Neuropsychiatric Lupus Research Articles

Association of Antiribosomal P Antibody with Neurological and Systemic Manifestations in Patients with Systemic Lupus Erythematosus in Southwestern Colombia.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous pathogenesis, various clinical manifestations, and a broad spectrum of autoantibodies which recognize different cellular components. This study examines the clinical significance and serological associations of serum antiribosomal P antibodies (anti-P) derived from SLE patients in a population from southwestern Colombia. We performed a cross-sectional study of 66 SLE patients. Serum antiribosomal P0 autoantibodies were detected by line immunoassay using the ANA-LIA MAXX kit and processed on the automated HumaBlot 44FA system (Human Diagnostics, Germany). Of the 66 SLE patients included in the study, 17 patients (25.76%) showed anti-P positivity by line immunoassay (IA), 47 (71.21%) were negative, and results from 2 patients were indeterminate. We did not find an association with neuropsychiatric SLE (NPSLE), renal, or hepatic disorders (P > 0.05). Laboratory findings indicated that anti-P positivity was significantly associated to anti-Smith (P = 0.001), anti-Ro60/SSA (P = 0.046), and anti-dsDNA antibodies (P = 0.034), the latter being true only when performed using indirect immunofluorescence (IIF). The anti-P antibodies are not associated with clinical manifestations such as NPSLE, lupus nephritis, or hepatic involvement in the southwest Colombian SLE population. Moreover, we confirmed previously reported association between anti-P antibody, serum anti-dsDNA, and anti-Smith.

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus

Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. To identify disease and non-disease related factors associated with NP manifestations in early SLE. We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. Independent factors associated with NP involvement were identified using a multivariable Cox regression model. Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

Hippocampal microglia CD40 mediates NPSLE cognitive dysfunction in mice

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the most serious and complicated clinical manifestation of lupus erythematosus. Cognitive dysfunction is the most common symptom of NPSLE. A variety of potential mechanisms or mediators related to the pathogenesis of NPSLE cognitive dysfunction have been proposed. However, the involvement of microglia CD40 has not been reported yet. This study aimed to investigate whether hippocampal microglia CD40 of MRL/MpJ-Faslpr (MRL/lpr) mice was involved in NPSLE cognitive dysfunction. This study found, using quantitative polymerase chain reaction, western blotting and immunohistochemistry, that hippocampal CD40 was aberrantly overexpressed in the MRL/lpr lupus mice. It also determined using flow cytometry and immunofluorescence that the aberrantly overexpressed CD40 was mainly derived from hippocampal microglia. The adeno-associated virus was used to inhibit microglia CD40 expression, and the brain damage and cognitive dysfunction of MRL/lpr mice improved. Also, imiquimod (IMQ)-induced lupus mice had the same NPSLE cognitive dysfunction, brain damage, and overexpressed hippocampal microglia CD40 as MRL/lpr mice. Therefore, IMQ-induced lupus mouse was proposed as one of the mouse models for studying NPSLE cognitive dysfunction for the first time in this study. The findings indicated that hippocampal microglia CD40 was involved in the development of NPSLE cognitive dysfunction, thus providing a novel research direction for the study of the pathogenesis of NPSLE.

Lupus or not? SLE Risk Probability Index (SLERPI): a simple, clinician-friendly machine learning-based model to assist the diagnosis of systemic lupus erythematosus

ObjectivesDiagnostic reasoning in systemic lupus erythematosus (SLE) is a complex process reflecting the probability of disease at a given timepoint against competing diagnoses. We applied machine learning in well-characterised patient...

Perfusion image guided mechanical thrombectomy combined with tirofiban successfully revascularize systemic lupus erythematosus related acute large vessel occlusion: A case report.

