Treatment Of Neuropsychiatric Systemic Lupus Erythematosus Research Articles

Pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus: A review

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.

Central Nervous System Systemic Lupus Erythematosus: Pathophysiologic, Clinical, and Imaging Features

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiple immunologic abnormalities and has the potential to involve the central nervous system (CNS). The prevalence of SLE seems to be growing, possibly because of earlier diagnosis and improved survival; however, the associated mortality is still high. The mortality is associated with disease-related risk factors such as lupus disease activity, young age, and organ damage or with antiphospholipid syndrome (APS). Neuropsychiatric SLE (NPSLE), which is caused by SLE-related CNS involvement, comprises a broad range of neurologic and psychiatric manifestations with varying severity, which can make this disease indistinguishable from other conditions that are unrelated to SLE. No unifying pathophysiology has been found in the etiology of NPSLE, suggesting that this condition has multiple contributors such as various immune effectors and the brain-intrinsic neuroimmune interfaces that are breached by the immune effectors. The postulated neuroimmune interfaces include the blood-brain barrier, blood-cerebrospinal fluid barrier, meningeal barrier, and glymphatic system. On the basis of the immunologic, pathologic, and imaging features of NPSLE, the underlying pathophysiology can be classified as vasculitis and vasculopathy, APS, demyelinating syndrome, or autoimmune antibody-mediated encephalitis. Each pathophysiology has different imaging characteristics, although the imaging and pathophysiologic features may overlap. Moreover, there are complications due to the immunocompromised status caused by SLE per se or by SLE treatment. Radiologists and clinicians should become familiar with the underlying mechanisms, radiologic findings, and complications of NPSLE, as this information may aid in the diagnosis and treatment of NPSLE. Online supplemental material is available for this article.©RSNA, 2022.

Neuropsychiatric Systemic Lupus Erythematosus: A 2021 Update on Diagnosis, Management, and Current Challenges.

Patients with systemic lupus erythematosus (SLE) experience neuropsychiatric symptoms. The term neuropsychiatric SLE (NPSLE) is a generic term that refers to a series of neurological and psychiatric symptoms directly related to SLE. In approximately 30% of patients with neuropsychiatric symptoms, SLE is the primary cause (NPSLE), and symptoms manifest more frequently around SLE onset. Neurovascular and psychotic conditions can also lead to NPSLE. Pathogenesis of NPSLE is implicated in both neuroinflammatory and ischemic mechanisms, and it is associated with high morbidity and mortality. After diagnosing and assigning causality, NPSLE treatment is individualized according to the type of neuropsychiatric manifestations, type of the predominant pathway, activity of SLE, and severity of the clinical manifestations. There are many problems to be addressed with regards to the diagnosis and management of NPSLE. Controlled clinical trials provide limited guidance for management, and observational cohort studies support symptomatic, antithrombotic, and immunosuppressive agents. The purpose of this review was to provide a detailed and critical review of the literature on the pathophysiology, diagnosis, and treatment of NPSLE. This study aimed to identify the shortcoming in diagnostic biomarkers, novel therapies against NPSLE, and additional research needs.

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.

Review: Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions.

The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.

Elevated levels of soluble fractalkine and increased expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus

The aim of the present study was to determine the levels of soluble fractalkine (sFKN) and expression of CX3CR1 in neuropsychiatric systemic lupus erythematosus (NPSLE). Disease activity of SLE was assessed using the SLE Disease Activity Index (SLEDAI). The mRNA expression levels of CX3CR1 and FKN were quantified using reverse transcription-quantitative polymerase chain reaction. Levels of sFKN in the serum and cerebrospinal fluid (CSF) were measured using enzyme-linked immunosorbent assays. The mRNA expression levels of CX3CR1 in peripheral blood mononuclear cells from patients with NPSLE, non-NPSLE and Behcet's disease were significantly higher than that of rheumatoid arthritis and healthy persons. Levels of sFKN in the serum and CSF of cells with diffuse NPSLE (DNPSLE) were significantly higher than those of focal NPSLE (FNPSLE) cells. Serum levels of sFKN were higher in patients with NPSLE or non-NPSLE than heathy persons. sFKN in CSF were significantly higher in DNPSLE than non-NPSLE cells, but there were no significant difference between FNPSLE and control. Treatment reduced sFKN in serum and CSF in patients with NPSLE. There was significant correlation between sFKN in the serum of patients with SLE and the SLEDAI. sFKN levels were correlated with IgG in CSF from patients with NPSLE. The mRNA expression levels of CX3CR1 in the brain tissue of lupus mice were significantly higher than normal mice; however, the mRNA expression of FKN was lower than normal mice. These results suggest that sFKN and CX3CR1 may be involved in vasculitis and SLE, particularly in DNPSLE, which may occur by damaging the blood-brain barrier or recruiting expression microglial cells of CX3CR1. Additionally, sFKN appears to be a serological marker in patients with SLE, and may be useful for the diagnosis and treatment of NPSLE.

Clinical Manifestations of Neuropsychiatric Systemic Lupus Erythematosus in Chinese Patients

©2014 Turkish League Against Rheumatism. All rights reserved. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a specific disease, and its clinical manifestations involves the central and the peripheral nervous system range from life-threatening manifestations to subtle abnormalities.1 Neuropsychiatric systemic lupus erythematosus may be the first indication of systemic lupus erythematosus (SLE) in patients without disease activity in other organ systems.2 It represents a major cause of morbidity and mortality in SLE patients.3-8 Therefore, recognition, early diagnosis and treatment of NPSLE are of great significance.

Nervous system involvement of connective tissue disease

Connective tissue diseases can present with a wide spectrum of neurological symptoms. The present review summarizes the neurological involvement in connective tissue diseases and highlights recent findings on the diagnosis of neurological manifestations and potential underlying mechanisms. The wide range in the prevalence of neurological manifestations in systemic lupus erythematosus (SLE) and Sjögren's syndrome reveals the necessity of clear decision algorithms for the association of neurological symptoms with a systemic autoimmune disease. For this purpose new recommendations for the diagnosis and treatment of neuropsychiatric SLE have been published. Recent studies identified potential paraclinical markers for the diagnosis of nervous system involvement in connective tissue diseases. Antiaquaporin-4 antibodies occur highly specifically in those patients with connective tissue diseases that present with symptoms typical for neuromyelitis optica. To date there is no specific marker available to prove neurological manifestation of connective tissue diseases. However, some progress has been achieved in characterizing typical clinical features and potential disease associated autoantibodies, which may lead to a better management of these patients.

Neuropsychiatric Involvement in Systemic Lupus Erythematosus:Current Therapeutic Approach

The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.