Laurent Goetz1,2,3, Manik Bhattacharjee1,2, Murielle U Ferraye1,2, Valérie Fraix1,2,4, Carina Maineri5,6, Daniela Nosko1,2,7, Albert J Fenoy5,8, Brigitte Piallat1,2, Napoléon Torres2,5,9, Alexandre Krainik1,2,10, Eric Seigneuret1,2,5, Olivier David1,2, Martin Parent3, André Parent3, Pierre Pollak1,2,4, Alim-Louis Benabid2,5,9, Bettina Debu1,2, Stéphan Chabardès1,2,5,9. 1. Grenoble Institute of Neurosciences, INSERM U1216 CEA-UJF-CHUGA, Grenoble, France. 2. University Grenoble Alpes, Grenoble, France. 3. CERVO Brain Research Center, Institut Universitaire en Santé Mentale de Québec, Department of Psychiatry and Neuroscience, Université Laval, Québec City, Canada. 4. Department of Neurology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France. 5. Department of Neurosurgery, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France. 6. Department of Pediatric Neurosurgery, Italian Hospital of Buenos Aires, Buenos Aires, Argentina. 7. Pediatric department, Örebro University Hospital, Örebro, Sweden. 8. Department of Neurosurgery, University of Texas Houston, Health Science Center, Houston, Texas. 9. CEA Clinatec-Minatec, Grenoble, France. 10. Department of Neuroradiology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France.
Abstract
BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PD patients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.
BACKGROUND: Experimental studies led to testing of deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) as a new therapy to treat freezing of gait (FOG) in Parkinson disease (PD). Despite promising initial results fueling a growing interest toward that approach, several clinical studies reported heterogeneity in patient responses. Variation in the position of electrode contacts within the rostral brainstem likely contributes to such heterogeneity. OBJECTIVE: To provide anatomoclinical correlations of the effect of DBS of the caudal mesencephalic reticular formation (cMRF) including the PPN to treat FOG by comparing the normalized positions of the active contacts among a series of 11 patients at 1- and 2-yr follow-up and to provide an optimal target through an open-label study. METHODS: We defined a brainstem normalized coordinate system in relation to the pontomesencephalic junction. Clinical evaluations were based on a composite score using objective motor measurements and questionnaires allowing classification of patients as "bad responders" (2 patients), "mild responders" (1 patient) and "good responders" (6 patients). Two patients, whose long-term evaluation could not be completed, were excluded from the analysis. RESULTS: Most effective DBS electrode contacts to treat FOG in PDpatients were located in the posterior part of the cMRF (encompassing the posterior PPN and cuneiform nucleus) at the level of the pontomesencephalic junction. CONCLUSION: In the present exploratory study, we performed an anatomoclinical analysis using a new coordinate system adapted to the brainstem in 9 patients who underwent PPN area DBS. We propose an optimal DBS target that allows a safe and efficient electrode implantation in the cMRF.
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Authors: Stephano J Chang; Iahn Cajigas; James D Guest; Brian R Noga; Eva Widerström-Noga; Ihtsham Haq; Letitia Fisher; Corneliu C Luca; Jonathan R Jagid Journal: Front Hum Neurosci Date: 2021-06-08 Impact factor: 3.169