestation of Cerebral Vasculitis in a Patient with Systemic Lupus Erythematosus: Diagnostic Approach and Challenges

The term Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses all neurologic and or psychologic symptoms arising in patients with SLE after other causes have been ruled out. Cerebral vasculitis as a manifestation of NPSLE is a rare case with a very broad spectrum of clinical presentation and severity. We report a case of a female with cerebral vasculitis presenting with diplopia as its early manifestation. Diagnosing cerebral vasculitis remains challenging given that biopsy as the gold standard is an invasive procedure and may not be available in many settings. A high suspicion of diagnosis requires clinicians’ judgement in reviewing combination of detailed history taking, physical examination, neuroimaging, and other available supporting modalities.

Mania in an individual with Systemic Lupus Erythematosus – A case report

Neuropsychiatric manifestations are common and occur in around 14-80% of patients with SLE. No particular neurologic or psychiatric manifestation is characteristic of SLE and the form and pattern of neuropsychiatric symptoms vary significantly. The American College of Rheumatology (ACR) Nomenclature provides case definition for 19 neuropsychiatric syndromes seen in SLE. However, these case definitions were not found to be effective in differentiating neuropsychiatric SLE (NPSLE) patients from those with neuropsychiatric manifestations not associated with SLE.Here we present a case of mania in a patient with SLE and discuss the differential diagnosis of neuropsychiatric manifestations of SLE and primary mood disorder. Symptoms of neuropsychiatric SLE vary significantly and psychiatric disturbances in a patient with SLE is a diagnosis of exclusion where other possibilities have to be considered including an independent comorbid psychiatric disorder. This case highlights the difficulty in the diagnostic process and the need for more studies on the differences between primary psychiatric disorders and neuropsychiatric SLE.

NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS: A NOVEL APPROACH TO REFRACTORY DISEASE

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) refers to involvement of the nervous system in patients with Systemic Lupus Erythematosus (SLE) either by inflammation or thrombosis. (1) Neuropsychiatric manifestations in SLE are prevalent with affecting up to 40 percent of patients. (2) We present a case of NPSLE presenting as Lupus cerebritis requiring pulse dose steroids and Immunosuppressive therapy. CASE PRESENTATION: A 40 year old female with a history of SLE presented with altered mental status. She had a dental procedure done 1 week ago. Her vitals on presentation were unremarkable. On physical examination she was an ill appearing female oriented to self with deep red confluent plaques with some crusting on her face. Initial work up showed leukopenia. Blood cultures were drawn. CT head was normal and a panorex showed periodontitis at the site of recent dental procedure. Workup was negative for any ischemic, metabolic, or toxic etiology for her confusion. A lumbar puncture was performed and the patient was started on empiric antibiotics. Spinal fluid analysis was unremarkable, including culture and viral encephalitis panel. ESR and CRP were elevated at 68 mm/hr and 1.4 mg/dl respectively. Autoimmune studies showed low C3 and C4 levels of 59 mg/dl and 3 mg/dl while dsDNA was 32 IU/ml. Diffusion Weighted images on MRI showed patchy cortical and subcortical lesions consistent with lupus cerebritis. EEG was negative for any seizure activity.The patient was diagnosed with Lupus Cerebritis (NPSLE) and was started on pulse dose steroids 1gm Methylprednisolone for 3 days and mycophenolate. There was significant improvement in her mental status and rash. Following her improvement steroids were decreased to 1mg/kg/day prednisone. Upon decreasing her steroids, she again developed worsening delirium. She was again started on a second course of pulse dose steroids with subsequent return to her baseline mental status. She was discharged on mycophenalate, hydroxychloroquine and tapering dose of prednisone starting at 1mg/kg with rheumatology follow up. DISCUSSION: NPSLE is a complication of SLE with substantial mortality. There is no gold standard test to diagnose it, other etiologies delirium must be ruled out. (3) NSPLE can be associated with cutaneous involvement. Generalized involvement of the central nervous system with inflammation leads to an acute state of confusion (Delirium). Treatment is with pulse dose steroids, methylprednisolone at 1 gm/day for 3 days followed by 1mg/kg/day. (3) In certain cases, additional immunosuppressive agents may be needed. Further, if there is incomplete response to pulse dose steroids, repeating or prolonging the course may be beneficial as was the case in our patient. CONCLUSIONS: In patients with NPSLE, physicians should consider prolonging the pulse dose steroids or repeating the course of pulse dose steroids if inadequate response to initial therapy. REFERENCE #1: The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999 Apr;42(4):599-608. doi: 10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F. PMID: 10211873. REFERENCE #2: Hanly JG, Urowitz MB, Su L, et al. ; Systemic Lupus International Collaborating Clinics (SLICC). Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2010 Mar;69(3):529-35. doi: 10.1136/ard.2008.106351. Epub 2009 Apr 8. PMID: 19359262; PMCID: PMC2929162. REFERENCE #3: Kivity, S., Agmon-Levin, N., Zandman-Goddard, G. et al. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 13, 43 (2015). https://doi.org/10.1186/s12916-015-0269-8 DISCLOSURES: No relevant relationships by Benjamin Goodman, source=Web Response No relevant relationships by Muhammad Ibrar Islam, source=Web Response

Electroencephalographic Findings in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Neuropsychiatric Manifestations

Abstract Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P &amp;lt; 0.01). ACL IgM positivity was higher in NPSLE group (P &amp;lt; 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

Serum BDNF and cognitive dysfunction in SLE: findings from a cohort of 111 patients

The association between brain-derived neurotrophic factor (BDNF) and neuropsychiatric systemic lupus erythematosus (NPSLE) is controversial in the literature. Cognitive dysfunction (CD) is a common, underdiagnosed NPSLE manifestation, but its pathophysiology is unknown. Thus, we investigate serum BDNF as a potential biomarker of CD in a cohort of SLE patients. We included 63 SLE patients, 48 NPSLE, and 57 age- and gender-matched controls (CON). All participants underwent neuropsychological assessment. Data on cardiovascular comorbidities, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics damage index (SLICC-DI) were compiled. Multiple regression analyses evaluated predictors of serum BDNF levels. Serum BDNF levels were lower in SLE and NPSLE patients than in CON (SLE 800.4 ± 502.7 vs. NPSLE 779.7 ± 426.3 vs. CON 1,345.5ng/mL ± 438.4; p < 0.001). In addition, hypertension (B: - 192.5, SE: 84.3, 95% CI: - 359.7 to - 25.3, p = 0.024) and SLICC-DI score (B: - 75.9, SE: 27.2, 95% CI: - 129.8 to - 22, p = 0.006) were predictors of serum BDNF levels in SLE. There was no relation between BDNF levels and CD. BDNF levels are lower in SLE patients than CON and inversely associated with hypertension and SLICC-DI scores. No association between BDNF levels and CD or NPSLE was observed in this cohort. These findings indicate that BDNF may be associated with overall burden in SLE rather than specific manifestations such as cognition impairment. Key Points • BDNF is associated with an overall burden in SLE rather than specific manifestations such as cognition dysfunction. • BDNF levels are reduced in patients with SLE, and higher SLICC-DI scores and hypertension are independent predictors of lower serum BDNF levels. • The cognitive dysfunction rate is elevated (46%) among Brazilian SLE patients.

Clinical and electrophysiological assessment of cranial and peripheral neuropathies in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo study the frequency of cranial and peripheral neuropathies in systemic lupus erythematosus (SLE), their clinical characteristics, electrophysiological pattern and relation to disease activity. Patients and methodsThe study included 30 SLE patients and 20 matched healthy controls. Electrophysiological assessment included routine nerve conduction studies for assessment of peripheral nerves and visual evoked potential, blink reflex, and brain stem auditory evoked potential for assessment of the second, fifth, seventh, and eighth cranial nerves, respectively. Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI) was assessed. ResultsThe mean age of the patients was 35.8 ± 8.6 years, 27 females and 3 males (9:1) with median disease duration 4.5(1.2–8) years and SELENA-SLEDAI of 12.09 ± 4.94. The mean complement-3 (C3) level was 81.2 ± 26.9 mg/dl and C4 was 11.5 ± 4.4 mg/dl. Peripheral neuropathy was detected electrophysiologically in 66.7% and clinically in 53.3% of the patients and was sensory more than motor. Sensory neuropathy was found in 9(30%), sensorimotor in 11(36.7%), demyelinating in 9(30%), axonal in 6(20%) and both axonal and demyelinating in 5(16.7%) patients. 13.3% had subclinical neuropathy. Sensorimotor and sensory neuropathies were detected in 36.7% and 30% of patients, respectively. Cranial neuropathy was not detected in any patient or control clinically or electrophysiologically. Peripheral neuropathy significantly correlated with SELENA-SLEDAI (r = 0.55, p = 0.002) and negatively with C3 and C4 (r = −0.65, p = 0.012 and r = −0.63, p = 0.015 respectively). ConclusionPeripheral neuropathy is a well-recognized but underestimated manifestation of neuropsychiatric SLE with predominance of sensorimotor variant. Peripheral neuropathy is associated with disease activity and complement consumption.

Association of serum neurofilament light chain levels and neuropsychiatric manifestations in systemic lupus erythematosus.

Background:The aim was to evaluate the diagnostic potential of serum neurofilament light chain (sNfL) measurements in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Methods:sNfL levels were determined by single molecule array assay in a retrospective cross-sectional cohort of 144 patients with systemic lupus erythematosus (SLE). After log-transformation of sNfL levels, mean sNfL levels were compared between NPSLE patients and SLE patients without neuropsychiatric disease using Student’s t test. Furthermore, the association of different neuropsychiatric manifestations with sNfL levels was assessed using a one-way analysis of variance (ANOVA) with post hoc analysis. Associations of sNfL with clinical and laboratory parameters were assessed by correlation and multiple linear regression analysis.Results:NPSLE patients (n = 69) had significantly higher sNfL levels than SLE patients without neuropsychiatric disease manifestations (n = 75; mean difference: 0.13, 95% CI: 0.04–0.22, p = 0.006). With regard to the category of NPSLE manifestation, mean sNfL levels were only increased in NPSLE patients with focal central nervous system (CNS) involvement (n = 45; mean difference: 0.16, 95% CI: 0.02–0.30, p = 0.019), whereas mean sNfL levels of NPSLE patients with diffuse CNS and peripheral nervous system involvement did not differ from those of SLE patients without neuropsychiatric manifestations. Age and serum creatinine concentrations were identified as relevant contributors to sNfL levels.Conclusion:sNfL is a promising, easily accessible biomarker for neuropsychiatric involvement in SLE patients and might therefore complement the diagnostic workup of SLE patients with suspected involvement of the nervous system.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with systemic lupus erythematosus

BackgroundChronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is an uncommon subtype of peripheral neuropathy (PN) and especially when associated with systemic lupus erythematosus (SLE). There are few reports characterizing PN-associated to SLE, in particular CIDP. This study reviewed the frequency and profile of SLE-related CIDP in our cohort and in the literature and propose a treatment scheme for CIDP associated with SLE. MethodWe reviewed our database to identify patients with CIDP and SLE. The literature was also reviewed following the guidelines of PRISMA and using the terms "Polyradiculoneuropathy", "Chronic inflammatory demyelinating polyradiculoneuropathy", "CIDP", "Systemic lupus erythematosus", "SLE", "Autoimmune diseases of the nervous system" until December 2019. Selected articles were published in English. ResultsWe identified 3 patients with SLE and CIDP in our cohort of 1,349 patients with SLE (0.2%). All patients were female, aged between 30 and 44 years and 2 (66.7%) had active disease in other organs. In the literature, we identified additional 16 patients. A predominance of women with disease activity, specially nephritis and hematological involvement, was observed. Treatment schemes are diverse, including corticosteroids and immunosuppressive drugs. ConclusionAlthough rare, CIDP has increased frequency in SLE. Women and younger age should rise suspicion of an underlying autoimmune disease. We suggest that CIDP should be included as a possible neuropsychiatric manifestation in SLE.

Neuropsychiatric manifestations associated with systemic lupus erythematosus: A case report and selective review of literature

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune condition affecting multiple organ systems including central nervous system. Its aetiology lies in abnormal antibody formation and complement activation. Neuropsychiatric manifestations are known to occur in patients with SLE, and vary from psychosis, depression, anxiety to cognitive impairment. Here we report a case of depression with psychotic symptoms and suicidal ideations associated with SLE. Case Summary: We present the case of a 30-year-old female who presented with irritability, crying spells, feeling of guilt, referential and persecutory ideations along with suicidal ideations. She was diagnosed with severe depression with psychotic symptoms associated with SLE. She improved over a period of 6 weeks with Quetiapine 300mg along with symptomatic management of underlying medical condition. Conclusions: Depression with psychotic symptoms is not an uncommon presentation of SLE. It needs comprehensive management and multidisciplinary approach. Hence physician has to be sensitized regarding neuropsychiatric manifestations of SLE for improving the morbidity and mortality associated with underlying depression. Keywords: SLE-Depression-Psychosis.

Lupus animal models and neuropsychiatric implications.

Systemic lupus erythematosus (SLE) that involves neurological complications is known as neuropsychiatric systemic lupus erythematosus (NPSLE). Research in humans is difficult due to the disease's great heterogeneity. Animal models are a resource for new discoveries. In this review, we examine experimental models of lupus that present neuropsychiatric manifestations. Spontaneous animal models such as NZB/W F1 and MRL/lpr are commonly used in NPSLE research; these models present few SLE symptoms compared to induced animal models, such as pristane-induced lupus (PIL). The PIL model is known to present eight of the main clinical and laboratory manifestations of SLE described by the American College of Rheumatology. Many cytokines associated with NPSLE are expressed in the PIL model, such as IL-6, TNF-α, and IFN. However, to date, NPSLE manifestations have been poorly studied in the PIL model. In this review article, we discuss whether the PIL model can mimic neuropsychiatric manifestations of SLE. Key Points • PIL model have a strong interferon signature. • Animals with PIL express learning and memory deficit.

Quantitative Identification of Functional Connectivity Disturbances in Neuropsychiatric Lupus Based on Resting-State fMRI: A Robust Machine Learning Approach.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients.