A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders: A Consensus Statement.

Purpose Of Review: The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP).

Safety and Efficacy of IPX203 in Parkinson's Disease: The RISE-PD Open-Label Extension Study.

Background: IPX203 is a novel oral extended-release formulation of carbidopa/levodopa (CD/LD) developed to address the short half-life of immediate-release CD/LD. In the phase 3 RISE-PD trial, IPX203 significantly improved "Good On" time in patients with Parkinson's disease compared with immediate-release CD/LD.

Objectives: To evaluate the safety and efficacy of IPX203 in an open-label extension of the pivotal phase 3 study.

Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial.

Background: Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease.

Methods: We report a 36-week, randomised, double-blind, placebo-controlled study of NLY01 in participants with early untreated Parkinson's disease conducted at 58 movement disorder clinics in the USA.

A Randomized Phase 3 Study Comparing P2B001 to its Components (Low-Dose Extended-Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended-Release Pramipexole in Early Parkinson's Disease.

Background: There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.

Objectives: The objective was to determine if P2B001 (a fixed, low-dose, extended-release [ER] combination of pramipexole 0.6 mg and rasagiline 0.

Impedance trend from a symptomatic perielectrode cystic cavity following deep brain stimulation: illustrative case.

Background: Deep brain stimulation (DBS) is a well-established neurosurgical intervention for a growing number of neurological and psychiatric diseases. Patients who are affected by Parkinson's disease may benefit from DBS of either the subthalamic nucleus or the globus pallidus internus. Patients who undergo DBS often notice a significant reduction in their clinical symptoms; however, the procedure is not without risks.

Improving levodopa delivery: IPX203, a novel extended-release carbidopa-levodopa formulation.

Introduction: IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson's disease (PD) patients.

Methods: IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations.

Clinical Efficacy and Dosing of Vibrotactile Coordinated Reset Stimulation in Motor and Non-motor Symptoms of Parkinson's Disease: A Study Protocol.

Enhanced neuronal synchronization of the subthalamic nucleus (STN) is commonly found in PD patients and corresponds to decreased motor ability. Coordinated reset (CR) was developed to decouple synchronized states causing long lasting desynchronization of neural networks. Vibrotactile CR stimulation (vCR) was developed as non-invasive therapeutic that delivers gentle vibrations to the fingertips.

Olfactory Deficits in the Freezing of Gait Phenotype of Parkinson's Disease.

Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures. To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait.

Best Practices in the Clinical Management of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Consensus Statement of the CurePSP Centers of Care.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS; the most common phenotype of corticobasal degeneration) are tauopathies with a relentless course, usually starting in the mid-60s and leading to death after an average of 7 years. There is as yet no specific or disease-modifying treatment. Clinical deficits in PSP are numerous, involve the entire neuraxis, and present as several discrete phenotypes.

Electrophysiologic Mapping for Target Acquisition in Deep Brain Stimulation May Become Unnecessary in the Era of Intraoperative Imaging.

Objective: Electrophysiologic mapping (EM) has been instrumental in advancing neuroscience and ensuring accurate lead placement for deep brain stimulation. However, EM is associated with increased operative time, expense, and potential risk. Intraoperative imaging to verify lead placement provides an opportunity to reassess the clinical role of EM.

Coordinated Reset Vibrotactile Stimulation Induces Sustained Cumulative Benefits in Parkinson's Disease.

Background: Abnormal synchronization of neuronal activity in dopaminergic circuits is related to motor impairment in Parkinson's disease (PD). Vibrotactile coordinated reset (vCR) fingertip stimulation aims to counteract excessive synchronization and induce sustained unlearning of pathologic synaptic connectivity and neuronal synchrony. Here, we report two clinical feasibility studies that examine the effect of regular and noisy vCR stimulation on PD motor symptoms.

Utility of objective gait measures in levodopa-unresponsive freezing in Parkinson's.

Levodopa-unresponsive gait freezing in Parkinson disease is debilitating. Gait kinematics, while time-consuming, can help optimize levodopa's benefit on gait stride length and stride velocity, and thereby improve freezing and falls in these patients.

