To characterize degree of damage along white matter (WM) tracts implicated in multiple sclerosis-related tremor (MS-T).

Tremor affects up to 50% of patients with multiple sclerosis (pwMS). Current treatments inadequately address etiology and outcomes of MS-T. Diffusion Tensor Imaging (DTI) quantitatively assesses structural integrity of WM. 

This prospective case-control study assessed pwMS with MS-T and a control group of pwMS without tremor (MS-C). 3.0 T MRI scans including 3D T1-weighted, T2-FLAIR, and DTI were performed. Tremor severity was clinically evaluated using the Essential Tremor Rating Assessment Scale (TETRAS). 

We previously identified tracts with mean diffusivity measures correlating with MS-T and TETRAS score.

In DSI studio, we generated tract profiles showing fractional anisotropy (FA) at 100 points along each pathway and averaged these into ten segments per tract. Group differences between MS-T and MS-C were calculated using Welch’s t-test and represented as Cohen’s d (d). For MS-T group, Spearman’s partial correlation coefficients were calculated for tract segment FA and correlated with TETRAS, adjusting for possible confounders. P-values were corrected for false discovery rate when appropriate. 

Tract analysis revealed segments with significant reductions in FA: near the genu in forceps minor (d=1.12, q-value < 0.0001) and left juxtacortical segment of forceps major (d=0.775, q-value=0.01) of the corpus callosum, and sections of medial lemniscus (ML) approaching the somatosensory cortex (Left: d=1.125, q-value < 0.0001; Right: d=0.845, q-value ≤ 0.0011).

Correlations between TETRAS scores and FA showed negative associations across tracts. The strongest correlations were near the genu and splenium of callosal fibers (rsp = -0.57 to -0.54, p < 0.001), subcortical segments of ML (rsp = -0.52 to -0.55, p ≤ 0.0015), and right dentatothalamic tract near the thalamus (rsp = -0.374, p=0.0295).