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      Gait Analysis in Parkinson’s Disease: An Overview of the Most Accurate Markers for Diagnosis and Symptoms Monitoring

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          Abstract

          The aim of this review is to summarize that most relevant technologies used to evaluate gait features and the associated algorithms that have shown promise to aid diagnosis and symptom monitoring in Parkinson’s disease (PD) patients. We searched PubMed for studies published between 1 January 2005, and 30 August 2019 on gait analysis in PD. We selected studies that have either used technologies to distinguish PD patients from healthy subjects or stratified PD patients according to motor status or disease stages. Only those studies that reported at least 80% sensitivity and specificity were included. Gait analysis algorithms used for diagnosis showed a balanced accuracy range of 83.5–100%, sensitivity of 83.3–100% and specificity of 82–100%. For motor status discrimination the gait analysis algorithms showed a balanced accuracy range of 90.8–100%, sensitivity of 92.5–100% and specificity of 88–100%. Despite a large number of studies on the topic of objective gait analysis in PD, only a limited number of studies reported algorithms that were accurate enough deemed to be useful for diagnosis and symptoms monitoring. In addition, none of the reported algorithms and technologies has been validated in large scale, independent studies.

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          Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study.

          Levodopa is the most effective therapy for Parkinson's disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube. In our 12-week, randomised, double-blind, double-dummy, double-titration trial, we enrolled adults (aged ≥ 30 years) with advanced Parkinson's disease and motor complications at 26 centres in Germany, New Zealand, and the USA. Eligible participants had jejunal placement of a percutaneous gastrojejunostomy tube, and were then randomly allocated (1:1) to treatment with immediate-release oral levodopa-carbidopa plus placebo intestinal gel infusion or levodopa-carbidopa intestinal gel infusion plus oral placebo. Randomisation was stratified by site, with a mixed block size of 2 or 4. The primary endpoint was change from baseline to final visit in motor off-time. We assessed change in motor on-time without troublesome dyskinesia as a prespecified key secondary outcome. We assessed efficacy in a full-analysis set of participants with data for baseline and at least one post-baseline assessment, and imputed missing data with the last observation carried forward approach. We assessed safety in randomly allocated patients who underwent the percutaneous gastrojejunostomy procedure. This study is registered with ClinicalTrials.gov, numbers NCT00660387 and NCT0357994. From baseline to 12 weeks in the full-analysis set, mean off-time decreased by 4.04 h (SE 0.65) for 35 patients allocated to the levodopa-carbidopa intestinal gel group compared with a decrease of 2.14 h (0.66) for 31 patients allocated to immediate-release oral levodopa-carbidopa (difference -1.91 h [95% CI -3.05 to -0.76]; p=0.0015). Mean on-time without troublesome dyskinesia increased by 4.11 h (SE 0.75) in the intestinal gel group and 2.24 h (0.76) in the immediate-release oral group (difference 1.86 [95% CI 0.56 to 3.17]; p=0.0059). In the safety analyses 35 (95%) of 37 patients allocated to the levodopa-carbidopa intestinal gel group had adverse events (five [14%] serious), as did 34 (100%) of 34 patients allocated to the immediate-release oral levodopa-carbidopa group (seven [21%] serious), mainly associated with the percutaneous gastrojejunostomy tube. Continuous delivery of levodopa-carbidopa with an intestinal gel offers a promising option for control of advanced Parkinson's disease with motor complications. Benefits noted with intestinal gel delivery were of a greater magnitude than were those obtained with medical therapies to date, and our study is, to our knowledge, the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study. AbbVie. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Gait impairments in Parkinson's disease

            Gait impairments are among the most common and disabling symptoms of Parkinson's disease. Nonetheless, gait is not routinely assessed quantitatively but is described in general terms that are not sensitive to changes ensuing with disease progression. Quantifying multiple gait features (eg, speed, variability, and asymmetry) under natural and more challenging conditions (eg, dual-tasking, turning, and daily living) enhanced sensitivity of gait quantification. Studies of neural connectivity and structural network topology have provided information on the mechanisms of gait impairment. Advances in the understanding of the multifactorial origins of gait changes in patients with Parkinson's disease promoted the development of new intervention strategies, such as neurostimulation and virtual reality, aimed at alleviating gait impairments and enhancing functional mobility. For clinical applicability, it is important to establish clear links between specific gait impairments, their underlying mechanisms, and disease progression to foster the acceptance and usability of quantitative gait measures as outcomes in future disease-modifying clinical trials.
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              Gait assessment in Parkinson's disease: toward an ambulatory system for long-term monitoring.

              An ambulatory gait analysis method using body-attached gyroscopes to estimate spatio-temporal parameters of gait has been proposed and validated against a reference system for normal and pathologic gait. Later, ten Parkinson's disease (PD) patients with subthalamic nucleus deep brain stimulation (STN-DBS) implantation participated in gait measurements using our device. They walked one to three times on a 20-m walkway. Patients did the test twice: once STN-DBS was ON and once 180 min after turning it OFF. A group of ten age-matched normal subjects were also measured as controls. For each gait cycle, spatio-temporal parameters such as stride length (SL), stride velocity (SV), stance (ST), double support (DS), and gait cycle time (GC) were calculated. We found that PD patients had significantly different gait parameters comparing to controls. They had 52% less SV, 60% less SL, and 40% longer GC. Also they had significantly longer ST and DS (11% and 59% more, respectively) than controls. STN-DBS significantly improved gait parameters. During the stim ON period, PD patients had 31% faster SV, 26% longer SL, 6% shorter ST, and 26% shorter DS. GC, however, was not significantly different. Some of the gait parameters had high correlation with Unified Parkinson's Disease Rating Scale (UPDRS) subscores including SL with a significant correlation (r = -0.90) with UPDRS gait subscore. We concluded that our method provides a simple yet effective way of ambulatory gait analysis in PD patients with results confirming those obtained from much more complex and expensive methods used in gait labs.
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                Author and article information

                Journal
                Sensors (Basel)
                Sensors (Basel)
                sensors
                Sensors (Basel, Switzerland)
                MDPI
                1424-8220
                22 June 2020
                June 2020
                : 20
                : 12
                : 3529
                Affiliations
                [1 ]Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome, Italy; a.disanto@ 123456unicampus.it (A.D.S.); m.caminiti@ 123456unicampus.it (M.L.C.); a.deliso@ 123456unicampus.it (A.D.L.); lorenzo.ricci@ 123456unicampus.it (L.R.); v.dilazzaro@ 123456unicampus.it (V.D.L.)
                [2 ]Usher Institute, Edinburgh Medical School: Molecular, Genetic and Population Health Sciences, The University of Edinburgh, EH16 4UX Edinburgh, UK; ahmar.shah@ 123456ed.ac.uk
                Author notes
                Author information
                https://orcid.org/0000-0002-3668-469X
                https://orcid.org/0000-0002-9113-5925
                Article
                sensors-20-03529
                10.3390/s20123529
                7349580
                32580330
                7494f6b6-a1be-4204-8e6f-6ffe2e8a19a1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 June 2020
                : 17 June 2020
                Categories
                Review

                Biomedical engineering
                parkinson’s disease,gait analysis,diagnosis,symptoms monitoring,wearable,home-monitoring,machine learning

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