Levodopa-carbidopa Intestinal Gel Research Articles

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel

BackgroundDysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. MethodsWe retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. ResultsA significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780–20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). ConclusionDysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Levodopa–carbidopa intestinal gel in advanced Parkinson’s disease: long-term results from COSMOS

BackgroundWhile immediate benefits of levodopa–carbidopa intestinal gel (LCIG) are evident in patients with Parkinson’s disease (PD), long-term LCIG effects require further study.ObjectivesWe explored long-term LCIG on motor symptoms, nonmotor symptoms (NMS), and LCIG treatment settings in patients with advanced PD (APD).MethodsData were obtained (medical records and patient visit) from COSMOS, a multinational, retrospective, cross-sectional post-marketing observational study in patients with APD. Patients were stratified into 5 groups based on LCIG treatment duration at the patient visit, from 1–2 to > 5 years LCIG. Between-group differences were assessed for changes from baseline in LCIG settings, motor symptoms, NMS, add-on medications, and safety.ResultsOut of 387 patients, the number of patients per LCIG group was: > 1– ≤ 2 years LCIG (n = 156); > 2– ≤ 3 years LCIG (n = 80); > 3– ≤ 4 years LCIG (n = 61); > 4– ≤ 5 years LCIG (n = 30); > 5 years LCIG (n = 60). Baseline values were similar; data reported are changes from the baseline. There were reductions in “off” time, dyskinesia duration, and severity across LCIG groups. Prevalence, severity, and frequency of many individual motor symptoms and some NMS were reduced amongst all LCIG groups, with few differences between groups. Doses for LCIG, LEDD and LEDD for add-on medications were similar across groups both at LCIG initiation and patient visit. Adverse events were similar across all LCIG groups and consistent with the established safety profile of LCIG.ConclusionsLCIG may provide sustained, long-term symptom control, while potentially avoiding increases in add-on medication dosages.Trial registrationClinicalTrials.gov Identifier: NCT03362879. Number and date: P16-831, November 30, 2017.

Enhancing Self-Management of Percutaneous Endoscopic Gastrostomy Tubes Through the Implementation of a Standardized Education and Assessment Pathway: A Quality Improvement Initiative.

Intraduodenal infusion of levodopa-carbidopa intestinal gel by percutaneous endoscopic gastrostomy tube with jejunal extension is a treatment option to reduce motor and nonmotor complications in patients with advanced Parkinson's disease when oral therapy no longer provides sufficient benefit. Medication management is of central focus; however, there was no standardized patient education on stoma-site care and tube maintenance, leading to the development of stoma-site complications. As a quality improvement (QI) initiative, a standardized education and assessment pathway was developed and implemented in an urban academic outpatient clinic to enhance patient self-management and reduce stoma-site complications. A retrospective chart review was conducted to establish baseline incidence of cutaneous stoma-site complications. QI interventions were implemented using a rapid-cycle improvement model. Routine stoma assessments by a nurse who specializes in wound, ostomy, and continence care were implemented at set points, and patient education on PEG tube care and maintenance was reinforced at each session. Results demonstrated a significant reduction in moderate-to-severe tube and stoma-site-related complication. Implementation of a similar standardized education and assessment pathway in patients with percutaneous endoscopic gastrostomy tubes may lead to a decrease in stoma-site-related complications and overall better patient self-management.

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

Revisiting levodopa for advanced Parkinson's disease

Treatment of fluctuating symptoms in advanced Parkinson's disease remains a challenge. The aim of such therapies is to deliver continuous dopamine levels to prevent the aberrant, pulsatile stimulation of striatal dopamine receptors that causes wearing off and dyskinesia. Neuromodulation using deep brain stimulation can be very effective, but only for carefully selected candidates. Lower risk, device-assisted options include subcutaneous infusion of apomorphine1 and levodopa-carbidopa intestinal gel.

Effects of Levodopa-Carbidopa Intestinal Gel Compared with Optimized Medical Treatment on Nonmotor Symptoms in Advanced Parkinson's Disease: INSIGHTS Study.

