Cognitive impairment in a Colombian cohort of patients with systemic lupus erythematosus: A cross-sectional study.

CONTEXT: Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. OBJECTIVE: To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. METHODS AND PATIENTS: This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. RESULTS: Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. CONCLUSION: In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.

Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment.

Systemic lupus erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect any organ in the body, including the neurological system. Multiple factors, such as environmental (infections), genetic (many HLA alleles including DR2 and DR3, and genes including C4), and immunological influences on self-antigens, such as nuclear antigens, lead to the formation of multiple autoantibodies that cause deleterious damage to bodily tissues and organs. The production of autoantibodies, such as anti-dsDNA, anti-SS(A), anti-SS(B), anti-Smith, and anti-neuronal DNA are characteristic features of this disease. This autoimmune disease results from a failure of the mechanisms responsible for maintaining self-tolerance in T cells, B cells, or both. Immune complexes, circulating antibodies, cytokines, and autoreactive T lymphocytes are responsible for tissue injury in this autoimmune disease. The diagnosis of SLE is a rheumatological challenge despite the availability of clinical criteria. NPSLE was previously referred to as lupus cerebritis or lupus sclerosis. However, these terms are no longer recommended because there is no definitive pathological cause for the neuropsychiatric manifestations of SLE. Currently, the treatment options are primarily based on symptomatic presentations. These include the use of antipsychotics, antidepressants, and anxiolytic medications for the treatment of psychiatric and mood disorders. Antiepileptic drugs to treat seizures, and immunosuppressants (e.g., corticosteroids, azathioprine, and mycophenolate mofetil), are directed against inflammatory responses along with non-pharmacological interventions.

Síndrome del ocho y medio secundario a vasculopatía lúpica: presentación de un caso / Eight-and-a-half syndrome secondary to lupus vasculopathy: a case presentation

RESUMEN Introducción: El manejo diagnóstico y terapéutico en los pacientes con lupus eritematoso sistémico que desarrollan una afectación neuropsiquiátrica representa un reto, debido a la heterogeneidad de las formas en que puede presentarse y la ausencia de criterios diagnósticos. Objetivo: Reconocer las formas clínicas de presentación de los síndromes neuroftalmológicos que traducen afectación pontina. Presentación del caso: Hombre de 71 años con antecedente de lupus eritematoso sistémico con afectación neuopsiquiátrica, que de forma aguda desarrolla un cuadro emético en el curso de una emergencia hipertensiva seguido de una parálisis de la mirada horizontal hacia la izquierda, una oftalmoplejía internuclear posterior derecha y una parálisis facial izquierda. En la neuroimagen se constata una afectación multifocal con marcado daño pontino. Conclusiones: Reconocer las formas clínicas de presentación de estos trastornos neuroftalmológicos raros que generalmente se presentan de forma aguda/subaguda permite al neurólogo realizar el diagnóstico topográfico de la lesión a nivel protuberancial con elevada precisión desde la Sala de Urgencias, así como reducir los posibles diagnósticos diferenciales a una etiología vascular, desmielinizante u ocupativa de espacio(AU)

ABSTRACT Introduction: The diagnostic and therapeutic management of patients with systemic lupus erythematosus who develop a neuropsychiatric involvement represents one of the biggest challenges due to the heterogeneity of the ways in which it can occur and the absence of diagnostic criteria. Objective: To recognize the clinical forms of presentation of neurophthalmological syndromes that express pontine involvement. Case presentation: Seventy-one-year-old man with history of systemic lupus erythematosus with neuropsychiatric involvement who acutely develops an emetic episode in the course of a hypertensive emergency followed by a paralysis of the horizontal gaze to the left, a right-sided posterior internuclear ophthalmoplegia and a left facial palsy. In the neuroimaging, a multifocal involvement with marked pontine damage is observed. Conclusions: Recognizing the clinical forms of presentation of these rare neurophthalmological disorders that generally occur in an acute or subacute form allows the neurologist to perform the topographic diagnosis of the lesion at a protuberancial level with high precision from the time when the patient attends the Emergency Department and reduces the possible differential diagnoses to a vascular, demyelinating or occupational etiology of space(AU)

Epidemiology, characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus.

INTRODUCTION: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice. Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events. Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.

Mimickers of neuropsychiatric manifestations in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), presenting with new onset or worsening neuropsychiatric (NP) symptoms, is a challenge in clinical practice. Mimickers such as infections, drug-induced side effects, metabolic abnormalities, malignancies, and alcohol-related disorders have to be excluded, before attributing the manifestations to disease activity. Proper diagnosis is essential to guide adequate management and reduce morbidity and mortality. In this review article, we will highlight clinical, laboratorial, and neuroradiological features that are helpful to assist in the differential diagnosis.