Rationale:Systemic lupus erythematosus (SLE) is an important cause of stroke, more than a half the cases present as acute ischemic stroke. Thrombolysis is an effective choice in most cases, but for large vessel occlusion, mechanical thrombectomy is more effective. Here we reported a case of SLE-related stroke with left middle cerebral artery (MCA) occlusion, who was successfully treated by MT and tirofiban.Patient concern:A 38-year-old female suffered from right hemiplegia and aphasia for 8 hours. She was diagnosed with SLE 20 years ago, and neuropsychiatric SLE was considered 8 months before this onset. One month ago, glucocorticoids were discontinued by herself because of deterioration of bilateral femoral head osteonecrosis.Diagnosis:Left MCA occlusion was confirmed by computed tomography perfusion.Intervention:Immediate mechanical thrombectomy was performed and tirofiban was given to prevent re-occlusion of left MCA. Twenty fourhours later oral antiplatelet was given after intracranial hemorrhage was ruled out.Outcomes:Her neurological symptom improved several days later, and she was transferred to further rehabilitation. At 4 months follow-up she can live independently with mild hypophrasia. There was no further events of ischemic stroke in 1-year follow-up.Lessons:Mechanical thrombectomy is a highly effective and indispensable treatment for SLE related large vessel occlusion. In addition, tirofiban may reduce vessel reocclusion in special cases such as SLE and artery stenosis.

Experience With Anti-Sclerostin Antibody for Osteoporosis Patient With End-Stage Renal Disease on Hemodialysis

Background: Romosozumab is a sclerostin inhibitor indicated for treatment of postmenopausal osteoporosis. Sclerostin inhibits Wnt/Beta-catenin signaling pathway. When sclerostin is inhibited, stimulation of this pathway leads to increased bone formation and production of osteoprotegerin, which also decreases bone resorption. Patients with chronic kidney disease (CKD) demonstrate increased levels of sclerostin that negatively correlates with the rate of bone formation; however, data is lacking for use of romosozumab in this patient population. The report herein details the experience of use of romosozumab in a patient with end-stage renal disease (ESRD) on hemodialysis (HD). Clinical Case: A 37-year-old old African American male was referred after multiple rib fractures and severe non-traumatic T8 compression fracture with nerve compression. His past medical history includes lupus nephritis and cerebritis, ESRD on HD since age 22 status post (s/p) failed renal transplant, and tertiary hyperparathyroidism complicated with fracture in iliac brown tumor and mediastinal parathyromatosis s/p three parathyroid surgeries. Bone mineral density by DXA (g/cm2, Z-score) were as follows: lumbar spine (0.700, -4.0) femoral neck (0.676, -3.8), total hip (0.628,-4.0), 1/3 radius(0.443,-6.2). No prior exposure to antiresorptive or osteoanabolic agents. Pertinent labs included serum calcium 8.5 mg/dL (nl 8.9–10.3 mg/dl), albumin 4.2 g/dL, alkaline phosphatase 319 U/L (nl 38–126), Phosphorus 3.1 mg/dL (2.4–4.7), Creatinine 5.62 mg/dl, 25-OH Vitamin D 31 ng/mL (nl 25 - 80), intact parathyroid hormone 17.9 pmol/L (nl 1.6–6.9). Patient was in excruciating pain and not a surgical candidate due to poor bone quality. Osteoanabolic therapy was recommended given the severity of osteoporosis; however, teriparatide and abaloparaitde were contraindicated given comorbidities. The patient was offered off-label use of Romosozumab with clear understanding that the drug is not approved for this indication and safety/efficacy data in ESRD is not known. The boxed warning regarding increased risk of stroke, myocardial infarction and death were discussed and patient was willing to proceed. Repeat DXA after eleven monthly doses of Romosozumab resulted in a remarkable improvement in bone mineral density at all sites: lumbar spine (+47%), femoral neck (+41%), total hip (+28%), 1/3 radius (+20%). Patient tolerated medication with no side effects or fractures. Serum calcium was monitored prior to initiation and before every dose. No doses were held due to abnormal laboratory values or side effects. Conclusion: This case report summarizes successful experience with the use of Romosozumab in one patient with ESRD on HD with favorable outcomes.

Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus by Deep Learning Enhanced Magnetic Resonance Spectroscopy

The neuropsychiatric systemic lupus erythematosus (NPSLE) has higher disability and mortality rates, which is one of the main causes of death in systemic lupus erythematosus (SLE) patients. Magnetic resonance spectroscopy (MRS) can detect the changes of metabolites in different intracranial areas in vivo in patients with SLE, so as to provide evidence for the early diagnosis of NPSLE. Different from the conventional single-voxel MRS, which can only screen one brain region with one metabolic change, we simultaneously detect 13 kinds of intracranial metabolic changes in nine brain regions by multivoxel proton MRS (MVS). We use a recursive feature elimination algorithm to select the most related metabolites for better identifying NPSLE. To accurately diagnosis NPSLE by these intracranial metabolites, we train a support vector machine deep stacked network (SVM-DSN) for quantitative analysis of these metabolites. Comparing with the conventional statistic method, which is about 70% of accuracy, the proposed model achieves 97.5% of accuracy for NPSLE diagnosis. We conclude the trained SVM-DSN can effectively analyze the metabolites obtained by multivoxel proton MRS for NPSLE diagnosis, which may help to early diagnosis and intervention of NPSLE, and alleviate the bias of manual screening.

