Co-stimulating the left vmPFC compensates for apathy after levodopa withdrawal in Parkinson's patients with STN DBS.

Introduction: Subthalamic nucleus deep brain stimulation (STN DBS) improves motor symptoms of Parkinson's disease (PD), but its effect on motivation is controversial. Apathy, the lack of motivation, commonly occurs in PD and is often exacerbated after surgery and its concomitant levodopa reduction. Apathy and reward processing are associated with the ventromedial prefrontal cortex (vmPFC), which standard targeting strategies avoid by targeting the dorsolateral STN.

Current and future applications of local field potential-guided programming for Parkinson's disease with the Percept™ rechargeable neurostimulator.

Deep brain stimulation (DBS) has been established as an effective neuromodulatory treatment for Parkinson's disease (PD) with motor complications or refractory tremor. Various DBS devices with unique technology platforms are commercially available and deliver continuous, open-loop stimulation. The Percept™ family of neurostimulators use BrainSense™ technology with five key features to sense local field potentials while stimulating, enabling integration of physiologic data into the routine practice of DBS programming.

Response to letter to the editor regarding "Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries".

The 5-2-1 criteria was developed to facilitate the identification and referral of patients with Parkinson's Disease (PD) inadequately controlled by oral medications. The criterion was not developed to screen patients with PD for device-aided therapy eligibility. The robust design and validation of the 5-2-1 criteria minimizes over or inappropriate referrals, and supports physicians in the timely identification of patients with PD who may warrant further evaluation for treatment optimization.

Multi-Shared-Task Self-Supervised CNN-LSTM for Monitoring Free-Body Movement UPDRS-III Using Wearable Sensors.

The Unified Parkinson's Disease Rating Scale (UPDRS) is used to recognize patients with Parkinson's disease (PD) and rate its severity. The rating is crucial for disease progression monitoring and treatment adjustment. This study aims to advance the capabilities of PD management by developing an innovative framework that integrates deep learning with wearable sensor technology to enhance the precision of UPDRS assessments.

Deutetrabenazine Provides Long-Term Benefit for Tardive Dyskinesia Regardless of Underlying Condition and Dopamine Receptor Antagonist Use: A Post Hoc Analysis of the 3-Year, Open-Label Extension Study.

Background: Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.

Methods: Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794).

Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.

Introduction: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted.

Methods: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD).

Safety and Efficacy of Long-Term Deutetrabenazine Use in Children and Adolescents with Tics Associated with Tourette Syndrome: An Open-Label Extension Study.

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics.

Objective: To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS.

Methods: Alternatives for Reducing Tics in TS (ARTISTS) open-label extension (OLE) (NCT03567291) was a 54-week, global, phase 3, open-label extension study of deutetrabenazine (6-48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2-week randomized withdrawal period.

Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum: Revelations from the MANAGE-PD validation cohort.

Introduction: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories.

Special Challenges in Pediatric Drug Development: First of Three Sets of Expanded Proceedings from the ISCTM Autumn Conference on Pediatric Drug Development.

This paper expands upon a session, entitled, "Special Challenges in Pediatric Drug Development," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Drug development in this age group is particularly important because many illnesses have their onset in this age group, many other illnesses that are more common in adults also occur in this time period, and many rare conditions that require special consideration (i.e.

White matter connectivity of subthalamic nucleus and globus pallidus interna targets for deep brain stimulation.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking.

Interactive mobile application for Parkinson's disease deep brain stimulation (MAP DBS): An open-label, multicenter, randomized, controlled clinical trial.

Introduction: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming.

Methods: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming.

Effective Management of "OFF" Episodes in Parkinson's Disease: Emerging Treatment Strategies and Unmet Clinical Needs.

Motor complications related to the chronic administration of levodopa and failure to prevent the neurodegenerative disease process counterbalance the pivotal discovery of levodopa as the cornerstone of PD treatment. Excellent motor control is offered early during the course of treatment, but this diminishes as pathological changes in the striatum lead to synaptic dopamine levels becoming completely dependent on exogenous dopamine. This non-physiologic stimulation of dopamine receptors eventually manifests as OFF episodes.

Dyskinesia Estimation of Imbalanced Data Using a Deep-Learning Model.

The collection of Parkinson's Disease (PD) time-series data usually results in imbalanced and incomplete datasets due to the geometric distribution of PD complications' sever-ity scores. Consequently, when training deep convolutional models on these datasets, the models suffer from overfitting and lack generalizability to unseen data. In this paper, we investigated a new framework of Conditional Generative Ad-versarial Netuwoks (cGANs) as a solution to improve the extrapolation and generalizability of the regression models in such datasets.

Activity Recognition in Parkinson's Patients from Motion Data Using a CNN Model Trained by Healthy Subjects.

Physical activity recognition in patients with Parkinson's Disease (PwPD) is challenging due to the lack of large-enough and good quality motion data for PwPD. A common approach to this obstacle involves the use of models trained on better quality data from healthy patients. Models can struggle to generalize across these domains due to motor complications affecting the movement patterns in PwPD and differences in sensor axes orientations between data.

Is essential tremor a disorder of GABA dysfunction? No.

Although essential tremor is common, its underlying pathophysiology remains uncertain, and several hypotheses seek to explain the tremor mechanism. The GABA hypothesis states that disinhibition of deep cerebellar neurons due to reduced GABAergic input from Purkinje cells results in increased pacemaker activity, leading to rhythmic output to the thalamo-cortical circuit and resulting in tremor. However, some neuroimaging, spectroscopy, and pathology studies have not shown a clear or consistent GABA deficiency in essential tremor, and animal models have indicated that large reductions of Purkinje cell inhibition may improve tremor.

Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study.

Background: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.

Trends in the Utilization of Teleneurology and Other Healthcare Resources Prior to and During the COVID-19 Pandemic in an Urban, Tertiary Health System.

Background: Patient groups traditionally affected by health disparities were less likely to use video teleneurology (TN) care during the initial COVID-19 pandemic surge in the United States. Whether this asymmetry persisted later in the pandemic or was accompanied with a loss of access to care remains unknown.

Methods: We conducted a retrospective cohort study using patient data from a multicenter healthcare system in New York City.

Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries.

Background: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD.

Neurologists' Attitudes Toward Use and Timing of Deep Brain Stimulation.

Objective: We sought to explore current perspectives and attitudes of general neurologists and movement disorder specialists toward deep brain stimulation (DBS) for Parkinson disease (PD), focusing on perspectives on its earlier use in the clinical course of the disease.

Methods: We designed a 30-question online survey comprised of Likert-type, multiple choice, and rank-order questions, which was distributed to 932 neurologist members of the American Academy of Neurology. We analyzed clinicians' sociodemographic information, treatment patterns used for patients with PD, reasons for and against patient referral for DBS, and general attitudes toward DBS.

Validation and clinical value of the MANAGE-PD tool: A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications.

Introduction: Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) is a clinician-reported tool designed to facilitate timely identification and management of patients with advancing Parkinson's disease (PD) with suboptimal symptom control while on standard therapy. The objective of this study was to evaluate the validity and clinical value of the tool.

Methods: Driven by structured inputs from a steering committee and panel of PD experts, the tool was developed to classify patients into 3 categories.