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1.
J Neurol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048014

RESUMO

BACKGROUND: Impaired gait plays an important role for quality of life in patients with Huntington's disease (HD). Measuring objective gait parameters in HD might provide an unbiased assessment of motor deficits in order to determine potential beneficial effects of future treatments. OBJECTIVE: To objectively identify characteristic features of gait in HD patients using sensor-based gait analysis. Particularly, gait parameters were correlated to the Unified Huntington's Disease Rating Scale, total motor score (TMS), and total functional capacity (TFC). METHODS: Patients with manifest HD at two German sites (n = 43) were included and clinically assessed during their annual ENROLL-HD visit. In addition, patients with HD and a cohort of age- and gender-matched controls performed a defined gait test (4 × 10 m walk). Gait patterns were recorded by inertial sensors attached to both shoes. Machine learning algorithms were applied to calculate spatio-temporal gait parameters and gait variability expressed as coefficient of variance (CV). RESULTS: Stride length (- 15%) and gait velocity (- 19%) were reduced, while stride (+ 7%) and stance time (+ 2%) were increased in patients with HD. However, parameters reflecting gait variability were substantially altered in HD patients (+ 17% stride length CV up to + 41% stride time CV with largest effect size) and showed strong correlations to TMS and TFC (0.416 ≤ rSp ≤ 0.690). Objective gait variability parameters correlated with disease stage based upon TFC. CONCLUSIONS: Sensor-based gait variability parameters were identified as clinically most relevant digital biomarker for gait impairment in HD. Altered gait variability represents characteristic irregularity of gait in HD and reflects disease severity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32086225

RESUMO

Mobile gait analysis using wearable inertial measurement units (IMUs) provides valuable insights for the assessment of movement impairments in different neurological and musculoskeletal diseases, for example Parkinson's disease (PD). The increase in data volume due to arising long-term monitoring requires valid, robust and efficient analysis pipelines. In many studies an upstream detection of gait is therefore applied. However, current methods do not provide a robust way to successfully reject non-gait signals. Therefore, we developed a novel algorithm for the detection of gait from continuous inertial data of sensors worn at the feet. The algorithm is focused not only on a high sensitivity but also a high specificity for gait. Sliding windows of IMU signals recorded from the feet of PD patients were processed in the frequency domain. Gait was detected if the frequency spectrum contained specific patterns of harmonic frequencies. The approach was trained and evaluated on 150 clinical measurements containing standardized gait and cyclic movement tests. The detection reached as sensitivity of 0.98 and a specificity of 0.96 for the best sensor configuration (angular rate around the medio-lateral axis). On an independent validation data set including 203 unsupervised, semi-standardized gait tests, the algorithm achieved a sensitivity of 0.97. Our algorithm for the detection of gait from continuous IMU signals works reliably and showed promising results for the application in the context of free-living and non-standardized monitoring scenarios.

3.
Eur J Cancer Care (Engl) ; : e13199, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829481

RESUMO

OBJECTIVE: Gait is a sensitive marker for functional declines commonly seen in patients treated for advanced cancer. We tested the effect of a combined exercise and nutrition programme on gait parameters of advanced-stage cancer patients using a novel wearable gait analysis system. METHODS: Eighty patients were allocated to a control group with nutritional support or to an intervention group additionally receiving whole-body electromyostimulation (WB-EMS) training (2×/week). At baseline and after 12 weeks, physical function was assessed by a biosensor-based gait analysis during a six-minute walk test, a 30-s sit-to-stand test, a hand grip strength test, the Karnofsky Index and EORTC QLQ-C30 questionnaire. Body composition was measured by bioelectrical impedance analysis and inflammation by blood analysis. RESULTS: Final analysis included 41 patients (56.1% male; 60.0 ± 13.0 years). After 12 weeks, the WB-EMS group showed higher stride length, gait velocity (p < .05), six-minute walking distance (p < .01), bodyweight and skeletal muscle mass, and emotional functioning (p < .05) compared with controls. Correlations between changes in gait and in body composition, physical function and inflammation were detected. CONCLUSION: Whole-body electromyostimulation combined with nutrition may help to improve gait and functional status of cancer patients. Sensor-based mobile gait analysis objectively reflects patients' physical status and could support treatment decisions.

4.
eNeuro ; 6(6)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31604813

RESUMO

Gait analysis of transgenic mice and rats modeling human diseases often suffers from the condition that those models exhibit genotype-driven differences in body size, weight, and length. Thus, we hypothesized that scaling by the silhouette length improves the reliability of gait analysis allowing normalization for individual body size differences. Here, we computed video-derived silhouette length and area parameters from a standard markerless gait analysis system using image-processing techniques. By using length- and area-derived data along with body weight and age, we systematically scaled individual gait parameters. We compared these different scaling approaches and report here that normalization for silhouette length improves the validity and reliability of gait analysis in general. The application of this silhouette length scaling to transgenic Huntington disease mice and Parkinson´s disease rats identifies the remaining differences reflecting more reliable, body length-independent motor functional differences. Overall, this emphasizes the need for silhouette-length-based intra-assay scaling as an improved standard approach in rodent gait analysis.

5.
J Neurol Phys Ther ; 43(4): 224-232, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31517749

RESUMO

BACKGROUND AND PURPOSE: Perturbation training is a promising approach to reduce fall incidence in persons with Parkinson disease (PwPD). This study aimed to evaluate interindividual differences in balance adaptations in response to perturbation treadmill training (PTT) and identify potential outcome predictors. METHODS: PwPD (n = 43, Hoehn & Yahr stage 1-3.5) were randomly assigned to either 8 weeks of PTT or conventional treadmill training (CTT) without perturbations. At baseline and following intervention, data from 4 domains of balance function (reactive, anticipatory, dynamic postural control, and quiet stance) were collected. Using responder analysis we investigated interindividual differences (responder rates and magnitude of change) and potential predictive factors. RESULTS: PTT showed a significantly higher responder rate in the Mini Balance Evaluation Systems Test (Mini-BESTest) subscore reactive postural control, compared with CTT (PTT = 44%; CTT = 10%; risk ratio = 4.22, confidence interval = 1.03-17.28). Additionally, while between-groups differences were not significant, the proportion of responders in the measures of dynamic postural control was higher for PTT compared with CTT (PTT: 22%-39%; CTT: 5%-10%). The magnitude of change in responders and nonresponders was similar in both groups. PTT responders showed significantly lower initial balance performance (4/8 measures) and cognitive function (3/8 measures), and were older and at a more advanced disease stage, based on descriptive evaluation. DISCUSSION AND CONCLUSIONS: Our findings suggest that PTT is beneficial to improve reactive balance in PwPD. Further, PTT appeared to be effective only for a part of PwPD, especially for those with lower balance and cognitive function, which needs further attention.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A1).

6.
J Parkinsons Dis ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31424420

RESUMO

BACKGROUND: Parkinson's disease (PD) is an age dependent neurodegenerative disorder with increasing prevalence. Digital technologies like computers and smartphones offer mobile telecommunication, diagnostic and monitoring and may connect the patient continuously with his healthcare team, providing disease related information, and support healthcare. Since the use of these technologies in western civilization is age dependent, possession and usage cannot be regarded as given in PD. In contrast to increasing efforts to implement digital technology into PD patient care, little is known about the use of computers, smartphones, and internet-affinity in PD patients. OBJECTIVE: We evaluated the use of digital technologies in different age groups of PD patients. METHODS: We developed a questionnaire adapted to the annual German microcensus on "use of digital communication technologies", allowing a comparison to the general population in Germany. RESULTS: 190 PD patients completed the questionnaire. About 75% of PD patients access disease related information on the internet. Patients across all age groups used computers and the internet as frequent or more frequently compared to the German population. Use of computers, smartphones, and the internet in PD was age dependent. Advanced PD patients with higher motor impairment used smartphones less often, while mobile phone usage was not reduced. CONCLUSION: The adoption of a digital lifestyle is present in the PD population, apart from smartphone usage, which is impaired by motor symptoms. Thus, future healthcare technologies are not hampered by the inability of PD patients to use the necessary tools, however, fine motor-skill requirements have to be acknowledged.

7.
Nervenarzt ; 90(8): 787-795, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31309270

RESUMO

Fitness and lifestyle trackers raise the awareness for wearable sensors in medical applications for clinical trials and healthcare. Various functional impairments of patients with neurological diseases are an ideal target to generate wearable-derived and patient-centered parameters that have the potential to support prevention, prediction, diagnostic procedures and therapy monitoring during the clinical work-up; however, substantial differences between clinical grade wearables and fitness trackers have to be acknowledged. For the application in clinical trials or individualized patient care distinct technical and clinical validation trials have to be conducted. The different test environments under laboratory conditions during standardized tests or under unsupervised home monitoring conditions have to be included in the algorithmic processing of sensor raw data in order to enable a clinical decision support under real-life conditions. This article presents the general understanding of the technical application for the most relevant functional impairments in neurology. While wearables used for sleep assessment have already reached a high level of technological readiness due to the defined test environment (bed, sleep), other wearable applications, e.g. for gait and mobility during home monitoring require further research in order to transfer the technical capabilities into real-life patient care.


Assuntos
Monitorização Ambulatorial , Doenças do Sistema Nervoso , Dispositivos Eletrônicos Vestíveis , Exercício , Monitores de Aptidão Física/normas , Marcha , Humanos , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/tendências , Doenças do Sistema Nervoso/terapia , Dispositivos Eletrônicos Vestíveis/normas
8.
Sensors (Basel) ; 19(14)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337067

RESUMO

Mobile gait analysis systems using wearable sensors have the potential to analyze and monitor pathological gait in a finer scale than ever before. A closer look at gait in Parkinson's disease (PD) reveals that turning has its own characteristics and requires its own analysis. The goal of this paper is to present a system with on-shoe wearable sensors in order to analyze the abnormalities of turning in a standardized gait test for PD. We investigated turning abnormalities in a large cohort of 108 PD patients and 42 age-matched controls. We quantified turning through several spatio-temporal parameters. Analysis of turn-derived parameters revealed differences of turn-related gait impairment in relation to different disease stages and motor impairment. Our findings confirm and extend the results from previous studies and show the applicability of our system in turning analysis. Our system can provide insight into the turning in PD and be used as a complement for physicians' gait assessment and to monitor patients in their daily environment.


Assuntos
Algoritmos , Monitorização Fisiológica/instrumentação , Doença de Parkinson/fisiopatologia , Sapatos , Dispositivos Eletrônicos Vestíveis , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Desenho de Equipamento , Feminino , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Reprodutibilidade dos Testes , Análise Espaço-Temporal
9.
J Neurosci Methods ; 326: 108367, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351096

RESUMO

BACKGROUND: Motor impairment appears as a characteristic symptom of several diseases and injuries. Therefore, tests for analyzing motor dysfunction are widely applied across preclinical models and disease stages. Among those, gait analysis tests are commonly used, but they generate a huge number of gait parameters. Thus, complications in data analysis and reporting raise, which often leads to premature parameter selection. NEW METHODS: In order to avoid arbitrary parameter selection, we present here a systematic initial data analysis by utilizing heat-maps for data reporting. We exemplified this approach within an intervention study, as well as applied it to two longitudinal studies in rodent models related to Parkinson's disease (PD) and Huntington disease (HD). RESULTS: The systematic initial data analysis (IDA) is feasible for exploring gait parameters, both in experimental and longitudinal studies. The resulting heat maps provided a visualization of gait parameters within a single chart, highlighting important clusters of differences. COMPARISON WITH EXISTING METHOD: Often, premature parameter selection is practiced, lacking comprehensiveness. Researchers often use multiple separated graphs on distinct gait parameters for reporting. Additionally, negative results are often not reported. CONCLUSIONS: Heat mapping utilized in initial data analysis is advantageous for reporting clustered gait parameter differences in one single chart and improves data mining.

10.
J Neuroeng Rehabil ; 16(1): 98, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349860

RESUMO

The original article [1] contained an error whereby Fig. 6 contained a minor shading glitch affecting its presentation. This has now been corrected.

11.
J Neuroeng Rehabil ; 16(1): 77, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242915

RESUMO

BACKGROUND: Gait symptoms and balance impairment are characteristic indicators for the progression in Parkinson's disease (PD). Current gait assessments mostly focus on straight strides with assumed constant velocity, while acceleration/deceleration and turning strides are often ignored. This is either due to the set up of typical clinical assessments or technical limitations in capture volume. Wearable inertial measurement units are a promising and unobtrusive technology to overcome these limitations. Other gait phases such as initiation, termination, transitioning (between straight walking and turning) and turning might be relevant as well for the evaluation of gait and balance impairments in PD. METHOD: In a cohort of 119 PD patients, we applied unsupervised algorithms to find different gait clusters which potentially include the clinically relevant information from distinct gait phases in the standardized 4x10 m gait test. To clinically validate our approach, we determined the discriminative power in each gait cluster to classify between impaired and unimpaired PD patients and compared it to baseline (analyzing all straight strides). RESULTS: As a main result, analyzing only one of the gait clusters constant, non-constant or turning led in each case to a better classification performance in comparison to the baseline (increase of area under the curve (AUC) up to 19% relative to baseline). Furthermore, gait parameters (for turning, constant and non-constant gait) that best predict motor impairment in PD were identified. CONCLUSIONS: We conclude that a more detailed analysis in terms of different gait clusters of standardized gait tests such as the 4x10 m walk may give more insights about the clinically relevant motor impairment in PD patients.

12.
Z Gerontol Geriatr ; 52(4): 316-323, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161336

RESUMO

BACKGROUND: Personal autonomy in advanced age critically depends on mobility in the environment. Geriatric patients are often not able to walk safely with sufficient velocity. In many cases, multiple factors contribute to the deficit. Diagnostic identification of single components enables a specific treatment. OBJECTIVE: This article describes the most common neurological causes of imbalance and impaired gait that are relevant for a pragmatic approach for the assessment of deficits in clinical and natural environments taking into account the physiology of balance and gait control, typical morbidities in older people and the potential of innovative assessment technologies. MATERIAL AND METHODS: Expert opinion based on a narrative review of the literature and with reference to selected research topics. RESULTS AND DISCUSSION: Common neurological causes of impaired balance and mobility are sensory deficits (reduced vision, peripheral neuropathy, vestibulopathy), neurodegeneration in disorders with an impact on movement control and motoric functions (Parkinsonian syndromes, cerebellar ataxia, vascular encephalopathy) and functional (psychogenic) disorders, particularly a fear of falling. Clinical tests and scores in laboratory environments are complemented by the assessment in the natural environment. Wearable sensors, mobile smartphone-based assessment of symptoms and functions and adopted strategies for analysis are currently emerging. Use of these data enables a personalized treatment. Furthermore, sensor-based assessment ensures that effects are measured objectively.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/terapia , Avaliação Geriátrica/métodos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Equilíbrio Postural , Idoso , Idoso de 80 Anos ou mais , Tontura/fisiopatologia , Tontura/psicologia , Marcha , Transtornos Neurológicos da Marcha/etiologia , Humanos , Doenças do Sistema Nervoso/complicações , Caminhada
13.
J Parkinsons Dis ; 9(2): 413-426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30958316

