Zona incerta deep-brain stimulation in orthostatic tremor: efficacy and mechanism of improvement

Abstract

Background: Orthostatic tremor is a rare hyperkinetic movement disorder that is characterized by a 13-18 Hz tremor in both legs while standing. Deep-brain stimulation of the caudal zona incerta has re-emerged as an alternate target for tremor control in various etiologies.

Object: Explore the clinical efficacy and mechanism of action of caudal zona incerta deep-brain stimulation in orthostatic tremor.

Methods: Four patients (63.1 ± 4.1 years, female = 50%) with orthostatic tremor were recruited for this open label study (63.1 ± 4.1 years, female = 50%). In two patients, the electrodes were externalized to determine the effectiveness of caudal zona incerta as a target. Surface EMG (leg muscles), EEG (leg motor cortex) and caudal zona incerta local field potential recordings were recorded. Data were recorded in sitting and standing positions with stimulation OFF and ON.

Results: EMG frequency analysis showed tremor frequency at 13-17 Hz. EMG-EEG coherence was found in the tremor frequency band and double tremor frequency band. EMG-caudal zona incerta coherence was higher in the tremor frequency band, while EEG coherence was higher in the double tremor frequency band. Upon stimulation, there was a selective reduction in tremor frequency band EEG-EMG coherence in all patients. All the patients had reduction in feeling of unsteadiness and increase in the stance duration.

Conclusions: Bilateral caudal zona incerta deep-brain stimulation is effective in refractory orthostatic tremor. Two independent central oscillations were found at tremor and double tremor frequency. Zona incerta DBS produces improvement in OT patients possibly by modifying the abnormal oscillatory proprioceptive input from leg muscles. Frequent changes in deep-brain stimulation settings were required for maintaining the clinical benefit.

Keywords: Basal ganglia; Deep-brain stimulation; Motor control; Neurophysiology; Parkinson’s disease.

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