{"doi":"10.3233/jpd-212793","title":"Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson’s Disease: Interim Results from a Randomized Double-Blind Clinical Trial","abstract":"<jats:p>Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results: The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.</jats:p>","journal":"Journal of Parkinson's Disease","year":2022,"id":646458,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1683818,"name":"Claire Olivier","orcid":null,"position":1,"is_corresponding":false},{"id":1393214,"name":"Hana You","orcid":null,"position":2,"is_corresponding":false},{"id":1683819,"name":"Antoine Collomb-Clerc","orcid":null,"position":3,"is_corresponding":false},{"id":356854,"name":"David Grabli","orcid":"0000-0001-6798-4567","position":4,"is_corresponding":false},{"id":1683820,"name":"Hayat Belaid","orcid":null,"position":5,"is_corresponding":false},{"id":1683821,"name":"Yannick Mullie","orcid":null,"position":6,"is_corresponding":false},{"id":929159,"name":"Chantal François","orcid":null,"position":7,"is_corresponding":false},{"id":863403,"name":"Virginie Czernecki","orcid":"0000-0002-0139-7957","position":8,"is_corresponding":false},{"id":1683822,"name":"Brian Lau","orcid":null,"position":9,"is_corresponding":false},{"id":1501713,"name":"Fernando Pérez-García","orcid":null,"position":10,"is_corresponding":false},{"id":1683823,"name":"Eric Bardinet","orcid":null,"position":11,"is_corresponding":false},{"id":1683824,"name":"Sara Fernandez-Vidal","orcid":null,"position":12,"is_corresponding":false},{"id":853089,"name":"Carine Karachi","orcid":"0000-0002-4011-6564","position":13,"is_corresponding":false},{"id":1393212,"name":"Marie-Laure Welter","orcid":null,"position":14,"is_corresponding":false},{"id":1683817,"name":"Julie Bourilhon","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pedunculopontine and Cuneiform Nuclei Deep Brain Stimulation for Severe Gait and Balance Disorders in Parkinson’s Disease: Interim Results from a Randomized Double-Blind Clinical Trial","abstract":"<jats:p>Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson’s disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and balance disorders, in a randomized double-blind cross-over trial. Methods: Six PD patients with dopa-resistant FOG and/or falls were operated for MLR-DBS. Patients received three DBS conditions, PPN, CuN, or Sham, in a randomized order for 2-months each, followed by an open-label phase. The primary outcome was the change in anteroposterior anticipatory-postural-adjustments (APAs) during gait initiation on a force platform Results: The anteroposterior APAs were not significantly different between the DBS conditions (median displacement [1st–3rd quartile] of 3.07 [3.12–4.62] cm with sham-DBS, 1.95 [2.29–3.85] cm with PPN-DBS and 2.78 [1.66–4.04] cm with CuN-DBS; p = 0.25). Step length and velocity were significantly higher with CuN-DBS vs. both sham-DBS and PPN-DBS. Conversely, step length and velocity were lower with PPN-DBS vs. sham-DBS, with greater double stance and gait initiation durations. One year after surgery, step length was significantly lower with PPN-DBS vs. inclusion. We did not find any significant change in clinical scales between DBS conditions or one year after surgery. Conclusion: Two months of PPN-DBS or CuN-DBS does not effectively improve clinically dopa-resistant gait and balance disorders in PD patients.</jats:p>","is_dataset_classified":null,"base_score":3.367295829986474,"endowment":3.367295829986474,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34744048","pmcid":null,"openalex_id":"https://openalex.org/W3213271020","authors":[],"funders":[{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-11-INBS-0006","title":null},{"funder_name":"European Commission","grant_id":"898265","title":"Locomotor issues in Parkinsonian's Mesencephalic Locomotor Region and Subthalamic nucleus"}],"total_grants":2,"fwci":1.4542,"citation_percentile":0.84818191,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":8},{"year":2025,"count":5},{"year":2026,"count":9}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://hal.sorbonne-universite.fr/hal-03579807/document","host_type":"repository"},{"url":"https://hal.sorbonne-universite.fr/hal-03579807/document","host_type":"repository"},{"url":"https://content.iospress.com/download?id=10.3233/JPD-212793","host_type":"publisher"},{"url":"https://hal.sorbonne-universite.fr/hal-03962391","host_type":"repository"},{"url":"https://doi.org/10.3233/jpd-212793","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34744048","host_type":"repository"},{"url":"https://hal.sorbonne-universite.fr/hal-03579807","host_type":"repository"},{"url":"https://doaj.org/article/8c4ffd6f819d41ca8a56c2c111c15748","host_type":"repository"},{"url":"https://dx.doi.org/10.3233/jpd-212793","host_type":""},{"url":"https://hal.sorbonne-universite.fr/hal-03579807v2","host_type":""},{"url":"https://hal.sorbonne-universite.fr/hal-03579807v2/document","host_type":""},{"url":"https://doi.org/https://doi.org/10.3233/JPD-212793","host_type":""}],"fields_of_study":["Neurological disorders and treatments","Parkinson's Disease and Spinal Disorders","Botulinum Toxin and Related Neurological Disorders","03 medical and health sciences","0302 clinical medicine","Deep Brain Stimulation","Dihydroxyphenylalanine","Gait","Gait Disorders, Neurologic","Humans","Parkinson Disease","Pedunculopontine Tegmental Nucleus"],"mesh_terms":["Dihydroxyphenylalanine","Gait","Humans","Parkinson Disease","Gait Disorders, Neurologic","Pedunculopontine Tegmental Nucleus","Deep Brain Stimulation"],"keywords":["Pedunculopontine nucleus","Deep brain stimulation","Balance (ability)","Gait","Parkinson's disease","Balance disorders","Movement disorders","Clinical trial","Freezing Of Gait","Postural Instability","Mesencephalic Locomotor Region","Parkinson’s Disease Patients","[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology","[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology","610","Parkinson Disease","Dihydroxyphenylalanine","Pedunculopontine Tegmental Nucleus","Humans","[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]","[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]","Gait Disorders, Neurologic"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T13:21:21.432553Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}