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1.
Clinics (Sao Paulo) ; 75: e1515, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321114

RESUMO

This study aimed to systematically review neuropsychiatric lupus erythematosus (NPSLE) and establish a simplified diagnostic criterion for NPSLE. Publications from 1994 to 2018 in the database (Wanfang data (http://www.wanfangdata.com.cn/index.html) and China National Knowledge Internet (http://www.cnki.net)) were included. In total, 284 original case reports and 24 unpublished cases were collected, and clinical parameters were analyzed. An attempt was made to develop a set of simplified diagnostic criteria for NPSLE based on cases described in the survey and literature; moreover, and pathophysiology and management guidelines were studied. The incidence rate of NPSLE was estimated to be 12.4% of SLE patients in China. A total of 408 NPSLE patients had 652 NP events, of which 91.2% affected the central nervous system and 8.8% affected the peripheral nervous system. Five signs (manifestations, disease activity, antibodies, thrombosis, and skin lesions) showed that negative and positive predictive values were more than 70%, included in the diagnostic criteria. The specificity, accuracy, and positive predictive value (PPV) of the revised diagnostic criteria were significantly higher than those of the American College of Rheumatology (ACR) criteria (χ2=13.642, 15.591, 65.010, p<0.001). The area under the curve (AUC) for revised diagnostic criteria was 0.962 (standard error=0.015, 95% confidence intervals [CI] =0.933-0.990), while the AUC for the ACR criteria was 0.900 (standard error=0.024, 95% CI=0.853-0.946). The AUC for the revised diagnostic criteria was different from that for the ACR criteria (Z=2.19, p<0.05). Understanding the pathophysiologic mechanisms leading to NPSLE is essential for the evaluation and design of effective interventions. The set of diagnostic criteria proposed here represents a simplified, reliable, and cost-effective approach used to diagnose NPSLE. The revised diagnostic criteria may improve the accuracy rate for diagnosing NPSLE compared to the ACR criteria.


Assuntos
Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , China , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Reumatologia , Inquéritos e Questionários
2.
Arthritis Rheumatol ; 72(7): 1134-1142, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32017464

RESUMO

OBJECTIVE: To identify potential clusters of systemic lupus erythematosus (SLE) organ-specific flares and their relationship to fine particulate matter pollution (PM2.5), temperature, ozone concentration, resultant wind, relative humidity, and barometric pressure in the Hopkins Lupus Cohort, using spatiotemporal cluster analysis. METHODS: A total of 1,628 patients who fulfilled the Systemic Lupus International Collaborating Clinics classification criteria for SLE and who had a home address recorded were included in the analysis. Disease activity was assessed using the Lupus Activity Index. Assessment of rash, joint involvement, serositis, and neurologic, pulmonary, renal, and hematologic activity was quantified on a 0-3 visual analog scale (VAS). An organ-specific flare was defined as an increase in VAS of ≥1 point compared to the previous visit. Spatiotemporal clusters were detected using SaTScan software. Regression models were used for cluster adjustment and included individual, county-level, and environmental variables. RESULTS: Significant clusters unadjusted for environmental variables were identified for joint flares (P < 0.05; n = 3), rash flares (P < 0.05; n = 4), hematologic flares (P < 0.05; n = 3), neurologic flares (P < 0.05; n = 2), renal flares (P < 0.001; n = 4), serositis (P < 0.001; n = 2), and pulmonary flares (P < 0.001; n = 2). The majority of the clusters identified changed in significance, temporal extent, or spatial extent after adjustment for environmental variables. CONCLUSION: We describe the first spatiotemporal clusters of lupus organ-specific flares. Seasonal, as well as multi-year, cluster patterns were identified, differing in extent and location for the various organ-specific flare types. Further studies focusing on each individual organ-specific flare are needed to better understand the driving forces behind these observed changes.