RESUMO

BACKGROUND: Impaired gait and postural stability are cardinal motor symptoms in Parkinson's disease (PD). Treadmill training improves gait characteristics in PD. OBJECTIVE: This study investigates if postural perturbations during treadmill training improve motor performance and particularly gait and postural stability in PD. METHODS: This work presents secondary outcome measures of a pilot randomized controlled trial. PD patients (n = 43) recruited at the University Hospital Erlangen were randomly allocated to the experimental (perturbation treadmill training, PTT, n = 21) or control group (conventional treadmill training, CTT, n = 22). Outcome measures were collected at baseline, after 8 weeks of intervention, and 3 months follow-up. Motor impairment was assessed by the Unified Parkinson Disease Rating Scale part-III (UPDRS-III), Postural Instability and Gait Difficulty score (PIGD), and subitems 'Gait' and 'Postural stability' by an observer blinded to the randomization. Intervention effects were additionally compared to progression rates of a matched PD cohort (n = 20) receiving best medical treatment (BMT). RESULTS: Treadmill training significantly improved UPDRS-III motor symptoms in both groups with larger effect sizes for PTT (-38%) compared to CTT (-20%). In the PTT group solely, PIGD -34%, and items 'Gait' -50%, and 'Postural stability' -40% improved significantly in comparison to CTT (PIGD -24%, 'Gait' -22%, 'Postural stability' -33%). Positive effects persisted in PTT after 3 months and appeared to be beneficial compared to BMT. CONCLUSIONS: Eight weeks of PTT showed superior improvements of motor symptoms, particularly gait and postural stability. Sustainable effects indicate that PTT may be an additive therapy option for gait and balance deficits in PD.

15.
Mov Disord ; 34(5): 657-663, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30901495

RESUMO

Obtaining reliable longitudinal information about everyday functioning from individuals with Parkinson's disease (PD) in natural environments is critical for clinical care and research. Despite advances in mobile health technologies, the implementation of digital outcome measures is hindered by a lack of consensus on the type and scope of measures, the most appropriate approach for data capture (eg, in clinic or at home), and the extraction of timely information that meets the needs of patients, clinicians, caregivers, and health care regulators. The Movement Disorder Society Task Force on Technology proposes the following objectives to facilitate the adoption of mobile health technologies: (1) identification of patient-centered and clinically relevant digital outcomes; (2) selection criteria for device combinations that offer an acceptable benefit-to-burden ratio to patients and that deliver reliable, clinically relevant insights; (3) development of an accessible, scalable, and secure platform for data integration and data analytics; and (4) agreement on a pathway for approval by regulators, adoption into e-health systems and implementation by health care organizations. We have developed a tentative roadmap that addresses these needs by providing the following deliverables: (1) results and interpretation of an online survey to define patient-relevant endpoints, (2) agreement on the selection criteria for use of device combinations, (3) an example of an open-source platform for integrating mobile health technology output, and (4) recommendations for assessing readiness for deployment of promising devices and algorithms suitable for regulatory approval. This concrete implementation guidance, harmonizing the collaborative endeavor among stakeholders, can improve assessments of individuals with PD, tailor symptomatic therapy, and enhance health care outcomes. © 2019 International Parkinson and Movement Disorder Society.

16.
Front Neurol ; 10: 5, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30723450

RESUMO

Background: Differentiating idiopathic Parkinson's disease (IPD) from atypical Parkinsonian disorders (APD) is challenging, especially in early disease stages. Postural instability and gait difficulty (PIGD) are substantial motor impairments of IPD and APD. Clinical evidence implies that patients with APD have larger PIGD impairment than IPD patients. Sensor-based gait analysis as instrumented bedside test revealed more gait deficits in APD compared to IPD. However, the diagnostic value of instrumented bedside tests compared to clinical assessments in differentiating APD from IPD patients have not been evaluated so far. Objective: The objectives were (a) to evaluate whether sensor-based gait parameters provide additional information to validated clinical scores in differentiating APD from matched IPD patients, and (b) to investigate if objective, instrumented gait assessments have comparable discriminative power to clinical scores. Methods: In a previous study we have recorded instrumented gait parameters in patients with APD (Multiple System Atrophy and Progressive Supranuclear Palsy). Here, we compared gait parameters to those of retrospectively pairwise disease duration-, age-, and gender-matched IPD patients in order to address this new research questions. To this aim, the PIGD score was calculated as sum of the MDS-UPDRS-3-items "gait," "postural stability," "arising from chair," and "posture." Gait characteristics were evaluated in standardized gait tests using an instrumented, sensor-based gait analysis system. Machine learning algorithms were used to extract spatio-temporal gait parameters. Receiver Operating Characteristic analysis was performed in order to detect the discriminative power of the instrumented vs. the clinical bedside tests in differentiating IPD from APD. Results: Sensor-based stride length, gait velocity, toe off angle, and parameters representing gait variability significantly differed between IPD and APD groups. ROC analysis revealed a high Area Under the Curve (AUC) for PIGD score (0.919), and UPDRS-3 (0.848). Particularly, the objective parameters stance time variability (0.841), swing time variability (0.834), stride time variability (0.821), and stride length variability (0.804) reached high AUC's as well. Conclusions: PIGD symptoms showed high discriminative power in differentiating IPD from APD supporting gait disorders as substantial diagnostic target. Sensor-based gait variability parameters provide metric, objective added value, and serve as complementary outcomes supporting clinical diagnostics and long-term home-monitoring concepts.