Nonmotor symptoms (NMS) are common in advanced Parkinson's disease (APD) and reduce health-related quality of life. The aim of the study was to evaluate levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) on NMS in APD. INSIGHTS was a phase 3b, open-label, randomized, multicenter study in patients with APD (LCIG or OMT, 26 weeks) (NCT02549092). Primary outcomes assessed were total NMS (NMS scale (NMSS) and PD sleep scale (PDSS-2)). Key secondary outcomes included the Unified PD Rating Scale (UPDRS) Part II, Clinical Global Impression of Change (CGI-C), and PD Questionnaire-8 (PDQ-8). Additional secondary measures of Patient Global Impression of Change (PGIC), King's PD Pain Scale (KPPS), and Parkinson Anxiety Scale (PAS) also were evaluated. Finally, safety was assessed. Out of 89 patients randomized, 87 were included in the analysis (LCIG, n = 43; OMT, n = 44). There were no significant differences in NMSS or PDSS-2 total score changes (baseline to Week 26) between LCIG and OMT; within-group changes were significant for NMSS (LCIG, p < 0.001; OMT, p = 0.005) and PDSS-2 (LCIG, p < 0.001; OMT, p < 0.001). Between-group treatment differences were nominally significant for UPDRS Part II (p = 0.006) and CGI-C (p < 0.001) at Week 26 in favor of LCIG; however, statistical significance could not be claimed in light of primary efficacy outcomes. PGIC (Week 26) and KPPS (Week 12) scores were nominally significantly reduced with LCIG versus OMT (p < 0.001; p < 0.05). There were no significant differences in PDQ-8 or PAS. Adverse events (AEs) were mostly mild to moderate; common serious AEs were pneumoperitoneum (n = 2) and stoma-site infection (n = 2) (LCIG). There were no significant differences between LCIG versus OMT in NMSS or PDSS-2; both LCIG and OMT groups significantly improved from baseline. AEs were consistent with the known safety profile.

Neurologists’ preferences for device-aided therapy for advanced Parkinson’s disease in Japan

Objective This study measures the relative preference for attributes of device-aided therapies (DATs) for advanced Parkinson’s Disease (PD) from the perspective of Japanese neurologists. Methods Attributes and levels were elicited based on literature and interviews with certified neurologists experienced with DATs. An online survey including a discrete choice experiment (DCE) was developed, pilot tested, and distributed through an online panel to neurologists treating advanced PD patients. Participants were asked to choose treatments among several choice sets of two hypothetical DATs described only by the attributes, or no DAT (continuing oral treatment). A conditional logit model using the Bayesian framework was developed to estimate the marginal utilities of attributes’ levels, and the relative utility of treatments available to Japanese advanced PD patients or being developed in Japan was assessed. Results The DCE survey completed by 308 neurologists showed that the attributes with the greatest influence on DAT selection were surgery requirement (relative importance of 28%), average increase in the duration of daily “on” time without dyskinesia which affects daily activities (15%), average change in cognitive function related to treatment introduction (15%), device management frequency (14%), average number of pills of oral PD medication after treatment introduction (13%), average influence of treatment on symptoms of depression (12%), and type of device (large/small) (3%). All attributes significantly influenced respondents’ choices, except for external device type. Experience with DATs did not influence the directions of preferences. Out of treatment profiles representing DATs, continuous subcutaneous infusion of levodopa-carbidopa had a higher preference score than levodopa-carbidopa intestinal gel infusion and deep brain stimulation. Conclusions Our findings suggest that Japanese neurologists would prefer a DAT without surgery requirement. Other factors related to efficacy, safety, and administration mode have a significant, but a smaller influence on prescription choices.

Effects of Levodopa-Carbidopa Intestinal Gel on Dyskinesia and Non-Motor Symptoms Including Sleep: Results from a Meta-Analysis with 24-Month Follow-Up.

In advanced Parkinson's disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need. To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model. Seventeen open-label studies evaluating 1243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (-1.10 [-1.69, -0.51] h/day) and 12 months (-1.35 [-2.07, -0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (-28.71 [-40.26, -17.15] points). Significant reduction of NMSS burden was maintained through 24 months (-17.61 [-21.52, -13.70] points). UPDRS I scores significantly improved at 3 months (-0.39 [-0.55, -0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies. Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.

An update on advanced therapies for Parkinson's disease: From gene therapy to neuromodulation.

Advanced Parkinson's disease (PD) is characterized by increasingly debilitating impaired movements that include motor fluctuations and dyskinesias. At this stage of the disease, pharmacological management can result in unsatisfactory clinical benefits and increase the occurrence of adverse effects, leading to the consideration of advanced therapies. The scope of this review is to provide an overview of currently available therapies for advanced PD, specifically levodopa–carbidopa intestinal gel, continuous subcutaneous apomorphine infusion, radiofrequency ablation, stereotactic radiosurgery, MRI-guided focused ultrasound, and deep brain stimulation. Therapies in clinical trials are also discussed, including novel formulations of subcutaneous carbidopa/levodopa, gene-implantation therapies, and cell-based therapies. This review focuses on the clinical outcomes and adverse effects of the various therapies and also considers patient-specific characteristics that may influence treatment choice. This review can equip providers with updated information on advanced therapies in PD to better counsel patients on the available options.

A Review on Response to Device-Aided Therapies Used in Monogenic Parkinsonism and GBA Variants Carriers: A Need for Guidelines and Comparative Studies.

Parkinson’s disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring.

Do we start too late? Insights from the real-world non-interventional BALANCE study on the present use of levodopa/carbidopa intestinal gel in advanced Parkinson's disease in Germany and Switzerland

IntroductionAdvanced Parkinson's disease is characterized by motor and non-motor fluctuations to oral dopamine replacement therapy. The BALANCE study evaluated the clinical practice in Germany and Switzerland, when patients eligible for levodopa/carbidopa intestinal gel (LCIG) therapy decided to either switch to LCIG or to stay on optimized standard of care (SoC) oral therapy as a non-randomized regular clinical decision. MethodsIn this non-interventional, multicenter, prospective observational study, patients were recruited between 2015 and 2020. We obtained comprehensive baseline characteristics in both groups. As primary endpoint, we evaluated whether LCIG led to higher quality-of-life (QoL) improvement than SoC after 12 months. As secondary endpoints, we studied several motor and non-motor outcomes. ResultsAbout half of the 137 patients decided for LCIG treatment (n = 73, 53.5%). Those were aged >70 years more often, had more advanced disease stage, higher burden of motor and neuropsychiatric symptoms, and cognitive impairment including dementia compared to SoC. QoL change after 12 months did not differ between groups (P = 0.286). The LCIG group improved in secondary outcomes, including the UPDRS III in ON, UPDRS IV, Unified Dyskinesia Rating Scale, and Non-Motor Symptoms Scale. Clinical Global Impression-Improvement scale improved in 78.0% and 19.5% of patients receiving LCIG and SoC, respectively. Caregiver burden remained stable in LCIG but worsened with SoC. ConclusionIn current practice, patients and physicians delayed LCIG treatment and started substantially beyond the established indication criteria. This practice bears the risk to produce inferior results compared to the results from existing high-level evidence.

Motor and nonmotor symptoms in patients treated with 24-hour daily levodopa-carbidopa intestinal gel infusion: Analysis of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS)

IntroductionPatients with advanced Parkinson's disease (APD) commonly experience motor and nonmotor symptoms (NMS) associated with functional limitations and decreased quality of life. We compared motor and nonmotor outcomes in patients with APD receiving 24- versus 16-h levodopa-carbidopa intestinal gel (LCIG). MethodsData from COSMOS, a large, real-world, retrospective and cross-sectional, observational study on LCIG and comedication in APD were obtained from medical records and a single patient visit for patients receiving 24- and 16-h LCIG infusion. Changes from baseline were evaluated for motor symptoms, NMS, and clinical characteristics. Safety was also assessed. ResultsData for 401 patients were included in this subanalysis. At the patient visit there were 35 patients on 24-h LCIG and 366 on 16-h LCIG. “Off” time and dyskinesia (duration and severity) were reduced in both groups. In both LCIG treatment groups, prevalence of most symptoms was reduced. There were significant differences in the change from baseline in severity and frequency of freezing of gait with 24-h LCIG versus 16-h LCIG (p = 0.011 and p = 0.038), severity of urinary symptoms (p = 0.006), and frequency of cognitive impairment (p = 0.014) with 24-h LCIG versus 16-h LCIG. Adverse events were similar for both treatment groups and considered tolerable. ConclusionsLCIG 24-h infusion may be a useful treatment option, when clinically justified, for select patients with APD. Clinical trial numberNCT03362879.

Tolcapone improves outcomes in patients with Parkinson disease treated by levodopa/carbidopa intestinal gel: A pilot study.

