A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial.

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial.

Parkinson's, where are we heading?

The prevalence of Parkinson's disease has rapidly increased over the last decade. This editorial discusses our current understanding of the pathophysiological basis for the condition, with a particular focus on the potential role of α-synuclein, and the consequent implications this has for both the development of new investigations and disease-modifying therapies. Specifically, the article discusses the development of a new diagnostic test for cerebrospinal fluid α-synuclein, the development of a new staging system for Parkinson's disease, which takes into account the α-synuclein, genetic and neuro-imaging status, and the results of two recently completed clinical trials, using monoclonal antibodies wherein α-synuclein is the principal target.

A Pragmatic Review on Spinal Cord Stimulation Therapy for Parkinson's Disease Gait Related Disorders: Gaps and Controversies.

Background: Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS.

The degeneration of locus coeruleus occurring during Alzheimer's disease clinical progression: a neuroimaging follow-up investigation.

The noradrenergic nucleus Locus Coeruleus (LC) is precociously involved in Alzheimer's Disease (AD) pathology, and its degeneration progresses during the course of the disease. Using Magnetic Resonance Imaging (MRI), researchers showed also in vivo in patients the disruption of LC, which can be observed both in Mild Cognitively Impaired individuals and AD demented patients. In this study, we report the results of a follow-up neuroradiological assessment, in which we evaluated the LC degeneration overtime in a group of cognitively impaired patients, submitted to MRI both at baseline and at the end of a 2.

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression.

Hypothalamic involvement in multiple system atrophy: A structural MRI study.

Objective: To investigate hypothalamic atrophy and its clinical correlates in multiple system atrophy (MSA) in-vivo.

Background: MSA is characterized by autonomic dysfunction and parkinsonian/cerebellar manifestations. The hypothalamus regulates autonomic and homeostatic functions and is also involved in memory and learning processes.

Frequency and outcomes of gastrostomy insertion in a longitudinal cohort study of atypical parkinsonism.

Background: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) show a high prevalence and rapid progression of dysphagia, which is associated with reduced survival. Despite this, the evidence base for gastrostomy is poor, and the optimal frequency and outcomes of this intervention are not known. We aimed to characterise the prevalence and outcomes of gastrostomy in patients with these three atypical parkinsonian disorders.

Developing a novel dual-injection FDG-PET imaging methodology to study the functional neuroanatomy of gait.

Gait is an excellent indicator of physical, emotional, and mental health. Previous studies have shown that gait impairments in ageing are common, but the neural basis of these impairments are unclear. Existing methodologies are suboptimal and novel paradigms capable of capturing neural activation related to real walking are needed.

Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials.

Background: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients.

Objectives: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years.

Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures.

Effects of an Exercise Program to Reduce Falls in Older People Living in Long-Term Care: A Randomized Controlled Trial.

Objectives: To investigate the effect of an exercise program on falls in intermediate and high-level long-term care (LTC) residents and to determine whether adherence, physical capacity, and cognition modified outcomes.

Design: Randomized controlled trial.

Setting And Participants: Residents (n = 520, aged 84 ± 8 years) from 25 LTC facilities in New Zealand.

Prevalence and severity of freezing of gait in a Danish cohort of people with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a widespread neurodegenerative disorder characterised by wide range of symptoms. Freezing of gait (FoG), a transient feeling that the patient's feet are nailed to the floor, resulting in an inability to move, is a particularly distressful symptom. The assessment of FoG can be challenging.

The Clinical Profile of Tremor in Parkinson's Disease.

Background: Tremor is one of the most troublesome manifestations of Parkinson's Disease (PD) and its response to dopaminergic medication is variable; an evidence-based framework of PD tremor is lacking yet needed to inform future investigations.

Objective: To perform a comprehensive longitudinal analysis on the clinical characteristics, course and response to dopaminergic medication of tremor in de-novo PD.

Methods: Three hundred ninety-seven participants were recruited in the Parkinson Progressive Markers Initiative, a prospective observational cohort study in early de-novo PD.

Exploring mobility dysfunction in people with and without impaired cognition in Parkinson disease.

Introduction: The relationship between mobility and cognition has been studied in the aging population and associations have been also reported in people with Parkinson's disease (PD).

Objective: To compare different aspects of gait and balance between individuals with PD who have normal cognition and those with impaired cognition, using both clinical and instrumented measures.

Methods: One-hundred forty-three participants with PD were divided into two groups: 1) normal cognition (n = 71) and 2) impaired cognition (n = 72) based on the Montreal Cognitive Assessment (MoCA) cut-off.

Lower back muscle activity during weight-shifting is affected by ageing and dual-tasking.

Purpose: Postural control deteriorates with age, especially under dual-task conditions. It is currently unknown how a challenging virtual reality weight-shifting task affects lower back muscle activity. Hence, this study investigated erector spinae neuromuscular control during mediolateral weight-shifting as part of an exergame during single- (ST) and dual-task (DT) conditions in young and older adults.

Different Patterns of Locus Coeruleus MRI Alteration in Alzheimer's and Dementia with Lewy Bodies.

Background: The integrity of Locus Coeruleus can be evaluated in vivo using specific Magnetic Resonance Imaging sequences. While this nucleus has been shown to be degenerated both in post-mortem and in vivo studies in Alzheimer's Disease, for other neurodegenerative dementias such as Dementia with Lewy Bodies this has only been shown ex-vivo.

Objective: To evaluate the integrity of the Locus Coeruleus through Magnetic Resonance Imaging in patients suffering from Dementia with Lewy Bodies and explore the possible differences with the Locus Coeruleus alterations occurring in Alzheimer's Dementia.

Corrigendum: The longitudinal progression of autonomic dysfunction in Parkinson's disease: a 7-year study.

[This corrects the article DOI: 10.3389/fneur.2023.

Capturing patient experience.

Patient experience is a crucial measure of the quality of patient care in healthcare settings. It encompasses all the patient's interactions with staff and their exposure to equipment, procedures, environment and service structure during one care episode. Capturing patient experience is one way of ensuring that patients' voices are heard and can form the basis of an audit or service improvement project designed to evaluate or enhance the patient-centredness of care.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Background: Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated.

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials.

The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months.

Safety and tolerability of adjunct non-invasive vagus nerve stimulation in people with parkinson's: a study protocol.

Background: Parkinson's disease (PD) is the fastest growing neurological condition worldwide. Recent theories suggest that symptoms of PD may arise due to spread of Lewy-body pathology where the process begins in the gut and propagate transynaptically via the vagus nerve to the central nervous system. In PD, gait impairments are common motor manifestations that are progressive and can appear early in the disease course.

DBS in tremor with dystonia: VIM, GPi or both? A review of the literature and considerations from a single-center experience.

Background: Deep brain stimulation (DBS) is an established treatment for dystonia and tremor. However, there is no consensus about the best surgical targeting strategy in patients with concomitant tremor and dystonia. Both the thalamic ventral intermediate nucleus (VIM) and the globus pallidus pars interna (GPi) have been proposed as targets.

Trial of Deferiprone in Parkinson's Disease.

Background: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.

Methods: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa.