Background Cerebral volume loss is evident in patients within 9 months of the diagnosis of SLE. As potentially neurotoxic autoantibodies can be present many years before SLE symptoms emerge, cerebral volume loss would theoretically commence even much earlier before the clinical onset of SLE. Also, while it has been suggested that SLE-related inflammation negatively impacts on brain volume, whether reducing SLE disease activity can improve cerebral volume in SLE patients is unknown.
Objectives We evaluated if the volumes of the gray matter (GMV) and white matter (WMV) of the brains of newly-diagnosed SLE patients would be reduced as compared to those of age-, sex- and IQ-matched healthy controls (HC). We also investigated for potential regional improvement of GMV and WMV after SLE patients achieved low disease activity (SLEDAI<4). If so, we would further address if reducing disease activity early in the course of SLE would correlate with enhanced cerebral volumes in SLE patients.
Methods T1-weighted MRI brain images acquired by a 1.5T Siemens Symphony MRI scanner were obtained from 14 HC and 14 SLE patients within 5 months of their diagnosis (S1) and after attaining low disease activity (S2) with ≥6 months of immunosuppressive therapy. Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between the SLE group at S1 and S2. To examine GMV and WMV changes within the SLE group between S1 and S2, whole brain voxelwise paired t-tests between subject-level GMV (and WMV) probabilistic maps in SLE patients at S1 and S2 was performed at p<0.001 with a minimum cluster size of 980 voxels. Patients with neuropsychiatric symptoms, traditional cardiovascular risk factors, anti-cardiolipin antibodies and lupus anticoagulant were excluded as these factors may engender cerebral volume loss independent of SLE.
Results The mean ± SD age of the SLE patients and HC was 39.38±13.9 and 34.07±14.4 years respectively, with 2 men in each group. The mean ± SD SLEDAI at S1 and S2 was 9.93±5.7 and 2.6±1.4 respectively (p<0.001). Compared to HC, SLE patients had lower GMV mainly in the frontal regions including bilateral middle cingulate cortex, right rolandic operculum, bilateral middle frontal gyrus (orbital part) and right supplementary motor area (SMA), and lower WMV in bilateral superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxelwise analysis of the SLE group revealed increased GMV in bilateral superior frontal gyrus (SFG), left middle frontal gyrus (MFG), right SMA, and right pre- and post-central gyrus (CG) in S2 compared to S1 (Figure A). The increase in GMV in the left SFG was significantly associated with reduction of SLEDAI amongst the lupus patients (r2 =0.560, p=0.002) (Figure B). No change in WMV was detected between S1 and S2 in the SLE group.
Conclusions Our findings suggest that GMV and WMV reduced very early in the course of SLE. Reduction of SLE disease activity was accompanied by region-specific improvement of GMV, mainly in the prefrontal region which is crucial to high-level cognitive and executive functioning.
Disclosure of Interest None declared