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Spinal cord stimulation therapy for gait dysfunction in progressive supranuclear palsy patients

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Abstract

Background

There are no effective symptomatic treatments for progressive supranuclear palsy (PSP). Recent studies report benefits of spinal cord stimulation (SCS) for freezing of gait (FOG) and gait disorders in Parkinson’s disease and atypical Parkinsonism patients. This is the first study to report therapeutic effects of SCS in Richardson’s syndrome PSP (PSP-RS) patients.

Methods

Epidural SCS was implanted in three female PSP-RS participants (3.2 ± 1.3 years with disease). Six programs (300–400 µs/30–130 Hz) were randomly tested at suprathreshold intensity on separate days. The setting that best improved gait/FOG was used daily by each participant in the study. Protokinetics walkway captured spatiotemporal gait measures and FOG episodes (turning on the spot and while walking) and clinical scales including FOG questionnaire, UPDRS-III (OFF-/ON-l-dopa), and participant-perceived global impression of change (GISC) were collected at pre-SCS, and 3, 6, 12 months post-SCS.

Results

Participant #1 demonstrated the highest GISC score (6.5/10) with a consistent reduction of FOGs by 43.8%, UPDRS-III score (− 5 points), and improved step length and stride velocity (33.6%) while maintaining a l-dopa response of ~ 12% over the 12 months. Participant #2, walking FOG frequency and turning duration was reduced by 39.0% (OFF-l-dopa), and ON-l-dopa UPDRS-III score worsened (+ 5 points) at 12 months. Participant #3, FOG frequency reduced by 75% up to 6 months rating a GISC 3/10 score, however disease severity worsened at 12 months. Ambulatory gait parameters universally improved by 29.6% in all participants.

Conclusion

The results support the benefit of SCS for FOG and gait symptoms in PSP-RS and suggests early SCS intervention for dopaminergic-resistant gait should be considered.

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References

  1. Respondek G, Höglinger GU (2016) The phenotypic spectrum of progressive supranuclear palsy. Parkin Relat Disord 22:S34–S36. https://doi.org/10.1016/j.parkreldis.2015.09.041

    Article  Google Scholar 

  2. Clerici I, Ferrazzoli D, Maestri R et al (2017) Rehabilitation in progressive supranuclear palsy: Effectiveness of two multidisciplinary treatments. PLoS ONE 12(2):e0170927. https://doi.org/10.1371/journal.pone.0170927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Williams DR, de Silva R, Paviour DC et al (2005) Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism. Brain 128(Pt 6):1247–1258. https://doi.org/10.1093/brain/awh488

    Article  PubMed  Google Scholar 

  4. Samotus O, Parrent A, Jog M (2018) Spinal cord stimulation therapy for gait dysfunction in advanced Parkinson’s disease patients. Mov Disord 33(5):783–792. https://doi.org/10.1002/mds.27299

    Article  CAS  PubMed  Google Scholar 

  5. Cai Y, Reddy RD, Varshney V, Chakravarthy KV (2020) Spinal cord stimulation in Parkinson’s disease: a review of the preclinical and clinical data and future prospects. Bioelectron Med 6:5. https://doi.org/10.1186/s42234-020-00041-9

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhang Y, Song T, Zhuang P et al (2020) Spinal cord stimulation improves freezing of gait in a patient with multiple system atrophy with predominant parkinsonism. Brain Stimul 13(3):653–654. https://doi.org/10.1016/j.brs.2020.02.006

    Article  PubMed  Google Scholar 

  7. Samotus O, Parrent A, Jog M (2020) Long-term update of the effect of spinal cord stimulation in advanced Parkinson's disease patients. Brain Stimul. https://doi.org/10.1016/j.brs.2020.06.004

    Article  PubMed  Google Scholar 

  8. dell'Aquila C, Zoccolella S, Cardinali V et al (2013) Predictors of survival in a series of clinically diagnosed progressive supranuclear palsy patients. Parkinsonism Relat Disord 19(11):980–985. https://doi.org/10.1016/j.parkreldis.2013.06.014

