Neuropsychiatric Features of a Cohort of Patients with Systemic Lupus Erythematosus

BackgroundNeuropsychiatric (NP) lupus is common among patient with systemic lupus erythematosus (SLE). It occurs in about 30%–56% of all SLE patients. However, the diagnosis of neuropsychiatric SLE (NPSLE) remains difficult....

Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. Objective: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE. Methods: The study included a predominantly population-based cohort with clinical and serological investigations of 208 patients with SLE, followed prospectively since 1995. All patients received immunosuppressive treatment. NMOSD was evaluated retrospectively based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria. Polymorphisms in programmed cell death protein 1 (PDCD-1) PD-1.3 G/A were genotyped. AGP4-IgG and other autoantibodies, including myelin oligodendrocyte glycoprotein (MOG), was determined blinded to clinical diagnosis. Results: Of 208 patients with SLE, 45(22%) had neuropsychiatric (NP) SLE, and CNS involvement predominated in 30 of 45 (67%) patients. Serum AQP4-IgG was detected in 2 of 30 (6.7%) neuropsychiatric SLE (NPSLE) patients both of whom had myelitis and antiphospholipid syndrome; one patient also had myasthenia gravis. None had MOG-IgG. PD-1.3A allele was not associated with SLE nor with NPSLE. Conclusion: AQP4-IgG autoimmune syndrome may rarely co-exist with SLE, and such patients have other NMOSD-typical syndromes such as myelitis.

Background and Objective Neuropsychiatric manifestations are frequently reported in 75% of Systemic Lupus Erythematosus (SLE) patients and that varied from mild subtle signs: headache or mood disturbance to life threatening conditions: acute confusional state, major fits, stroke or transverse myelitis. Electroencephalography (EEG) was used to determine whether there is a lateralized pattern of electrophysiologic dysfunction in SLE patients or not. So, this study was done to describe EEG findings in a cohort of Egyptian SLE patients with Neuropsychiatric SLE (NPSLE), its possible correlation with any of the disease activity parameters and comparing them to patients with Non-NPSLE. Patients and Methods This case-control study was conducted on 60 SLE patients who fulfilled the 2015 ACR/SLICC Classification Criteria for SLE. They were classified into 2 groups: 30 patients with NPSLE as cases and 30 patients without NPSLE (Non-NPSLE) as controls. All patients were subjected to detailed medical history taking together with full clinical examination and calculations of SLE disease activity using the SLE disease activity index (SLEDAI) score. Laboratory investigations including CBC, ESR, CRP, BUN, creatinine, urine analysis, P/C ratio, C3, C4, Lupus Anticoagulant (LAC) and Anticardiolipin (ACL) antibodies and EEG were done for all patients. MRI brain was done for patients with NPSLE. Results There were 6 neuropsychiatric manifestations in the NPSLE group; the commonest was seizure disorders (43.3%), followed by psychosis (20.0%), cerebrovascular disease (16.7%), acute confusional state (13.3%), headache (10.0%) and lastly demyelinating syndrome (6.7%). SLEDAI score was higher in NPSLE group (Median=16) than nonNPSLE group (Median=4) (P < 0.01). ACL IgM positivity was higher in NPSLE group (P < 0.05). 53.3% of NPSLE group had abnormal MRI brain findings, the most common finding was periventricular white matter lesion (23.3%), followed by infarction (13.3%), subcortical white matter lesion and demyelinating lesion (6.7%). Lastly was sinus thrombosis, cerebral edema and encephalomalacia (3.3% each). 12 patients out of 30 (40.0%) with NPSLE had EEG abnormalities, while all 30 patients with non-NPSLE had no EEG abnormalities. The most common EEG abnormalities in NPSLE group were diffuse slowing (20.0%), followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7% each). 50% of patients with abnormal EEG had normal MRI. 13 patients out of 30 with NPSLE had seizure disorders (43.3%), 8 of them had abnormal EEG (61.5%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in diagnosing and studying the different manifestations of NPSLE especially seizure disorder and acute confusional state, but it cannot be used as a screening test alone for detecting NPSLE and must be supplemented by neuroimaging studies.

