Clinicians' viewpoints on current paradigms of care and research in Parkinson's disease.

Aim of this review is to discuss the value of current ongoing research initiatives in Parkinson's disease from the clinicians' point of view. The repeat, recent failures on progress slowing reflect the drifting apart between initially promising experimental and then disappointing clinical outcomes in the translational trials with well selected Parkinson's disease patients. A similar development concerns the emerging gap between novel developed drugs with improved pharmacokinetic behaviour and their limited use in the clinical practice following approval.

Absorption Correction for 3D Elemental Distributions of Dental Composite Materials Using Laboratory Confocal Micro-X-ray Fluorescence Spectroscopy.

Confocal micro-X-ray fluorescence (micro-XRF) spectroscopy facilitates three-dimensional (3D) elemental imaging of heterogeneous samples in the micrometer range. Laboratory setups using X-ray tube excitation render the method accessible for diverse research fields but interpretation of results and quantification remain challenging. The attenuation of X-rays in composites depends on the photon energy as well as on the composition and density of the material.

Simulation-Assisted Augmentation of Missing Wedge and Region-of-Interest Computed Tomography Data.

This study reports a strategy to use sophisticated, realistic X-ray Computed Tomography (CT) simulations to reduce Missing Wedge (MW) and Region-of-Interest (RoI) artifacts in FBP (Filtered Back-Projection) reconstructions. A 3D model of the object is used to simulate the projections that include the missing information inside the MW and outside the RoI. Such information augments the experimental projections, thereby drastically improving the reconstruction results.

Micro-CT analysis and mechanical properties of low dimensional CFR-PEEK specimens additively manufactured by material extrusion.

Material extrusion of thermoplastic polymers enables the realization of complex specific designs with high performance composites. The present study aims at evaluating the mechanical properties of carbon fiber-reinforced semi-crystalline thermoplastic polymer polyether ether ketone (CFR-PEEK) manufactured by material extrusion and correlating them with results obtained by micro-CT. Samples in the shape of small bars were provided by Kumovis (Munich, Germany).

Diffraction Enhanced Imaging Analysis with Pseudo-Voigt Fit Function.

Diffraction enhanced imaging (DEI) is an advanced digital radiographic imaging technique employing the refraction of X-rays to contrast internal interfaces. This study aims to qualitatively and quantitatively evaluate images acquired using this technique and to assess how different fitting functions to the typical rocking curves (RCs) influence the quality of the images. RCs are obtained for every image pixel.

Renaming of Hallervorden-Spatz disease: the second man behind the name of the disease.

Hallervorden-Spatz disease (HSD) has been recently renamed to pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA), mainly due to the unethical behavior of Julius Hallervorden in the National Socialist (NS) euthanasia program of the Nazi Third Reich. The role of the second name giver in the NS euthanasia program is less clear. Hugo Spatz was the director of the Kaiser Wilhelm Institute for Brain Research in Berlin-Buch during World War II (WWII), renamed to Max Planck Institute after 1945.

Suppression of Cone-Beam Artefacts with Direct Iterative Reconstruction Computed Tomography Trajectories (DIRECTT).

The reconstruction of cone-beam computed tomography data using filtered back-projection algorithms unavoidably results in severe artefacts. We describe how the Direct Iterative Reconstruction of Computed Tomography Trajectories (DIRECTT) algorithm can be combined with a model of the artefacts for the reconstruction of such data. The implementation of DIRECTT results in reconstructed volumes of superior quality compared to the conventional algorithms.

Long-term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia.

Objective: Observational study to evaluate long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD).

Background: More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long-term data are sparse.

Methods: We retrospectively analyzed a cohort of seven MD patients with either separate (n = 1, VIM) or combined GPi- DBS and VIM-DBS (n = 6).

Scattering and phase-contrast X-ray methods reveal damage to glass fibers in endodontic posts following dental bur trimming.

Objectives: There is concern that the integrity of fiberglass dental posts may be affected by chairside trimming during treatment. We hypothesize that hard X-ray methods of phase contrast-enhanced micro-CT (PCE-CT) and synchrotron based X-ray refraction (SXRR) can reliably identify and help characterize the extent of damage.

Methods: Fiberglass posts were imaged both as manufactured and following trimming with a diamond bur.

Subthalamic beta oscillations correlate with dopaminergic degeneration in experimental parkinsonism.

Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal models. Recent evidence suggests that enhanced beta oscillations may play a central role in the pathophysiology of the disorder and that beta activity may be directly linked to the motor impairment. However, the temporal evolution of exaggerated beta oscillations during the ongoing dopaminergic neurodegeneration and its relation to the motor impairment and histological changes are still unknown.

Direct Iterative Reconstruction of Computed Tomography Trajectories Reconstruction from limited number of projections with DIRECTT.

X-ray computed tomography has many applications in materials science and non-destructive testing. While the standard filtered back-projection reconstruction of the radiographic datasets is fast and simple, it typically fails in returning accurate results from missing or inconsistent projections. Among the alternative techniques that have been proposed to handle such data is the Direct Iterative REconstruction of Computed Tomography Trajectories (DIRECTT) algorithm.

Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16 years.

Objective: Observational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia.

Background: Dystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an established treatment for severe isolated dystonia but long-term data are sparse.

Correction approach of detector backlighting in radiography.

In various kinds of radiography, deficient transmission imaging may occur due to backlighting inside the detector itself arising from light or radiation scattering. The related intensity mismatches barely disturb the high resolution contrast, but its long range nature results in reduced attenuation levels which are often disregarded. Based on X-ray observations and an empirical formalism, a procedure is developed for a first order correction of detector backlighting.

Neuronal oscillations of the pedunculopontine nucleus in progressive supranuclear palsy: Influence of levodopa and movement.

Objective: The pedunculopontine nucleus (PPN) has been proposed as a new deep brain stimulation (DBS) target for the treatment in idiopathic Parkinson's syndrome (IPS) and progressive supranuclear palsy (PSP). In IPS, levodopa has been shown to induce alpha activity in the PPN, indicating a possible physiological role for these oscillations in movement control. Despite shared clinical features, the PPN is more severely affected in PSP than IPS.

Evaluation of a programming algorithm for deep brain stimulation in dystonia used in a double-blind, sham-controlled multicenter study.

Background: Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia.

Methods: A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.

Long-term outcomes of semi-implantable functional electrical stimulation for central drop foot.

Background: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on.

Electric stimulation of the medial forebrain bundle influences sensorimotor gaiting in humans.

Background: Prepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders.

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

Objective: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.

Methods: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.

Longterm outcome of cognition, affective state, and quality of life following subthalamic deep brain stimulation in Parkinson's disease.

Normal cognition is an established selection criteria for subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD), while concern has been raised as to aggravated cognitive decline in PD patients following STN-DBS. The present longterm study investigates cognitive status in all patients (n = 104) suffering from PD, who were treated via continuous bilateral STN-DBS between 1997 and 2006 in a single institution. Preoperative neuropsychological results were available in 79/104 of the patients.

Neurostimulation in tardive dystonia/dyskinesia: A delayed start, sham stimulation-controlled randomized trial.

Introduction: Growing evidence suggests that pallidal deep brain stimulation represents a potential new therapeutic avenue in tardive dystonia/dyskinesia, but controlled and blinded randomized studies (RCT) are missing. The present RCT compares dystonia/dyskinesia severity of pallidal neurostimulation in patients with tardive dystonia using a delayed-start design paradigm.

Methods: Dystonia/dyskinesia severity was assessed via blinded videos following pallidal neurostimulation at 3 (blinded phase) and 6 months (open extension phase).

[Effectiveness and safety of safinamide as add-on to levodopa in patients with parkinson's disease: non-interventional study].

Aim: Safinamide (Xadago) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD). The X-TRA study investigated the efficacy and tolerability of the substance under clinical practice conditions.

Methods: Prospective, observational study in unselected patients in line with safinamide product specifications.

Pallidal Stimulation Modulates Pedunculopontine Nuclei in Parkinson's Disease.

Background: In advanced Parkinson’s disease, the pedunculopontine nucleus region is thought to be abnormally inhibited by gamma-aminobutyric acid (GABA) ergic inputs from the over-active globus pallidus internus. Recent attempts to boost pedunculopontine nucleus function through deep brain stimulation are promising, but suffer from the incomplete understanding of the physiology of the pedunculopontine nucleus region.

Methods: Local field potentials of the pedunculopontine nucleus region and the globus pallidus internus were recorded and quantitatively analyzed in a patient with Parkinson’s disease.

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

Background: The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders.

Methods: Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities.

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial.

Background: Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone.

Methods: We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9).