Neuropsychiatric Systemic Lupus Erythematosus Group Research Articles

Correlation between the changes of brain amplitude of low-frequency fluctuation and cognitive impairment in patients with neuropsychiatric lupus.

To explore the relationship between brain function changes and clinical serological indicators and behavioral cognitive assessment in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), and understand the pathogenesis of NPSLE from the perspective of imaging. The resting-state functional imaging data, clinical serological, and behavioral cognitive assessment scores of 28 patients with NPSLE and 22 healthy controls (HC) were prospectively collected. The resting-state amplitude of low-frequency fluctuation (ALFF) values obtained from the analysis and processing were correlated with the serological data and behavioral cognitive assessment scores to determine the relationship between these data. The average age of the patients of the NPSLE group was older than that of the HC group; significant differences in education level, Auditory Verbal Learning Test Hua Shan Version (AVLT-H), and Trail Making Test scores were observed between the two groups. The NPSLE group demonstrated increased brain activity in the insula, precentral gyrus, and superior temporal gyrus, and decreased brain activity in the superior parietal gyrus. The ALFF value of the insula positively correlated with the Anti-β2gp1 antibody and negatively correlated with the anti-nucleosome antibody and the AVL-recall (RC) score. The ALFF of the precentral gyrus negatively correlated with the AVL-immediate recall (I). The ALFF value of the superior temporal gyrus negatively correlated with the AVL-RC score. The left superior parietal gyrus positively correlated with the c-reactive protein. The right superior parietal gyrus positively correlated with the System Lupus Erythematosus Disease Activity Index and negatively correlated with the AVL-I score. Patients with NPSLE show different brain activity changes in different brain regions, and the abnormal brain regions are correlated with certain lupus antibodies, inflammatory factors, and cognitive assessment, thereby suggesting that the correlation between the three could provide novel insights into the pathogenesis of NPSLE.

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.

Cortical thickness and diffusion tensor imaging in patients with neuropsychiatric systemic lupus erythematosus, with normal structure on brain MRI.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with adverse outcomes; however, imaging abnormalities are only detectable by conventional brain magnetic resonance imaging (MRI) in up to 50% of patients. This study investigated the variability in cortical thickness and diffusion tensor imaging (DTI) parameters among patients with NPSLE whose brain morphology appeared normal on conventional MRI. This retrospective study enrolled 27 female patients with NPSLE (median age: 41.0 years, range: 22-63years) and 34 female healthy controls (median age: 37.0years, range: 24-55years). None exhibited evident abnormalities on conventional MRI. Regional volumes, cortical thickness, and DTI parameters, including fractional anisotropy (FA) and mean diffusivity (MD), were compared. Age-adjusted multivariable logistic regression analysis was conducted to detect significant NPSLE-associated differences. No significant differences in grey or white matter volume fractions were observed between the groups. However, the NPSLE group demonstrated significant cortical thinning in the right pars opercularis (2.45 vs 2.52mm, p = 0.007), reduced FA values in the fornix (0.35 vs 0.40, p = 0.001) and left anterior limb of internal capsule (0.50 vs 0.52, p = 0.012), and increased MD in the fornix (1.71 vs 1.48, p = 0.009) and left posterior corona radiata (0.80 vs 0.76, p = 0.005) compared with those of healthy controls. Cortical thickness measurements and DTI analyses can be used to detect differential variations in patients with NPSLE who exhibit an otherwise normal brain structure on conventional MRI, indicating the existence of subtle changes despite the absence of obvious macrostructural central nervous system involvement of lupus.

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.

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.

Cerebral blood flow abnormalities in neuropsychiatric systemic lupus erythematosus.

To investigate the clinical characteristics, imaging changes and early diagnostic methods of neuropsychiatric systemic lupus erythematosus (NPSLE). Thirty-five SLE patients, of which 16 had overt neuropsychiatric symptoms, underwent examination for multiple autoantibodies, including anti-double-stranded DNA (anti-dsDNA) antibody, anti-nucleosome antibody, anti-cardiac-phospholipid antibody (aCL)-IgG, aCL-IgM, anti-β2-glycoprotein I antibody and anti-ribosomal P antibody, and the SLEDAI score of every patient was recorded. All patients further received neuropsychological tests, including the Mini-Mental State Examination, the Self-Rating Anxiety Scale and the Self-Rating Depression Scale. Imaging examination using 3D arterial spin labeling was performed on 3.0 T MRI scanners. After processing the 3D arterial spin labeling image, the cerebral blood flow map was obtained and the cerebral blood flow value was calculated. The values of anti-dsDNA, anti-nucleosome antibody, aCL-IgG and anti-β2-glycoprotein I antibodies were significantly higher in the NPSLE group than those in the SLE group. The SLEDAI scores of the NPSLE group were significantly higher than those of the SLE group. There were no significant differences between the NPSLE group and the SLE group in the directional ability, memory, attention, numeracy, recall ability or language ability scores on the Mini-Mental State Examination scale. Furthermore, there were no symptoms of anxiety or depression in any of the patients, according to the Self-Rating Anxiety Scale and Self-Rating Depression Scale. In the 35 patients with SLE, decreases in blood perfusion were seen in some areas, and were unilateral and asymmetrically distributed. There was obvious asymmetry between sides in areas including the frontal lobe, temporal lobe, parietal lobe and occipital lobe. The incidence of perfusion decreases in frontal lobe in the NPSLE group was significantly higher than in the SLE group. Neurological lesions in SLE patients can be detected by arterial spin labeling. Cerebral blood flow abnormalities may be helpful for the early diagnosis of neurological lesions in NPSLE.

Identification of Levels of Serum Amyloid A and Apolipoprotein A1 in Serum Proteomic Analysis of Neuropsychiatric Systemic Lupus Erythematosus Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) has multiple pathogenic mechanisms that cause diverse manifestations and whose diagnosis is challenging because of the absence of appropriate diagnostic tests. In the present study the application of proteomics using two-dimensional electrophoresis (2D) and mass spectrometry (MS) allowed the comparison of the protein profile of the serum low and high abundance protein fractions of NPSLE patients (NPSLE group) and SLE without neuropsychiatric syndromes (SLE group), Neuropsychiatric syndromes not associated with SLE (NPnoSLE groups), and healthy controls (CTRL group). The gels obtained were digitalized and analyzed with the PDQuest software. The statistical analysis of the spots was performed using the nonparametric Kruskal Wallis and Dunn's multiple comparison tests. Two spots showed significant differences and were identified by MS. Spot 4009 was significantly lower in NPSLE with regard to NPnoSLE (p= 0,004) and was identified as apolipoprotein A1 (APOA1) (score 809-1132). Spot 8001 was significantly higher in NPSLE regarding CTRL and NPnoSLE (p= 0,01 y 0,03, respectively) and was identified as serum amyloid A (SAA) (score 725-2488). The proinflammatory high density lipoproteins (HDL) have been described in SLE. In this HDL the decrease of APOA1 is followed by an increase in SAA. This altered level of both proteins may be related to the inflammatory state that is characteristic of an autoimmune disease like SLE, but this is not specific for NPSLE.

Novel anti-suprabasin antibodies may contribute to the pathogenesis of neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is often difficult to diagnose and distinguish from other diseases, because no NPSLE-specific antibodies have been identified. We developed a novel proteomic strategy for identifying and profiling antigens in immune complexes in the cerebrospinal fluid (CSF), and applied this strategy to 26 NPSLE patients. As controls, we also included 25 SLE patients without neuropsychiatric manifestations (SLE), 15 with relapsing remitting multiple sclerosis (MS) and 10 with normal pressure hydrocephalus (NPH). We identified immune complexes of suprabasin (SBSN) in the CSF of the NPSLE group. The titer of anti-SBSN antibodies was significantly higher in the CSF of the NPSLE group compared to those of the SLE, MS and NPH groups. Microarray data showed that the senescence and autophagy pathways were significantly changed in astrocytes exposed to anti-SBSN antibodies. Our findings indicate that SBSN could be a novel autoantibody for the evaluation of suspected NPSLE.

[The clinical significance of anti- ubiquitin C-terminal hydrolase L1 autoantibodies in the diagnosis of neuropsychiatric systemic lupus erythematosus].

