LSVT LOUD and LSVT BIG: Behavioral Treatment Programs for Speech and Body Movement in Parkinson Disease

Recent advances in neuroscience have suggested that exercise-based behavioral treatments may improve function and possibly slow progression of motor symptoms in individuals with Parkinson disease (PD). The LSVT (Lee Silverman Voice Treatment) Programs for individuals with PD have been developed and researched over the past 20 years beginning with a focus on the speech motor system (LSVT LOUD) and more recently have been extended to address limb motor systems (LSVT BIG). The unique aspects of the LSVT Programs include the combination of (a) an exclusive target on increasing amplitude (loudness in the speech motor system; bigger movements in the limb motor system), (b) a focus on sensory recalibration to help patients recognize that movements with increased amplitude are within normal limits, even if they feel “too loud” or “too big,” and (c) training self-cueing and attention to action to facilitate long-term maintenance of treatment outcomes. In addition, the intensive mode of delivery is consistent with principles that drive activity-dependent neuroplasticity and motor learning. The purpose of this paper is to provide an integrative discussion of the LSVT Programs including the rationale for their fundamentals, a summary of efficacy data, and a discussion of limitations and future directions for research

An autopsy-confirmed case of progressive supranuclear palsy with predominant postural instability

Postural instability and supranuclear gaze palsy represent the key symptoms of Richardson's syndrome, the most frequent clinical manifestation of progressive supranuclear palsy (PSP). However, a proportion of PSP patients never develops ocular motor symptoms, which prevents clinicians from establishing the diagnosis during lifetime according to current diagnostic criteria. We present one instructive autopsy-confirmed PSP case with prospective video-documented clinical course, showing striking temporal divergence of initially present postural instability and delayed development of ocular motor dysfunction. Brain imaging and autopsy findings were typical of PSP, but the temporal sequence of symptoms was unusual with isolated postural instability predominating the clinical course for many years and slowing of vertical saccades/supranuclear gaze palsy evolving not until the 9th/11th year after disease onset. Although other differential diagnoses were unlikely, this patient did not pass the threshold for possible or probable diagnosis of PSP according to current diagnostic criteria until very late in the disease course. This first well documented, autopsy confirmed case of PSP with predominant postural instability further expands the clinical spectrum of PSP and points out the need of new clinical diagnostic criteria with sufficient sensitivity and specificity for an early and reliable diagnosis

Data from an Observational Study

Introduction Effective management and development of new treatment strategies for response fluctuations in advanced Parkinson’s disease (PD) largely depends on clinical rating instruments such as the PD home diary. The Parkinson’s kinetigraph (PKG) measures movement accelerations and analyzes the spectral power of the low frequencies of the accelerometer data. New algorithms convert each hour of continuous PKG data into one of the three motor categories used in the PD home diary, namely motor Off state and On state with and without dyskinesia. Objective To compare quantitative motor state assessment in fluctuating PD patients using the PKG with motor state ratings from PD home diaries. Methods Observational cohort study on 24 in-patients with documented motor fluctuations who completed diaries by rating motor Off, On without dyskinesia, On with dyskinesia, and asleep for every hour for 5 consecutive days. Simultaneously collected PKG data (recorded between 6 am and 10 pm) were analyzed and calibrated to the patient’s individual thresholds for Off and dyskinetic state by novel algorithms classifying the continuous accelerometer data into these motor states for every hour between 6 am and 10 pm. Results From a total of 2,040 hours, 1,752 hours (87.4%) were available for analyses from calibrated PKG data (7.5% sleeping time and 5.1% unclassified motor state time were excluded from analyses). Distributions of total motor state hours per day measured by PKG showed moderate-to-strong correlation to those assessed by diaries for the different motor states (Pearson’s correlations coefficients: 0.404–0.658), but inter-rating method agreements on the single- hour-level were only low-to-moderate (Cohen’s κ: 0.215–0.324). Conclusion The PKG has been shown to capture motor fluctuations in patients with advanced PD. The limited correlation of hour-to-hour diary and PKG recordings should be addressed in further studies

The Shaking Palsy of the Larynx—Potential Biomarker for Multiple System Atrophy: A Pilot Study and Literature Review

In its early stages multiple system atrophy (MSA), a neurodegenerative movement disorder, can be difficult to differentiate from idiopathic Parkinson's disease (PD), and emphasis has been put on identifying premotor symptoms to allow for its early identification. The occurrence of vegetative symptoms in addition to motor impairment, such as orthostatic hypotension and neurogenic bladder dysfunction, enable the clinical diagnosis in the advanced stages of the disease. Usually with further disease progression, laryngeal abnormalities become clinically evident and can manifest in laryngeal stridor due to impaired vocal fold motion, such as vocal fold abduction restriction, mostly referred to as vocal fold paresis, or paradoxical vocal fold adduction during inspiration. While the pathogenesis of laryngeal stridor is discussed controversially, its occurrence is clearly associated with reduced life expectancy. Before the clinical manifestation of laryngeal dysfunction however, abnormal vocal fold motion can already be seen in patients that might not yet fulfill the diagnostic criteria of MSA. In this article we summarize the current literature on pharyngolaryngeal findings in MSA and report preliminary findings from a pilot study investigating eight consecutive MSA patients. Patients showed varying speech abnormalities. Only 2/8 patients exhibited laryngeal stridor. However, during FEES, all patients presented with irregular arytenoid cartilages movements and vocal fold abduction restriction. 3/8 showed vocal fold fixation and 1/8 paradoxical vocal fold motion. All patients presented with oropharyngeal dysphagia, 5/8 with penetration or aspiration events. We suggest that specific abnormal vocal fold motion can help identifying MSA patients and may allow for delimiting this disorder from idiopathic PD. These findings therefore may serve as a novel clinical biomarker for MSA. Based on the available data and our preliminary clinical experience we developed a standardized easy-to-implement task-protocol to be performed during flexible endoscopic evaluation of swallowing (FEES) for detection of MSA-related pharyngolaryngeal movement disorders. Furthermore, we initiated a prospective study to evaluate the diagnostic utility of this protocol

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Altered moral decision-making in patients with idiopathic Parkinson's disease

Background: Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. Methods: Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented altruistic choices to self-beneficial egoistic choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. Results: PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. Conclusions: This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits. (C) 2015 Elsevier Ltd. All rights reserved

De Bibliothecis, Laudatis. Maiorum Institutis : ut Venerandi Dnn. Inspectores, Patroni, Fautores, Amici Faciles in auscultando Dicturis quibusdam Scholae Alumnis se praebeant Kal. Novembr. A.O.R. MDCXCV. ab Hora IIX. Matutina Maximo rogat opere M. David Winter/ Rector

Nicht identisch mit VD17 35:719570N (abweichende Zeilenbrechung auf der Titels.)Vorlagform des Erscheinungsverm.: Cygneae, Literis BittorffianisMit Einladung zu den Vorträgen von Christoph Müller aus Übigau, Salomon Deyling aus Lengefeld und Johann Georg Ebersbach aus Elsterber

Disease stage dependency of motor and non-motor fluctuations in Parkinson's disease

Recent data suggested a decrease in non-motor fluctuations in late-stage Parkinson's disease (PD), but systematic data on non-motor fluctuations over the whole disease course are mainly lacking. We performed a meta-analysis of two studies with very similar cross-sectional cohort designs, namely the German multicenter Non Motor Fluctuation in PD study and the Swedish part of the European multicenter study Care for Late Stage Parkinsonism. We included only patients with documented motor fluctuations in the analyses. Disease stage was estimated using the Hoehn and Yahr score, motor symptoms using the Unified PD Rating Scale part III motor score and non-motor symptom (NMS) fluctuations using the modified version of the NMS scale assessing a broad range of NMS in motor On and Off state. We included 101 patients (55% men; median age: 71 (interquartile range, IQR 65-78) years with Hoehn and Yahr stages ranging from 1 to 5 [median (IQR) 3.0 (2.0-4.0); distribution of patients in Hoehn and Yahr stages was n = 42 (42%) in stages 2/3 and n = 48 (48%) in stages 4/5]. We found a clear dependency of non-motor burden on Hoehn and Yahr stage with increasing symptom severity, but decreasing fluctuation amplitudes for motor and NMS (difference of symptom severity between On and Off state) with disease stage progression. Indeed, in Hoehn and Yahr stage 5, we did not detect significant NMS fluctuations. Multivariate regression with major demographic and clinical covariates confirmed these results. In conclusion, NMS fluctuations showed a similar disease stage dependency as observed for motor fluctuations with decreasing fluctuation amplitude with disease progression

Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson’s Disease

Nonmotor symptoms (NMS) fluctuate in conjunction with motor oscillations in advanced Parkinson's disease (PD), though little is known about the variability of NMS fluctuations in individual patients. We aimed to assess within-patient variability in frequency and severity of NMS during a series of five patient-perceived motor On and Off periods in 38 fluctuating PD patients from the multicenter NonMotorFluctuations in PD study using a visual analogue scale. NMS frequency and severity appeared moderately variable in both motor states within individual patients. Symptom severity ranges between motor states showed high variability and were larger in motor Off states for most NMS