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

Journal of Neurology volume 266, pages 2829–2837 (2019)Cite this article

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.

References

  1. Britton TC, Thompson PD, van der Kamp W et al (1992) Primary orthostatic tremor: further observations in six cases. J Neurol 239:209–217. https://doi.org/10.1007/BF00839142

    Article  CAS  PubMed  Google Scholar 

  2. Yaltho TC, Ondo WG (2014) Orthostatic tremor: a review of 45 cases. Parkinsonism Relat Disord 20:723–725. https://doi.org/10.1016/j.parkreldis.2014.03.013

    Article  PubMed  Google Scholar 

  3. Espay AJ, Duker AP, Chen R et al (2008) Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observations. Mov Disord 23:2357–2362. https://doi.org/10.1002/mds.22271

    Article  PubMed  Google Scholar 

  4. Guridi J, Rodriguez-Oroz MC, Arbizu J et al (2008) Successful thalamic deep brain stimulation for orthostatic tremor. Mov Disord 23:1808–1811. https://doi.org/10.1002/mds.22001

    Article  PubMed  Google Scholar 

  5. Magariños-Ascone C, Ruiz FM, Millán AS et al (2010) Electrophysiological evaluation of thalamic DBS for orthostatic tremor. Mov Disord 25:2476–2477. https://doi.org/10.1002/mds.23333

    Article  PubMed  Google Scholar 

  6. Lyons MK, Behbahani M, Boucher OK et al (2012) Orthostatic tremor responds to bilateral thalamic deep brain stimulation. Tremor Other Hyperkinet Mov (N Y) 2:2–5. https://doi.org/10.7916/D8TQ608K

    Article  Google Scholar 

  7. Contarino MF, Bour LJ, Schuurman PR et al (2015) Thalamic deep brain stimulation for orthostatic tremor: clinical and neurophysiological correlates. Parkinsonism Relat Disord 21:1005–1007. https://doi.org/10.1016/j.parkreldis.2015.06.008

    Article  PubMed  Google Scholar 

  8. Muthuraman M, Hellriegel H, Paschen S et al (2013) The central oscillatory network of orthostatic tremor. Mov Disord 28:1424–1430. https://doi.org/10.1002/mds.25616

    Article  PubMed  Google Scholar 

  9. Gallea C, Popa T, García-Lorenzo D et al (2016) Orthostatic tremor: a cerebellar pathology? Brain 139:2182–2197. https://doi.org/10.1093/brain/aww140

    Article  PubMed  PubMed Central  Google Scholar 

  10. Velasco FC, Molina-Negro P, Bertrand C, Hardy J (1972) Further definition of the subthalamic target for arrest of tremor. J Neurosurg 36:184–191. https://doi.org/10.3171/jns.1972.36.2.0184

    Article  CAS  PubMed  Google Scholar 

  11. Fytagoridis A, Åström M, Samuelsson J, Blomstedt P (2016) Deep Brain stimulation of the caudal zona incerta: tremor control in relation to the location of stimulation fields. Stereotact Funct Neurosurg 94:363–370. https://doi.org/10.1159/000448926

    Article  PubMed  Google Scholar 

  12. Shammah-Lagnado SJ, Negrão N, Ricardo JA (1985) Afferent connections of the zona incerta: a horseradish peroxidase study in the rat. Neuroscience 15:109–134. https://doi.org/10.1016/0306-4522(85)90127-7

    Article  CAS  PubMed  Google Scholar 

  13. Ellenbogen RG, Sekhar LN, Kitchen ND (2018) Principles of neurological surgery

  14. Yen CT, Conley M, Hendry SH, Jones EG (1985) The morphology of physiologically identified GABAergic neurons in the somatic sensory part of the thalamic reticular nucleus in the cat. J Neurosci 5:2254–2268

    Article  CAS  Google Scholar 

  15. Plaha P, Ben-Shlomo Y, Patel NK, Gill SS (2006) Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism. Brain 129:1732–1747. https://doi.org/10.1093/brain/awl127

    Article  PubMed  Google Scholar 

  16. Plaha P, Khan S, Gill SS (2008) Bilateral stimulation of the caudal zona incerta nucleus for tremor control. J Neurol Neurosurg Psychiatry 79:504–513. https://doi.org/10.1136/jnnp.2006.112334

    Article  CAS  PubMed  Google Scholar 

  17. Deuschl G, Bain P, Brin M (1998) Consensus statement of the Movement disorder society on tremor: Ad Hoc Scientific Committee. Mov Disord 13(Suppl 3):2–23. https://doi.org/10.7235/hort.2013.12183

    Article  PubMed  Google Scholar 

  18. Blomstedt P, Sandvik U, Tisch S (2010) Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor. Mov Disord 25:1350–1356. https://doi.org/10.1002/mds.22758

    Article  PubMed  Google Scholar 

  19. Li X, Morgan PS, Ashburner J et al (2016) The first step for neuroimaging data analysis: DICOM to NIfTI conversion. J Neurosci Methods 264:47–56. https://doi.org/10.1016/j.jneumeth.2016.03.001

    Article  PubMed  Google Scholar 

  20. Modat M, Ridgway GR, Taylor ZA et al (2010) Fast free-form deformation using graphics processing units. Comput Methods Programs Biomed 98:278–284. https://doi.org/10.1016/j.cmpb.2009.09.002

    Article  PubMed  Google Scholar 

  21. Fedorov A, Beichel R, Kalpathy-Cramer J et al (2012) 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging 30:1323–1341. https://doi.org/10.1016/j.mri.2012.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  22. Halliday DM, Rosenberg JR, Amjad a M, et al (1995) A framework for the analysis of mixed time series/point process data—theory and application to the study of physiological tremor, single motor unit discharges and electromyograms. Prog Biophys Mol Biol 64:237–278. https://doi.org/10.1016/S0079-6107(96)00009-0

    Article  CAS  PubMed  Google Scholar 

  23. Grosse P, Guerrini R, Parmeggiani L et al (2003) Abnormal corticomuscular and intermuscular coupling in high-frequency rhythmic myoclonus. Brain 126:326–342. https://doi.org/10.1093/brain/awg043

    Article  CAS  PubMed  Google Scholar 

  24. Blomstedt P, Stenmark Persson R, Hariz G-M et al (2018) Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson’s disease: a randomised blinded evaluation. J Neurol Neurosurg Psychiatry 89:710–716. https://doi.org/10.1136/jnnp-2017-317219

    Article  PubMed  PubMed Central  Google Scholar 

  25. Krauss JK, Weigel R, Blahak C et al (2006) Chronic spinal cord stimulation in medically intractable orthostatic tremor. J Neurol Neurosurg Psychiatry 77:1013–1016. https://doi.org/10.1136/jnnp.2005.086132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Blahak C, Sauer T, Baezner H et al (2016) Long-term follow-up of chronic spinal cord stimulation for medically intractable orthostatic tremor. J Neurol 263:2224–2228. https://doi.org/10.1007/s00415-016-8239-4

    Article  PubMed  Google Scholar 

  27. Coleman RR, Starr PA, Katz M et al (2016) Bilateral Ventral intermediate nucleus thalamic deep brain stimulation in orthostatic tremor. Stereotact Funct Neurosurg 94:69–74. https://doi.org/10.1159/000444127

    Article  PubMed  Google Scholar 

  28. Fung VS, Sauner D, Day BL (2001) A dissociation between subjective and objective unsteadiness in primary orthostatic tremor. Brain 124:322–330. https://doi.org/10.1103/PhysRevB.51.17618

    Article  CAS  PubMed  Google Scholar 

  29. Raethjen J, Govindan RB, Muthuraman M et al (2009) Cortical correlates of the basic and first harmonic frequency of Parkinsonian tremor. Clin Neurophysiol 120:1866–1872. https://doi.org/10.1016/j.clinph.2009.06.028

    Article  PubMed  Google Scholar 

  30. Merola A, Fasano A, Hassan A et al (2017) Thalamic deep brain stimulation for orthostatic tremor: a multicenter international registry. Mov Disord 32:1240–1244. https://doi.org/10.1002/mds.27082

    Article  PubMed  Google Scholar 

  31. Ramirez-Zamora A, Smith H, Kumar V et al (2016) Evolving Concepts in posterior subthalamic area deep brain stimulation for treatment of tremor: surgical neuroanatomy and practical considerations. Stereotact Funct Neurosurg 94:283–297. https://doi.org/10.1159/000449007

    Article  PubMed  Google Scholar 

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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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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

Keywords

  • Deep-brain stimulation
  • Motor control
  • Basal ganglia
  • Parkinson’s disease
  • Neurophysiology