Neuropsychiatric Lupus Erythematosus Research Articles

Significance of immunoglobulins synthesis with central nervous system involvement in Neuro-Behçet’s disease

ObjectivesDemyelination and immunocyte-infiltrated lesions have been found in neuro-Behçet’s disease (NBD) pathology. Lacking satisfying laboratory biomarkers in NBD impedes standard clinical diagnostics. We aim to explore the ancillary indicators for NBD diagnosis unveiling its potential etiology. Methods28 NBD with defined diagnosis, 29 patients with neuropsychiatric lupus erythematosus, 30 central nervous system idiopathic inflammatory demyelination diseases (CNS-IIDD), 30 CNS infections, 30 cerebrovascular diseases, and 30 noninflammatory neurological diseases (NIND) were retrospectively enrolled. Immunoglobulins (Ig) in serum and cerebral spinal fluid (CSF) were detected by immunonephelometry and myelin basic protein (MBP) by quantitative enzyme-linked immunosorbent assay. ResultsIgA index is almost twice enhanced in NBD than NIND with an accuracy of 0.8488 in differential diagnosis, the sensitivity and specificity of which were 75.00 % and 90.00 % when the cutoff was > 0.6814. The accuracy of CSF Ig and quotient of Ig all exceed 0.90 in discerning NBD with damaged and intact blood–brain barrier (BBB). Clustering analyses divided NBD into two different phenotypes: one with BBB damage has lower Ig synthesis, the other with extra-synthesis in parenchymal sites but with intact BBB. MBP index is significantly correlated with kappa (KAP) index and lambda (LAM) index (r = 0.358, 0.575, P < 0.001), hinting the NBD pathogenesis of CNS demyelination in triggering excessive intrathecal Ig productions and humoral responses. ConclusionsIgA index acts as a potential diagnostic indicator in differentiating NBD from NIND and CNS-IIDD. Excessive immunoglobulin production induced by CNS inflammation and demyelination might be latent immunopathogenesis of NBD.

Treatment with lysophosphatidic acid improves glomerulonephritis through the suppression of macrophage activation in a murine model of systemic lupus erythematosus.

Several therapeutic agents have been developed and used for the clinical treatment of systemic lupus erythematosus (SLE). In cases where SLE is accompanied by severe organ failures, such as neuropsychiatric lupus erythematosus (NPSLE) and acute onset of lupus nephritis, the use of potent immunosuppressive drugs, such as cyclophosphamide, is necessary. However, potent immunosuppressive drugs are known to increase infection risks. Thus, the development of therapeutic agents with novel mechanisms is urgently required. Previously, we reported that treatment with lysophosphatidic acid (LPA) prevents depression-like behaviours by suppressing microglial activation in MRL/lpr mice. In this study, we examined whether the treatment with LPA improves glomerulonephritis by affecting systemic immunity in MRL/lpr mice. Eighteen-week-old MRL/lpr mice were treated with a vehicle or LPA for 3 weeks. After treatment, the glomerular inflammation and damage parameters were compared between the 2 groups. Moreover, we examined the effects of LPA on immune cells by flow cytometry using isolated splenocytes. LPA treatment in MRL/lpr mice significantly reduced the daily urinary albumin content and suppressed the CD68-positive cells and Periodic acid-Schiff (PAS)-positive areas in the glomeruli. The treatment also suppressed plasma anti-dsDNA antibodies and inflammatory cytokines in MRL/lpr mice. Although LPA did not significantly affect the total number of splenocytes, the treatment significantly reduced CD11b+Ly6G-Ly6C- cells (mature macrophages), as well as CD11b+Ly6G-Ly6C-CD68+ cells (activated mature macrophages). These results suggest that LPA may improve glomerulonephritis by suppressing macrophage activation in MRL/lpr mice.

A - 91 Serial Neuropsychological Evaluations of a Woman with Neuropsychiatric Systemic Lupus Erythematosus and Immunotherapy Treatment.

