[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

BACKGROUND: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making. MATERIAL AND METHODS: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis. RESULTS: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents. DISCUSSION: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers.

Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson's disease and atypical Parkinsonian syndromes.

The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard.

[Treatment practice of patients with Parkinson's disease in Saxony : A secondary data-based analysis of utilization in the observation period 2011-2019]. / Versorgungssituation von Parkinson-Patienten in Sachsen : Eine sekundärdatenbasierte Analyse der Inanspruchnahme im Beobachtungszeitraum 2011 bis 2019.

BACKGROUND: The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required. OBJECTIVE: To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019? MATERIAL AND METHODS: The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder. RESULTS: Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4­fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist. DISCUSSION: The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care.

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

[Parkinson Networks in Germany: Future or Utopia?] / Parkinson-Netzwerke in Deutschland: Zukunft oder Utopie?

BACKGROUND: Parkinson's disease requires a close interaction between different care partners from the point of diagnosis in order to provide the best possible care for patients. However, the treatment reality shows that there are often still significant gaps in care. In recent years it has been recognised that the formation of networks can contribute to improving the care of Parkinson's patients. OBJECTIVES: To present the current status of the development of Parkinson's networks in Germany, the available evidence and the future of Parkinson's networks. MATERIAL AND METHODS: Experiences from existing networks in Germany were systematically recorded on the basis of personal reports and publications. The existing national and international evidence was summarised, and critical success factors and hurdles were analysed. In addition, possible future scenarios were developed. RESULTS: There are many integrated approaches to improve the care of Parkinson's patients. However, this is usually subject to the initiative at individual locations, without binding conditions being created for this by the legislator or the funding agencies outside of model projects. DISCUSSION: It must be noted that it is currently very difficult to implement a problem-free and cost-efficient development of intersectoral network structures within the existing possibilities of the German health care system. The high personal commitment of individual actors currently forms the basis of existing regional networks. An overarching health policy concept is needed to further promote the content and infrastructure of Parkinson's disease networks.

[The role of inhibitors of COMT and MAO-B in the therapy of Parkinson's disease]. / Grundlagen und Stellenwert der COMT- und MAO-B-Inhibitoren in der Therapie des idiopathischen Parkinson-Syndroms.

Inhibitors of COMT and MAO-B are well established in the pharmacotherapy of Parkinson's disease (PD). MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Both classes of compounds prolong the response duration of levodopa and optimise its clinical benefit. As a result, the ON-times are prolonged significantly. In the past, MAO-B inhibitors were also adminstered for neuroprotection; however, despite convincing scientific reasoning in support of neuroprotective effects, these could not be substantiated in clinical studies performed so far.

Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.

OBJECTIVE: The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). METHODS: This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. RESULTS: Patients carrying the MAOBCC/(C)/CT genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. CONCLUSIONS: The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Quenching of the luminescence intensity of GaN nanowires under electron beam exposure: impact of C adsorption on the exciton lifetime.

Electron irradiation of GaN nanowires in a scanning electron microscope strongly reduces their luminous efficiency as shown by cathodoluminescence imaging and spectroscopy. We demonstrate that this luminescence quenching originates from a combination of charge trapping at already existing surface states and the formation of new surface states induced by the adsorption of C on the nanowire sidewalls. The interplay of these effects leads to a complex temporal evolution of the quenching, which strongly depends on the incident electron dose per area. Time-resolved photoluminescence measurements on electron-irradiated samples reveal that the carbonaceous adlayer affects both the nonradiative and the radiative recombination dynamics.

Accurate detection of Parkinson's disease in tremor syndromes using olfactory testing.

BACKGROUND/AIMS: The diagnostic value of olfactory testing for the discrimination of tremor-dominant Parkinson's disease (PD) from other tremor disorders remains enigmatic. We evaluated whether olfactory testing can accurately detect PD in tremor patients. METHODS: A retrospective analysis of 299 consecutive subjects referred for the differential diagnosis of a tremor disorder was done. Olfactory testing was performed using 'Sniffin' Sticks', resulting in a composite TDI score of odor threshold (T), discrimination (D), and identification (I). Receiver operating curve (ROC) plots were used to calculate sensitivity/specificity for the detection of PD. RESULTS: Of all subjects, 167 (55.9%) had PD and 85 (28.4%) had essential tremor (ET). The mean TDI score in PD was significantly reduced compared to those in ET and other tremor disorders with no differences between ET and other tremor disorders. ROC analysis revealed strong correlations of TDI scores with PD [area under the curve: 0.85 (95% CI: 0.80-0.89); p < 0.001]. The highest Youden index was observed for a TDI score <25 (Youden index: 0.58). Using this cutoff score and that generated from normative data of healthy controls, the TDI score provided high sensitivity (negative predictive value) and specificity (positive predictive value) of approximately 80% for detecting PD. CONCLUSION: Olfactory testing is a useful, easily applied and inexpensive diagnostic test which is helpful to detect PD among tremor patients.

Luminous efficiency of axial In(x)Ga(1-x)N/GaN nanowire heterostructures: interplay of polarization and surface potentials.

Using continuum elasticity theory and an eight-band k·p formalism, we study the electronic properties of GaN nanowires with axial InxGa1-xN insertions. The three-dimensional strain distribution in these insertions and the resulting distribution of the polarization fields are fully taken into account. In addition, we consider the presence of a surface potential originating from Fermi level pinning at the sidewall surfaces of the nanowires. Our simulations reveal an in-plane spatial separation of electrons and holes in the case of weak piezoelectric potentials, which correspond to an In content and layer thickness required for emission in the blue and violet spectral range. These results explain the quenching of the photoluminescence intensity experimentally observed for short emission wavelengths. We devise and discuss strategies to overcome this problem.

Strain engineering of nanowire multi-quantum well demonstrated by Raman spectroscopy.

An analysis of the strain in an axial nanowire superlattice shows that the dominating strain state can be defined arbitrarily between unstrained and maximum mismatch strain by choosing the segment height ratios. We give experimental evidence for a successful strain design in series of GaN nanowire ensembles with axial InxGa1-xN quantum wells. We vary the barrier thickness and determine the strain state of the quantum wells by Raman spectroscopy. A detailed calculation of the strain distribution and LO phonon frequency shift shows that a uniform in-plane lattice constant in the nanowire segments satisfactorily describes the resonant Raman spectra, although in reality the three-dimensional strain profile at the periphery of the quantum wells is complex. Our strain analysis is applicable beyond the InxGa1-xN/GaN system under study, and we derive universal rules for strain engineering in nanowire heterostructures.

Effects of rasagiline on olfactory function in patients with Parkinson's disease.

BACKGROUND: Impairment of olfactory function is a well recognized nonmotor manifestation of Parkinson's disease(PD). The aim of this investigation was to determine if the MAO-B inhibitor rasagiline can improve olfaction in PD patients. METHODS: Thirty-four PD patients participated in this single-center, prospective, randomized, controlled,double-blind study. Seventeen patients were randomly assigned to rasagiline and 17 patients to placebo. Orthoand retronasal olfactory testing and recording of event related potentials were performed before and after 120 days of rasagiline versus placebo intake. RESULTS: When comparing olfactory score differences between baseline and after 120 days between the 2 groups, the level of significance was not reached. CONCLUSIONS: The primary end point of the study was not reached, and therefore, a specific effect of rasagiline on olfactory function in PD could not be demonstrated.

Anticoagulation management of myocardial infarction after deep brain stimulation: a comparison of two cases.

Deep brain stimulation (DBS) is an established treatment of various diseases, particularly used for idiopathic Parkinson's disease. Frequently, DBS patients are multimorbid and managing them may be challenging, since postoperative complications can become more likely with age. In this article, we present two cases of myocardial infarction after DBS with different therapeutic strategies. Case 1 was anticoagulated with a heparin infusion with a target partial thromboplastine time (PTT) between 50 and 60 s after the myocardial infarction and showed 3 days later, after an initial postoperative inconspicuous cranial computer tomography, an intracerebral haematoma, which was evacuated without explanting the DBS lead. Case 2 was only treated with enoxaparine 40 mg s.c. twice a day after the myocardial infarction without any further complications. Both cases benefited from the DBS with respect to the motor fluctuations, but case 1 continued to suffer from psychomotor slowdown, mild hemiparesis of the left side, visual neglect and a gaze paresis. Unfortunately, there are no established guidelines or therapy recommendations for the management of such patients. An individual therapy regime is necessary for this patient population regarding the bleeding risk, the cardial risk and the symptoms of the patient. Retrospectively, the rejection of the intravenous application of heparin in case 2 seems to be the right decision. But regarding the small number of cases, it remains still an individual therapy. Further experience will help us to develop optimal therapy strategies for this patient population.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives: To judge the long-term outcome of patients with STN-DBS. Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

High-Resolution Mapping of Strain Partitioning and Relaxation in InGaN/GaN Nanowire Heterostructures.

Growing an Inx Ga1- x N/GaN (InGaN/GaN) multi-quantum well (MQW) heterostructure in nanowire (NW) form is expected to overcome limitations inherent in light-emitting diodes (LEDs) based on the conventional planar heterostructure. The epitaxial strain induced in InGaN/GaN MQW heterostructure can be relaxed through the sidewalls of NW, which is beneficial to LEDs because a much larger misfit strain with higher indium concentration can be accommodated with reduced piezoelectric polarization fields. The strain relaxation, however, renders highly complex strain distribution within the NW heterostructure. Here the authors show that complementary strain mapping using scanning transmission electron microscopy and dark-field inline holography can comprehend the strain distribution within the axial In0.3 Ga0.7 N/GaN MQW heterostructure embedded in GaN NW by providing the strain maps which can cover the entire NW and fine details near the sidewalls. With the quantitative evaluation by 3D finite element modelling, it is confirmed that the observed complex strain distribution is induced by the strain relaxation leading to the strain partitioning between InGaN quantum disk, GaN quantum well, and the surrounding epitaxial GaN shell. The authors further show that the strain maps provide the strain tensor components which are crucial for accurate assessment of the strain-induced piezoelectric fields in NW LEDs.

Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson's Disease.

Identification of individual risk factors for motor complications in Parkinson's disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOB CC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089-0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039-0.520]; p=0.003) than MAOB TT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD.

Comparison of dopamine turnover, dopamine influx constant and activity ratio of striatum and occipital brain with ¹8F-dopa brain PET in normal controls and patients with Parkinson's disease.

PURPOSE: The aim of the study was to estimate normal ranges and test-retest measures for various parameters characterising dopamine metabolism from a prolonged (18)F-dopa positron emission tomography (PET) measurement using a reference tissue model and compare their value for the detection of early Parkinson's disease (PD). METHODS: Healthy volunteers (n = 9) and patients (n = 36) in an early stage of PD underwent an (18)F-dopa PET measurement lasting 4 h. The influx rate constant k(occ) and the effective distribution volume ratio (EDVR, its inverse is an indicator for dopamine turnover) were estimated by a graphical approach using dynamic data in the striatum and, as a reference region, the occipital cortex. Furthermore, ratios of activity concentrations between striatum and occipital brain taken for three time intervals completed the data analysis. All parameters were determined both in eight small volumes of interest placed in the striatum as well as averaged for caudate nucleus and putamen. For the control group, reproducibility was checked in a second study 3 months later and ranges for normal values were derived from mean ± 2 standard deviations. Receiver-operating characteristic (ROC) analyses were performed to assess the value of the parameters for diagnostic purposes. RESULTS: Patients with early-stage PD and healthy volunteers could be separated by the values of the putamen, not the caudate nucleus. The normal ranges of the putamen were 0.0151-0.0216/min for the influx rate constant k(occ) and 2.02-3.00 for EDVR. For the various time intervals used the striato-occipital ratios yielded 2.24-3.06, 2.43-3.42 and 2.35-3.21, respectively. Patients were characterised by significantly lower values (p < 0.001) and significant differences between ipsi- and contralateral sides (p < 0.001) with regard to their clinical symptoms and a rostrocaudal gradient. EDVR as well as k(occ) for the putamen were able to effectively differentiate between groups (sensitivity >97%, specificity 100%). In contrast, striato-occipital ratios showed a sensitivity of about only 85%. CONCLUSION: For clinical applications, our data do not demonstrate any superiority of the EDVR determination compared to influx rate constant, while requiring long and tedious acquisition protocols. The normal range estimates do not represent absolute quantitative measures for dopamine metabolism but are specific for the chosen acquisition and processing procedures.

AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials.

Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society.