Genetic and Epidemiological Insights into RAB32-Linked Parkinson's Disease.

Background: The p.Ser71Arg RAB32 variant was recently associated with Parkinson's disease (PD).

Objective: The aim was to investigate the presence of RAB32 variants in a large multiethnic group of individuals affected and unaffected by PD.

Alpha synuclein PET imaging, a step closer to in vivo neuropathology in Parkinson's disease and related disorders.

In this issue of Neuron, Endo et al. develop a PET tracer capable of detecting alpha-synuclein (ɑ-syn). With validation in animal models and humans, this tracer brings us closer to being able to monitor the synuclein aggregation process and associated pathological changes in Parkinson's disease (PD) and other synucleinopathies.

Nigrostriatal blood-brain barrier opening in Parkinson's disease.

Background: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods: Three patients underwent MRgFUS for midbrain and putamen BBB-O.

Skull Density Ratio as Arm-Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson's Disease.

Background: MR-guided focused ultrasound (FUS) thermoablation is an established therapy for movement disorders. FUS candidates must meet a predefined threshold of skull density ratio (SDR), a parameter that accounts for the efficiency in reaching ablative temperatures. Randomized sham-controlled trials to provide definitive therapeutic evidence employ pure randomization of subjects into active treatment or control arms.

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease.

Importance: Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored.

Objective: To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD.

Misfolded protein deposits in Parkinson's disease and Parkinson's disease-related cognitive impairment, a [C]PBB3 study.

Parkinson's disease (PD) is associated with aggregation of misfolded α-synuclein and other proteins, including tau. We designed a cross-sectional study to quantify the brain binding of [C]PBB3 (a ligand known to bind to misfolded tau and possibly α-synuclein) as a proxy of misfolded protein aggregation in Parkinson's disease (PD) subjects with and without cognitive impairment and healthy controls (HC). In this cross-sectional study, nineteen cognitively normal PD subjects (CN-PD), thirteen cognitively impaired PD subjects (CI-PD) and ten HC underwent [C]PBB3 PET.

Continuous Levodopa Delivery with an Intraoral Micropump System: An Open-Label Pharmacokinetics and Clinical Study.

Background: Double-blind studies have demonstrated that motor complications in Parkinson's disease (PD) can be reduced with continuous delivery of levodopa. The DopaFuse system is a novel, intraoral micropump that attaches to a retainer and uses a propellant to deliver levodopa/carbidopa (LD/CD) continuously into the mouth.

Objectives: Evaluate the safety, pharmacokinetics, and efficacy of LD/CD delivered via the DopaFuse system compared to treatment with intermittent doses of standard oral LD/CD in PD patients with motor fluctuations.

MR-guided focused ultrasound in movement disorders and beyond: Lessons learned and new frontiers.

The development of MR-guided focused ultrasound (MRgFUS) has provided a new therapeutic tool for neuropsychiatric disorders. In contrast to previously available neurosurgical techniques, MRgFUS allows precise impact on deep brain structures without the need for incision and yields an immediate effect. In its high-intensity modality (MRgHIFU), it produces accurate therapeutic thermoablation in previously selected brain targets.

Exploring Asymmetric Fine Motor Impairment Trends in Early Parkinson's Disease via Keystroke Typing.

Background: The nQiMechPD algorithm transforms natural typing data into a numerical index that characterizes motor impairment in people with Parkinson's Disease (PwPD).

Objectives: Use nQiMechPD to compare asymmetrical progression of PD-related impairment in dominant (D-PD) versus non-dominant side onset (ND-PD) de-novo patients.

Methods: Keystroke data were collected from 53 right-handed participants (15 D-PD, 13 ND-PD, 25 controls).

Unilateral focused ultrasound subthalamotomy in early Parkinson's disease: a pilot study.

Background: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD).

Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease.

Background And Objectives: Unilateral magnetic resonance-guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of patients with PD treated with unilateral FUS-STN.

Update in the clinical application of focused ultrasound.

Purpose Of Review: To review the most recent evidence about the clinical applicability of transcranial MRI-guided focused ultrasound (MRgFUS), including clinical evidence and indications, recent technical developments for its use and future prospects.

Recent Findings: Unilateral MRgFUS thalamotomy for both essential and parkinsonian tremors is an approved and well established therapy. Recent studies have focused on its long-term safety and efficacy as well as technical advances for refining the approach.

Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study.

Background: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD.

Bilateral staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of essential tremor: a case series study.

Background: Unilateral magnetic resonance-guided focused ultrasound (FUS) thalamotomy is efficacious for the treatment of medically refractory essential tremor (ET). Viability of bilateral FUS ablation is unexplored.

Methods: Patients diagnosed with medically refractory ET and previously treated with unilateral FUS thalamotomy at least 5 months before underwent bilateral treatment.

Serotonergic System Impacts Levodopa Response in Early Parkinson's and Future Risk of Dyskinesia.

Background: The serotonergic system is known to contribute to levodopa-derived dopamine release in advanced Parkinson's disease.

Objective: We investigated the role of the serotonergic system in determining response to treatment in early disease and risk for complications concurrently with dopaminergic alterations.

Methods: Eighteen patients with early and stable Parkinson's disease underwent multitracer positron emission tomography using [ C]dihydrotetrabenazine (vesicular monoamine transporter 2 marker), [ C]methylphenidate (dopamine transporter marker), [ C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB, serotonin transporter marker), and [ C]raclopride (D2 marker) to investigate relationships between striatal dopaminergic and serotonergic alterations and levodopa-induced dopamine release, related to motor response to treatment and risk for dyskinesias, using a novel joint pattern analysis.

A data mining approach for classification of orthostatic and essential tremor based on MRI-derived brain volume and cortical thickness.

Objective: Orthostatic tremor (OT) is an extremely rare, misdiagnosed, and underdiagnosed disorder affecting adults in midlife. There is debate as to whether it is a different condition or a variant of essential tremor (ET), or even, if both conditions coexist. Our objective was to use data mining classification methods, using magnetic resonance imaging (MRI)-derived brain volume and cortical thickness data, to identify morphometric measures that help to discriminate OT patients from those with ET.

Diffusion tensor imaging in orthostatic tremor: a tract-based spatial statistics study.

Objective: The pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT-related white matter changes and their correlations with scores from a neuropsychological testing battery.

Methods: Diffusion tensor imaging measures were compared between 14 OT patients and 14 age- and education-matched healthy controls, using whole-brain tract-based spatial statistics analysis.

Remote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer.

Objective: The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting.

Methods: We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls.