Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion.

Background And Purpose: Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha-synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion.

Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder.

Background: Using C-(R)-PK11195-PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified.

Objectives: The objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD.

Prevalence and severity of freezing of gait in a Danish cohort of people with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a widespread neurodegenerative disorder characterised by wide range of symptoms. Freezing of gait (FoG), a transient feeling that the patient's feet are nailed to the floor, resulting in an inability to move, is a particularly distressful symptom. The assessment of FoG can be challenging.

Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease.

Progression of brain cholinergic dysfunction in patients with isolated rapid eye movement sleep behavior disorder.

Background: Reduced cortical acetylcholinesterase activity, as measured by C-donepezil positron emission tomography (PET), has been reported in patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD). However, its progression and clinical implications have not been fully investigated. Here, we explored the relationship between longitudinal changes in brain acetylcholinesterase activity and cognitive function in iRBD.

Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study.

Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinson's disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD.

Mapping Cholinergic Synaptic Loss in Parkinson's Disease: An [18F]FEOBV PET Case-Control Study.

Background: Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns.

Objective: To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients.

[F]FEOBV positron emission tomography may not be a suitable method to measure parasympathetic denervation in patients with Parkinson's disease.

Introduction: The peripheral autonomic nervous system may be involved years before onset of motor symptoms in some patients with Parkinson's disease (PD). Specific imaging techniques to quantify the cholinergic nervous system in peripheral organs are an unmet need. We tested the hypothesis that patients with PD display decreased [F]FEOBV uptake in peripheral organs - a sign of parasympathetic denervation.

Spinal cord stimulation therapy for patients with Parkinson's disease and gait problems (STEP-PD): study protocol for an exploratory, double-blind, randomised, placebo-controlled feasibility trial.

Introduction: Gait difficulties are common in Parkinson's disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD.

Brain proteome profiling implicates the complement and coagulation cascade in multiple system atrophy brain pathology.

Background: Multiple system atrophy (MSA) is a rare, progressive, neurodegenerative disorder presenting glia pathology. Still, disease etiology and pathophysiology are unknown, but neuro-inflammation and vascular disruption may be contributing factors to the disease progression. Here, we performed an ex vivo deep proteome profiling of the prefrontal cortex of MSA patients to reveal disease-relevant molecular neuropathological processes.

Reduced Synaptic Density in Patients with Lewy Body Dementia: An [ C]UCB-J PET Imaging Study.

Background: Patients with Parkinson's disease (PD) often develop dementia, but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking.

Objective: The objective of this study was to assess the density of synapses in non-demented PD (nPD) subjects (N = 21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N = 13), and age-matched healthy controls (N = 15).

Brain-first versus body-first Parkinson's disease: a multimodal imaging case-control study.

Parkinson's disease is characterized by the presence of abnormal, intraneuronal α-synuclein aggregates, which may propagate from cell-to-cell in a prion-like manner. However, it remains uncertain where the initial α-synuclein aggregates originate. We have hypothesized that Parkinson's disease comprises two subtypes.

Access and Use of Device-Aided Therapies for Parkinson's Disease in Denmark.

Background: In Denmark's five regions, there is potential inequality in access to device-aided therapy (DAT) for Parkinson's disease (PD) based on structural or socioeconomic factors. It is unclear how long DAT is maintained and affects concomitant medication.

Objectives: To investigate access to DAT by comparing the proportion of patients with DBS, subcutaneous apomorphine infusion (SCAI), or levodopa/carbidopa intestinal gel (LCIG) in Danish regions 2008-2016 and describe demographics of patients, changes in use of comedication, and maintenance of DAT.

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients.

Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases.

[Dystonia].

This review presents the newest classification of dystonia, new evidence regarding aetiology, the diagnosis of dystonia, and the most common forms of treatment. Dystonia is a rare and heterogeneous movement disorder defined as a syn-drome of sustained muscle contractions with twisting and abnormal postures, and tremor. Dystonia is a collective term for different syndromes, primary idiopathic forms as well as genetic and secondary forms.

An Observational Study of the Effect of Levodopa-Carbidopa Intestinal Gel on Activities of Daily Living and Quality of Life in Advanced Parkinson's Disease Patients.

Introduction: Continuous delivery of levodopa-carbidopa intestinal gel (LCIG) by percutaneous endoscopic gastrojejunostomy (PEG-J) in advanced Parkinson's disease (PD) patients reduces variability in plasma levels, providing better control of motor fluctuations ("on" and "off" states). The MONOTREAT study assessed the effect of LCIG on activities of daily living, motor and non-motor symptoms, and quality of life in advanced PD patients.

Methods: This prospective, observational study included patients with advanced, levodopa-responsive PD with either 2-4 h of "off" time or 2 h of dyskinesia daily.

Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients.

Objective: It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase.

Methods: We used the Danish National Pathology Registry to identify archived paraffin-embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks).

Imaging acetylcholinesterase density in peripheral organs in Parkinson's disease with 11C-donepezil PET.

Parkinson's disease is associated with early parasympathetic dysfunction leading to constipation and gastroparesis. It has been suggested that pathological α-synuclein aggregations originate in the gut and ascend to the brainstem via the vagus. Our understanding of the pathogenesis and time course of parasympathetic denervation in Parkinson's disease is limited and would benefit from a validated imaging technique to visualize the integrity of parasympathetic function.

[OCD and orofacial dyskinesia caused by a rare basal ganglia disorder].

Movement disorders presenting in a psychiatric setting are usually caused by extrapyramidal side effects of antipsychotic medications. We present an unusual and rare case of orofacial dyskinesia, tongue dystonia, and choreatic movements in a 31-year-old Turkish man suffering from OCD.

Elevated [(18)F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson's disease.

PET studies with the DOPA decarboxylase substrate 6-[(18)F]fluoro-l-DOPA (FDOPA) reveal the storage of [(18)F]-fluorodopamine within synaptic vesicles, mainly of dopamine fibres. As such, FDOPA PET is a sensitive indicator of the integrity of the nigrostriatal dopamine innervation. Nonetheless, there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods.

Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography.

The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 binding sites in healthy brain. Therefore, we used quantitative autoradiography to measure the saturation binding parameters for [3H]PK11195 in cryostat sections from young Landrace pigs.

Quantitative autoradiography of ligands for dopamine receptors and transporters in brain of Göttingen minipig: comparison with results in vivo.

The pig has been used as animal model for positron emission tomography (PET) studies of dopamine (DA) receptors and pharmacological perturbations of DA neurotransmission. However, the binding properties of DA receptors and transporters in pig brain have not been characterized in vitro. Therefore, the saturation binding parameters of [3H]SCH 23390 for DA D1 receptors and [3H]raclopride for DA D2/3 receptors were measured by quantitative autoradiography in cryostat sections from brain of groups of 8 week old and adult female Göttingen minipigs.

Dopamine storage capacity in caudate and putamen of patients with early Parkinson's disease: correlation with asymmetry of motor symptoms.

Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [(18)F]fluorodopa (FDOPA) assumes irreversible trapping of [(18)F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [(18)F]fluorodopamine from the brain (k(loss)), from which can be calculated an effective distribution volume (EDV(1)), which is an index of [(18)F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k(loss) and EDV, here defined as EDV(2).