Diffusion tensor imaging of white matter involvement in essential tremor

Abstract

This study set out to determine whether there is white matter involvement in essential tremor (ET), the most common movement disorder. We collected diffusion MRI and analysed differences in fractional anisotropy (FA) and mean diffusivity (MD) between ET patients and control subjects as markers of white matter integrity. We used both classical ROI-based statistics and whole-brain analysis techniques, including voxel-wise analysis with SPM5 and tract-based spatial statistics (TBSS). Using region of interest (ROI) analysis, we found increased MD bilaterally in the inferior cerebellar peduncles (ICP) and reduced FA in the right-sided ICP of ET patients. Whole-brain analyses with TBSS detected increased MD distributed in both motor and nonmotor white matter fibers of ET patients predominantly in the left parietal white matter, while there were no significant FA differences in these areas between ET patients and controls. Voxel-wise analysis with SPM detected significant increase of MD congruent with the highest probability of difference as detected by TBSS. VBM analysis of T1 images did not detect significant differences in either gray or white matter density between our study groups. In summary, we found evidence for changes in white matter MRI properties in ET. The circumscript pathology of the ICP corroborates the pathogenetic concept of the cerebellum and its projections as key structures for tremor generation in ET. Moreover, increased diffusivity in white matter structures of both hemispheres suggests widespread alterations of fiber integrity in motor and nonmotor networks in ET patients. The underlying cause of the DTI changes observed remains to be elucidated.

White matter measures correlate with essential tremor severity—A pilot diffusion tensor imaging study

“…Similarly, forceps minor located in the ventral part of the corpus callosum showed a significant correlation with both objective combined score and frequency but not the clinical rating scales. While the absence of correlation between diffusion measurements and clinical ET rating scales in our study corroborates two previous DTI studies conducted on the larger sample of 22 and 25 ET patients (Nicoletti et al., 2010; Saini et al., 2012), others showed significant association between frontoparietal WM and Fahn score in smaller samples of 14 and 19 ET patients, respectively (Klein et al., 2011; Pelzer et al., 2017). These discrepancies may be explained by lower inter‐rater reliability and the subjective nature of the clinical rating scales (Elble et al., 2013).…”

“…WM microstructure in abovementioned bundles was related to various neuropsychological outcomes in ET (Bhalsing et al., 2015), while our study linked WM blobs within these tracts to objective tremor measurements reflecting abnormal motor functions. These relationships were in partial agreement with an association between FTM scale and fronto‐parietal WM deficits demonstrated previously (Klein et al., 2011). In ATR (Mamah et al., 2010), which spreads from thalamus to frontal regions, were the tremor‐related areas located directly in the thalamus.…”

“…Previous DTI studies in ET confirmed an involvement of the CTC (Jia, Jia‐lin, Qin, Qing, & Yan, 2011; Klein et al., 2011; Nicoletti et al., 2010; Saini et al., 2012) but also of areas outside the “tremor network” (Klein et al., 2011; Saini et al., 2012) when a whole‐brain DTI analysis using tract‐based spatial statistics (TBSS) (Smith et al., 2006) was applied. The areas outside CTC were linked to nonmotor ET symptoms (Benito‐León et al., 2017; Bhalsing et al., 2014, 2015), which provides further evidence for the pathophysiological complexity of ET.…”

“…The widespread and variable WM alterations in ET (Jia et al., 2011; Klein et al., 2011; Nicoletti et al., 2010; Saini et al., 2012) shown in prior studies emphasize the need to further investigate the correlation of WM microstructure changes with motor signs in ET and to identify potential morphological markers of tremor severity. Identifying the relevant WM areas responsible for motor and nonmotor signs in ET would help explain the variable pharmacotherapy response in ET (Hedera, Cibulčík, & Davis, 2013) and potentially contribute to the development of reliable measures of therapeutic interventions (Ondo, 2016).…”

“…Identifying the relevant WM areas responsible for motor and nonmotor signs in ET would help explain the variable pharmacotherapy response in ET (Hedera, Cibulčík, & Davis, 2013) and potentially contribute to the development of reliable measures of therapeutic interventions (Ondo, 2016). Several DTI studies (Klein et al., 2011; Nicoletti et al., 2010; Pelzer et al., 2017; Saini et al., 2012) utilized clinical rating scales (e.g., Fahn‐Tolosa‐Marin [FTM] and Bain scales) as a measure of tremor severity; however, only two studies found a correlation between the FTM score and frontoparietal WM microstructure (Klein et al., 2011; Pelzer et al., 2017). The lower inter‐rater reliability and the subjective nature of the clinical rating scales (Elble et al., 2013) can be mitigated by objective accelerometry measures (i.e., the tremor frequency and amplitude), which may provide a more accurate representation of the disease pathophysiological features.…”