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

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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.

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Data availability

The data and analysis scripts that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Greydon Gilmore and Aditya Murgai have contributed equally to the manuscript.

Authors and Affiliations

  1. School of Biomedical Engineering, Western University, London, Canada

    Greydon Gilmore & Mandar Jog

  2. Department of Clinical Neurological Sciences, University Hospital, 339 Windermere Road, London, ON, N655, Canada

    Greydon Gilmore, Aditya Murgai, Andrew Parrent & Mandar Jog

  3. Department of Neurosurgery, University Hospital, London, Canada

    Abdulrahman Nazer & Andrew Parrent

Authors
  1. Greydon Gilmore
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  2. Aditya Murgai
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  3. Abdulrahman Nazer
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Corresponding author

Correspondence to Aditya Murgai.

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Conflicts of interests

Greydon Gilmore has received graduate funding from the Canadian Institute of Health Research, AGE-WELL and Mitacs. Aditya Murgai: none. Abdulrahman Nazer: none. Andrew Parrent: has received an honorarium from Boston Scientific. Mandar Jog receives research grants from Allergan, Merz Pharmaceuticals, Abbvie, and Medtronic. Dr. Jog also receives speaker honoraria fees from the same companies and serves on advisory boards of these companies from time to time.

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Gilmore, G., Murgai, A., Nazer, A. et al. Zona incerta deep-brain stimulation in orthostatic tremor: efficacy and mechanism of improvement. J Neurol 266, 2829–2837 (2019). https://doi.org/10.1007/s00415-019-09505-8

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  • DOI: https://doi.org/10.1007/s00415-019-09505-8

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