Cilia Roberto, Colucci Fabiana, Cereda Emanuele, Elia Antonio E, Leta Valentina, Barca Silvia, Zibetti Maurizio, Carecchio Miryam, Bonvegna Salvatore, Calandra-Buonaura Giovanna, Cerroni Rocco, De Micco Rosa, Tamburin Stefano, Magistrelli Luca, Lena Francesco, Mascia Marcello M, Picillo Marina, Cossu Giovanni, Marano Massimo, Zampogna Alessandro, Pellicano Clelia, Fioravanti Valentina, Pilotto Andrea, Zangaglia Roberta, Avenali Micol, Sorbera Chiara, Di Biasio Francesca, Arienti Federica, Nicoletti Alessandra, Bagella Caterina, Malaguti Maria Chiara, Ranghetti Alessandra, Caputo Elena, Alimonti Dario, Torre Elena, Oggioni Gaia D, Leuzzi Catia, Romito Luigi M, Andreasi Nico Golfrè, Devigili Grazia, Telese Roberta, Braccia Arianna, Gaudiano Gianfranco, Mazzetti Samanta, Invernizzi Federica, Garavaglia Barbara, Imbalzano Gabriele, Ledda Claudia, Antenucci Pietro, Gozzi Andrea, Bonato Giulia, Percetti Marco, Giannini Giulia, Sambati Luisa, Schirinzi Tommaso, D'Anna Martina, Rinaldi Domiziana, Cavallieri Francesco, Liccari Marco, Priori Alberto, Sessa Maria, Tamma Filippo, Canesi Margherita, Solla Paolo, Zappia Mario, Di Fonzo Alessio, Avanzino Laura, Quartarone Angelo, Valente Enza Maria, Pacchetti Claudio, Padovani Alessandro, Valzania Franco, Pontieri Francesco E, Suppa Antonio, Pellecchia Maria Teresa, Modugno Nicola, Comi Cristoforo, Tinazzi Michele, Tessitore Alessandro, Stefani Alessandro, Cortelli Pietro, Isaias Ioannis U, Antonini Angelo, Sensi Mariachiara, Lopiano Leonardo, Eleopra Roberto
Parkinson and Movement Disorders Unit, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Azienda Ospedaliera Universitaria S. Anna, U.O. Neurologia, Ferrara, Italy.
Eur J Neurol. 2025 Jul;32(7):e70179. doi: 10.1111/ene.70179.
The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA-PD) remains uncertain.
To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants.
This multicenter, retrospective, longitudinal "real-world" study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1-, 5-year, and last-available follow-up.
Data from 512 PD patients (59% male, mean age and disease duration at LCIG initiation 67.0 ± 8.0 and 12.9 ± 5.0 years, respectively) were analyzed. GBA1 genotyping was available for 306 patients (60%), of whom 40 (13%) had GBA1 mutations or risk variants. Mean follow-up on LCIG was 3.9 ± 2.9 years; 5-year follow-up data were available for 159 subjects. At baseline, GBA-PD had a younger age, shorter PD duration, worse cognition, and more hallucinations than noncarriers. At 1- and 5-year follow-up, LCIG improved motor and non-motor symptoms, OFF-time, and dyskinesias in the entire population. In GBA-PD, MDS-UPDRS parts I, II, and III scores did not change, while part IV score improved significantly less than in noncarriers; cognition and orthostatic hypotension symptoms worsened more rapidly. Multivariate analysis of predictors for adverse events and LCIG discontinuation found no significant contribution from GBA1 mutation status.
GBA1 status does not increase the risk of adverse events or LCIG discontinuation. LCIG is a safe option for advanced GBA-PD, even in patients with cognitive impairment at baseline. However, GBA-PD experiences lower efficacy on motor disability and complications and faster cognitive decline than noncarriers.
左旋多巴/卡比多巴肠凝胶（LCIG）治疗携带GBA1突变的帕金森病患者（GBA-PD）的疗效仍不确定。
评估LCIG在大型帕金森病队列中的安全性和有效性，重点关注GBA1变异。
这项多中心、回顾性、纵向的“真实世界”研究纳入了意大利31个中心接受LCIG治疗的晚期帕金森病患者；在基线、1年、5年及最后一次随访时收集数据。
分析了512例帕金森病患者的数据（59%为男性，开始使用LCIG时的平均年龄和病程分别为67.0±8.0岁和12.9±5.0年）。306例患者（60%）进行了GBA1基因分型，其中40例（13%）有GBA1突变或风险变异。LCIG的平均随访时间为3.9±2.9年；159例受试者有5年随访数据。基线时，与非携带者相比，GBA-PD患者年龄更小、帕金森病病程更短、认知功能更差且幻觉更多。在1年和5年随访时，LCIG改善了整个人群的运动和非运动症状、关期时间和异动症。在GBA-PD患者中，MDS-UPDRS第一、二、三部分评分未改变，而第四部分评分改善明显低于非携带者；认知功能和体位性低血压症状恶化更快。对不良事件和停用LCIG的预测因素进行多变量分析发现，GBA1突变状态无显著影响。
GBA1状态不会增加不良事件风险或停用LCIG的风险。LCIG是晚期GBA-PD患者的安全选择，即使是基线时有认知障碍的患者。然而，与非携带者相比，GBA-PD患者在运动障碍和并发症方面疗效较低，认知功能下降更快。