17.
Hum Mov Sci ; 64: 123-132, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30711905

RESUMO

BACKGROUND: Gait impairment is a major motor symptom in Parkinson's disease (PD), and treadmill training is an effective non-pharmacological treatment option. RESEARCH QUESTION: In this study, the time course, sustainability and transferability of gait adaptations to treadmill training with and without additional postural perturbations were investigated. METHODS: 38 PD patients (Hoehn & Yahr 1-3.5) were randomly allocated to eight weeks of treadmill training, performed twice-weekly for 40 min either with (perturbation treadmill training [PTT], n = 18) or without (conventional treadmill training [CTT], n = 20) additional perturbations to the treadmill surface. Spatiotemporal gait parameters were assessed during treadmill walking on a weekly basis (T0-T8), and after three months follow-up (T9). Additional overground gait analyses were performed at T0 and T8 to investigate transfer effects. RESULTS: Treadmill gait variability reduced linearly over the course of 8 weeks in both groups (p < .001; Cohen's d (range): -0.53 to -0.84). Only the PTT group significantly improved in other gait parameters (stride length/time, stance-/swing time), with stride time showing a significant between-group interaction effect (Cohen's d = 0.33; p = .05). Additional between-group interactions indicated more sustained improvements in stance (Cohen's d = 0.85; p = .02) and swing time variability in the PTT group (Cohen's d = 0.82; p = .03) at T9. Overground gait improvements at T8 existed only in stance (d = -0.73; p = .04) and swing time (d = 0.73; p = .04). DISCUSSION: Treadmill stride-to-stride variability reduced substantially and linearly, but transfer to overground walking was limited. Adding postural perturbations tended to increase efficacy and sustainability of several gait parameters. However, since between-group effects were small, more work is necessary to support these findings.


Assuntos
Doença de Parkinson/fisiopatologia , Caminhada/fisiologia , Adaptação Fisiológica/fisiologia , Idoso , Teste de Esforço/métodos , Feminino , Marcha/fisiologia , Análise da Marcha/métodos , Transtornos Neurológicos da Marcha , Humanos , Masculino , Resultado do Tratamento
18.
Sci Rep ; 9(1): 544, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679445

RESUMO

Cell-to-cell propagation of aggregated alpha synuclein (aSyn) has been suggested to play an important role in the progression of alpha synucleinopathies. A critical step for the propagation process is the accumulation of extracellular aSyn within recipient cells. Here, we investigated the trafficking of distinct exogenous aSyn forms and addressed the mechanisms influencing their accumulation in recipient cells. The aggregated aSyn species (oligomers and fibrils) exhibited more pronounced accumulation within recipient cells than aSyn monomers. In particular, internalized extracellular aSyn in the aggregated forms was able to seed the aggregation of endogenous aSyn. Following uptake, aSyn was detected along endosome-to-lysosome and autophagosome-to-lysosome routes. Intriguingly, aggregated aSyn resulted in lysosomal activity impairment, accompanied by the accumulation of dilated lysosomes. Moreover, analysis of autophagy-related protein markers suggested decreased autophagosome clearance. In contrast, the endocytic pathway, proteasome activity, and mitochondrial homeostasis were not substantially affected in recipient cells. Our data suggests that extracellularly added aggregated aSyn primarily impairs lysosomal activity, consequently leading to aSyn accumulation within recipient cells. Importantly, the autophagy inducer trehalose prevented lysosomal alterations and attenuated aSyn accumulation within aSyn-exposed cells. Our study underscores the importance of lysosomes for the propagation of aSyn pathology, thereby proposing these organelles as interventional targets.

19.
Behav Brain Res ; 363: 199-215, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30599154

RESUMO

Gait and postural control dysfunction are prototypical symptoms compromising quality of life for patients with Parkinson's disease (PD). Hallmarks of cellular pathology are dopaminergic degeneration and accumulation of the cytosolic protein alpha-synuclein, linked to impaired autophagy-lysosome pathway (ALP) clearance. Physical exercise improves gait in PD patients and motor function in rodent lesion models. Moreover, exercise is considered neuroprotective and ALP induction has been reported, e.g. in human skeletal muscle, rodent peripheral and cerebral tissues. A combined analysis of how distinct exercise paradigms affect motor and central biochemical aspects of PD could maximize benefits for patients. Here we examine the effect of 4 weeks treadmill exercise intervention in 7-8 month non-lesioned mice on a) distinct gait categories, b) ALP activity, c) dopaminergic and alpha-synuclein homeostasis. The study includes wild type, alpha-synuclein knockout, and mice exclusively expressing human alpha-synuclein. Parameters of gait regularity and stability, activity, and dynamic postural control during unforced walk, were assessed by an automated system (CatWalk XT). At baseline, alpha-synuclein mouse models exhibited irregular and less active gait, with impaired dynamic postural control, compared to wild type mice. Treadmill exercise particularly improved speed and stride length, while increasing dual diagonal versus three-paw body support in both the alpha-synuclein knockout and transgenic mice. Biochemical analyses showed higher striatal tyrosine hydroxylase immuno-reactivity and reduced higher-order alpha-synuclein species in the cerebral cortex. However, no significant cerebral ALP induction was measured. In summary, treadmill exercise improved gait activity and postural stability, and promoted dopaminergic and alpha-synuclein homeostasis, without robustly inducing cerebral ALP.


Assuntos
Marcha/fisiologia , Condicionamento Físico Animal/fisiologia , Esforço Físico/fisiologia , Animais , Autofagia/fisiologia , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Terapia por Exercício/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/fisiologia , Neuroproteção , Doença de Parkinson/fisiopatologia , Postura/fisiologia , Substância Negra/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , alfa-Sinucleína/fisiologia
20.
IEEE J Biomed Health Inform ; 23(4): 1618-1630, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30137018

RESUMO

Parkinson's disease is a neurodegenerative disorder characterized by a variety of motor symptoms. Particularly, difficulties to start/stop movements have been observed in patients. From a technical/diagnostic point of view, these movement changes can be assessed by modeling the transitions between voiced and unvoiced segments in speech, the movement when the patient starts or stops a new stroke in handwriting, or the movement when the patient starts or stops the walking process. This study proposes a methodology to model such difficulties to start or to stop movements considering information from speech, handwriting, and gait. We used those transitions to train convolutional neural networks to classify patients and healthy subjects. The neurological state of the patients was also evaluated according to different stages of the disease (initial, intermediate, and advanced). In addition, we evaluated the robustness of the proposed approach when considering speech signals in three different languages: Spanish, German, and Czech. According to the results, the fusion of information from the three modalities is highly accurate to classify patients and healthy subjects, and it shows to be suitable to assess the neurological state of the patients in several stages of the disease. We also aimed to interpret the feature maps obtained from the deep learning architectures with respect to the presence or absence of the disease and the neurological state of the patients. As far as we know, this is one of the first works that considers multimodal information to assess Parkinson's disease following a deep learning approach.


Assuntos
Aprendizado Profundo , Doença de Parkinson/classificação , Processamento de Sinais Assistido por Computador , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Marcha/fisiologia , Análise da Marcha , Escrita Manual , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Curva ROC , Fala/classificação
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