Objective: To investigate possible dopaminergic pathophysiology of essential tremor (ET) by focusing on tremor asymmetry.

Background: Essential tremor (ET) is considered a non-dopaminergic movement disorder. Previous studies using functional brain imaging have demonstrated generally normal striatal dopamine transporter (DAT) binding in ET patients. However, there are several lines of evidence supporting a partial dopaminergic mechanism in ET and a link between ET and Parkinson’s disease (PD). We hypothesized that a dopaminergic mechanism could be detected in ET in association with tremor asymmetry and hemispheric differences.

Method: Asymmetries of upper extremity tremor and striatal DAT binding were compared between 46 ET patients, and 165 PD patients. Each patient was scanned with [¹²³I]FP-CIT SPECT and clinically examined immediately before imaging with MDS-UPDRS part III including tremor ratings. DAT binding asymmetry index was calculated from specific binding ratios (SBR; [right-left]/[right+left]). To take into account tremor severity, a severity asymmetry index (SAI) of kinetic, postural and rest tremor was calculated: tremor asymmetry ([right-left]/[right+left] x MDS-UPDRS item score from the predominant side of tremor). Asymmetry indices were compared between groups using Mann-Whitney U-tests. Correlations between tremor SAIs and DAT-binding asymmetries were calculated using Spearman’s correlation coefficients.

Results: In ET, posterior putamen DAT binding asymmetry correlated with kinetic tremor SAI (r = 0.31, p-value = 0.047; more severe tremor side associated with contralateral DAT loss) but not with postural or rest tremor SAI (r=-0.06 to -0.16, p>0.36). ET patients had more tremor compared to PD patients (median [IQR] general tremor score = 8.0 [5.3] vs 4.0 [5.0], p<0.001). Rest and postural tremor SAI was higher in PD as compared to ET (p<0.03). Striatal DAT-binding asymmetry was higher in PD compared to ET (p<0.001) and it correlated with postural, kinetic and rest tremor SAI in PD patients (p<0.001).

Conclusion: There is a relationship between the asymmetry of kinetic tremor and the asymmetry of dopaminergic function in ET. These results support a partial dopaminergic pathophysiology in ET. The unsatisfactory treatment efficacy of non-dopaminergic pharmacotherapies in some ET patients could be in part due to the underlying dopaminergic mechanisms of tremor.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/asymmetry-of-striatal-dopaminergic-function-in-essential-tremor-is-associated-with-kinetic-tremor-asymmetry/