Gait and heart rate: do they measure trait or state physical fatigue in people with multiple sclerosis?

BACKGROUND: Trait and state physical fatigue (trait-PF and state-PF) negatively impact many people with multiple sclerosis (pwMS) but are challenging symptoms to measure. In this observational study, we explored the role of specific gait and autonomic nervous system (ANS) measures (i.e., heart rate, HR, r-r interval, R-R, HR variability, HRV) in trait-PF and state-PF. METHODS: Forty-eight pwMS [42 ± 1.9 years, 65% female, EDSS 2 (IQR: 0-5.5)] completed the Timed Up and Go test (simple and with dual task, TUG-DT) and the 6-min walk test (6MWT). ANS measures were measured via a POLAR H10 strap. Gait was measured using inertial-measurement units (OPALs, APDM Inc). Trait-PF was evaluated via the Modified Fatigue Impact Scale (MFIS) motor component. State-PF was evaluated via a Visual Analog Scale (VAS) scale before and after the completion of the 6MWT. Multiple linear regression models identified trait-PF and state-PF predictors. RESULTS: Both HR and gait metrics were associated with trait-PF and state-PF. HRV at rest was associated only with state-PF. In models based on the first 3 min of the 6MWT, double support (%) and cadence explained 47% of the trait-PF variance; % change in R-R explained 43% of the state-PF variance. Models based on resting R-R and TUG-DT explained 39% of the state-PF. DISCUSSION: These findings demonstrate that specific gait measures better capture trait-PF, while ANS metrics better capture state-PF. To capture both physical fatigue aspects, the first 3 min of the 6MWT are sufficient. Alternatively, TUG-DT and ANS rest metrics can be used for state-PF prediction in pwMS when the 6MWT is not feasible.

Association Between Frailty and Free-Living Walking Performance in People With Multiple Sclerosis.

OBJECTIVE: The purpose of this study was to examine the association between frailty and the quantity and quality of free-living walking and the mediating effect of frailty on the relationship between disability and walking performance in people with multiple sclerosis (MS). METHODS: Ninety-nine people with relapsing-remitting MS (mean age = 49.3 [SD = 9.8] years; 73.7% women; Expanded Disability Status Scale [EDSS] score range = 2.0-6.0) wore a triaxial accelerometer for 7 days. Recorded measures reflected the quantity (daily step counts, number of 30-second walking bouts, and signal vector magnitude [SVM]) and quality (gait speed, step cadence, step and stride regularity, and sample entropy) of walking. For each walking quality measure, the typical (median), best (90th percentile), and worst (10th percentile) values were calculated. Frailty was evaluated through a 38-item frailty index. RESULTS: Participants were classified as not frail (n = 31), moderately frail (n = 34), and severely frail (n = 34) on the basis of established procedures. Patients who were moderately and severely frail exhibited poorer performance in all measures of walking quantity and quality, except for sample entropy, than individuals who were not frail. No differences in free-living walking performance were observed between the moderately and severely frail groups. Frailty did not mediate the relationship between disability (EDSS) and measures of walking quality. Conversely, frailty had a significant mediating effect on the relationship between disability and measures of walking quantity, such as daily step counts (indirect effect: b = -220.42, 95% CI = -452.03 to -19.65) and SVM (indirect effect: b = -1.00, 95% CI = -1.86 to -0.30). CONCLUSION: Frailty is associated with poorer free-living walking performance in people with MS. The study findings suggest that frailty, rather than disability, may be primarily responsible for the lower amount of physical activity performed by people with MS in the real world. IMPACT: The observation that frailty and disability are differently related to measures of walking quality and quantity underscores the importance of a targeted approach to rehabilitation in people with MS.

Treadmill training with virtual reality to enhance gait and cognitive function among people with multiple sclerosis: a randomized controlled trial.

BACKGROUND: Motor and cognitive impairments impact the everyday functioning of people with MS (pwMS). The present randomized controlled trial (RCT) evaluated the benefits of a combined motor-cognitive virtual reality training program on key motor and cognitive symptoms and related outcomes in pwMS. METHODS: In a single-blinded, two-arm RCT, 124 pwMS were randomized into a treadmill training with virtual reality (TT + VR) group or a treadmill training alone (TT) (active-control) group. Both groups received three training sessions per week for 6 weeks. Dual-tasking gait speed and cognitive processing speed (Symbol Digit Modalities Test, SDMT, score) were the primary outcomes. Secondary outcomes included additional tests of cognitive function, mobility, and patient-reported questionnaires. These were measured before, after, and 3 months after training. RESULTS: Gait speed improved (p < 0.005) in both groups, similarly, by about 10 cm/s. The TT + VR group (n = 53 analyzed per-protocol) showed a clinically meaningful improvement of 4.4 points (95% CI 1.9-6.8, p = 0.001) in SDMT, compared to an improvement of only 0.8 points in the TT (n = 51 analyzed per-protocol) group (95% CI 0.9-2.5 points, p = 0.358) (group X time interaction effect p = 0.027). Furthermore, TT + VR group-specific improvements were seen in depressive symptoms (lowered by 31%, p = 0.003), attention (17%, p < 0.001), and verbal fluency (11.6% increase, p = 0.002). DISCUSSION: These findings suggest that both TT and TT + VR improve usual and dual-task gait in pwMS. Nonetheless, a multi-modal approach based on VR positively impacts multiple aspects of cognitive function and mental health, more than seen after treadmill-treading alone. Trial registered at ClinicalTrials.Gov NCT02427997.

Fragmentation, circadian amplitude, and fractal pattern of daily-living physical activity in people with multiple sclerosis: Is there relevant information beyond the total amount of physical activity?

BACKGROUND: Physical activity is lower in people with multiple sclerosis (pwMS) compared to healthy controls. Previous work focused on studying activity levels or activity volume, but studies of daily-living rest-activity fragmentation patterns, circadian rhythms, and fractal regulation in pwMS are limited. Based on findings in other cohorts, one could suggest that these aspects of daily-living physical activity will provide additional information about the health and well-being of pwMS. Therefore, here, we aimed to (1) identify which fragmentation, fractal, and circadian amplitude measures differ between pwMS and healthy controls, (2) evaluate the relationship between fragmentation, fractal, and circadian amplitude measures and disease severity, and (3) begin to evaluate the added value of those measures, as compared to more conventional measures of physical activity (e.g., mean signal vector magnitude (SVM). A global measure of the overall volume of physical activity). METHODS: 132 people with relapsing-remitting MS (47±11 yrs, 69.7% female, Expanded Disability Status Scale, EDSS, median (IQR): 3 (2-4)) and 90 healthy controls (46±11 yrs, 47.8% female) were asked to wear a 3D accelerometer on their lower back for 7 days. Rest-activity fragmentation, circadian amplitude, fractal regulation, and mean SVM metrics were extracted. PwMS and healthy controls were compared using independent samples t-tests and linear regression, including comparisons adjusted for mean SVM to control for the effect of physical activity volume. Spearman correlations between measures and logistic regressions were used to identify the clinical condition based on the measures that differed significantly after adjusting for SVM. All analyses included adjustments for demographic and clinical parameters (e.g., age, sex). RESULTS: Multiple measures of activity fragmentation significantly differed between pwMS and healthy controls, reflecting a more fragmented active behavior in pwMS. PwMS had a lower circadian rhythm amplitude, indicating a smaller amplitude in the circadian changes of daily activity, and weaker temporal correlations as based on the fractal analysis. When taking into account physical activity volume, one circadian amplitude measure and one fractal measure remained significantly different in pwMS and controls. Fragmentation measures and circadian amplitude measures were significantly associated with disability level as measured by the EDSS; the association with circadian amplitude remained significant, even after adjusting for the mean SVM. CONCLUSION: The physical activity patterns of pwMS differ from those of healthy individuals in rest-activity fragmentation, the amplitude of the circadian rhythm, and fractal regulation. Measures describing these aspects of activity provide information that is not captured in the total volume of physical activity and could, perhaps, augment the monitoring of disease progression and evaluation of the response to interventions.

Neural Variability in the Prefrontal Cortex as a Reflection of Neural Flexibility and Stability in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Functional near-infrared spectroscopy (fNIRS) studies provide direct evidence of the important role of the prefrontal cortex (PFC) during walking in aging and Parkinson disease (PD). Most studies explored mean hemoglobin (HbO2) levels, while moment-to-moment variability measures have rarely been investigated. Variability measures can inform on flexibility, which is imperative for adaptive function. We hypothesized that patients with PD will show less variability in HbO2 signals during walking compared to healthy controls. METHODS: Two hundred six participants, 57 healthy controls (age 68.9 ± 1.0 years, 27 women) and 149 patients with idiopathic PD (age 69.8 ± 0.6 years, 50 women, disease duration 8.27 ± 5.51 years), performed usual walking and dual-task walking (serial 3 subtractions) with an fNIRS sensor placed on the forehead. HbO2 variability was calculated from the SD, range, and mean detrended time series of fNIRS-derived HbO2 signal evaluated during each walking task. HbO2 variability was compared between groups and between walking tasks with mixed model analyses. RESULTS: Higher variability (SD, range, mean detrended time series) was observed during dual-task walking compared to usual walking (p < 0.025), but this was derived from the differences within the healthy control group (group × task interaction p < 0.007). On the other hand, task repetition demonstrated reduced variability in healthy controls but increased variability in patients with PD (interaction group × walk repetition p < 0.048). The Movement Disorder Society Unified Parkinson's Disease Rating Scale motor score correlated with HbO2 range (r = 0.142, p = 0.050) and HbO2 SD (r = 0.173, p = 0.018) during usual walking among all participants. DISCUSSION: In this study, we suggest a new way to interpret changes in HbO2 variability. We relate increased HbO2 variability to flexible adaptation to environmental challenges and decreased HbO2 variability to the stability of performance. Our results show that both are limited in PD; however, further investigation of these concepts is required. Moreover, HbO2 variability measures are an important aspect of brain function that add new insights into the role of PFC during walking with aging and PD. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT01732653. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with PD have more variability within HbO2 signals during usual walking compared to healthy controls but not during dual-task walking.