Assuntos
Poluição do Ar/estatística & dados numéricos , Pressão Atmosférica , Lúpus Eritematoso Sistêmico/fisiopatologia , Material Particulado , Exacerbação dos Sintomas , Tempo (Meteorologia) , Adulto , Artrite/fisiopatologia , Estudos de Coortes , Exantema/fisiopatologia , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Umidade , Pneumopatias/fisiopatologia , Nefrite Lúpica/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Ozônio , Serosite/fisiopatologia , Análise Espaço-Temporal , Temperatura , Vento
4.
Arthritis Rheumatol ; 72(1): 67-77, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390162

RESUMO

OBJECTIVE: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. RESULTS: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. CONCLUSION: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.


Assuntos
Doenças dos Nervos Cranianos/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Fatores Etários , Estudos de Coortes , Doenças dos Nervos Cranianos/etiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Mononeuropatias/etiologia , Mononeuropatias/fisiopatologia , Análise Multivariada , Doenças do Sistema Nervoso Periférico/etiologia , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Adulto Jovem
5.
J Cell Mol Med ; 23(11): 7382-7394, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31536674

RESUMO

Involvement of the central nervous system (CNS) is an uncommon feature in systemic lupus erythematosus (SLE), making diagnosis rather difficult and challenging due to the poor specificity of neuropathic symptoms and neurological symptoms. In this work, we used human-induced pluripotent stem cells (hiPSCs) derived from CNS-SLE patient, with the aim to dissect the molecular insights underlying the disease by gene expression analysis and modulation of implicated pathways. CNS-SLE-derived hiPSCs allowed us to provide evidence of Erk and Akt pathways involvement and to identify a novel cohort of potential biomarkers, namely CHCHD2, IDO1, S100A10, EPHA4 and LEFTY1, never reported so far. We further extended the study analysing a panel of oxidative stress-related miRNAs and demonstrated, under normal or stress conditions, a strong dysregulation of several miRNAs in CNS-SLE-derived compared to control hiPSCs. In conclusion, we provide evidence that iPSCs reprogrammed from CNS-SLE patient are a powerful useful tool to investigate the molecular mechanisms underlying the disease and to eventually develop innovative therapeutic approaches.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Biomarcadores/metabolismo , Feminino , Expressão Gênica/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , MicroRNAs/metabolismo , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia
6.
Lupus ; 28(13): 1510-1523, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31474191

RESUMO

OBJECTIVE: Many systemic lupus erythematosus patients display a type I interferon (IFN) signature, and IFNα levels positively correlate with disease severity. Previous studies blocking the type I IFN pathway systemically in lupus models showed some beneficial effects. However, its effects on neuropsychiatric manifestations have yet to be carefully assessed, even though IFNα has been associated with induction of depression. Our aim was to investigate whether disrupting the type I IFN pathway would attenuate the development of murine neuropsychiatric lupus. METHODS: Female MRL/lpr mice were administered an antitype I IFN receptor (IFNAR) antibody or a control antibody intraperitoneally three times weekly for 12 weeks starting at age 4-5 weeks. Behavior was assessed during and at the end of the treatment schedule. RESULTS: No significant differences were seen between the anti-IFNAR- and control-treated mice when assessing for depression-like behavior or cognitive dysfunction, although anti-IFNAR antibody-treated mice displayed significant decreases in levels of IFN-stimulated genes. Anti-IFNAR treatment also did not significantly improve brain histology, cellular infiltration, or blood-brain barrier integrity. CONCLUSIONS: Surprisingly, our results showed no improvement in neuropsychiatric disease and suggest that the role of IFNAR signaling in the pathogenesis of neuropsychiatric lupus continues to need to be carefully assessed.


Assuntos
Anticorpos/administração & dosagem , Lúpus Eritematoso Sistêmico/terapia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Receptor de Interferon alfa e beta/imunologia , Animais , Anticorpos/imunologia , Comportamento Animal , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Depressão/etiologia , Depressão/terapia , Modelos Animais de Doenças , Feminino , Interferon Tipo I/imunologia , Interferon-alfa/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Camundongos , Camundongos Endogâmicos MRL lpr , Índice de Gravidade de Doença
7.
Lupus ; 28(9): 1128-1133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31315530

RESUMO

OBJECTIVE: To investigate the clinical characteristics, imaging changes and early diagnostic methods of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: 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-ß2-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. RESULTS: The values of anti-dsDNA, anti-nucleosome antibody, aCL-IgG and anti-ß2-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. CONCLUSION: 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.


Assuntos
Circulação Cerebrovascular , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Adolescente , Autoanticorpos/sangue , DNA/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Testes Neuropsicológicos , Marcadores de Spin , Adulto Jovem
8.
JCI Insight ; 4(11)2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167973

RESUMO

The central nervous system manifestations of systemic lupus erythematosus (SLE) remain poorly understood. Given the well-defined role of autoantibodies in other lupus manifestations, extensive work has gone into the identification of neuropathic autoantibodies. However, attempts to translate these findings to patients with SLE have yielded mixed results. We used the MRL/MpJ-Faslpr/lpr mouse, a well-established, spontaneous model of SLE, to establish the immune effectors responsible for brain disease. Transcriptomic analysis of the MRL/MpJ-Faslpr/lpr choroid plexus revealed an expression signature driving tertiary lymphoid structure formation, including chemokines related to stromal reorganization and lymphocyte compartmentalization. Additionally, transcriptional profiles indicated various stages of lymphocyte activation and germinal center formation. The extensive choroid plexus infiltrate present in MRL/MpJ-Faslpr/lpr mice with overt neurobehavioral deficits included locally proliferating B and T cells, intercellular interactions between lymphocytes and antigen-presenting cells, as well as evidence for in situ somatic hypermutation and class switch recombination. Furthermore, the choroid plexus was a site for trafficking lymphocytes into the brain. Finally, histological evaluation in human lupus patients with neuropsychiatric manifestations revealed increased leukocyte migration through the choroid plexus. These studies identify a potential new pathway underlying neuropsychiatric lupus and support tertiary lymphoid structure formation in the choroid plexus as a novel mechanism of brain-immune interfacing.


Assuntos
Plexo Corióideo , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Estruturas Linfoides Terciárias , Animais , Plexo Corióideo/metabolismo , Plexo Corióideo/patologia , Plexo Corióideo/fisiopatologia , Modelos Animais de Doenças , Feminino , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Camundongos , Camundongos Endogâmicos MRL lpr , Estruturas Linfoides Terciárias/metabolismo , Estruturas Linfoides Terciárias/patologia , Estruturas Linfoides Terciárias/fisiopatologia , Transcriptoma
9.
Med Sci Monit ; 25: 532-539, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30657743

RESUMO

BACKGROUND Brain microvessel endothelial cells constitute an important component in the blood-brain barrier. Cell-culture-based models of the blood-brain barrier (BBB) have been extensively applied in pharmacology, pathology and physiology. This study investigated effects of anti-N-methyl-D-aspartic acid receptor 2 (anti-NR2), N-methyl-D-aspartic acid (NMDA) receptor antibodies, NMDA receptor antagonists, and NMDA receptor agonists on brain microvessel endothelial cell models, and verified the effect of anti-NR2 antibody on the BBB as a receptor agonist. MATERIAL AND METHODS The primary brain microvessel endothelial cells were isolated and cultured, and an in vitro BBB model was established based on microvessel endothelial cells. Anti-NR2 antibody, glutamic acid, ifenprodil, and memantine were added in the BBB model to analyze changes in transepithelial electrical resistance (TEER) and to examine the permeability of the brain microvessel endothelial cell model. RESULTS The results showed that TEER values were significantly decreased by the addition of anti-NR2 antibody and glutamate, but were significantly increased by the addition of ifenprodil and memantine. TEER values showed no changes when treated by anti-NR2 antibody and ifenprodil, as well as anti-NR2 antibody and memantine. When dexamethasone was added, the TEER values increased by 23.8%, 39.4%, and 29.6% by treating with anti-NR2 antibody, positive cerebrospinal fluid, and positive serum, respectively. CONCLUSIONS Our findings show that anti-NR2 antibody in neuropsychiatric lupus serum can damage the BBB and enter the brain.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Animais , Autoanticorpos/imunologia , Transporte Biológico , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/metabolismo , China , Modelos Animais de Doenças , Impedância Elétrica , Células Endoteliais/metabolismo , Espaço Extracelular/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Microvasos/metabolismo , N-Metilaspartato/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo
10.
Adv Clin Exp Med ; 28(2): 185-192, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29963787

RESUMO

BACKGROUND: Cognitive impairment (CI) is a frequent problem in lupus patients, regardless of their overt neuropsychiatric (NP) involvement. OBJECTIVES: The aim of our study was to test cognitive abilities in systemic lupus erythematosus (SLE) patients by means of neuropsychological testing and event-related potentials (ERPs), and to search for their cognitive abilities correlations with a wide range of auto-antibodies. MATERIAL AND METHODS: A total of 37 SLE patients were subjected to a battery of neuropsychological tests, recommended by the American College of Rheumatology (ACR), and to ERPs. They were also tested for a wide range of auto-antibodies (anti-cardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2-GPI), lupus anticoagulant, anti-dsDNA, anti-nucleosome, anti-ribosomal P (anti-Rib-P), anti-ganglioside, anti-Ro/SS-A, and anti-La/SS-B. RESULTS: Cognitive impairment was found in 35% of patients, mostly with NP SLE (NPSLE), and was associated with higher disease activity, measured by the SLE Disease Activity Index (SLEDAI), and with a longer duration of central nervous system (CNS) involvement. There were no differences in the immunological status between CI patients and those without cognitive decline, but some antibodies were correlated with worse results in certain neuropsychological tests (anti-dsDNA and worse results of Rey Complex Figure Test - RCFTc for copying and RCFTr for recall, and of verbal fluency test (VFT); aCL IgG and worse results in Digit Span (DS) and in RCFTc). Event-related potentials showed prolonged N200 and P300 latencies in SLE patients in comparison to controls, but no differences were found between SLE and NPSLE patients. Mean P300 latency was significantly longer in patients without anti-nucleosome antibodies. CONCLUSIONS: Event-related potentials can be used as a complementary tool in assessing CI in SLE patients. The immunological status of patients with CI did not differ from that of patients without cognitive problems.


Assuntos
Anticorpos Antinucleares/imunologia , Transtornos Cognitivos/imunologia , Transtornos Cognitivos/fisiopatologia , Potenciais Evocados , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Testes Neuropsicológicos , Transtornos Cognitivos/sangue , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , beta 2-Glicoproteína I
11.
Arthritis Rheumatol ; 71(1): 33-42, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29927108

RESUMO

The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.


Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Autoanticorpos/imunologia , Barreira Hematoencefálica/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Isquemia Encefálica/fisiopatologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/terapia , Citocinas/imunologia , Humanos , Inflamação/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons
12.
Am J Med Sci ; 356(3): 304-308, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30049410

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) presents a diagnostic challenge as there is no unified pathophysiological process driving its presentation. Case reports are limited in detailing manifestations and outcomes of NPSLE. This case highlights a unique presentation of NPSLE and discusses challenges associated with diagnosis. A 27-year-old man with systemic lupus erythematosus presented with altered mentation. Initial laboratory results and computed tomography of the brain were unremarkable, but magnetic resonance imaging of the brain revealed ring-enhancing lesions reported as NCC. This led to an extensive infectious disease evaluation, but ultimately there was no evidence of infection. The patient was diagnosed with NPSLE; treatment with intravenous glucocorticoids and cyclophosphamide led to dramatic clinical improvement. Repeat brain magnetic resonance imaging showed resolution of the ringed lesions. This case illustrates the importance of thorough evaluation in immunocompromised patients and warns of the risk of anchoring bias that can lead to diagnostic delays.


