Year: 2025
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: The objective was to evaluate the effects of deep brain stimulation (DBS) in an international cohort of patients with VPS16-related dystonia. METHODS: This observational study collected preoperative and postoperative demographic, clinical, stimulation, genetic, neuroimaging, and neurophysiological data of medically refractory DYT-VPS16 patients with implanted DBS in 10 international centers. Motor symptoms and disability outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale Motor (BFMDRS-M) and Disability (BFMDRS-D) scales. A cut-off threshold for considering response to DBS was set at 25% of BFMDRS-M improvement at the last follow-up (FU) compared to baseline. RESULTS: The cohort consisted of 26 participants (17 men, 65.4%). Age at dystonia onset and surgery was 17.8 ± 10.9 and 35.3 ± 14.8 years, respectively. At the last FU, 102.5 ± 57.3 months (range, 2-216), the mean BFMDRS-M improvement was 41.6 ± 37.3% (26/26 patients) and 34.8 ± 42.6% for the BFMDRS-D (23/26 patients). Most patients (19/26, 73%) were considered responders. Higher motor improvement was associated with stimulation of the ventroposterior portion of the internal globus pallidus. A significant inverse relationship was observed between improvement in BFMDRS-M at last FU, and the presence of spasticity (p = 0.027) and fixed skeletal deformities (p = 0.001) before surgery. Non-responders had a younger age at disease onset and at implantation, shorter disease duration at DBS surgery, and higher baseline BFMDRS scores. INTERPRETATION: DBS was an effective treatment for three-quarters of patients with pathogenic VPS16 variants in our cohort. Mean motor improvement was most pronounced at the 1-year FU, but persisted at the last FU despite disease progression. ANN NEUROL 2025;98:711-725.
Source: Annals of Neurology
DOI: 10.1002/ana.27290
Authors: Tatiana Svorenova, Luigi M. Romito, Ahmet Kaymak, Eoin Mulroy, Laura Cif, Elena Moro, Kirsten E. Zeuner, Simone Zittel, Jan Niklas Petry‐Schmelzer, Doreen Gruber, Liesanne Centen, Alberto Albanese, Miriama Ostrozovicova, Vladimir Han, Veronika Magocova, Kamil Knorovsky, Aurelia Kollova, Barbara Garavaglia, Nico Golfrè‐Andreasi, Chiara Reale, Alberto Mazzoni, Giovanna Zorzi, Roberto Eleopra, Vincenzo Levi, Thomas Foltynie, Patricia Limousin, Harith Akram, Ludvic Zrinzo, Francesca Magrinelli, David Murphy, Henry Houlden, Manju A. Kurian, Claudio Baiata, Steffen Paschen, Katja Lohmann, Jens Volkmann, Wolfgang Hamel, Michael T. Barbe, Martje E. van Egmond, MAJ Tijssen, Lubos Ambro, Veronika Jurkova, Robert Jech, Petra Havrankova, Juliane Winkelmann, Michael Zech, Matej Skorvanek
Institutions: University of Pavol Jozef Šafárik, Univerzitná Nemocnica Louisa Pasteura, Fondazione IRCCS Istituto Neurologico Carlo Besta, Scuola Superiore Sant'Anna, UCL Queen Square Institute of Neurology, University College London, Centre Hospitalier Universitaire Vaudois, Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, University of Lausanne, Grenoble Institute of Neurosciences, Université Grenoble Alpes, University Hospital Schleswig-Holstein, University Medical Center Hamburg-Eppendorf, University of Cologne, University Hospital Cologne, Neurologisches Fachkrankenhaus für Bewegungsstörungen/Parkinson, University Medical Center Groningen, University of Groningen, Fondazione Istituto Neurologico Nazionale Casimiro Mondino, Great Ormond Street Hospital, Centre Hospitalier Universitaire de Grenoble, University of Lübeck, University of Würzburg, Charles University, General University Hospital in Prague, Helmholtz Munich, Munich Cluster for Systems Neurology, Institut für Humangenetik, Technical University of Munich
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,700
Funders: Michael J. Fox Foundation for Parkinson's Research, American Parkinson Disease Association, Australian Government, National Institute for Health and Care Research, Parkinson's UK, University College London, European Commission, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Else Kröner-Fresenius-Stiftung, Ministero della Salute, Fondazione Pierfranco e Luisa Mariani, Agentúra na Podporu Výskumu a Vývoja, Technische Universität München, UCLH Biomedical Research Centre, Institute for Advanced Study, Technische Universität München, NextGenerationEU
Awards: Biomarkery prodromálnych a genetických foriem Parkinsonovej choroby, G1595660153, Dissecting PSMF1 as a new gene for early-onset Parkinson’s disease/parkinsonism, G1940663492, G2062271078, G2072208183, PREDYT - Prädiktive Biomarker für die Dystonie: Vom Paradigma der monogenen Subtypen zur Diagnose und Prognose der genetisch nicht-diagnostizierten Formen, G4346918154, G4520290932, Ganzgenom und Transkriptomsequenzierung zur Identifizierung neuer Krankheitsgene für Dystonie, G6693067474, G6948331134, G7578079922, G7988924909, G8237195310, Exploring genetic changes in early onset Parkinson’s, G889583617
OpenAlex ID: W4411496014