Orthostatic tremor: current challenges and future prospects

This review provides an outlook of orthostatic tremor (OT), a rare adult-onset tremor characterized by subjective unsteadiness during standing that is relieved by sitting or walking. Recent case series with a long-time follow-up have shown that the disease is slowly progressive, spatially spreads to the upper limbs, and other neurological disorders may develop in about one-third of the patients. The diagnosis of OT hinges on the typical history of unsteadiness during standing, which is confirmed by electromyographic findings of a 13-18 Hz tremor that is typically absent during tonic activation while the patient is sitting and lying. Although the tremor is generated by a central oscillator, cerebellar and/or basal ganglia dysfunction are needed for its manifestation (double lesion hypothesis). However, functional neuroimaging findings have not consistently implicated the dopaminergic system in its pathogenesis. Drug treatments have been largely disappointing with no sustained benefits, although thalamic deep brain stimulation has helped some patients. Large-scale follow-up studies, more drug trials, and novel therapies are urgently needed.