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Peduncolopontine nucleus stimulation in progressive supranuclear palsy: a randomised trial
  1. Emma Scelzo1,2,3,
  2. Andres M Lozano4,
  3. Clement Hamani4,
  4. Yu-Yan Poon5,
  5. Amaal Aldakheel1,
  6. Cindy Zadikoff6,
  7. Anthony E Lang5,
  8. Elena Moro1,5
  1. 1 Division of Neurology, CHU Grenoble, Grenoble Alpes University, Grenoble, France
  2. 2 Clinical Center for Neurotechnology, Neurostimulation and Movement Disorders, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  3. 3 Department of Neurology, Policlinico San Donato, University of Milan, Milan, Italy
  4. 4 Division of Neurosurgery, Toronto Western Hospital, University of Toronto, University Health Network, Toronto, Ontario, Canada
  5. 5 Movement Disorders Center, Division of Neurology, Toronto Western Hospital, University of Toronto, University Health Network, Toronto, Ontario, Canada
  6. 6 Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
  1. Correspondence to Dr Elena Moro, Division of Neurology, CHU Grenoble, Grenoble Alpes University, INSERM U1416, 38043 Grenoble Cedex 9, Grenoble, France ; elenamfmoro{at}gmail.com

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Axial signs and cognitive disorders are the major source of disability in progressive supranuclear palsy (PSP). Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN), a structure involved in locomotion and posture control, has showed to improve freezing and falls in patients with Parkinson’s disease (PD).1 In this pilot trial, we investigated the effectiveness and safety of unilateral PPN DBS on gait and balance in patients with Richardson’s syndrome (RS) phenotype of PSP.

Between April 2006 and December 2010, eight patients with RS-PSP were enrolled at the Movement Disorders Center of the Toronto Western Hospital. The study was approved by the University Health Network, and the Toronto Rehab Research Ethics Boards. All patients gave their written consent to the study.

Both the surgical procedure and the PPN DBS programming were similar to those already used in patients with PD.2 Patients were assessed at baseline, and at 6 and 12 months after surgery, when they were randomly assigned to be evaluated both in the OFF and in the ON stimulation condition, after being 1 week in each stimulation condition. Patients and raters were blinded to the stimulation conditions. All assessments were videotaped, and adverse events were recorded. Main outcome was the difference between the ON and OFF stimulation conditions at 6 and 12-month follow-up in gait, postural stability and fall subitems of the PSP Rating Scale (PSPRS). Secondary outcomes were differences in the total scores of the motor Unified Parkinson Disease Rating Scale (UPDRS) and PSPRS; the PSP Staging System (PSPSS) score; rigidity, bradykinesia, arising from a chair and posture UPDRS items; history, mental, bulbar examination, supranuclear ocular motor examination, limb examination and gait/midline examination subscores of the PSPRS; withdrawal, sleep difficulty, disorientation, bradyphrenia and emotional incontinence items of the PSPRS. …

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Footnotes

  • Contributors ES and CZ have participated in the collection, analysis and interpretation of data.

    AML and CH have participated in the design and execution of the study and in the interpretation of data. Y-YP has participated in the collection, design, execution and interpretation of data.

    A

    A has participated in the analysis and interpretation of data.AEL has participated in the design, analysis and interpretation of data. EM has participated in the design and execution of the study and in the collection, analysis and interpretation of data.

  • Funding This study was supported by a CurePSP grant.

  • Competing interests EL has received honoraria from Medtronic, Boston Scientific, St Jude, Aleva for consulting and is co-founder of Functional Neuromodulation. CZ has received honoraria or consulting fees from AbbVie, Merz, Teva, Lundbeck, UCB, Acadia and Cynapsus. AEL has served as an advisor for Abbvie, Acorda, Avanir Pharmaceuticals, Bristol Myers Squibb, Cipla, Intekrin and Merck; received honoraria from Medichem, Medtronic, Teva, UCB, AbbVie; received grants from Brain Canada, Canadian Institutes of Health Research, Edmond J Safra Philanthropic Foundation, Michael J. Fox Foundation, the Ontario Brain Institute, National Parkinson Foundation, Parkinson Society Canada, Physicians Services Incorporated, W. Garfield Weston Foundation; received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. EM has received honoraria from Medtronic for consulting services and lecturing and research grant support from Merz and AGIR.

  • Patient consent Obtained.

  • Ethics approval Toronto Rehab Research Ethics Boards.

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

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