International Journal of Rheumatic Diseases 2013; 16: 715–723

ORIGINAL ARTICLE

Neuropsychiatric manifestations in a consecutive cohort of systemic lupus erythematosus; a single center study Amal Bakry ABDUL-SATTAR,1 Tarek GODA2 and Mohamed G. NEGM3 Departments of 1Rheumatology and Rehabilitation, 2Neurology, and 3Psychiatry, Faculty of medicine, Zagazig University, Zagazig, Egypt

Abstract Objectives: To identify the prevalence and the possible risk factors of occurrence and severity of neuropsychiatric (NP) manifestations in systemic lupus erythematosus (SLE). Patients and Methods: This is a cross-sectional study. The assessment of SLE patients is based on rheumatologic, neurologic and psychiatric evaluation, immunoserologic testing, and cerebral magnetic resonance imaging (MRI). Factors associated with NP manifestations were explored using regression models. Results: Of 84 SLE patients included in this study, 36 (42.9%) had neuropsychiatric manifestations. Among these 36 patients, 34 (94.4%) were female and two (5.6%) were male. The most frequent manifestations were mood disorders, headache and anxiety disorder. Of 36 patients with NP-SLE; 16 patients have severe NP manifestations (≥ 3 NP manifestations). In univariate analysis, the risk factors that associated with severe NP manifestations included more organ damage, cutaneous vasculitis, nephritis flare, the presence of antiphospholipid antibodies, particularly lupus anticoagulant and anti-cardiolipin immunoglobulin G (IgG aCL), abnormal MRI of the brain and aggressive use of immunosuppressives. However, in multiple regression analysis, nephritis, cutaneous vasculitis, and IgG aCL were the only risk factors of severe NP manifestations. Conclusions: Due to the high prevalence of NP manifestations and its severity in SLE patients, systematic assessment to provide prompt diagnosis, early recognition of risk factors and appropriate intervention for NP lupus are essential. Key words: neuropsychiatric manifestations, prevalence, risk factors, systemic lupus erythematosus.

INTRODUCTION Systemic lupus erythematosus (SLE) is an autoimmune, chronic inflammatory disorder affecting the connective tissue of multiple organ systems. It occurs on the background of disturbances of environmental, hormonal and genetic factors. It is nine times more common in women.1 Neurologic and psychiatric (NP) manifestations of unknown etiology are common in SLE and

Correspondence: Dr Amal Bakry Abdul-Sattar, Department of Rheumatology and Rehabilitation, Faculty of medicine, Zagazig University, 16 El-Emam Ali St. Villat El Jamaa., Zagazig, Sharkia governorate, Zagazig, Egypt. Email: [email protected]

have been proposed to represent a more severe form of the disease.2 Approximately 40% of NP-SLE manifestations develop before the onset of SLE or at the time of diagnosis and about 60% within the first year after diagnosis.3 It affects patients with SLE physically, mentally and also lowers their quality of life.4 Classification and nomenclature of nervous system disorders in lupus have evolved from the first proposed in 1979 by Kassan and Lockshin,5 through Singer and Denburg6 criteria to the current classification of neuropsychiatric systemic lupus erythematosus (NP-SLE), published in 1999 by the American College of Rheumatology (ACR) Research Committee. ACR classification of NPSLE recognizes five groups of psychiatric disorders: mood disorder, anxiety disorder, cognitive dysfunction, psychosis and acute

© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd

A. B. Abdul-Sattar et al.

confusional state.7 Estimates of the prevalence of clinical NP-SLE vary from 13%8 to 91%.9 Brey et al.10 have shown that NP lesions are present in more than twothirds of patients with SLE. Although there is evidence to implicate primary immunopathogenic mechanisms in NP-SLE, such as vasculopathy, auto-antibodies and mediators of inflammation,11 the lack of specificity of most of the NP manifestations raises the possibility of alternative etiologies which has important implications for the management and prognosis of individual SLE patients who present with NP events.12 The predictors of NP damage have been difficult to ascertain. The heterogeneity of NP manifestations preceding NP damage, the problems with adequate classification of these NP manifestations, and the different types of NP damage (which may have different predictors) probably explain the paucity of literature on this subject.13 Furthermore, the NP manifestations previously recognized among the ACR criteria for the classifications of patients with SLE14,15 include only seizure and psychosis and not others that may be followed by NP damage. Using the revised ACR nomenclature and case definitions of NPSLE7 as well as the individual items of the NP domains of the Damage Index for Systemic Lupus Erythematosus (SDI) as endpoints, we have now reassessed the risk factors associated with significant NP damage in a contemporary SLE cohort. The aim of our study is identifying the prevalence and risk factors for occurrence and severity of NP manifestations in SLE.

