Alterations of white matter structural networks in patients with non-neuropsychiatric systemic lupus erythematosus identified by probabilistic tractography and connectivity-based analyses

Abstract

PurposeSystemic lupus erythematosus (SLE) is a chronic inflammatory female-predominant autoimmune disease that can affect the central nervous system and exhibit neuropsychiatric symptoms. In SLE patients without neuropsychiatric symptoms (non-NPSLE), recent diffusion tensor imaging studies showed white matter abnormalities in their brains. The present study investigated the entire brain white matter structural connectivity in non-NPSLE patients by using probabilistic tractography and connectivity-based analyses.MethodsWhole-brain structural networks of 29 non-NPSLE patients and 29 healthy controls (HCs) were examined. The structural networks were constructed with interregional probabilistic connectivity. Graph theory analysis was performed to investigate the topological properties, and network-based statistic was employed to assess the alterations of the interregional connections among non-NPSLE patients and controls.ResultsCompared with HCs, non-NPSLE patients demonstrated significantly decreased global and local network efficiencies and showed increased characteristic path length. This finding suggests that the global integration and local specialization were impaired. Moreover, the regional properties (nodal efficiency and degree) in the frontal, occipital, and cingulum regions of the non-NPSLE patients were significantly changed and negatively correlated with the disease activity index. The distribution pattern of the hubs measured by nodal degree was altered in the patient group. Finally, the non-NPSLE group exhibited decreased structural connectivity in the left median cingulate-centered component and increased connectivity in the left precuneus-centered component and right middle temporal lobe-centered component.ConclusionThis study reveals an altered topological organization of white matter networks in non-NPSLE patients. Furthermore, this research provides new insights into the structural disruptions underlying the functional and neurocognitive deficits in non-NPSLE patients.

Metabolic and microstructural alterations in the SLE brain correlate with cognitive impairment

“…Additional longitudinal studies are needed to verify this prediction. While several studies have reported WM alterations in NPSLE compared with HC subjects in segments of the CC, the forceps, anterior corona radiata, thalamus, and parietal and frontal lobes (33-36) and overall diminished volume of the CC (34, 37), our results support the growing body of literature demonstrating significant WM abnormalities in SLE subjects without acute neuropsychiatric manifestations (38)(39)(40)(41)(42). Most of these studies in SLE subjects without neuropsychiatric manifestations failed to demonstrate significant correlations between diminished WM integrity and cognition.…”

Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosus

“…A study in 52 normal individuals at the beginning of the 8th decade of life observed that despite WMH having similar effects on tract infrastructure, whether they be intersecting or nearby, differences in tract water diffusion properties around WMH suggest that tract degeneration may propagate along the white matter tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. 47 This study also complements findings by other studies in smaller SLE samples, which found altered structural network parameters in SLE patients 13,14 compared to controls, with only few differences in functional hub measures. 14…”

“…12 Another study found that brain connectivity networks in SLE patients had decreased efficiency and increased characteristic path length compared to healthy controls. 13 Complementary to the previously mentioned study, 12 regional network degree and nodal efficiency in frontal, occipital and cingulum regions negatively correlated with disease activity in this smaller SLE cohort. 13 Another study also found abnormal global efficiency and network path length in SLE patients compared to controls despite similar functional hub connectivity measurements.…”

Nervous System Disease in Systemic Lupus Erythematosus: Current Status and Future Directions

“…Abnormalities in NPSLE likely represent demyelination and/or altered network connectivity not seen with conventional MRI sequences . Using brain connectivity analysis of diffusion MRI data, reduced nodal efficiency in the brain network was observed in patients with NPSLE, compared to controls .…”

“…Preliminary studies in SLE suggest compensatory adaptation of neuronal function through recruitment of additional cortical pathways. These compensatory responses maintain cognitive function in the short term but may eventually be overcome and manifest as overt cognitive impairment . Even SLE patients without clinical NP disease have abnormal fMRI resting‐state brain intrinsic connectivity , raising the possibility of preclinical detection .…”