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PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study

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Abstract

Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson’s disease (PD). Low-frequency stimulation of the pedunculopontine nucleus area (PPNa-DBS) has been recently proposed to treat these symptoms with variable clinical results. To further understand the effects of PPNa-DBS on resistant gait and balance disorders, we performed a randomised double-blind cross-over study in six PD patients. Evaluation included clinical assessment of parkinsonian disability, quality of life and neurophysiological recordings of gait. Evaluations were done 1 month before, 4 and 6 months after surgery with four double-blinded conditions assessed: with and without PPNa-DBS, with and without levodopa treatment. Four patients completed the study and two patients were excluded from the final analysis because of peri-operative adverse events (haematoma, infection). Clinically, the combination of PPNa-DBS and levodopa treatment produced a significant decrease of the freezing episodes. The frequency of falls also decreased in three out of four patients. From a neurophysiological point of view, PPNa-DBS significantly improved the anticipatory postural adjustments and double-stance duration, but not the length and speed of the first step. Interestingly, step length and speed improved after surgery without PPNa-DBS, suggesting that the lesioning effect of PPNa-DBS surgery alleviates parkinsonian akinesia. Quality of life was also significantly improved with PPNa-DBS. These results suggest that PPNa-DBS could improve gait and balance disorders in well-selected PD patients. However, this treatment may be riskier than others DBS surgeries in these patients with an advanced form of PD.

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Acknowledgments

This study was supported by the Institut National de la Recherche Médicale (INSERM), the ‘Institut du Cerveau et de la Moelle Epinière’ (ICM) Foundation, the ‘Régie Autonome des Transports Parisiens’ (RATP), the ‘Fondation pour la Recherche Medicale’ (FRM) and the programme ‘Investissements d’avenir’ (ANR-10-IAIHU-06). We extend our deepest thanks to all the patients who participated in this research with great dedication.

Conflicts of interest

This study was sponsored by the INSERM. ML Welter received research support from the ‘Institut du Cerveau de la Moelle épinière’ (ICM) Foundation and the Agence Nationale de la Recherche, and consulting fees from Medtronic, Boston Scientific and Teva-Lundbeck. A Demain received a research grant from the ICM Foundation. C Ewenzcyk received a research grant (doctoral fellowship) from the ‘Fondation pour la Recherche Médicale’. V Czernecki reports no financial disclosure. B Lau reports no financial disclosure. A El Helou reports no financial disclosure. H Belaid reports no financial disclosure. J Yelnik reports no financial disclosure. C François reports no financial disclosure. E Bardinet received a research grant from Medtronic. C Karachi reports no financial disclosure. D Grabli received lectures fees and travel grants from Lundbeck, Teva, Novartis, UCB, Boerhinger-Ingelheim and AbbVIe. He has consulting activity for AbbVie, and research grants from the Direction Générale de l’Organisation des Soins (DGOS), Institut National de la Santé et de la Recherche Médicale (INSERM), Michael J. Fox Foundation for Parkinson Research, France Parkinson association and the French association for Essential Tremor (APTES).

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Authors and Affiliations

  1. U1127, Inserm, 75013, Paris, France

    Marie-Laure Welter, Adele Demain, Claire Ewenczyk, Brian Lau, Jérôme Yelnik, Chantal François, Eric Bardinet, Carine Karachi & David Grabli

  2. UMRS 1127, Sorbonne Universités, UPMC Univ Paris 06, 75013, Paris, France

    Marie-Laure Welter, Adele Demain, Claire Ewenczyk, Brian Lau, Jérôme Yelnik, Chantal François, Eric Bardinet, Carine Karachi & David Grabli

  3. UMR 7225, ICM, CNRS, 75013, Paris, France

    Marie-Laure Welter, Adele Demain, Claire Ewenczyk, Brian Lau, Jérôme Yelnik, Chantal François, Eric Bardinet, Carine Karachi & David Grabli

  4. Institut du Cerveau et de la Moelle épinière, ICM, 75013, Paris, France

    Marie-Laure Welter, Adele Demain, Claire Ewenczyk, Brian Lau, Amine El Helou, Jérôme Yelnik, Chantal François, Eric Bardinet, Carine Karachi & David Grabli

  5. AP-HP, Hôpital de la Salpêtrière, Centre d’Investigation Clinique, 75013, Paris, France

    Marie-Laure Welter, Adele Demain, Claire Ewenczyk & David Grabli

  6. AP-HP, Hôpital de la Salpêtrière, Neurology Department, 75013, Paris, France

    Marie-Laure Welter, Claire Ewenczyk, Virginie Czernecki, Hayat Belaid, Carine Karachi & David Grabli

  7. Centre de Neuroimagerie de Recherche (CENIR), ICM, 75013, Paris, France

    Eric Bardinet

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  1. Marie-Laure Welter
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  2. Adele Demain
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  3. Claire Ewenczyk
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  4. Virginie Czernecki
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  5. Brian Lau
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  6. Amine El Helou
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  7. Hayat Belaid
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  8. Jérôme Yelnik
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  9. Chantal François
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  10. Eric Bardinet
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  11. Carine Karachi
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  12. David Grabli
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Corresponding author

Correspondence to Marie-Laure Welter.

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ClinicalTrials.gov Registration: NCT02055261.

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Welter, ML., Demain, A., Ewenczyk, C. et al. PPNa-DBS for gait and balance disorders in Parkinson’s disease: a double-blind, randomised study. J Neurol 262, 1515–1525 (2015). https://doi.org/10.1007/s00415-015-7744-1

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  • DOI: https://doi.org/10.1007/s00415-015-7744-1

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