Abstract

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.

Highlights

  • Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production and deposition of autoantibodies and involvement of different organs, such as the kidneys, lungs, joints, skin, and the brain

  • Neuropsychiatric systemic lupus erythematosus (NPSLE) patients showed a higher white matter hyperintensities (WMH) volume compared to SLE patients with neuropsychiatric syndromes not attributed to SLE

  • NPSLE patients with inflammatory phenotype showed lower white matter and total brain volumes compared to NPSLE patients with ischemic phenotype

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Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production and deposition of autoantibodies and involvement of different organs, such as the kidneys, lungs, joints, skin, and the brain. Neuropsychiatric (NP) symptoms are common in patients with SLE and can be directly associated with the disease (NPSLE) or can be explained by another etiology, such as side effects of medication or involvement of other organs (non-NPSLE) [1]. The inflammatory pathway is thought to be caused by production of inflammatory mediators as well as increased permeability of the blood-brain barrier, leading to focal (e.g., seizure) and diffuse NP manifestations (e.g., psychosis) [4]. The ischemic pathway is thought to be caused by injury of large- or small-caliber vessels or by immune system activation, often leading to focal (e.g., stroke) and diffuse NP events (e.g., cognitive dysfunction) [4]

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