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.

Inhaled levodopa in Parkinson's disease patients with OFF periods: A randomized 12-month pulmonary safety study.

Introduction: CVT-301 is an orally inhaled levodopa therapy approved for the intermittent treatment of OFF episodes in Parkinson's disease patients who are taking a standard oral levodopa regimen. This open-label, randomized, controlled study over 12 months characterizes the safety, including pulmonary safety, of CVT-301 84 mg (nominal respirable levodopa fine-particle dose, 50 mg).

Methods: Patients experiencing motor fluctuations were randomized 2:1 to CVT-301 or an observational cohort (OC) receiving oral standard of care.

An Acute Randomized Controlled Trial of Noninvasive Peripheral Nerve Stimulation in Essential Tremor.

Objective: To evaluate the safety and effectiveness of a wrist-worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in-office session.

Methods: This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40-minute stimulation session.

Dosing Patterns during Conversion to IPX066, Extended-Release Carbidopa-Levodopa (ER CD-LD), in Parkinson's Disease with Motor Fluctuations.

Background: IPX066 is an extended-release (ER) oral formulation of carbidopa-levodopa (CD-LD). Following an initial peak at about one hour, plasma LD concentrations are maintained for about 4-5 hours.

Objective: To present dosing factors that may affect the successful conversion to ER CD-LD from other LD formulations.

Qualitative Evaluation of the Personal KinetiGraphTM Movement Recording System in a Parkinson's Clinic.

Background: Wearable sensors provide accurate, continuous objective measurements, quantifying the variable motor states of patients with Parkinson's disease (PD) in real time.

Objectives: To evaluate the impact of using continuous objective measurement using the Personal KinetiGraph™ (PKG®) Movement Recording System in the routine clinical care of patients with PD (PwP).

Methods: Physicians employed the use of the PKG in patients for whom they were seeking objective measurement.

Procedural Variables Influencing Stereotactic Accuracy and Efficiency in Deep Brain Stimulation Surgery.

Background: Deep brain stimulation (DBS) is well-established, evidence-based therapy for Parkinson disease, essential tremor, and primary dystonia. Clinical outcome studies have recently shown that "asleep" DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional "awake" DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency.

Objective: To identify procedural variables in DBS surgery associated with improved surgical efficiency and stereotactic accuracy.

Clinical outcomes following awake and asleep deep brain stimulation for Parkinson disease.

Objective: Recent studies have shown similar clinical outcomes between Parkinson disease (PD) patients treated with deep brain stimulation (DBS) under general anesthesia without microelectrode recording (MER), so-called “asleep” DBS, and historical cohorts undergoing “awake” DBS with MER guidance. However, few studies include internal controls. This study aims to compare clinical outcomes after globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS using awake and asleep techniques at a single institution.

Association of metabolic syndrome and change in Unified Parkinson's Disease Rating Scale scores.

Objective: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).

Methods: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III.

Downward finger displacement distinguishes Parkinson disease dementia from Alzheimer disease.

Unlabelled: Purpose/Aim of the study: To study finger displacement in patients with Parkinson disease dementia (PDD) and in patients with Alzheimer disease (AD).

Methods: We examined 56 patients with PDD and 35 with AD. Patients were examined during their regular outpatient clinic visit.

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.

Awake versus asleep deep brain stimulation for Parkinson's disease: a critical comparison and meta-analysis.

Objective: No definitive comparative studies of the efficacy of 'awake' deep brain stimulation (DBS) for Parkinson's disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques.

Methods: We conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up.

Optimizing extended-release carbidopa/levodopa in Parkinson disease: Consensus on conversion from standard therapy.

Purpose Of Review: To help clinicians optimize the conversion of a patient's Parkinson disease pharmacotherapy from immediate-release carbidopa/levodopa (IR CD/LD) to an extended-release formulation (ER CD/LD).

Recent Findings: Eleven movement disorders specialists achieved consensus positions on the modification of trial-based conversion guidelines to suit individual patients in clinical practice.

Summary: Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected.