Objective: To study white matter differences between essential tremor (ET) and Parkinson’s disease (PD) using standard diffusion tensor magnetic resonance imaging (DTI) and fixel-based analysis.

Background: ET is a common slowly-progressive neurologic disorder and is predominantly characterized by kinetic tremor involving bilateral upper limbs [1]. Although ET shares motor similarities with PD, it is widely accepted that there is no relationship between ET and PD [2]. While PD is characterized pathologically by neurodegeneration, the pathophysiology of ET remains controversial [3-4]. MRI-based biomarkers may lend insight into the underlying pathophysiology of ET and PD. Here, we used DTI and fixel-based analysis (FBA) [5] to evaluate white matter (WM) microstructural differences between PD and ET.

Method: This retrospective study included 17 ET (4 females; age 69±8) and 68 PD (20 females; age 67±10). Diffusion MRI data were acquired from two scanners (GE and Philips) with different number of diffusion directions. MRtrix3 [6] was used for data pre-processing. Fractional anisotropy (FA) maps were generated by FSL [7], and FBA was performed using MRtrix3 to obtain fibre density (FD), fibre bundle (FC), and fibre density bundle cross-section (FDC). Group differences were assessed using analysis of covariance (ANCOVA, family-wise error rate (FWE) corrected) with age, sex, and scanner as covariates. Effect-size (Hedges’ g) between groups was also calculated. Significance was set at FWE<0.05 and at large effect size g>0.80.

Results: No differences were found in age between the two groups (t=0.96; p=0.34). Compared with PD, significantly lower values of FD, FC, and FDC were found in ET compared to PD in the corpus callosum (CC) and left tapetum [figure1 and table1]. Additionally, significantly lower FA values were found in ET compared to PD principally in CC, corona radiata, cingulum, and left tapetum [figure2].

Conclusion: Previous studies have demonstrated WM differences using FA between ET and PD [8], consistent with our findings. The present study extends these findings using FBA, which is more specific to WM fibre bundles and may thus improve interpretation of observed differences [5]. Reduced WM fibre integrity may indicate unique vulnerability of the CC in ET compared to PD, though further studies are needed to assess the clinical implications of these findings.

References: [1] Lorraine N Clark, Elan D Louis. Essential tremor. Handb Clin Neurol. 2018;147:229-239
[2] R Pahwa, W C Koller. Is there a relationship between Parkinson’s disease and essential tremor? Clin Neuropharmacol. 1993 Feb;16(1):30-5.
[3] Ali H Rajput, Charles H Adler, Holly A Shill, Alex Rajput. Essential tremor is not a neurodegenerative disease. Neurodegener Dis Manag. 2012 Jun; 2(3): 259–268.
[4] Elan D. Louis. The Essential Tremors: A Family of Neurodegenerative Disorders? Arch Neurol. 2009 Oct; 66(10): 1202–1208.
[5] Thijs Dhollander, Adam Clemente, et al. Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities. NeuroImage, Volume 241, 2021, 118417
[6] J.-D. Tournier, R. E. Smith, D. Raffelt, R. Tabbara, T. Dhollander, M. Pietsch, D. Christiaens, B. Jeurissen, C.-H. Yeh, and A. Connelly. MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation. NeuroImage, 202 (2019), pp. 116–37.
[7] M. Jenkinson, C.F. Beckmann, T.E. Behrens, M.W. Woolrich, S.M. Smith. FSL. NeuroImage, 62:782-90, 2012
[8] Meher R Juttukonda, Giulia Franco, et al. White matter differences between essential tremor and Parkinson disease. Neurology. 2019 Jan 1;92(1):e30-e39.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/white-matter-microstructural-differences-between-essential-tremor-and-parkinsons-disease-evaluated-using-advanced-mri-biomarkers/