Chemotherapy-Induced Peripheral Neuropathy and Falls in Cancer Survivors Relate to Digital Balance and Gait Impairments.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls. METHODS: Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures. RESULTS: PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers. CONCLUSION: Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.

Standing Balance Conditions and Digital Sway Measures for Clinical Trials of Friedreich's Ataxia.

BACKGROUND: Progressive loss of standing balance is a feature of Friedreich's ataxia (FRDA). OBJECTIVES: This study aimed to identify standing balance conditions and digital postural sway measures that best discriminate between FRDA and healthy controls (HC). We assessed test-retest reliability and correlations between sway measures and clinical scores. METHODS: Twenty-eight subjects with FRDA and 20 HC completed six standing conditions: feet apart, feet together, and feet tandem, both with eyes opened (EO) and eyes closed. Sway was measured using a wearable sensor on the lumbar spine for 30 seconds. Test completion rate, test-retest reliability with intraclass correlation coefficients, and areas under the receiver operating characteristic curves (AUCs) for each measure were compared to identify distinguishable FRDA sway characteristics from HC. Pearson correlations were used to evaluate the relationships between discriminative measures and clinical scores. RESULTS: Three of the six standing conditions had completion rates over 70%. Of these three conditions, natural stance and feet together with EO showed the greatest completion rates. All six of the sway measures' mean values were significantly different between FRDA and HC. Four of these six measures discriminated between groups with >0.9 AUC in all three conditions. The Friedreich Ataxia Rating Scale Upright Stability and Total scores correlated with sway measures with P-values <0.05 and r-values (0.63-0.86) and (0.65-0.81), respectively. CONCLUSION: Digital postural sway measures using wearable sensors are discriminative and reliable for assessing standing balance in individuals with FRDA. Natural stance and feet together stance with EO conditions suggest use in clinical trials for FRDA. © 2024 International Parkinson and Movement Disorder Society.

Digital Measures of Postural Sway Quantify Balance Deficits in Spinocerebellar Ataxia.

BACKGROUND: Maintaining balance is crucial for independence and quality of life. Loss of balance is a hallmark of spinocerebellar ataxia (SCA). OBJECTIVE: The aim of this study was to identify which standing balance conditions and digital measures of body sway were most discriminative, reliable, and valid for quantifying balance in SCA. METHODS: Fifty-three people with SCA (13 SCA1, 13 SCA2, 14 SCA3, and 13 SCA6) and Scale for Assessment and Rating of Ataxia (SARA) scores 9.28 ± 4.36 and 31 healthy controls were recruited. Subjects stood in six test conditions (natural stance, feet together and tandem, each with eyes open [EO] and eyes closed [EC]) with an inertial sensor on their lower back for 30 seconds (×2). We compared test completion rate, test-retest reliability, and areas under the receiver operating characteristic curve (AUC) for seven digital sway measures. Pearson's correlations related sway with the SARA and the Patient-Reported Outcome Measure of Ataxia (PROM ataxia). RESULTS: Most individuals with SCA (85%-100%) could stand for 30 seconds with natural stance EO or EC, and with feet together EO. The most discriminative digital sway measures (path length, range, area, and root mean square) from the two most reliable and discriminative conditions (natural stance EC and feet together EO) showed intraclass correlation coefficients from 0.70 to 0.91 and AUCs from 0.83 to 0.93. Correlations of sway with SARA were significant (maximum r = 0.65 and 0.73). Correlations with PROM ataxia were mild to moderate (maximum r = 0.56 and 0.34). CONCLUSION: Inertial sensor measures of extent of postural sway in conditions of natural stance EC and feet together stance EO were discriminative, reliable, and valid for monitoring SCA. © 2024 International Parkinson and Movement Disorder Society.

Digital gait measures, but not the 400-meter walk time, detect abnormal gait characteristics in people with Prediabetes.

BACKGROUND AND AIM: Abnormal gait characteristics have been observed in people with diabetic neuropathy, but it is unclear if subtle changes in gait occur in prediabetic people with impaired fasting glucose (IFG). The aims of this study were: (1) to investigate if digital gait measures discriminate people with prediabetes from healthy control participants (HC) and (2) to investigate the relationship between gait measures and clinical scores (concurrent validity). METHODS: 108 people with prediabetes (71.20 ± 5.11 years) and 63 HC subjects (70.40 ± 6.25 years) wore 6 inertial sensors (Opals by APDM, Clario) while performing the 400-meter fast walk test. Fifty-five measures across 5 domains of gait (Lower Body, Upper Body, Turning, and Variability) were averaged. Analysis of Covariance was used to investigate the group differences, with body mass index as a covariate. Pearson's correlation coefficient assessed the association between the gait measures and the Short Physical Performance Battery (SPPB) score. RESULTS: Nine gait measures were significantly different (p < 10-4) between IFG and HC groups. Step duration, cadence, and turn velocity were the most discriminative measures. In contrast, traditional stop-watch time was not significantly different between groups (p = 0.13), after controlling for BMI. Cadence (r = -0.37, p < 0.001), step duration (r = -0.39, p < 0.001), and turn velocity (r = 0.47, p < 0.001) showed a significant correlation with the SPPB score. CONCLUSION: Body-worn inertial sensors detected gait impairments in people with prediabetes that related to clinical balance test performance, even when the traditional stop-watch time was not prolonged for the 400-meter walk test.

Gait and turning characteristics from daily life increase ability to predict future falls in people with Parkinson's disease.

Objectives: To investigate if digital measures of gait (walking and turning) collected passively over a week of daily activities in people with Parkinson's disease (PD) increases the discriminative ability to predict future falls compared to fall history alone. Methods: We recruited 34 individuals with PD (17 with history of falls and 17 non-fallers), age: 68 ± 6 years, MDS-UPDRS III ON: 31 ± 9. Participants were classified as fallers (at least one fall) or non-fallers based on self-reported falls in past 6 months. Eighty digital measures of gait were derived from 3 inertial sensors (Opal® V2 System) placed on the feet and lower back for a week of passive gait monitoring. Logistic regression employing a "best subsets selection strategy" was used to find combinations of measures that discriminated future fallers from non-fallers, and the Area Under Curve (AUC). Participants were followed via email every 2 weeks over the year after the study for self-reported falls. Results: Twenty-five subjects reported falls in the follow-up year. Quantity of gait and turning measures (e.g., number of gait bouts and turns per hour) were similar in future fallers and non-fallers. The AUC to discriminate future fallers from non-fallers using fall history alone was 0.77 (95% CI: [0.50-1.00]). In contrast, the highest AUC for gait and turning digital measures with 4 combinations was 0.94 [0.84-1.00]. From the top 10 models (all AUCs>0.90) via the best subsets strategy, the most consistently selected measures were variability of toe-out angle of the foot (9 out of 10), pitch angle of the foot during mid-swing (8 out of 10), and peak turn velocity (7 out of 10). Conclusions: These findings highlight the importance of considering precise digital measures, captured via sensors strategically placed on the feet and low back, to quantify several different aspects of gait (walking and turning) during daily life to improve the classification of future fallers in PD.

Opal Actigraphy (Activity and Sleep) Measures Compared to ActiGraph: A Validation Study.

Physical activity and sleep monitoring in daily life provide vital information to track health status and physical fitness. The aim of this study was to establish concurrent validity for the new Opal Actigraphy solution in relation to the widely used ActiGraph GT9X for measuring physical activity from accelerometry epic counts (sedentary to vigorous levels) and sleep periods in daily life. Twenty participants (age 56 + 22 years) wore two wearable devices on each wrist for 7 days and nights, recording 3-D accelerations at 30 Hz. Bland-Altman plots and intraclass correlation coefficients (ICCs) assessed validity (agreement) and test-retest reliability between ActiGraph and Opal Actigraphy sleep durations and activity levels, as well as between the two different versions of the ActiGraph. ICCs showed excellent reliability for physical activity measures and moderate-to-excellent reliability for sleep measures between Opal versus Actigraph GT9X and between GT3X versus GT9X. Bland-Altman plots and mean absolute percentage error (MAPE) also show a comparable performance (within 10%) between Opal and ActiGraph and between the two ActiGraph monitors across activity and sleep measures. In conclusion, physical activity and sleep measures using Opal Actigraphy demonstrate performance comparable to that of ActiGraph, supporting concurrent validation. Opal Actigraphy can be used to quantify activity and monitor sleep patterns in research and clinical studies.

