Neuropsychiatric Lupus Research Articles

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.

Psychiatric manifestations of rheumatic diseases

Introduction and purpose of the work: Rheumatic diseases are chronic diseases that cause symptoms in many systems of the human body. Their most common symptoms include pain and symptoms of arthritis, their deformities, fatigue, and malaise. The aim of the article is to present the symptoms and mental disorders occurring in the course of selected rheumatic diseases.
 State of knowledge: The psychological symptoms are characteristic of systemic lupus erythematosus. Specified is a form of lupus called NSPLE (neuropsychiatric systemic lupus erythematosus), which includes neuropsychiatric symptoms in the course of systemic lupus erythematosus. Psychiatric symptoms are also present in the course of other rheumatic diseases. Neuropsychiatric symptoms may affect up to 80% of patients with primary Sjogren's syndrome, with 50% to 80% ahead of diagnosis. It has been proven that systemic slcerosis causes microvascular damage, which may cause neuropsychiatric symptoms in the form of mood disorders, anxiety and cognitive disorders. In one study, 59% of patients with fibromyalgia experienced mania, which was more than twice as high as in the control group.
 Summary: In the course of all rheumatic diseases presented by us, there are symptoms and mental disorders. They are often mood, cognitive and sleep disturbances. It should be emphasized that the etiology of psychiatric symptoms is multifactorial.

0818 Psychosis associated with sodium oxybate

Abstract Introduction Sodium oxybate is commonly used to treat narcolepsy with cataplexy. At the approved doses, the most common side effects are typically described as nausea, vomiting, dizziness, hypersomnia, urinary disturbances, and weight loss. Cases of medication-induced psychosis have been reported in the literature but remain exceedingly rare. We present a case of rapid-onset psychosis in a patient with systemic lupus erythematosus, which added complexity to the evaluation, treatment and clinical course. Report of Cases: The patient is a 42 year old woman with a past history of fibromyalgia, lupus and a prior diagnosis of narcolepsy evaluated for daytime hypersomnia and poor night time sleep. Prior medications included sodium oxybate which was effective; and modafinil and amphetamines which created intolerable side effects. Prior sleep studies were not available and a repeat PSG/MSLT were performed. PSG did not show sleep disordered breathing or nocturnal movements and MSLT showed an average sleep latency of 5.4 minutes and 4 SOREMs. HLA DQB10602 was positive. The patient was reinitiated on sodium oxybate and titrated to 4.5g twice nightly. A few weeks later the patient developed visual hallucinations, persecutory delusions, and insomnia for 3 days. She was admitted for an evaluation to rule out lupus cerebritis, and auto-immune vs. infectious encephalitis. MRI/MRA, lumbar puncture, as well as inflammatory markers and rheumatologic and infectious work up were unrevealing. Sodium oxybate was discontinued on the day of admission and the patient’s mentation returned to baseline over the next few days. Discharge diagnosis was psychosis secondary to sodium oxybate. Conclusion Psychosis is an extremely rare side effect of sodium oxybate therapy among patients treated for cataplectic narcolepsy. It remains a diagnosis of exclusion, and any alternative diagnoses must be explored prior to making the diagnosis of psychosis secondary to sodium oxybate, particularly in the medically complex patient. Support (If Any) None

Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.

The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ER stress, GRP78 evades retention mechanisms and is translocated to the cell surface (csGRP78) where it functions as an autoantigen. Autoantibodies to GRP78 appear in prostate, ovarian, gastric, malignant melanoma, and colorectal cancers. They are also found in autoimmune pathologies such as rheumatoid arthritis (RA), neuromyelitis optica (NMO), anti-myelin oligodendrocyte glycoprotein antibody-associated disorder (AMOGAD), Lambert-Eaton myasthenic syndrome (LEMS), multiple sclerosis (MS), neuropsychiatric systemic lupus erythematosus (NPSLE) and type 1 diabetes (T1D). In NMO, MS, and NPSLE these autoantibodies disrupt and move across the blood-brain barrier (BBB), facilitating their entry and that of other pathogenic antibodies to the brain. Although csGRP78 is common in both cancer and autoimmune diseases, there are major differences in the specificity of its autoantibodies. Here, we discuss how ER mechanisms modulate csGRP78 antigenicity and the production of autoantibodies, permitting this chaperone to function as a dual compartmentalized receptor with independent signaling pathways that promote either pro-proliferative or apoptotic signaling, depending on whether the autoantibodies bind csGRP78 N- or C-terminal regions.

Aptamer-Based Screen of Neuropsychiatric Lupus Cerebrospinal Fluid Reveals Potential Biomarkers That Overlap With the Choroid Plexus Transcriptome.

As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform. CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases. Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, α2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins. Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential.

The correlation between proteoglycan 2 and neuropsychiatric systemic lupus erythematosus

The proposed pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) mainly includes ischemia and neuroinflammation mechanisms. Protein encoded by Proteoglycan 2 (PRG2) mRNA is involved in the immune process related to eosinophils, also being found in the placenta and peripheral blood of pregnant women. We evaluated the correlation between PRG2 and NPSLE for the first time and found that PRG2 protein was overexpressed in the serum of patients with NPSLE and correlated with the SLE disease activity index (SLEDAI) subset scores of psychosis. Moreover, we investigated the correlation between hippocampal PRG2 level and hippocampally dependent learning and memory ability in MRL/lpr mice, and discovered that the number of PRG2+GFAP+ astrocytes in the cortex and hypothalamus and the number of PRG2+IBA-1+ microglia in the hippocampus and cortex significantly increased in the MRL/lpr mice. These data provided a reference for the follow-up exploration of the role of PRG2 in SLE or other diseases.

Demyelinating Syndromes in Systemic Lupus Erythematosus: Data From the "Attikon" Lupus Cohort.

BackgroundThe demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs.ObjectivesTo characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE).MethodsPatients from the “Attikon” lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study.ResultsWe identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008–0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014–0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76–188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively).ConclusionsDemyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.

(PO-084) Catatonia in Neuropsychiatric Lupus: A Case Report and Review of Literature

(PO-084) Catatonia in Neuropsychiatric Lupus: A Case Report and Review of Literature

HMGB1‐mediated microglial activation as a mechanism for cognitive dysfunction in neuropsychiatric lupus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the presence of anti‐nuclear antibodies as well as a broad array of clinical manifestations spanning nearly every organ system. Neuropsychiatric syndromes affect over one half of SLE patients, presenting most commonly as cognitive dysfunction or headache. The pathophysiology of neuropsychiatric lupus is not fully understood; however, a critical mechanism has been identified, which involves passage of inflammatory cytokines and anti‐brain antibodies through the blood‐brain barrier.We previously developed a mouse model to study the effects of anti‐dsDNA antibodies that cross‐react with the NMDA receptor (NMDAR), termed DNRAbs, which are present in approximately 30% of SLE patients and whose presence in the CSF is associated with non‐focal CNS manifestations of neuropsychiatric lupus. In this mouse model, non‐spontaneously autoimmune mice are immunized with DWEYS peptide, a DNA mimotope that elicits production of DNRAb antibodies, which act as positive allosteric modulators of the NMDAR. DNRAbs only enter the brain when the blood‐brain barrier is porous; so, we administer LPS, which breaches the blood‐brain barrier in the hippocampus. In this model, we discovered two stages of brain injury. In the first stage, lasting up to a week, we observed excitotoxic neuronal death, secondary to DNRAb‐mediated NMDAR activation. In the second stage, lasting months, we identified an inflammatory homeostasis, consisting of microglial activation, loss of dendritic arborization in surviving hippocampal neurons, and neuronal secretion of HMGB1, a chromatin protein that can be secreted to act as a damage‐associated molecular pattern (DAMP). Once secreted by neurons, HMGB1 interacts with two important receptors —RAGE and TLR4 — inducing a cascade of downstream inflammatory events. In addition, HMGB1 binds to the GluN2B subunit of NMDARs and the complement component C1q, forming a molecular bridge that facilitates synaptic pruning.Here we show that HMGB1 acts directly on microglia, where it activates microglia through RAGE and TLR4 signaling. We found that HMGB1 stimulates microglia to secrete IFNa, transcriptionally upregulating interferon regulatory factors, including IRF7. We also show that IFNa secreted by microglia acts in an autocrine fashion, regulating IFN‐response genes such as MX1; IFNa also induces C3 and C1q transcription in microglia. HMGB1 also stimulates microglia to secrete TNFa and IL‐1b, which enhances the inflammatory milieu in surrounding neurons.In addition, we found that the ACE‐inhibitor captopril reverses dendritic pruning in DWEYS‐immunized mice­­ — an essential component of the second stage of DNRAb‐related damage — by regulating expression of the inhibitory receptor LAIR1 in microglia. Whereas captopril reverses dendritic pruning in DWEYS‐immunized wildtype mice, captopril has no such effect on LAIR1 knockout mice. We are currently analyzing RNA sequencing data from microglia isolated from captopril‐treated, DWEYS immunized mice, to characterize the transcriptional program responsible for this process.

C57BL/6 Mouse Transgenic for Human MeCP2 as a Murine Model of Neuropsychiatric Lupus

Abstract Introduction Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). To dissect the underlying disease mechanism and to discover novel drug targets of NPSLE, a robust animal model of NPSLE is highly desirable. Methods C57BL/6 mice transgenic for human MeCP2 (B6.MECP2Tg1) were phenotyped, including autoantibody profiling, analysis of cellularity and activation of splenic immune cells, proteinuria, as well as neuropsychiatric functions. Results The protein expression and phosphorylation of MeCP2 were significantly elevated in the brain of a spontaneous lupus mouse model MRL/lpr, compared to normal B6 mice. The B6.MECP2Tg1 transgenic mice exhibited elevated proteinuria, increased proinflammatory cytokines, altered autoantibody profiles, augmented IgG deposition and macrophage infiltration in the kidney, compared to B6 mice. Effector memory T cells, germinal center B cells and plasma B cells were markedly increased in the female B6.MeCP2Tg1 mice. In addition, B6.MECP2Tg1 mice exhibited anxiety and depression-like behavior, as well as cognitive disorders as early as 9 weeks of age. The abnormal behaviors of the B6.MECP2Tg1 mice are associated with the aberrant neurogenesis and inflammation in the hippocampus, immune cell infiltration in the choroid plexus, as well as the disrupted blood-brain barrier (BBB) and activated microglia, as demonstrated by immunofluorescence microscopy. Conclusion Collectively, this work demonstrates that B6.MECP2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting it may represent a new animal model for NPSLE.

STREM-1 promotes the phagocytic function of microglia to induce hippocampus damage via the PI3K\u2013AKT signaling pathway

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a soluble form of TREM-1 released during inflammation. Elevated sTREM-1 levels have been found in neuropsychiatric systemic lupus erythematosus (NPSLE) patients; yet, the exact mechanisms remain unclear. This study investigated the role of sTREM-1 in brain damage and its underlying mechanism. The sTREM-1 recombinant protein (2.5 μg/3 μL) was injected into the lateral ventricle of C57BL/6 female mice. After intracerebroventricular (ICV) injection, the damage in hippocampal neurons increased, and the loss of neuronal synapses and activation of microglia increased compared to the control mice (treated with saline). In vitro. after sTREM-1 stimulation, the apoptosis of BV2 cells decreased, the polarization of BV2 cells shifted to the M1 phenotype, the phagocytic function of BV2 cells significantly improved, while the PI3K–AKT signal pathway was activated in vivo and in vitro. PI3K–AKT pathway inhibitor LY294002 reversed the excessive activation and phagocytosis of microglia caused by sTREM-1 in vivo and in vitro, which in turn improved the hippocampus damage. These results indicated that sTREM-1 activated the microglial by the PI3K–AKT signal pathway, and promoted its excessive phagocytosis of the neuronal synapse, thus inducing hippocampal damage. sTREM-1 might be a potential target for inducing brain lesions.

Pseudotumor cerebri syndrome in children with systemic lupus erythematosus: case series and review

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that typically affects multiple organs and can lead to potentially fatal complications. Central nervous system (CNS) involvement in SLE is common, especially in children, and can present nonspecifically with various neuropsychiatric manifestations, described as neuropsychiatric SLE (NPSLE). Chronic headache is a common feature of NPSLE, secondary to increased intracranial pressure (also called pseudotumor cerebri (PTC)) due to inflammation or medication. Here, we highlight the importance of evaluating refractory headache (HA) in SLE patients to rule out PTC as a cause of severe morbidity.MethodsSingle tertiary care pediatric center case series of 8 children who developed NPSLE in the form of intracranial hypertension at or after SLE diagnosis.ConclusionNeurologic and ophthalmologic evaluation of refractory HA in patients with SLE, especially children, is warranted to decrease the burden of the disease and rule out treatable causes like PTC.

Autoantibodies against specific post-translationally modified proteins are present in patients with lupus and associate with major neuropsychiatric manifestations

BackgroundAlthough autoantibodies are an important hallmark of systemic lupus erythematosus (SLE), most are not specific for SLE or any of its clinical manifestations. Autoantibodies against post-translationally modified (PTM) proteins have...

Cerebrovascular changes in neuro-Behcet's disease and neuropsychiatric lupus by transcranial Doppler ultrasonography and magnetic resonance imaging

IntroductionTranscranial Doppler ultrasonography (TCD) is a technique that allows measurement of blood flow from the basal intracerebral vessels. It is relatively inexpensive, non-invasive, can be performed at the bedside, and allows monitoring in acute emergency settings and for prolonged periods with a high temporal resolution, making it ideal for studying the haemodynamics within the intracranial arteries in neuro-Behcet's disease (NBD) and neuro-psychiatric lupus (NPSLE). Our aim was to assess the cerebral haemodynamic patterns in patients with NBD and NPSLE using TCD, while brain lesions were examined using magnetic resonance imaging (MRI). Material and methodsCase–control prospective study of 30 neuro-Behcet's disease patients, 25 neuro-psychiatric lupus patients and 26 healthy age-matched volunteers. All patients and healthy controls were examined by TCD. Only the groups of patients underwent cranial magnetic resonance imaging (MRI). ResultsTranscranial Doppler (TCD) values for middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), vertebral artery (VA) and basilar artery (BA) in NBD, NPSLE and control groups were measured. The results showed that there was a significant decrease in mean blood flow velocities in all the arteries examined in NBD and NPSLE patients. There was also a significant increase in the pulsatile index of PCA, VA and BA between NBD and NPSLE patients. The same results were obtained when comparing NBD versus controls. However, there was no significant difference between the NPSLE patients and the control group. The MRI lesions described were parenchymal lesions in 14 patients (46.7%), and vascular lesions in 4 patients (13.3%). Vascular lesions co-existed with parenchymal lesions (mixed lesion). Parenchymal lesions were in white matter (40%), thalamus (26.7%), brain stem (26.7%) and cerebellum (20%). While, in NPSLE, 23 patients were normal (92%) and only two patients had a vascular lesion (8%). ConclusionThere was a significant decrease in mean blood flow and a significant increase in the pulsatile index among both NBD and NPSLE patients, according to the TCD values.

Neuropsychiatric Systemic Lupus Erythematosus Presenting as Mania With Psychosis Treated Successfully With Intravenous Immunoglobulin: A Diagnosis of Associations and Exclusions.

Neuropsychiatric Systemic Lupus Erythematosus Presenting as Mania With Psychosis Treated Successfully With Intravenous Immunoglobulin: A Diagnosis of Associations and Exclusions.

Measurement of anti-suprabasin antibodies, multiple cytokines and chemokines as potential predictive biomarkers for neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) varies in presentation and is one of the leading causes of morbidity and mortality among patients with SLE. This study determined the most critical serum biomarkers for the development of NPSLE as they may have clinical utility prior to the onset of neuropsychiatric symptoms. We retrospectively analyzed 35 NPSLE patients, 34 SLE patients, 20 viral meningitis (VM) patients, and 16 relapsing-remitting multiple sclerosis (MS) patients. We measured anti-suprabasin antibodies concentrations in serum by using Luciferase immunoprecipitation system (LIPS) assay. The serum concentrations of cytokines/chemokines were measured by using multiplex bead-based assay. We found serum FGF-2 level was significantly higher in the NPSLE group compared to the SLE group and the healthy control group. The anti-suprabasin antibody relative concentration (SRC) has high positive predictive values for the development of NPSLE. The most essential biomarkers are VEGF, anti-suprabasin antibodies, sCD40L, IL-10, GRO, MDC, IL-8, IL-9, TNF-α, MIP-1α.

The expanding role of synthetic nucleic acids for diagnosis and treatment.

The presence of autoantibodies is a characteristic and diagnostic index of systemic lupus erythematosus (SLE). Antidouble-stranded DNA (antids-DNA) antibodies are the most frequent autoantibodies found in SLE related to the diagnosis and disease activity of SLE, and are measured by established methods like ELISA as a polyclonal autoantibody. However, there is no reliable data on the relationship between the respective reactivity of these polyclonal antids-DNA antibodies against different epitopes generated from the original antigen and the disease phenotype. Of the complications in SLE, neuropsychiatric SLE (NPSLE) is a troublesome and frequent phenotype of the disease but no specific diagnostic autoantibodies in serum have been found. First in this review, the possibility of antids-DNA antibodies for identifying primary NPSLE in patients with SLE based on the reactivity of different synthetic nucleic acids is described as a diagnostic marker. The purpose of this review is to examine diagnostic and therapeutic opportunities to modulate autoimmune in the central nervous system (CNS) developing the CNS inflammatory disorders. Khatri et al. investigated antids-DNA antibodies in order to develop a reliable method based on the application of synthetic nucleic acids and protein-based antigen arrays to characterize autoreactive antibodies specially for NPSLE. They found autoantibodies in three particular synthetic double stranded antigens and the antinuclear antibody patterns in ordinary lupus and NPSLE. These discoveries are leading to precision medicine in the CNS inflammatory disorders. Verifying the similarity of antids-DNA obtained from patients with NPSLE can be useful as a diagnostic marker. mRNA vaccination can locally suppress autoimmunity in the CNS associated with critical steps for the develop of CNS autoinflammation. Synthetic nuclei acids may provide a diagnostic and therapeutic target in patients with autoimmune CNS inflammatory disorders.

Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus.

Background:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients.Methods:This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, i.e., with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis.Results:Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P < 0.001). In addition, the patients with hyperintense WM lesions exhibited a higher frequency of proteinuria (P = 0.009) and higher levels of CD8+ T cells (P = 0.005). In the multivariate logistic analysis, hyperuricemia and higher CD8+ T cells percentages were significantly correlated with hyperintense WM lesions in SLE patients (P = 0.019; OR 2.129, 95% confidence interval [CI] 1.313–4.006 and P < 0.001; OR 1.056, 95% CI 1.023–1.098, respectively).Conclusions:Hyperintense WM lesions are common in SLE patients and significantly associated with systemic involvement, including NPSLE, LN, polyserous effusions, cardiac involvement, and disease damage. Hyperuricemia and a higher number of CD8+ T cells were independent factors associated with hyperintense WM lesions in SLE.

Relationship Between Vitamin D Status and Brain Perfusion in Neuropsychiatric Lupus.

Neuropsychiatric manifestation of lupus (NPSLE) is related with vitamin D (vit-D) deficiency which is possibly amenable to supplementation. This study was done to explore link of serum vit-D level and clinical mini-mental state examination (MMSE) with brain perfusion SPECT (BS) in patients with NPSLE. Patients who underwent BS with the diagnosis of NPSLE and had serum levels of vit-D and MMSE within a span of 1 month were retrospectively included. The BS DICOM data were used to generate 3D surface images of brain for visual identification of regional hypoperfusion, and the z-scores from eZIS software and then to perform voxel-based regression analysis in order to explore association between serum vit-D level and cerebral perfusion deficit using SPM8. Distribution of serum vit-D level was checked across MMSE and BS z-score using R. A total 19 patients with means ± SD age of 28.4 ± 9.2 years, having mean levels of serum vit-D of 18.7 ± 9.8 ng/ml and mean MMSE scores 24.2 ± 1.6, had undergone BS. The eZIS-derived z-score fall in the category of normal in six (31.6%), mild perfusion deficit (PD) in 10 (52.6%) and moderate PD in three (15.8%) with the means ± SD of z-score being 0.52 ± 0.2, 1.72 ± 0.2, and 2.33 ± 0.2. Voxel-based analysis revealed significant positive correlation between vit-D level and hypoperfusion in brain regions related to cognitive function (p<0.05). Serum vit-D levels were significantly lower in NPSLE patients with lower MMSE scores as well as in higher eZIS z-score (p < 0.01). Our results may support the utility of vit-D supplementation in NPSLE and applicability of BS as a clinical adjunct for monitoring response to vit-D supplementation.

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.