Continuous, subcutaneous apomorphine infusion for Parkinson disease motor fluctuations: Results from the phase 3, long-term, open-label United States InfusON study.

Background: Continuous subcutaneous apomorphine infusion (CSAI) has been used globally since the 1980s for Parkinson disease (PD) motor fluctuations but has not been available in the United States (US).

Objective: Evaluate CSAI for motor fluctuations in the US setting.

Methods: This open-label study (NCT02339064) enrolled patients with PD experiencing ≥3 hours (h) daily OFF time despite optimized levodopa and current/prior use of at least one other adjunctive therapy.

Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson's disease experiencing OFF episodes: A modified Delphi panel.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment.

Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets.

Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.

BoNT clinical trial update: Sialorrhea.

Sialorrhea is the excessive accumulation of saliva, a prevalent symptom among a number of neurologic conditions in both pediatric and adult patients. Over the years, the management of sialorrhea has evolved and included a variety of interventions, ranging from nonpharmacologic, pharmacologic, and surgical treatment options. The most common option for treatment has been the use of botulinum toxin injections in the management of sialorrhea.

Should "on-demand" treatments for Parkinson's disease OFF episodes be used earlier?

We discuss a shift in the treatment paradigm for OFF episode management in patients with Parkinson's disease, based on clinical experience in the United States (US). Three "on-demand" treatments are currently available in the US as follows: subcutaneous apomorphine, levodopa inhalation powder, and sublingual apomorphine. We empirically propose that "on-demand" treatments can be utilized as a complementary treatment when OFF episodes emerge and can be utilized when needed rather than reserving these treatments only until other treatment approaches (adjustment of baseline treatment and/or addition of adjunctive treatment with "ON-extenders") have failed.

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients.

Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor.

Tears - more to them than meets the eye: why tears are a good source of biomarkers in Parkinson's disease.

Tears are a known source of biomarkers for both ocular and systemic diseases with particular advantages; specifically, the noninvasiveness of sample collection and a unique and increasingly better-defined protein composition. Here, we discuss our rationale for use of tears for discovery of biomarkers for Parkinson's disease (PD). These reasons include literature supporting changes in tear flow and composition in PD, and the interconnections between the ocular surface system and neurons affected in PD.

Levels of oligomeric α-Synuclein in reflex tears distinguish Parkinson's disease patients from healthy controls.

Due to active engagement of sensory and afferent nerve fibers in reflex tearing which could be affected in Parkinson's disease (PD), we tested reflex tears as a source of potential PD biomarkers. Reflex tears collected from 84 PD and 84 age- and sex-equivalent healthy controls (HC) were used to measure levels of oligomeric α-Syn (α-Syn), total α-Syn (α-Syn), CCL2, DJ-1, lactoferrin and MMP9. α-syn (p < 0.

Oligomeric α-synuclein is increased in basal tears of Parkinson's patients.

Secretion of proteins into basal tears of Parkinson's disease (PD) patients may be altered by changes in nerve function. Oligomeric α-Syn and total α-Syn, CCL-2, DJ-1, LF and MMP-9 were measured in basal tears from 93 PD patients and 82 age- and sex-equivalent healthy controls. α-Syn was decreased (p = 0.

Targeting neurons in the gastrointestinal tract to treat Parkinson's disease.

Background: Parkinson's disease (PD) is associated with α-synuclein (αS) aggregation within the enteric nervous system (ENS) and constipation. Squalamine displaces proteins that are electrostatically bound to intracellular membranes and through this mechanism suppresses aggregation of αS monomers into neurotoxic oligomers.

Objective: We sought to evaluate the safety of ENT-01 oral tablets (a synthetic squalamine salt), its pharmacokinetics, and its effect on bowel function in PD patients with constipation.

Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial.

Background: Patients with Parkinson's disease chronically treated with levodopa commonly have delayed or unpredictable onset of its benefits after oral intake. In this study, we assessed the safety and efficacy of CVT-301, a self-administered levodopa oral inhalation powder, for the treatment of patients with Parkinson's disease during off periods.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, patients were recruited at 65 sites in Canada, Poland, Spain, and the USA.

Use of botulinum toxin in Parkinson's disease.

Botulinum toxin has emerged as an important therapeutic intervention within the realm of movement disorders, especially for focal and generalized dystonias. Botulinum toxin has additionally been used for a variety of symptoms associated with parkinsonism. In this review, we will specifically evaluate use of botulinum toxin in idiopathic Parkinson's disease.

Long-term safety and efficacy of levodopa-carbidopa intestinal gel in advanced Parkinson's disease.

Background: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program.

Methods: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673).

RimabotulinumtoxinB in sialorrhea: systematic review of clinical trials.

Objective: The aim of this study was to examine the efficacy, safety and dosing practices of rimabotulinumtoxinB (BoNT-B) for the treatment of patients with sialorrhea based on a systematic review of clinical trials.

Methods: A systematic literature review was performed to identify randomized controlled trials and other comparative clinical studies of BoNT-B for the treatment of sialorrhea published in English between January 1999 and December 2015. Medical literature databases (PubMed, Cochrane Library, and EMBASE) were searched and a total of 41 records were identified.

Multicenter observational study of abobotulinumtoxinA neurotoxin in cervical dystonia: The ANCHOR-CD registry.

Background: The ANCHOR-CD prospective observational registry study evaluated the effectiveness of abobotulinumtoxinA in adult idiopathic cervical dystonia (CD) in clinical practice.

Methods: Adults with CD were eligible. Treating physicians determined abobotulinumtoxinA dose and treatment interval.

A randomized trial of a low-dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease.

Background: Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo-controlled study to determine whether 2 doses of a novel slow-release, low-dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD.

Methods: Previously untreated patients with early PD were randomized (1:1:1) to once-daily treatment with P2B001 (0.