Background/Purpose: SLE patients experience deterioration in cognitive function over time but attribution to disease-related mechanisms is confounded by medication effects, psychiatric disease, hormonal influences and infection. The hippocampus and thalamus are interconnected subcortical structures associated with memory, attention, and other higher cortical functions. Decreased hippocampal and thalamic volumes have been reported in SLE subjects with and without cognitive and behavioral impairment. By contrast, metabolic changes in these regions have been consistently associated with memory impairment. The purpose of this study is to use  magnetic resonance diffusion tensor imaging (DTI) to evaluate changes in the integrity of pathways (i.e., anatomical connectivity) linking these two structures, as well as other pairs of regions exhibiting metabolic abnormalities  in SLE subjects.

Methods: 17 SLE patients with inactive disease and no history of CNS involvement and 14 gender, age-matched healthy control (HC) subjects were imaged using DTI with a 3T MRI scanner (57 slices of 2.5 mm thickness, FOV 240 mm, data acquisition matrix 128 x128 zero filled to 256 x 256, TR 15s).  Five b=0 images and 33 diffusion weighted images with b=800 s/mm2 were acquired.  The DTI images were processed using FSL routines (FMRIB software library: www.fmrib.ox.ac.uk/fsl), and FA and MD maps were calculated. Group tractography was performed to evaluate the integrity (anatomical connectivity) of projection pathways linking areas with significant metabolic abnormalities in SLE subjects.¹ Tracts connecting the hippocampus, thalamus, putamen, and parietal cortex were reconstructed based on clusters identified by voxel-wise comparison of FDG PET scans from SLE and HC subjects using TrackVis software.

Results: Relative to HC, the SLE group displayed a 28% reduction in hippocampal-thalamic (HT) tract count. The basal ganglia-thalamic tract was preserved in the SLE group (% 8.5 difference), whereas hippocampal-parietal tract number was increased (+30%) relative to HC.

Conclusion: This is the first study to show abnormal HT tracts in SLE subjects. Although the SLE subjects had inactive disease and no history of CNS involvement, HT tract number was reduced in this group. Importantly, the hippocampus and thalamus are areas of the brain known to be integral to cognitive processes and metabolic increases in these areas have been found to correlate with memory impairment. In contrast, other tracts between the hippocampus and parietal lobe or basal ganglia and thalamus are preserved or increased. Abnormalities in the HT tract have been associated with impaired learning and memory as well as with increased symptoms in individuals at high risk for schizophrenia. Additional analyses of other imaging studies and neuropsychological testing are planned to evaluate the functional effects of this novel structural finding. 1.      Mackay M. et al., Brain metabolism and autoantibody titers predict functional impairment in Systemic Lupus Erythematosus. Lupus SCi Med, 2015. 2(1): p. e000074.