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Background: Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim. Objective: To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery. Methods: Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function. Results: Eighty-three patients were included (median (interquartile range) age 63 (56–68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models. Conclusion: Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.

Estuarine salt intrusion causes problems with freshwater availability in many deltas. Water managers require timely and accurate forecasts to be able to mitigate and adapt to salt intrusion. Data-driven models derived with machine learning are ideally suited for this, as they can mimic complex non-linear systems and are computationally efficient. We set up a Long Short Term Memory (LSTM) model to forecast salt intrusion in the Rhine-Meuse delta. It forecasts chloride concentrations up to 7 days ahead at Krimpen aan den IJssel, an important location for freshwater provision. The model forecasts baseline concentrations and peak timing well, but peak height is underestimated, a problem that becomes worse with increasing lead time. Between lead times of 1 and 7 days, forecast precision declines from 0.9 to 0.7 and forecast recall declines from 0.7 to 0.5 on average. Given these results, we aim to extend the model to other locations in the delta. We expect that a similar setup can work in other deltas, especially those with a similar or simpler channel network.

Background: In Parkinson’s disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but their impact remains unclear with limited application in research or clinical practice. Objective: To critically evaluate PD subtyping systems. Methods: We conducted a systematic review of PD subtypes, assessing the characteristics of the studies reporting a subtyping system for the first time. We completed a critical appraisal of their methodologic quality and clinical applicability using standardized checklists. Results: We included 38 studies. The majority were cross-sectional (n = 26, 68.4%), used a data-driven approach (n = 25, 65.8%), and non-clinical biomarkers were rarely used (n = 5, 13.1%). Motor characteristics were the domain most commonly reported to differentiate PD subtypes. Most of the studies did not achieve the top rating across items of a Methodologic Quality checklist. In a Clinical Applicability Checklist, the clinical importance of differences between subtypes, potential treatment implications and applicability to the general population were rated poorly, and subtype stability over time and prognostic value were largely unknown. Conclusion: Subtyping studies undertaken to date have significant methodologic shortcomings and most have questionable clinical applicability and unknown biological relevance. The clinical and biological signature of PD may be unique to the individual, rendering PD resistant to meaningful cluster solutions. New approaches that acknowledge the individual-level heterogeneity and that are more aligned with personalized medicine are needed.

Purpose: The ability to adapt walking is important for safe ambulation. Assessments of impairments in walking adaptability with the Interactive Walkway may aid in the development of individualized therapy strategies of stroke patients. The Interactive Walkway is an overground walkway with Kinect v2 sensors for a markerless registration of full-body kinematics, which can be augmented with (gait-dependent) visual context to assess walking adaptability. This study aims to evaluate the potential of the Interactive Walkway as a new technology for assessing walking adaptability in stroke patients. Materials and methods: 30 stroke patients and 30 controls performed clinical tests, quantitative gait assessments and various walking-adaptability tasks on the Interactive Walkway. Outcome measures were compared between stroke patients and controls to examine known-groups validity. Pearson’s correlation coefficients were calculated to assess the relationship between walking-adaptability outcomes and commonly used clinical test scores of walking ability and spatiotemporal gait parameters of unconstrained walking. Results: Good known-groups validity for walking-adaptability outcomes was demonstrated. In addition, the vast majority of walking-adaptability outcomes did not or only moderately correlate with clinical test scores of walking ability and unconstrained walking parameters. Conclusion: Interactive Walkway walking-adaptability outcomes have good known-groups validity and complement standard clinical tests and spatiotemporal gait parameters.IMPLICATIONS FOR REHABILITATION The Interactive Walkway allows for a comprehensive walking-adaptability assessment. Good known-groups validity for walking-adaptability tasks was demonstrated and walking-adaptability tasks complemented clinical tests and gait parameters. The Interactive Walkway has potential for monitoring recovery of walking after stroke. Assessments of walking adaptability may contribute to individualized interventions.

Background Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. Objectives To identify the genetic determinants of PD age at onset. Methods Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. Results We estimated that the heritability of PD age at onset attributed to common genetic variation was similar to 0.11, lower than the overall heritability of risk for PD (similar to 0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. Conclusions Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. (c) 2019 International Parkinson and Movement Disorder Society

A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 x 10(-11)), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 x 10(-8)) and WWOX (HR = 2.12, P = 2.37 x 10(-8)) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.A genome-wide survival study identifies variants at RIMS2 associated with progression of Parkinson's disease to dementia and highlights divergence in the genetic architecture of disease onset and progression.

Parkinson’s disease (PD) is a complex neurodegenerative disorder. Males are on average ∼1.5 times more likely to develop PD compared to females. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease etiology in a sex-specific manner.In an effort to study sex-specific genetic factors associated with PD, we explored two large genetic datasets from the International Parkinson’s Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases.In total 19 genome-wide significant regions were identified, and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWASes was identified (rg=0.877) and heritability estimates were identical between male and female PD cases (∼20%).We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus females.

