Abstract
BackgroundTo measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity.MethodsIn this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients.ResultsFormal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n = 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54–0.66) with neuropsychiatric scores and disease activity among cSLE patients.ConclusionsThere is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.
Highlights
To measure regional brain microvascular and microstructural changes in childhood-onset Systemic lupus erythematosus (SLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity
A variety of immunosuppressive medications were in use by the childhood-onset SLE (cSLE) patients (3 mycophenolate mofetil, 2 leflunomide, 1 tocilizumab, 1 methotrexate)
Associations of imaging parameters with cSLE features and cognitive performance Focusing on the intersection region, shown in Fig. 2a, where the spectrum of intravoxel incoherent motion (IVIM) parameters was commonly impacted by cSLE, we found some IVIM parameters to be correlated with cognitive performance or with SLE disease activity index (SLEDAI) scores
Summary
To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity. Childhood-onset systemic lupus erythematosus (cSLE) is a systemic autoimmune disease often associated with neurocognitive deficits [1, 2]. A plausible route of brain injury by SLE is through disruption of the neurovascular unit (NVU), a physiological construct describing the interplay between neurons, glia, and supporting vasculature. A key component of the NVU is the blood-brain barrier (BBB), the selectively permeable interface between blood and parenchymal cells. We and others have reported regionally increased permeability of the BBB in SLE in comparison to matched healthy controls [5, 6]. Various studies have detected alteration of cerebral blood perfusion in association with SLE [9, 10]
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