The role of infections in neuropsychiatric lupus.

Opportunistic infections can cause manifestations that resemble neuropsychiatric systemic lupus erythematosus and they can also trigger lupus flares. Therefore, central nervous system infections as differential diagnosis in neuropsychiatric systemic lupus erythematosus may be difficult, leading to delayed diagnosis and specific treatment. Central nervous system infection in systemic lupus erythematosus is not common but, if left misdiagnosed and not treated promptly, can be fatal. Complementary diagnosis tests are generally non-specific and disappointing. Caution with immunosuppressive drug treatment should be emphasized while an opportunistic infection cannot be ruled out. In this review, we discuss the various types of central nervous system infections reported in systemic lupus erythematosus patients, highlighting the importance of their early recognition in order to improve morbidity and mortality. Prevention with vaccination is a recommended approach.

Vascular endothelial growth factor G1612A (rs10434) gene polymorphism and neuropsychiatric manifestations in systemic lupus erythematosus patients / Polimorfismo genético do fator de crescimento vascular endotelial G1612A (rs10434) e manifestações neuropsiquiátricas em pacientes com lúpus eritematoso sistêmico

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.

Vascular endothelial growth factor G1612A (rs10434) gene polymorphism and neuropsychiatric manifestations in systemic lupus erythematosus patients.

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.

Wernicke's encephalopathy mimicking neuropsychiatric symptoms in patients with systemic lupus erythematosus: a report of three cases and literature review.

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.

Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus.

OBJECTIVE: The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. RESULTS: The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. CONCLUSIONS: TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.

Electroconvulsive therapy for catatonia in juvenile neuropsychiatric lupus.

Neuropsychiatric manifestations are serious and frequent complications of systemic lupus erythematous (SLE). Catatonia is a neuropsychiatric disorder characterized by motor disturbance (including waxy flexibility and catalepsy), stupor, excitement, negativism, mutism, echopraxia and echolalia. Catatonia associated with SLE has been only rarely reported, especially in children. Here we present a case of a 14-year-old patient encountered in consultation-liaison psychiatry who presented catatonia associated with SLE. Her catatonia was refractory to treatment with pulse methylprednisolone, intravenous cyclophosphamide and rituximab. The patient responded to a combined therapy of electroconvulsive therapy and benzodiazepines. The present case suggests that although rarely reported, catatonia seen in the background of SLE should be promptly identified and treated to reduce the morbidity.

Neuro-Behçet's disease, its mimickers and anti-TNF therapy: a case-based review.

When the central nervous system is the primary affected site in an initial attack of Behçet's disease (BD), the differential diagnosis is particularly challenging. Because the specificity of immunobiologic therapy is growing, the specific diagnosis may impact the chosen therapy. For instance, anti-tumour necrosis factor agents are efficacious in BD but may be harmful in multiple sclerosis or systemic lupus erythematosus. We present two cases with similar neurological features but different diagnosis (BD and systemic lupus erythematosus) as a starting point to review diagnostic and therapeutic approaches for neuro-BD and its differential diagnoses.

Utility of interferon-α as a biomarker in central neuropsychiatric involvement in systemic lupus erythematosus.

OBJECTIVE: To assess the utility of interferon-α (IFN-α) in serum and cerebrospinal fluid (CSF) as a biomarker of disease activity in central neuropsychiatric systemic lupus erythematosus (cNPSLE). METHODS: Serum and CSF samples were drawn at hospitalization in 34 patients with cNPSLE, 16 surgical SLE, 4 primary neuropsychiatric conditions, and 25 with nonautoimmune conditions, except in 44 non-NPSLE patients in whom only serum was studied. Six months later, serum/CSF and serum samples were taken in 20 cNPSLE and 35 non-NPSLE patients, respectively. SLE activity was assessed at hospitalization, and 6 months later in cNPSLE and non-NPSLE patients. IFN-α was detected by Luminex technology. RESULTS: The mean ± SD age of patients with cNPSLE was 31.4 ± 12.2 years, which was similar across the study groups (p = 0.46). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores among cNPSLE, non-NPSLE, and SLE-surgical patients were 15.3 ± 8.2, 12.4 ± 8.2, and 3.8 ± 1.5, respectively. IFN-α levels in serum were higher in cNPSLE than in nonautoimmune patients (p = 0.02), but were similar to non-NPSLE and SLE-surgical groups. In CSF samples, IFN-α levels were higher in cNPSLE than in nonautoimmune patients (p = 0.03), and were nonsignificantly higher than in SLE-surgical and primary neuropsychiatric patients. Six months later, serum levels of IFN-α did not vary from baseline values despite a significant decrease in SLEDAI-2K score in cNPSLE and non-NPSLE patients. IFN-α levels in the CSF of patients with cNPSLE also remained stable. Among specific cNPSLE syndromes, CSF IFN-α levels were significantly higher among patients with acute confusional syndrome. CONCLUSION: IFN-α does not seem to represent a useful biomarker of cNPSLE syndromes; its utility in specific cNPSLE manifestations merits further investigation.

Antinuclear antibodies testing as a routine screening for systemic lupus erythematosus in patients presenting first-episode psychosis.

AIMS: This report discusses the use of antinuclear antibody (ANA) detection as a screening test for neuropsychiatry systemic lupus erythematosus (NPSLE) in patients presenting a first-episode psychosis. METHODS: We reviewed the medical records of 85 patients admitted to an emergency service due to first-episode psychosis, during a 1-year period, for whom ANA detection was performed through an IFI HEp2 cell assay. ANA-positive patients were subsequently evaluated for autoantibodies and neuroimaging exams. RESULTS: Three patients presented as ANA positive in the initial screening and further investigation confirmed NPSLE in two patients. The patients were treated with antipsychotics and cyclophosphamide pulses with satisfactory outcomes. CONCLUSION: Even though ANA detection is not specific, it is a low-cost procedure and could be an important screening test for NPSLE in the early-onset psychosis.

Neuropsychiatric manifestations in systemic lupus erythematosus: epidemiology, pathophysiology and management.

Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease with CNS involvement occurring in up to 75% of patients. However, the frequency of neuropsychiatric manifestations in SLE studies varies widely, depending on the type of manifestations included and the method used for evaluation. CNS involvement may be considered primary if directly related to SLE activity in the CNS or secondary when related to treatment, infections, metabolic abnormalities or other systemic manifestations such as uraemia and hypertension. The pathogenesis of neuropsychiatric SLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. However, independent of the aetiology of the insult, the final common pathway in neuropsychiatric SLE is the involvement of the cerebral microvasculature. The diagnosis of primary CNS involvement by SLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. Treatment is mostly empirical, although one randomized controlled trial has shown that cyclophosphamide in addition to methylprednisolone is superior to methylprednisolone alone in severe neuropsychiatric SLE.

Clinical, laboratory and neuroimage findings in juvenile systemic lupus erythematosus presenting involvement of the nervous system.

OBJECTIVE: To characterize neurological involvement in juvenile systemic lupus erythe-matosus. METHOD: The charts of all patients with the diagnosis of systemic lupus erythematosus before the age of 16 years, followed at the Rheumatology Unit of Pequeno Príncipe Hospital, from January 1992 to January 2006, were retrospectively reviewed, highlighting neuropsychiatric aspects. RESULTS: Forty-seven patients were included. Neuropsychiatric syndromes were found 29 (61.7%): seizures (17 / 36.2%), intractable headache (7 / 14.9%), mood disorders (5 / 10.6%), cerebrovascular disease (4 / 8.5%), acute confusional state (3 / 6.4%), aseptic meningitis (3 / 6.4%), psychosis (3 / 6.4%), chorea (3 / 6.4%), Guillain-Barré syndrome (2 / 4.3%) and cranial neuropathy (1 / 2.1%). Morbidity indexes (SLEDAI and SLICC) were higher among patients with neuropsychiatric manifestations (p<0.05). CONCLUSION: Neuropsychiatric syndromes are frequent, and add significant morbidity to juvenile systemic lupus erythematosus.

Clinical, laboratory and neuroimage findings in juvenile systemic lupus erythematosus presenting involvement of the nervous system

OBJECTIVE: To characterize neurological involvement in juvenile systemic lupus erythe-matosus. METHOD: The charts of all patients with the diagnosis of systemic lupus erythematosus before the age of 16 years, followed at the Rheumatology Unit of Pequeno Príncipe Hospital, from January 1992 to January 2006, were retrospectively reviewed, highlighting neuropsychiatric aspects. RESULTS: Forty-seven patients were included. Neuropsychiatric syndromes were found 29 (61.7 percent): seizures (17 / 36.2 percent), intractable headache (7 / 14.9 percent), mood disorders (5 / 10.6 percent), cerebrovascular disease (4 / 8.5 percent), acute confusional state (3 / 6.4 percent), aseptic meningitis (3 / 6.4 percent), psychosis (3 / 6.4 percent), chorea (3 / 6.4 percent), Guillain-Barré syndrome (2 / 4.3 percent) and cranial neuropathy (1 / 2.1 percent). Morbidity indexes (SLEDAI and SLICC) were higher among patients with neuropsychiatric manifestations (p<0.05). CONCLUSION: Neuropsychiatric syndromes are frequent, and add significant morbidity to juvenile systemic lupus erythematosus.

OBJETIVO: Caracterizar o comprometimento neurológico no lupus eritematoso sistêmico juvenil. MÉTODO: Os prontuários dos pacientes com o diagnóstico de lupus eritematoso sistêmico antes dos 16 anos de idade, em acompanhamento na Unidade de Reumatologia do Hospital Pequeno Príncipe, de janeiro de 1992 a janeiro de 2006, foram revisados retrospectivamente enfatizando aspectos neuropsiquiátricos. RESULTADOS: Quarenta e sete pacientes foram incluídos. Síndromes neuropsiquiátricas foram encontradas em 29 (61,7 por cento): crises convulsivas (17 / 36,2 por cento), cefaléia intratável (7 / 14,9 por cento), distúrbios do humor (5 / 10,6 por cento), doença cerebrovascular (4 / 8,5 por cento), estado confusional agudo (3 / 6,4 por cento), meningite asséptica (3 / 6,4 por cento), psicose (3 / 6,4 por cento), coréia (3 / 6,4 por cento), síndrome de Guillain-Barré (2 / 4,3 por cento) e neuropatia craniana (1 / 2,1 por cento). índices de morbidade (SEDAI e SLICC) foram maiores em pacientes com manifestações neuropsiquiátricas (p<0,05). CONCLUSÃO: Síndromes neuropsiquiátricas são um achado freqüente que acrescenta morbidade significativa ao lupus eritematoso sistêmico juvenil.

Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus.

OBJECTIVE: To define the cytokine and chemokine profile in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Forty-two SLE patients who had been hospitalized because of NP manifestations were studied. Patients were evaluated at hospitalization and 6 months later; a CSF sample was obtained at each evaluation. As controls, CSF from 6 SLE patients with septic meningitis, 16 SLE patients with no history of NP manifestations (non-NPSLE), and 25 patients with nonautoimmune diseases were also studied. Soluble molecules, including cytokines (interleukin-2 [IL-2], IL-4, IL-6, IL-10, tumor necrosis factor alpha [TNFalpha], and interferon-gamma [IFNgamma]) and chemokines (monocyte chemotactic protein 1 [MCP-1], RANTES, IL-8, monokine induced by IFNgamma [MIG], and interferon-gamma-inducible 10-kd protein [IP-10]), were measured with the use of cytometric bead array kits. RESULTS: CSF levels of the following molecules were significantly increased in NPSLE patients as compared with non-NPSLE and nonautoimmune diseases control patients, respectively: IL-6 (32.7 versus 3.0 and 2.96 pg/ml), IL-8 (102.8 versus 29.97 and 19.7 pg/ml), IP-10 (888.2 versus 329.7 [P not significant] and 133.6 pg/ml), RANTES (3.8 versus 2.5 and 2.2 pg/ml), MCP-1 (401.7 versus 257.9 [P not significant] and 136.9 pg/ml), and MIG (35.4 versus 11.4 and 3.5 pg/ml). Low levels of IL-2, IL-4, IL-10, TNFalpha, and IFNgamma were found in all groups. All cytokines and chemokines, except TNFalpha, were significantly higher among the SLE patients with septic meningitis than among the NPSLE patients. Six months later and in the absence of NP manifestations, all elevated molecule levels, except RANTES, in patients with NPSLE had decreased significantly, and no differences were noted between the NPSLE and non-NPSLE groups. CONCLUSION: A central nervous system response composed of IL-6 and chemokines, but not Th1/Th2 cytokines, is associated with NP manifestations in SLE patients.

Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus.

OBJECTIVE: To determine the value of voxel-based morphometry (VBM) of brain SPECT (single-photon emission computed tomography) images (BSI) in discriminating active central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Forty SLE patients (mean age 33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were screened for the presence of CNS involvement following the American College of Rheumatology (ACR) case definition. Patients with CNS infections, uraemia, diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige) with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the statistical parametric mapping. After normalization, segmentation and smoothing the groups of SLE patients with active and inactive CNS manifestations and healthy volunteers were compared using VBM. Post-processed images were compared voxel-by-voxel using t-test in order to determine differences of intensity between groups. This analysis included grand mean scaling, proportional threshold masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of 32 were taken into consideration. RESULTS: VBM analyses of BSI did not show any differences between SLE patients with inactive CNS involvement and normal controls. However, the group of SLE patients with active CNS involvement had a global hypoperfusion, more intense in the frontal, dorsolateral and medial temporal lobe when compared with SLE patients without CNS involvement (P = 0.001) and healthy volunteers (P = 0.001). CONCLUSION: VBM of BSI is a useful and objective method for detecting perfusion abnormalities in SLE patients, which is indicative of active CNS involvement. However, it is not helpful in differentiating the clinical sub-types of CNS involvement according to the ACR classification.