The patchy tremor landscape: recent advances in pathophysiology.

Abstract

We focus on new insights in the pathophysiology of Parkinson's disease tremor, essential tremor, tremor in dystonia, and orthostatic tremor. Neuroimaging findings suggest that Parkinson's disease resting tremor is associated with dopaminergic dysfunction, serotonergic dysfunction, or both. Not all tremors in Parkinson's disease have the same pathophysiology: postural tremor in Parkinson's disease can be subdivided into pure postural tremor, which involves nondopaminergic mechanisms, and re-emergent tremor, which has a dopaminergic basis. Unlike Parkinson's disease tremor, essential tremor has an electrophysiological signature suggestive of a single (or several tightly coupled) oscillators. Visual feedback increases essential tremor and enhances cerebral activity in the cerebello-thalamo-cortical circuit, supplementary motor area, and parietal cortex. Little is known about dystonic tremor but the available evidence suggests that both the basal ganglia and the cerebellum play a role. Finally, recent work in orthostatic tremor points towards the role of the pontine tegmentum and dysfunctional cerebellar-SMA circuitry. Many pathological tremors involve the cerebello-thalamo-cortical circuitry, and the clinical and pathophysiological boundaries between tremor disorders are not always clear. Differences between tremor disorders - or even individual patients - may be explained by the specific balance of neurotransmitter degeneration, by distinct circuit dynamics, or by the role of regions interconnected to the cerebello-thalamo-cortical circuit.