Assuntos
Encéfalo , Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino
13.
Curr Rheumatol Rev ; 14(3): 213-218, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29637864

RESUMO

Neuropsychiatric (NP) syndromes are an important cause of morbi-mortality in patients with Systemic Lupus Erythematosus (SLE). Despite remarkable recent progress, there are no definite methods to diagnose neuropsychiatric SLE (NPSLE) or to differentiate primary NPSLE from secondary causes. NPSLE remains a diagnosis of exclusion, and the clinical judgment is still the main approach to the correct diagnosis. Within this complex context, the Magnetic Resonance Imaging (MRI) has both a diagnostic role, by showing the nervous system involvement on one hand and excluding other causes on the other hand, and a prognostic role, help in assessing the lesions and monitoring the evolution. Conventional MRI shows brain involvement in around half of the patients, although the described findings are rather non-specific and present in many other diseases. However, many advanced MRI techniques are becoming increasingly used over the last period, showing abnormalities even in normal-appearing brains on conventional MRI. These MRI techniques hold promise to have a higher sensitivity and specificity than conventional MRI for NPSLE related changes. This review explores the place and the future perspectives of different advanced MRI techniques in NPSLE.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/terapia , Valor Preditivo dos Testes , Prognóstico
14.
J Int Neuropsychol Soc ; 24(6): 629-639, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29553037

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its most prevalent manifestation is neuropsychiatric SLE (NP-SLE), which is characterized by increased involvement of the nervous system, with relevant symptoms, such as marked cognitive deficits, which are directly involved in subsequent functional disability. The objective of this study is to identify and compare the profile of cognitive deficits in patients with NP-SLE and patients with non-neuropsychiatric SLE (nonNP-SLE) by means of a systematic review and meta-analysis. METHODS: We performed a systematic literature search based on the key words "cogn* OR neurocogn* AND lupus AND neuropsychiatry*" and included articles published between April 1999 and December 2016. A total of 244 articles were retrieved. We excluded reviews and meta-analyses, experiments not performed in humans, and single case reports. We included studies that used standardized cognitive measures and had included at least the subgroups NP-SLE and non NP-SLE. RESULTS: The meta-analysis was finally based on six studies, and 10 neuropsychological variables were examined. Significant differences were observed between the groups for six variables. In the remaining four variables, we observed marked heterogeneity between the groups or a low number of studies. CONCLUSIONS: The data obtained indicate greater cognitive impairment among NP-SLE patients than among nonNP-SLE patients, at least for the cognitive domains of visuomotor coordination, attention, executive function, visual learning and memory, and phonetic fluency. The identification and definition of cognitive deficits in SLE patients is necessary to develop adequate cognitive remediation programs to improve functional outcomes. (JINS, 2018, 24, 629-639).


Assuntos
Disfunção Cognitiva/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Disfunção Cognitiva/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações
15.
J Int Med Res ; 46(1): 485-491, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28823196

RESUMO

Objective Neuropsychiatric systemic lupus erythematosus (NPSLE) is a manifestation of systemic lupus erythematosus (SLE). Central nervous system (CNS) infection is a consequence of intensive immunosuppressive therapy that patients with SLE might undergo. This study aimed to compare the differences between NPSLE and CNS infections in patients with SLE. Methods Patients with SLE and NPSLE or CNS infections were retrospectively reviewed. Clinical manifestations, laboratory test results, and prognoses were recorded. The independent sample t-test or chi-square test was used to compare data. Results Patients with CNS infections (n = 20) had more serious headache, high fever (>39.0°C), and vomiting compared with patients with NPSLE (n = 48). Patients with CNS infections also had a larger prednisone dose at the time of symptom onset, larger cumulative dosages over the preceding year, lower SLE Disease Activity Index (SLEDAI) scores, higher rate of nephritis, lower albumin levels, higher C-reactive protein (CRP) levels, higher 24-h-urine protein levels, higher cerebrospinal fluid (CSF) white blood cell levels, and lower protein and glucose levels than those with NPSLE. Conclusions For patients with SLE presenting with CNS symptoms, serious headache, high fever, a high dose of corticosteroids, low SLEDAI scores, and abnormal CSF are more important indicators for CNS infections than NPSLE.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Febre/diagnóstico , Cefaleia/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Anti-Inflamatórios/uso terapêutico , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/metabolismo , Infecções do Sistema Nervoso Central/fisiopatologia , Líquido Cefalorraquidiano/citologia , Diagnóstico Diferencial , Feminino , Febre/tratamento farmacológico , Febre/metabolismo , Febre/fisiopatologia , Cefaleia/tratamento farmacológico , Cefaleia/metabolismo , Cefaleia/fisiopatologia , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo
16.
BMJ Open ; 7(5): e015546, 2017 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-28554934

RESUMO

OBJECTIVE: To validate the Italian algorithm of attribution of neuropsychiatric (NP) events to systemic lupus erythematosus (SLE) in an external international cohort of patients with SLE. METHODS: A retrospective cohort diagnostic accuracy design was followed. SLE patients attending three tertiary care lupus clinics, with one or more NP events, were included. The attribution algorithm, applied to the NP manifestations, considers four weighted items for each NP event: (1) time of onset of the event; (2) type of NP event (major vs minor), (3) concurrent non-SLE factors; (4) favouring factors. To maintain blinding, two independent teams of assessors from each centre evaluated all NP events: the first provided an attribution diagnosis on the basis of their own clinical judgement, assumed as the 'gold standard'; the second applied the algorithm, which provides a probability score ranging from 0 to 10. The performance of the algorithm was evaluated by calculating the area under curve (AUC) of thereceiver operating characteristic curve. RESULTS: The study included 243 patients with SLE with at least one NP manifestation, for a total of 336 events. 285 (84.8%) NP events involved the central nervous system and 51 (15.2%) the peripheral nervous system. The attribution score for the first NP event showed good accuracy with an AUC of 0.893 (95% CI 0.849 to 0.937) using dichotomous outcomes for NPSLE (related vs uncertain/unrelated). The best single cut-off point to optimise classification of a first NPSLE-related event was≥7 (sensitivity 87.9%, specificity 82.6%). Satisfactory accuracy was observed also for subsequent NP events. CONCLUSIONS: Validation exercise on an independent international cohort showed that the Italian attribution algorithm is a valid and reliable tool for the identification of NP events attributed to SLE.


Assuntos
Algoritmos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Adulto , Área Sob a Curva , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
17.
Lupus ; 26(12): 1252-1259, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28420059

RESUMO

Objective Assess quality of life in patients with systemic lupus erythematosus (SLE) presenting with neuropsychiatric symptoms (neuropsychiatric SLE, NPSLE). Methods Quality of life was assessed using the Short-Form 36 item Health Survey (SF-36) in patients visiting the Leiden NPSLE clinic at baseline and at follow-up. SF-36 subscales and summary scores were calculated and compared with quality of life of the general Dutch population and patients with other chronic diseases. Results At baseline, quality of life was assessed in 248 SLE patients, of whom 98 had NPSLE (39.7%). Follow-up data were available for 104 patients (42%), of whom 64 had NPSLE (61.5%). SLE patients presenting neuropsychiatric symptoms showed a significantly reduced quality of life in all subscales of the SF-36. Quality of life at follow-up showed a significant improvement in physical functioning role ( p = 0.001), social functioning ( p = 0.007), vitality ( p = 0.023), mental health ( p = 0.014) and mental component score ( p = 0.042) in patients with neuropsychiatric symptoms not attributed to SLE, but no significant improvement was seen in patients with NPSLE. Conclusion Quality of life is significantly reduced in patients with SLE presenting neuropsychiatric symptoms compared with the general population and patients with other chronic diseases. Quality of life remains considerably impaired at follow-up. Our results illustrate the need for biopsychosocial care in patients with SLE and neuropsychiatric symptoms.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Qualidade de Vida , Adulto , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Pessoa de Meia-Idade , Países Baixos
18.
Rev. bras. reumatol ; 57(2): 149-153, Mar.-Apr. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-844225

RESUMO

Abstract Aim: To investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. Patients and methods: Sixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR). Results: Statistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p < 0.001] and GG [10% vs 66.7%, p < 0.001]). Conclusion: Polymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.