Neuropsychiatric System Lupus Erythematosus (NP-SLE) is a subtype of SLE characterized by chronic or episodic neurologic and/or psychiatric central nervous system features. The neuropsychological profile of NP-SLE is not well-established. Here we present serial evaluations of a woman with confirmed NP-SLE who underwent subsequent medical intervention. This case study adds to the growing body of literature demonstrating the role neuropsychology plays in the care of patients with NP-SLE. This was an evaluation of a 25-year-old woman with NP-SLE. Initial testing took place inpatient prior to treatment with immunotherapy treatment subsequent evaluations were outpatient at 1month, 4months and 8months post-treatment. Inpatient evaluation revealed a woman of at least average premorbid abilities with suboptimal performances across cognitive domains including reduced speed of processing and notable difficulty with planning and organization. Evaluation 1month later evidenced worsening cognitive and motoric performances across tasks which led to adjustment of medical management. Evaluation at 4months demonstrated a positive trend and some improved cognitive functioning; 8-month evaluation confirmed improvement in global cognition and functioning with suspected return to premorbid abilities. This case provides an example of NP-SLE neuropsychological profile over time and demonstrates the beneficial impact of correct diagnosis and medical regimen. It also highlights the role of serial neuropsychological assessment in the management of complex neurological disease.

Interleukin 6: at the interface of human health and disease.

Interleukin 6 (IL-6) is a pleiotropic cytokine executing a diverse number of functions, ranging from its effects on acute phase reactant pathways, B and T lymphocytes, blood brain barrier permeability, synovial inflammation, hematopoiesis, and embryonic development. This cytokine empowers the transition between innate and adaptive immune responses and helps recruit macrophages and lymphocytes to the sites of injury or infection. Given that IL-6 is involved both in the immune homeostasis and pathogenesis of several autoimmune diseases, research into therapeutic modulation of IL-6 axis resulted in the approval of a number of effective treatments for several autoimmune disorders like neuromyelitis optica spectrum disorder (NMOSD), rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis (GCA), and cytokine release syndrome, associated with SARS-CoV2 pneumonia. This review discusses downstream inflammatory pathways of IL-6 expression and therapeutic applications of IL-6 blockade, currently investigated for the treatment of several other autoimmune conditions such as autoimmune encephalitis, autoimmune epilepsy, as well as myelin oligodendrocyte glycoprotein associated demyelination (MOGAD). This review further highlights the need for clinical trials to evaluate IL-6 blockade in disorders such neuropsychiatric lupus erythematosus (SLE), sarcoidosis and Behcet's.

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.

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

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

The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement.

Type I interferons (IFNs) are major mediators of innate immunity, with well-known antiviral, antiproliferative, and immunomodulatory properties. A growing body of evidence suggests the involvement of type I IFNs in the pathogenesis of central nervous system (CNS) manifestations in the setting of chronic autoimmune and autoinflammatory disorders, while IFN-β has been for years, a well-established therapeutic modality for multiple sclerosis (MS). In the present review, we summarize the current evidence on the mechanisms of type I IFN production by CNS cellular populations as well as its local effects on the CNS. Additionally, the beneficial effects of IFN-β in the pathophysiology of MS are discussed, along with the contributory role of type I IFNs in the pathogenesis of neuropsychiatric lupus erythematosus and type I interferonopathies.

Neuropsychiatric lupus erythematosus with neurogenic pulmonary edema and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor limbic encephalitis: a case report

BackgroundSystemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease predominantly found in women of child-bearing age. Neurogenic pulmonary edema (NPE) is a recalcitrant complication that occurs after injury to the central nervous system and has an acute onset and rapid progression. Limbic encephalitis is an inflammatory encephalopathy caused by viruses, immune responses, or other factors involving the limbic system. NPE caused by SLE is rare.Case presentationHere, we report a case of a 21-year-old woman with SLE who experienced five episodes of generalized tonic–clonic seizure after headache and dyspnea. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 2 antibody was tested positive in the serum and cerebrospinal fluid. Electrocardiography (EEG) indicated paroxysmal or sporadic medium amplitude theta activity. In addition, chest computed tomography (CT) showed multiple diffuse consolidations and ground-glass opacities. We finally considered a diagnosis of NPE and AMPAR limbic encephalitis. The patient's symptoms improved obviously after methylprednisolone pulse therapy and antiepileptic treatment.ConclusionsNPE can be a complication of neuropsychiatric lupus erythematosus (NPSLE). AMPAR2 antibodies may be produced in NPSLE patients, especially in those with high polyclonal IgG antibody titers. More basic and clinical studies are required to confirm these observations and elucidate the pathogenicity of encephalitis-related autoantibodies in SLE patients.

Neuropsychiatric lupus erythematosus in a cohort of Egyptian patients

BackgroundThe neuropsychiatric lupus erythematosus (NPSLE) is a severe complication of systemic lupus erythematosus (SLE) that is characterized by a variety of neurological manifestations involving both central and peripheral nervous system with variable mechanisms. This study aimed to investigate the frequency of NPSLE and its relation to other clinical and laboratory findings in SLE patients.ResultsWe retrieved the medical records of 134 SLE patients during the study period; of them, 68 patients (50.7%) had NPSLE. Headache (55. 9%) was the most frequent NPSLE manifestation followed by seizures (54.4%), psychosis was the third most frequent one with a percentage of 41.2. The demographic data didn’t differ in patients with and without NPSLE. NPSLE patients had lower complement 3 (C3) (p = 0.025) and C4 (p = 0.008) levels, more lupus anticoagulant level (p = 0.033) and more frequency of antiphospholipid syndrome (p = 0.030). There was no statistical difference regarding the drug intake or other laboratory findings. Disease activity and damage indices didn’t differ in both groups.ConclusionThe prevalence of NPSLE in this study was 50.7%. Headache, seizures and psychosis were the most frequent neuropsychiatric manifestations in the studied patients. SLE patients with neuropsychiatric manifestations had lower complement levels, higher lupus anticoagulant antibodies and antiphospholipid syndrome.

Treatment with lysophosphatidic acid（LPA）improves depressive behaviors in neuropsychiatric lupus erythematosus (NPSLE) model mice through LPA receptor

Treatment with lysophosphatidic acid（LPA）improves depressive behaviors in neuropsychiatric lupus erythematosus (NPSLE) model mice through LPA receptor

Prevalence, involved domains, and predictor of cognitive dysfunction in systemic lupus erythematosus

Cognitive Dysfunction (CD) can occur in Systemic Lupus Erythematosus (SLE) before the occurrence of Neuropsychiatric Lupus Erythematosus (NPSLE). Given the reversibility and fluctuation of SLE-related CD, the research for possible predictors is of great significance for early detection and intervention. We sought to determine the prevalence, involved domains, and possible predictors of CD in SLE patients. We conducted a retrospective cross-sectional study at Nanfang Hospital from 2018 to 2019. A total of 78 SLE patients were recruited. The Montreal Cognitive Assessment (MoCA) scale was used to screen cognitive function. Demographic, clinical, and laboratory characteristics were collected. The serum anti-methyl-d-aspartate receptor (anti-NMDAR) antibody and S100β were measured by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression analysis and ROC curve were used to assess the predictor of SLE-related CD. Of 78 recruited patients,53 (67.9%) had CD. It mainly involved delayed recall, abstract generalization, verbal repetition, and fluency. The disease activity index (SLEDAI) was not associated with SLE-related CD (p > 0.05). Multivariate logistic regression showed that an increase in each year of education there was a decrease in the likelihood of CD (OR 0.261, CI 0.080-0.857, p = 0.027) whereas with each unit increase in serum anti-NMDAR antibody there was an increased likelihood of SLE-related CD (OR 1.568, CI 1.073-2.292, p = 0.020). The prevalence of SLE-related CD was 67.9% in our study and SLE-related CD was not associated with disease activity. Serum anti-NMDAR antibody can be used as a predictor for SLE-related CD.

Lupus serum IgG induces microglia activation through Fc fragment dependent way and modulated by B-cell activating factor

BackgroundNeuropsychiatric manifestations are frequent in patients with systemic lupus erythematosus (SLE), yet the etiology and pathogenesis of brain damage in SLE remains unclear. Because the production of autoantibodies, formation and deposition of immunocomplexes are major serological characteristics of SLE, the elevated level of serum immunoglobulin may contribute to brain tissue injury of SLE. To testify this, in this study, we examined whether immunoglobulin G (IgG) in the serum of SLE patients affects the cellular functions in central nervous system and the potential mechanism.MethodsIn vivo intracerebral injection of SLE-serum in mouse was used to activate microglia and the production of pro-inflammatory cytokine was assessed by ELISA. Sera was divided into IgG and IgG depleted fractions, while IgG was further divided into Fc and Fab fragments to examine which part has an effect on microglia. Flow cytometry, immunofluorescence and quantitative PCR (qPCR) were used to verify the synergistic effect of B-cell activating factor (BAFF) on IgG stimulation of microglia.ResultsWe found that IgG in lupus sera can induce M1 activation of brain microglia following intraventricular injection into normal mice, and BAFF facilitates this process. In vitro, we identified that IgG bound to microglia through Fc rather than Fab fragments, and BAFF up-regulated the expression of Fc receptors (FcγR) on the surface of microglia, consequently, promote IgG binding to microglia.ConclusionOur results suggest that lupus serum IgG causes inflammatory responses of microglia by involving the Fc signaling pathway and the activity could be up-regulated by BAFF. Accordingly, disruption of the FcγR-mediated signaling pathway and blockade of microglia activation may be a therapeutic target in patients with neuropsychiatric lupus erythematosus.

A challenging case of neuropsychiatric systematic lupus erythematosus with recurrent antiphospholipid- related stroke: A case report and literature review.

Neuropsychiatic systematic lupus erythematosus (NPSLE) is a form of SLE involves the inflammation and/or thrombotic event in the nervous system. Patients with NPSLE are likely to have a positive antiphospholipid antibody (aPL), therefore are at higher risk of recurrent ischemic stroke. The management of NPSLE with aPLrelated stroke is rather different from the traditional ischemic stroke. One must treat it with anticoagulation and immunosuppressive therapy. The present case is a 47-yearold Taiwanese female with NPSLE and positive aPL, presented with a recurrent MCA ischemic stroke. Initial laboratory results showed significantly elevated levels of anti-ANA, anti-dsDNA, anti-cardiolipin, and decreased complement levels. Due to multiple contraindications for tPA, she was treated with antiplatelet, anticoagulation, steroid pulse therapy, and plasmapheresis during the hospitalization. Despite treatments, her stroke progressed to multi-focal lesions, involving the ACA, MCA, and basal ganglion. On follow up of her brain CT scan showed tissue edema and suspicious for subfalcine herniation. Responding to this clinical deterioration, we stopped warfarin and started mannitol. Eventually, her condition improved and was transferred to the rehabilitation program. Currently, there is no unified guideline regarding the secondary prevention of ischemic stroke in NPSLE with aPL patients. Additionally, previously reported use of steroid pulse therapy and plasmapheresis can potentially harm the patient. Clinicians must be cautious when treating such patient.

Clinical features of central nervous system infections and experience in differential diagnosis from neuropsychiatric lupus erythematosus in a cohort of 8491 patients with systemic lupus erythematosus

BackgroundIn clinical practice, discrimination between central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE) and neuropsychiatric lupus erythematosus (NPSLE) could be urgent and critical yet extremely challenging. Given this, this study aimed to investigate the clinical features and outcomes of infections in the CNS in patients with SLE and to establish a simplified scoring system for guiding the discrimination of CNS infections from NPSLE.MethodsA total of 95 patients who were identified as having CNS infections among 8491 SLE patients between January 1992 and January 2018 were included in this retrospective study. NPSLE patients admitted at the same period were randomly selected for comparison. Key factors either clinically valuable or statistically significant for discriminating CNS infections from NPSLE were integrated to build a simplified scoring system. Another group of 22 SLE patients complicated with suspected newly onset of CNS infections or NPSLE admitted after January 2018 was enrolled to verify the utility of the scoring system.ResultsSixty-three positive pathogens were identified in 59 patients of the total 95 CNS infection cases. Compared with the NPSLE group, the CNS infections group had a longer disease duration (21.0 [3.0–50.0] vs. 1.0 [0–22.0] months, P < 0.05), exhibited more fever (96.8% vs. 23.2%, P < 0.001) and polymorphonuclear leukocyte leukocytosis in the cerebrospinal fluid (CSF) (45.6% vs. 0.5%, P < 0.05), and had significantly decreased CSF glucose (2.0 ± 1.3 vs. 3.3 ± 0.9 mmol/L, P < 0.01), whereas hypocomplementemia seemed to be a strong hint of NPSLE (44.6% vs. 77.4%, P < 0.001). A simplified scoring system integrated with 8 key factors was established for guiding clinical differential diagnosis. By setting the cutoff value at 4 and verifying in a group of SLE patients complicated with newly occurred suspected CNS infection or NPSLE, a sensitivity of 85.7% and specificity of 93.3% with the area under the curve (AUC) being 0.93 (95%CI 0.80–1.00) were obtained.ConclusionsCNS infections are a fatal complication of SLE and can be difficult to discriminate from NPSLE. A simplified scoring system may help to make preliminary discrimination of CNS infections from NPSLE.

Clinical significance of anti-DNA/N-methyl-D-aspartate receptor 2 antibodies in de novo and post-steroid cases with neuropsychiatric systemic lupus erythematosus.

Anti-DNA/N-methyl-D-aspartate receptor 2 (NR2) antibodies (anti-DNA/NR2 antibodies) are a subset of anti-DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric system lupus erythematosus (NPSLE) can develop after initiation of corticosteroids (post-steroid neuropsychiatric manifestation: PSNP) or before treatment (de novo NPSLE); however, pathophysiological differences between these subtypes remain unclear. The objective of this study was to clarify the prevalence of anti-DNA/NR2 antibodies in patients with NPSLE. This study involved a cohort of patients with NPSLE admitted to our hospital. NPSLE patients were classified into two groups, de novo NPSLE and PSNP-SLE. Serum anti-DNA antibodies and anti-DNA/NR2 antibodies were measured by enzyme-linked immunosorbent assays. Serum samples were obtained from 24 patients with de novo NPSLE, 25 with PSNP-SLE and 76 healthy controls (HC). The level of anti-DNA/NR2 antibodies in patients with de novo NPSLE and PSNP-SLE were also higher than those in HC. Positive correlation between anti-DNA antibodies and anti-DNA/NR2 antibodies were found in PSNP-SLE, but was not significant in de novo NPSLE. The levels of anti-DNA/NR2 antibodies in PSNP-SLE were similar to those in de novo NPSLE. Anti-DNA/NR2 antibodies in PSNP-SLE were suggested as a dominant subset of anti-DNA antibodies, indicating that anti-DNA/NR2 antibodies may be a predictive factor in PSNP-SLE.

Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus

ObjectivesCerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion...