Objective: To develop and validate an outcome scale for the cervical radicular syndrome and to build a mapping, predicting EQ-5D utility from the new scale. Study design and setting: An item pool was developed based on literature and patient and clinician interviews. Item selection was based on symptomatology, factor analysis, and internal consistency. We assessed: (a) test–retest reliability by standard error of measurement and intraclass correlation coefficients; (b) construct validity by testing 22 hypotheses on relationships with existing measures and known-group differences. For the mapping, performance was assessed by mean absolute error and root mean squared error. Results: A total of 254 patients with cervical radicular syndrome completed the first questionnaire, 61 stable patients a retest. Item selection led to a 21-item questionnaire consisting of three subscales: Symptoms, Energy and postures, and Actions and activities. Standard error of measurement values ranged from 6.7 to 11.2 on a 0 to 100 scale. All subscales showed good reliability (intraclass correlation coefficients: 0.84, 0.87, and 0.94). All hypotheses for construct validity were confirmed. A linear utility mapping was preferred, with reasonable statistical performance. Conclusion: We developed a reliable and valid cervical radicular syndrome specific outcome scale, called the Cervical Radiculopathy Impact Scale (CRIS). This new questionnaire may facilitate (cost-)effectiveness studies in this field.Implications for RehabilitationThe cervical radicular syndrome is a frequently occurring and invalidating health problem, which causes severe radiating pain in the arm and/or hand, which can be accompanied by motor and/or sensory deficits.The Cervical Radiculopathy Impact Scale (CRIS) is a newly developed self-report questionnaire which covers measurement of symptoms and limitations in patients with cervical radiculopathy due to irradiating pain, tingling sensations and sensory loss in the arm in combination with neck disability.The CRIS consists of 21 items divided over three subscales: (i) symptoms, (ii) energy and postures, and (iii) actions and activities.The CRIS shows good content validity, test-retest reliability, construct validity and is able to discriminate between groups.The CRIS predicts EQ-5D utility and is therefore useful for (cost)effectiveness studies in this field. The cervical radicular syndrome is a frequently occurring and invalidating health problem, which causes severe radiating pain in the arm and/or hand, which can be accompanied by motor and/or sensory deficits. The Cervical Radiculopathy Impact Scale (CRIS) is a newly developed self-report questionnaire which covers measurement of symptoms and limitations in patients with cervical radiculopathy due to irradiating pain, tingling sensations and sensory loss in the arm in combination with neck disability. The CRIS consists of 21 items divided over three subscales: (i) symptoms, (ii) energy and postures, and (iii) actions and activities. The CRIS shows good content validity, test-retest reliability, construct validity and is able to discriminate between groups. The CRIS predicts EQ-5D utility and is therefore useful for (cost)effectiveness studies in this field.

Objective Although subthalamic Deep Brain Stimulation (STN DBS) is proven effective in improving symptoms of Parkinson's Disease (PD), previous literature demonstrates a discrepancy between objective improvement and patients' perception thereof. We aimed to examine whether postoperative stimulation challenge tests (SCT) alters patients' satisfaction after STN DBS for PD. Methods Fifty-four PD patients underwent preoperative levodopa challenge tests and were routinely invited for SCT 1-2 years postoperatively. SEverity of predominantly Nondopaminergic Symptoms in PD (SENS-PD) scores quantified non-dopaminergic disease severity. Motor functioning was quantified using Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores; a ratio between conditions ON and OFF (preoperative Med-ON vs. Med-OFF, and postoperative Med-ON/Stim-ON vs. Med-OFF/Stim-OFF) reflected treatment benefit. ‘Global Impression of Change’ (GIC) and ‘Global Satisfaction with Surgery’ (GSS) Likert scales were filled out before and immediately after SCT. Results Postoperative Med-ON/Stim-ON severity was lower than preoperative ON severity. Disease severity scores were not different between assessments. GIC and GSS scores were higher after SCT versus before (GIC: Z = -3.80, r = 0.37, subjects indicating maximum scores before SCT: 32.1%, after SCT: 57.1%; GSS: Z = -3.69, r = 0.35, maximum scores before SCT: 25.0%, after SCT: 46.4%). Higher non-dopaminergic disease severity was associated with lower GIC and GSS scores (GIC: OR 1.2 (95%CI 1.0–1.3); GSS: OR 1.2 (95%CI 1.1–1.3), while motor-scores and magnitude of DBS-effects were not. Conclusion SCT improves patients’ satisfaction and is recommended especially in case of suboptimal subjective valuations. This information should be considered in clinical practice and in the context of clinical trials.

Background Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are considered subtypes of the α-synucleinopathy continuum that show similar and dissimilar clinical and morphological features. Objective To further our understanding of brain abnormalities that might differentiate both disorders more clearly, we performed quantitative magnetic resonance (MR) imaging of the subcortical and cortical grey matter. Methods Three-dimensional T1 weighted 3 tesla MR images of 14 DLB and 62 age- and gender-matched PD patients were examined to study cortical and subcortical grey matter structure. We used volumetric measurements to study total grey matter, and volumes of the pallidum, amygdala, putamen, caudate nucleus, thalamus and hippocampus. Whole-brain and structural network-based methods were used to identify local differences in grey matter and vertex-based shape analysis was used to assess focal hippocampal changes. Results Volumetric, whole-brain and network-based analyses showed reduced hippocampal (p = 0.008) and right parahippocampal region volumes (p = 0.030) in DLB compared to PD patients. Shape analysis showed atrophy in the head and body of the right (p = 0.040) and in the head of the left (p = 0.030) hippocampus of DLB patients. Conclusion DLB patients showed atrophy of the hippocampus and parahippocampal gyrus compared to PD patients with a differential involvement of the head and body of the hippocampus. Further studies should examine if these group-based findings can be used to differentiate both disorders on an individual level.

Background The standard clinical assessment tool in Huntington's disease is the Unified Huntington's Disease Rating Scale (UHDRS). In patients with advanced Huntington's disease ceiling and floor effects of the UHDRS hamper the detection of changes. Therefore, the UHDRS-For Advanced Patients (UHDRS-FAP) has been designed for patients with late-stage Huntington's disease. Objectives This cross-sectional study aims to examine if the UHDRS-FAP can differentiate better between patients with advanced Huntington's disease than the UHDRS. Methods Forty patients, who were institutionalized or received day-care, were assessed with the UHDRS, UHDRS-FAP, and Care Dependency Scale (CDS). The severity of Huntington's disease was defined by the Total Functional Capacity (TFC). Comparisons between consecutive TFC stages were performed for all domains of the UHDRS, UHDRS-FAP, and CDS using Mann-Whitney U tests. Results The motor scores of the UHDRS-FAP and UHDRS were the only subscales with significantly worse scores in TFC stage 5 compared to stage 4. In TFC stages 4-5, the range of the UHDRS-FAP motor score was broader, the standard error of measurement was lower, and the effect size r was higher than for the UHDRS motor score. The CDS declined significantly across all TFC stages. Conclusions Our results suggest that the UHDRS-FAP motor score might differentiate better between patients with severe Huntington's disease than the UHDRS motor score. Therefore, the UHDRS-FAP motor score is potentially a better instrument than the UHDRS motor score to improve disease monitoring and, subsequently, care in patients with advanced Huntington's disease in long-term care facilities.