PATIENTS AND METHODS Eighty-four patients affected with SLE, as diagnosed according to the 1982 ACR revised criteria, modified in 1997,14,15 were consecutively recruited from the outpatient clinics of the Rheumatology Department, Faculty of Medicine, Zagazig University Hospital in this cross-sectional study during the period from July, 2011 to December, 2012. The regional ethics committee of Zagazig University Hospital approved the study and written informed consent was obtained from each patient. The medical records of all patients were reviewed, with particular attention to history of central nervous system (CNS) manifestations. Demographics data, including educational years, past medical history with date of disease onset, which was defined as the time at which a patient met four ACR criteria for the classification of SLE, comorbidities, previous and concomitant treatments, and cardiovascular risk factors, were recorded for all patients. Exclusion criteria included: (i) age < 18 years; (ii) presence of secondary lesions of the nervous system

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related to infections, electrolyte disturbances, drug intake (neuroleptics, L-dopa), concurrent syndromes, such as chronic renal failure, or diseases such as hyperthyroidism; and (iii) drug abuse. All patients underwent the following assessments.

Evaluation of clinical disease activity and damage indices Clinical activity was assessed using the SLE Disease Activity Index (SLEDAI),16 while chronic damage was evaluated using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index.17 Nephritis was defined as mesangial, focal proliferative, diffuse proliferative or membranous glomerulonephritis according to the WHO classification on histopathology, or persistent proteinuria > 0.5 g/day, or proteinuria > 3.5 g/day, or cellular casts of any kind according to ACR criteria.14,15

Immunological examinations Antinuclear antibodies (ANA) were measured with an immunofluorescence test using rat liver as the substrate and following the WHO recommendations.18 Serum samples were diluted 1/10 for detection of antibodies against double-stranded DNA (ds-DNA) on Crithidia luciliae assay19; C3 and C4 complement components were tested by nephelometry; anti-Ro/SSA (Sj€ ogren’s Syndrome antigen A) and anti-La/SSB antibodies were tested using the traditional Ouchterlony double immunodiffusion method.20 Anti-Smith (Sm) and anti-ribonucleoproteic particle (anti-RNP) antibodies were detected using a commercial enzyme-linked immunosorbent assay (ELISA), and if these antibodies fluctuated over time on repeated testing an immunoprecipitation test was performed to confirm these antibodies.21 Lupus anticoagulant (LAC) was ascertained using the guidelines established by the 1991 Scientific Subcommittee criteria, later simplified by Exner22; anti-IgM (immunoglobulin M) and IgG anticardiolipin (aCL) antibodies were measured using a commercial ELISA kit (Pharmacia, Uppsala, Sweden).23 The cutoff values were 10 units/mL for both IgG and IgM aCL antibodies and patients with antibodies (> 10 units) on two occasions, at least 12 weeks apart, were considered to be positive.

Neuropsychological assessment An extensive neuropsychological assessment was performed for each patient by a psychiatrist and neurologist using the ACR nomenclature to define major NP manifestations.7 Only patients with a definite diagnosis based on neurologic or psychiatric evaluations were

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classified as having NP-SLE. Mini-Mental Status Examination (MMSE) was used to evaluate the cognitive function, where orientation (time and place), attention, language, short-term memory, calculation and complex commands are considered. The MMSE score ranges from 0 to 30.24 In the present study, cognitive impairment was diagnosed if the MMSE score was ≤ 21.25 Mood was assessed by the Hamilton Depression Scale which is a widely used and reliable scale and not specific for elderly people.26 The cutoff point of depression in this scale is ≥ 17, according to Michele and Bolino,27 while anxiety disorder was measured by the Hamilton Anxiety Scale which lists 14 types of symptoms. The total score ranges from 0 to 56. A total score of 18 or more indicates anxiety.28 According to the Mkdashi and Handwerger study,13 we divided the patients into three groups according to the NP damage index: (i) no NP damage, NPDI = 0; (ii) mild NP damage, NPDI = 1 or 2; (iii) sever NP damage, NPDI ≥ 3, to determine the risk factors that may be associated with sever NP-SLE not simply the presence of NP manifestations.

Imaging study Cerebral magnetic resonance imaging (MRI) was performed by an SP-Siemens 1.5 T scanner (Siemens, Erlangen, Finland). MRI was performed without a contrast medium, using spin-echo proton density and T2weighted sequences in the axial plane. Imaging was evaluated by a radiologist unaware of the patient’s cognitive and clinical status. MRI images were analyzed for the presence of: (i) cortical atrophy and (ii) size and location of areas of increased signal intensity according to McCune et al.29 and Molad et al.30 The size of the lesions was defined as micro (6 mm), macro (6–10 mm), or large (10 mm). The following locations were considered: frontal, parietal, temporal and occipital lobes (cortical, juxtacortical and subcortical), as well as other locations (cerebellum, basal ganglia and diencephalon). A scan that revealed two small focal lesions was considered a normal scan.

Statistical analysis Categorical data were reported as percentages and continuous data as the mean  SD. Student’s t-test was used to assess normally distributed continuous data and Wilcoxon rank sum test for non-normally distributed continuous data outcome. The Chi-squared test was used to compare categorical data outcomes. Univariate logistic regression analyses were applied to evaluate the association of the independent variables with NP manifestations. Analytical results of univariate analyses were

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Table 1 Demographic, clinical and radiological features of the all studied systemic lupus erythematosus patients Female/male Age, mean  SD Educational years, mean  SD SLE duration, mean  SD Cumulative ACR SLE criteria, mean  SD Malar rash Discoid rash Photosensitivity Oral ulcers Non-erosive arthritis Pleuritis or pericarditis Renal disorder Neurologic disorder Hematologic disorder Immunologic disorder ANA positive SLEDAI score, mean  SD SDI score, mean  SD NP manifestations, no. (%) Mood disorder Headache Anxiety disorder Cerebrovascular disease Cognitive disorder Seizure disorder Psychosis Polyneuropathy Mononeuropathy MMSE, mean  SD Hamilton Depression Scale, mean  SD Hamilton Anxiety Scale, mean  SD Medication received, no. (%) Corticosteroids Azathioprin Antimalarial agents Cyclophosphamide Abnormal brain MRI, no. (%) Abnormal T2 weighted image Parietal gliosis Mild cerebral atrophy

79/5 30.9  11.7 10.5  4.3 5.6  4.7 5.3  1.1 22 (27) 24 (28.5) 25 (30) 21 (25) 12 (14) 20 (24) 28 (33.3) 36 (42.8) 23 (27) 73 (87) 81 (96.4) 6.1  5.9 1.0  0.5 36 (44) 16 (44) 10 (27.7) 7 (19.4) 6 (16.6) 1 (2.7) 3 (8) 4 (11) 4 (11) 2 (2) 22  3 14  4 84 84 (100) 40 (47.6) 32 (38) 30 (35.7) 19 (22.6) 10 (52.6) 3 (15.7) 2 (10.5)

Values are the number (percentage) unless otherwise indicated, ACR, American College of Rheumatology; ANA, antinuclear antibody; MMSE, Mini-Mental Status Examination; MRI, magnetic resonance imaging; NP, neuropsychiatric; SLEDAI, SLE Disease Activity Index; SDI, Systemic Lupus International Collaborating Clinics/ACR Damage Index.

presented as the crude odds ratios (ORs) and 95% confidence intervals (CIs). All variables with P < 0.20 in univariate analysis were included in subsequent multivariate logistic regression analyses, whereas those with P < 0.10 were retained in the final model. The independent variables were the same as in the univariate analysis, while the dependent variable was the number of NP

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Table 2 Clinical manifestations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric (NP) manifestations Variables

SLE patients without NP (n = 48)

SLE patients with NP (n = 36)

P-value

Age, years, mean  SD Age at onset < 35 years, no. (%) Gender: female, no (%) Disease duration, years, mean  SD Dermatologic flare, no. (%) Arthritis flare, no. (%) Major organ flare, no. (%) Hematologic Nephritis Serositis Cardiopulmonary Gastrointestinal Cutaneous vasculitis Antibodies positivity, no. (%) Anti-cardiolipin IgG Anti-cardiolipin IgM Lupus anticoagulant Anti-RO/SSA Anti-La/SSB ANA Anti-dsDNA SLEDAI, mean  SD SDI, mean  SD C3 < 53 mg, no. (%) C4 < 20 mg, no. (%) Abnormal brain MRI, no. (%) Pregnancy loss, no. (%) Prednisolone, mg/day, mean  SD Cyclophosphamide use, no. (%) Cardiovascular risk factors, no. (%) Hypertension Dyslipidemia Ischemic heart disease

29  7.4 35 (72.9) 45 (93.75) 5.6  2.1 11 (22.9) 8 (16.6)

31  8.9 32 (88.8) 34 (94.4) 6.7  1.3 12 (33.3) 6 (16.6)

0.463 0.300 0.554 0.11 0.026 0.969

8 (16.6) 10 (20.8) 13 (27.0) 2 (4.16) 1 (2.1) 8 (16.6)

15 (41.6) 18 (50) 6 (16.6) 1 (2.7) 2 (5.5) 11 (30.5)

0.001* 0.001* 0.130 0.785 0.72 0.01*

8 (16.6) 6 (12.5) 1 (2.1) 17 (35.4) 5 (10.4) 45 (93.75) 42 (87.5) 5.0  2.3 0.5  0.72 4 (8) 10 (21) 2 (4.16) 3 (6.3) 4.5  3.4 10 (20.8)

14 (38.8) 6 (16.6) 5 (13.8) 14 (38.8) 2 (5.5) 36 (100) 31 (86.1) 15.6  2.1 4.0  1.5 9 (26) 17 (49) 17 (47.2) 11 (30.5%) 12.0  6.5 18 (50)

0.03* 0.560 0.030* 0.830 0.400 0.650 0.953 0.001* 0.001* 0.003* 0.001* 0.001* 0.003* 0.001* 0.001*

8 (16.6) 17 (35.4) 3 (6.25)

8 (22.2) 14 (38.8) 5 (13.8)

0.72 0.830 0.785

*P-value is significant if < 0.05. Values are the number (percentage) unless otherwise indicated. NP, neuropsychiatric; SLE, systemic lupus erythematosus; ANA, antinuclear antibodies; anti-dsDNA, anti-double-stranded DNA; SLEDAI, SLE Disease Activity Index; SDI, the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index; MRI, magnetic resonance imaging.

manifestations that determine the severity of NP. So, we can determine the risk factors that are associated with sever NP-SLE. All of the statistical tests were two-tailed and a P-value of < 0.05 was required for statistical significance. Statistical analyses were performed using SPSS software version 11.0 (SPSS Inc., Chicago, IL, USA).

RESULTS Eighty-four patients (94% female) with SLE were studied. The mean age of the patients was 30.9  11.7 years, while the mean age of disease onset

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was 28.4  10.6 years and the mean SLE disease duration was 5.6  4.7 years. The mean cumulative ACR SLE criteria was 5.3  1.1. The most frequent SLE manifestations were immunologic disorder (86.9%), NP manifestations (42%), photosensitivity (30%) and renal disorder (28%). Among the NP manifestations in 36 patients, nine of the 19 ACR NP-SLE syndromes were identified and 16 patients (44.4%) had severe NP (NPDI ≥ 3). CNS manifestations accounted for 83.3% (30/36 patients), while involvement of the PNS was 13.7% (6/36 patients). The three most frequent NP manifestations were mood disorders (44%), headache

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Table 3 Univariate analyses of factors associated with severe NP damage (NPDI ≥ 3) Variables

Age of onset < 35 years (n = 32) ≥ 35 years (n = 4) Gender Female (n = 34) Male (n = 2) Post-secondary education No (n = 32) Yes (n = 4) SDI 0 (n = 21) ≥ 1 (n = 15) Nephritis flare No (n = 18) Yes (n = 18) Hematologic flare No (n = 21) Yes (n = 15) Serositis flare No (n = 30) Yes (n = 6) Cardiopulmonary flare No (n = 35) Yes (n = 1) Gastrointestinal flare No (n = 34) Yes (n = 2) Cutaneous vasculitis No (n = 25) Yes (n = 11) Arthritis Flare No (n = 30) Yes (n = 6) Dermatologic flare No (n = 24) Yes (n = 12) Anti-cardiolipin IgG positivity No (n = 22) Yes (n = 14) Anti-cardiolipin IgM positivity No (n = 30) Yes (n = 6) Lupus anti-coagulant positivity No (n = 31) Yes (n = 5) Anti-Ro-SSA positivity No (n = 22) Yes (n = 14)

No. of patients with severe NP damage ≥ 3, no. (%)

OR (95%CI)

P-value

14 (43.75) 2 (50)

07 (0.4–1.2)

0.20

15 (44.1) 1 (50)

1.1 (0.5–2.7)

0.83

14 (43.75) 1 (25)

0.8 (0.6–1.3)

0.21

6 (28) 10 (66.6)

6.8 (2–23.6)

0.0015*

5 (22.7) 10 (55.5)

4.7 (1.3–17.1)

0.027*

10 (47.6) 6 (40)

0.7 (0.3–1.5)

0.35

14 (46.6) 2 (33.3)

1.8 (0.6–5.4)

0.29

16 (45.7) 0 15 (44) 1 (50)





1.1 (0.5–2.7)

0.83

2.4 (1.25–4.23)

0.03*

13 (43.3) 3 (50)

0.7 (0.4–1.2)

0.20

11 (45.8) 5 (41.6)

1.3 (0.6–2.7)

0.56

7 (31.8) 9 (64.2)

4.2 (1.9–10.9)

0.001*

14 (46.6) 2 (33.3)

1.8 (0.6–5.4)

0.29

12 (38.7) 4 (80)

3.2 (1.02–10.4)

0.043

0.7 (0.4–1.2)

0.35

9 (36) 7 (63.6)

9 (40.9) 7 (50)

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Table 3 (continued) Variables

No. of patients with severe NP damage ≥ 3, no. (%)

OR (95%CI)

15 (44.1) 1 (50)

1.8 (0.6–5.4)

0.2

2 (40) 14 (45.2)

0.8 (0.2–1.1)

0.832

4 (22.2) 12 (66.6)

5.1 (2.32–11.6)

0.001*

5 (26.3) 10 (58.8)

2.45 (1.38–4.33)

Anti-La_SSA positivity No (n = 34) Yes (n = 2) Anti-dsDNA positivity No (n = 5) Yes (n = 31) Cyclophosphamid use No (n = 18) Yes (n = 18) MRI changes of brain No (n = 19) Yes (n = 17)

P-value

< 0.01*

*P-value is significant if < 0.05. Values are the number (percentage). anti-dsDNA, anti-double- stranded DNA; CI, confidence interval; MRI, magnetic resonance imaging; NP, neuropsychiatric; NPDI, Neuropsychiatric Damage Index; OR, odds ratio; SDI, the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index; SSA, Sj€ ogren’s syndrome antigen A.

Table 4 Multivariate analyses of factors associated with severe NP damage Independent variables

B

T

P

Nephritis flare IgG aCL Cutaneous vasculaitis

1.37 1.34 2.17

2.22 2.22 1.79

0.03 0.04 0.03

P-value is significant if < 0.05. IgG aCL, anti-cardiolipin IgG; NP, neuropsychiatric.

(27.7%), and anxiety disorder (19.4%). The mean of the Hamilton Depression Scale was 14  4, while the mean of the Hamilton Anxiety Scale was 8  4. Abnormal brain MRI findings were showed in 17 NP-SLE patients and two patients without NP manifestations. Table 1 shows the demographic, clinical and radiological features of the all studied SLE patients. In order to identify the risk factors that were related to the development of neuropsychiatric manifestations, we analyzed the relatioship between clinical, radiological and laboratory abnormalities in SLE patients with and without neuropsychiatric manifestations (Table 2). Table 3 shows the potential associations of severe NP manifestations (NPDI ≥ 3) with various clinical and laboratory characteristics in univariate relationships. Factors associated with severe NP manifestations in the univariate analysis were entered into a multiple logistic regression model as shown in Table 4; nephritis flare, cutaneous vasculitis and IgG aCL were risk factors for severe NP manifestations.

