Examination of the shared genetic architecture between multiple sclerosis and systemic lupus erythematosus facilitates discovery of novel lupus risk loci.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations, including neurological and psychiatric symptoms. Genetic association studies in SLE have been hampered by insufficient sample size and limited power compared to many other diseases. Multiple Sclerosis (MS) is a chronic relapsing autoimmune disease of the central nervous system (CNS) that also manifests neurological and immunological features. Here, we identify a method of leveraging large-scale genome wide association studies (GWAS) in MS to identify novel genetic risk loci in SLE. Statistical genetic comparison methods including linkage disequilibrium score regression (LDSC) and cross-phenotype association analysis (CPASSOC) to identify genetic overlap in disease pathophysiology, traditional 2-sample and novel PPI-based mendelian randomization to identify causal associations and Bayesian colocalization were applied to association studies conducted in MS to facilitate discovery in the smaller, more limited datasets available for SLE. Pathway analysis using SNP-to-gene mapping identified biological networks composed of molecular pathways with causal implications for CNS disease in SLE specifically, as well as pathways likely causal of both pathologies, providing key insights for therapeutic selection.

Kikuchi-Fujimoto disease evolves into lupus encephalopathy characterized by venous sinus thrombosis: a case report.

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological injuries can occur in both diseases, albeit with distinct presentations. Venous sinus thrombosis is a serious cerebrovascular complication in patients with neuropsychiatric SLE but is rarely observed in patients with KFD. The involvement of various antibodies, particularly antiphospholipid antibodies, can cause vascular endothelial cell injury, resulting in focal cerebral ischemia and intracranial vascular embolism in SLE. However, there are cases in which thrombotic pathology occurs without antiphospholipid antibody positivity, attributed to vascular lesions. In this report, we present a case of KFD and lupus encephalopathy featuring cerebral venous sinus thrombosis, despite the patient being negative for antiphospholipid antibody. We also conducted a comparative analysis of C3 and C4 levels in cerebrospinal fluid (CSF) and peripheral blood, along with the protein ratio in CSF and serum, to elucidate the pathological changes and characteristics of lupus encephalopathy.

Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project.

OBJECTIVE: Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge, and symptom under-reporting contributes to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. METHODS: Quantitative and qualitative data analysed included: prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids, and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system. RESULTS: We recruited 2,817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients' quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (p< 0.001) in the comparisons with IA patients for severe headache. Clinician and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritised for discussion and treatment. CONCLUSION: We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be-currently under-estimated-direct effects on the nervous system in IA and other systemic rheumatological diseases.

Microglia orchestrate synaptic and neuronal stripping: Implication in neuropsychiatric lupus.

Systemic lupus erythematosus (SLE), a multifactorial autoimmune disease, can affect the brain and cause neuropsychiatric dysfunction, also named neuropsychiatric lupus (NPSLE). Microglial activation is observed in NPSLE patients. However, the mechanisms regulating microglia-mediated neurotoxicity in NPSLE remain elusive. Here, we showed that M1-like proinflammatory cytokine levels were increased in the cerebrospinal fluid (CSF) of SLE patients, especially those with neuropsychiatric symptoms. We also demonstrated that MRL/lpr lupus mice developed anxiety-like behaviours and cognitive deficits in the early and active phases of lupus, respectively. An increase in microglial number was associated with upregulation of proinflammatory cytokines in the MRL/lpr mouse brain. RNA sequencing revealed that genes associated with phagocytosis and M1 polarization were upregulated in microglia from lupus mice. Functionally, activated microglia induced synaptic stripping in vivo and promoted neuronal death in vitro. Finally, tofacitinib ameliorated neuropsychiatric disorders in MRL/lpr mice, as evidenced by reductions in microglial number and synaptic/neuronal loss and alleviation of behavioural abnormalities. Thus, our results indicated that classically activated (M1) microglia play a crucial role in NPSLE pathogenesis. Minocycline and tofacitinib were found to alleviate NPSLE by inhibiting micrglial activation, providing a promising therapeutic strategy.

