Objectives: The main objective of this study is to evaluate the effect of DBS and LCIG on axial symptoms of PD. Secondly, it aims to compare the variations in axial, motor and non-motor symptoms, and motor fluctuations between the two treatment groups. Finally, it plans to explore in a subgroup whether the genetic mutation of the GBA1 gene modifies the clinical outcome within the groups and between the two groups. Background: Device-assisted therapies (DAT) like Deep Brain Stimulation (DBS) and Levodopa-Carbidopa Intestinal Gel (LCIG) are established treatments for advanced Parkinson's disease (PD). However, evidence comparing their effectiveness on axial symptoms, motor/non-motor symptoms, and the impact of genetic factors remains limited. Methods: This observational cohort study included 317 patients (203 DBS, 114 LCIG) treated between 2005-2023 at two Italian centers. Assessments were conducted at baseline, 12±3 months, and when available at 5 years±6 months. Motor symptoms were evaluated using UPDRS/MDS-UPDRS Part III, with axial items analyzed separately. Motor fluctuations were assessed using UPDRS/MDS-UPDRS Part IV. Non-motor symptoms and GBA1 genetic status were also evaluated. Results: LCIG patients were older at implant (65.7 vs 56.9 years, p<0.000001) with greater clinical severity. At 12 months, both groups showed similar motor improvement (UPDRS-III ON, LCIG: -2.76±6.37 vs DBS: -2.50±8.53, p=ns) and reduction in motor fluctuations. LCIG showed greater benefits for falls and hallucinations but less improvement in dyskinesias. At 5 years, both groups demonstrated similar motor deterioration while maintaining benefits for motor fluctuations. DBS showed more pronounced deterioration in gait, posture, and freezing long-term. GBA1 mutations were similarly prevalent (DBS 15.6%, LCIG 18.2%) with comparable long-term outcomes. Conclusions: Both therapies effectively improve motor symptoms and fluctuations initially, but neither stops disease progression. LCIG shows better long-term control of axial symptoms compared to DBS. The similar presence and outcomes of GBA1 mutations suggest that treatment choice should be based on clinical characteristics rather than genetic factors. Combined treatment might offer better overall outcomes.
Obiettivi: L'obiettivo principale di questo studio è valutare l'effetto di DBS e LCIG sui sintomi assiali del morbo di Parkinson. In secondo luogo, mira a confrontare le variazioni nei sintomi assiali, motori e non motori, e le fluttuazioni motorie tra i due gruppi di trattamento. Infine, intende esplorare in un sottogruppo se la mutazione genetica del gene GBA1 modifichi l'esito clinico all'interno dei gruppi e tra i due gruppi. Background: Le terapie assistite da dispositivi (DAT) come la Stimolazione Cerebrale Profonda (DBS) e il Gel Intestinale di Levodopa-Carbidopa (LCIG) sono trattamenti consolidati per il morbo di Parkinson avanzato. Tuttavia, le evidenze che confrontano la loro efficacia sui sintomi assiali, i sintomi motori/non motori e l'impatto dei fattori genetici rimangono limitate. Metodi: Questo studio di coorte osservazionale ha incluso 317 pazienti (203 DBS, 114 LCIG) trattati tra il 2005-2023 in due centri italiani. Le valutazioni sono state condotte al basale, a 12±3 mesi e, quando disponibili, a 5 anni±6 mesi. I sintomi motori sono stati valutati utilizzando UPDRS/MDS-UPDRS Parte III, con gli item assiali analizzati separatamente. Le fluttuazioni motorie sono state valutate utilizzando UPDRS/MDS-UPDRS Parte IV. Sono stati valutati anche i sintomi non motori e lo stato genetico GBA1. Risultati: I pazienti LCIG erano più anziani al momento dell'impianto (65,7 vs 56,9 anni, p<0,000001) con maggiore gravità clinica. A 12 mesi, entrambi i gruppi hanno mostrato un simile miglioramento motorio (UPDRS-III ON, LCIG: -2,76±6,37 vs DBS: -2,50±8,53, p=ns) e riduzione delle fluttuazioni motorie. LCIG ha mostrato maggiori benefici per le cadute e le allucinazioni ma un minor miglioramento nelle discinesie. A 5 anni, entrambi i gruppi hanno dimostrato un simile deterioramento motorio mantenendo i benefici per le fluttuazioni motorie. DBS ha mostrato un deterioramento più pronunciato nella deambulazione, postura e freezing a lungo termine. Le mutazioni GBA1 erano prevalenti in modo simile (DBS 15,6%, LCIG 18,2%) con esiti a lungo termine comparabili. Conclusioni: Entrambe le terapie migliorano efficacemente i sintomi motori e le fluttuazioni inizialmente, ma nessuna delle due ferma la progressione della malattia. LCIG mostra un miglior controllo a lungo termine dei sintomi assiali rispetto a DBS. La presenza simile e gli esiti delle mutazioni GBA1 suggeriscono che la scelta del trattamento dovrebbe basarsi sulle caratteristiche cliniche piuttosto che sui fattori genetici. Un trattamento combinato potrebbe offrire risultati complessivi migliori.
Studio comparativo tra infusione di gel intestinale di levodopa-carbidopa e stimolazione cerebraale profonda del nucleo subtalamico nella malattia di Parkinson avanzata
COLUCCI, FABIANA
2025
Abstract
Objectives: The main objective of this study is to evaluate the effect of DBS and LCIG on axial symptoms of PD. Secondly, it aims to compare the variations in axial, motor and non-motor symptoms, and motor fluctuations between the two treatment groups. Finally, it plans to explore in a subgroup whether the genetic mutation of the GBA1 gene modifies the clinical outcome within the groups and between the two groups. Background: Device-assisted therapies (DAT) like Deep Brain Stimulation (DBS) and Levodopa-Carbidopa Intestinal Gel (LCIG) are established treatments for advanced Parkinson's disease (PD). However, evidence comparing their effectiveness on axial symptoms, motor/non-motor symptoms, and the impact of genetic factors remains limited. Methods: This observational cohort study included 317 patients (203 DBS, 114 LCIG) treated between 2005-2023 at two Italian centers. Assessments were conducted at baseline, 12±3 months, and when available at 5 years±6 months. Motor symptoms were evaluated using UPDRS/MDS-UPDRS Part III, with axial items analyzed separately. Motor fluctuations were assessed using UPDRS/MDS-UPDRS Part IV. Non-motor symptoms and GBA1 genetic status were also evaluated. Results: LCIG patients were older at implant (65.7 vs 56.9 years, p<0.000001) with greater clinical severity. At 12 months, both groups showed similar motor improvement (UPDRS-III ON, LCIG: -2.76±6.37 vs DBS: -2.50±8.53, p=ns) and reduction in motor fluctuations. LCIG showed greater benefits for falls and hallucinations but less improvement in dyskinesias. At 5 years, both groups demonstrated similar motor deterioration while maintaining benefits for motor fluctuations. DBS showed more pronounced deterioration in gait, posture, and freezing long-term. GBA1 mutations were similarly prevalent (DBS 15.6%, LCIG 18.2%) with comparable long-term outcomes. Conclusions: Both therapies effectively improve motor symptoms and fluctuations initially, but neither stops disease progression. LCIG shows better long-term control of axial symptoms compared to DBS. The similar presence and outcomes of GBA1 mutations suggest that treatment choice should be based on clinical characteristics rather than genetic factors. Combined treatment might offer better overall outcomes.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14242/218689
URN:NBN:IT:UNIFE-218689