Abstract
Object: The purpose of this study was to uncover the pathology of restless legs syndrome (RLS) by exploring brain structural alterations and their corresponding functional abnormality.Method: Surface-based morphometry (SBM) and voxel-based morphometry (VBM) were performed to explore the alterations in cortical and sub-cortical gray matter volume (GMV) in a cohort of 20 RLS and 18 normal controls (NC). Furthermore, resting-state functional connectivity (RSFC) was also performed to identify the functional alterations in patients with RLS.Results: We found significant alterations of sub-cortical GMV, especially the bilateral putamen (PUT), rather than alterations of cortical GMV in patients with RLS compared to NC using both SBM and VBM. Further sub-regional analysis revealed that GMV alterations of PUT was mostly located in the left dorsal caudal PUT in patients with RLS. In addition, altered RSFC patterns of PUT were identified in patients with RLS compared to NC. Moreover, correlation analyses showed that the GMV of the left caudate and the left ventral rostral PUT were positively correlated with disease duration in patients with RLS.Conclusions: The alterations of subcortical GMV might imply that the primarily affected areas are located in sub-cortical areas especially in the sub-region of PUT by the pathologic process of RLS, which might be used as potential biomarkers for the early diagnosis of RLS.
Highlights
Restless legs syndrome (RLS) is a common sensorimotor disorder, which is characterized by a nearly irresistible urge to move legs; the symptoms fluctuate in severity with the diurnal cycle, worsening during the night-time hours [1, 2]
We found increased gray matter volume (GMV) of the PUT.L and bilateral brainstem in patients with RLS compared to normal controls (NC) (Figure 2, Table 2)
We found significant alterations of subcortical GMV, especially the PUT, rather than alterations of cortical GMV in patients with RLS compared to NC using both surface-based morphometry (SBM) and voxel-based morphometry (VBM)
Summary
Restless legs syndrome (RLS) is a common sensorimotor disorder, which is characterized by a nearly irresistible urge to move legs; the symptoms fluctuate in severity with the diurnal cycle, worsening during the night-time hours [1, 2]. Since symptoms usually worsen during the night, which caused sleep problem, it was reported that widespread encephalic regions including areas related to motion, sensation, and arousal [3] were activated in patients with RLS. FMRI studies demonstrated that areas including the somatosensory and sensorimotor related cortices, the cerebellum and the thalamus are activated in patients with RLS [6, 8, 10, 11]. Voxel-based morphometry (VBM) study demonstrated gray matter (GM) changes in various brain areas in patients with RLS. A study found decreased regional GMV in the left hippocampal gyrus, bilateral parietal lobes, medial frontal areas and cerebellum in patients with RLS [15]. As one region of the brain usually involves various functions, the sub-regional changes might explain the inconsistence of structural and functional abnormality in patients with RLS.
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