Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study

Tatiana Svorenova^#^{1

2}, Luigi M Romito^#³, Ahmet Kaymak^#⁴, Eoin Mulroy⁵, Laura Cif^{6

7}, Elena Moro⁸, Kirsten E Zeuner⁹, Simone Zittel¹⁰, Jan Niklas Petry-Schmelzer¹¹, Doreen Gruber¹², Liesanne Centen^{13

14}, Alberto Albanese¹⁵, Miriama Ostrozovicova^{1

2

16}, Vladimir Han^{1

2}, Veronika Magocova^{17

18}, Kamil Knorovsky^{17

18}, Aurelia Kollova^{17

18}, Barbara Garavaglia¹⁹, Nico Golfrè-Andreasi³, Chiara Reale¹⁹, Alberto Mazzoni⁴, Giovanna Zorzi²⁰, Roberto Eleopra³, Vincenzo Levi²¹, Thomas Foltynie⁵, Patricia Limousin⁵, Harith Akram⁵, Ludvic Zrinzo⁵, Francesca Magrinelli²², David Murphy²², Henry Houlden²³, Manju A Kurian^{24

25}, Claudio Baiata²⁶, Steffen Paschen⁹, Katja Lohmann²⁷, Jens Volkmann²⁸, Wolfgang Hamel²⁹, Michael T Barbe¹¹, Martje E van Egmond^{13

14}, Maj Tijssen^{13

14}, Lubos Ambro³⁰, Veronika Jurkova³¹, Robert Jech³², Petra Havrankova³², Juliane Winkelmann^{33

34

35}, Michael Zech^{33

34

36}, Matej Skorvanek^#^{1

2}

Affiliations

¹ Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic.
² Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic.
³ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁴ The BioRobotics Institute, Scuola Superiore Sant' Anna, Pisa, Italy.
⁵ Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
⁶ Department of Neurosurgery, Gui de Chauliac Hospital, University Hospital Montpellier, Montpellier, France.
⁷ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁸ Grenoble Alpes University, Division of Neurology, CHU of Grenoble, Grenoble Institute of Neurosciences, Grenoble, France.
⁹ Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
¹⁰ Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹² Movement Disorders Hospital, Beelitz-Heilstätten, Germany.
¹³ Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁴ Expertise Center Movement Disorders Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹⁵ Department of Neurology, IRCCS Fondazione Mondino, Pavia, Italy.
¹⁶ Laboratory of Clinical Neurosciences, University Science Park MEDIPARK, P. J. Safarik University, Kosice, Slovak Republic.
¹⁷ Department of Neurosurgery, P.J. Safarik University, Kosice, Slovak Republic.
¹⁸ Department of Neurosurgery, University Hospital of L. Pasteur, Kosice, Slovak Republic.
¹⁹ Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁰ Department of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²¹ Neurosurgery Department, Functional Neurosurgery Unit, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milan, Italy.
²² Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
²³ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.
²⁴ Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Institute of Child Health, London, UK.
²⁵ Department of Neurology, Great Ormond Street Hospital for Children, London, UK.
²⁶ Division of Neurology, CHU of Grenoble, Grenoble, France.
²⁷ Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
²⁸ Department of Neurology, University of Würzburg, Würzburg, Germany.
²⁹ Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁰ Center for Interdisciplinary Biosciences, Technology and Innovation Park, P.J. Safarik University, Kosice, Slovak Republic.
³¹ Department of Health Psychology and Research Methodology, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic.
³² Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Praha, Prague, Czech Republic.
³³ Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
³⁴ Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
³⁵ Munich Cluster for Systems Neurology, SyNergy, Munich, Germany.
³⁶ Institute for Advanced Study, Technical University of Munich, Garching, Germany.

^# Contributed equally.

PMID: 40539388
DOI: 10.1002/ana.27290

Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study

Tatiana Svorenova et al. Ann Neurol. 2025.

. 2025 Jun 20.

doi: 10.1002/ana.27290. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic.
² Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic.
³ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁴ The BioRobotics Institute, Scuola Superiore Sant' Anna, Pisa, Italy.
⁵ Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
⁶ Department of Neurosurgery, Gui de Chauliac Hospital, University Hospital Montpellier, Montpellier, France.
⁷ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
⁸ Grenoble Alpes University, Division of Neurology, CHU of Grenoble, Grenoble Institute of Neurosciences, Grenoble, France.
⁹ Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
¹⁰ Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
¹² Movement Disorders Hospital, Beelitz-Heilstätten, Germany.
¹³ Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁴ Expertise Center Movement Disorders Groningen, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
¹⁵ Department of Neurology, IRCCS Fondazione Mondino, Pavia, Italy.
¹⁶ Laboratory of Clinical Neurosciences, University Science Park MEDIPARK, P. J. Safarik University, Kosice, Slovak Republic.
¹⁷ Department of Neurosurgery, P.J. Safarik University, Kosice, Slovak Republic.
¹⁸ Department of Neurosurgery, University Hospital of L. Pasteur, Kosice, Slovak Republic.
¹⁹ Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁰ Department of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²¹ Neurosurgery Department, Functional Neurosurgery Unit, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milan, Italy.
²² Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
²³ Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, UK.
²⁴ Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Institute of Child Health, London, UK.
²⁵ Department of Neurology, Great Ormond Street Hospital for Children, London, UK.
²⁶ Division of Neurology, CHU of Grenoble, Grenoble, France.
²⁷ Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
²⁸ Department of Neurology, University of Würzburg, Würzburg, Germany.
²⁹ Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁰ Center for Interdisciplinary Biosciences, Technology and Innovation Park, P.J. Safarik University, Kosice, Slovak Republic.
³¹ Department of Health Psychology and Research Methodology, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic.
³² Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Praha, Prague, Czech Republic.
³³ Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
³⁴ Institute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
³⁵ Munich Cluster for Systems Neurology, SyNergy, Munich, Germany.
³⁶ Institute for Advanced Study, Technical University of Munich, Garching, Germany.

^# Contributed equally.

PMID: 40539388
DOI: 10.1002/ana.27290

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.

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References

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Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study

Affiliations

Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study

Authors

Affiliations

Abstract

References

Grants and funding

LinkOut - more resources

Full Text Sources