A case of neuropsychiatric lupus Erythematosus characterized by the Owl\u2019s eye sign: a case report

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder characterized by multiple affected systems. More than half of SLE patients will suffer from neuropsychiatric lupus erythematosus (NPSLE) during the course of their disease. Although nearly half of the NPSLE patients have normal MRI manifestations, the abnormalities found in the remainder can be located anywhere in the brain, and especially in the subcortical white matter of the frontal and temporal lobe. However, NPSLE involving the medulla oblongata and spinal cord which presents as the “owl’s eye” sign has to our best knowledge not been reported to date.Case presentationA 19-year-old girl presented at our hospital with a 7-day history of fever and headache since a one day’s exertion, accompanied by 2 days of weakness. The patient had slurred speech. Neurological examination revealed the presence of horizontal nystagmus and a limitation of bilateral eye movement when looking up and down. At the same time, she showed difficulty in raising the jaw, accompanied by a weak pharyngeal reflex. Muscle strength was remarkably decreased in all four extremities: the MRCS grade of the upper limbs was 4/5, while in the lower limbs it was 0/5. Hypotonia was apparent in the lower extremities. Regarding subjective sensation, the patient appeared to be experiencing an increased sense of pain in the whole body, and especially in the cervical region, abdomen, and feet. An examination of shallow reflex documented the reinforcement of the abdominal reflex. Deep tendon reflexes were symmetric: absent in lower, normal in upper extremities. The patient also had a stiff neck with a positive Kernig’s sign. The laboratory examination showed elevated C - reactive protein and rheumatoid factor, as well as complement components 3 and 4. Symptomatic treatments were applied, but she did not respond well, after which we did immunological laboratory examinations. The results showed the presence of anti-nRNP/Sm, anti-dsDNA and anti-AMA M2 antibodies. An MRI scan and enhancement of the cervical and thoracic regions displayed abnormal signs in the medulla and bilateral anterior horn of the lower thoracic spine. Following the exclusion of other possible diseases, neuropsychiatric lupus was diagnosed. High-dose intravenous gamma-globulin combined with methylprednisolone gradually improved her condition.ConclusionWe report the first case of NPSLE presenting with medulla oblongata and spinal cord involvement, manifesting as the “owl’s eye” sign in MRI.

Jaw Dystonia and Reversible Basal Ganglia Changes as an Initial Presentation of Systemic Lupus Erythematosus

Dystonia as a manifestation of neuropsychiatric lupus erythematosus (NPSLE) is uncommon. We report a 25-year-old woman who experienced progressive confusion, reduced speech, and difficulty opening her mouth approximately 2 weeks after development of a facial rash. Brain imaging showed bilateral, symmetric signal abnormalities within the basal ganglia and subcortical white matter. Despite treatment with high-dose steroids, she continued to have difficulty speaking with evidence of jaw dystonia on examination. Jaw dystonia rapidly improved with the initiation of levodopa. Repeat evaluation 3 months later exhibited the absence of jaw dystonia and near resolution of the imaging abnormalities. Our patient demonstrated a unique presentation with jaw dystonia refractory to traditional treatment for NPSLE. Such a presentation likely represents a severe variant of NPSLE requiring both immunosuppressive and symptomatic therapies.

Rituximab as First-Line Therapy in Severe Lupus Erythematosus with Neuropsychiatric and Renal Involvement: A Case-Report and Review of the Literature.

Neuropsychiatric and renal involvement are common in systemic lupus erythematosus with negative impact on patient survival. Glucocorticoids, antiproliferative and cytotoxic agents represent first-line therapies, but are often ineffective and are burdened by significant toxicities. Despite the negative results of two randomized controlled trials, rituximab is still widely used as second- or third-line therapy in similar cases. No case has been reported so far where rituximab has been used as first-line therapy.We report the case of a 60-year-old cCaucasian woman with concurrent neuropsychiatric and renal lupus erythematous treated with one cycle of rituximab therapy at disease onset. Treatment was well tolerated and at 24 months the patient is in complete remission and free of immunosuppression. To the best of our knowledge, this is the first case of neuropsychiatric and renal lupus erythematosus successfully treated with rituximab as first-line therapy.

IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.

To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE. 52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-α in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-α concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA. The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-α, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL-8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 × 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 × 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients. In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE.