Aspects Of Gait Research Articles

The Influence of Dopaminergic Medication on Regularity and Determinism of Gait and Balance in Parkinson’s Disease: A Pilot Analysis

Background/Objectives: Understanding how dual-tasking and Parkinson’s disease medication affect gait and balance regularity can provide valuable insights to patients, caregivers, and clinicians regarding frailty and fall risk. However, dual-task gait and balance studies in PD most often only employ linear measures to describe movement regularity. Some have used nonlinear techniques to analyze PD performances, but only in the on-medication state. Thus, it is unclear how the nonlinear aspects of gait or standing balance are affected by PD medication. This study aimed to assess how dopaminergic medication influenced the regularity and determinism of joint angle and anterior–posterior (AP) and medial–lateral (ML) center of pressure (COP) path time-series data while single- and dual-tasking in PD. Methods: Sixteen subjects with PD completed single- and dual-task gait and standing balance trials for 3 min off and on dopaminergic medication. Sample entropy and percent determinism were calculated for bilateral hip, knee, and shoulder joints, and the AP and ML COP path. Results: There were no relevant medication X task interactions for either the joint angles series or the balance series. Instead, the results supported independent effects of medication, dual-tasking, or standing with eyes closed. Balance task difficulty (i.e., eyes open vs. eyes closed) was detected by the nonlinear analyses, but the nonlinear measures yielded opposing results such that standing with eyes closed simultaneously yielded less regular and more deterministic signals. Conclusions: When juxtaposed with previous findings, these results suggest that medication-induced functional improvements in people with PD might be accompanied by a shift from lesser to greater signal consistency, and the effects of dual-tasking and standing with eyes closed were mixed. Future studies would benefit from including both linear and nonlinear measures to better describe gait and balance performance and signal complexity in people with PD.

Effects of Foot Orthoses and Kinesio Tape on Spatiotemporal and Kinetic Gait Parameters during Running in Individuals with Flatfoot

Flatfoot is a common condition that influences gait and can cause discomfort for patients under higher loaded condition, such as running. Identifying the most effective treatment necessitates a comprehensive analysis of each therapy's impact on gait. Our research delved into the effects of Foot Orthosis and Kinesio Tape on the spatiotemporal and kinetic aspects of gait in individuals with flatfoot during running. Twenty female rearfoot strike runners with flatfoot participated in the running tasks at 3.3±5% m/s on the Zebris Medical GmbH treadmill. Gait data were collected under three conditions: shoe (A), shoe with Foot Orthoses (B), and shoe with Kinesio Tape (C). A one-way repeated measures ANOVA was employed to analyzed the gait parameters during the stance phase. Under conditions B and C, the foot rotation angle significantly decreased compared to condition A. Additionally, in condition B, it was significantly lower than in condition C. Under conditions B and C, the maximum force and pressure of forefoot significantly increased, whereas it in the midfoot significantly decreased, relative to condition A. Foot Orthosis and Kinesio Tape both effectively diminished peak midfoot pressure during running. Additionally, Foot Orthosis surpassed Kinesio Tape in enhancing foot stability and function throughout the running. These findings offered valuable insights for the selection of intervention measures for patients with flat feet during running.

Natural history of gait patterns in untreated children with bilateral cerebral palsy in a low-income country setting.

To assess a group of ambulant, untreated children with bilateral spastic cerebral palsy, in a resource-poor setting, who had never been assessed by a health care professional or received any treatment, to help establish the natural history of gait patterns in this condition. At CURE Children's Hospital of Ethiopia, 46 children with no prior health care contact were assessed in a cross-sectional cohort study, through a detailed history, clinical examination, and instrumented gait analysis using a motion capture system. There was a large spread in the data reflecting the high natural heterogeneity in this population. The severity of gait pathology did not correlate with age; however, a small but significant reduction in sagittal hip and knee range of motion with increasing age was observed. There was also a trend towards reduced passive knee extension with age. Improved understanding of the aspects of gait that are likely to naturally improve, deteriorate, or remain stable over time helps guide treatment decisions in this population.

