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Original research
Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping
  1. Kazuaki Yamamoto1,
  2. Can Sarica1,
  3. Gavin J B Elias1,
  4. Alexandre Boutet1,2,
  5. Jurgen Germann1,
  6. Aaron Loh1,
  7. Suresh E Joel3,
  8. Luca Bigioni4,
  9. Dave Gwun1,
  10. Robert Gramer1,
  11. Stanley Xiangyu Li5,
  12. Ajmal Zemmar6,7,
  13. Artur Vetkas1,8,
  14. Musleh Algarni9,
  15. Gabriel Devenyi10,11,
  16. Mallar Chakravarty10,11,
  17. Kullervo Hynynen4,12,
  18. Nadia Scantlebury13,
  19. Michael L Schwartz13,
  20. Andres M Lozano1,14,
  21. Alfonso Fasano9,14,15
  1. 1 Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
  2. 2 Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
  3. 3 GE Global Research, Bangalore, India
  4. 4 Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  5. 5 Schulich School of Medicine and Dentistry, London, Ontario, Canada
  6. 6 Department of Neurosurgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
  7. 7 Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China
  8. 8 Department of Neurosurgery, University of Tartu, Tartu, Tartumaa, Estonia
  9. 9 Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada
  10. 10 Cerebral Imaging Center, Douglas Mental Health University Institute, Montreal, Quebec, Canada
  11. 11 Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal, Quebec, Canada
  12. 12 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
  13. 13 Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  14. 14 Krembil Research Institute, Toronto, Ontario, Canada
  15. 15 Division of Neurology, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Professor Alfonso Fasano, Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, 7 Mc412, Toronto, Ontario, Canada; alfonso.fasano{at}uhn.ca

Abstract

Background MR-guided focused ultrasound (MRgFUS) thalamotomy has been shown to be a safe and effective treatment for essential tremor (ET).

Objective To investigate the effects of MRgFUS in patients with ET with an emphasis on ipsilateral-hand and axial tremor subscores.

Methods Tremor scores and adverse effects of 100 patients treated between 2012 and 2018 were assessed at 1 week, 3, 12, and 24 months. A subgroup analysis of ipsilateral-hand tremor responders (defined as patients with ≥30% improvement at any time point) and non-responders was performed. Correlations and predictive factors for improvement were analysed. Weighted probabilistic maps of improvement were generated.

Results Significant improvement in axial, contralateral-hand and total tremor scores was observed at all study visits from baseline (p<0.0001). There was no significant improvement in ipsilateral subscores. A subset of patients (n=20) exhibited group-level ipsilateral-hand improvement that remained significant through all follow-ups (p<0.001). Multivariate regression analysis revealed that higher baseline scores predict better improvement in ipsilateral-hand and axial tremor. Probabilistic maps demonstrated that the lesion hotspot for axial improvement was situated more medially than that for contralateral improvement.

Conclusion MRgFUS significantly improved axial, contralateral-hand and total tremor scores. In a subset of patients, a consistent group-level treatment effect was observed for ipsilateral-hand tremor. While ipsilateral improvement seemed to be less directly related to lesion location, a spatial relationship between lesion location and axial and contralateral improvement was observed that proved consistent with the somatotopic organisation of the ventral intermediate nucleus.

Trial registration numbers NCT01932463, NCT01827904, and NCT02252380.

  • TREMOR
  • STEREOTAXIC SURGERY
  • FUNCTIONAL NEUROLOGICAL DISORDER
  • NEUROSURGERY
  • MOVEMENT DISORDERS

Data availability statement

Data are available upon reasonable request. Anonymised data will be shared by request from any qualified investigator.

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Data availability statement

Data are available upon reasonable request. Anonymised data will be shared by request from any qualified investigator.

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Footnotes

  • KY and CS are joint first authors.

  • Twitter @DrAlfonsoFasano

  • Contributors KY: drafting/revising the manuscript, figures and tables; statistical analysis; imaging analysis; and interpretation of data. CS: drafting/revising the manuscript and tables and interpretation of data. GJBE, AB, AL: revising the manuscript, imaging analysis and interpretation of data. JG: revising the manuscript, statistical analysis and interpretation of data. SEJ: imaging analysis. LB, DG, RG, SXL: acquisition of data. AZ, AV: revising the manuscript. MA, GD, MC, KH, NS, MLS: acquisition of data. AML: revising the manuscript, study concept or design, interpretation of data, accepts responsibility for conduct of research and will give final approval, acquisition of data, study supervision. AF: revising the manuscript, study concept or design, statistical analysis, interpretation of data, accepts responsibility for conduct of research, will give final approval, acquisition of data and study supervision, and is responsible for the overall content as the guarantor.

  • Competing interests KY, GJBE, AB, JG, AML, LB, DG, RG, SXL, AZ, AV, MA, GD, MC, KH, NS and MLS report no disclosures relevant to the manuscript. CS has been receiving fellowship grants from Michael and AD Foundation and Turkish Neurosurgical Society. SEJ receives salary from General Electric. AML is scientific director for Functional Neuromodulation and a consultant to Medtronic, Abbott, Boston Scientific, Insightec and Focused Ultrasound Foundation. AF reports the following: consultancies from Abbvie, Medtronic, Boston Scientific, Sunovion, Chiesi Farmaceutici, UCB and Ipsen; membership in advisory boards of Abbvie, Boston Scientific and Ipsen; receiving honoraria from Abbvie, Medtronic, Boston Scientific, Sunovion, Chiesi farmaceutici, UCB and Ipsen; receiving grants from University of Toronto, Weston foundation, Abbvie, Medtronic and Boston Scientific.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.