Frailty and Falls in People Living With Multiple Sclerosis.

OBJECTIVE: To explore the association between frailty and history of falls in people living with multiple sclerosis (MS). DESIGN: Secondary analysis. SETTING: University research laboratories in the United States and Israel. PARTICIPANTS: A total of 118 people (N=118) with relapsing-remitting MS (mean age, 48.9±10.0 years; 74.6% female; Expanded Disability Status Scale [EDSS] range, 1.0-6.0) were studied in this cross-sectional analysis. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A frailty index was calculated from 40 health deficits by following standard validated procedures. The number of falls (12-month history) was recorded. RESULTS: Overall, 33.9%, 29.7%, and 36.4% of participants were classified as nonfrail, moderately frail, and severely frail, respectively. The frailty index was significantly correlated (ρ=0.37, P<.001) with higher scores on the EDSS. In univariable negative binomial regression analysis, the frailty index was associated with a higher number of falls (incidence rate ratio [IRR]=3.33; 95% CI, 1.85-5.99; P<.001). After adjustment for age, sex, and EDSS, frailty remained strongly associated with history of falls (IRR=2.78; 95% CI, 1.51-5.10; P=.001). CONCLUSIONS: The current study identifies a significant relationship between frailty and history of falls in MS, independent of age, sex, and disease severity. These findings support the notion that frailty is a syndrome related to but independent of disability in MS.

Sensor-Based and Patient-Based Assessment of Daily-Living Physical Activity in People with Parkinson's Disease: Do Motor Subtypes Play a Role?

The benefits of daily-living physical activity are clear. Nonetheless, the relationship between physical activity levels and motor subtypes of Parkinson's disease (PD), i.e., tremor dominant (TD) and postural instability gait difficulty (PIGD), have not been well-studied. It is also unclear if patient perspectives and motor symptom severity are related to objective, sensor-based assessment of daily-living activity in those subtypes. To address these questions, total daily-living physical activity was quantified in 73 patients with PD and 29 healthy controls using a 3D-accelerometer worn on the lower back for at least three days. We found that individuals with the PIGD subtype were significantly less active than healthy older adults (p = 0.007), unlike individuals with the TD subtype. Among the PIGD subtype, higher daily physical activity was negatively associated with more severe ON bradykinesia (rS = -0.499, p = 0.002), motor symptoms (higher ON MDS-UPDRS (Unified Parkinson's Disease Rating Scale motor examination)-III scores), gait difficulties (rS = -0.502, p = 0.002), motor complications (rS = 0.466, p = 0.004), and balance (rS = 0.519, p = 0.001). In contrast, among the TD subtype, disease-related characteristics were not related to daily-living physical activity. Intriguingly, physical activity was not related to self-report of ADL difficulties (scores of the MDS-UPDRS Parts I or II) in both motor subtypes. These findings highlight the importance of objective daily-living physical activity monitoring and suggest that self-report does not necessarily reflect objective physical activity levels. Furthermore, the results point to important differences in factors related to physical activity in PD motor subtypes, setting the stage for personalized treatment programs.

Associations between daily-living physical activity and laboratory-based assessments of motor severity in patients with falls and Parkinson's disease.

INTRODUCTION: Recent work suggests that wearables can augment conventional measures of Parkinson's disease (PD). We evaluated the relationship between conventional measures of disease and motor severity (e.g., MDS-UPDRS part III), laboratory-based measures of gait and balance, and daily-living physical activity measures in patients with PD. METHODS: Data from 125 patients (age: 71.7 ±â€¯6.5 years, Hoehn and Yahr: 1-3, 60.5% men) were analyzed. The MDS-UPDRS-part III was used as the gold standard of motor symptom severity. Gait and balance were quantified in the laboratory. Daily-living gait and physical activity metrics were extracted from an accelerometer worn on the lower back for 7 days. RESULTS: In multivariate analyses, daily-living physical activity and gait metrics, laboratory-based balance, demographics and subject characteristics together explained 46% of the variance in MDS-UPDRS-part III scores. Daily-living measures accounted for 62% of the explained variance, laboratory measures 30%, and demographics and subject characteristics 7% of the explained variance. Conversely, demographics and subject characteristics, laboratory-based measures of gait symmetry, and motor symptom severity together explained less than 30% of the variance in total daily-living physical activity. MDS-UPDRS-part III scores accounted for 13% of the explained variance, i.e., <4% of all the variance in total daily-living activity. CONCLUSIONS: Our findings suggest that conventional measures of motor symptom severity do not strongly reflect daily-living activity and that daily-living measures apparently provide important information that is not captured in a conventional one-time, laboratory assessment of gait, balance or the MDS-UPDRS. To provide a more complete evaluation, wearable devices should be considered.