Microstructural abnormalities of the dentato-rubro-thalamo-cortical tract in tremor dominant Parkinson's disease and essential tremor plus syndrome

Purpose: The dentato-rubro-thalamo-cortical tract (DRTC) is considered to play a crucial role across tremor disorders including tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP). This study aims to comprehensively evaluate microstructural integrity of the DRTC using single-compartment, i.e., DTI, and multi-compartment, i.e., neurite orientation dispersion and distribution imaging (NODDI), and free water (FW) based analysis.

Methods: DTI, NODDI and FW based metrics were estimated for 25 TDPD, 25 ETP (Essential tremor with rest tremor) and 22 healthy controls (HC). TBSS was carried out followed by voxelwise statistics on respective metric skeletons with TFCE correction and custom FA skeleton masks for left and right DRTC tracts. Masks generated from significant clusters, and whole tract masks were utilised in quantitative analysis. ROI based subject space analysis was also carried out for whole tract and TBSS cluster values. Quantitative analysis was carried out using MANCOVA with age and gender as covariates. Clinical features between TDPD and ETP were compared using t-test.

Results: There was no difference in the Fahn-Tolosa-Marin tremor rating scale score. Compared to HC, TDPD showed lower neurite density index, higher axial diffusivity (AD), mean diffusivity (MD), FW corrected MD in the thalamo-cortical section of the left DRTC. No statistically significant differences were observed between ETP and HC or TDPD and ETP.

Conclusions: TDPD demonstrated asymmetric reduction in neurite density and increased MD, fwMD and AD in the thalamo-cortical section of DRTC. The absence of differences between ETP and TDPD may suggest the possibility of similarities in tremor pathogenesis.