Psychiatric manifestations of systemic lupus erythematosus: A brief review with two case-reports.

Neuropsychiatric systemic lupus erythematosus is a severe neurological and psychiatric manifestation following systemic lupus erythematosus. Neuropsychiatric systemic lupus erythematosus is a global concern with limited data on its impact on quality of life in Africa. Furthermore, there is a lack of published research on neuropsychiatric systemic lupus erythematosus in Ethiopia. In this article, we present two case reports of Ethiopian patients with systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus, highlighting the challenges of diagnosing neuropsychiatric systemic lupus erythematosus worldwide. Although the patients were treated with alternative pharmacological agents based on available medications, interdisciplinary collaboration between psychologists, psychiatrists, neurologists, and internists is necessary to decrease the burden of systemic lupus erythematosus patients with neuropsychiatric manifestations. Overall, symptomatic therapy for neuropsychiatric systemic lupus erythematosus in developing countries is a good approach until future evidence-based pharmacotherapy is developed.

Three cases of systemic lupus erythematosus presenting with ischemic stroke as the initial symptom: Case reports and literature review.

BACKGROUND: Ischemic stroke constitutes a grave complication within the context of systemic lupus erythematosus (SLE), typically manifesting several years postdiagnosis of SLE. Incidents where ischemic stroke precedes and acts as an initial symptom of SLE are comparatively rare in its early stages, and such presentations are frequently misdiagnosed as ischemic cerebrovascular diseases, posing significant diagnostic challenges. CASE REPORTS: This article presents three cases of young females in whom ischemic stroke emerged as the initial manifestation of SLE. It incorporates a review of 17 case reports published over the past two decades, focusing on patients with SLE where ischemic stroke was a primary symptom. This discussion encompasses the clinical presentation, outcomes, and therapeutic approaches for these patients. CONCLUSION: In young patients, particularly females presenting with ischemic stroke and especially in cases accompanied by hematologic or multisystemic involvement, there should be heightened vigilance for SLE-induced ischemic stroke. Early diagnosis and treatment significantly enhance patients' quality of life and survival rates.

Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Impaired serotonin synthesis in hippocampus of murine lupus represents an early neuropsychiatric event.

BACKGROUND: Despite significant progress in understanding the mechanisms underlying hippocampal involvement in neuropsychiatric systemic lupus erythematosus (NPSLE), our understanding of how neuroinflammation affects the brain neurotransmitter systems is limited. To date, few studies have investigated the role of neurotransmitters in pathogenesis of NPSLE with contradictory results. METHODS: Hippocampal tissue from NZB/W-F1 lupus-prone mice and age-matched control strains were dissected in both pre-nephritic (3-month-old) and nephritic (6-month-old) stages. High-Performance Liquid Chromatography (HPLC) was used to evaluate the level of serotonin (5-HT), dopamine (DA), and their metabolites 5-HIAA and DOPAC, respectively, in mouse hippocampi. RESULTS: Lupus mice exhibit decreased levels of serotonin at the early stages of the disease, along with intact levels of its metabolite 5-HIAA. The 5-HT turnover ratio (5-HIAA/5-HT ratio) was increased in the hippocampus of lupus mice at pre-nephritic stage suggesting that low hippocampal serotonin levels in lupus are attributed to decreased serotonin synthesis. Both DA and DOPAC levels remained unaffected in lupus hippocampus at both early and late stages. CONCLUSION: Impaired hippocampal serotonin synthesis in the hippocampus of lupus-prone mice represents an early neuropsychiatric event. These findings may have important implications for the use of symptomatic therapy in diffuse NPSLE.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Attribution of neuropsychiatric symptoms and prioritisation of evidence in the diagnosis of neuropsychiatric lupus: mixed methods analysis of patient and clinician perspectives from the international INSPIRE study.

OBJECTIVE: Neuropsychiatric lupus (NPSLE) is challenging to diagnose. Many neuropsychiatric symptoms, such as headache and hallucinations, cannot be verified by tests or clinician assessment. We investigated prioritisations of methods for diagnosing NPSLE and attributional views. METHODS: Thematic and comparative analyses were used to investigate how clinicians prioritise sources of evidence from a 13-item list, and explore discordances in clinician and patient perspectives on attribution. RESULTS: We identified high levels of variability and uncertainty in clinicians' assessments of neuropsychiatric symptoms in SLE patients. In attributional decisions, clinicians (surveys n = 400, interviews n = 50) ranked clinicians' assessments above diagnostic tests (many of which they reported were often unenlightening in NPSLE). Clinicians ranked patient opinion of disease activity last, and 46% of patients reported never/rarely having been asked if their SLE was flaring, despite experienced patients often having "attributional insight". SLE Patients (surveys n = 676, interviews n = 27) estimated higher attributability of neuropsychiatric symptoms to the direct effects of SLE on the nervous system than clinicians (p < 0.001 for all symptoms excluding mania), and 24% reported that their self-assessment of disease activity was never/rarely concordant with their clinicians. Reports of misattributions were common, particularly of non-verifiable diffuse symptoms. Terminology differed between clinicians and influenced attribution estimates. CONCLUSION: NPSLE diagnostic tests and clinician assessments have numerous limitations, particularly in detecting diffuse neuropsychiatric symptoms that can be directly attributable and benefit from immunosuppression. Our findings suggest that incorporating patient attributional insights-although also subject to limitations-may improve attribution decision-making. Consensus regarding terminology and interpretations of "direct attributability" is required.

Cognitive dysfunction in pediatric systemic lupus erythematosus: current knowledge and future directions.

Cognitive dysfunction (CD) is a neurologic complication of pediatric systemic lupus erythematosus (SLE) that remains poorly understood and understudied, despite the potential negative effects of CD on long-term socioeconomic status and quality of life. Data regarding the prevalence and risk factors for CD in pediatric SLE as well as the optimal screening, treatment, and long-term outcomes for CD are lacking. In this review, we present current knowledge on CD in pediatric SLE with a focus on the application to clinical practice. We discuss the challenges in diagnosis, clinical screening methods, potential impacts, and interventions for this complication. Finally, we discuss the remaining gaps in our knowledge of CD in pediatric SLE, and avenues for future research efforts.

Extensive Longitudinal Transverse Myelitis in Systemic Lupus Erythematosus: Presentation of a Case and Literature Review.

Acute transverse myelitis (TM) is an inflammatory disease that manifests with motor, sensory, and autonomic symptoms of rapid progression with catastrophic outcomes; the three main causes of acute TM are demyelinating diseases, infections, and autoimmune inflammatory diseases such as systemic lupus erythematosus (SLE). TM is one of the 19 neuropsychiatric diseases associated with SLE according to the American College of Rheumatology (ACR) and has been described as affecting 1 to 2% of all cases of SLE and is frequently misdiagnosed, leading to a high rate of morbidity and mortality. This report highlights the case of a 25-year-old woman with a history of SLE who consulted for a progressive decrease in lower limb strength and loss of sphincter control, accompanied by dysesthesias from the abdomen to the feet. Upon examination, she exhibited severe paraparesis and preserved myotendinous reflexes, and a sensory level at T10 was documented. A contrast-enhanced MRI of the thoracolumbar spine was performed, showing signal hyperintensity on T2 and Short Tau Inversion Recovery (STIR) from T6 to T10. These findings are compatible with TM. Given the refractory response to initial management, the use of cyclophosphamide was required. After one week of hospital treatment, the patient achieved partial neurological recovery and was discharged for continued outpatient rheumatology care. For the diagnosis of TM in patients with SLE, a high clinical suspicion is required. Recognizing and immediately addressing this condition is crucial to prevent catastrophic outcomes and the high morbidity and mortality that stem from this association.

Prevalence of cognitive impairment and cognitive improvement in patients with systemic lupus erythematosus during a 6-month follow-up study.

OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a simple and reliable screening tool for early detection for cognitive impairment in systemic lupus erythematosus (SLE). Most previous studies were cross-sectional with small samples. Research on long-term cognitive changes and reversibility is limited. This study aimed to establish the prevalence of cognitive impairment and changes in SLE patients after 6 months and the associated factors. METHODS: A prospective study was conducted in 200 patients with SLE between April 2021 and March 2022. Demographic data, disease activity, and medications were recorded. MoCA was administered at baseline and 6 months; for Thais, scores 17-24 indicate mild cognitive impairment, while ≤16 signifies severe impairment. Multivariate analysis identified factors associated with cognitive impairment and improvement. RESULTS: The patients' median age was 44 years (range: 19-73), 96% were female, and 55% had < 12 years of education. The median disease duration was 11 years (range: 0-51.8), and 79% of patients had inactive disease. Cognitive impairment was found in 70% of patients (mild, 63%; severe, 7%). The most often affected domains were delayed recall (82%), abstraction (80.5%), language (76%) and visuospatial/executive function (70.5%), whereas orientation and naming were the least involved. Factors significantly associated with cognitive impairment were age > 40 years (OR, 3.71; 95% CI, 1.72-8.00), formal education < 12 years (OR, 3.11; 95% CI, 1.45-6.63), and prednisolone use (OR, 2.21; 95% CI, 1.08-4.51). Sixty-six (38.2%) of 173 patients completing the 6-month re-evaluation exhibited cognitive changes (52 [30.1%] improved; 14 [8.1%] deteriorated). Except for delayed recall, all commonly affected domains showed significant improvement. Disease activity, prednisolone, antimalarials, or immunosuppressant use did not predict cognitive improvement. CONCLUSIONS: Mild cognitive impairment is prevalent among patients with SLE. Due to the possibility of reversibility, early recognition and additional research to identify relevant factors are required.

Parkinsonism as the presenting manifestation of lupus: A case-based review.

INTRODUCTION: Neuropsychiatric manifestations in systemic lupus erythematosus (SLE) occur in about half of the patients; however, movement disorders like Parkinsonism are rare. We describe a case of SLE who presented solely with features of Parkinsonism. CASE REPORT: 50-year-old female presented with global slowing of movements and slowing of speech since 2 months. On examination, she had mask-like facies with a faint malar rash sparing the nasolabial folds, hard palate ulcer, cog-wheel rigidity, and proximal muscle weakness. Lab evaluation revealed lymphopenia, high ESR, elevated lactate dehydrogenase, creatinine phosphokinase, AST, and ALT levels. She had high anti-dsDNA levels with low complements. Urinalysis showed proteinuria and hematuria. ANA was positive at a titer of 1:320, and she had positive anti-ribosomal-P antibody. She had severe flare with a SLEDAI of 33. She was treated with pulse IV methylprednisolone followed by cyclophosphamide (NIH protocol). At 4 weeks follow-up, she had dramatic improvement in her Parkinsonian symptoms and her proximal muscle weakness. DISCUSSION: The prevalence of movement disorders in cases of neuropsychiatric SLE is very low at 0.7%, with chorea being most frequent and Parkinsonism rare. The pathogenesis is multifactorial including anti-dopaminergic antibodies or associated anti-phospholipids causing microvascular thrombosis or vasculitis of the thalamostriatal arteries or disease activity itself. As in our case, immunosuppression and optimal treatment of active lupus reverts symptoms in most cases. CONCLUSION: A high index of suspicion needs to be exercised in cases of SLE presenting with Parkinsonism as adequate immunosuppression translates to near-complete recovery.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. RESULTS: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. CONCLUSION: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Performance of eye sign combined with increased interleukin-6 in cerebrospinal fluid in patients with neuropsychiatric lupus erythematosus.

OBJECTIVES: To ascertain whether microvascular alterations of eye sign combined with intrathecal concentrations of interleukin-6 (IL-6) can predict the development of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Cerebrospinal fluid (CSF) and serum samples of IL-6 were collected and measured at the same time for patients with SLE who were consecutively enrolled. Patients with a diagnosis of NPSLE were identified. Eye sign examinations according to our criteria were performed and scored for all SLE patients. Demographic and clinical parameters were compared between groups to identify potential predictors for NPSLE using multivariable logistic regression analysis. The performance of potential predictors from eye sign along with IL-6 in the CSF was assessed. RESULTS: A total of 120 patients with SLE were enrolled; 30 with NPSLE and 90 with non-NPSLE. No significant positive correlation was observed between CSF level and serum level of IL-6. CSF IL-6 was significant higher in the NPSLE group than the non-NPSLE (P < 0.001) group. Multivariable logistic analysis revealed that total score, ramified loops, and microangioma of eye sign were predictors for NPSLE after adjusting for SLE Disease Activity Index (SLEDAI) and antiphospholipid antibody (APL). Total score, ramified loops, microangioma of eye sign, and SLEDAI remain significant predictors for NPSLE after adjusting for CSF IL-6. Using receiver operating characteristics curve analysis, the cut-off point of potential predictors was applied in multivariable logistic analysis; APL, total score, ramified loops, and microangioma of eye sign remain significant predictors for NPSLE after adjusting for CSF IL-6. CONCLUSION: Specific microvascular alterations of eye sign are predictors for the development of NPSLE in addition to increased IL-6 in the CSF.

Anorexia Nervosa in Juvenile Systemic Lupus Erythematosus (SLE): A Causality Dilemma.

Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disorder with multifaceted clinical findings in different organ systems. Neuropsychiatric manifestations affect more than half of SLE patients, and there is increasing evidence that anorexia nervosa (AN), a feeding and eating disorder (FED) characterized by significantly reduced energy intake, is among them. Herein, a review of the literature on the potential association between jSLE and AN was performed. Reported clinical cases were identified, and putative pathophysiological mechanisms were sought that could potentially explain the observed relationship between these two pathological entities. Four reports of isolated cases and a case series including seven patients were identified. In this limited patient pool, the diagnosis of AN preceded that of SLE in the majority of cases, whereas in all cases both entities were diagnosed within a time span of two years. Many explanations for the observed relationships have been proposed. AN has been associated with the stress of chronic disease diagnosis; on the other hand, the chronic inflammation associated with AN may contribute to the development/appearance of SLE. Adverse childhood experiences, concentrations of leptin, shared autoantibodies, and genetic traits appear to be important factors in this well-established interplay. In essence, it seems important to increase clinician awareness of the concomitant development of AN and SLE and invite further research on the subject.

Neuropsychiatric Systemic Lupus Erythematosus and Posterior Reversible Encephalopathy Syndrome in a Young Woman: A Case Report.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with variable clinical presentation, including neuropsychiatric manifestations. It has a different diagnostic approach and several different therapeutic options. CASE REPORT: We describe a case of a young woman who first presented with arthritis, serositis, and pancreatitis, and was treated with mycophenolate mofetil initially. The patient presented with neurological symptoms suggestive of neuropsychiatric manifestations three weeks later, confirmed by Brain Magnetic Resonance Imaging (MRI). The treatment was changed to cyclophosphamide; however, the day after the infusion, she developed status epilepticus and was admitted to the intensive care unit. Repeated brain MRI revealed Posterior Reversible Encephalopathy Syndrome (PRES). Cyclophosphamide was discontinued and rituximab was initiated. The patient's neurological manifestations improved, and she was discharged after 25 days of use. CONCLUSION: Immunosuppressive agents, such as cyclophosphamide have been described as a potential risk factor for PRES; however, it is not clear from the available literature whether cyclophosphamide therapy is just a marker of more severe SLE or a true risk factor for PRES.

In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.