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.

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.

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.

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.

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.

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.

Connectivity Predicts deep brain stimulation outcome in Parkinson disease.

OBJECTIVE: The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. METHODS: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. RESULTS: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. INTERPRETATION: Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.

[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.

Bilateral thalamic deep brain stimulation for essential tremor in elderly patients.

The purpose of this study was to assess the influence of age on thalamic deep brain stimulation (DBS) in essential tremor (ET). Tremor, cognition, mood and adverse events in patients with thalamic DBS for ET were evaluated in 26 consecutive patients with established standardized methods for tremor and cognition. Twelve patients <70 and 14 patients ≥70 years were included and followed for 2 years. Clinical outcomes did not differ significantly. DBS seems to be safe and effective for ET independent of age.

Disease-specific longevity of impulse generators in deep brain stimulation and review of the literature.

Deep brain stimulation (DBS) represents an established and internationally approved therapy for movement disorders. In the present retrospective analysis, we evaluated disease-specific longevity of dual channel impulse generators (IPG) used in different movement disorders. We correlated the battery lifetime with electrical stimulation settings, "total electrical energy delivered" (TEED), stimulation modi (monopolar, double monopolar and bipolar) and targets. Specifically, we reviewed the longevity and stimulation settings of 464 IPGs implanted between 1996 until 2011 in a single university center. Disease entities comprised Parkinson's disease (PD, n = 257), dystonia (n = 130) and essential tremor (ET, n = 50). Further subanalyses aimed at assessing differential longevity in different subtypes of PD and dystonia. The main finding relates to longer IPG longevity in ET (thalamic DBS) and PD (subthalamic DBS) vs. dystonia (pallidal DBS; 71.9 ± 6.7 vs. 51.5 ± 2.3 vs. 37 ± 2 months). In PD the tremor-dominant type was associated with a significant shorter battery survival than in the akinetic-rigid type without tremor or the "balanced" type with tremor, bradykinesia and rigidity (38.8 ± 3.9 vs. 53.6 ± 3.4 vs. 58.8 ± 4.1 months), while there were no significant differences in longevity between the subtypes of dystonia. Frequency, amplitude, pulse widths and TEED correlated inversely with battery lifetime. Pallidal DBS in dystonia is associated with a shorter lifetime of IPGs than subthalamic or thalamic DBS for PD or ET. The present results may contribute to the rapidly evolving refinement of DBS devices. Future studies that assess energy consumption both in patients with and without IPG replacement could help to avoid potential underestimation of longevity of IPGs.

Postoperative MRI localisation of electrodes and clinical efficacy of pallidal deep brain stimulation in cervical dystonia.

INTRODUCTION: Pallidal deep brain stimulation (DBS) has been shown to be effective in cervical dystonia (CD) with an improvement of about 50-60% in the Toronto Western Spasmodic Torticollis Rating (TWSTR) Scale. However, predictive factors for the efficacy of DBS in CD are missing with the anatomical location of the electrodes being one of the most important potential predictive factors. METHODS: In the present blinded observational study we correlated the anatomical localisation of DBS contacts with the relative clinical improvement (CI %) in the TWSTR as achieved by DBS at different pallidal contacts in 20 patients with CD. Localisations of DBS contacts were derived from postoperative MRI-data following anatomical normalisation into the standard Montreal Neurological Institute stereotactic space. The CIs following 76 bilateral test stimulations of 24 h were mapped to stereotactic coordinates of the corresponding bilateral 152 active contacts and were allocated to low CI (<30%; n=74), intermediate CI (≥30%; <60%; n=52) or high CI (≥60%; n=26). RESULTS: Euclidean distances between contacts and the centroid differed between the three clusters (p<0.001) indicating different anatomical variances between clusters. The Euclidean distances between contacts and the centroid of the cluster with high CIs correlated with the individual level of CIs (r=-0.61; p<0.0001). This relationship was best fitted with an exponential regression curve (r(2)=0.41). DISCUSSION: Our data show that the clinical effect of pallidal DBS on CD displays an exponential decay over anatomical distance from an optimised target localisation within a subregion of the internal pallidum. The results will allow a comparison of future DBS studies with postoperative MRI by verifying optimised (for instance pallidal) targeting in DBS-treated patients.

Missing wedge computed tomography by iterative algorithm DIRECTT.

A strategy to mitigate typical reconstruction artefacts in missing wedge computed tomography is presented. These artefacts appear as elongations of reconstructed details along the mean direction (i.e. the symmetry centre of the projections). Although absent in standard computed tomography applications, they are most prominent in advanced electron tomography and also in special topics of X-ray and neutron tomography under restricted geometric boundary conditions. We investigate the performance of the DIRECTT (Direct Iterative Reconstruction of Computed Tomography Trajectories) algorithm to reduce the directional artefacts in standard procedures. In order to be sensitive to the anisotropic nature of missing wedge artefacts, we investigate isotropic substructures of metal foam as well as circular disc models. Comparison is drawn to filtered backprojection and algebraic techniques. Reference is made to reconstructions of complete data sets. For the purpose of assessing the reconstruction quality, Fourier transforms are employed to visualize the missing wedge directly. Deficient reconstructions of disc models are evaluated by a length-weighted kernel density estimation, which yields the probabilities of boundary orientations. The DIRECTT results are assessed at different signal-to-noise ratios by means of local and integral evaluation parameters.

Involvement of human internal globus pallidus in the early modulation of cortical error-related activity.

The detection and assessment of errors are a prerequisite to adapt behavior and improve future performance. Error monitoring is afforded by the interplay between cortical and subcortical neural systems. Ample evidence has pointed to a specific cortical error-related evoked potential, the error-related negativity (ERN), during the detection and evaluation of response errors. Recent models of reinforcement learning implicate the basal ganglia (BG) in early error detection following the learning of stimulus-response associations and in the modulation of the cortical ERN. To investigate the influence of the human BG motor output activity on the cortical ERN during response errors, we recorded local field potentials from the sensorimotor area of the internal globus pallidus and scalp electroencephalogram representing activity from the posterior medial frontal cortex in patients with idiopathic dystonia (hands not affected) during a flanker task. In error trials, a specific pallidal error-related potential arose 60 ms prior to the cortical ERN. The error-related changes in pallidal activity-characterized by theta oscillations-were predictive of the cortical error-related activity as assessed by Granger causality analysis. Our findings show an early modulation of error-related activity in the human pallidum, suggesting that pallidal output influences the cortex at an early stage of error detection.

Levodopa inhibits habit-learning in Parkinson's disease.

Mixed dopaminergic medication, comprising dopamine agonists and levodopa, may affect habit-learning in patients with Parkinson's disease (PD). However, the specific impact of levodopa on this effect is unknown. We assessed habit-learning in 20 non-demented PD-patients both with and without levodopa. We observed intact habit-learning in PD-patients OFF-medication. In contrast, the administration of 200 mg of levodopa impaired habit-learning. We conclude that potential deficits in habit-learning in PD may be attributed to the intake of levodopa.

6-Hydroxydopamine impairs mitochondrial function in the rat model of Parkinson's disease: respirometric, histological, and behavioral analyses.

Mitochondrial defects have been shown to be associated with the pathogenesis of Parkinson's disease (PD). Yet, experience in PD research linking mitochondrial dysfunction, e.g., deregulation of oxidative phosphorylation, with neuronal degeneration and behavioral changes is rather limited. Using the 6-hydroxydopamine (6-OHDA) rat model of PD, we have investigated the potential role of mitochondria in dopaminergic neuronal cell death in the substantia nigra pars compacta by high-resolution respirometry. Mitochondrial function was correlated with the time course of disease-related motor behavior asymmetry and dopaminergic neuronal cell loss, respectively. Unilateral 6-OHDA injections (>2.5 µg/2 µl) into the median forebrain bundle induced an impairment of oxidative phosphorylation due to a decrease in complex I activity. This was indicated by increased flux control coefficient. During the period of days 2-21, a progressive decrease in respiratory control ratio of up to -58 % was observed in the lesioned compared to the non-lesioned substantia nigra of the same animals. This decrease was associated with a marked uncoupling of oxidative phosphorylation. Mitochondrial dysfunction, motor behavior asymmetry, and dopaminergic neuronal cell loss correlated with dosage (1.25-5 µg/2 µl). We conclude that high-resolution respirometry may allow the detection of distinct mitochondrial dysfunction as a suitable surrogate marker for the preclinical assessment of potential neuroprotective strategies in the 6-OHDA model of PD.

Spasticity treatment with onabotulinumtoxin A: data from a prospective German real-life patient registry.

This study aimed at providing real-life baseline, injection and outcome data for the treatment of various forms of spasticity with onabotulinumtoxin A in Germany. Prospective data were collected in an open multicenter patient registry from 2005 until 2010, encompassing the experience of ten specialized German centers in the treatment of spasticity using onabotulinumtoxin A in 508 patients with a total of 2005 treatment sessions. Disease entities comprised spasticity following stroke (both ischemic and hemorrhagic), traumatic brain injury, multiple sclerosis, cerebral palsy, and anoxia. Sustained improvement was observed in a variety of outcome parameters including goal attainment and motor performance scores for up to five repeated injection sessions. No significant differences between disease entities or between upper and lower limb treatment were observed with regard to efficacy and safety following onabotulinumtoxin A treatment. Minor to moderate side effects were reported in <1 % of the study population. We conclude that repetitive treatment of focal and multifocal spasticity with onabotulinumtoxin A provides a safe and efficacious therapeutic strategy for patients with different disease entities of the central nervous system.

Impact of physical exercise on reaction time in patients with Parkinson's disease-data from the Berlin BIG Study.

OBJECTIVE: To determine whether physical activity may affect cognitive performance in patients with Parkinson's disease by measuring reaction times in patients participating in the Berlin BIG study. DESIGN: Randomized controlled trial, rater-blinded. SETTING: Ambulatory care. PARTICIPANTS: Patients with mild to moderate Parkinson's disease (N=60) were randomly allocated to 3 treatment arms. Outcome was measured at the termination of training and at follow-up 16 weeks after baseline in 58 patients (completers). INTERVENTIONS: Patients received 16 hours of individual Lee Silverman Voice Treatment-BIG training (BIG; duration of treatment, 4wk), 16 hours of group training with Nordic Walking (WALK; duration of treatment, 8wk), or nonsupervised domestic exercise (HOME; duration of instruction, 1hr). MAIN OUTCOME MEASURES: Cued reaction time (cRT) and noncued reaction time (nRT). RESULTS: Differences between treatment groups in improvement in reaction times from baseline to intermediate and baseline to follow-up assessments were observed for cRT but not for nRT. Pairwise t test comparisons revealed differences in change in cRT at both measurements between BIG and HOME groups (intermediate: -52ms; 95% confidence interval [CI], -84/-20; P=.002; follow-up: 55ms; CI, -105/-6; P=.030) and between WALK and HOME groups (intermediate: -61ms; CI, -120/-2; P=.042; follow-up: -78ms; CI, -136/-20; P=.010). There was no difference between BIG and WALK groups (intermediate: 9ms; CI, -49/67; P=.742; follow-up: 23ms; CI, -27/72; P=.361). CONCLUSION: Supervised physical exercise with Lee Silverman Voice Treatment-BIG or Nordic Walking is associated with improvement in cognitive aspects of movement preparation.

Diffusion tensor imaging in idiopathic Parkinson's disease and multisystem atrophy (Parkinsonian type).

BACKGROUND: Differentiation between Parkinson's disease (PD) and atypical Parkinson syndromes (AP) is usually based on clinical examination, but can be challenging especially at early stages of the diseases. Diffusion tensor imaging (DTI) allows for differentiation between PD and AP with good specificity. It is a promising tool for clinical application, but has not been elaborated completely with respect to methodology and validity. OBJECTIVE: In this study we evaluated differences of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within white brain matter between patients with PD and multisystem atrophy of the parkinsonian type (MSAp). MATERIALS AND METHODS: DTI data of 9 PD and 9 MSAp patients were compared by means of a hypothesis-free whole-brain analysis algorithm (TBSS) focusing on changes within white matter. RESULTS: We found significantly higher values of the ADC in the MSAp group in the anterior limb of the inner capsule, superior parts of the corona radiata, and lateral periputaminal white matter. Group differences in FA values were not significant. CONCLUSION: Changes of the ADC close to the putamen proved most consistent and seem to be promising for the ongoing clinical implementation of DTI for the differentiation of hypokinetic-rigid movement disorders.

Scaling of movement is related to pallidal γ oscillations in patients with dystonia.

Neuronal synchronization in the gamma (γ) band is considered important for information processing through functional integration of neuronal assemblies across different brain areas. Movement-related γ synchronization occurs in the human basal ganglia where it is centered at ~70 Hz and more pronounced contralateral to the moved hand. However, its functional significance in motor performance is not yet well understood. Here, we assessed whether event-related γ synchronization (ERS) recorded from the globus pallidus internus in patients undergoing deep brain stimulation for medically intractable primary focal and segmental dystonia might code specific motor parameters. Pallidal local field potentials were recorded in 22 patients during performance of a choice-reaction-time task. Movement amplitude of the forearm pronation-supination movements was parametrically modulated with an angular degree of 30°, 60°, and 90°. Only patients with limbs not affected by dystonia were tested. A broad contralateral γ band (35-105 Hz) ERS occurred at movement onset with a maximum reached at peak velocity of the movement. The pallidal oscillatory γ activity correlated with movement parameters: the larger and faster the movement, the stronger was the synchronization in the γ band. In contrast, the event-related decrease in beta band activity was similar for all movements. Gamma band activity did not change with movement direction and did not occur during passive movements. The stepwise increase of γ activity with movement size and velocity suggests a role of neuronal synchronization in this frequency range in basal ganglia control of the scaling of ongoing movements.

Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia.

INTRODUCTION: Previously, controlled trials have demonstrated the efficacy and tolerability of fixed doses of incobotulinumtoxinA (Xeomin, NT 201, botulinum toxin type A free from complexing proteins) to treat cervical dystonia (CD). To explore the clinical relevance of these findings, this study evaluated long-term use of flexible dosing regimens of incobotulinumtoxinA in a setting close to real-life clinical practice. METHODS: Patients with CD received five injection sessions of incobotulinumtoxinA using flexible intervals (10-24 weeks) and dosing (≤300 Units) based on patients' needs. Outcome measures included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Dystonia Discomfort Scale (DDS), Investigator Global Assessment of Efficacy (IGAE) and Patient Evaluation of Global Response (PEGR). RESULTS: Of 76 patients enrolled (men: 34%; naïve to botulinum toxin: 25%), 64 completed the study, receiving treatment over a duration of 49.3-114.1 weeks (total maximum duration: 121 weeks). Mean TWSTRS-Total and DDS scores significantly improved from study baseline to 4 weeks after each injection session (ranges of improvement: TWSTRS-Total: -11.7 to -14.3; DDS: -20.2 to -23.0). Up to 81.6% of investigators rated the efficacy as 'good' or 'very good' (IGAE) and up to 78.9% of patients rated the treatment response as 'improved' (PEGR). The most common adverse events were dysphagia, nasopharyngitis and headache. CONCLUSIONS: In this long-term study, incobotulinumtoxinA was administered using more flexible dosing regimens than those permitted in previous controlled trials. Repeated injections of highly purified incobotulinumtoxinA are effective and well tolerated for the treatment of CD in a setting close to real-life clinical practice.