Systemic Lupus Erythematosus Patient with Bicytopenia and Motor Aphasia

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune condition with unclear cause that shows a broad ranging clinical symptoms, course and prognosis. Cerebrovascular illness, a severe symptom SLE in the central nervous system by neuropsychiatric SLE (NPSLE). Aphasia is considered to be one of the rarer signs, produced by secondary antiphospolipid syndrome (APS), of a cerebrovascular condition of NPSLE. Case: A 37 years-old married woman that has background of miscarriage in SLE with speech blocking, motor aphasia, and had nasal voice was diagnosed with NPSLE with APS. After initiating therapy with cyclophospamide and aspilet the patient’s clinical condition improved significantly. Conclusion: APS needs to bear in mind in SLE patients that has background of miscarriage or thrombosis. The diagnosis was based on history, clinical, and laboratory examinations which include phospholipid antibodies, There was dramatic improvement after 12 days of 500 mg of cyclophospamide and oral aspilet 100 mg daily therapy.

Therapeutic Strategies of Neuropsychiatric Systemic Lupus Erythematosus

Damage of the central and peripheral nervous systems associated with systemic lupus erythematosus (SLE) is termed neuropsychiatric SLE (NPSLE). In this review, we have discussed SLE encephalopathy, which is associated with neurological symptoms in particular. At the time of diagnosis, disease severity should be evaluated based on clinical findings, imaging, laboratory tests, including cerebrospinal fluid tests and neurophysiological tests, of the patient. Subsequently, treatment involving both definitive therapy and symptomatic treatment is initiated. After introducing definitive therapy, it is further desirable to adopt an appropriate treatment approach by identifying the predominant type of pathogenesis (inflammatory or vascular). A collaborative approach involving specialists in collagen vascular disease, neurologists, and psychiatrists is important for appropriate management of NPSLE.

Distinct spatial profile of inflammatory gene expression in the brain of a mouse model of neuropsychiatric lupus

Abstract Systemic Lupus Erythematosus (SLE) is an incurable autoimmune disease that results in central nervous system (CNS) involvement in up to 80% of patients, with clinical manifestations ranging from anxiety and fatigue to overt psychosis. However, the mechanisms and cellular components underlying these neuropsychiatric symptoms (NPSLE) remain largely unknown. An elevated type 1 interferon (IFN) signature has been commonly observed in SLE patients, particularly within the CNS of NPSLE patients (Crow et. al., 2014, Shiozawa et. al., 1992). Given the diversity of clinical CNS manifestations, we hypothesized that type 1 interferon-mediated inflammation occurs in spatially distinct regions within the CNS, resulting in differential behavioral outcomes depending on the impacted brain region. To test this hypothesis, we first characterized behavioral phenotypes in the Sle1, Yaa mouse model, and show that these mice exhibit anxiety-like, and fatigue-like behaviors consistent with the major clinical manifestations of NPSLE. To assess the spatial distribution of inflammatory gene expression, we utilized MERFISH (Moffitt et. al., 2016), a multiplexed spatial transcriptomics platform, and observed strikingly distinct patches of interferon stimulated gene (ISG) expression within the subcortical regions of Sle1, Yaa mouse brains. Preliminary single nucleus sequencing (sNuc-Seq) and in situ hybridization results implicate astrocytes and oligodendrocytes as the major cell classes enriched in these ISG patches. In summary, our results validate a mouse behavioral model of NPSLE, and show spatially distinct regions of ISG expression within the CNS, opening up a new avenue of investigation into the fundamental mechanisms of NPSLE.

Different phenotypes of neuropsychiatric systemic lupus erythematosus are related to a distinct pattern of structural changes on brain MRI

ObjectivesThe underlying structural brain correlates of neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) remain unclear, thus hindering correct diagnosis.We compared brain tissue volumes between a clinically well-defined cohort of patients with NPSLE and SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE). Within the NPSLE patients, we also examined differences between patients with two distinct disease phenotypes: ischemic and inflammatory.MethodsIn this prospective (May 2007 to April 2015) cohort study, we included 38 NPSLE patients (26 inflammatory and 12 ischemic) and 117 non-NPSLE patients. All patients underwent a 3-T brain MRI scan that was used to automatically determine white matter, grey matter, white matter hyperintensities (WMH) and total brain volumes. Group differences in brain tissue volumes were studied with linear regression analyses corrected for age, gender, and total intracranial volume and expressed as B values and 95% confidence intervals.ResultsNPSLE patients showed higher WMH volume compared to non-NPSLE patients (p = 0.004). NPSLE inflammatory patients showed lower total brain (p = 0.014) and white matter volumes (p = 0.020), and higher WMH volume (p = 0.002) compared to non-NPSLE patients. Additionally, NPSLE inflammatory patients showed lower white matter (p = 0.020) and total brain volumes (p = 0.038) compared to NPSLE ischemic patients.ConclusionWe showed that different phenotypes of NPSLE were related to distinct patterns of underlying structural brain MRI changes. Especially the inflammatory phenotype of NPSLE was associated with the most pronounced brain volume changes, which might facilitate the diagnostic process in SLE patients with neuropsychiatric symptoms.Key Points• Neuropsychiatric systemic lupus erythematosus (NPSLE) patients showed a higher WMH volume compared to SLE patients with neuropsychiatric syndromes not attributed to SLE (non-NPSLE).• NPSLE patients with inflammatory phenotype showed a lower total brain and white matter volume, and a higher volume of white matter hyperintensities, compared to non-NPSLE patients.• NPSLE patients with inflammatory phenotype showed lower white matter and total brain volumes compared to NPSLE patients with ischemic phenotype.

O17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register

Abstract Background/Aims Neuro-psychiatric (NP) involvement in systemic lupus erythematosus (SLE) can occur in 56.3% cases. Rituximab (RTX) has been demonstrated to be safe and efficacious in the treatment of refractory SLE although there is limited evidence for its use in NP-SLE. We aim to describe the baseline characteristics and short-term effectiveness of RTX in patients treated for NP-SLE within the British Isles Lupus Assessment Group Biologics Register (BILAG-BR). Methods Patients with active NP involvement; scoring BILAG A or B and/or on SLEDAI-2K were included. Baseline characteristics, disease activity and oral steroid dose pre and 5 - 9 months post-treatment were analysed. Paired Wilcoxon-Signed-Ranked Test was used to determine changes in disease activity scores and steroid dose. Results We identified 74 patients of whom 61 (82%) were female and 48 (74%) Caucasian. Median age [interquartile range (IQR)] was 45.5 years [37 - 58] and disease duration 11.5 years [7 - 18.8]. 68 patients had active disease on BILAG (A = 34, B = 34) with 6 scoring on SLEDAI-2K only. The majority (n = 71/74, 96%) had at least one other organ involved. Central nervous system (CNS) disease occurred in 45/65 (69%) cases, 12/65 (18%) had peripheral nervous system (PNS) disease and 8/65 (12%) CNS/PNS overlap. Anti-Ro was the commonest identified antibody (n = 26/57, 46%) and 42 of 59 (71%) patients had a raised anti-dsDNA and/or low complement. The majority (n = 64/74, 86%) were taking glucocorticoids and median prednisolone dose was 15mg [IQR 10 - 20]. Pre and post-RTX BILAG, total SLEDAI-2K and oral steroid dose were available in 50, 57 and 27 patients respectively. Following RTX, patients with NP BILAG A or B reduced from 50 to 11 (p < 0.0001). 4 of the 6 patients with NP-SLE on SLEDAI-2K alone, improved. Total median SLEDAI-2K score reduced from 12 [IQR 14 - 18] to 2 [IQR 0 - 4] (p < 0.0001). Median steroid dose reduced from 15mg [IQR 11.3 - 25] to 10mg [IQR 6.9 - 18.8] (p = 0.009). For 53 patients, active CNS, PNS and overlap disease reduced from 37 (70%) to 6 (11%), 10 (19%) to 3 (6%) and 6 (11%) to 4 (8%) respectively. In 9 patients treated with concomitant CYC, none had persistent NP disease. In contrast, 11 of 41 patients who had RTX alone had persistent NP disease. Conclusion RTX use is associated with improvement in NP-SLE with reduction in oral steroid dose. Concomitant CYC may enhance the level of improvement seen with RTX. Large scale studies are therefore warranted to establish the effectiveness of RTX alone or in combination with CYC in the treatment of NP-SLE. Disclosure T. David: None. R. Hum: None. E. Sutton: None. B. Parker: None. E. McCarthy: None. I. Bruce: None.

