Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE)

doi:10.1053/berh.2001.0223

Best Practice & Research Clinical Rheumatology

Volume 16, Issue 2, April 2002, Pages 229-244

https://doi.org/10.1053/berh.2001.0223 Get rights and content

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) involves a wide range of focal and diffuse central and peripheral nervous system disorders and affects up to 75% of SLE patients. NPSLE can occur any time in the course of SLE, even during periods in which no SLE disease activity is detected, and is likely to be caused by multiple factors, including autoantibody production, microvasculopathy and pro-inflammatory cytokines. Central to the diagnosis of NPSLE is the question of whether the presenting neuropsychiatric symptoms are due to SLE-mediated organ dysfunction, infection, medication side-effects or metabolic abnormalities (e.g. uraemia), or are due to an unrelated condition. The diagnostic inference of NPSLE can be made only after these secondary causes have been excluded. There is no one single diagnostic tool specific to NPSLE, and clinical diagnostic impressions must be based on the combined use of immunoserological testing, functional and/or structural neuroimaging and standardized neurological, rheumatological, psychiatric and neuropsychological assessments. The management of NPSLE includes symptomatic and/or immunosuppressive treatment strategies depending on the specific presenting neuropsychiatric symptoms and whether these occur in the setting of an SLE disease activity flare.

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Neuropsychiatric lupus erythematosus can involve both the central and peripheral nervous systems and also represents a major cause of mortality and morbidity affecting up to 75% of patients with lupus.48,49 Neuropsychiatric SLE can have multiple presentations, such as headaches, cognitive dysfunction, or affective disorders,48,49 as well as the development of sudden life-threatening cerebrovascular events. These symptoms are caused by inflammatory pathology in the brain, in which autoantibodies have been proposed to play a dominant role50,51 but concrete evidence for ancestry bias is lacking.
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Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review
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The neurological and psychiatric manifestations of systemic lupus erythematosus (NPSLE) are a heterogeneous group of conditions with variable clinical presentation and significant morbidity and mortality.
Our aim was to comprehensively assess and present the evidence for treatments used in the management of inflammatory NPSLE.
Medline, Embase, CINHAL and Cochrane CENTRAL were searched from 1990 to end of March 2019 using key words that related to NPSLE and treatment. Included studies comprised clinical trials, observational studies or case series with ≥5 patients and sufficient data related to treatment and outcome in NPSLE patients.
There were 7222 studies identified in the search, of which 90 were included in the review. There was a notable paucity of clinical trials, with only two randomised controlled trials and one pilot study. Treatment categories included corticosteroids (14 studies), cyclophosphamide (18 studies), synthetic DMARDs (7 studies), biologic therapies (14 studies), therapeutic plasma exchange (6 studies), intravenous immunoglobulin (2 studies), autologous stem cell transplant (3 studies), other therapies (8 studies), combination therapies (6 studies), studies with grouped outcome data (5 studies) and observational studies with therapy-specific associations (7 studies). Corticosteroids are accepted as first line treatment in NPSLE and there is low-moderate evidence supporting their benefit. Moderate evidence, based on consistent data in numerous studies and some trial data, supports the use of cyclophosphamide in the treatment of NPSLE. Limited data support some synthetic DMARDs such as mycophenolate, azathioprine and intrathecal methotrexate. In refractory disease, low-moderate evidence supports rituximab therapy and limited evidence supports benefit following autologous stem cell transplant. Regarding adjuvant treatments, limited evidence favours addition of plasma exchange, intravenous immunoglobulin and hydroxychloroquine. There exists very limited data for other therapies.
There are multiple therapeutic options for the management of inflammatory NPSLE including systemic, biologic and interventional therapies; however, currently there is a paucity of high-quality trial data to guide firm recommendations. In order to better understand the optimal treatment of NPSLE and its different subtypes, further well-designed clinical trials are needed.
A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus
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Citation Excerpt :
This may explain why cross-sectional studies fail to find an association between anti-RibP and NPSLE. In a rare disorder such as NPSLE with severe morbidity and mortality [96–99] it may be advantageous to have a more sensitive antigen to allow for earlier detection and treatment. If initial testing with C22 peptide is performed and is negative on a patient highly suspicious for NPSLE, the clinician might consider repeating the test using P0, P1, and P2 or ribosomes.
The discovery of autoantibodies to ribosomal proteins (anti-RibP) dates back more than fifty years when antibodies to ribosomes were identified in systemic lupus erythematosus (SLE) sera. Over the years, anti-RibP autoantibodies have been the subject of extensive study and became known as a highly specific biomarker for the diagnosis of SLE and were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN) and hepatitis (LH). As demonstrated by studies on cultured human cells and of murine models, there is evidence to suggest that anti-RibP may have a pathogenic role in LN and NPSLE. Despite a wealth of evidence, in comparison to other SLE autoantibodies such as anti-Sm and anti-dsDNA, anti-RibP has not been included in classification criteria for SLE. A significant challenge is the variability of assays used to detect anti-RibP, including the antigens and diagnostic platforms employed. This may account for the marked variation in frequencies (10–47%) in SLE and its association with clinical and demographic features reported in SLE cohorts. We performed a systematic literature review and meta-analysis to help clarify its prevalence, various clinical and serological associations in SLE based on the different RibP antigens and assay platforms used.
Serological comparison of systemic lupus erythematosus with neuropsychiatric lupus using synthetic nucleic acid antigens
2020, Journal of Translational Autoimmunity
Neuropsychiatric systemic lupus erythematosus is an autoimmune disorder characterized by an irregular exchange between the central nervous system and the immune system, leading to the outbreak of neurological conditions with possible disabling effects. Although neuropsychiatric systemic lupus erythematosus is the most common expression of lupus condition, it is still poorly understood. In this study, we focus on the development of an advantageous method based on the application of synthetic nucleic acids and protein-based antigen arrays in order to characterize autoreactive antibodies in neuropsychiatric systemic lupus erythematosus. We confirmed the benefits of using synthetic oligonucleotides such as assay reproducibility, elevated affinity and specificity to autoreactive antibodies. We also demonstrated presence of autoantibodies towards three particular synthetic double stranded antigens and verify similarity of antinuclear antibody patterns in ordinary lupus and neuropsychiatric systemic lupus erythematosus.
TNF-α regulates microglial activation via the NF-κB signaling pathway in systemic lupus erythematosus with depression
2019, International Journal of Biological Macromolecules
This study aimed to investigate the effects of tumor necrosis factor-α (TNF-α) on systemic lupus erythematosus (SLE). The animal model of MRL/MpJ-Faslpr mice (MRL/lpr; lupus-prone mice) showed depression-like behaviors based on tail suspension, sucrose preference, and open field tests. Brain microglia were significantly activated with obvious increases in proinflammatory cytokines. In addition, in vitro experiments showed that TNF-α activated microglia by upregulating the NF-κB signaling pathway and proinflammatory cytokines. PDTC, a specific NF-κB inhibitor, effectively reduced TNF-α-mediated inflammatory signaling in microglia. These results suggest that TNF-α-induced microglial activation has a major role in neuroinflammation of SLE with depression.
Catatonia Associated With Systemic Lupus Erythematosus (SLE): A Report of Two Cases and a Review of the Literature
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Systemic lupus erythematosus (SLE) is known to cause neuropsychiatric symptoms (NPSLE). While not formally recognized as a syndrome associated with NPSLE, catatonia has frequently been reported.
It is important for clinicians to recognize and treat catatonia as a potential manifestation of NPSLE. We present 2 cases of SLE with catatonia and review the cases reported in the literature.
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Regular ArticleDiagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE)

Abstract

Seminars in Arthritis & Rheumatism

General Hospital Psychiatry

American Journal of Medicine

American Journal of Medicine

American Journal of Medicine

American Journal of Medical Science

American Journal of Medicine

Lancet

Arthritis & Rheumatism

Vasculitis in systemic lupus erythematosus

Lupus

The neurologic manifestation of systemic lupus erythematosus: a clinical-pathological study of 24 cases and review of the literature

Medicine

Central nervous system infections: disorders that mimic central nervous system infections

Neurologic Clinics

Neuroimaging in neuropsychiatric systemic lupus erythematosus

Arthritis & Rheumatism

Association between clinical factors, socio-economic status, and organ damage in recent onset systemic lupus erythematosus

Journal of Rheumatology

Prevalence of neuropsychiatric syndromes in patients with systemic lupus erythematosus

Lupus

Neuropsychiatric lupus syndromes (NPSLE): Prevalence using standardized definitions

Lupus

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes: Analysis of 527 patients

Lupus

Risk factors for central nervous system involvement in systemic lupus erythematosus

Quarterly Journal of Medicine

Central nervous system disease in patients with systemic lupus erythematosus

Neurology

The association between the antiphospholipid antibody syndrome and neuropsychological impairment in SLE

Lupus

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations

Lupus

Cognitive impairment in systemic lupus erythematosus: a follow up study

Journal of Neurology

Neuropsychological function in SLE: a five-year longitudinal study

Lupus

A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus

Arthritis & Rheumatism

A longitudinal analysis of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus

Arthritis & Rheumatism

Validating repeatable neuropsychological battery for hispanic SLE patients

Lupus

Pattern of neuropsychologic dysfunction in inactive systemic lupus erythematosus

Neuropsychiatry, Neuropsychology, and Behavioral Neurology

Autoantibody contributions to cognitive function in SLE

Lupus

Evoked potential study and radiological findings in patients with systemic lupus erythematosus

Electromyography and Clinical Neurophysiology

Decreased regional metabolic rate for glucose in systemic lupus erythematosus patients with psychiatric symptoms

European Neurology

The clinical relevance of antibodies to ribosomal-P common epitope in two targeted systemic lupus erythematosus populations: a large cohort of consecutive patients and patients with active central nervous system disease

Annals of the Rheumatic Diseases

Ribosomal P antibodies in systemic lupus erythematosus

Arthritis & Rheumatism

Differential roles on the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus

Arthritis & Rheumatism

Diagnostic and Statistical Manual of Mental Disorders

Adverse neurologic effects of glucocorticosteroids

Journal of General Internal Medicine

Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus

Archives of Internal Medicine

Lexicon of Psychiatry, Neurology, and the Neurosciences

Psychologic side effects of therapy with corticosteroids

American Review of Respiratory Diseases

Seminars in Psychiatry

Mild presentation of systemic lupus erythematosus in elderly patients assessed by SLEDAI

Lupus

Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus

Lupus

Regular Article
Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE)