<p><i>GBA1</i> variants represent the most common genetic risk factor for Parkinson’s disease (PD) and are associated with higher risk of developing cognitive decline and axial motor impairment. While cognitive outcomes following subthalamic deep brain stimulation (STN-DBS) have recently received growing attention, axial signs progression remains poorly defined in this population. In this retrospective multicentric study, we analyzed a cohort of 353 PD patients who underwent bilateral STN-DBS surgery (75 GBA+ and 253 GBA−). 5-year follow-up data were available for 233 patients, including 43 mutated subjects. Lower off-medication UPDRS III score and levodopa responsiveness at baseline were identified as independent predictors of axial signs worsening after DBS, while <i>GBA1</i> genotype was not identified as risk factor. The presence of <i>GBA1</i> variants did not exert a detrimental effect on axial signs in PD patients up to five years following STN-DBS, supporting its consideration as a valid therapeutic option in this genetic subgroup.</p>

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Unraveling the role of GBA1 genotype in axial signs response to subthalamic deep brain stimulation

  • Francesco Bove,
  • Danilo Genovese,
  • Alessandro De Biase,
  • Alberto Albanese,
  • Angelo Antonini,
  • Carlo Alberto Artusi,
  • Laura Avanzino,
  • Micol Avenali,
  • Luca Baldelli,
  • Giovanna Calandra-Buonaura,
  • Ilaria Cani,
  • Niccolò Casasoli,
  • Francesco Cavallieri,
  • Roberto Cilia,
  • Antoniangela Cocco,
  • Fabiana Colucci,
  • Francesca Di Biasio,
  • Valentina D’Onofrio,
  • Roberto Eleopra,
  • Valentina Fioravanti,
  • Giulia Giannini,
  • Nico Golfre’ Andreasi,
  • Andrea Guerra,
  • Gabriele Imbalzano,
  • Alessandro Izzo,
  • Claudia Ledda,
  • Marco Liccari,
  • Leonardo Lopiano,
  • Maria Chiara Malaguti,
  • Raffaella Minardi,
  • Pierfrancesco Mitrotti,
  • Luigi Michele Romito,
  • Enza Maria Valente,
  • Franco Valzania,
  • Roberta Zangaglia,
  • Paolo Calabresi,
  • Carla Piano,
  • Anna Rita Bentivoglio,
  • C. Caltagirone,
  • A. Costa,
  • F. R. Giardina,
  • A. Peppe,
  • C. Pellicano,
  • F. E. Pontieri,
  • F. Piras,
  • F. Sommaruga,
  • G. Sancesario,
  • S. Zabberoni,
  • R. Cilia,
  • F. De Giorgi,
  • G. Devigili,
  • R. Eleopra,
  • A. Elia,
  • B. Garavaglia,
  • G. Giaccone,
  • M. Grisoli,
  • V. Leta,
  • F. Moda,
  • B. Reggiori,
  • L. M. Romito,
  • I. Tramacere,
  • S. Piacentini,
  • M. Avenali,
  • R. Bergamaschi,
  • R. Calabrese,
  • S. Cerri,
  • G. Cosentino,
  • G. Cuconato,
  • R. De Icco,
  • C. Galandra,
  • A. Imarisio,
  • P. Mitrotti,
  • C. Pacchetti,
  • I. Palmieri,
  • M. Picascia,
  • A. Pichiecchio,
  • A. Pisani,
  • C. Tassorelli,
  • E. M. Valente,
  • F. Valentino,
  • R. Zangaglia,
  • C. Agliardi,
  • F. Baglio,
  • A. Caronni,
  • F. Guerini,
  • R. Mancuso,
  • A. Mannini,
  • M. Meloni,
  • F. Saibene,
  • S. Sorbi,
  • F. Vannetti,
  • A. Ciammola,
  • L. Maderna,
  • B. Poletti,
  • A. Ratti,
  • V. Silani,
  • N. Ticozzi,
  • F. Triulzi,
  • F. Verde,
  • G. Zebellin,
  • F. Agosta,
  • S. Amadio,
  • V. Broccoli,
  • R. Cardamone,
  • M. Filippi,
  • S. Galantucci,
  • L. Gianolli,
  • M. Morelli,
  • E. Sarasso,
  • J. Sassone,
  • M. R. Terreni,
  • M. A. Volontè,
  • R. Bellazzi,
  • E. Brigonzi,
  • M. Buonocore,
  • R. Campini,
  • F. Cossa,
  • E. Federici,
  • M. Gennuso,
  • E. Losavio,
  • A. Losurdo,
  • C. Lunetta,
  • G. Maggioni,
  • A. Malovini,
  • C. Morasso,
  • M. Nolano,
  • E. Parati,
  • C. Pistarini,
  • D. M. Rossi,
  • M. Terzaghi,
  • V. Tibollo,
  • L. Avanzino,
  • G. Bonanno,
  • L. Boni,
  • C. Campi,
  • E. Capello,
  • G. Ferrara,
  • A. Gaudio,
  • G. Lagravinese,
  • P. Mandich,
  • R. Marchese,
  • F. Massa,
  • S. Morbelli,
  • F. Nobili,
  • P. Origone,
  • E. Pelosin,
  • L. Roccatagliata,
  • L. Trevisan,
  • A. Arcella,
  • G. Battaglia,
  • D. Belvisi,
  • A. Berardelli,
  • D. Centonze,
  • R. Ferese,
  • S. Gambardella,
  • A. Gialluisi,
  • F. Giangaspero,
  • C. Limatola,
  • N. Modugno,
  • P. Pantano,
  • L. Pavone,
  • S. Puglisi Allegra,
  • A. Brigandì,
  • G. Di Lorenzo,
  • V. Lo Buono,
  • S. Marino,
  • S. Silvestro,
  • C. Sorbera,
  • S. Bonassi,
  • F. Brancati,
  • M. F. De Pandis,
  • B. Picconi,
  • P. M. Rossini,
  • F. Stocchi,
  • L. Vacca,
  • A. Albanese,
  • L. Antunovic,
  • A. Cocco,
  • T. De Santis,
  • R. Gatti,
  • S. Lalli,
  • E. Lauranzano,
  • M. Matteoli,
  • R. Mineri,
  • E. Paraboschi,
  • E. Perdixi,
  • L. Politi,
  • P. Polverino,
  • D. Pozzi,
  • G. Savini,
  • A. R. Bentivoglio,
  • F. Bove,
  • P. Calabresi,
  • A. Cimmino,
  • A. De Biase,
  • G. Di Lazzaro,
  • D. Di Giuda,
  • D. Genovese,
  • M. R. Lo Monaco,
  • M. Petracca,
  • C. Piano,
  • F. D. Tiziano,
  • M. G. Vita,
  • G. Arcara,
  • R. Barresi,
  • V. Camparini,
  • P. Cudia,
  • G. Ferrazzi,
  • K. Koutsikos,
  • N. Manzo,
  • F. Pellizzari,
  • A. Arighi,
  • F. Blandini,
  • F. Cogiamanian,
  • M. Castellani,
  • F. Colucci,
  • M. Cribiù,
  • A. Di Fonzo,
  • G. Franco,
  • E. Frattini,
  • C. Losa,
  • F. Mameli,
  • E. Monfrini,
  • E. Scola,
  • I. Trezzi,
  • M. G. Bacalini,
  • L. Baldelli,
  • G. Calandra-Buonaura,
  • I. Cani,
  • L. Caporali,
  • V. Carelli,
  • P. Cortelli,
  • P. Ghedini,
  • P. Guaraldi,
  • G. Giannini,
  • G. Lopane,
  • R. Minardi,
  • A. Fiorentino,
  • F. Nonino,
  • R. Pantieri,
  • P. Parchi,
  • F. Provini,
  • C. Tonon,
  • L. Sambati

摘要

GBA1 variants represent the most common genetic risk factor for Parkinson’s disease (PD) and are associated with higher risk of developing cognitive decline and axial motor impairment. While cognitive outcomes following subthalamic deep brain stimulation (STN-DBS) have recently received growing attention, axial signs progression remains poorly defined in this population. In this retrospective multicentric study, we analyzed a cohort of 353 PD patients who underwent bilateral STN-DBS surgery (75 GBA+ and 253 GBA−). 5-year follow-up data were available for 233 patients, including 43 mutated subjects. Lower off-medication UPDRS III score and levodopa responsiveness at baseline were identified as independent predictors of axial signs worsening after DBS, while GBA1 genotype was not identified as risk factor. The presence of GBA1 variants did not exert a detrimental effect on axial signs in PD patients up to five years following STN-DBS, supporting its consideration as a valid therapeutic option in this genetic subgroup.