Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose-Driven Approach.

The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

Background: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy.

Summary: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level.

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

Background: Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety.

Objective: The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI).

Psychotropic medication use in Huntington's disease: A retrospective cohort study.

Background: Whereas the treatment of motor symptoms in Huntington's disease (HD) receives much attention, less is known about the treatment of neuropsychiatric symptoms.

Objective: We aim to give an overview of psychotropic drug use in the treatment of neuropsychiatric symptoms across disease stages in HD.

Methods: We conducted a descriptive cross-sectional study of psychotropic drug prescriptions in a large longitudinal database of HD patients, Enroll HD.

Machine learning-based prediction of cognitive outcomes in de novo Parkinson's disease.

Cognitive impairment is a debilitating symptom in Parkinson's disease (PD). We aimed to establish an accurate multivariate machine learning (ML) model to predict cognitive outcome in newly diagnosed PD cases from the Parkinson's Progression Markers Initiative (PPMI). Annual cognitive assessments over an 8-year time span were used to define two cognitive outcomes of (i) cognitive impairment, and (ii) dementia conversion.

Brain network characteristics and cognitive performance in motor subtypes of Parkinson's disease: A resting state fMRI study.

Introduction: Parkinson's disease (PD) is a heterogeneous disorder with great variability in motor and non-motor manifestations. It is hypothesized that different motor subtypes are characterized by different neuropsychiatric and cognitive symptoms, but the underlying correlates in cerebral connectivity remain unknown. Our aim is to compare brain network connectivity between the postural instability and gait disorder (PIGD) and tremor-dominant (TD) subtypes, using both a within- and between-network analysis.

Network analysis in Gamma Knife capsulotomy for intractable obsessive-compulsive disorder.

Introduction: Gamma-knife Ventral Capsulotomy (GVC) has been suggested as an efficacious treatment for a subset of patients with treatment refractory obsessive compulsive disorder (OCD).

Research Question: The goal of this study was to investigate neural correlates of GVC and investigate the predictive value of white matter tracts that are known to be associated with clinical outcome to Deep Brain Stimulation (DBS).

Material And Methods: MR images of 8 treatment-refractory OCD patients with a minimum follow-up of 3-years who underwent GVC were used to correlate lesion characteristics with symptom improvement.

Phenomenology of Atypical Anxiety Disorders in Parkinson's Disease: A Systematic Review.

Objective: Anxiety is a prominent concern in Parkinson's disease (PD) that negatively impacts quality of life, increases functional disability, and complicates clinical management. Atypical presentations of anxiety are under-recognized and inadequately treated in patients with PD, compromising global PD care.

Methods: This systematic review focuses on the prevalence, symptomology and clinical correlates of atypical presentations of PD-related anxiety following PRISMA guidelines.

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience.

Introduction: Although deep brain stimulation (DBS) is effective for treating a number of neurological and psychiatric indications, surgical and hardware-related adverse events (AEs) can occur that affect quality of life. This study aimed to give an overview of the nature and frequency of those AEs in our center and to describe the way they were managed. Furthermore, an attempt was made at identifying possible risk factors for AEs to inform possible future preventive measures.

Cognitive Outcome After Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: A Systematic Review.

Introduction: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects, and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s).

Background: This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s).

A neural network for tics: insights from causal brain lesions and deep brain stimulation.

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed 'lesion network mapping' to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain.

Resting-State Functional Connectivity in Frontostriatal and Posterior Cortical Subtypes in Parkinson's Disease-Mild Cognitive Impairment.

Background: The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits.

Objective: The aim was to identify resting-state functional modifications associated with these subtypes.

Methods: Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available.

Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms.

Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson's Disease.

: Cognitive impairments are common in patients with Parkinson's disease (PD) and are heterogeneous in their presentation. The "dual syndrome hypothesis" suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia.

When is lack of scientific integrity a reason for retracting a paper? A case study.

Objective: The journal received a request to retract a paper reporting the results of a triple-blind randomized placebo-controlled trial. The present and immmediate past editors expand on the journal's decision not to retract this paper in spite of undisputable evidence of scientific misconduct on behalf of one of the investigators.

Methods: The editors present an ethical reflection on the request to retract this randomized clinical trial with consideration of relevant guidelines from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE) applied to the unique contextual issues of this case.

Parkinson's Disease Subtypes: Critical Appraisal and Recommendations.

Background: In Parkinson's disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice.

Cognitive Behavioral Therapy for Anxiety in Parkinson's Disease: A Randomized Controlled Trial.

Background: Anxiety disorders are among the most prevalent and disabling neuropsychiatric syndromes in patients with Parkinson's disease (PD), but no randomized controlled treatment trials of anxiety have been published to date.

Objective: The aim of this study was to assess the effectiveness of cognitive behavioral therapy (CBT) in the treatment of anxiety in patients with PD.

Methods: Forty-eight patients with PD with anxiety were randomized 1:1 between CBT and clinical monitoring only (CMO).

Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome.

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients' symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes.

Brainstem Pathologies Correlate With Depression and Psychosis in Parkinson's Disease.

Background: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g.