Deep Brain Stimulation for VPS16 ‐Related Dystonia: A Multicenter 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.
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BibTeX
@article{svorenova2026deep,
title = {{Deep Brain Stimulation for VPS16 ‐Related Dystonia: A Multicenter Study}},
author = {Tatiana Svorenova and Luigi Romito and Ahmet Kaymak and Eoin Mulroy and Laura Cif and Elena Moro and Kirsten Zeuner and Simone Zittel and Jan Niklas Petry-Schmelzer and Doreen Gruber and Liesanne Centen and Alberto Albanese and Miriama Ostrozovicova and Vladimir Han and Veronika Magocova and Kamil Knorovsky and Aurelia Kollova and Barbara Garavaglia and Nico Golfrè-Andreasi and Chiara Reale and Alberto Mazzoni and Giovanna Zorzi and Roberto Eleopra and Vincenzo Levi and Thomas Foltynie and Patricia Limousin and Harith Akram and Ludvic Zrinzo and Francesca Magrinelli and David Murphy and Henry Houlden and Manju Kurian and Claudio Baiata and Steffen Paschen and Katja Lohmann and Jens Volkmann and Wolfgang Hamel and Michael Barbe and Martje van Egmond and Maj Tijssen and Lubos Ambro and Veronika Jurkova and Robert Jech and Petra Havrankova and Juliane Winkelmann and Michael Zech and Matej Skorvanek},
journal = {Annals of Neurology},
year = {2026},
month = sep,
doi = {10.1002/ana.27290},
url = {https://hal.science/hal-05735316v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Deep Brain Stimulation for VPS16 ‐Related Dystonia: A Multicenter Study
AU - Tatiana Svorenova
AU - Luigi Romito
AU - Ahmet Kaymak
AU - Eoin Mulroy
AU - Laura Cif
AU - Elena Moro
AU - Kirsten Zeuner
AU - Simone Zittel
AU - Jan Niklas Petry-Schmelzer
AU - Doreen Gruber
AU - Liesanne Centen
AU - Alberto Albanese
AU - Miriama Ostrozovicova
AU - Vladimir Han
AU - Veronika Magocova
AU - Kamil Knorovsky
AU - Aurelia Kollova
AU - Barbara Garavaglia
AU - Nico Golfrè-Andreasi
AU - Chiara Reale
AU - Alberto Mazzoni
AU - Giovanna Zorzi
AU - Roberto Eleopra
AU - Vincenzo Levi
AU - Thomas Foltynie
AU - Patricia Limousin
AU - Harith Akram
AU - Ludvic Zrinzo
AU - Francesca Magrinelli
AU - David Murphy
AU - Henry Houlden
AU - Manju Kurian
AU - Claudio Baiata
AU - Steffen Paschen
AU - Katja Lohmann
AU - Jens Volkmann
AU - Wolfgang Hamel
AU - Michael Barbe
AU - Martje van Egmond
AU - Maj Tijssen
AU - Lubos Ambro
AU - Veronika Jurkova
AU - Robert Jech
AU - Petra Havrankova
AU - Juliane Winkelmann
AU - Michael Zech
AU - Matej Skorvanek
PY - 2026
DA - 2026/09/02
JO - Annals of Neurology
DO - 10.1002/ana.27290
UR - https://hal.science/hal-05735316v1
AB - 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.
SN - 0364-5134
SN - 1531-8249
ER -