Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?

Abstract

Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed ‘dimmer-switch model’ that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression.

Parkinson's disease severity and motor subtype influence physical capacity components

“…Also, AR presents a closer relationship between physical capacity components and disease impairments than TD. Based on the recent literature that TD presents lesions in brain areas other than the striato-thalamic-cortical pathway (Benninger et al, 2009;Helmich et al, 2012;Lewis et al, 2011) and that this group presents a higher performance in the tests described here, mainly with the disease advance, two hypothesis were developed to explain our results: i) the striato-thalamic-cortical pathway has a closer relation with the physical capacity components performance; ii) the ageing process develops faster in AR patients.…”

“…AR is mainly characterized by a reduction in the movement velocity (bradykinesia), difficulties in the initiation of movements (akinesia) and an increase in muscle tone (rigidity). In another way, TD presents a resting or postural tremor in the head, trunk or limbs that can vary between 4-5 to 8-10Hz (Helmich, Hallett, Deuschl, Toni, & Bloem, 2012). Patients can have either primary rigidity and bradykinesia with minimal tremor or tremor with minimal rigidity (Lewis et al, 2011).…”

“…Patients can have either primary rigidity and bradykinesia with minimal tremor or tremor with minimal rigidity (Lewis et al, 2011). In some cases AR patients show no tremor during their entire lifetime (Helmich et al, 2012). It is accepted that both subgroups are distinguished by different morphological factors (Benninger et al, 2009): AR patients present disturbances in the striatum-thalamo-cortical pathway, while TD patients have deficits in the cerebellum-thalamo-cortical pathway (Benninger et al, 2009;Eggers et al, 2011;Lewis et al, 2011).…”

Inhibitory system overstimulation plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis

“…However, because these tremors occur at rest (and not during active motion or while countering the effects of gravity), the muscles involved are likely innervated by SI pathways, making rest tremors an SI-specific phenomenon. This is further illustrated by the finding that rest tremors resolve when the affected body part becomes involved in locomotion, stance, or maintaining inertia 67 , actions that involve muscles that are controlled by RI 61 . Interestingly, the hand tremor that is most specific to patients with Parkinson’s disease—the so-called “pill-rolling tremor”—also results from muscles that are innervated solely by SI pathways.…”

“…The pathways that underlie rest tremors have not been identified, and the fact that rest tremors resolve during voluntary movement is one of the most puzzling observations associated with Parkinson’s disease 67 . However, because these tremors occur at rest (and not during active motion or while countering the effects of gravity), the muscles involved are likely innervated by SI pathways, making rest tremors an SI-specific phenomenon.…”