Purpose
Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of SLE patients. Using diffusion tensor imaging, various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate if changes can be detected in the individual white matter tracts in SLE patients regardless if neuropsychiatric symptoms are present or not.
Materials and Methods
Magnetic resonance diffusion tractography in several individual white matter tracts that are involved in language and memory tasks, including tracts to cortical association areas, was applied in 21 patients with NPSLE (mean age: 40.7 ± 12.8 years; range: 22–67 years), 18 patients with non-neurologic systemic lupus erythematosus (non-NPSLE) (mean age: 40.6 ± 12 years; range: 22–67 years), and 20 healthy control (HC) individuals (mean age: 40.64 ± 12.7 years; range: 19–60 years). Additional patients were evaluated; however, because of the inability to complete the scans required, they were excluded from the study. The fractional anisotropy of individual fiber tracts was measured and correlated with cognitive function and lupus disease severity index (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) to assess predictability and diagnostic value of these measures for NPSLE.
Results
Analyses of variance of the tractography data from the analysis of 21 tracts revealed decreased fractional anisotropy in uncinate fasciculus in the NPSLE patients when compared to non-NPSLE lupus patients and HC individuals ( P = 0.002). Non-NPSLE patients also demonstrated decreased fractional anisotropy when compared to healthy patients ( P = 0.03). Decreased fractional anisotropy was also identified in the corpus callosum and corona radiata in NPSLE patients when compared to HC individuals; however, these tracts did not show a significant difference between NPSLE and non-NPSLE patients. Decreased fractional anisotropy in the uncinate fasciculus correlated with low SLEDAI score (R 2 = 0.32).
Conclusions
Diffusion tensor tractography corroborates findings of decreased white matter integrity within the anterior corona radiate as well as the corpus callosum as previously described. Specifically, our study identified changes in the uncinate fasciculus in NPSLE and non-NPSLE patients that correlate with clinical changes (SLEDAI scores) and are independent of conventional T2 lesion burden.
Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs of the body and is affecting 0.05–0.1% of the general population . Neuropsychiatric systemic lupus erythematosus (NPSLE) has been classified as a complex neurologic disorder categorized by 19 diagnostic criteria set forth by the American College of Rheumatology (ACR) based on the presence of SLE and neuropsychiatric conditions. NPSLE is reported to occur in 30–72% of patients with SLE and is associated with increased morbidity and mortality .
Magnetic resonance imaging (MRI) has become routine in the clinical management of SLE patients with or withoutneuropsychiatric conditions to evaluate for complications of the disease that may contribute to neurologic sequela. MRI is also helpful in diagnosing or excluding cerebral pathologies, such as hemorrhage, cerebral venous thrombosis, or stroke . Conventional MR sequences such as T2-weighted and fluid attenuation inversion recovery (FLAIR) have demonstrated focal hyperintense lesions in periventricular white matter in up to 70% of NPSLE patients ; however, these hyperintense lesions are non-specific and can be present in both NPSLE and non-NPSLE patients, as well as in other unrelated conditions such as small vessel disease, aging, or demyelinating disease . White matter T2 signal changes are also a relatively common finding in cognitively healthy elderly .
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Materials and Methods
Patients and Healthy Control Subjects
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Data Acquisition
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Imaging Post-processing and Analysis
DTI Post-processing
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The Tract-based White Matter Burden Evaluation
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Statistical Analysis
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Results
Morphology and Atrophy
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Tract-based White Matter Burden
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DTI Analysis
Fractional Anisotropy (FA)
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TABLE 1
Significant Values ( P Values) for Variance of Fractional Anisotropy Identified by ANOVA Between the Groups for Each Tract
Tract Significance Genu of the corpus callosum 0.028 Left anterior corona radiata 0.178 Left anterior limb of the internal capsule 0.294 Left cingulum 0.428 Left external capsule 0.404 Left inferior longitudinal fasciculus 0.033 Left corticospinal tract 0.055 Left superior fronto-orbital fasciculus 0.835 Left superior longitudinal fasciculus 0.181 Left uncinate fasciculus 0.034 Right anterior corona radiata 0.018 Right anterior limb of the internal capsule 0.026 Right cingulum 0.906 Right external capsule 0.252 Right inferior longitudinal fasciculus 0.25 Right corticospinal tract 0.372 Right superior fronto-orbital fasciculus 0.661 Right superior longitudinal fasciculus 0.1 Right uncinate fasciculus 0.002
ANOVA, analysis of variance.
These findings demonstrate that there is clear difference between the groups in the uncinate fasciculus, genu of the corpus callosum, and the corona radiata. This analysis exemplifies structural differences between patients with neuropsychiatric systemic lupus erythematosus when compared to both healthy control patients and other patients with systemic lupus.
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Apparent Diffusion Coefficient (ADC)
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TABLE 2
Significant Values ( P Values) for Variance of Apparent Diffusion Coefficient Identified by ANOVA Between the Groups for Each Tract
Tract Significance Genu of the corpus callosum 0.038 Left anterior corona radiata 0.461 Left anterior limb of the internal capsule 0.05 Left cingulum 0.165 Left external capsule 0.213 Left inferior longitudinal fasciculus 0.417 Left corticospinal tract 0.981 Left superior fronto-orbital fasciculus 0.005 Left superior longitudinal fasciculus 0.622 Left uncinate fasciculus 0.742 Right anterior corona radiata 0.246 Right anterior limb of the internal capsule 0.159 Right cingulum 0.328 Right external capsule 0.055 Right inferior longitudinal fasciculus 0.637 Right corticospinal tract 0.857 Right superior fronto-orbital fasciculus 0.011 Right superior longitudinal fasciculus 0.023 Right uncinate fasciculus 0.01
ANOVA, analysis of variance; HC, healthy control; NPSLE, neuropsychiatric systemic lupus erythematosus; SLE, systemic lupus erythematosus.
These findings further support differences between NPSLE patients and SLE or HC control patients within the uncinate fasciculus and genu of the corpus callosum.
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Discussion
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Limitations and Future Directions
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Conclusions
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Acknowledgments
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