Resumo Objetivo: Investigar a relação entre o polimorfismo genético do fator de crescimento vascular endotelial (VEGF) em pacientes com lúpus eritematoso sistêmico (LES) e manifestações neuropsiquiátricas relacionadas com o lúpus. Pacientes e métodos: Foram recrutados 60 pacientes adultos com LES nos departamentos de Reumatologia e Neurologia de hospitais universitários do Cairo e classificados em dois grupos; grupo A: 30 pacientes com manifestações neuropsiquiátricas (LESNP) e grupo B: 30 pacientes sem manifestações neuropsiquiátricas. Genotipou-se o SNP G1612A (rs10434) do gene VEGF em ambos os grupos por reação em cadeia da polimerase em tempo real (RT-PCR). Resultados: Foi encontrada diferença estatisticamente significativa nas frequências genotípicas e alélicas entre os dois grupos (AA [70% vs. 13,3%, p < 0,001] e GG [10% vs. 66,7%, p < 0,001]). Conclusão: O polimorfismo no gene que codifica o VEGF pode estar associado ao aumento na incidência de lúpus neuropsiquiátrico em pacientes com LES.


Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Predisposição Genética para Doença/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Projetos Piloto , Estudos Transversais , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Perfilação da Expressão Gênica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Genótipo , Pessoa de Meia-Idade
19.
Rev Bras Reumatol Engl Ed ; 57(2): 149-153, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28343620

RESUMO

AIM: To investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. PATIENTS AND METHODS: Sixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR). RESULTS: Statistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p<0.001] and GG [10% vs 66.7%, p<0.001]). CONCLUSION: Polymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients.


Assuntos
Predisposição Genética para Doença/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
20.
Scand J Rheumatol ; 46(6): 474-483, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28293972

RESUMO

OBJECTIVES: We compared patients' assessments of systemic lupus erythematosus (SLE) disease activity by a Swedish version of the Systemic Lupus Activity Questionnaire (SLAQ) with physicians' assessments by the Systemic Lupus Activity Measure (SLAM) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). We also explored the performance of the SLAQ in patients with short (< 1 year) versus long (≥ 1 year) disease duration. METHOD: Patients filled out the SLAQ before physicians' assessments. Correlations between SLAQ total, subscales (Symptom score, Flares, Patients global) and SLAM and SLEDAI-2K, as well as between the corresponding items in SLAQ and SLAM, were evaluated using Spearman's ρ. Comparisons between patients with different disease durations were performed with Mann-Whitney U or chi-squared tests. RESULTS: We included 203 patients (79% women), with a median age of 45 years [interquartile range (IQR) 33-57 years] and disease duration of 5 years (IQR 0-14 years). Correlations between physicians' SLAM without laboratory items (SLAM-nolab) and patients' assessments were: SLAQ total, ρ = 0.685, Symptom score, ρ = 0.651, Flares, ρ = 0.547, and Patients global, ρ = 0.600. Of the symptom items, fatigue (ρ = 0.640), seizures (ρ = 0.635), and headache (ρ = 0.604) correlated most closely. Neurology/stroke syndrome, skin, and lymphadenopathy correlated less well (ρ < 0.24). Patients' and physicians' assessments were notably more discordant for patients with short disease durations. CONCLUSION: We confirm that the SLAQ can be used to monitor disease activity. However, the discrepancy between patients' and physicians' assessments was greater for patients with short versus long disease duration. We encourage further use of the SLAQ, but would like to develop a shorter version which would be valuable in modern, partly web-based, clinical care.


Assuntos
Fadiga/fisiopatologia , Cefaleia/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Convulsões/fisiopatologia , Adulto , Progressão da Doença , Fadiga/etiologia , Feminino , Cefaleia/etiologia , Humanos , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Cutâneo/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Linfadenopatia/etiologia , Linfadenopatia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Convulsões/etiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Inquéritos e Questionários , Suécia
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