Exploring White Matter Microstructure with Symptom Severity and Outcomes Following Deep Brain Stimulation in Tremor Syndromes.

Background: Essential tremor (ET) and dystonic tremor (DT) are movement disorders that cause debilitating symptoms, significantly impacting daily activities and quality of life. A poor understanding of their pathophysiology, as well as the mediators of clinical outcomes following deep brain stimulation (DBS), highlights the need for biomarkers to accurately characterise and optimally treat patients.

Objectives: We assessed the white matter microstructure of pathways implicated in the pathophysiology and therapeutic intervention in a retrospective cohort of patients with DT (n = 17) and ET (n = 19). We aimed to identity associations between white matter microstructure, upper limb tremor severity, and tremor improvement following DBS.

Methods: A fixel-based analysis pipeline was implemented to investigate white matter microstructural metrics in the whole brain, cerebello-thalamic pathways and tracts connected to stimulation volumes following DBS. Associations with preoperative and postoperative severity were analysed within each disorder group and across combined disorder groups.

Results: DBS led to significant improvements in both groups. No group differences in stimulation positions were identified. When white matter microstructural data was aligned according to the maximally affected upper limb, increased fiber density, and combined fiber density & cross-section of fixels in the left cerebellum were associated with greater tremor severity across DT and ET patients. White matter microstructure did not show associations with postoperative changes in cerebello-thalamic pathways, or tracts connected to stimulation volumes.

Discussion: Diffusion changes of the cerebellum are associated with the severity of upper limb tremor and appear to overlap in essential or dystonic tremor disorders.