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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 In total, 284 original case reports and 24 unpublished cases were collected, and clinical parameters were analyzed.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.
Ann Rheum Dis ; 79(3): 356-362, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31915121

RESUMO

OBJECTIVES: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients. METHODS: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states. RESULTS: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001). CONCLUSIONS: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/mortalidade , Vasculite Associada ao Lúpus do Sistema Nervoso Central/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multinível , Estudos Prospectivos , Qualidade de Vida
3.
Lupus ; 28(14): 1678-1689, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31718491

RESUMO

The study examined the hypothesis that hypoperfusion in brain areas known to be involved in emotional disturbances in primary psychiatric disorders is also linked to emotional difficulties in systemic lupus erythematosus (SLE) and that these are not secondary to the physical and social burden incurred by the disease. Nineteen SLE patients without overt neuropsychiatric manifestations (non-NPSLE), 31 NPSLE patients, and 23 healthy controls were examined. Dynamic susceptibility contrast MRI was used and cerebral blood flow and cerebral blood volume values were estimated in six manually selected regions of interest of brain regions suspected to play a role in anxiety and depression (dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate cortex, hippocampi, caudate nuclei and putamen). NPSLE patients reported high rates of anxiety and depression symptomatology. Significantly reduced cerebral blood flow and cerebral blood volume values were detected in the NPSLE group compared to healthy controls in the dorsolateral prefrontal cortex and ventromedial prefrontal cortex, bilaterally. Within the NPSLE group, anxiety symptomatology was significantly associated with lower perfusion in frontostriatal regions and in the right anterior cingulate gyrus. Importantly, the latter associations appeared to be specific to anxiety symptoms, as they persisted after controlling for depression symptomatology and independent of the presence of visible lesions on conventional MRI. In conclusion, hypoperfusion in specific limbic and frontostriatal regions is associated with more severe anxiety symptoms in the context of widespread haemodynamic disturbances in NPSLE.


Assuntos
Ansiedade/etiologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Depressão/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise de Regressão
4.
Lupus ; 28(5): 685-694, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018814

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an important cause of morbidity and mortality. We undertook this observational retrospective study of patients with NPSLE who had brain magnetic resonance imaging (MRI) to determine the indications for MRI and the correlation of clinical and laboratory findings with MRI. We identified 83 NPSLE patients (84.3% women) seen at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, between June 2003 and May 2017. The mean age at SLE diagnosis was 26.24 ± 12.81 years and the median interval to NPSLE was 11.0 (interquartile range, 4.0-39.0) months. The most common indications for MRI were seizures (45.8%), psychosis (18.1%) and cerebrovascular disease (18.1%). The MRI was abnormal in 68 (81.9%) with small-vessel disease in 65 (78.3%) and large-vessel disease in eight (9.6%). The small-vessel abnormalities were white-matter hyperintensities (WMH) (59.0%), atrophy (55.4%) and lacunae (4.6%). Our patients had high disease activity at NPSLE. Cerebrovascular disease was associated with an abnormal MRI ( p = 0.018) and large-vessel disease ( p = 0.014) on MRI. Our NPSLE patients were younger and had high disease activity, and seizures were more common compared with other studies. The most common MRI abnormalities were WMH and cortical atrophy, in agreement with other studies.


Assuntos
Encéfalo/patologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Adolescente , Adulto , Atrofia , Encéfalo/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/patologia , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imagem por Ressonância Magnética , Masculino , Fenótipo , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/patologia , África do Sul , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem
5.
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
6.
Lupus ; 27(13): 2101-2111, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30282561

RESUMO

OBJECTIVE: A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. METHODS: TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients. Furthermore, we estimated the general intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in cerebrospinal fluid, and explored whether these variables were associated with neuropsychiatric manifestations. RESULTS: No associations were found between TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in SLE nor in primary Sjögren's syndrome patients. Furthermore, no associations were found between neuropsychiatric manifestations and indicators of blood-brain barrier integrity or astroglial activity. Anti-NR2 antibodies were associated with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor functioning (odds ratio 6.0, P = 0.006). CONCLUSION: No clinical neuropsychiatric manifestations could be attributed to impaired integrity of the blood-brain barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient group. The TWEAK concentration was considerably higher in the cerebrospinal fluid than in blood, which indicates intrathecal production. We hypothesize that increased TWEAK and S100B result from immunological stress caused by brain-reactive antibodies produced by brain residing immune cells.


Assuntos
Barreira Hematoencefálica/patologia , Citocina TWEAK/sangue , Citocina TWEAK/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Síndrome de Sjogren/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Modelos Lineares , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/psicologia
7.
Front Immunol ; 9: 2189, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319641

RESUMO

About 40% of patients with systemic lupus erythematosus experience diffuse neuropsychiatric manifestations, including impaired cognition and depression. Although the pathogenesis of diffuse neuropsychiatric SLE (NPSLE) is not fully understood, loss of brain barrier integrity, autoreactive antibodies, and pro-inflammatory cytokines are major contributors to disease development. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, prevents lymphocyte egress from lymphoid organs through functional antagonism of S1P receptors. In addition to reducing the circulation of autoreactive lymphocytes, fingolimod has direct neuroprotective effects such as preserving brain barrier integrity and decreasing pro-inflammatory cytokine secretion by astrocytes and microglia. Given these effects, we hypothesized that fingolimod would attenuate neurobehavioral deficits in MRL-lpr/lpr (MRL/lpr) mice, a validated neuropsychiatric lupus model. Fingolimod treatment was initiated after the onset of disease, and mice were assessed for alterations in cognitive function and emotionality. We found that fingolimod significantly attenuated spatial memory deficits and depression-like behavior in MRL/lpr mice. Immunofluorescent staining demonstrated a dramatic lessening of brain T cell and macrophage infiltration, and a significant reduction in cortical leakage of serum albumin, in fingolimod treated mice. Astrocytes and endothelial cells from treated mice exhibited reduced expression of inflammatory genes, while microglia showed differential regulation of key immune pathways. Notably, cytokine levels within the cortex and hippocampus were not appreciably decreased with fingolimod despite the improved neurobehavioral profile. Furthermore, despite a reduction in splenomegaly, lymphadenopathy, and circulating autoantibody titers, IgG deposition within the brain was unaffected by treatment. These findings suggest that fingolimod mediates attenuation of NPSLE through a mechanism that is not dependent on reduction of autoantibodies or cytokines, and highlight modulation of the S1P signaling pathway as a novel therapeutic target in lupus involving the central nervous system.


Assuntos
Depressão/imunologia , Cloridrato de Fingolimode/farmacologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Lisofosfolipídeos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esfingosina/análogos & derivados , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Autoanticorpos/imunologia , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/imunologia , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Citocinas/imunologia , Depressão/tratamento farmacológico , Depressão/psicologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Cloridrato de Fingolimode/uso terapêutico , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Lisofosfolipídeos/imunologia , Camundongos , Camundongos Endogâmicos MRL lpr , Microglia/efeitos dos fármacos , Microglia/imunologia , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/imunologia , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais/imunologia , Esfingosina/imunologia , Esfingosina/metabolismo , Resultado do Tratamento
8.
Pediatrics ; 142(3)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30072574

RESUMO

A 14-year-old boy presented to our institution with a 1-month history of neurocognitive decline and intermittent fevers. His history was significant for fevers, headaches, and a 10-lb weight loss. Previous examinations by multiple medical providers were significant only for bilateral cervical lymphadenopathy. Previous laboratory workup revealed leukopenia, neutropenia, and elevated inflammatory markers. Despite improvement in his laboratory values after his initial presentation, his fevers persisted, and he developed slowed and "jerky" movements, increased sleep, slurred speech, delusions, visual hallucinations, and deterioration in his school performance. A brain MRI performed at an outside hospital before admission at our institution was concerning for patchy, increased T2 and fluid-attenuated inversion recovery signal intensity in multiple areas, including the basal ganglia. After transfer to our institution and admission to the pediatric hospital medicine team, the patient had an acute decompensation. Our subspecialists will discuss the initial evaluation, workup, differential diagnosis, definitive diagnosis, and subsequent management of this patient.


Assuntos
Febre/diagnóstico por imagem , Leucopenia/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Transtornos Neurocognitivos/diagnóstico por imagem , Neutropenia/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Febre/sangue , Febre/psicologia , Humanos , Leucopenia/sangue , Leucopenia/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/psicologia , Neutropenia/sangue , Neutropenia/psicologia
9.
Lupus ; 27(8): 1363-1367, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29466913

RESUMO

Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can affect the central nervous system in multiple ways, including causing cognitive dysfunction. Cognitive dysfunction is a common complaint of SLE patients yet diagnosis is challenging, time consuming, and costly. This study evaluated the Self-Administered Gerocognitive Exam (SAGE) as a screening test for cognitive impairment in a cohort of SLE patients. Methods A total of 118 SLE patients completed the SAGE. Providers completed the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborative Clinics Damage Index (SLICC-DI). SAGE scores were grouped into normal (>16) and abnormal (≤16) categories. Univariate and multivariate analyses were performed. Results Of the 118 participants, 21(18%) scored ≤16 on the SAGE instrument. In univariate analysis, race, ethnicity, household income, and SLICC-DI scores were associated with the SAGE ( p < 0.05). In multivariable analysis, abnormal SAGE score was independently associated with higher SLICC-DI score (odds ratio (OR) = 1.44, 95% confidence intervals 1.04-1.99, p = 0.03)), Hispanic ethnicity (OR = 43.4, 95% CI 3.1-601, p = 0.005), and lower household income (OR = 11.9 for ≤$15,000 vs >$50,000, 95% CI 2.45-57, p = 0.002). Conclusions In SLE patients, this study demonstrates an independent relationship between neurocognitive impairment (as measured by the SAGE) and higher lupus-related damage, as measured by the SLICC-DI, and lower household income. Abnormal SAGE scores were also associated with Hispanic ethnicity. A language barrier could explain this because the SAGE instrument was conducted in English only. The SAGE was feasible to measure in the clinic setting.


Assuntos
Disfunção Cognitiva/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Autoavaliação , Adulto , Estudos de Coortes , Feminino , Hispano-Americanos , Humanos , Renda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ohio , Índice de Gravidade de Doença
10.
Lupus ; 27(4): 688-693, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29241417

RESUMO

Objectives The objectives of this paper are to look at the prevalence of neuropsychiatric manifestations and assess their impact on quality of life in North Indian lupus patients. Methods The study included consecutive patients with systemic lupus erythematosus (SLE) who were older than 18 years and met the SLICC 2012 criteria. A diagnosis of a neuropsychiatric syndrome was made as per ACR 1999 definitions. Manifestations occurring at any point in time after the diagnosis of SLE were considered if a reliable history and medical records were available. Quality of life was assessed by EuroQol-5D questionnaire. Means were compared by student t test for normally distributed data. Comparison of quality of life between groups was performed by the Kruskal-Wallis test and Mann-Whitney U test. Results This study included 101 patients of SLE with mean (±SD) age of 32.3 ± 10.0 years and a majority ( n = 92) were females. Mean (±SD) age of diagnosis of SLE was 27.8 ± 9.2 years and disease duration (after diagnosis) was 4.6 ± 4.5 years. Thirty-three patients had neuropsychiatric manifestations with a total of 42 events. The most common manifestation was headache (10%) followed by anxiety disorder (5%) and peripheral neuropathy (9%). Other NPSLE syndromes observed in the study are seizure (4%), cognitive dysfunction (4%), depression (4%), acute confusional state (2%), autonomic neuropathy (2%), movement disorder (1%), and mononeuritis multiplex (1%). On comparing the groups of NPSLE, nephritis, and neither, there was a significant difference in mobility, self-care, pain, and worry. On post hoc test, there was a significant difference between the NPSLE and neither group. Conclusion Neuropsychiatric manifestations significantly affect quality of life in North Indian SLE patients.


Assuntos
Efeitos Psicossociais da Doença , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Qualidade de Vida , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Masculino , Prevalência , Adulto Jovem
11.
Zhonghua Yi Xue Za Zhi ; 97(42): 3316-3319, 2017 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-29141377

RESUMO

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.


Assuntos
Autoanticorpos/análise , Lúpus Eritematoso Sistêmico/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Ubiquitina Tiolesterase/imunologia , Anticorpos Antinucleares , Ensaio de Imunoadsorção Enzimática , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia
12.
Nature ; 546(7659): 539-543, 2017 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-28614301

RESUMO

Systemic lupus erythematosus (SLE) is an incurable autoimmune disease characterized by autoantibody deposition in tissues such as kidney, skin and lungs. Notably, up to 75% of patients with SLE experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and, in rare cases, psychosis-collectively this is referred to as central nervous system (CNS) lupus. In some cases, certain autoantibodies, such as anti-NMDAR or anti-phospholipid antibodies, promote CNS lupus. However, in most patients, the mechanisms that underlie these symptoms are unknown. CNS lupus typically presents at lupus diagnosis or within the first year, suggesting that early factors contributing to peripheral autoimmunity may promote CNS lupus symptoms. Here we report behavioural phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signalling. Furthermore, we show that type I IFN stimulates microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. These findings and our observation of increased type I IFN signalling in post-mortem hippocampal brain sections from patients with SLE may instruct the evaluation of ongoing clinical trials of anifrolumab, a type I IFN-receptor antagonist. Moreover, identification of IFN-driven microglia-dependent synapse loss, along with microglia transcriptome data, connects CNS lupus with other CNS diseases and provides an explanation for the neurological symptoms observed in some patients with SLE.


Assuntos
Interferon Tipo I/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Microglia/imunologia , Microglia/patologia , Sinapses/patologia , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Comportamento Animal , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Interferon Tipo I/antagonistas & inibidores , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Camundongos , Microglia/metabolismo , Fenótipo , Transdução de Sinais , Sinapses/imunologia , Transcriptoma
13.
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
14.
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
15.
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
16.
Lupus ; 26(2): 170-178, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27387599

RESUMO

Objective Inflammation secondary to autoantibody-mediated effects occurring in multiple organs is a hallmark of systemic lupus erythematosus (SLE). The inflammatory response to SLE-mediated damage in brain parenchyma has been postulated in both normal and cognitively impaired individuals. Our goal is to use molecular imaging to investigate the distribution within the brain of the mitochondrial translocator protein (TSPO) that is upregulated during glial cell activation, and is considered as a marker of brain injury and repair. Methods We sought to characterize TSPO distribution in the brain of SLE patients using positron emission tomography (PET) and [11C]DPA-713 (DPA), a radiopharmaceutical that targets TSPO. We imaged 11 healthy controls and 10 patients with SLE (years of diagnosis: 13.0 ± 7.7), all between the ages of 22 and 52. RESULTS: Among the nine brain regions studied, no statistically significant increases in DPA binding were observed in SLE. Instead, there was a significant decrease in TSPO distribution in the cerebellum and hippocampus of SLE patients, as compared to healthy controls. Such decreases were most significant in cognitively normal SLE subjects, but showed pseudo-normalization in those with cognitive impairment, due to higher cerebellar and hippocampal DPA binding in the cognitively impaired (versus normal) SLE brain. Conclusions Results from this pilot study suggest a link between diminished regional TSPO expression in the brain of patients with SLE, as well as possible glial cell activation within the cerebellum and hippocampus of cognitively impaired individuals with SLE. Further studies are needed to elucidate how mitochondrial dysfunction and glial cell activation may act together in SLE and SLE-mediated neurocognitive deficits.


Assuntos
Acetamidas/administração & dosagem , Encéfalo/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico por imagem , Imagem Molecular/métodos , Neuroimagem/métodos , Animais de Estimação , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Receptores de GABA/metabolismo , Adulto , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Estudos de Casos e Controles , Cognição , Regulação para Baixo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Adulto Jovem
17.
Lupus ; 26(2): 195-199, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27416844

RESUMO

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs and systems. Nervous system involvement in SLE encompasses neurological and psychiatric disorders, and remains a diagnostic and therapeutic challenge. Wernicke's encephalopathy (WE) is a neurological disorder that occurs as a consequence of thiamine deficiency, and its clinical presentation resembles the neuropsychiatric events attributed to SLE (NPSLE). Differentiation between these two entities is crucial because their treatment differs greatly and can change prognosis. We describe three cases of patients with SLE who presented with initial clinical findings suggestive of NPSLE that, at the end of a thorough clinical investigation, were actually found to represent WE. In all of these cases, treatment with thiamine resulted in significant improvement. WE should be considered as a differential diagnosis in SLE patients with neuropsychiatric signs and symptoms, especially when risk factors for thiamine deficiency are present.


Assuntos
Imagem de Difusão por Ressonância Magnética , Lúpus Eritematoso Sistêmico/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Encefalopatia de Wernicke/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tiamina/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/uso terapêutico , Encefalopatia de Wernicke/complicações , Encefalopatia de Wernicke/tratamento farmacológico , Encefalopatia de Wernicke/psicologia
18.
Rheumatology (Oxford) ; 56(suppl_1): i14-i23, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27744358

RESUMO

Neurological and psychiatric syndromes, collectively referred to as NPSLE, occur frequently in SLE. The frequency of NPSLE varies from 21 to 95%; however, only 13-38% of neuropsychiatric (NP) events could be attributable to SLE in the NPSLE SLICC inception cohort. This variability in the frequency of NPSLE is attributable to the low specificity of the ACR case definitions for SLE-attributed NP syndromes, inclusion of minor NP events in the ACR nomenclature, difficulty in ascertainment of NP events and diverse experience of rheumatologists in the clinical assessment of NP events. Making the correct and early attribution of NP events to SLE is important to institute appropriate immunosuppressive treatment for favourable outcomes. Various attribution models using composite decision rules have been developed and used to ascribe NP events to SLE. This review will focus on the various clinical presentations, diagnostic work-up and attributions of the common NPSLE syndromes, including other NP events not included in the ACR nomenclature but which have come to attention in recent years.


Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/fisiopatologia , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Meningite Asséptica/diagnóstico , Meningite Asséptica/etiologia , Meningite Asséptica/fisiopatologia , Mononeuropatias/diagnóstico , Mononeuropatias/etiologia , Mononeuropatias/fisiopatologia , Transtornos do Humor/diagnóstico , Transtornos do Humor/etiologia , Transtornos do Humor/fisiopatologia , Transtornos do Humor/psicologia , Neuromielite Óptica/diagnóstico , Polineuropatias/diagnóstico , Polineuropatias/etiologia , Polineuropatias/fisiopatologia , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/fisiopatologia
19.
Autoimmun Rev ; 16(2): 114-122, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27988431

RESUMO

BACKGROUND/PURPOSE: Neuropsychiatric (NP) events are found in patients with rheumatic diseases, commonly in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). The standard nomenclature and case definitions for 19 NPSLE syndromes by the American College of Rheumatology (ACR) Committee on Research cover a wide range of NP events seen in both SLE and SS. Despite advances in the understanding of SLE and SS, NP syndromes continue to pose diagnostic challenges. Correct attribution of NP events is critical in determining the correct treatment and prognosis. Anti-N-methyl-d-aspartate receptor subunits NR2A/B (anti-NR2A/B) antibodies have been demonstrated in the sera of SLE and SS patients and have been associated with collective or specific NP syndromes, though not consistently. Interpretation of anti-NR2A/B antibody data in the medical literature is rendered difficult by small sample size of patient groups. By combining different studies to generate a pooled effect size, a meta-analysis can increase the power to detect differences in the presence or absence of NP syndromes. Hence, we set out to perform a meta-analysis to assess the association between anti-NR2A/B antibodies and NP syndromes in SLE and SS. METHODS: A literature search was conducted using PubMed and other databases from inception to June 2016. We abstracted data relating to anti-NR2A/B antibodies from the identified studies. The random effects model was used to calculate overall combined odds ratio (OD) with its corresponding 95% confidence interval (CI) to evaluate the relationship between anti-NR2A/B antibodies and NP syndromes in SLE and SS patients with and without NP events. We also included our own cohort of 57 SLE patients fulfilling the ACR 1997 revised classification criteria and 58 healthy controls (HCs). RESULTS: In total, 17 studies with data on anti-NR2A/B antibodies in 2212 SLE patients, 66 SS patients, 99 disease controls (DCs) (e.g. antiphospholipid syndrome, myasthenia gravis and autoimmune polyendocrine syndrome I) and 538 HCs were used in this analysis. Overall pooled prevalence of serum/plasma anti-NR2A/B antibodies was higher in SLE patients [24.6% (95% CI 18.5-32.0%)] and SS patients [19.7% (95% CI 11.8-31.0%)] compared to DCs [14.8% (95% CI 2.2-56.9)] and HCs [7.6% (95% CI 4.6-12.4%)] (p=0.001). There was a significantly greater proportion of SLE and SS patients with NP syndromes who demonstrated positivity for serum/plasma anti-NR2A/B antibody [pooled OR=1.607 (95% CI 1.041-2.479), p=0.032] as compared to SLE and SS patients without NP syndromes in 13 studies. Usable data for cerebrospinal fluid anti-NR2A/B antibodies were available in only 4 studies [pooled OR=0.831 (95% CI 0.365-1.888), p=0.658]. Among the 19 NP syndromes, serum/plasma anti-NR2A/B antibodies were not specifically associated with any NP syndrome, including cognitive dysfunction (p=0.259) and mood disorder (p=0.503). Meta-regression identified proportion of anti-double-stranded deoxyribonucleic acid antibody positivity (p=0.009) and SLE Disease Activity Index (p=0.028) as moderators for the heterogeneity of serum/plasma anti-NR2A/B antibodies. CONCLUSION: Circulating anti-NR2A/B antibody testing has a diagnostic value for NP syndromes in SLE and SS collectively. However, the evidence to date suggests that anti-NR2A/B antibody positivity cannot distinguish specific NP syndromes.


Assuntos
Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Receptores de N-Metil-D-Aspartato/metabolismo , Síndrome de Sjogren/psicologia , Adulto , Estudos de Coortes , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Masculino , Receptores de N-Metil-D-Aspartato/imunologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia
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