The nature of postural tremor in Parkinson disease

Abstract

Objective: To disentangle the different forms of postural tremors in Parkinson disease (PD).

Methods: In this combined observational and intervention study, we measured resting and postural tremor characteristics in 73 patients with tremulous PD by using EMG of forearm muscles. Patients were measured both "off" medication (overnight withdrawal) and after dispersible levodopa-benserazide 200/50 mg. We performed an automated 2-step cluster analysis on 3 postural tremor characteristics: the frequency difference with resting tremor, the degree of tremor suppression after posturing, and the dopamine response.

Results: The cluster analysis revealed 2 distinct postural tremor phenotypes: 81% had re-emergent tremor (amplitude suppression, frequency difference with resting tremor 0.4 Hz, clear dopamine response) and 19% had pure postural tremor (no amplitude suppression, frequency difference with resting tremor 3.5 Hz, no dopamine response). This finding was manually validated (accuracy of 93%). Pure postural tremor was not associated with clinical signs of essential tremor or dystonia, and it was not influenced by weighing.

Conclusion: There are 2 distinct postural tremor phenotypes in PD, which have a different pathophysiology and require different treatment. Re-emergent tremor is a continuation of resting tremor during stable posturing, and it has a dopaminergic basis. Pure postural tremor is a less common type of tremor that is inherent to PD, but has a largely nondopaminergic basis.

Figure 1. Example power spectra and participant classification

Power spectrum example of a patient with a re-emergent tremor (left panel in A) and an example of a patient with pure postural tremor (right panel in A; downscaled with factor 3 for illustration purposes). (B) Overview of all patients demonstrating the number of patients without a postural tremor (gray piece) and division of patients with a postural tremor according to the 2-step clustering (blue and red pieces). (C) Values of the variables used for clustering. Blue data points indicate patients from the re-emergent tremor cluster, whereas red indicates patients from the pure postural tremor cluster.

Figure 2. Tremor subgroup comparison

The difference between re-emergent and pure postural tremor for Δ frequency (A; postural minus rest tremor frequency), dopamine response (B; mean tremor power in “off” minus “on”), and the effect of wrist extension on tremor amplitude (C; log-transformed tremor power at individual tremor frequency ± 1.5 Hz to accommodate slight changes in tremor frequency).

Figure 3. Rest vs re-emergent tremor

(A) Dopamine response (on the y-axis, tremor power “off” minus “on,” ± SEM) for resting and re-emergent tremor, with a larger dopamine response for rest tremor than for re-emergent tremor (same patient group). (B, C) Correlation of (log-transformed) tremor power (B) and dopamine response (log-transformed tremor power “off” minus “on” corrected for absolute “off” state tremor power, C) between resting tremor (x-axis) and re-emergent tremor (y-axis). The dashed lines indicate a reference line when x = y.