The pathoanatomy of RLS revisited: evidence for cortical and subcortical alterations

The pathoanatomical correlate of the restless legs syndrome (RLS) remains undetermined up to date. Various neuroimaging approaches including advanced MRI techniques, PET and SPECT have indicated widespread spinal, mesencephalic and cerebral involvement. The aim of the present study was to address potential alterations of both gray and white matter within the same group of patients suffering from idiopathic RLS by combined application of the optimal MRI technique each, i.e. voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

Therefore, a large patient sample from the outpatient clinic for movement disorders of the University of Ulm underwent MRI scans including a high-resolution T1w MRI data set and a DTI EPI-sequence. Post-processing on 3-D data (RLS patients: n=63) was performed using optimized VBM in comparison to an age-matched normal data base (n=40). The post-processing steps of the DTI data sets included the compilation of a customized template of all single data sets (RLS: n=45) and a whole-brain based statistical analysis of the fractional anisotropy (FA) in comparison to a control sample (n=31).

Areas of regional decrease in gray matter volume were observed by VBM at p<0.05, corrected for small volumes. The largest voxel clusters were localized in the somatosensory cortex of the right and left hemisphere almost symmetrically and in the left-hemispheric motor cortex. The DTI analysis revealed large, bihemispherically localized voxel clusters of a significant FA reduction at p<0.05. The pattern of the subcortical FA alterations ranged from prefrontal over premotor to motor areas, the latter in close proximity to the cortical areas revealed by VBM.

These results demonstrated the involvement of both cerebral gray matter structures and subcortical white matter areas, as structural pathoanatomical correlates in RLS.