Neuropsychiatric Lupus Research Articles

Systemic administration of Shikonin ameliorates cognitive impairment and neuron damage in NPSLE mice

Shikonin is an anti-inflammatory natural herbal drug extracted from Lithospermum erythrorhizon and its therapeutic effect on neuropsychiatric systemic lupus erythematosus (NPSLE) is yet unknown. In our study, Shikonin significantly reversed the cognitive impairment and alleviated the brain tissue damage in NPSLE mice. The permeability of blood-brain barrier was also verified to be repaired in Shikonin-treated NPSLE mice. In particular, we found that Shikonin alleviated neuroinflammation through inhibiting β-catenin signaling pathway, thereby depressing the activation of microglia and the loss of neuronal synapses. Overall, Shikonin may be a promising candidate drug for NPSLE through diminishing neuroinflammation and repairing neuron damage.

Predictive Factors of the Use of Rituximab and Belimumab in Spanish Lupus Patients.

Objectives: To analyze the characteristics and the predictive factors of the use of rituximab and belimumab in daily practice in patients from the inception cohort Registro Español de Lupus (RELES). Material and methods: The study included 518 patients. We considered patients treated with biologics who received at least one dose of rituximab or belimumab, and possible indications of those manifestations registered at the same time or in the previous 2 months of the start of the therapy. Results: In our cohort, 37 (7%) patients received at least one biological treatment. Rituximab was prescribed in 26 patients and belimumab in 11. Rituximab was mainly prescribed for hemolytic anemia or thrombocytopenia (11 patients, 42%), lupus nephritis and neuropsychiatric lupus (5 patients each, 19%). Belimumab was mostly used for arthritis (8 patients, 73%). In the univariate analysis, the predictive factors at diagnosis for the use of biologic therapy were younger age (p = 0.022), a higher SLEDAI (p = 0.001) and the presence of psychosis (p = 0.011), organic mental syndrome (SOCA) (p = 0.006), hemolytic anemia (p = 0.001), or thrombocytopenia (p = 0.01). In the multivariant model, only younger age, psychosis, and hemolytic anemia were independent predictors of the use of biologics. Conclusions: Rituximab is usually given to patients with hematological, neuropsychiatric and renal involvement and belimumab for arthritis. Psychosis, hemolytic anemia and age at the diagnosis of lupus were independent predictive factors of the use of biological agents. Their global effects are beneficial, with a significant reduction in SLE activity and a low rate of side effects.

Cytoarchitectureal changes in hippocampal subregions of the NZB/W F1 mouse model of lupus

Over 50% of clinical patients affected by the systemic lupus erythematosus disease display impaired neurological cognitive functions and psychiatric disorders, a form called neuropsychiatric systemic lupus erythematosus. Hippocampus is one of the brain structures most sensitive to the cognitive deficits and psychiatric disorders related to neuropsychiatric lupus. The purpose of this study was to compare, layer by layer, neuron morphology in lupus mice model NZB/W F1 versus Wild Type mice.By a morphometric of cells identified on Nissl-stained sections, we evaluated structural alterations between NZB/W F1 and Wild Type mice in seven hippocampal subregions: Molecular dentate gyrus, Granular dentate gyrus, Polymorph dentate gyrus, Oriens layer, Pyramidal layer, Radiatum layer and Lacunosum molecular layer. By principal component analysis we distinguished healthy Wild Type from NZB/W F1 mice. In NZB/W F1 mice hippocampal cytoarchitecture, the neuronal cells resulted larger in size and more regular than those of Wild Type. In NZB/W F1, neurons were usually denser than in WT. The Pyramidal layer neurons were much denser in Wild Type than in NZB/W F1. Application of principal component analysis, allowed to distinguish NZB/W F1 lupus mice from healthy, showing as NZBW subjects presented a scattered distribution and intrasubject variability.Our results show a hypertrophy of the NZB/W F1 hippocampal neurons associated with an increase in perikaryal size within the CA1, CA2, CA3 region and the DG. These results help advance our understanding on hippocampal organization and structure in the NZB/W F1 lupus model, suggesting the hypothesis that the different subregions could be differentially affected in neuropsychiatric systemic lupus erythematosus disease. Leveraging an in-depth analysis of the morphology of neural cells in the hippocampal subregions and applying dimensionality reduction using PCA, we propose an efficient methodology to distinguish pathological NZBW mice from WT mice.”

The challenging clinical dilemma of posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

Posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus (SLE) is achallenging clinical dilemma. Aretrospective single-center study was performed to investigate the clinical features, risk factors, outcomes, and clinical determinants of the prognosis of PRES in SLE. Aretrospective study was performed from January2015 to December2020. 19episodes of lupus PRES and 19episodes of non-lupus PRES were identified. 38cases of patients presenting with neuropsychiatric lupus (NPSLE) hospitalized during the same period were selected as controls. Survival status was acquired via outpatient and telephone follow-up in December2022. The clinical neurological presentation of PRES in lupus patients was similar to that of the non-SLE-related PRES and NPSLE populations. Nephritis-induced hypertension is the predominant trigger of PRES in SLE. Disease flare and renal failure-triggered PRES were identified in half of the patients with SLE. The mortality rate of lupus-related PRES during the 2‑year follow-up was 15.8%, the same as that of NPSLE. For patients with lupus-related PRES, multivariate analysis indicated that high diastolic blood pressure (OR =1.762, 95% CI: 1.031 ~ 3.012, p = 0.038), renal involvement (OR = 3.456, 95% CI: 0.894 ~ 14.012, p = 0.049), and positive proteinuria (OR = 1.231, 95% CI: 1.003 ~ 1.511, p = 0.047) were independent risk factors compared to NPSLE. Astrong connection between the absolute counts of Tand/or Bcells and prognosis in lupus patients with neurological manifestations was found (p < 0.05). The lower the counts of Tand/or Bcells, the worse the prognosis. Lupus patients with renal involvement and disease activity are more likely to develop PRES. The mortality rate of lupus-related PRES is similar to that of NPSLE. Focusing on immune balance might reduce mortality.

Diagnosis of Lupus Cerebritis with Balint Syndrome: A Unique Case Report

Introduction: Among the wide variety of clinical manifestations in Systemic Lupus Erythematosus (SLE), cognitive dysfunction (CD) is a subtle finding, where the reported prevalence ranges from 3-88% due to CD assessment inconsistencies and challenges with SLE correlations. Cognitive dysfunction may also be a cornerstone element for a diagnosis of Neuropsychiatric Systemic Lupus Erythematosus (NP-SLE). We present a case of Lupus Cerebritis displaying seizures and oculomotor dysfunctions referred to as Balint Syndrome. To our knowledge, no publications to date have shown a correlation between Lupus Cerebritis and Balint Syndrome. Case Report: A 35-year-old female with a history of lupus, seizures, and migraines presented complaining of a severe headache associated with vomiting. The patient stated the onset of her symptoms was three days prior and had been worsening. While in the emergency room, the patient had a generalized tonic-clonic seizure lasting around 2 minutes at which point neurology was consulted for seizure management. The patient had been seen about a year prior for similar complaints and was started on Keppra to control her epilepsy. The patient was seizure free for about 6 months so Keppra was discontinued. Discussion: A wide array of symptoms are associated with Lupus Cerebritis, which is a rare manifestation following a diagnosis of SLE. Our patient was having seizures and complaints of migraine with severe Balint Syndrome consisting of oculomotor apraxia, optic ataxia, and simultagnosia. Due to some patients’ rapid decline following a diagnosis of SLE and the complex diversity of symptoms, it is crucial to prevent organ failure by treating them immediately, and furthermore, to equip and educate clinicians in identifying atypical presentations. Conclusion: Due to the complexity of autoimmune diseases, patients may present with a plethora of symptomatology, ranging from mild to severe, making a thorough medical history and physical examination imperative elements of a complete workup. Since NP-SLE is a nuanced diagnosis requiring specific management, it is essential to have close follow-ups with neurology.

Altered hippocampal connectivity dynamics predicts memory performance in neuropsychiatric lupus: a resting-state fMRI study using cross-recurrence quantification analysis

ObjectiveΤo determine whole-brain and regional functional connectivity (FC) characteristics of patients with neuropsychiatric SLE (NPSLE) or without neuropsychiatric manifestations (non-NPSLE) and examine their association with cognitive performance.MethodsCross-recurrence quantification analysis (CRQA)...

An evaluation of neuropsychiatric manifestations in systemic lupus erythematosus patients in Saudi Arabia and their associated factors.

To establish the prevalence of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) symptoms in Saudi Arabia and the variables that are linked to it. This cross-sectional study was conducted in June 2021 among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26. Two hundred and eight SLE patients participated in the study (females 91.3% vs. males 8.7%). In addition, 13.5% of patients had a family history of SLE, and 26% had SLE for one to 3 years. The most common symptoms of NPSLE were alteration or loss of sensation (53.4%), followed by fear (52.4%), and headache (48.1%). The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE CONCLUSION: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.

Clinical Manifestations of Systemic Lupus Erythematosus in a Tertiary Center in Saudi Arabia.

Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multisystemic involvement. The clinical presentation and immunological findings of SLE patients from different regions in Saudi Arabia have been studied. There have been no studies on the clinical manifestations of SLE in patients in Saudi Arabia's southern region. This article aims to explore the clinical manifestations of SLE in a tertiary center in the southern region of Saudi Arabia. Methods A retrospective study was carried out on 108 SLE patients who were seen in the rheumatology clinicat Aseer Central Hospital over six months from January 2022 to June 2022. Patients' demographics, clinical and serological characteristics, and therapeutic data were reviewed. Results The male-to-female ratio was 1:12.5, with a mean age at presentationof 28.6 ± 10 years. The mean disease duration was 9.06 ± 5.96 years. Mucocutaneous and musculoskeletal manifestations were the most common, accounting for 76% and 57% of all cases, respectively. Neuropsychiatric involvement and lupus nephritis were present in 29% and 31% of patients, respectively. The hematological abnormalities that were present included anemia (60%), leukopenia (37%), and thrombocytopenia (15%). Antinuclear antibody (ANA) was detected in 100%, anti-double-stranded DNA (anti-dsDNA) antibody in 55%, anti-Smith antibody in 13%, and hypocomplementemia in 52% of patients. Hydroxychloroquine was received by 98% and oral steroids by 41% of the patients. Other drugs include azathioprine (23%), mycophenolate mofetil (15%), methotrexate (23%), belimumab (9%), cyclophosphamide (10%), and rituximab (6%). Conclusion The main clinical features of our patients were in parallel with previous studies in Saudi Arabia as well as in Arab countries. We found a lower prevalence of lupus nephritis, serositis, and anti-dsDNA antibody.Further multicenter studies are required to investigate the long-term outcome and survival of SLE patients.

Systemic Lupus Erythematous Presenting as a Grand Mal Seizure: Case Report

A 30-year-old female presented to their local emergency department with an active, unprovoked generalized tonic-clonic seizure in progress. Past medical and family history of the patient did not include inflammatory or autoimmune conditions nor epilepsy or seizure. The patient’s toxicology screen was negative, along with neurological and infectious differentials assessed for rule-outs. This case report includes updated guidelines for the diagnosis and treatment of neuropsychiatric systemic lupus erythematosus for advanced practice providers.

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma.

To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis. Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities.

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

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). 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. 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. Specific microvascular alterations of eye sign are predictors for the development of NPSLE in addition to increased IL-6 in the CSF.

Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice

ObjectivesNeuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE.MethodsSerum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect.ResultsThe level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice.ConclusionGRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.

Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model

Among systemic lupus erythematosus (SLE) patients, neuropsychiatric symptoms are highly prevalent, being observed in up to 80% of adult and 95% of pediatric patients. Type 1 interferons, particularly interferon alpha (IFNα), have been implicated in the pathogenesis of SLE and its associated neuropsychiatric symptoms (NPSLE). However, it remains unclear how type 1 interferon signaling in the central nervous system (CNS) might result in neuropsychiatric sequelae. In this study, we validate an NPSLE mouse model and find an elevated peripheral type 1 interferon signature alongside clinically relevant NPSLE symptoms such as anxiety and fatigue. Unbiased single-nucleus sequencing of the hindbrain and hippocampus revealed that interferon-stimulated genes (ISGs) were among the most highly upregulated genes in both regions and that gene pathways involved in cellular interaction and neuronal development were generally repressed among astrocytes, oligodendrocytes, and neurons. Using image-based spatial transcriptomics, we found that the type 1 interferon signature is enriched as spatially distinct patches within the brain parenchyma of these mice. Our results suggest that type 1 interferon in the CNS may play an important mechanistic role in mediating NPSLE behavioral phenotypes by repressing general cellular communication pathways, and that type 1 interferon signaling modulators are a potential therapeutic option for NPSLE.

Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.

Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics. A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group.

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

BackgroundNeuroinflammation 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.ResultsOptogenetic 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-1β), 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.ConclusionOur 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.

Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus.

The pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined. To identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s). We enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients' sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients' sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies. In conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI.

New-onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination: a rare case report

BackgroundRare cases of COVID-19 infection- and vaccine-triggered autoimmune diseases have been separately reported in the literature. In this paper, we report the first and unique case of new onset acute psychosis as a manifestation of lupus cerebritis following concomitant COVID-19 infection and vaccination in a previously healthy 26-year-old Tunisian female.Case presentationA 26-years old female with a family history of a mother diagnosed with schizophrenia, and no personal medical or psychiatric history, was diagnosed with mild COVID-19 infection four days after receiving the second dose of Pfizer-BioNTech COVID-19 vaccine. One month after receiving the vaccine, she presented to the psychiatric emergency department with acute psychomotor agitation, incoherent speech and total insomnia evolving for five days. She was firstly diagnosed with a brief psychotic disorder according to the DSM-5, and was prescribed risperidone (2 mg/day). On the seventh day of admission, she reported the onset of severe asthenia with dysphagia. Physical examination found fever, tachycardia, and multiple mouth ulcers. Neurological evaluation revealed a dysarthria with left hemiparesis. On laboratory tests, she had severe acute kidney failure, proteinuria, high CRP values, and pancytopenia. Immune tests identified the presence of antinuclear antibodies. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the left fronto-parietal lobes and the cerebellum. The patient was diagnosed with systemic lupus erythematosus (SLE) and put on anti-SLE drugs and antipsychotics, with a favorable evolution.ConclusionsThe chronological relationship between COVID-19 infection, vaccination and the first lupus cerebritis manifestations is highly suggestive, albeit with no certainty, of the potential causal link. We suggest that precautionary measures should be taken to decrease the risk of SLE onset or exacerbation after COVID-19 vaccination, including a systematic COVID-19 testing before vaccination in individuals with specific predisposition.

A Case of Neuropsychiatric Systemic Lupus Erythematosus as A Sequela of Kikuchi’s Disease

The aetiology of Kikuchi’s Disease (KD), a benign condition associated with multiple lymph node enlargements, remains unknown but several reported cases associate it with systemic lupus erythematosus (SLE). A 34-year-old Indonesian woman presented with multiple painless lymph node enlargements around the neck with three weeks of fever, myalgia, arthralgia, night sweats, and weight loss. Laboratory examination showed pancytopenia and elevated ESR. HIV and tuberculin skin testing were negative. Lymph node biopsy confirmed the diagnosis of KD. One week later, despite improvement in lymphadenopathy, she developed fever. Her ANA, anti-Smith antibodies, and anti-Ribosomal-P protein antibodies were positive. She was diagnosed with SLE and managed as an inpatient with high dose methylprednisolone. One week later, the patient developed psychotic symptoms and fever. The results of Laboratory examinations with lumbar puncture were unremarkable. She was diagnosed with neuropsychiatric SLE (NPSLE) and managed with methylprednisolone, paracetamol, folic acid, alprazolam, and amitriptyline. One month later, the patient returned with three days of fever and dyspnea. Despite improvement in neuropsychiatric symptoms, pneumonia and tonsillopharyngitis were diagnosed based on physical examination and chest X- rays. Her condition deteriorated into septic shock. She suffered cardiac arrest and was pronounced dead, despite attempted resuscitation.While KD is a benign condition, diagnosis is challenging due to its rarity and similarity to other lymphadenopathy diseases. Its association with SLE and NPSLE carries poor prognosis with higher mortality rate from the disease progression and adverse medication effects. Thus, early intervention and prevention of complications are crucial in managing patientswith KD.

Systemic Lupus Erythematosus Flare-Up Manifestation as Intramedullary and Posterior Pharynx Hemorrhage

Systemic lupus erythematosus (SLE) is a common clinical condition, and one of its more common complications is bleeding. Intramedullary and posterior pharynx hemorrhage in SLE is rare and disastrous. We present a patient with a predominantly neurological clinical presentation, which on examination was thought to be the result of active SLE complicated by intramedullary and pharynx hemorrhage. Intravenous glucocorticoids were administered for the acute SLE flare-up. The patient's neurological deficits improved gradually. She could walk independently when she was discharged. Early magnetic resonance imaging detection and early glucocorticoid treatment can halt the progression of neuropsychiatric SLE.

Reversible Bilateral Basal Ganglia and Brainstem Lesions in Neuropsychiatric Systemic Lupus Erythematosus: A Case Report

&lt;p&gt;The pathophysiology behind neuropsychiatric SLE (NPSLE) remains poorly understood and its clinical and radiological manifestations are highly varied. In this report, we present a complex case of an adolescent female patient with a three-week history of systemic symptoms (fever, nausea, vomiting, weight-loss, polyarticular joint pain), progressive motor weakness, tremor, and altered mental status. Physical examination was significant for oromandibular and cervical dystonia rigidity, and general weakness with imposed right-sided hemiparesis. A head MRI demonstrated bilateral hyperintense lesions of the basal ganglia and brainstem, SS without restricted diffusion. The patient was diagnosed with NPSLE, lupus nephritis, electrolyte imbalance, severe hypoalbuminemia, lupus cardiomyopathy, autoimmune hemolytic anemia, pulmonary tuberculosis, and sepsis. The patient was given treatment in the ICU with pulse dose corticosteroids, intravenous antibiotics, intravenous immunoglobulins (IVIg), and supportive treatment with correction of hematologic and electrolyte abnormalities. Her condition improved rapidly. Full alertness was regained, and symptoms of oromandibular dystonia, tremor, and weakness diminished significantly. A follow-up MRI three weeks later revealed complete disappearance of lesions, which we attribute to resolution of the inflammatory process in the brain.&lt;/p&gt;