Application of Wearable Electronics Sensors for Public Health Monitoring and Disease Prevention

Each component of contemporary technology depends on sensors. Improved and more advanced sensors have the potential to advance technological advancements and ultimately contribute to a better quality of life for humans. Adopting more modern materials, designs, and sensing mechanism types is crucial to the development of sensors. Wearable sensors can be used to monitor several aspects of human gait by placing them on the hip, knee, wrist, and foot, among other parts of the body. Measurements of public health, including body temperature, heart rate, pulse oxygenation, respiration rate, blood pressure, blood glucose, ECG signal, and disease prevention, can be made with these sensors. Numerous recent studies have taken into consideration wearable sensor-based systems. With an emphasis on monitoring human physiological indicators, the research work aimed to demonstrate new sensor utilisation in the development of wearable devices for biomonitoring applications.

Uncertainty-aware ensemble model for stride length estimation in gait analysis

Deep neural network (DNN) models have become highly effective tools for function estimation in regression tasks, with applications in various domains, including human gait stride length estimation. Several studies have developed DNN models that use gait cycle data from wearable devices equipped with inertial measurement units to accurately predict stride lengths within a cycle. However, many of these deep learning approaches do not quantify predictive uncertainty and fail to consider individual gait characteristics. To address these limitations, we introduced an ensemble model based on a heteroscedastic neural network that quantifies the uncertainty in stride length predictions. Additionally, we proposed a novel stride training strategy that uses the average stride instead of individual strides to optimize the training process and improve model efficiency. Our extensive performance evaluations demonstrate the robustness and adaptability of our model, accurately predicting both the uncertainty of individual stride lengths and the specific stride lengths for each gait cycle. Our study represents a significant advancement in stride length estimation, addressing the challenges of uncertainty quantification and capturing the unique aspects of human gait. The proposed model has considerable potential for practical applications in gait analysis and related fields.

The efficacy of 3D gait analysis to evaluate surgical (and rehabilitation) outcome after degenerative lumbar surgery

BackgroundLumbar degenerative conditions are a major cause of back pain and disability in individuals aged 45 and above. Gait analysis utilizes sensor technology to collect movement data, aiding in the evaluation of various gait aspects like spatiotemporal parameters, joint angles, neuromuscular activity, and joint forces. It is widely used in conditions such as cerebral palsy and knee osteoarthritis. This research aims to assess the effectiveness of 3D gait analysis in evaluating surgical outcomes and postoperative rehabilitation for lumbar degenerative disorders.MethodsA prospective self-controlled before-after study (n = 85) carried out at our Hospital (Sep 2018 - Dec 2021) utilized a 3D motion analysis system to analyze gait in patients with lumbar degenerative diseases. The study focused on the multifidus muscle, a crucial spinal muscle, during a minimally invasive lumbar interbody fusion surgery conducted by Shandong Weigao Pharmaceutical Co., Ltd. Pre- and postoperative assessments included time-distance parameters (gait speed, stride frequency, stride length, stance phase), hip flexion angle, and stride angle. Changes in 3D gait parameters post-surgery and during rehabilitation were examined. Pearson correlation coefficient was employed to assess relationships with the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) scores. Patient sagittal alignment was evaluated using “Surgimap” software from two types of lateral radiographs to obtain parameters like pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), intervertebral space height (DH), posterior height of the intervertebral space (PDH) at the operative segment, and anterior height of the intervertebral space (ADH).ResultsBy the 6th week post-operation, significant improvements were observed in the VAS score, JOA score, and ODI score of the patients compared to preoperative values (P < 0.05), along with notable enhancements in 3D gait quantification parameters (P < 0.05). Pearson correlation analysis revealed a significant positive correlation between improvements in 3D gait quantification parameters and VAS score, JOA score, and ODI value (all P < 0.001).Conclusion3D gait analysis is a valuable tool for evaluating the efficacy of surgery and rehabilitation training in patients.

Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy

Cerebral microhemorrhages (CMHs) are of paramount importance as they not only signify underlying vascular pathology but also have profound implications for cognitive function and neurological health, serving as a critical indicator for the early detection and management of vascular cognitive impairment (VCI). This study aimed to investigate the effects of hypertension-induced CMHs on gait dynamics in a mouse model, focusing on the utility of advanced gait metrics as sensitive indicators of subclinical neurological alterations associated with CMHs. To induce CMHs, we employed a hypertensive mouse model, using a combination of Angiotensin II and L-NAME to elevate blood pressure, further supplemented with phenylephrine to mimic transient blood pressure fluctuations. Gait dynamics were analyzed using the CatWalk system, with emphasis on symmetry indices for Stride Length (SL), Stride Time (ST), and paw print area, as well as measures of gait entropy and regularity. The study spanned a 30-day experimental period, capturing day-to-day variations in gait parameters to assess the impact of CMHs. Temporary surges in gait asymmetry, detected as deviations from median gait metrics, suggested the occurrence of subclinical neurological signs associated with approximately 50% of all histologically verified CMHs. Our findings also demonstrated that increases in gait entropy correlated with periods of increased gait asymmetry, providing insights into the complexity of gait dynamics in response to CMHs. Significant correlations were found between SL and ST symmetry indices and between these indices and the paw print area symmetry index post-hypertension induction, indicating the interdependence of spatial and temporal aspects of gait affected by CMHs. Collectively, advanced gait metrics revealed sensitive, dynamic alterations in gait regulation associated with CMHs, resembling the temporal characteristics of transient ischemic attacks (TIAs). This underscores their potential as non-invasive indicators of subclinical neurological impacts. This study supports the use of detailed gait analysis as a valuable tool for detecting subtle neurological changes, with implications for the early diagnosis and monitoring of cerebral small vessel disease (CSVD) in clinical settings.

Synchronization of Neurophysiological and Biomechanical Data in a Real-Time Virtual Gait Analysis System (GRAIL): A Proof-of-Principle Study.

The investigation of gait and its neuronal correlates under more ecologically valid conditions as well as real-time feedback visualization is becoming increasingly important in neuro-motor rehabilitation research. The Gait Real-time Analysis Interactive Lab (GRAIL) offers advanced opportunities for gait and gait-related research by creating more naturalistic yet controlled environments through immersive virtual reality. Investigating the neuronal aspects of gait requires parallel recording of brain activity, such as through mobile electroencephalography (EEG) and/or mobile functional near-infrared spectroscopy (fNIRS), which must be synchronized with the kinetic and /or kinematic data recorded while walking. This proof-of-concept study outlines the required setup by use of the lab streaming layer (LSL) ecosystem for real-time, simultaneous data collection of two independently operating multi-channel EEG and fNIRS measurement devices and gait kinetics. In this context, a customized approach using a photodiode to synchronize the systems is described. This study demonstrates the achievable temporal accuracy of synchronous data acquisition of neurophysiological and kinematic and kinetic data collection in the GRAIL. By using event-related cerebral hemodynamic activity and visually evoked potentials during a start-to-go task and a checkerboard test, we were able to confirm that our measurement system can replicate known physiological phenomena with latencies in the millisecond range and relate neurophysiological and kinetic data to each other with sufficient accuracy.

Transhumeral prosthesis use affects upper body kinematics and kinetics

BackgroundTranshumeral (TH) limb loss leads to loss of body mass and reduced shoulder range of motion. Despite most owning a prosthesis, prosthesis abandonment is common. The consequence of TH limb loss and prosthesis use and disuse during gait may be compensation in the upper body, contributing to back pain or injury. Understanding the impact of not wearing a TH prosthesis on upper body asymmetries and spatial-temporal aspects of gait will inform how TH prosthesis use and disuse affects the body. Research questionDoes TH limb loss alter upper body asymmetries and spatial-temporal parameters during gait when wearing and not wearing a prosthesis compared to able-bodied controls? MethodsEight male TH limb loss participants and eight male control participants completed three gait trials at self-selected speeds. The TH limb loss group performed trials with and without their prosthesis. Arm swing, trunk angular displacement, trunk-pelvis moment, and spatial-temporal aspects were compared using non-parametric statistical analyses. ResultsBoth TH walking conditions showed greater arm swing in the intact limb compared to the residual (p≤0.001), resulting in increased asymmetry compared to the control group (p≤0.001). Without the prosthesis, there was less trunk flexion and lateral flexion compared to the control group (p≤0.001). Maximum moments between the trunk and pelvis were higher in the TH group than the control group (p≤0.05). Spatial-temporal parameters of gait did not differ between the control group and either TH limb loss condition. SignificanceProsthesis use affects upper body kinematics and kinetics, but does not significantly impact spatial-temporal aspects of gait, suggesting these are compensatory actions. Wearing a prosthesis helps achieve more normative upper body kinematics and kinetics than not wearing a prosthesis, which may help limit back pain. These findings emphasize the importance of encouraging at least passive use of prostheses for individuals with TH limb loss.

Limb and joint kinetics during walking in individuals with Mild-Moderate Parkinson’s disease

Given the known deficits in spatiotemporal aspects of gait for people with Parkinson’s disease (PD), we sought to determine the underlying gait abnormalities in limb and joint kinetics, and examine how deficits in push-off and leg swing might contribute to the shortened step lengths for people with PD. Ten participants with PD and 11 age-matched control participants walked overground and on an instrumented treadmill. Participants with PD then walked on the treadmill with a posteriorly directed restraining force applied to 1) the pelvis to challenge push-off and 2) the ankles to challenge leg swing. Spatiotemporal, kinematic, and force data were collected and compared between groups and conditions. Despite group differences in spatiotemporal measures during overground walking, we did not observe these differences when the groups walked on a treadmill at comparable speeds. Nevertheless, the hip extension impulse appeared smaller in the PD group during their typical walking. When challenging limb propulsion, participants in the PD group maintained step lengths by increasing the propulsive impulse. Participants with PD were also able to maintain their typical step length against resistance intended to impede swing limb advancement, and even increased step lengths with cuing. The presence of reduced hip extension torque might be an early indicator of gait deterioration in this neurodegenerative disease. Our participants with PD were able to increase hip extension torque in response to needed demands. Additionally, participants with PD were able to increase limb propulsion and leg swing against resistance, suggesting a reserve in limb mechanics.

Morphology and transverse alignment of the patella have no effect on knee gait characteristics in healthy Chinese adults over the age of 40years.

Background: The influence of patella morphology and horizontal alignment on knee joint kinematics and kinetics remains uncertain. This study aimed to assess patella morphology and transverse alignment in relation to knee kinetics and kinematics in individuals without knee conditions. A secondary objective was to investigate the impact of femur and tibia alignment and shape on knee gait within this population. Patients and methods: We conducted a prospective collection of data, including full-leg anteroposterior and skyline X-ray views and three-dimensional gait data, from a cohort comprising 54 healthy individuals aged 40years and older. Our study involved correlation and logistic regression analyses to examine the influence of patella, femur, and tibia morphology and alignment on knee gait. Results: The patellar tilt angle or the patella index did not show any significant relationships with different aspects of gait in the knee joint, such as velocity, angle, or moment (p > 0.05, respectively). Using multivariate logistic regression analysis, we found that the tibiofemoral angle and the Q angle both had a significant effect on the adduction angle (OR = 1.330, 95%CI 1.033-1.711, p = 0.027; OR = 0.475, 95%CI 0.285-0.792, p = 0.04; respectively). The primary variable influencing the knee adduction moment was the tibiofemoral angle (OR = 1.526, 95% CI 1.125-2.069, p = 0.007). Conclusion: In healthy Chinese individuals aged over 40, patella morphology and transverse alignment do not impact knee gait. However, the femoral-tibial angle has a big impact on the knee adduction moment.

Golexanolone reduces glial activation in the striatum and improves non-motor and some motor alterations in a rat model of Parkinson's disease.

Parkinson's disease (PD) affects more than 6 million people worldwide. Along with motor impairments, patients and animal models exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease. A body of evidence suggests that increased GABA levels contribute to the reduced expression of tyrosine hydroxylase (TH) and accompanying behavioral deficits. TH expression may be restored by blocking GABAA receptors. We hypothesized that golexanolone (GR3027), a well-tolerated GABAA receptor-modulating steroid antagonist (GAMSA), may improve Parkinson's symptoms in a rat model of PD. The aims of this study were to assess whether golexanolone can ameliorate motor and non-motor symptoms in a rat model of PD and to identify some underlying mechanisms. We used the unilateral 6-OHDA rat model of PD. The golexanolone treatment started 4 weeks after surgery. Motor symptoms were assessed using Motorater and CatWalk tests. We also analyzed fatigue (using a treadmill test), anhedonia (via the sucrose preference test), anxiety (with an open field test), and short-term memory (using a Y maze). Glial activation and key proteins involved in PD pathogenesis were analyzed using immunohistochemistry and Western blot. Rats with PD showed motor incoordination and impaired locomotor gait, increased fatigue, anxiety, depression, and impaired short-term memory. Golexanolone treatment led to improvements in motor incoordination, certain aspects of locomotor gait, fatigue, anxiety, depression, and short-term memory. Notably, golexanolone reduced the activation of microglia and astrocytes, mitigated TH loss at 5 weeks after surgery, and prevented the increase of α-synuclein levels at 10 weeks. Golexanolone may be useful in improving both motor and non-motor symptoms that adversely affect the quality of life in PD patients, such as anxiety, depression, fatigue, motor coordination, locomotor gait, and certain cognitive alterations.

The effect of single and dual task on spatiotemporal gait parameters in children with spastic cerebral palsy

Abstract Aim: Children can walk in clinical settings but have difficulty walking in schools, parks, and outdoor activity playgrounds. Most environmental distractors, namely noise from the background, and diverting visual and aural stimuli may be a source of this lack of carryover from indoor to outside settings, which is why they are unable to carry-out their activities of daily living successfully and precisely. This study was aimed to assess the impact of dual task activities on spatiotemporal aspects of gait in children with spastic cerebral palsy (CP). Materials and Methods: After screening and informed consent, participants were asked to walk on a 10-m walkway while performing a dual task (walking with visual, auditory recognition, and backward counting). Three trials of each task were obtained and spatiotemporal parameters, including speed, step length, step width, and stride length, cadence) were measured. Result: Spatiotemporal parameters, such as speed, step width, step length, right stride length, and cadence, showed significant difference with dual-task walking compared with normal walking. Conclusion: The results suggest that dual-task training should receive more attention in clinical evaluations, as well as therapy strategies for children with spastic CP.

Motion Analysis of a Frontal Plane Adaptable Prosthetic Foot.

ABSTRACT Introduction An objective of designing a prosthetic foot is to achieve the natural adaptability of the foot and ankle on various surfaces and different forms of gait. Frontal plane position of the foot relative to the shank changes with many functional aspects of gait, such as turning, stairs, and walking on uneven ground. Prosthetic foot designs have variable frontal plane adaptability. An investigation foot with a linkage with ±10° of frontal plane motion was developed to improve frontal plane response under various conditions. The purpose of this study was to compare the kinematics of locked and unlocked conditions of a frontal plane adaptable prosthetic foot and the person’s usual foot while walking forward on a level surface, on an unstable rock surface, and sidestep, using a crossover design. These different conditions result in changes in frontal plane motion in the anatomical foot and ankle, and the current study evaluates whether there are similar trends in prosthetic feet. Materials and Methods People were included if they had a unilateral below-knee amputation, intact residual limb skin, were over 16 years old, and were able to walk more than 400 m on level ground without using a walking aid and without an increase in pain. The control group was people without amputations who completed the procedures once. Participants with amputations completed forward walking on level ground, on an unstable rock surface, and sidestep with their usual foot. Then after 2 weeks of accommodation, participants repeated these tests with the investigational foot unlocked and locked. Motion analysis data were collected with a 12-camera optically based system. Primary outcomes were sagittal and frontal plane motions of the foot relative to the shank. In addition, step length, step width, and stride velocity were obtained from the kinematic measures. Paired t-tests were used for statistical inference for individual participant comparisons. Unpaired t-tests were used for comparisons between the controls and people with amputations. Results Twenty-one people with amputations and 10 controls completed the tests. Participants with amputation had 16 different usual feet. There was a wide variation in usual foot motion during forward walking, whereas investigational foot conditions showed less variability. During level walking, control subjects had more frontal plane motion than any of the foot conditions, and the unlocked had more frontal plane motion than the usual foot and locked condition. Walking across an unstable rock surface showed similar trends, with control participants having more sagittal and frontal plane ankle motion compared with any prosthetic foot condition. Also, the unlocked had statistically greater frontal plane motion than the usual foot or locked condition. Sidestep results were also consistent with other gait tests. The control participants’ sagittal plane ankle range of motion was significantly more than the prosthetic sagittal plane motion for all foot conditions, whether the prosthetic side was leading or trailing. There was significantly more frontal plane motion with the unlocked than the usual foot and locked condition when the prosthetic foot was trailing or leading. Discussion and Conclusions Wide variation in usual foot range of motions in the frontal and sagittal planes confirmed the need for additional controls when considering the effect of the linkage alone. The unlocked had increased frontal plane ranges of motion compared with the locked and the majority of usual foot for all gait conditions, including level walking. This finding demonstrated that people with amputations were functionally using the additional range of motion provided by the linkage. However, control subjects used more range of motion in both the sagittal and frontal planes for the unstable rock surface and sidestepping. Increased frontal plane range of motion did not translate into improved stride length and velocity, step width, or center of mass deviations. Clinical Relevance The person-specific functional activities should be considered when choosing a prosthetic foot. A prosthesis with frontal plane motion may be applicable for a person who moves in a sidestep pattern or on uneven ground.

Exploring mobility dysfunction in people with and without impaired cognition in Parkinson disease

IntroductionThe relationship between mobility and cognition has been studied in the aging population and associations have been also reported in people with Parkinson's disease (PD). ObjectiveTo compare different aspects of gait and balance between individuals with PD who have normal cognition and those with impaired cognition, using both clinical and instrumented measures. MethodsOne-hundred forty-three participants with PD were divided into two groups: 1) normal cognition (n = 71) and 2) impaired cognition (n = 72) based on the Montreal Cognitive Assessment (MoCA) cut-off. Groups were compared using instrumented and clinical measures of gait and balance in the following domains: Sensory Orientation, Anticipatory Postural Adjustments, Automatic Postural Responses and Dynamic Balance for Gait. Instrumented measures were obtained via wearable sensors while performing eight different motor tasks and clinical measures were obtained with the Mini-BESTest. ResultsThe total Mini-BESTest score was not different between groups. However, the Dynamic Gait domain was worse in individuals with impaired cognition. Among the instrumented measures across domains, all significant group differences were in the Dynamic Gait domain, specifically, dual-task gait speed, dual-task stride length, stance time, and turn velocity. ConclusionsDynamic balance during gait was more impaired in people with PD who had abnormal cognition than those with normal cognition, for both clinical and instrumented measures. All other balance domains did not differ between groups, for both instrumented and clinical measures.

Fall Prevalence and Associated Risk Factors in the Hospitalised Adult Population: A Crucial Step Towards Improved Hospital Care.

Background Falls among the adult population are a major global health concern with severe repercussions for individuals and healthcare systems. The purpose of this study was to investigate the prevalence and associated risk factors of falls in hospitalized patients in order to improve hospital care for elderly adults. Materials and methods The research was conducted at two institutions of tertiary care in Abbottabad, Pakistan. After extensive screening and obtaining informed consent, a total of 210 participants aged 50 and older were enrolled in the study. Mental status, history of falls, ambulation/elimination status, vision, gait/balance, systolic blood pressure, medication use, and predisposing diseases were evaluated using the Long Term Care Fall Risk Assessment Form. Additionally, the Dynamic Gait Index was utilized to evaluate various aspects of gait. Results 58.6% of participants reported a history of falls in the previous year, according to the findings. BMI, imbalance, vertigo, and fear of falling were significantly associated with an increased risk of falls in older individuals. The Long-Term Care Fall Risk Assessment, the Montreal Cognitive Assessment (MoCA), the Dynamic Gait Index (DGI), and the Mini-BESTest scores revealed that patients with a history of falls had inferior functional and cognitive outcomes. Falls were more common among individuals with a robust BMI, especially men. Conclusions The study results highlight the multifactorial nature of falls in the adult population and the need for targeted interventions to address modifiable risk factors. To enhance hospital care for high-risk patients, proactive fall prevention strategies, including regular risk assessments and individualized interventions, should be implemented. This study provides important insights into the prevalence and causes of accidents among hospitalized patients, particularly in developing nations such as Pakistan. ​​​​​​.

In vivo effects of the alpha-synuclein misfolding inhibitor minzasolmin supports clinical development in Parkinson’s disease

Direct targeting of alpha-synuclein (ASYN) has emerged as a disease-modifying strategy for Parkinson’s disease and other synucleinopathies which is being approached using both small molecule compounds and ASYN-targeted biologics. Minzasolmin (UCB0599) is an orally bioavailable and brain-penetrant small molecule ASYN misfolding inhibitor in clinical development as a disease-modifying therapeutic for Parkinson’s disease. Herein the results of preclinical evaluations of minzasolmin that formed the basis for subsequent clinical development are described. Pharmacokinetic evaluations of intraperitoneal 1 and 5 mg/kg minzasolmin in wildtype mice revealed parallel and dose-proportional exposures in brain and plasma. Three-month administration studies in the Line 61 transgenic mouse model of PD were conducted to measure ASYN pathology and other PD-relevant endpoints including markers of CNS inflammation, striatal DAT labeling and gait. Reductions in ASYN pathology were correlated with improved aspects of gait and balance, reductions in CNS inflammation marker abundance, and normalized striatal DAT levels. These findings provide support for human dose determinations and have informed the translational strategy for clinical trial design and biomarker selection for the ongoing clinical studies of minzasolmin in patients living with early-stage Parkinson’s disease (ClinicalTrials.gov ID: NCT04658186; EudraCT Number 2020–003265).

Predicting Sit-to-Stand Body Adaptation Using a Simple Model

Mathematical models that simulate human motion are used widely due to their potential in predicting basic characteristics of human motion. These models have been involved in investigating various aspects of gait and human-related tasks, especially walking and running. This study uses a simple model to study the impact of different factors on sit-to-stand motion through the formulation of an optimization problem that aims at minimizing joint torques. The simulated results validated experimental results reported in the literature and showed the ability of the model to predict the changes in kinetic and kinematic parameters as adaptation to any change in the speed of motion, reduction in the joint strength, and change in the seat height. The model discovered that changing one of these determinants would affect joint angular displacement, joint torques, joint angular velocities, center of mass position, and ground reaction force.

FMG-BASED INFORMATION MEASUREMENT SYSTEM FOR CONTROLLING A LOWER LIMB PROSTHESIS

Disability is one of the most pressing health and social problems worldwide. Despite significant medical advances, there are situations in which the only and most effective treatment is amputation. Most often people lose their legs as a result of accidents, wars and industrial injuries. A person's mobility is severely limited by the loss of a lower limb, which has a negative impact on both their physical and emotional health. It definitely reduces the quality of his life. In order for a person who has had an amputation to lead a full and active life in the future, it is necessary to have a well-designed prosthesis that can simulate the normal function of the lost limb as much as possible. There are different types of prostheses with different designs and functions, but the most advanced are those with built-in microprocessors. However, even these prostheses have problems integrating movement and adjusting their operation to the individual characteristics of the patient, which makes it necessary to create and improve modern prosthetic control systems. This research proposes the consideration of an information-measuring system based on the reading of muscle activity signals and their further analysis by means of Fourier transform. As a result, the prosthesis may be controlled more precisely and smoothly, normalizing the biomechanical aspects of human gait. Keywords: Limb prosthesis, amputation, biomedical systems, force myography, signal processing, Fourier transform

Combination of Clinical and Gait Measures to Classify Fallers and Non-Fallers in Parkinson's Disease.

Individuals with mild-to-moderate PD were classified as fallers (n = 31) or non-fallers (n = 96) based on the previous 12 months' falls. Clinical measures (demographic, motor, cognitive and patient-reported outcomes) were assessed with standard scales/tests, and gait parameters were derived from wearable inertial sensors (Mobility Lab v2); participants walked overground, at a self-selected speed, for 2 min under single and dual-task walking conditions (maximum forward digit span). Receiver operating characteristic curve analysis identified measures (separately and in combination) that best discriminate fallers from non-fallers; we calculated the area under the curve (AUC) and identified optimal cutoff scores (i.e., point closest-to-(0,1) corner). Single gait and clinical measures that best classified fallers were foot strike angle (AUC = 0.728; cutoff = 14.07°) and the Falls Efficacy Scale International (FES-I; AUC = 0.716, cutoff = 25.5), respectively. Combinations of clinical + gait measures had higher AUCs than combinations of clinical-only or gait-only measures. The best performing combination included the FES-I score, New Freezing of Gait Questionnaire score, foot strike angle and trunk transverse range of motion (AUC = 0.85). Multiple clinical and gait aspects must be considered for the classification of fallers and non-fallers in PD.