    Article  PubMed  Google Scholar 

  9. Snijders AH, Haaxma CA, Hagen YJ, Munneke M, Bloem BR (2012) Freezer or non-freezer: clinical assessment of freezing of gait. Parkinsonism Relat Disord 18(2):149–154. https://doi.org/10.1016/j.parkreldis.2011.09.006

    Article  PubMed  Google Scholar 

  10. van Dijsseldonk K, Wang Y, van Wezel R, Bloem BR, Nonnekes J (2018) Provoking freezing of gait in clinical practice: turning in place is more effective than stepping in place. J Parkinsons Dis 8(2):363–365. https://doi.org/10.3233/JPD-181332

    Article  PubMed  Google Scholar 

  11. Hubsch C, D’Hardemare V, Ben Maacha M, Ziegler M, Patte-Karsenti N, Thiebaut JB, Gout O, Brandel JP (2019) Tonic spinal cord stimulation as therapeutic option in Parkinson disease with axial symptoms: effects on walking and quality of life. Parkinsonism Relat Disord 63:235–237. https://doi.org/10.1016/j.parkreldis.2019.02.044

    Article  CAS  PubMed  Google Scholar 

  12. Fuentes R, Petersson P, Nicolelis MAL (2010) Restoration of locomotive function in Parkinson’s disease by spinal cord stimulation: mechanistic approach. Eur J Neurosci 32(7):1100–1108. https://doi.org/10.1111/j.1460-9568.2010.07417.x

    Article  PubMed  PubMed Central  Google Scholar 

  13. Perez Parra S, McKay JL, Factor SA (2020) diphasic worsening of freezing of gait in Parkinson's Disease. Mov Disord Clin Pract 7(3):325–328. https://doi.org/10.1002/mdc3.12918

    Article  PubMed  PubMed Central  Google Scholar 

  14. Espay AJ, Fasano A, van Nuenen BF, Payne MM, Snijders AH, Bloem BR (2012) "On" state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication. Neurology 78(7):454–457. https://doi.org/10.1212/WNL.0b013e3182477ec0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bloem BR, Hausdorff JM, Visser JE, Giladi N (2004) Falls and freezing of gait in Parkinson's disease: a review of two interconnected, episodic phenomena. Mov Disord 19(8):871–884. https://doi.org/10.1002/mds.20115

    Article  PubMed  Google Scholar 

  16. Fleury V, Pollak P, Gere J et al (2016) Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait. Mov Disord 31(9):1389–1397. https://doi.org/10.1002/mds.26545

    Article  CAS  PubMed  Google Scholar 

  17. Mei S, Li J, Middlebrooks EH et al (2019) New Onset On-Medication Freezing of Gait After STN-DBS in Parkinson's Disease. Front Neurol 10:659. https://doi.org/10.3389/fneur.2019.00659

    Article  PubMed  PubMed Central  Google Scholar 

  18. de Souza CP, Hamani C, Oliveira Souza C, Lopez Contreras WO, Dos Santos Ghilardi MG et al (2017) Spinal cord stimulation improves gait in patients with Parkinson’s disease previously treated with deep brain stimulation. Mov Disord Off J Mov Disord Soc 32:278–282. https://doi.org/10.1002/mds.26850

    Article  Google Scholar 

  19. Mazzone P, Viselli F, Ferraina S et al (2019) High cervical spinal cord stimulation: a one year follow-up study on motor and non-motor functions in Parkinson’s Disease. Brain Sci 9(4):78. https://doi.org/10.3390/brainsci9040078

    Article  CAS  PubMed Central  Google Scholar 

  20. Rohani M, Kalsi-Ryan S, Lozano AM, Fasano A (2017) Spinal cord stimulation in primary progressive freezing of gait. Mov Disord 32(9):1336–1337. https://doi.org/10.1002/mds.27103

    Article  PubMed  Google Scholar 

  21. de Souza CP, Dos Santos MGG, Hamani C, Fonoff ET (2018) Spinal cord stimulation for gait dysfunction in Parkinson's disease: Essential questions to discuss. Mov Disord 33(11):1828–1829. https://doi.org/10.1002/mds.27508

    Article  PubMed  Google Scholar 

  22. Fonoff ET, de Lima-Pardini AC, Coelho DB et al (2019) Spinal cord stimulation for freezing of gait: from bench to bedside. Front Neurol 10:905. https://doi.org/10.3389/fneur.2019.00905

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kobayashi R, Kenji S, Taketomi A, Murakami H, Ono K, Otake H (2018) New mode of burst spinal cord stimulation improved mental status as well as motor function in a patient with Parkinson’s disease. Parkinsonism Relat Disord 57:82–83. https://doi.org/10.1016/j.parkreldis.2018.07.002

    Article  PubMed  Google Scholar 

  24. Yearwood TL, Hershey B, Bradley K, Lee D (2010) Pulse width programming in spinal cord stimulation: a clinical study. Pain Phys 13:321–335

    Google Scholar 

  25. Ginis P, Nackaerts E, Nieuwboer A, Heremans E (2018) Cueing for people with Parkinson's disease with freezing of gait: a narrative review of the state-of-the-art and novel perspectives. Ann Phys Rehabil Med 61(6):407–413. https://doi.org/10.1016/j.rehab.2017.08.002

    Article  PubMed  Google Scholar 

  26. de Lima-Pardini AC, Coelho DB, Souza CP et al (2018) Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait. Elife 7:e37727. https://doi.org/10.7554/eLife.37727

    Article  PubMed  PubMed Central  Google Scholar 

  27. Duarte RV, McNicol E, Colloca L, Taylor RS, North RB, Eldabe S (2020) Randomized placebo-/sham-controlled trials of spinal cord stimulation: a systematic review and methodological appraisal. Neuromodulation 23(1):10–18. https://doi.org/10.1111/ner.13018

    Article  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the contribution by the participants and by the research personnel and volunteer staff at the National Parkinson Foundation Centre of Excellence, London Movement Disorder Centre, located in the London Health Sciences Centre, London, Ontario, Canada. We also extend recognition to the neurosurgical team of Dr. Andrew Parrent in the planning and coordination of this study at University Hospital, London Health Sciences Centre.

Funding

There are no financial disclosures to report for the conduct of this study.

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Authors and Affiliations

  1. Department of Clinical Neurological Sciences, London Health Sciences Centre, Lawson Health Research Institute, 339 Windermere Road, A10-026, London, ON, N6A 5A5, Canada

    Olivia Samotus, Andrew Parrent & Mandar Jog

  2. Schulich School of Medicine and Dentistry, University of Western, 1151 Richmond Street, London, ON, N6A 3K7, Canada

    Olivia Samotus, Andrew Parrent & Mandar Jog

Authors
  1. Olivia Samotus
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  2. Andrew Parrent
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  3. Mandar Jog
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Contributions

OS: conceptualization, methodology, software, formal analysis, investigation, resources, data curation, writing (original), writing (editing and review), visualization, project administration. AP: conceptualization, methodology, investigation, resources, project administration. MJ: conceptualization, methodology, investigation, resources, writing (editing and review), project administration.

Corresponding author

Correspondence to Mandar Jog.

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Conflict of interest

Dr. Jog is a scientific advisor and receives research financial support from the following companies: AbbVie, Allergan Inc., Boston Scientific, Ipsen, MDDT Inc., Medtronic, Merz Pharma, Novartis, and Teva Pharmaceuticals. Dr. Parrent and Ms. Samotus report no conflict of interests.

Ethical approval

The study reported in this manuscript has been approved by the Western University Health Sciences Research Ethics Board (REB) and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study were omitted.

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Samotus, O., Parrent, A. & Jog, M. Spinal cord stimulation therapy for gait dysfunction in progressive supranuclear palsy patients. J Neurol 268, 989–996 (2021). https://doi.org/10.1007/s00415-020-10233-7

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  • DOI: https://doi.org/10.1007/s00415-020-10233-7

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