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DISCUSSION This study analyzed the main factors affecting the occurrence and severity of NP dysfunctions in Egyptian patients with SLE. The prevalence of NP manifestation in our study was 42.9%. In the study by Ainiala et al.9 at least one NP syndrome was identified in 42 patients (91%); Afeltra et al.31found that NP manifestations that were consistent with the diagnosis of NP-SLE occurred in 44 (72%) of their patients. However, Unterman et al.32 reported that of their 407 study patients with SLE, 11.3% had NP complications. This variation may be due to different populations and regions (including race, socioeconomic status) and study methodology, as suggested.8 The three most common NP manifestations in our study were mood disorders (44.4%), headache (27.7%) and anxiety disorder (19.4%). Previous studies9,33 found that headache was one of the most frequent NP manifestations in SLE patients. Also, Unterman et al.32 reported that the most prevalent NP manifestations in SLE patients were headache (28.3%) and mood disorders (20.7%). The age of disease onset and duration of disease were not associated with NP-SLE in this study. These findings were similar to previous studies13,34,35 and in contrast with one other study.8 Similar to a previous study,13 patients with NP manifestations were more likely to be treated more aggressively, as evidenced by the more frequent use of immunosuppressive therapy and use of a higher dose of corticosteroids. Also, Hanly et al.36 concluded that the

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occurrence of NP disease is associated with more frequent use of corticosteroids and immunosuppressive drugs. In our study, lupus disease activity and cumulative organ damage were higher in the NPSLE group. These results are in accordance with previous studies10,13,35,37 which found more organ damage in the NPSLE group, which was, as expected, due to neurological disease. Recently, Conti et al.38 concluded that disease activity and chronic damage are associated with cognitive dysfunction in SLE. The risk factors for the development of significant NP manifestations in our study were nephritis, cutaneous vasculitis and antiphospholipid antibodies (LAC and IgG aCL). Prior studies have shown that NP manifestations were more common in SLE patients with greater cutaneous vasculitis,8,39,40 diffuse glomerulonephritis13,41 and antiphospholipid antibodies.31,38,42–44 Our findings showed that the presence of ANA and antibodies to ds-DNA did not associate with NP manifestations and they were not risk factors for NP-SLE. This result is in accordance with previous findings40,45 that some patients with active NP-SLE may lack serum ANA and antibodies to ds-DNA. In contrast to a previous study,39 we found that the low serum levels of C3 and C4 complement components was not associated with NP manifestations and were not a predictor of NP-SLE in our multivariate analyses. Our results are in contrast with previous studies13,46 which identified an association between abnormal MRI of the brain and NP manifestation. In the present study, most of our patients were female (94%) and pregnancy loss was significantly associated with NP manifestations. This finding is in accordance with a previous study.39 We found that arthritis, serositis and dermatologic flare were not associated with NP manifestations. These results agreed with results of other studies.13,37 On the other hand, one study40 showed a trend toward a smaller prevalence of articular manifestations in a NPSLE group compared with that of SLE control patients. In contrast to our study, Govoni et al.47concluded that modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions in SLE patients. Regarding factors that associated with severe NP manifestations, we found that nephritis flare, cutaneous vasculitis and IgG aCL were independent predictors of severe NP manifestations in the multiple logistic regression analysis. A previous study13 has shown that the

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independent predictors of severe NP damage included cutaneous vasculitis and antiphospholipid antibodies. In conclusion, NP manifestations are highly prevalent among SLE patients. Minor NP-SLE manifestation such as mood disorders, headache and anxiety are more common in active SLE patients and are associated with lupus nephritis, IgG aCL and cutaneous vasculitis. The definition of a group of SLE patients with risk factors for NP manifestations is important for preventive and therapeutic purposes. Limitations of this study must be taken in account. The cross-sectional design limits the ability to determine temporal relationships. Thus, further longitudinal study with a larger sample is necessary to confirm the finding of this study. Surprisingly, the prevalence of cognitive disorder was low in this study. This may be due to using the MMSE which is a relatively insensitive tool for cognitive assessment. Finally, we did not study antibodies in the cerebral spinal fluid.

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Neuropsychiatric manifestations in a consecutive cohort of systemic lupus erythematosus; a single center study.

To identify the prevalence and the possible risk factors of occurrence and severity of neuropsychiatric (NP) manifestations in systemic lupus erythema...
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