Background The clinical assessment of motor symptoms in Huntington's disease is usually performed with the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS). A high interrater reliability is desirable to monitor symptom progression. Therefore, a teaching video and a system for annual online certification has been developed and implemented. Objectives The aim of this study is to investigate the interrater reliability of the UHDRS-TMS and of its subitems, and to examine the performance of raters in consecutive years. Methods Data from the online UHDRS-TMS certification were used. The interrater reliability was assessed for all first-time participants (n = 944) between 2009 and 2016. Intraclass correlation coefficients (ICC) were calculated for each year separately and the mean was taken as the total ICC. Results The UHDRS-TMS (ICC = 0.847), tandem walking (0.824), pronate/supinate hands left (0.713), and retropulsion pull test (0.706) showed good interrater reliability. Poor interrater reliability was found for maximal dystonia of the left and right upper extremity (0.187 and 0.322, respectively), maximal dystonia of the left and right lower extremity (0.200 and 0.256, respectively), and maximal dystonia of the trunk (0.389), tongue protrusion (0.266), and rigidity arms left (0.390). Raters performed significantly worse on follow-up certification compared to their first certification. Conclusions Our results suggest that the rating of dystonia (absent, slight, mild, moderate, or marked) is subjective and difficult to interpret, especially on video. Therefore, changing the dystonia items of the UHDRS-TMS should be explored. We also recommend that raters should watch the UHDRS-TMS teaching video before each certification.

© 2017 European Pain Federation - EFIC® Background: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. Objectives: To define recovery from the patients’ perspective and better understand their priorities for treatment approaches. Methods: Establishing an international consortium, we used a 2-Round Delphi-based study in eight countries across Europe and North America. Participants ≥18years who met, or had met, Budapest clinical criteria were included. Round 1 participants completed the statement: ‘I would/do consider myself recovered from CRPS if/because…’ alongside demographic and health questionnaires. Data were thematically organised and represented as 62 statements, from which participants identified and ranked their recovery priorities in Round 2. Results: Round 1 (N=347, 80% female, 91% non-recovered) dominant ICF themes were: activities of daily living; bodily functions; external factors; participation and personal factors. The top five priority statements in Round 2 (N=252) were: no longer having (1) CRPS-related pain, (2) generalised pain and discomfort, (3) restricted range of movement, (4) need for medication, (5) stiffness in the affected limb. With very few exceptions, priorities were consistent, irrespective of patient demographics/geography. Symptoms affecting daily activities were among those most frequently reported. Conclusions: Our data showed a small number of themes are of highest importance to CRPS patients’ definition of recovery. Patients want their pain, movement restriction and reliance on medication to be addressed, above all other factors. These factors should therefore be foremost concerns for future treatment and rehabilitation programmes. Significance: Those with longstanding CRPS may no longer meet diagnostic criteria but still be symptomatic. Defining recovery is therefore problematic in CRPS. Our study has identified patients’ definition of recovery from CRPS, in order of priority, as relief from: their CRPS-related pain, generalised pain, movement restriction, reliance on medication, and stiffness.

Cognitive impairment is one of the main features of Huntington's disease and is present across the disease spectrum. As part of the International Parkinson's Disease and Movement Disorder Society-sponsored project to review all clinical rating scales used in Huntington's disease, a systematic review of the literature was performed to identify cognitive scales used in Huntington's disease and make recommendations for their use. A total of 17 cognitive scales were identified and evaluated. None of the scales met criteria for a "recommended" status. For assessing severity of cognitive dysfunction, the Montreal Cognitive Assessment was "recommended with caveats." The UHDRS Cognitive Assessment, the UHDRS-For Advanced Patients cognitive section, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Frontal Assessment Battery, the Mattis Dementia Rating Scale, the Mini-Mental State Examination, and the Repeatable Battery for the Assessment of Neuropsychological Status were "suggested" for evaluating severity of cognitive impairment. The MoCA was "suggested" as a screening tool for cognitive impairment. The major challenge in the assessment of cognition in Huntington's disease is the lack of a formal definition of dementia and/or mild cognitive impairment in this disease. The committee concluded that there is a need to further validate currently available cognitive scales in Huntington's disease, but that it is premature to recommend the development of new scales. Recently developed Huntington's disease-specific scales, such as the Huntington's Disease-Cognitive Assessment Battery, hold promise but require the completion of more comprehensive clinimetric development. © 2017 International Parkinson and Movement Disorder Society.

Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual's subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of ≥4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.

Akinesia, hypokinesia, and bradykinesia are extensively used to describe motor execution disturbances, but are applied inconsistently and cover more conditions than their Greek translations would suggest. We investigated the origins and changes in meaning of these terms over time, particularly in relation to Parkinson's disease (PD). We searched the literature from 1817 to 2015 for use and interpretation of the words akinesia, bradykinesia, hypokinesia, and PD. We found that akinesia and hypokinesia appeared as terms in the 19th century, opposite to hyperkinesia, but were used in the context of PD since 1920, while at the same time the 'bradykinetic syndrome' was introduced. Use of all terms increased in this period due to the encephalitis-lethargica-epidemic, and increased again with the discovery of levodopa from 1961. With the extensive use of criteria sets from the 1980s, bradykinesia replaced akinesia as the most commonly used term. The advent of the internet led to an increase in publications and an associated increase in heterogeneity in the use of the terms. This review shows the variation over time and the lack of unity in the terminology used to describe the range of movement execution disturbances. The current terminology fails to capture the nuances of the challenges we face in documenting these disturbances. We therefore recommend that the current situation may benefit from an objective and computationally solid approach using insights from network and circuitry technology and new developments in assessment technology. It is expected that this will contribute to a new framework for terminology in movement disorders.

Introduction Insomnia is a debilitating symptom in Parkinson's disease (PD) that has been scarcely investigated in a longitudinal design. Knowledge of factors associated with occurrence of insomnia may provide clues for an increased understanding of underlying pathophysiology and facilitate early detection. The objective of this study is to examine the course and factors associated with longitudinal changes in insomnia severity in patients with PD. Methods Analyses were performed in data of the SCOPA-PROPARK cohort, a 5-year longitudinal cohort study (2003–2011) of 421 PD patients who have been examined annually. Linear mixed models were used to identify factors associated with longitudinal changes in scores of the SCOPA-SLEEP-Nighttime sleep (NS) problems section. A generalized estimating equations (GEE) analysis was performed to determine which baseline variables were associated with the different aspects of insomnia (sleep initiation or maintenance difficulty). Results Baseline SCOPA-SLEEP-NS scores were available for 412 patients, of whom 110 (27%) had insomnia (i.e. score ≥ 7). Of the remaining 302 patients, 99 (33%) developed insomnia at some point during follow-up. More severe depressive symptoms, motor fluctuations, higher dopamine agonist doses and sleep medication use were independently associated with higher SCOPA-SLEEP-NS scores over time. GEE analysis did not identify an unique set of determinants that affected specific aspects of insomnia. Conclusion The presence of depressive symptoms, motor fluctuations and the use of higher doses of dopamine agonists are associated with more severe insomnia. Attention to these aspects could potentially contribute to a better management of insomnia symptoms in PD.

Patients with advanced Parkinson's Disease (PD) may be eligible for Deep Brain Stimulation (DBS) in case of medication-related motor fluctuations or tremor refractory to oral medication. However, several PD symptoms are unresponsive to DBS and constitute relative contra-indications for DBS. Patients referred for DBS undergo an eligibility screening during which motor functioning and contra indications for surgery are assessed. During this pre-screening the potential benefits and drawbacks of surgery are discussed, together with patients' expectations of the results of DBS. Unrealistic expectations on the benefits of DBS may contribute to reduced patient satisfaction and poor clinical outcomes after surgery. The aim of this multicenter study (289 patients) was to assess the reasons for rejection after an outpatient-based pre-screening visit for DBS referrals, with particular emphasis on the role of patient expectations of DBS. The most frequent reason contributing to rejection was suboptimal oral treatment or satisfying symptom-control with oral medication (50% of rejections). Unrealistic expectations were identified in 38% of rejected patients and were the singular reason for rejection in 4%. Incorporating the assessment of unrealistic expectations increased the accuracy (Area Under the Curve) of determining DBS eligibility from 0.92 ((95% confidence interval (95%CI) 0.88-0.97) to 0.97 (95%CI 0.96-0.99). Patients' expectations of DBS are easily checked, and better education of patients and treating neurologists with regard to unrealistic expectations of this procedure may improve efficiency of referrals and avoid unnecessary stress and disappointments during screening.

As age and Parkinson's disease (PD) both play a role in the degeneration of brain white matter, we aimed to investigate a possible interaction effect of age and disease presence on white matter integrity in patients with PD. We studied white matterhyperintensity volume, global fractional anisotropy, mean diffusivity and mean magnetization transfer ratio of normal appearing white matter in 163 patients with PD and 218 age- and gender-matched healthy control subjects. We investigated the relationship between age and these parameters in both groups, and interaction between age and disease presence. Patients with PD had a higher load of white matter hyperintensities with a preferential periventricular and anterior distribution as compared with healthy control subjects. Visuospatial functioning was related to total and postural instability and gait difficultywas related to periventricular white matter hyperintensity volume in patients with PD. The age-related decline of white matter integrity was similar for both groups. Global microstructural integrity of the normal appearing white matter did not differ betweenpatients and healthy control subjects, suggesting that PD-specific changes do not exceed normal age-associated change in white matter without lesions. (C) 2019 The Authors. Published by Elsevier Inc.

Background It is unknown whether intraoperative testing during awake Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) can be used to postoperatively identify the best settings for chronic stimulation. Objective To determine whether intraoperative test stimulation is indicative of postoperative stimulation results. Methods Records of consecutive Parkinson's Disease patients who received STN DBS between September 2012 and December 2017 were retrospectively analyzed. The best depth identified after intraoperative stimulation via the microelectrode's stimulation tip was compared with the depth of the contact selected for chronic stimulation after a standard monopolar contact review. Moreover, thresholds for induction of clinical effects (optimal improvement of rigidity and induction of side-effects) were compared between stimulation at the postoperatively selected contact and at the corresponding intraoperative depth. Results Records of 119 patients were analyzed (mean (SD) age 60.5 (6.5) years, 31.9% female, 238 STNs). In 75% of cases, the postoperatively selected contact corresponded with the intraoperative depth with the largest therapeutic window or was immediately dorsal to it. Higher stimulation intensities were required postoperatively than intraoperatively to relieve rigidity (p = 0.002) and induce capsular side-effects (p = 0.016). Conclusion In the majority of cases, the postoperative contact for chronic stimulation was at a similar level or immediately dorsal with respect to the identified best intraoperative depth. Postoperatively, relief of rigidity and induction of capsular side-effects occur at higher stimulation intensities than during intraoperative test stimulation.

Background and purpose Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication-refractory motor complications in patients with Parkinson's disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality. Methods Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson's disease. Results In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction. Conclusion Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease-related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided.

Background: Most falls occur during walking and are due to trips, slips or misplaced steps, which suggests a reduced walking adaptability. The objective of this study was to evaluate the potential merit of a walking-adaptability assessment for identifying prospective fallers and risk factors for future falls in a cohort of stroke patients, Parkinson’s disease patients, and controls (n = 30 for each group). Research question: Does an assessment of walking-adaptability improve the identification of fallers compared to generic fall-risk factors alone? Methods: This study comprised an evaluation of subject characteristics, clinical gait and balance tests, a quantitative gait assessment and a walking-adaptability assessment with the Interactive Walkway. Subjects’ falls were registered prospectively with falls calendars during a 6-month follow-up period. Generic and walking-related fall-risk factors were compared between prospective fallers and non-fallers. Binary logistic regression and Chi-square Automatic Interaction Detector analyses were performed to identify fallers and predictor variables for future falls. Results: In addition to fall history, obstacle-avoidance success rate and normalized walking speed during goal-directed stepping correctly classified prospective fallers and were predictors of future falls. Compared to the use of generic fall-risk factors only, the inclusion of walking-related fall-risk factors improved the identification of prospective fallers. Significance: If cross-validated in future studies with larger samples, these fall-risk factors may serve as quick entry tests for falls prevention programs. In addition, the identification of these walking-related fall-risk factors may help in developing falls prevention strategies.

BackgroundParkinson disease is an intractable disorder with heterogeneous clinical presentation that may reflect different underlying pathogenic mechanisms. Surrogate indicators of pathogenic processes correlating with clinical measures may assist in better patients stratification. Mitochondrial function - which is impaired in and central to PD pathogenesis - may represent one of such surrogate indicators.MethodsMitochondrial function was assessed by respirometry experiment in fibroblasts derived from idiopathic patients (n=47) in normal conditions and in experimental settings that do not permit glycolysis and therefore force energy production through mitochondrial function. Respiratory parameters and clinical measures were correlated with bivariate analysis. Machine learning based classification and regression trees were used to classify patients on the basis of biochemical and clinical measures. Effects of mitochondrial respiration on alpha-synuclein stress was assessed monitoring the protein phosphorylation in permitting versus restrictive glycolysis conditions.ResultsBioenergetics properties in peripheral fibroblasts correlate with clinical measures in idiopathic patients and correlation is stronger with predominantly non-dopaminergic signs. Bioenergetics analysis under metabolic stress, in which energy is produced solely by mitochondria, shows that patients’ fibroblasts can augment respiration, therefore indicating that mitochondrial defects are reversible. Forcing energy production through mitochondria, however, favors alpha-synuclein stress in different cellular experimental systems. Machine learning-based classification identified different groups of patients in which increasing disease severity parallels higher mitochondrial respiration.ConclusionSuppression of mitochondrial activity in Parkinson disease may be an adaptive strategy to cope with concomitant pathogenic factors. Moreover, mitochondrial measures are potential biomarkers to follow disease progression.

Objective: Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)–dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications. Methods: Linear mixed models were applied to data from the Profiling Parkinson9s disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson9s disease [SCOPA]–Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA–Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA–Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365). Results: The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results. Conclusions: In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself.

BACKGROUND: Disorders of posture, gait, and balance in Parkinson's disease (PD) are common and debilitating. This MDS-commissioned task force assessed clinimetric properties of existing rating scales, questionnaires, and timed tests that assess these features in PD. METHODS: A literature review was conducted. Identified instruments were evaluated systematically and classified as "recommended," "suggested," or "listed." Inclusion of rating scales was restricted to those that could be used readily in clinical research and practice. RESULTS: One rating scale was classified as "recommended" (UPDRS-derived Postural Instability and Gait Difficulty score) and 2 as "suggested" (Tinetti Balance Scale, Rating Scale for Gait Evaluation). Three scales requiring equipment (Berg Balance Scale, Mini-BESTest, Dynamic Gait Index) also fulfilled criteria for "recommended" and 2 for "suggested" (FOG score, Gait and Balance Scale). Four questionnaires were "recommended" (Freezing of Gait Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, Survey of Activities, and Fear of Falling in the Elderly-Modified). Four tests were classified as "recommended" (6-minute and 10-m walk tests, Timed Up-and-Go, Functional Reach). CONCLUSION: We identified several questionnaires that adequately assess freezing of gait and balance confidence in PD and a number of useful clinical tests. However, most clinical rating scales for gait, balance, and posture perform suboptimally or have been evaluated insufficiently. No instrument comprehensively and separately evaluates all relevant PD-specific gait characteristics with good clinimetric properties, and none provides separate balance and gait scores with adequate content validity for PD. We therefore recommend the development of such a PD-specific, easily administered, comprehensive gait and balance scale that separately assesses all relevant constructs. (c) 2016 International Parkinson and Movement Disorder Society.

ObjectiveTo assess the relevance of quantitative EEG (qEEG) measures as outcomes of disease severity and progression in Parkinson disease (PD).MethodsMain databases were systematically searched (January 2018) for studies of sufficient methodologic quality that examined correlations between clinical symptoms of idiopathic PD and cortical (surface) qEEG metrics.ResultsThirty-six out of 605 identified studied were included. Results were classified into 4 domains: cognition (23 studies), motor function (13 studies), responsiveness to interventions (7 studies), and other (10 studies). In cross-sectional studies, EEG slowing correlated with global cognitive impairment and with diffuse deterioration in other domains. In longitudinal studies, decreased dominant frequency and increased θ power, reflecting EEG slowing, were biomarkers of cognitive deterioration at an individual level. Results on motor dysfunction and treatment yielded contrasting findings. Studies on functional connectivity at an individual level and longitudinal studies on other domains or on connectivity measures were lacking.ConclusionqEEG measures reflecting EEG slowing, particularly decreased dominant frequency and increased θ power, correlate with cognitive impairment and predict future cognitive deterioration. qEEG could provide reliable and widely available biomarkers for nonmotor disease severity and progression in PD, potentially promoting early diagnosis of nonmotor symptoms and an objective monitoring of progression. More studies are needed to clarify the role of functional connectivity and network analyses.

Increasing evidence supports an extensive and complex genetic contribution to Parkinson’s disease (PD). Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age of onset are largely unknown. Here we performed an age of onset GWAS based on 28,568 PD cases. We estimated that the heritability of PD age of onset due to common genetic variation was ~0.11, lower than the overall heritability of risk for PD (~0.27) likely in part because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni corrected significant effect at other known PD risk loci, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. In addition, we identified that GBA coding variant carriers had an earlier age of onset compared to non-carriers. Notably, SNCA, TMEM175, SCARB2, BAG3 and GBA have all been shown to either directly influence alpha-synuclein aggregation or are implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci such as GCH1, MAPT and RAB7L1/NUCKS1 (PARK16) did not show a significant effect on age of onset of PD. While for some loci, this may be a measure of power, this is clearly not the case for the MAPT locus; thus genetic variability at this locus influences whether but not when an individual develops disease. We believe this is an important mechanistic and therapeutic distinction. Furthermore, these data support a model in which alpha-synuclein and lysosomal mechanisms impact not only PD risk but also age of disease onset and highlights that therapies that target alpha-synuclein aggregation are more likely to be disease-modifying than therapies targeting other pathways.

Background The standard clinical assessment tool in Huntington’s disease is the Unified Huntington’s Disease Rating Scale (UHDRS). In patients with advanced Huntington’s disease ceiling and floor effects of the UHDRS hamper the detection of changes. Therefore, the UHDRS-For Advanced Patients (UHDRS-FAP) has been designed for patients with late stage Huntington’s disease. Aims The aim of this cross-sectional study was to examine if the UHDRS-FAP can differentiate better between patients with advanced Huntington’s disease than the UHDRS. Methods Forty patients, who were institutionalized or received day-care, were assessed with the UHDRS, UHDRS-FAP, and Care Dependency Scale (CDS). Severity of Huntington’s disease was defined by the Total Functional Capacity (TFC). Comparisons between consecutive TFC stages were performed for all domains of the UHDRS, UHDRS-FAP, and CDS using Mann-Whitney U tests. Results The motor scores of the UHDRS-FAP and UHDRS were the only subscales with significantly worse scores in TFC stage 5 compared to stage 4. In TFC stages 4–5, the range of the UHDRS-FAP motor score was broader, the standard error of measurement was lower, and the effect size r was higher than for the UHDRS motor score. The CDS declined significantly across all TFC stages. Conclusions Our results suggest that the UHDRS-FAP motor score differentiates better between patients with severe Huntington’s disease than the UHDRS motor score. Therefore, the UHDRS-FAP motor score is potentially a better instrument than the UHDRS motor score to improve disease monitoring and, subsequently, care in patients with advanced Huntington’s disease in long-term care facilities.

Summary Non-motor symptoms (NMS) of Parkinson's disease can be predominant as the disease advances, thereby constituting a major source of disease burden for patients and caregivers. However, current understanding of NMS is incomplete, particularly as a result of the absence of standardisation of outcome definitions and the heterogeneity of the risk factors that are assessed. The best data on risk factors for NMS in Parkinson's disease come from longitudinal studies, with the strongest evidence identifying factors for cognitive impairment and dementia, hallucinations, depression, apathy, excessive daytime sleepiness, insomnia, and impulse-control disorders. Cognitive impairment, hallucinations, and depression have several common risk factors, and many other NMS share a few risk factors, showing the interdependence between NMS with advancing Parkinson's disease. Disease severity, sex, age, and antiparkinsonian medication might have roles in the development of different NMS, although only antiparkinsonian medication is potentially modifiable. Until disease-modifying therapies are developed, increased knowledge of risk factors could ameliorate early identification of patients who are at an increased risk of developing specific NMS and potentially allow improvement of symptom management or prevention of specific NMS.

markdownabstractAbstract Background: Complex regional pain syndrome (CRPS) is much more prevalent in women than men but potential differences in clinical phenotype have not been thoroughly explored to date. Differences in the clinical presentation between sexes may point at new avenues for a more tailored management approach of CRPS. We therefore explored if in CRPS, the patient's sex is associated with differences in clinical and psychological characteristics. Methods: In this cross‐sectional study of 698 CRPS patients (599 females) fulfilling the Budapest clinical or research criteria, CRPS signs and symptoms, CRPS severity, pain (average pain intensity in the previous week and McGill pain rating index), pain coping (Pain Coping Inventory), physical limitations (Radboud Skills Questionnaire (upper limb), Walking and Rising questionnaire (lower limb)), anxiety and depression (Hospital Anxiety and Depression scale) and kinesiophobia (Tampa scale for kinesiophobia) were evaluated. Results: Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia. Conclusion: Sex‐related differences are present in CRPS, but the effect is generally small and mainly concerns psychological functioning. A greater awareness of sex‐ specific factors in the management of CRPS may contribute to achieving better outcomes. Significance: What is known? Nonsex‐specific clinical data of CRPS patients. What is new? Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.

Contains fulltext : 193399.pdf (Publisher’s version ) (Open Access) The aim of the study was to examine the oral health status of Parkinson's disease (PD) patients, to compare their oral health status to that of a control group, and to relate it to the duration and severity of PD. Materials and Methods. 74 PD patients and 74 controls were interviewed and orally examined. Among PD patients, the duration and the Hoehn and Yahr stage (HY) of the disease were registered. Results. More PD patients than controls reported oral hygiene care support as well as chewing/biting problems, taste disturbance, tooth mobility, and xerostomia, whereas dentate patients had more teeth with carious lesions, tooth root remnants, and biofilm. Both longer duration and higher HY were associated with more chewing problems and, in dentates, more teeth with restorations. In dentates, longer duration of the disease was associated with higher number of mobile teeth. Higher HY was associated with more oral hygiene care support as well as biting problems and, in dentates, more teeth with carious lesions and tooth root remnants. Conclusions. Comparatively, PD patients had weakened oral health status and reduced oral hygiene care. Both duration and severity of the disease were associated with more oral health and hygiene care problems.

Research and clinical practice have focused on effects of a cognitive dual‐task on highly automated motor tasks such as walking or maintaining balance. Despite potential importance for daily life performance, there are only a few small studies on dual‐task effects on upper‐limb motor control. We therefore developed a protocol for assessing cognitive‐motor interference (CMI) during upper‐limb motor control and used it to evaluate dual‐task effects in 57 healthy individuals and two highly prevalent neurological disorders associated with deficits of cognitive and motor processing (57 patients with Parkinson's disease [PD], 57 stroke patients). Performance was evaluated in cognitive and motor domains under single‐ and dual‐task conditions. Patterns of CMI were explored to evaluate overall attentional capacity and attention allocation. As expected, patients with neurological deficits showed different patterns of CMI compared to healthy individuals, depending on diagnosis (PD or stroke) and severity of cognitive and/or motor symptoms. Healthy individuals experienced CMI especially under challenging conditions of the motor task. CMI was greater in PD patients, presumably due to insufficient attentional capacity in relation to increased cognitive involvement in motor control. Although no general increase of CMI was observed in stroke patients, correlation analyses suggested that especially patients with severe motor dysfunction experienced CMI. Clinical ratings of cognitive and motor function were weakly associated with CMI, suggesting that CMI reflects a different construct than these unidimensional clinical tests. It remains to be investigated whether CMI is an indicator of difficulties with day‐to‐day activities.

BACKGROUND: The standard clinical assessment tool in Huntington's disease is the Unified Huntington's Disease Rating Scale (UHDRS). In patients with advanced Huntington's disease ceiling and floor effects of the UHDRS hamper the detection of changes. Therefore, the UHDRS‐For Advanced Patients (UHDRS‐FAP) has been designed for patients with late‐stage Huntington's disease. OBJECTIVES: This cross‐sectional study aims to examine if the UHDRS‐FAP can differentiate better between patients with advanced Huntington's disease than the UHDRS. METHODS: Forty patients, who were institutionalized or received day‐care, were assessed with the UHDRS, UHDRS‐FAP, and Care Dependency Scale (CDS). The severity of Huntington's disease was defined by the Total Functional Capacity (TFC). Comparisons between consecutive TFC stages were performed for all domains of the UHDRS, UHDRS‐FAP, and CDS using Mann‐Whitney U tests. RESULTS: The motor scores of the UHDRS‐FAP and UHDRS were the only subscales with significantly worse scores in TFC stage 5 compared to stage 4. In TFC stages 4‐5, the range of the UHDRS‐FAP motor score was broader, the standard error of measurement was lower, and the effect size r was higher than for the UHDRS motor score. The CDS declined significantly across all TFC stages. CONCLUSIONS: Our results suggest that the UHDRS‐FAP motor score might differentiate better between patients with severe Huntington's disease than the UHDRS motor score. Therefore, the UHDRS‐FAP motor score is potentially a better instrument than the UHDRS motor score to improve disease monitoring and, subsequently, care in patients with advanced Huntington's disease in long‐term care facilities.

Background In Parkinson's disease (PD), the relation between cortical brain atrophy on MRI and clinical progression is not straightforward. Determination of changes in structural covariance networks - patterns of covariance in grey matter density - has shown to be a valuable technique to detect subtle grey matter variations. We evaluated how structural network integrity in PD is related to clinical data. Methods 3 Tesla MRI was performed in 159 PD patients. We used nine standardized structural covariance networks identified in 370 healthy subjects as a template in the analysis of the PD data. Clinical assessment comprised motor features (Movement Disorder Society-Unified Parkinson's Disease Rating Scale; MDS-UPDRS motor scale) and predominantly non-dopaminergic features (SEverity of Non-dopaminergic Symptoms in Parkinson's Disease; SENS-PD scale: postural instability and gait difficulty, psychotic symptoms, excessive daytime sleepiness, autonomic dysfunction, cognitive impairment and depressive symptoms). Voxel-based analyses were performed within networks significantly associated with PD. Results The anterior and posterior cingulate network showed decreased integrity, associated with the SENS-PD score, p = 0.001 (β = − 0.265, ηp2 = 0.070) and p = 0.001 (β = − 0.264, ηp2 = 0.074), respectively. Of the components of the SENS-PD score, cognitive impairment and excessive daytime sleepiness were associated with atrophy within both networks. Conclusions We identified loss of integrity and atrophy in the anterior and posterior cingulate networks in PD patients. Abnormalities of both networks were associated with predominantly non-dopaminergic features, specifically cognition and excessive daytime sleepiness. Our findings suggest that (components of) the cingulate networks display a specific vulnerability to the pathobiology of PD and may operate as interfaces between networks involved in cognition and alertness., Highlights • A novel approach, structural covariance networks, was used in Parkinson's disease. • Loss of integrity and atrophy in two cingulate networks was found in patients. • Structural changes were associated with cognition and alertness.

BACKGROUND: The clinical assessment of motor symptoms in Huntington's disease is usually performed with the Unified Huntington's Disease Rating Scale‐Total Motor Score (UHDRS‐TMS). A high interrater reliability is desirable to monitor symptom progression. Therefore, a teaching video and a system for annual online certification has been developed and implemented. OBJECTIVES: The aim of this study is to investigate the interrater reliability of the UHDRS‐TMS and of its subitems, and to examine the performance of raters in consecutive years. METHODS: Data from the online UHDRS‐TMS certification were used. The interrater reliability was assessed for all first‐time participants (n = 944) between 2009 and 2016. Intraclass correlation coefficients (ICC) were calculated for each year separately and the mean was taken as the total ICC. RESULTS: The UHDRS‐TMS (ICC = 0.847), tandem walking (0.824), pronate/supinate hands left (0.713), and retropulsion pull test (0.706) showed good interrater reliability. Poor interrater reliability was found for maximal dystonia of the left and right upper extremity (0.187 and 0.322, respectively), maximal dystonia of the left and right lower extremity (0.200 and 0.256, respectively), and maximal dystonia of the trunk (0.389), tongue protrusion (0.266), and rigidity arms left (0.390). Raters performed significantly worse on follow‐up certification compared to their first certification. CONCLUSIONS: Our results suggest that the rating of dystonia (absent, slight, mild, moderate, or marked) is subjective and difficult to interpret, especially on video. Therefore, changing the dystonia items of the UHDRS‐TMS should be explored. We also recommend that raters should watch the UHDRS‐TMS teaching video before each certification.

