| Contributors: |
Cilia, R.; Colucci, F.; Cereda, E.; Elia, A. E.; Leta, V.; Barca, S.; Zibetti, M.; Carecchio, M.; Bonvegna, S.; Calandra Buonaura, G.; Cerroni, R.; De Micco, R.; Tamburin, S.; Magistrelli, L.; Lena, F.; Mascia, M. M.; Picillo, M.; Cossu, G.; Marano, M.; Zampogna, A.; Pellicano, C.; Fioravanti, V.; Pilotto, A.; Zangaglia, R.; Avenali, M.; Sorbera, C.; Di Biasio, F.; Arienti, F.; Nicoletti, A.; Bagella, C.; Malaguti, M. C.; Ranghetti, A.; Caputo, E.; Alimonti, D.; Torre, E.; Oggioni, G. D.; Leuzzi, C.; Romito, L. M.; Andreasi, N. G.; Devigili, G.; Telese, R.; Braccia, A.; Gaudiano, G.; Mazzetti, S.; Invernizzi, F.; Garavaglia, B.; Imbalzano, G.; Ledda, C.; Antenucci, P.; Gozzi, A.; Bonato, G.; Percetti, M.; Giannini, G.; Sambati, L.; Schirinzi, T.; D'Anna, M.; Rinaldi, D.; Cavallieri, F.; Liccari, M.; Priori, A.; Sessa, M.; Tamma, F.; Canesi, M.; Solla, P.; Zappia, M.; Di Fonzo, A.; Avanzino, L.; Quartarone, A.; Valente, E. M.; Pacchetti, C.; Padovani, A.; Valzania, F.; Pontieri, F. E.; Suppa, A.; Pellecchia, M. T.; Modugno, N.; Comi, C.; Tinazzi, M.; Tessitore, A.; Stefani, A.; Cortelli, P.; Isaias, I. U.; Antonini, A.; Sensi, M.; Lopiano, L.; Eleopra, R. |
| Description: |
Background: The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA-PD) remains uncertain. Objective: To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants. Methods: 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. Results: 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. Conclusions: 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. |