Continuous subcutaneous foslevodopa/foscarbidopa infusion for the treatment of motor fluctuations in Parkinson's disease: Considerations for initiation and maintenance.

Background: As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations by the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady dopaminergic stimulation that can reduce symptom fluctuation.

Objective: Our aim is to review the initiation, optimization, and maintenance of LDp/CDp therapy, identify possible challenges, and share potential mitigations.

Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study.

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD.

Levodopa Carbidopa Intestinal Gel in Advanced Parkinson's Disease: DUOGLOBE Final 3-Year Results.

Background: Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD).

Objective: To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713).

Methods: DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care.

Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited.

Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289).

Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial.

Background: Levodopa is the most effective symptomatic therapy for Parkinson's disease, but patients with advanced Parkinson's disease develop motor fluctuations with chronic oral levodopa therapy. Foslevodopa-foscarbidopa is a soluble formulation of levodopa and carbidopa prodrugs that is delivered as a 24-h/day continuous subcutaneous infusion, and we aimed to assess the safety and efficacy of this formulation in patients with advanced Parkinson's disease.

Methods: A 12-week randomised, double-blind, double-dummy, active-controlled study was done at 65 academic and community study centres in the USA and Australia.

Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease.

Mutations in leucine-rich repeat kinase 2 () are the most common genetic risk factors for Parkinson's disease (PD). Increased LRRK2 kinase activity is thought to impair lysosomal function and may contribute to the pathogenesis of PD. Thus, inhibition of LRRK2 is a potential disease-modifying therapeutic strategy for PD.

Patterns of Daily Motor-Symptom Control with Carbidopa/Levodopa Enteral Suspension Versus Oral Carbidopa/Levodopa Therapy in Advanced Parkinson's Disease: Clinical Trial Post Hoc Analyses.

Introduction: A clinical trial in advanced Parkinson's disease (APD) has established the superiority of carbidopa/levodopa enteral suspension (CLES) in reducing total patient "off" time (OFF) and increasing total "on" time without troublesome dyskinesia (ON-woTD) over orally administered immediate-release carbidopa/levodopa tablets (IR-CL). However, temporal patterns of these improvements throughout the waking day have not been examined. In this analysis, time to ON-woTD after waking and patterns of motor-symptom control throughout the waking day were compared between CLES and IR-CL.

Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel.

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson's disease (PD), and that improvements in these metrics are correlated.

Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms.

Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD.

DUOGLOBE: One-Year Outcomes in a Real-World Study of Levodopa Carbidopa Intestinal Gel for Parkinson's Disease.

Background: Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non-motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long-term data in routine clinical practice are limited.

Objective: Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real-world routine clinical practice.

The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on 'Off'-time in Patients with Advanced Parkinson's Disease: A Systematic Review.

Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.

Application of the '5-2-1' screening criteria in advanced Parkinson's disease: interim analysis of DUOGLOBE.

A Delphi expert consensus panel proposed that fulfilling ≥1 of the '5-2-1 criteria' (≥five-times daily oral levodopa use, ≥two daily hours with 'Off' symptoms or ≥one daily hour with troublesome dyskinesia) suggests advanced Parkinson's disease (PD). DUOdopa/Duopa in Patients with Advanced PD - a GLobal OBservational Study Evaluating Long-Term Effectiveness (DUOGLOBE) - is a single-arm, postmarketing, observational, long-term effectiveness study of levodopa-carbidopa intestinal gel (LCIG) for advanced PD. This 6-month interim analysis (n = 139) affirms that most (98%) enrolled patients fulfill ≥1 of the 5-2-1 criteria.

An Open-Label, 8-Week Study of Safety and Efficacy of Pimavanserin Treatment in Adults with Parkinson's Disease and Depression.

Background: Many patients with Parkinson's disease (PD) experience depression.

Objective: Evaluate pimavanserin treatment for depression in patients with PD.

Methods: Pimavanserin was administered as monotherapy or adjunctive therapy to a selective serotonin reuptake inhibitor or serotonin/noradrenaline reuptake inhibitor in this 8-week, single-arm, open-label phase 2 study (NCT03482882).

Non-invasive MRI quantification of cerebrospinal fluid dynamics in amyotrophic lateral sclerosis patients.

Background: Developing novel therapeutic agents to treat amyotrophic lateral sclerosis (ALS) has been difficult due to multifactorial pathophysiologic processes at work. Intrathecal drug administration shows promise due to close proximity of cerebrospinal fluid (CSF) to affected tissues. Development of effective intrathecal pharmaceuticals will rely on accurate models of how drugs are dispersed in the CSF.

Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054.

Background: Pathological and genetic evidence implicates toxic effects of aggregated α-synuclein in the pathophysiology of neuronal dysfunction and degeneration in Parkinson's disease. Immunotherapy targeting aggregated α-synuclein is a promising strategy for delaying disease progression.

Objective: This study (NCT02459886) evaluated the safety, tolerability, and pharmacokinetics of BIIB054, a human-derived monoclonal antibody that preferentially binds to aggregated α-synuclein, in healthy volunteers and participants with Parkinson's disease.

Deep Brain Stimulation Generator Replacement in End-Stage Parkinson Disease.

Background: The decision to replace deep brain stimulation (DBS) generators in end-stage Parkinson disease (PD) is based on the patients' clinical status and the risks of this surgery. The infection rates of initial DBS implantation surgery and generator replacement surgery are well established. But the risks of DBS generator replacement for the severely disabled end-stage PD patient have not been described.

Implementing Levodopa-Carbidopa Intestinal Gel for Parkinson Disease: Insights from US Practitioners.

Background: Levodopa-carbidopa intestinal gel (LCIG, designated in the United States as carbidopa-levodopa enteral suspension, CLES) was approved in the United States in 2015 for the treatment of refractory motor fluctuations in individuals with Parkinson disease (PD). Many neurologists in the United States have not had personal experience with implementation and management of the unique delivery system for this treatment.

Methods And Findings: This educational review was developed to provide practitioners with an understanding of LCIG use from the clinician's point of view.

National randomized controlled trial of virtual house calls for Parkinson disease.

Objective: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable.

Methods: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale.

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers.

Background: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited.

Materials And Methods: Connect.

Post-traumatic shoulder movement disorders: A challenging differential diagnosis between organic and functional.

Peripheral trauma may be a trigger for the development of various movement disorders though the pathophysiology remains controversial and some of these patients have a functional (psychogenic) disorder. We report 3 cases of shoulder movement disorders following trauma to the shoulder region. Physiology was done in all the patients to extend the physical examination.

The past, present, and future of telemedicine for Parkinson's disease.

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD.

Are high doses of carbidopa a concern? A randomized, clinical trial in Parkinson's disease.

Recommended doses of carbidopa are 75-200 mg/day. Higher doses could inhibit brain aromatic amino-acid decarboxylase and reduce clinical effects. We compared 4-week outpatient treatments with carbidopa (75 and 450 mg/day) administered with L-dopa on the subjects' normal schedule.