Differential tractography identifies a distinct pattern of white matter alterations in essential tremor with or without resting tremor

Essential Tremor (ET) is characterized by action tremor often associated with resting tremor (rET). Although previous studies have identified widespread brain white matter (WM) alterations in ET patients, differences between ET and rET have been less explored. In this study we employed differential tractography to investigate WM microstructural alterations in these tremor disorders. We conducted a Diffusion Tensor Imaging (DTI) study on age- and sex-matched cohorts: 25 healthy controls (HC), 30 ET, and 30 rET patients. Differential tractography using DSI Studio was employed to pairwise compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) among cohorts. ET and rET patients compared to HC exhibited similar widespread MD increase especially in basal ganglia and brainstem projections. WM changes were more pronounced in the left cerebral hemisphere and cerebellum (crus I and II) in ET, while in rET patients WM alterations were prevalent in right cerebral hemisphere and cerebellum crus I. Small FA decrease was found in rET but not in ET patients. ET patients showed changes in the left non-decussating dentato-rubro-thalamic tract (ndDRTT), whereas rET patients showed changes in both left ndDRTT and right decussating DRTT. In conclusion, our findings confirmed the DRTT involvement in essential tremor and demonstrated that ET and rET exhibited similar microstructural WM changes in the brain, with different hemispheric involvement-greater on the left side in ET and on the right side in rET-suggesting that these tremor disorders may be distinct subtypes of the same disease.