Objective: To analyze the clinical significance of anti- ubiquitin C-terminal hydrolase L1(UCHL-1)autoantibodies in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods: Autoantibodies in cerebrospinal fluid specimen of 56 inpatients were detected by using indirect enzyme-linked immunosorbent assay (ELISA) and the fullmedical history and clinical manifestations were analyzed retrospectively. Results: The levels of anti-UCHL-1 autoantibodies in NPSLE group were significant higher than that in other controls (P<0.05). The positive rate of anti-UCHL-1 autoantibodies in NPSLE group was 23.7% (9/38), which was higher than that in the control groups (0%). A significant difference of anti-UCHL-1 autoantibodies was observed in the patients with blood system involvement (P=0.012). The positive rates of anti-UCHL autoantibodies in the patients with negative SLE related autoantibodies including AnuA, anti-dsDNA, Acl, anti-nRNP, anti-rRNP and anti-Smantibody negative were 41.7%, 29.4%, 29.2%, 25.9%, 25.0%, 25.0%, respectively.The levels of anti-UCHL-1 autoantibodies had a positive correlation with 24-hours proteinuria (r=0.361, P=0.039). Conclusion: Anti-UCHL-1 autoantibodies had promising value in the diagnosis of neuropsychiatric systemic lupus erythematosus.

The Neurochemical and Microstructural Changes in the Brain of Systemic Lupus Erythematosus Patients: A Multimodal MRI Study.

The diagnosis and pathology of neuropsychiatric systemic lupus erythematosus (NPSLE) remains challenging. Herein, we used multimodal imaging to assess anatomical and functional changes in brains of SLE patients instead of a single MRI approach generally used in previous studies. Twenty-two NPSLE patients, 21 non-NPSLE patients and 20 healthy controls (HCs) underwent 3.0 T MRI with multivoxel magnetic resonance spectroscopy, T1-weighted volumetric images for voxel based morphometry (VBM) and diffusional kurtosis imaging (DKI) scans. While there were findings in other basal ganglia regions, the most consistent findings were observed in the posterior cingulate gyrus (PCG). The reduction of multiple metabolite concentration was observed in the PCG in the two patient groups, and the NPSLE patients were more prominent. The two patient groups displayed lower diffusional kurtosis (MK) values in the bilateral PCG compared with HCs (p < 0.01) as assessed by DKI. Grey matter reduction in the PCG was observed in the NPSLE group using VBM. Positive correlations among cognitive function scores and imaging metrics in bilateral PCG were detected. Multimodal imaging is useful for evaluating SLE subjects and potentially determining disease pathology. Impairments of cognitive function in SLE patients may be interpreted by metabolic and microstructural changes in the PCG.

Impact analysis of autoantibody level and NR2 antibody level in neuropsychiatric SLE treated by methylprednisolone combined with MTX and DXM intrathecal injection.

The objective is to explore the clinical curative effects of methylprednisolone combined with MTX and DXM intrathecal injection in treating neuropsychiatric systemic lupus erythematosus (NPSLE) and its effects on autoantibody level and anti-N-methyl-D-aspartate receptor subtype NR2a/2b antibody (anti-NR2 antibody) level. Thirty six admitted NPSLE patients were treated by methylprednisolone combined with MTX and DXM intrathecal injection. Thirty six SLE patients without neuropsychiatric symptoms were selected as non-NPSLE group. Clinical indexes including SLE activity index, erythrocyte sedimentation rate (ESR), cerebrospinal fluid pressure (CSFP), cerebrospinal fluid protein were observed before and after treatment. Autoantibodies including anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA antibody), anti-extractable nuclear antigen antibody (ENA-Ab) were detected before and after treatment. Enzyme linked immunosorbent assay was used to detect NR2 antibody level before and after treatment in two groups. Upon treatment of methylprednisolone combined with MTX and DXM intrathecal injection, SLE activity index, ESR, CSFP, cerebrospinal fluid protein of 36 NPSLE patients were significantly decreased. Before treatment, positive rates of ANA, anti-dsDNA antibody, and anti-ENA antibody in both NPSLE group and non-NPSLE group had no significant difference. However, positive rate of anti-NR2 antibody in NPSLE group was significantly higher than that of non-NPSLE group. After treatment, positive rates of autoantibodies and anti-NR2 antibody in both NPSLE and non-NPSLE group were significantly decreased. Anti-NR2 antibody can be a screening index of NPSLE, and methylprednisolone combined with MTX and DXM intrathecal injection has significant curative effects and can effectively decrease autoantibody level and anti-NR2 antibody level.

Cortical thickness and subcortical gray matter reductions in neuropsychiatric systemic lupus erythematosus.

