Microstructural Changes in the Corpus Callosum in Systemic Lupus Erythematous

Abstract

Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.

Effects of Systemic Lupus Erythematosus on the Brain: A Systematic Review of Structural MRI Findings and their Relationships with Cognitive Dysfunction

“…Within SLE subgroups, one study reported large affected areas in SLE patients with and without memory deficits vs controls (lower FA and higher MD/RD) 30 . Another study evaluated patients with cSLE vs aSLE and reported lower FA and higher diffusivities in the corpus callosum in the former relative to the latter subgroup 26 , while no diffusion differences were observed between NPSLE and non-NPSLE patients in two manuscripts 19,24 . No changes in diffusion metrics in patients with SLE after the follow-up period were observed in the DTI publication with longitudinal data 25 .…”

“…Three manuscripts reported information regarding race/ethnicity, and in two of them over half of the patients were African-Americans (6/11 – 55%, and 14/20 – 70% of their respective cohorts 25,27 ). Cohort ages ranged 14.7-48.9 years on average with a pooled mean of 35.5 years; 16/18 studies examined adult patients with SLE, 2/18 included patients with cSLE 27,28 , and one compared patients with aSLE versus cSLE 26 . Healthy controls with age and sex distributions comparable to their respective SLE cohorts were utilized for group comparisons in 16/18 studies.…”

“…Screening tests are recurrently used to evaluate multiple domains and provide a quick global estimate of cognitive function. These screening tools were applied in six studies: Mini Mental State Examination (MMSE, 6/18) 20,30–32,34,35 , Montreal Cognitive Assessment (MoCA, 3/18) 20,26,34 , Addenbrooke’s Cognitive Examination (ACE, 3/18) 20,32,34 , and National Adult Reading Test (NART, 2/18) 20,34 . The use of screening tests has increased during the last decade as they might complement subjective assessments and guide additional neuropsychological tests to evaluate specific cognitive domains of interest in patients with SLE.…”

“…They were mainly computed with tractography, tract-based spatial statistics, or voxel-wise analyses. One tractography study focused on the corpus callosum, cingulum and uncinate fasciculus tracts 19 while another study solely retrieved metrics from corpus callosum automated segmentations 26 . IVIM-derived diffusion-perfusion metrics were examined in one study 27 .…”

“…With regard to diffusion MRI metrics, for total WM, higher MD was associated with lower overall cognitive function 20 . The corpus callosum was the WM structure that was most recurrently associated with CD (3/18 studies), with higher MD 26 and lower FA 24 correlating with worse overall cognitive function, lower FA 24 and higher free water 21 being associated with poor attention, and lower FA with visual memory and psychomotor speed 24 . Lower FA in the cingulum associated with slower psychomotor speed and worse cognitive flexibility (executive functioning domain) 19 , while higher free water was associated with worse attention 21 .…”