Abstract
We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease (PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [123I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.
Highlights
Tremor in Parkinson disease (PD) is characterized by 4–6 Hz activity at rest in the limbs with distal predominance
The tremor in PD is remarkable for several features: (1) it is neither a consistent nor a homogeneous feature across patients or within an individual patient’s disease course; (2) it may diminish in the end-stage of PD; (3) it occurs predominantly at rest and is reduced or disappears by action; (4) it increases in amplitude or can be triggered by maneuvers such as walking or psychological states as anxiety or stress (Deuschl et al, 1998); (5) it is not present during sleep; (6) it may be the predominant or the only clinical sign for years before the appearance of akinesia (Brooks et al, 1992); and (7) it poorly correlates with the nigrostriatal dopaminergic deficits (Isaias et al, 2007)
There is increasing evidence that resting tremor in PD is associated with a distinct cerebello-thalamic circuit involving the ventral intermediate nucleus of the thalamus (Vim), the cerebellum, and the motor cortex
Summary
Tremor in Parkinson disease (PD) is characterized by 4–6 Hz activity at rest in the limbs with distal predominance. The tremor in PD is remarkable for several features: (1) it is neither a consistent nor a homogeneous feature across patients or within an individual patient’s disease course; (2) it may diminish in the end-stage of PD; (3) it occurs predominantly at rest and is reduced or disappears by action; (4) it increases in amplitude or can be triggered by maneuvers such as walking or psychological states as anxiety or stress (specific tasks, like simple arithmetic calculation, may induce stress-related tremor) (Deuschl et al, 1998); (5) it is not present during sleep; (6) it may be the predominant or the only clinical sign for years before the appearance of akinesia (Brooks et al, 1992); and (7) it poorly correlates with the nigrostriatal dopaminergic deficits (Isaias et al, 2007). Preliminary evidence of a role of adrenaline and noradrenaline (NA) in parkinsonian tremor emerged from studies published in the 1960s and 1980s (Constas, 1962; Colpaert, 1987; Wilbur et al, 1988)
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