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study

ObjectiveTo examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).MethodsResting-state fMRI (rs-fMRI) was performed...

It’s never lupus: A case of atypical psychosis and neuropsychiatric lupus

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease involving the production of autoantibodies with consequent involvement of multiple organ systems. Although not an uncommon condition, its pleomorphic neuropsychiatric manifestations imply consideration of SLE as a relevant differential diagnosis. As many as 50% of patients with SLE have neurological involvement throughout their disease course and it is associated with impaired quality of life, high morbidity and mortality rates.ObjectivesCase report study and discussion.MethodsThe authors present a case of a 50-year old woman without previous psychiatric history presenting to the psychiatric department with suicidal ideation in association with psychotic symptoms of rapid onset. She presented with various somatic symptoms including butterfly rash, alopecia, nail dystrophy and generalized myalgia and arthralgia. After conducting a thorough clinical investigation with subsequent unveiling of various alterations including those in the antibody panels and abnormal magnetic resonance imaging results, a diagnosis of neuropsychiatric lupus was established.ResultsImprovements in initial psychiatric symptoms were noted after completing pulse corticoid therapy for SLE with adjunct antipsychotic medication. On follow-up, the patient demonstrated a complete return to previous mental functioning with no reported relapses.ConclusionsThis case demonstrates the heterogeneous presentations that neuropsychiatric lupus can assume. The vast array of psychopathological signs and symptoms in SLE continue to exist as a significant diagnostic and therapeutic challenge. Timely identification resulting from a proactive approach in maintaining lupus as part of our differentials may prevent the significant morbidity and mortality commonly associated with the resultant central nervous system involvement in SLE.DisclosureNo significant relationships.

Relevant domains and outcome measurement instruments in neuropsychiatric systemic lupus erythematosus: a systematic literature review.

Although neuropsychiatric involvement in SLE (NPSLE) is one of the most complex and troubling manifestations of the disease, validated outcome instruments to be used as sensitive endpoints in controlled clinical trials are lacking. We performed a systematic literature review (SLR) to identify outcome measurement instruments and domains used to assess NPSLE. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. Articles available in English (1967-2020), listed in PubMed, Embase, PsycINFO, Cochrane Library and the EULAR outcome measures library were screened. All domains and outcome measurement instruments were characterized according to the OMERACT Filter 2.1, considering core areas (manifestations/abnormalities, life impact, death/lifespan, societal/resource use) and contextual factors. Of 3392 abstracts evaluated, 83 studies were included in the SLR (15 974 patients, females 89.9%). Eligible studies included domains and instruments pertinent to all core areas defined by the OMERACT, except for 'societal/resource use'. The most common core areas were 'manifestations/abnormalities', covering 10 domains pertinent to laboratory and instrumental markers, indexes and neuropsychiatric dimension (cognitive, neurologic and psychiatric field), and 'life impact', covering 7 domains related to physical function (from both the perspective of the patient and the physician), pain and quality of life. Our study revealed great heterogeneity in the instruments derived from populations with NPSLE and none of these had high-quality evidence. This supports the need to develop and further validate a core domain set and outcome measurement instruments to promote clinical research in this field, enhancing comparability across studies.

Fatigue in patients with systemic lupus erythematosus and neuropsychiatric symptoms is associated with anxiety and depression rather than inflammatory disease activity.

IntroductionWe aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies.MethodsPatients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007–2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education.Results348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (β: 0.8 (95% CI −4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (β: −3.7 (95% CI: −6.9; −0.5) and β: −1.0 (95% CI −1.6; −0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements.ConclusionThis study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.