Neuropsychiatric (NP) manifestations pose diagnostic and therapeutic challenges in systemic lupus erythematosus (SLE). Less than one-third of these events can be directly attributed to SLE; accordingly attribution to SLE remains a considerable challenge. Increased generalized SLE disease activity or damage, previous or concurrent major neuropsychiatric SLE (NPSLE) events, and persistently positive moderate-to-high antiphospholipid antibody titers are established risk factors. NPSLE patients have increased genetic burden and novel genomic approaches are expected to elucidate its pathogenesis. In animals with disturbed blood-brain barrier, autoantibodies against the NR2 subunits of the N-methyl-D-aspartate receptor and 16/6 idiotype antibodies, may cause diffuse NP manifestations through neuronal apoptosis or brain inflammation; data in humans are still circumstantial. In NPSLE, advanced neuroimaging uncovers structural and metabolic abnormalities in brain regions with normal appearance on conventional magnetic resonance imaging. The European League Against Rheumatism (EULAR) has published evidence and expert based opinion for the management of NPSLE(1).. According to them, diagnostic evaluation is guided by the presenting manifestation with MRI used to visualize brain or spinal pathologies. For neuropsychiatric events believed to reflect an immune or inflammatory process, or when these events occur in the context of active generalized disease, evidence (primarily from uncontrolled studies) supports the use of glucocorticoids alone or in combination with immunosuppressive therapy. In refractory cases, uncontrolled studies suggest a beneficial role of rituximab. Antiplatelet and/or anticoagulation therapy is recommended for NPSLE manifestations related to antiphospholipid antibodies, especially for thrombotic cerebrovascular disease. For the future, we anticipate that novel biomarkers and advanced neuroimaging tests will better define the underlying pathologic mechanisms of SLE-related neuropsychiatric disease, and help guide therapeutic decisions.

Neuropsychiatric systemic lupus erythematosus (NPSLE) has varied manifestations. To study the pattern of neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE). Hospital based cross sectional and retrospective study. Patients admitted with a diagnosis of SLE, during a period of 16 months, were evaluated and any NP syndrome present classified as per the American College of Rheumatology (ACR) nomenclature. SPSS software Version 10 was used for descriptive analysis and correlative study. Out of 50 patients with SLE, all the patients with NPSLE [39 (78%)] were females, mean age 25.66 years (range: 11-44). The commonest manifestation was headache [20 (55.6%)]. Seizures were seen in 8 (20.51%) and psychosis in 6 (16.2%). Fine distal tremor was seen in 8 (20.51%) of patients. Headache is a frequent NP syndrome. Fine distal tremor is a syndrome not included in ACR classification but seen is 20% of our patients with NPSLE.

Objective To analyze the laboratory indexes and clinical symptoms of patients with neuropsychiatric systemic lupus erythematosus (NPSLE), so as to provide the basis for the condition judgment and individual treatment of NPSLE patients. Methods The laboratory indexes and clinical manifestations of 136 cases of NPSLE and 146 cases of non-NPSLE were compared and analyzed. Results The distribution of C-reactive protein, neutrophils, neutrophil rate, antinuclear antibodies (ANA) and hepatitis B virus DNA copies in NPSLE group were higher than those in non-NPSLE group (P<0.05), while the distribution of serum albumin, erythrocyte sedimentation rate, immune globulin G, and immune globulin E concentrations, lymphocytes and lymphocyte ratio were lower than those in non-NPSLE group (P<0.05). The systemic lupus erythematosus disease activity index (SLEDAI) score in NPSLE group was significantly higher than in that non-NPSLE group (P<0.05). In addition to the neuropsychological manifestations, the clinical symptoms of low complement (89.71%), 24 hours proteinuria (59.50%) and fever (58.82%) are also common in NPSLE group. Conclusions The activity of NPSLE patients was related to the decrease of lymphocyte count and proportion while ANA was positive in serum. Hepatitis B virus infection may be related to NPSLE, which should be paid more attention in clinical diagnosis and treatment. Key words: Lupus; Nervous system; Laboratory index; Clinical symptoms

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

ObjectiveSubstantial proportions of systemic lupus erythematosus (SLE) patients report severe fatigue and adverse Health-related Quality of Life (HRQoL). Particularly neuropsychiatric manifestations have been associated with reduced HRQoL. Our objective was...

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

PV021 / #98Poster Topic:AS03 - Antiphospholipid SyndromeBackground/PurposeUnderstanding how, when and in whom Antiphospholipid Syndrome (APS) and thromboembolic events (TE) develops in Systemic Lupus Erythematosus (SLE) is important as it may facilitate risk stratification and preventive strategies. Here, we aimed to track patients from SLE diagnosis and assess relationships between APS, TE and antiphospholipid antibodies (aPL) during follow-up.MethodsWe included all new SLE patients residing in Southeast Norway 2000-2017. All patients had chart review confirmed diagnosis, fulfilled the 2019 European League Against Rheumatism and American College of Rheumatology SLE classification criteria and were captured within 1 year of diagnosis. Follow-up ended 1 January 2018. APS was defined by the 2006 Sydney classification criteria and aPL positivity referred to positive anticardiolipin, anti-b2glycoprotein and/or lupus anticoagulant following international guidelines. TE were defined by both arterial and venous events and included ischemic stroke, transient ischemic attack, myocardial infarction, angina pectoris or syndromes caused by occlusion of major venous vessel identified either by chart review or by ICD-10 code (I20-22, I63, G46, R96, I26, I80-I82) in The National Cause of Death Register. We estimated APS- and TE-free survival using Kaplan-Meier methods and identified factors associated with TE with Cox regression analysis.ResultsAmong 700 new SLE patients, 79 (11%) had co-occurring APS after a mean follow-up of 8 years (SD 5). Compared to non-APS patients, APS patients more frequently had thrombocytopenia (25/79, 32% vs 123/621, 20%, p-value&lt;0.012), neuropsychiatric lupus (6/79, 8% vs 16/621, 3%, p-value&lt;0.016) and anti-dsDNA antibodies (66/79, 84% vs 450/621, 72%, p-value&lt;0.035) at the time of SLE diagnosis, but mean age at SLE diagnosis (37, SD 15 vs 39, SD 17, p-value=0.309) and frequency of LN were the same (29/79, 37% vs 195/621, 31%, p-value=0.341). During follow-up, 54 SLE patient developed a new APS. At the time of SLE diagnosis, 45 of these 54 patients (83%) were aPL positive, 5 (9%) were aPL-negative and 4 (7%) had an unknown aPL status. The 5-year APS-free survival was higher in aPL-negative (0.99, 95% CI 0.97-1.00) than aPL-positive patients (0.80, 95% CI 0.74-0.85, p&lt;0.001). (Figure 1) By the end of follow-up, 156 (22%) patients had experienced at least 1 TE, with a clear clustering around SLE diagnosis. Of the 36 TEs occurring in the same year as SLE diagnosis, 26 (64%) were related to new APS. (Figure 2) Excluding those with TE or APS prior to SLE diagnosis, we found that TE developed in 45/206 (22%) of aPL-positive patients, 31/332 (9%) of aPL-negative patients and in 13/88 (15%) of patients with unknown aPL status at time of SLE diagnosis. Overall, 10-year TE-free survival was 0.84 (95% CI 0.81-0.87). TE-free survival was lower in the aPL-positive patients than in the aPL-negative already 1 year after SLE diagnosis (0.88, 95% CI 0.83-0.92 vs 0.98, 95% CI 0.96-0.99, p-value&lt;0.001). Stratified by age, aPL-negative patients &lt;50 years at diagnosis had persistently high TE-free survival, while patients ≥50 at SLE diagnosis continued to develop TE across the follow-up period, both in aPL-negative and aPL-positive patients. (Figure 2) In multivariable analyses lupus anticoagulant, ≥2 aPLs and older age at SLE diagnosis were the individually factors with highest hazard ratios for new TE when adjusting for sex, ethnic ancestry and age.Figure 1.Figure 2.ConclusionsThis population-level study reveals a heightened risk of TE, particularly in the context of APS, around SLE onset. The elevated thromboembolic risk in new SLE requires attention and may call for preventive measures.

Neuropsychiatric Lupus: The Prevalence and Autoantibody Associations Depend on the Definition: Results from the 1000 Faces of Lupus Cohort

The aim was to study the prevalence of epilepsy in a hospital-based systemic lupus erythematosus (SLE) cohort and to investigate the relationship between epilepsy and other manifestations of neuropsychiatric SLE (NPSLE). The study population consisted of 440 SLE patients recruited from 1998 to 2012. An epilepsy-screening questionnaire was sent to all patients, where those screening positive were invited to a neurological examination with documentation of NPSLE symptoms according to the American College of Rheumatology nomenclature. Occurrences of autoantibodies (double stranded DNAantibody, antinuclear antibody, lupus anticoagulant, Sjögren's syndrome A, Sjögren's syndrome B) and the antiphospholipid syndrome (APS) were tabulated. Out of 440 patients, 14% were dead and 2.7% were lost to follow-up. The questionnaire was sent to 368 patients; 312 (85%) responded. Of these, 131 (42%) screened positive. Epilepsy was confirmed in 36 (11.5%), of whom 30 (83%) had focal onset. Ten (3.2%) patients had isolated or provoked seizures. Manifestations of NPSLE occurred in 50%. The rates of cerebrovascular disease and psychosis were elevated two- and three-fold in NPSLE patients with epilepsy versus NPSLE patients without epilepsy, respectively (P=0.001 and P=0.0006). APS was more common in patients with epilepsy compared to epilepsy-free SLE patients with or without NPSLE (P=0.02). In 50% of patients with epilepsy, no other etiology than SLE was detected. A high prevalence of epilepsy in SLE patients is reported, with association to concurrent cerebrovascular disease, APS and psychosis. Our findings support the notion of a multifactorial background for epilepsy in SLE including both vascular disease and features consistent with autoimmunity.

NPSLE diagnosis is still challenging because of many SLE-related and non-SLE-related processes that can be presented in patient. The report of NPSLE in Indonesia is still limited. This study aim to describe the clinical features, nutrition status, and laboratory characteristics of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) and compared to non NPSLE case in Indonesian children. The study is a retrospective cohort study. Data were collected from the complete medical record of Juvenile Systemic lupus Erythematosus (jSLE) patients 2016 - 2020 at the Allergy Immunology Outpatient clinic at Dr. Soetomo General Academic Hospital. We include all patients with ages ranging from age 0-18 years old with a diagnosis of Systemic lupus Erythematosus (SLE). The diagnosis fo SLE based on American College of Rheumatology (ACR) criteria 1997 and Neuropsychiatric (NP) manifestations were classified using the standardized nomenclature and case definitions for the 19 NP manifestations linked to SLE developed in 1999 by the ACR ad hoc Committee. Disease activity SLE was defined according to the American Mexican-Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) criteria. Statistical analysis conducted in this study was descriptive analysis, paired T-test (NPSLE vs. non-NPSLE as the dependent variable), Fischer exact test, and Pearson Chi-square test using SPSS ver. 21. A total of 90 patients with juvenile SLE were enrolled, but only 71 patients were eligible as participants with complete medical records obtained. Mex-SLEDAI score was significantly higher on NPSLE compared to non-NPSLE (p=0.001).

BackgroundThe diagnosis of NPSLE becomes challenging for rheumatologists, both at a diagnostic and therapeutic level. The 1999 ACR criteria had a high sensitivity (91%), but a low specificity (46%) [1].ObjectivesTo...

Neuropsychiatric manifestations are not rarely associated with systemic lupus erythematosus (SLE). Magnetic resonance angiography and positron emission tomography can provide excellent images of cerebral perfusion and metabolism whereas information is still lacking on a possible diagnostic role of ultrasound. In this study we aim to assess whether duplex sonography of neck and intracranial vessels may be useful in distinguishing patients with and without neuropsychiatric SLE (NPSLE). Neck and transcranial duplex sonography was performed by a single operator on 33 women affected by SLE (mean age +/- SD: 47.69+/-8.17 years) and on 15 healthy control subjects. Nineteen patients presented NPSLE. Pulsatility and resistivity indices (PI and RI) were automatically calculated by the ultrasound instrument in internal carotid (ICA) and middle cerebral artery (MCA), on both sides, according to standard methods. No significant haemodynamic differences were found in mean and median PI and RI values of ICA and MCA comparing SLE with NPSLE patients and with healthy control subjects. No correlation was found between MCA and ICA parameters in the same group of patients. Duplex sonography of cerebral vessels is unable to distinguish SLE and NPSLE patients. Heterogeneity of causes in the pathogenesis of NPSLE and the different vascular adaptation of cerebral macrocirculation as opposed to cerebral microcirculation may represent possible reasons that explain the inability of ultrasound to differentiate SLE patients from NPSLE patients.