Effect of Levodopa and Environmental Setting on Gait and Turning Digital Markers Related to Falls in People with Parkinson's Disease.

Background: It is unknown whether medication status (off and on levodopa) or laboratory versus home settings plays a role in discriminating fallers and non-fallers in people with Parkinson's disease (PD). Objectives: To investigate which specific digital gait and turning measures, obtained with body-worn sensors, best discriminated fallers from non-fallers with PD in the clinic and during daily life. Methods: We recruited 34 subjects with PD (17 fallers and 17 non-fallers based on the past 6 month's falls). Subjects wore three inertial sensors attached to both feet and the lumbar region in the laboratory for a 3-minute walking task (both off and on levodopa) and during daily life activities for a week. We derived 24 digital (18 gait and 6 turn) measures from the 3-minute walk and from daily life. Results: In clinic, none of the gait and turning measures collected during on levodopa state were significantly different between fallers and non-fallers. In contrast, digital measures collected in the off levodopa state were significantly different between groups, (average turn velocity, average number of steps to complete a turn, and variability of gait speed, P < 0.03). During daily life, the variability of average turn velocity (P = 0.023) was significantly different in fallers than non-fallers. Last, the average number of steps to complete a turn was significantly correlated with the patient-reported outcomes. Conclusions: Digital measures of turning, but not gait, were different in fallers compared to non-fallers with PD, in the laboratory when off medication and during a daily life.

Inertial Sensor Algorithm to Estimate Walk Distance.

The "total distance walked" obtained during a standardized walking test is an integral component of physical fitness and health status tracking in a range of consumer and clinical applications. Wearable inertial sensors offer the advantages of providing accurate, objective, and reliable measures of gait while streamlining walk test administration. The aim of this study was to develop an inertial sensor-based algorithm to estimate the total distance walked using older subjects with impaired fasting glucose (Study I), and to test the generalizability of the proposed algorithm in patients with Multiple Sclerosis (Study II). All subjects wore two inertial sensors (Opals by Clario-APDM Wearable Technologies) on their feet. The walking distance algorithm was developed based on 108 older adults in Study I performing a 400 m walk test along a 20 m straight walkway. The validity of the algorithm was tested using a 6-minute walk test (6MWT) in two sub-studies of Study II with different lengths of a walkway, 15 m (Study II-A, n = 24) and 20 m (Study II-B, n = 22), respectively. The start and turn around points were marked with lines on the floor while smaller horizontal lines placed every 1 m served to calculate the manual distance walked (ground truth). The proposed algorithm calculates the forward distance traveled during each step as the change in the horizontal position from each foot-flat period to the subsequent foot-flat period. The total distance walked is then computed as the sum of walk distances for each stride, including turns. The proposed algorithm achieved an average absolute error rate of 1.92% with respect to a fixed 400 m distance for Study I. The same algorithm achieved an absolute error rate of 4.17% and 3.21% with respect to an averaged manual distance for 6MWT in Study II-A and Study II-B, respectively. These results demonstrate the potential of an inertial sensor-based algorithm to estimate a total distance walked with good accuracy with respect to the manual, clinical standard. Further work is needed to test the generalizability of the proposed algorithm with different administrators and populations, as well as larger diverse cohorts.

Closed-Loop Deep Brain Stimulation to Treat Medication-Refractory Freezing of Gait in Parkinson's Disease.

Background: Treating medication-refractory freezing of gait (FoG) in Parkinson's disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS). Methods: In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when "on" PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate. Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both "on" and "off" medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit. Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson's Disease.

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson's disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1-8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD. Clinical Trial Registration: Clinicaltrials.gov identifier; NCT02318927.

Biomechanical Analysis of Dance for Parkinson's Disease: A Paradoxical Case Study of Balance and Gait Effects?

OBJECTIVES: This study aimed to measure the effects of a dance training program on subjective and objective balance and gait measures in a person with Parkinson's disease. DESIGN AND SETTING: The participant was measured via clinical scales and biomechanical balance and gait analyses pre- and post-16 weeks of dance participation at the University Center for Arts in Medicine. The dance program consisted of 75 minute sessions three days a week. RESULTS: Improved clinical scales included the Schwab and England scale (+10%), falls efficacy scale (-11 points), six-minute walk (+15.54m), and timed up and go (1.38s). Balance measures during three conditions (eyes open, eyes closed, and narrow stance) all demonstrated an increase (24-112%) in center of pressure path length, velocity (anteroposterior and mediolateral), sway area, and approximate entropy (anteroposterior and mediolateral). Spatiotemporal gait parameters improved during forward walking: velocity (+0.12m/s), cadence (+3.89steps/min), double support time (-2.02%), stride length (+0.07m), stride time (-0.03s), and backward walking: single support (+3.47%), double support (-7.0%), swing time (+3.4%), and stance time (-3.4%). CONCLUSIONS: Classic interpretation of the above measures may indicate a detriment in biomechanical balance effects concomitant with an improvement in gait. Alternative explanations explored suggest this paradox to be illusory.

Freezing-of-Gait detection using temporal, spatial, and physiological features with a support-vector-machine classifier.

Freezing-of-Gait (FoG) is a syndrome of Parkinson's disease defined by episodes when patients show a complete inability to take a step or continue with their locomotion. In order to develop closed-loop therapeutic strategies, including deep brain stimulation, a reliable means of detecting freezing episodes is required. By using wearable accelerometers, freezing episodes can be detected with energy-based algorithms when the ratio of the energy in the freeze band (3 to 8 Hz) to that of the locomotion band (0.5 to 3 Hz) is above a patient-specific threshold. However, due to the great variability in patient activity type, walking style, and freezing pattern, this detection method often does not work. Here we describe a new FoG-detection method that captures temporal, spatial, and physiological features and uses a support-vector-machine to classify freezing episodes. Since our method uses more diverse features, it is able to more robustly detect FoG events. We have shown that when the energy-based method fails (e.g., area under the receiver operator curve is ~0.5), our new method performs well (e.g., area under ROC curve is 0.96).

Effects of Popular Diets without Specific Calorie Targets on Weight Loss Outcomes: Systematic Review of Findings from Clinical Trials.

The present review examined the evidence base for current popular diets, as listed in the 2016 U.S. News & World Report, on short-term (≤six months) and long-term (≥one year) weight loss outcomes in overweight and obese adults. For the present review, all diets in the 2016 U.S. News & World Report Rankings for "Best Weight-Loss Diets", which did not involve specific calorie targets, meal replacements, supplementation with commercial products, and/or were not categorized as "low-calorie" diets were examined. Of the 38 popular diets listed in the U.S. News & World Report, 20 met our pre-defined criteria. Literature searches were conducted through PubMed, Cochrane Library, and Web of Science using preset key terms to identify all relevant clinical trials for these 20 diets. A total of 16 articles were identified which reported findings of clinical trials for seven of these 20 diets: (1) Atkins; (2) Dietary Approaches to Stop Hypertension (DASH); (3) Glycemic-Index; (4) Mediterranean; (5) Ornish; (6) Paleolithic; and (7) Zone. Of the diets evaluated, the Atkins Diet showed the most evidence in producing clinically meaningful short-term (≤six months) and long-term (≥one-year) weight loss. Other popular diets may be equally or even more effective at producing weight loss, but this is unknown at the present time since there is a paucity of studies on these diets.