Skin temperature changes due to vasomotor disturbances are important features of complex regional pain syndrome (CRPS). Because this phenomenon has only been studied under controlled conditions, information on daily circadian variability is lacking. Also, studies in chronic CRPS patients with abnormal posturing, in which coldness of the affected extremity is more common, do not exist. We examined the response to external heating as well as circadian temperature changes over several days in the affected legs of 14 chronic CRPS patients with abnormal posturing and 17 controls. Skin temperatures were recorded hourly for 14 days using wireless sensors. Although the patients' affected extremities were significantly colder before external heating, the vasodilatory response was similar in the 2 groups. Additionally, median skin temperature differences between both legs and their variability was larger in patients than in controls during the day, but not during the night. These findings indicate that the mechanisms underlying impaired skin circulation in CRPS during daytime are reversible under certain circumstances. The large variation in skin temperature differences during the day questions the validity of using a single measurement in the diagnosis of CRPS, and our results indicate that only temperature differences >1.0 degrees C should be considered to reflect vasomotor disturbances. Perspective: This article shows that chronic CRPS patients have a normal vasodilatory response to external heating and that skin temperature differences between the affected and unaffected lower limbs, which were highly variable during daytime, disappeared during sleep. This indicates that part of the vasomotor regulation in these patients is still functional. (C) 2015 by the American Pain Society

OBJECTIVE:In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD.METHODS:Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ± 7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III.RESULTS:The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + β) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters.CONCLUSIONS:EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD.SIGNIFICANCE:The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD.

Background The timing of diagnosis of complex regional pain syndrome (CRPS) 1 remains a challenge due to the large heterogeneity of clinical presentations. We describe the distribution and differences in outcomes and clinical manifestations between time points and patient groups with and without CRPS 1 following an initiating event. Methods Prospective cohort study with a consecutive registration of patients presenting with painful swelling of the affected extremity after an initiating event and follow-up visits after 3, 6 and 12 months. Results Forty-two patients were enrolled (37 females, mean age 55.1 years). At baseline, 35 participants (83%, females n = 30) fulfilled the diagnostic criteria for CRPS 1. At 3 months, 19 out of the initial 35 CRPS 1 patients (54%) did not meet the diagnostic criteria anymore. Besides our inclusion criteria of a painful swelling, early manifestations indicating a CRPS 1 primarily include an impaired quality of life (SF-35, EQ5-D), more pain (NRS, MPQ) and restricted range of motion. Conclusions CRPS 1 develops within 8 weeks following a noxious event. Although many CRPS 1 patients reach partial remission within the first 3 months, signs and symptoms do not improve significantly at 1 year. In order to identify prognostic risk factors large prospective cohort studies are needed. Significance This prospective cohort study follows patients with complaints most suspected for complex regional pain syndrome (CRPS) 1. CRPS 1 develops within 8 weeks following a noxious event. Although many CRPS 1 patients reach partial remission within the 3 months, symptoms do not improve significantly at 1 year.

Background Evaluation of therapies for Parkinson's disease (PD) may benefit from objective quantification of the separate movement components of bradykinesia (i.e., velocity, amplitude, and rhythm). This study evaluated the sensitivity and reliability of parameters derived from recently available optical hand tracking techniques for patient-friendly, automated quantification of bradykinesia of the upper extremity in PD. Methods Fifty-seven patients with PD and 57 healthy individuals (controls) performed repetitive finger tapping (RFT), alternating hand movements (AHM), and alternating forearm movements (AFM). Movement components of bradykinesia (i.e., velocity, frequency, amplitude, hesitations, and halts) were quantified using optical hand tracking. Reliability was quantified using intraclass correlation coefficients in a subgroup of 12 patients with PD and 12 controls (test-retest) and in all 57 controls (intra-trial). Results RFT and AHM were successfully recorded in 94% of all participants. Movement components differed between patients with PD and controls and were correlated with clinical ratings. Velocity and halt duration appeared to be most useful (i.e., the largest difference between the PD and control groups, good reliability) for the quantification of RFT, whereas frequency appeared to be most useful for the quantification of AHM. Other variables, such as frequency and amplitude of RFT, showed poor test-retest reliability, because they were susceptible to changes in movement strategy. AFM was excluded from the analysis because of problems with hand recognition. Conclusion Novel optical hand tracking techniques yield promising results for patient-friendly quantification of bradykinesia of the upper extremity in PD. Future work should aim to optimize optical hand tracking and reduce susceptibility to changes in strategy.

Background and purpose Anxiety is common in Parkinson's disease (PD) and has a great influence on quality of life. However, little is known about risk factors for development of anxiety in PD. We investigated which factors were associated with longitudinal changes in severity of anxiety symptoms and development of future anxiety in patients who were not anxious at baseline. Methods Analyses were performed on data of the PROfiling PARKinson's disease (PROPARK) cohort, a 5-year hospital-based longitudinal cohort of over 400 patients with PD who have been examined annually. Linear mixed models were used to identify factors associated with longitudinal changes in Hospital Anxiety and Depression Scale – Anxiety (HADS-A) scores. Survival analysis using data of patients who were not anxious at baseline was performed to identify predictors of future anxiety (i.e. HADS-A ≥ 11). Results Of 409 patients who were included at baseline, 67 (16%) had anxiety, whereas 64 (19%) of the remaining 342 non-anxious patients developed anxiety after a mean (SD) follow-up of 2.6 (1.3) years. Seventy percent of the patients with anxiety were also depressed. Female gender, cognitive impairment, depressive symptoms, dysautonomia, insomnia and excessive daytime sleepiness (EDS) at baseline were associated with higher HADS-A scores over time and, except for female gender and EDS, all of these variables were independent predictors of development of anxiety in patients who were not anxious at baseline. Conclusions Anxiety is highly prevalent in PD. Higher anxiety scores over time and future development of anxiety are associated with female gender, cognitive impairment, autonomic dysfunction, insomnia and EDS. Anxiety and depression usually coexist and share similar determinants, suggesting a common pathophysiological mechanism.