Background:Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage.Objective:The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone—as an add-on therapy to LCIG in patients with PD—on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters.Methods:We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment.Results:The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (–17.73 ± 11.82) and tolcapone groups (–8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (–0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089).Conclusion:Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

Ten-year trends of the characteristics in patients with advanced Parkinson's disease at the time of intestinal gel therapy introduction

Introduction: Parkinson's disease is a neurodegenerative disease, the symptoms of which can be treated reasonably well; however, therapeutic recommendations need to be refined based on the observations from everyday practice. Objective: We aimed to analyze the extent by which published expert recommendations were reflected in the manage-ment of patients with advanced Parkinson's disease, prior to the introduction of the intestinal gel. Method: Data from patients treated with levodopa-carbidopa intestinal gel were retrospectively examined. The period from 2011 to 2021 was divided into two five-year periods, prior and after the usage of the 5-2-1 rule in clinical decision-making. Results: Levodopa-carbidopa intestinal gel treatment was initiated in 150 patients during the study period. In the second five-year period, the mean age of the patients was lower and the time from diagnosis was shorter. Also, there were significantly fewer patients with peak-dose dyskinesias (p = 0.02), biphasic dyskinesias (p<0.001), and early morning akinesias (p = 0.02). Furthermore, in the last five years of the study, fewer patients were affected by delayed on (p = 0.03), no on (p = 0.02), and freezing (p = 0.01). The mean score measured on the Hoehn-Yahr scale was also lower in the second period, while the mean MMSE score was higher (p<0.001). Daily doses of levodopa were higher (p<0.01) in the second period, but with similar dosing frequency. Conclusion: Our retrospective analysis of trends during a ten-year period revealed that, in the second five-year period, levodopa-carbidopa intestinal gel was started in advanced Parkinson's disease patients with a significantly better physical and cognitive state. Compared to expert recommendations, our patients still had a more severe clinical pic -ture at the start of device-aided therapy, but acceptance of this invasive method has improved both for patients and for general practitioners and neurologists.

The Prephase Nursing in Levodopa Carbidopa Intestinal Gel Therapy.

INTRODUCTION: Parkinson disease (PD) affects approximately 1% of women and men worldwide, particularly older than 60 years. It is a multisystem and neurodegenerative disease with genetics and environmental factors that result in deficits in the production of neurotransmitters, including dopamine. The levodopa-carbidopa intestinal gel (LCIG) system delivers a continuous infusion of levodopa directly into the proximal small intestine via percutaneous endoscopic jejunostomy, largely bypassing gastric emptying and absorption problems and producing more stable plasma concentrations of levodopa, eliminating the development of motor complications (dyskinesias). The aim of this review was to summarize scientific evidence on the nursing role that, together with the multidisciplinary team, made the patient's choice in this therapeutic path (pre-LCIG phase). METHODS: A literature review was carried out, conducted on the MEDLINE databases (through PubMed), The Cochrane Library, Google Scholar, and CINAHL (through EBSCO). Relevant articles for the topic were found to identify indexed primary studies that investigated the relationship between the nurse and the patient/caregiver with PD who undertakes treatment with LCIG according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. RESULTS: Nineteen studies were included in the review. The selected studies suggested how the pre-LCIG phase of patient choice and the subsequent education and training could avoid selection errors for these therapeutic paths. CONCLUSION: Trained and specialized nursing staff who carry out an adequate pre-LCIG phase associated to the multidisciplinary team improved the choice of the patient and the start of treatment and, consequently, the quality of life of PD patients.

Movement disorders in COVID-19 times: impact on care in movement disorders and Parkinson disease.

The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP). As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine. COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.