Within systemic lupus erythematosus (SLE) patients can be divided into groups with and without central nervous system involvement, the latter being subcategorized as neuropsychiatric systemic lupus erythematosus (NPSLE). While a number of research groups have investigated NPSLE, there remains a lack of consistent application of this diagnostic criteria within neuroimaging studies. Previous neuroimaging research suggests that SLE patients have reduced subcortical and regional gray matter volumes when compared to controls, and that these group differences may be driven by SLE patients with neuropsychiatric symptoms. The current study sought to compare measures of cortical thickness and subcortical structure volume between NPSLE, SLE, and healthy controls. We hypothesized that patients with NPSLE (N = 21) would have thinner cortex and reduced subcortical gray matter volumes when compared to SLE (N = 16) and control subjects (N = 21). All subjects underwent MRI examinations on a 1.5 Tesla Siemens Sonata scanner. Anatomical reconstruction and segmentation were performed using the FreeSurfer image analysis suite. Cortical and subcortical volumes were extracted from FreeSurfer and analyzed for group differences, controlling for age. The NPSLE group exhibited decreased cortical thickness in clusters of the left frontal and parietal lobes as well as in the right parietal and occipital lobes compared to control subjects. Compared to the SLE group, the NPSLE group exhibited comparable thinning in clusters of the frontal and temporal lobes. Controlling for age, we found that between group effects for subcortical gray matter structures were significant for the thalamus (F = 3.06, p = .04), caudate nucleus (F = 3.19, p = .03), and putamen (F = 4.82, p = .005). These results clarify previous imaging work identifying cortical atrophy in a mixed SLE and NPSLE group, and suggest that neuroanatomical abnormalities are specific to SLE patients diagnosed with neuropsychiatric symptoms. Future work should help elucidate the underlying mechanisms underlying the emerging neurobiological profile seen in NPSLE, as well as clarify the apparent lack of overlap between cortical thinning and functional activation results and other findings pointing to increased functional activation during cognitive tasks.

Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFalpha, IFN gamma, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus.

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects. Levels of uPA, tPA, and PAI-1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non-NPSLE group]) and from 53 age-matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing. In the group of patients with NPSLE, intrathecal PAI-1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI-1 correlated significantly with CSF levels of interleukin-6 (IL-6) (r = 0.34, P < 0.001) and IL-8 (r = 0.33, P < 0.001). Importantly, increased PAI-1 and D-dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF. Intrathecal release of PAI-1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.

Comparison of the Clinical Manifestations, Brain MRI and Prognosis between NeuroBehçet's Disease and Neuropsychiatric Lupus

BackgroundNeuropsychiatric systemic lupus erythematosus (NPSLE) shows some similarities to neuroBehçet's disease (NBD) in that both conditions have some analogous clinical features and they are both pathologically associated cerebral vasculopathy. This study compared the clinical manifestations, brain MRI findings and prognosis of NPSLE and NBD patients.MethodsForty three patients with NPSLE (n = 25) or NBD (n = 18), who were monitored at a single center, were enrolled in this study. We retrospectively analyzed the clinical and brain MRI data. The neuropsychiatric manifestations were classified in both groups according to the new American College of Rheumatology nomenclature for NPSLE.ResultsThe diffuse symptoms that included mood disorders, psychosis, confusion, cognitive dysfunctions, generalized seizures and headaches other than migraine or cluster headaches were more commonly observed in the NPSLE patients, while the frequency of focal diseases such as cranial neuropathy tended to be higher in the NBD patients. The brain MRI revealed that the NBD patients had more abnormalities in the brain stem than did the NPSLE patients. Most of the patients improved, at least partially, after being treated with glucocorticoid and/or immune suppressants. However, the disease course differed significantly between the two groups. There were more episodic cases in the NPSLE group of patients, while there were more remittent cases in the NBD group of patients.ConclusionNPSLE had a tendency to cause diffuse neuropsychiatric manifestations, and it has a different predilection of brain lesions compared with NBD. The NBD patients showed a poorer outcome than did the NPSLE patients, suggesting that different therapeutic strategies for the two diseases need to be considered.

Clinical significance of neuro-reactive autoantibodies in neuro-psychiatric systemic lupus erythematosus

To investigate the clinical significance of specific/non-specific neuro-reactive autoantibodies in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). Samples of serum and cerebrospinal fluid (CSF) were collected from 25 NPSLE patients, 11 patients with SLE complicated with central nervous system (CNS) infection (control group 1), and 10 SLE patients without CNS infection (non-NPSLE, control group 2)) were detected, Indirect immunofluorescence technique was used to detect the anti-nuclear antibody (ANA) based on the slides with human epithelium cell of laryngocarcinoma of the line Hep-2 or on the slides with cerebellum and peripheral nerve of monkey, he type of immunofluorescence were assayed. The percentages of ANA positive serum of the NPSLE, SLE control 1, and SLE control 2 groups were 92% (23/25), 100% (11/11), and 100% (10/10) respectively without significant differences between any 2 groups (all P > 0.05). The percentage of ANA positive CSF of the NPSLE was 60% (15/25), significantly higher than that of the SLE control group 1 (27%, 3/11, P < 0.01). There was no significant correlation between the titer of serum ANA and the titer of CSF ANA (P > 0.05). The positive rate of neuro-reactive autoantibodies was 40% (10/25), significantly higher than those of the 2 control groups (both 0, both P > 0.001). (1) The ANA positivity in the CSF of the NPSLE group is associated with the disease activity and CNS involvement, the higher the titer of autoantibodies the severe the clinical manifestations. (2) The neuro-reactive autoantibodies in the serum may associate with NPSLE with still unknown mechanism.

Detection of cerebral involvement in patients with active neuropsychiatric systemic lupus erythematosus by the use of volumetric magnetization transfer imaging

To determine whether volumetric magnetization transfer imaging (MTI) histogram analysis can detect abnormalities in patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) and to compare the MTI findings in patients with active NPSLE, chronic NPSLE, and multiple sclerosis (MS), as well as in normal control subjects. Eight female and 1 male patient with active nonthromboembolic NPSLE (mean +/- SD age 39 +/- 9 years), 10 female patients with chronic NPSLE (age 33 +/- 11 years), 10 female patients with SLE and no history of NPSLE (non-NPSLE; age 34 +/- 11 years), 10 female patients with inactive MS (age 41 +/- 6 years), and 10 healthy control subjects (age 33 +/- 11 years) underwent MTL. Using the MTI scans, histograms were composed from which we derived a variety of parameters that quantitatively reflect the uniformity of the brain parenchyma as well as the ratio of cerebrospinal fluid to intracranial volume, which reflects atrophy. The magnetization transfer ratio (MTR) histograms in the non-NPSLE group and the healthy control group were similar, whereas those in the chronic NPSLE and MS groups were flatter. There was also flattening of the histograms in the active NPSLE group, but with a shift toward higher MTRs. Our results indicate that volumetric MTI analysis detects cerebral changes in the active phase of NPSLE. The abnormalities in the brain parenchyma of patients with chronic NPSLE produced MTI values that were the same as those in patients with inactive MS. MTI values in the active phase of NPSLE differed from those in the chronic phase, which might reflect the presence of inflammation. These preliminary results suggest that MTI might provide evidence for the presence of active NPSLE. MTI might also prove to be a valuable technique for monitoring treatment trials.

Evidence of central nervous system damage in patients with neuropsychiatric systemic lupus erythematosus, demonstrated by magnetization transfer imaging.

The clinical symptoms of neuropsychiatric systemic lupus erythematosus (NPSLE) are usually reversible, but whether the associated brain damage is also reversible is still a matter of debate. Since magnetization transfer imaging (MTI) is more sensitive than conventional magnetic resonance imaging (MRI) in demonstrating brain damage, it has become a useful tool in the detection and quantification of diffuse brain disorders such as multiple sclerosis. In this study, MTI was applied to investigate whether central nervous system (CNS) damage is present in patients with a history of NPSLE. Eleven female patients with a history of NPSLE and no previous or concurrent primary neurologic or psychiatric disease (ages 17-49 years), 11 female patients with SLE without a history of NPSLE (non-NPSLE; ages 15-51 years), and 10 healthy female controls (ages 17-47 years) underwent MTI. From these MTI scans, quantitative data on the uniformity of the brain parenchyma and atrophy were derived. One NPSLE and 1 non-NPSLE patient were excluded from this study due to infarctions detected with conventional MRI. MTI measures normalized for intracranial volume, reflecting abnormalities of the brain parenchyma as well as atrophy, were lower (P < 0.001) in the NPSLE group than in both control groups. A higher (P < 0.005) mean ratio of cerebrospinal fluid to intracranial volume, indicative of atrophy, was present in the NPSLE group compared with either the non-NPSLE patients or healthy controls. Still, the MTI measures solely reflecting uniformity of the brain parenchyma (normalized for brain volume) were also significantly (P < 0.001) lower in the NPSLE patients than in both control groups. This study demonstrates that using MTI, CNS damage can be demonstrated in patients with a history of NPSLE. MTI might, therefore, be an alternative and sensitive tool to detect brain injury in NPSLE, and might also be useful in studying the natural history of the disease.