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Probabilistic characterisation of deep brain stimulation in patients with tardive syndromes
  1. Lais M Oliveira1,2,
  2. Han Yan3,
  3. Musleh Algarni1,4,
  4. Gavin J B Elias3,
  5. Jurgen Germann3,
  6. Alexandre Boutet3,5,
  7. Mojgan Hodaie2,3,6,
  8. Renato P Munhoz1,2,
  9. Andres M Lozano2,3,6,
  10. Alfonso Fasano1,2,6,
  11. Suneil K Kalia2,3,6
  1. 1 Edmond J. Safra Program in Parkinson’s Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
  2. 2 Krembil Research Institute, Toronto, Ontario, Canada
  3. 3 Division of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
  4. 4 Division of Neurology, East Jeddah Hospital, Jeddah, Saudi Arabia
  5. 5 Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
  6. 6 CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
  1. Correspondence to Dr. Suneil K Kalia, Division of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario, Canada; suneil.kalia{at}

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Tardive syndromes (TS) are characterised by hyperkinetic motor signs that commonly develop after using antidopaminergics. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been successful in treating refractory TS, although a minority of patients have minimal response.1 The location of active contacts or volume of tissue activated (VTA) by DBS or stimulation of adjacent tracts may explain some of this outcome variability.

Group-level neuroimaging analyses can demonstrate optimal stimulation areas, tracts and functional networks associated with maximal clinical benefits during DBS. To our knowledge, this approach has not yet been applied to TS. The objectives of this study were to (1) retrospectively examine clinical outcomes from seven patients with TS GPi-DBS and (2) use neuroimaging analysis to investigate brain circuits possibly related to efficacy.


This retrospective study followed the Helsinki Declaration.

Clinical treatment

Seven patients (five men and two women) with medication-refractory TS underwent bilateral DBS surgery between 1999 and 2017 at Toronto Western Hospital. GPi electrodes (model 3387; Medtronic, Minneapolis, Minnesota) were implanted based on routine stereotactic targeting methods. Microelectrode recordings and postoperative MRI was used to verify accurate placement. Initial programming was performed on average 8 weeks after implantation with weekly or biweekly adjustments in the early postoperative phase.

Abnormal movements were graded using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for cases with predominant tardive dystonia and the Abnormal Involuntary Movement Scale (AIMS) for cases showing predominant classic tardive dyskinesia. Scores were recorded at preoperative baseline (ie, the last evaluation before surgery: B) and at various postoperative time points. The postoperative time of the maximum benefit/side effect ratio was defined as ‘time of maximal benefit’ (TMB). The percentage change in BFMDRS or AIMS from B to TMB was calculated.

Neuroimaging analysis

Full details are available in online supplemental methods. Briefly, DBS electrodes were localised on postoperative MRI …

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  • Twitter @mhodaie, @DrAlfonsoFasano, @kalialabs

  • LMO and HY contributed equally.

  • Contributors LMdO acquired and interpreted data, performed a literature review, wrote and edited the manuscript, revised the final manuscript. HY conceived of the study, acquired data and performed literature review, wrote and edited the manuscript, coordinated revisions to reviewers. MA, GE, JG and AB were involved in data acquisition, data analysis, figure design and creation and revision of the final manuscript. MH, RM, AML and AF were involved in data acquisition, data analysis and critical reviews and revisions of the final manuscript. SKK conceived the study, managed personnel, acquired data and revised the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Full financial disclosures of all authors for the past year, outside the submitted work: LMO:- Received funding for travel from Medtronic. HY: None. MA:- Received funding for travel from Medtronic and AbbVie. GJBE: None. JG: None. AB: None. MH:- Grants: Fujitsu Canada. RPM:- Advisory Boards: Medtronic- Grants: Medtronic, travel grants. AML:- Scientific Director at Functional Neuromodulation- Consultancies: Medtronic, Boston Scientific, Abbott, Insightec. AF:- Consultancies: AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi farmaceutici, UCB, Ipsen- Advisory Boards: AbbVie, Boston Scientific, Ipsen- Honoraria: AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi farmaceutici, UCB, Ipsen- Grants: University of Toronto, Weston foundation, AbbVie, Medtronic, Boston Scientific. SKK:- Consultancies: Medtronic- Honoraria: Medtronic- Grants: CIHR, Weston, CFI.

  • 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.

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