Use of levodopa-carbidopa intestinal gel to treat patients with multiple system atrophy

BackgroundLevodopa-carbidopa intestinal gel (LCIG) is an effective treatment for late-stage Parkinson's disease (PD) but had not been evaluated in levodopa-responsive patients with the parkinsonian variant of multiple system atrophy (MSA-P) and motor fluctuations. We aimed to assess the safety of LCIG in MSA-P patients. MethodsIn a retrospective, single-center study, we analyzed clinical and treatment-related data for all patients with MSA-P or PD treated with LCIG between December 2004 and November 2017. Adverse events (AEs) were classified into three classes: AEs related to gastrointestinal effects or to the PEG-J procedure, AEs related to the device, and AEs related to the pharmacological effect of LCIG. Results7 MSA-P and 63 PD patients had been treated with LCIG for a median [interquartile range] period of 31 [16;43] and 19 [8;45] months, respectively. There were no significant intergroup differences in safety. Enteral nutrition was introduced at the same time as LCIG treatment in 4 (57%) MSA-P patients. In the MSA-P and PD groups, LCIG was associated with a better Global Clinical Impression score and discontinuation of oral anti-parkinsonian drugs (in 43% and 27% of cases, respectively). ConclusionsLCIG treatment is feasible in MSA-P patients with severe motor complications. The safety profile is similar to that seen in PD.

Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease: Observations and Dilemmas after 10 Years of Real-Life Experience.

Advanced Parkinson’s disease (APD) cannot be treated efficiently using the classical medications however, in recent decades invasive therapeutical methods were implemented and confirmed as effective. One of these methods makes it possible to continue the levodopa (LD) supplementation as a gel administered directly into the upper intestine. However, there are a number of unanswered questions regarding this method. Therefore, we retrospectively analyzed a 10-year period of selected patients that were treated with levodopa/carbidopa intestinal gel (LCIG). We included all APD patients with motor fluctuations and dyskinesia at presentation. LCIG treatment was started in 150 patients: on average these patients received LD for 10.6 ± 4.4 years with a frequency of 5.2 ± 1.0/day until the introduction of LCIG. The estimated and the real LCIG dose differed significantly (mean: 1309 ± 321 mg vs. 1877 ± 769 mg). The mean duration of LCIG administration was 19.8 ± 3.6 h, but in a number of 62 patients we had to administer it for 24 h, to maximize the therapeutic benefit. A carefully and individually adjusted LCIG treatment improves the quality of life of APD patients, but questions remain unresolved even after treating a large number of patients. It is important to share the ideas and observations based on the real-life experience related to the optimal timing, the appropriate dose and duration of administration of the LCIG.

The Gut Microbiome in Parkinson's Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies.

BackgroundAltered gut microbiome (GM) composition has been established in Parkinson’s disease (PD). However, few studies have longitudinally investigated the GM in PD, or the impact of device-assisted therapies.ObjectivesTo investigate the temporal stability of GM profiles from PD patients on standard therapies and those initiating device-assisted therapies (DAT) and define multivariate models of disease and progression.MethodsWe evaluated validated clinical questionnaires and stool samples from 74 PD patients and 74 household controls (HCs) at 0, 6, and 12 months. Faster or slower disease progression was defined from levodopa equivalence dose and motor severity measures. 19 PD patients initiating Deep Brain Stimulation or Levodopa-Carbidopa Intestinal Gel were separately evaluated at 0, 6, and 12 months post-therapy initiation.ResultsPersistent underrepresentation of short-chain fatty-acid-producing bacteria, Butyricicoccus, Fusicatenibacter, Lachnospiraceae ND3007 group, and Erysipelotrichaceae UCG-003, were apparent in PD patients relative to controls. A sustained effect of DAT initiation on GM associations with PD was not observed. PD progression analysis indicated that the genus Barnesiella was underrepresented in faster progressing PD patients at t = 0 and t = 12 months. Two-stage predictive modeling, integrating microbiota abundances and nutritional profiles, improved predictive capacity (change in Area Under the Curve from 0.58 to 0.64) when assessed at Amplicon Sequence Variant taxonomic resolution.ConclusionWe present longitudinal GM studies in PD patients, showing persistently altered GM profiles suggestive of a reduced butyrogenic production potential. DATs exerted variable GM influences across the short and longer-term. We found that specific GM profiles combined with dietary factors improved prediction of disease progression in PD patients.

Long-term Motor and Non-Motor Symptom Benefits in Patients With Advanced Parkinson’s Disease Treated With Levodopa-Carbidopa Intestinal Gel: Final Analysis of the 36-Month DUOGLOBE Real-world Multinational Observational Study (P1-1.Virtual)

Long-term Motor and Non-Motor Symptom Benefits in Patients With Advanced Parkinson’s Disease Treated With Levodopa-Carbidopa Intestinal Gel: Final Analysis of the 36-Month DUOGLOBE Real-world Multinational Observational Study (P1-1.Virtual)