White and Gray Matter Abnormalities in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Diffusion-Tensor Imaging and Voxel-Based Morphometry Study

Objective: We applied diffusion-tensor imaging (DTI) including measurements of mean diffusivity (MD), a parameter of brain tissue integrity, fractional anisotropy (FA), a parameter of neuronal fiber integrity, as well as voxel-based morphometry (VBM), a measure of gray and white matter volume, to detect brain tissue changes in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Methods: Magnetic resonance imaging (MRI) was performed in 26 patients with iRBD (mean disease duration, 9.2 +/- 6.4 years) and 14 age-matched healthy control subjects. Statistical parametric mapping (SPM) was applied to objectively identify focal changes of MRI parameters throughout the entire brain volume. Results: SPM localized significant decreases of FA in the tegmentum of the midbrain and rostral pons and increases of MD within the pontine reticular formation overlapping with a cluster of decreased FA in the midbrain (p < 0.001). VBM revealed increases of gray matter densities in both hippocampi of iRBD patients (p < 0.001). Interpretation: The observed changes in the pontomesencephalic brainstem localized 2 areas harboring key neuronal circuits believed to be involved in the regulation of REM sleep and overlap with areas of structural brainstem damage causing symptomatic RBD in humans. Bilateral increases in gray matter density of the hippocampus suggest functional neuronal reorganization in this brain area in iRBD. This study indicates that DTI detects distinct structural brainstem tissue abnormalities in iRBD in the regions where REM is modulated. Further studies should explore the relationship between MRI pathology and the risk of patients with iRBD of developing alpha-synuclein-related neurodegenerative diseases like Parkinson disease. ANN NEUROL 2011;69:400-407