Action Tremor Asymmetry Profile Does Not Aggregate in Families with Essential Tremor

Abstract

Background: Action tremor is the hallmark feature of essential tremor (ET). While the tremor typically is mildly asymmetric, in some patients, it is markedly asymmetric. There are few data on factors that influence this asymmetry. ET is also a highly familial disease. Whether the tremor asymmetry profile (i.e., differential expression of tremor in each arm in a given patient) is similar across family members is not known. The alternative possibility is that this feature is not heritable. There are no published data addressing this issue. The aim of this study was to determine whether the extent of action tremor asymmetry ran in ET families.

Methods: ET probands and relatives were enrolled in a genetic study at Yale and Columbia Universities. An in-person evaluation included a videotaped neurological examination, including a detailed assessment of tremors. A senior movement disorders neurologist reviewed all videotaped examinations, and the severity of postural and kinetic arm tremors was rated on 12 examination items using a reliable rating scale. The tremor asymmetry index = right arm tremor score - left arm tremor score. We used a bivariate linear regression model to assess the predictors of the tremor asymmetry index in relatives; this model used the tremor asymmetry index in the proband as a primary predictor of interest. In an analysis of variance (ANOVA), we tested for heterogeneity across families in the tremor asymmetry index (i.e., to see whether there was a significant family effect).

Results: There were 187 enrollees (59 probands, 128 affected relatives). In a bivariate linear regression model, the tremor asymmetry index in the proband was not a predictor of the tremor asymmetry index in their relatives (p = 0.66). In an ANOVA, family grouping did not explain a significant proportion of the total variance in the tremor asymmetry index (p = 0.56).

Conclusion: Tremor asymmetry did not aggregate in families with ET. Therefore, this does not seem to be a disease feature that is heritable. These data will provide added value to the clinical dialog, giving patients one more piece of information about the way the disease manifests within families.

Keywords: clinical; essential tremor; familial aggregation; genetics; movement disorders.

Figure 1

Tremor asymmetry index in probands (open circles) and relatives (closed squares). A value of 0 indicates that the tremor was equal on both sides. Positive values indicate that tremor is greater on the right side, and negative values indicate that tremor is greater on the left side. Vertical grid lines run through the data points in each family.

Figure 2

Tremor asymmetry index in probands (open circles) and relatives (closed squares) whose tremor asymmetry index had extreme values (i.e., value was above or below a certain threshold). A value of 0 indicates that the tremor was equal on both sides. Positive values indicate that tremor is greater on the right side, and negative values indicate that tremor is greater on the left side. Vertical grid lines run through the data points in each family.

Figure 3

Tremor asymmetry index in probands (open circles) and relatives (closed squares). We selected the extreme quartiles of probands whose tremor asymmetry index had extreme values. These were the 10% of probands whose tremor asymmetry index value was ≤−2.5 and the 10% of probands whose tremor asymmetry index value was ≥2.0. A value of 0 indicates that the tremor was equal on both sides. Positive values indicate that tremor is greater on the right side, and negative values indicate that tremor is greater on the left side. Vertical grid lines run through the data points in each family.