Long-Term Outcomes of Deep Brain Stimulation for Pediatric Dystonia.

Background: Deep brain stimulation (DBS) has been utilized for over two decades to treat medication-refractory dystonia in children. Short-term benefit has been demonstrated for inherited, isolated, and idiopathic cases, with less efficacy in heredodegenerative and acquired dystonia. The ongoing publication of long-term outcomes warrants a critical assessment of available information as pediatric patients are expected to live most of their lives with these implants.

Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.

Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson's disease. However, non-motor symptoms of Parkinson's disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson's disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation.

The role of the locus coeruleus/norepinephrine system in the pathogenesis of neurodegenerative disorders: An update.

Purpose Of Review: The aim of this review was to provide an update on current and emerging knowledge of the neuropathological processes affecting the locus coeruleus/norepinephrine (LC/NE) system, their effect on Alzheimer's disease and Parkinson's disease symptomatology, including efforts to translate these notions into therapeutic actions targeting the noradrenergic system.

Recent Findings: Over the past 2 years, work from multiple groups has contributed to support an early role of locus coeruleus degeneration and/or hyperactivation in the neurodegenerative process, including a trigger of neuroinflammation. Imaging advances are allowing the quantification of locus coeruleus structural features in vivo, which is critical in the early stages of disease.

Three-dimensional simultaneous brain mapping of T1, T2, and magnetic susceptibility with MR Multitasking.

Purpose: To develop a new technique that enables simultaneous quantification of whole-brain T , T , , as well as susceptibility and synthesis of six contrast-weighted images in a single 9.1-minute scan.

Methods: The technique uses hybrid T -prepared inversion-recovery pulse modules and multi-echo gradient-echo readouts to collect k-space data with various T1, T2, and weightings.

Short- and Long-Term Effects of DBS on Gait in Parkinson's Disease.

The aim was to compare the short and long-term effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait dysfunction and other cardinal symptoms of Parkinson's disease (PD). Two groups of patients were studied. The first group (short-term DBS, = 8) included patients recently implanted with STN DBS (mean time since DBS 15.

Stimulation of the Subthalamic Nucleus Changes Cortical-Subcortical Blood Flow Patterns During Speech: A Positron Emission Tomography Study.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD) but can have an adverse effect on speech. In normal speakers and in those with spinocerebellar ataxia, an inverse relationship between regional cerebral blood flow (rCBF) in the left inferior frontal (IFG) region and the right caudate (CAU) is associated with speech rate. This pattern was examined to determine if it was present in PD, and if so, whether it was altered by STN-DBS.

Steering the Volume of Tissue Activated With a Directional Deep Brain Stimulation Lead in the Globus Pallidus Pars Interna: A Modeling Study With Heterogeneous Tissue Properties.

To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi). Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS.

Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson's disease (INTREPID): a multicentre, double-blind, randomised, sham-controlled study.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease.

Methods: This trial took place at 23 implanting centres in the USA.

Differential response to pallidal deep brain stimulation among monogenic dystonias: systematic review and meta-analysis.

Objective: Genetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common monogenic dystonias.

Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines.

iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates.

Young-onset Parkinson's disease (YOPD), defined by onset at <50 years, accounts for approximately 10% of all Parkinson's disease cases and, while some cases are associated with known genetic mutations, most are not. Here induced pluripotent stem cells were generated from control individuals and from patients with YOPD with no known mutations. Following differentiation into cultures containing dopamine neurons, induced pluripotent stem cells from patients with YOPD showed increased accumulation of soluble α-synuclein protein and phosphorylated protein kinase Cα, as well as reduced abundance of lysosomal membrane proteins such as LAMP1.

Speech Intelligibility During Clinical and Low Frequency.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson's disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results.

The role of Personal KinetiGraph™ fluctuator score in quantifying the progression of motor fluctuations in Parkinson's disease.

Motor fluctuations (MF) are important determinants of quality of life in Parkinson's disease (PD). To determine whether the Personal Kineti Graph (PKG), a wearable motion tracking device, can define MF progression, we correlated PKG fluctuator scores (FS) with clinical motor fluctuator profiles in a case-control cohort study. 54 subjects completed a 6-day PKG trial and completed a standardized motor diary.

Sustained quality-of-life improvements over 10 years after deep brain stimulation for dystonia.

Background: Little is known about the quality of life of people with dystonia and DBS beyond 5 years. The objectives of this study were (1) to examine the long-term quality-of-life outcomes in a large cohort of people with dystonia and DBS, (2) to determine the incidence of stimulation-induced parkinsonism, and (3) to elucidate the potential long-term cognitive impact of DBS in this cohort.

Methods: Fifty-four subjects with dystonia and DBS for more than 5 years were contacted via social media and were offered to complete a quality-of-life survey comparing current-day life and life prior to DBS.

Novelty-Sensitive Dopaminergic Neurons in the Human Substantia Nigra Predict Success of Declarative Memory Formation.

The encoding of information into long-term declarative memory is facilitated by dopamine. This process depends on hippocampal novelty signals, but it remains unknown how midbrain dopaminergic neurons are modulated by declarative-memory-based information. We recorded individual substantia nigra (SN) neurons and cortical field potentials in human patients performing a recognition memory task.

High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson's Disease.

Background: Reduced glucose tolerance has been long recognized as a potential risk factor for Parkinson's disease (PD), and increasing scrutiny is currently being placed on insulin resistance (IR) as a pathologic driver of neurodegeneration. However, the prevalence of IR in PD is unknown.

Objective: To determine IR prevalence in non-diabetic patients with PD and to correlate IR with other metabolic indicators, motor and non-motor symptoms (NMS) of PD, and quality of life (QoL).

Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency.

Deep Brain Stimulation and Nonmotor Symptoms.

Deep brain stimulation (DBS) is currently the treatment of choice for advanced Parkinson's disease (PD). Several brain targets, including the subthalamic nucleus and the globus pallidus internus, have been successfully employed, with excellent motor outcomes. Despite less established knowledge, DBS may be a powerful tool for managing a wide variety of nonmotor symptoms (NMS) in PD patients, either directly or indirectly due to motor benefit or reduction of dopaminergic drug load.

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.

Global and multi-focal changes in cerebral blood flow during subthalamic nucleus stimulation in Parkinson's disease.

Electrical stimulation of subthalamic nuclei (STN) is a widely used therapy in Parkinson's disease (PD). While deep brain stimulation (DBS) of the STN alters the neurophysiological activity in basal ganglia, the therapeutic mechanism has not been established. A positron emission tomography (PET) study of cerebral blood flow (CBF) during speech production in PD subjects treated with STN-DBS found significant increases in global (whole-brain) CBF.

GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function.

N-methyl-d-aspartate receptors (NMDARs) play important roles in brain development and neurological disease. We report two individuals with similar dominant de novo GRIN1 mutations (c.1858 G>A and c.

Micronutrients and Risk of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Although the precise pathogenetic mechanisms of PD remain undetermined, there appears to be both genetic and environmental factors that contribute to the risk of developing PD. With regard to environmental risk factors, there has been significant interest related to the role of diet, nutrition, and nutrients on the onset and progression of PD.

Acute Ischemic Stroke During Deep Brain Stimulation Surgery of Globus Pallidus Internus: Report of 5 Cases.

Background: Cerebrovascular accident (CVA) is a potentially devastating complication of deep brain stimulation (DBS) surgery. Although there are substantial data reporting the incidence and cause of hemorrhagic CVA, reports of acute ischemic infarctions during DBS implantation surgery are rare.

Objective: To present a series of 5 patients who experienced clinically significant ischemic CVA during microelectrode-guided globus pallidus internus (GPi) DBS, and evaluate the potential risk factors and mechanisms.