Treatment of neuropsychiatric systemic lupus erythematosus: clinical challenges and future perspectives

ABSTRACT Introduction: Neuropsychiatric (NP) involvement represents an emerging frontier in systemic lupus erythematosus (SLE), posing significant challenges due to its clinical diversity and obscure pathophysiology. The authors herein discuss selected aspects in the management of NPSLE based on existing literature and our experience, aiming to facilitate routine medical care. Areas covered: Research related to diagnosis, neuroimaging, treatment and outcome is discussed, focusing on data published in PubMed during the last 5 years. Selected translational studies of clinical relevance are included. Expert opinion: Identification of NPSLE patients who may benefit from appropriate treatment can be facilitated by attribution algorithms. Immunosuppressants are typically indicated in recurrent seizures, optic neuritis, myelopathy, psychosis and peripheral nerve disease, although a low threshold is recommended for cerebrovascular disease and other NP manifestations, especially when SLE is active. With the exception of stroke with positive antiphospholipid antibodies, anti-coagulation is rarely indicated in other syndromes. Refractory NPSLE can be treated with rituximab, whereas the role of other biologics remains unknown. Advances in the fields of biomarkers, neuroimaging for brain structural, perfusion or functional abnormalities, and design of novel compounds targeting not only systemic autoimmunity but also inflammatory and regenerative pathways within the nervous system, hold promise for optimizing NPSLE management.

Clinical and electrophysiological assessment of cranial and peripheral neuropathies in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo study the frequency of cranial and peripheral neuropathies in systemic lupus erythematosus (SLE), their clinical characteristics, electrophysiological pattern and relation to disease activity. Patients and methodsThe study included 30 SLE patients and 20 matched healthy controls. Electrophysiological assessment included routine nerve conduction studies for assessment of peripheral nerves and visual evoked potential, blink reflex, and brain stem auditory evoked potential for assessment of the second, fifth, seventh, and eighth cranial nerves, respectively. Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI) was assessed. ResultsThe mean age of the patients was 35.8 ± 8.6 years, 27 females and 3 males (9:1) with median disease duration 4.5(1.2–8) years and SELENA-SLEDAI of 12.09 ± 4.94. The mean complement-3 (C3) level was 81.2 ± 26.9 mg/dl and C4 was 11.5 ± 4.4 mg/dl. Peripheral neuropathy was detected electrophysiologically in 66.7% and clinically in 53.3% of the patients and was sensory more than motor. Sensory neuropathy was found in 9(30%), sensorimotor in 11(36.7%), demyelinating in 9(30%), axonal in 6(20%) and both axonal and demyelinating in 5(16.7%) patients. 13.3% had subclinical neuropathy. Sensorimotor and sensory neuropathies were detected in 36.7% and 30% of patients, respectively. Cranial neuropathy was not detected in any patient or control clinically or electrophysiologically. Peripheral neuropathy significantly correlated with SELENA-SLEDAI (r = 0.55, p = 0.002) and negatively with C3 and C4 (r = −0.65, p = 0.012 and r = −0.63, p = 0.015 respectively). ConclusionPeripheral neuropathy is a well-recognized but underestimated manifestation of neuropsychiatric SLE with predominance of sensorimotor variant. Peripheral neuropathy is associated with disease activity and complement consumption.

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity

It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.

Remodeling of Neurotransmission, Chemokine, and PI3K-AKT Signaling Genomic Fabrics in Neuropsychiatric Systemic Lupus Erythematosus.

Cognitive dysfunction and mood changes are prevalent and especially taxing issues for patients with systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its cognate receptor Fn14 have been shown to play an important role in neurocognitive dysfunction in murine lupus. We profiled and compared gene expression in the cortices of MRL/+, MRL/lpr (that manifest lupus-like phenotype) and MRL/lpr-Fn14 knockout (Fn14ko) adult female mice to determine the transcriptomic impact of TWEAK/Fn14 on cortical gene expression in lupus. We found that the TWEAK/Fn14 pathway strongly affects the expression level, variability and coordination of the genomic fabrics responsible for neurotransmission and chemokine signaling. Dysregulation of the Phosphoinositide 3-kinase (PI3K)-AKT pathway in the MRL/lpr lupus strain compared with the MRL/+ control and Fn14ko mice was particularly prominent and, therefore, promising as a potential therapeutic target, although the complexity of the transcriptomic fabric highlights important considerations in in vivo experimental models.