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

Abstract

Objectives The 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. Methods In 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. Results NPSLE 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. Conclusion We 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.

White matter hyperintensities associate with cognitive slowing in patients with systemic lupus erythematosus and neuropsychiatric symptoms

“…8 9 In a recent study, we demonstrated that patients with inflammatory NPSLE have reduced brain volumes and increased white matter hyperintensity (WMH) volume compared with other NPSLE phenotypes. 10 Whether structural brain changes in patients with different NPSLE phenotypes are associated with cognitive dysfunction remains to be elucidated.…”

“…All participants were scanned with a standardised scanning protocol, that included a 3-D T1-weighted scan (voxel size = 1.17 × 1.17 × 1.2 mm 3 ; repetition time (TR)/ echo time (TE) = 9.8/4.6 ms) and a 2-D or 3-D fluid-attenuated inversion recovery (FLAIR) scan. A total of 109 participants were scanned with a 2-D-multislice FLAIR scan (voxel size = 1.0 × 1.0 × 3.6 mm 3 ; TR/TE/ inversion time (TI) = 10 000/120/2800 ms) and 54 participants were scanned with a 3-D FLAIR scan (voxel size = 1.10 × 1.11 × 0.56 mm 3 ; TR/TE/TI = 4800/576/1650 ms) (for more details see 10 ). The change in the FLAIR scan occurred in February 2013.…”

MRI-Based Classification of Neuropsychiatric Systemic Lupus Erythematosus Patients With Self-Supervised Contrastive Learning

“…The potential relevance of WMH shape in the radiological diagnostic process has been already demonstrated in diabetes ( De Bresser et al, 2018 ), cerebral small vessel disease ( Kant et al, 2019 ) and stroke ( Ghaznawi et al, 2021 ). Evidence for ventricular and periventricular structural differences between NPSLE phenotypes, including between NPSLE and non-NPSLE, have been already given, including in our own studies ( Inglese et al, 2021 ), and it is possible that the features detected by the ML algorithm in the NPSLE population is a combined effect of volume and shape characteristics. Finally, there is no consistent reporting on direct involvement of the basal cisterns per se in SLE or NPSLE, barred few case reports ( Kawamata et al, 1991 ; Tsushima and Kubo, 1999 ).…”

“…3D T 1 -weighted images were segmented using the CAT12 toolbox from the statistical parametric mapping software to determine total grey matter (GM), white matter (WM), and cerebral-spinal fluid (CSF) volumes ( Inglese et al, 2021 ). Total intracranial volume was calculated as the sum of gray matter, white matter, and cerebral-spinal fluid volumes.…”

Tract-based white matter hyperintensity patterns in patients with Systemic Lupus Erythematosus using an unsupervised machine learning approach

“…WMH location in patients with arterial diseases can provide prognostic survival information 14 . WMH in SLE patients has not been shown to be homogeneous across subgroups 15 . One study reported that the prevalence of WMH in the splenium of the corpus callosum, in the right superior longitudinal fasciculus and in some small clusters in the right corona radiata was higher in NPSLE patients compared to SLE patients without NP involvement 16 .…”