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. For confocal micro-XRF, attenuation severely impacts elemental distribution information, as the signal from deeper layers is distorted by superficial layers. Absorption correction and quantification of fluorescence measurements in heterogeneous composite samples have so far not been reported. Here, an absorption correction approach for confocal micro-XRF combining density information from microcomputed tomography (micro-CT) data with laboratory X-ray absorption spectroscopy (XAS) and synchrotron transmission measurements is presented. The energy dependency of the probing volume is considered during the correction. The methodology is demonstrated on a model composite sample consisting of a bovine tooth with a clinically used restoration material.

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). The determination of surface roughness and density was followed by three-point bending tests. To reveal the pore distribution as well as the fusion quality of CFR PEEK when applied with external forces, micro-CT scans were performed with an X-ray microscope before and after the mechanical test to localize the sites where the fracture is generated. The density of CFR-PEEK bars indicated that they had superior mechanical properties compared with our previous study on unfilled 3D printed PEEK (bending modulus: (5.4 ± 0.5) GPa vs. (1.05 ± 0.05) GPa to (1.48 ± 0.10) GPa; bending strength: (167 ± 11) MPa vs. (51 ± 15) to (193 ± 7) MPa). Micro-CT analyses revealed the local 3D-distribution of voids. Voids of 30 µm diameter are nearly spherical and make up the main part of the total porosity. The larger the voids, the more they deviate from a spherical shape. Significant lack-of-fusion voids are located between the deposited filaments. By growing and merging, they act as seeds for the forming fracture line in the region of the flexural specimens where the maximum local tensile stresses occurred under bending load. Our work provides a detailed analysis of printed PEEK with fiber additive and relates this with mechanical properties.

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. An X-ray CT dataset of a selected object is modified to mimic various degrees of RoI and MW problems. The results are evaluated in comparison to a standard FBP reconstruction of the complete dataset. In all cases, the reconstruction quality is significantly improved. Small inclusions present in the scanned object are better localized and quantified. The proposed method has the potential to improve the results of any CT reconstruction algorithm.

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. This allows the separate determination of the absorption and the refraction properties of the material in a position-sensitive manner. Comparison of various types of fitting functions reveals that the Pseudo-Voigt (PsdV) function is best suited to fit typical RCs. A robust algorithm was developed in the Python programming language, which reliably extracts the physically meaningful information from each pixel of the image. We demonstrate the potential of the algorithm with two specimens: a silicone gel specimen that has well-defined interfaces, and an additively manufactured polycarbonate specimen.

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. After the war, he headed the Max Planck Institute for Brain Research in Frankfurt am Main. The present study investigates the potential involvement of Hugo Spatz in the NS euthanasia program. In the present study, we compared a list of euthanasia victims from the German Federal Archive Berlin (30.146 cases published after the reunification of Germany, BArch R179) with the files of the collection of specimens from 1940 until 1945 of Hugo Spatz as listed in the Archive of the Max Planck Society Berlin-Dahlem (n = 305). Furthermore, the old term HSD and the new terms PKAN and NBIA were systematically searched in PubMed from 1946, through January 2019 to evaluate the renaming process from HSD to PKAN/NBIA. Following Hugo Spatz's death in 1969 growing evidence indicated that he may have taken part in the NS euthanasia program. This study identifies 4 euthanized victims in the patient files of Hugo Spatz from 1940 to 1945, suggesting involvement of Hugo Spatz in the NS euthanasia program. This further strengthens the argument that the former HSD should be exclusively referred to as PKAN or NBIA.

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). Myoclonus, dystonia and disability were rated at baseline (BL), short-term (ST-FU) and long-term follow-up (LT-FU) using the United Myoclonus Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Tsui rating scale, respectively. Quality of life (QoL) and mood were evaluated using the SF-36 and Beck Depression Inventory questionnaires, respectively. RESULTS: Patients reached a significant reduction of myoclonus at ST-FU (62% ± 7.3%; mean ± SE) and LT-FU (68% ± 3.4%). While overall motor BFMDRS changes were not significant at LT-FU, patients with GPi-DBS alone responded better and predominant cervical dystonia ameliorated significantly up to 54% ± 9.7% at long-term. Mean disability scores significantly improved by 44% ± 11.4% at ST-FU and 58% ± 14.8% at LT-FU. Mood and QoL remained unchanged between 5 and up to 20 years postoperatively. No serious long-lasting stimulation-related adverse events were observed. CONCLUSIONS: We present a cohort of MD patients with very long follow-up of pallidal and/or thalamic DBS that supports the GPi as the favourable stimulation target in MD with safe and sustaining effects on motor symptoms (myoclonus>dystonia) and disability.

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. Each of the posts was imaged by SXRR and by PCE-CT. Datasets from PCE-CT were used to visualize and quantify 2D and 3D morphological characteristics of intact and of damage-affected regions caused by trimming. RESULTS: The SXRR images revealed fiber inhomogeneities from manufacturing with a significant increase in internal surfaces in sample regions corresponding to damage from trimming. PCE-CT volumes unveiled the micromorphology of single fibers in the posts and some damage in the trimmed area (e.g. fractures, splinters and cracks). Area, perimeter, circularity, roundness, volume and thickness of the glass fibers in the trimmed area were statistically different from the control (p < 0.01). SIGNIFICANCE: The integrity of single fibers in the post is critical for bending resistance and for long-term adhesion to the cement in the root canals. Damage to the fibers causes substantial structural weakening across the post diameter. Glass fragments produced due to contact with the dental bur may separate from the post and may significantly reduce bond capacity. The above mentioned synchrotron-based imaging techniques can further facilitate assessment of the structural integrity and the appearance of defects in posts (e.g. after mechanical load).

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. We investigated motor behavioral, in-vivo electrophysiological (subthalamic nucleus, motor cortex) and histological changes (striatum, substantia nigra compacta) 2, 5, 10 and 20-30 days after a 6-hydroxydopamine injection into the medial forebrain bundle in Wistar rats. We found strong correlations between subthalamic beta power and motor impairment. No correlation was found for beta power in the primary motor cortex. Only subthalamic but not cortical beta power was strongly correlated with the histological markers of the dopaminergic neurodegeneration. Significantly increased subthalamic beta oscillations could be detected before this increase was found in primary motor cortex. At the latest observation time point, a significantly higher percentage of long beta bursts was found. Our study is the first to show a strong relation between subthalamic beta power and the dopaminergic neurodegeneration. Thus, we provide additional evidence for an important pathophysiological role of subthalamic beta oscillations and prolonged beta bursts in Parkinson's disease.

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. We describe a new approach to the algorithm, which significantly decreases the computational time while achieving a better reconstruction quality than that of other established algorithms.

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. Here we investigated neuronal oscillations in the PPN in PSP and the influence of levodopa and movement. METHODS: Local field potentials were recorded bilaterally from the PPN of 4 PSP patients at rest, with levodopa and during self-paced leg movements. RESULTS: During rest, levodopa administration was associated with significantly increased alpha and reduced gamma activity in the PPN. Without levodopa, continuous movements were associated with reduced alpha and beta power. These differences between oscillatory power during movement and resting state were not observed with levodopa administration. CONCLUSION: In PSP the changes in neuronal oscillations in the PPN region on levodopa administration are similar to those reported in IPS. The enhancement of lower frequency oscillations in the PPN is possibly influenced by a dopaminergic activation of the striatal pathway and a reduced pallidal inhibition. SIGNIFICANCE: Levodopa influences neuronal oscillations at low and high frequencies in the PPN region in Parkinsonian disorders.

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. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. METHODS: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. RESULTS: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001). CONCLUSIONS: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.

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. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans. RESULTS: Separate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation. CONCLUSIONS: Our data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner.

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. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups (p < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group. CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.

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. Thirty-seven of these patients were additionally assessed after 6.3 ± 2.2 years (range 3.6-10.5 years) postsurgery via neuropsychological and motor test batteries, classifying cognitive conditions according to established criteria. At DBS-surgery patients, available for longterm follow-up (n = 37; mean age 67.6 ± 6.9 years, mean disease duration 11.3 ± 4.1 years), showed no (24.3%; 9/37) or mild preoperative cognitive impairment (MCI, 75.7%; 28/37). Postoperatively (mean disease duration: 17.1 ± 5.1 years), 19% of the patients (7/37) had no cognitive impairment, while 41% of the patients presented with either MCI or dementia (15/37, respectively). Preoperative MCI correlated with conversion to dementia by trend. Overall, STN-DBS-treated patients deteriorated by 1.6/140 points/year in the Mattis dementia rating scale. Disease duration, but not age, at DBS-surgery negatively correlated with postoperative cognitive decline and positively correlated with conversion to dementia. This observational, "real-life" study provides longterm results of cognitive decline in STN-DBS-treated patients with presurgical MCI possibly predicting the conversion to dementia. Although, the present data is lacking a control group of medically treated PD patients, comparison with other studies on cognition and PD do not support a disease-modifying effect of STN-DBS on cognitive domains.

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 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming. RESULTS: The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (n = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (n = 63) and 53 ± 31% at 5 years (n = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (n = 9) correlated significantly with improvement after 3 years, but not 5 years. CONCLUSIONS: Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT00142259.

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. A backlighting factor is modeled as a function of the relative detector coverage by the sample projection. Different cases of sample transmission are regarded at different backlight factors and detector coverage. The additional intensity of backlighting may strongly affect the values of materials' attenuation up to a few 10%. The presented scenario provides a comfortable procedure for corrections of X-ray or neutron transmission imaging data.

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). Primary endpoint was the percentage change of dystonia severity (Burke-Fahn-Marsden-Dystonia-Rating-Scale, BFMDRS) at 3 months between active vs. sham neurostimulation using blinded-video assessment. Secondary endpoints comprised clinical rating scores for movement disorders. Clinicaltrials.gov NCT00331669. RESULTS: Twenty-five patients were randomized (1:1) to active (n = 12) or sham neurostimulation (n = 13). In the intention-to-treat analyses the between group difference of dystonia severity (BFMDRS) between active vs. sham stimulation was not significant at 3 months. Three months post-randomisation dystonia severity improved significantly within the neurostimulation by 22.8% and non-significantly within the sham group (12.0%) compared to their respective baseline severity. During the open-label extension with both groups being actively treated, significant and pronounced improvements of 41.5% were observed via blinded evaluation. Adverse events (n = 10) occurred in 10/25 of patients during the 6 months, mostly related to surgical implantation of the device; all resolved without sequelae. CONCLUSION: The primary endpoint of this randomized trial was not significant, most likely due to incomplete recruitment. However, pronounced improvements of most secondary endpoints at 3 and 6 months provide evidence for efficacy and safety of pallidal neurostimulation in tardive dystonia.

[Effectiveness and safety of safinamide as add-on to levodopa in patients with parkinson's disease: non-interventional study]. / Wirksamkeit und Sicherheit von Safinamid als Zusatztherapie zu Levodopa bei Parkinson-Patienten: eine nicht-interventionelle Beobachtungsstudie.

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. RESULTS: Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions. CONCLUSIONS: Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet.

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. In particular, we compared the local field potentials from the pedunculopontine nucleus region at rest and during deep brain stimulation of the globus pallidus internus. RESULTS: At rest, the spectrum of local field potentials in the globus pallidus internus was mainly characterized by delta-theta and beta frequency activity whereas the spectrum of the pedunculopontine nucleus region was dominated by activity only in the delta and theta band. High-frequency deep brain stimulation of the globus pallidus internus led to increased theta activity in the pedunculopontine nucleus region and enabled information exchange between the left and right pedunculopontine nuclei. Therefore, Conclusions: When applying deep brain stimulation in the globus pallidus internus, its modulatory effect on pedunculopontine nucleus physiology should be taken into account.