Margherita Fabbri1,2,3, Maurizio Zibetti1, Mario Giorgio Rizzone1, Giulia Giannini4,5, Linda Borellini6, Alessandro Stefani7, Francesco Bove8, Andrea Bruno9, Giovanna Calandra-Buonaura4,5, Nicola Modugno9, Carla Piano8, Antonella Peppe10, Gianluca Ardolino6, Alberto Romagnolo1, Carlo Alberto Artusi1, Paola Berchialla11, Elisa Montanaro1, Pietro Cortelli4,5, Romito Luigi12, Roberto Eleopra12, Brigida Minafra13, Claudio Pacchetti13, Tommaso Tufo14, Filippo Cogiamanian6, Leonardo Lopiano1. 1. Department of Neuroscience "Rita Levi Montalcini,", University of Torino, Turin, Italy. 2. Center CIC1436, Departments of Clinical Pharmacology and Neurosciences, NS-Park/FCRIN network and NeuroToul Center of Excellence for Neurodegeneration, INSERM, University Hospital of Toulouse and University of Toulouse, Toulouse, France. 3. Department of Neurosciences, Clinical Investigation Center CIC 1436, Parkinson Toulouse Expert Center, NS-Park/FCRIN Network and NeuroToul COEN Center, Toulouse University Hospital; INSERM; University of Toulouse 3, Toulouse, France. 4. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. 5. Department of Biomedical and NeuroMotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy. 6. U.O. Neurofisiopatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. 7. Department of System Medicine, UOSD Parkinson, University of Rome "Tor Vergata,", Rome, Italy. 8. U.O.C. Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. 9. IRCCS Neuromed, Pozzilli, Italy. 10. IRCCS Santa Lucia Foundation, Rome, Italy. 11. Department of Clinical and Biological Sciences, University of Torino, Torino, Italy. 12. Department of Clinical Neurosciences, Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 13. Parkinson and Movement Disorder Unit, IRCCS Mondino Foundation, Pavia, Italy. 14. U.O.C. Neurochirurgia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Abstract
BACKGROUND:Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. METHODS: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment. RESULTS:Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred. CONCLUSIONS: The vast majority of late-stage PD patients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD.
RCT Entities:
BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PDpatients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. METHODS: Late-stage PDpatients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment. RESULTS: Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred. CONCLUSIONS: The vast majority of late-stage PDpatients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD.