Safety & efficacy of a robotic hip exoskeleton on outpatient stroke rehabilitation.

OBJECTIVE: The objective of this study was to analyze the safety and efficacy of using a robotic hip exoskeleton designed by Samsung Electronics Co., Ltd., Korea, called the Gait Enhancing and Motivating System-Hip (GEMS-H), in assistance mode only with the poststroke population in an outpatient-rehabilitation setting. METHODS: Forty-one participants with an average age of 60 and average stroke latency of 6.5 years completed this prospective, single arm, interventional, longitudinal study during the COVID-19 pandemic. Significant modifications to the traditional outpatient clinical environment were made to adhere to organizational physical distancing policies as well as guidelines from the Centers for Disease Control. All participants received gait training with the GEMS-H in assistance mode for 18 training sessions over the course of 6-8 weeks. Performance-based and self-reported clinical outcomes were assessed at four time points: baseline, midpoint (after 9 training sessions), post (after 18 training sessions), and 1-month follow up. Daily step count was also collected throughout the duration of the study using an ankle-worn actigraphy device. Additionally, corticomotor excitability was measured at baseline and post for 4 bilateral lower limb muscles using transcranial magnetic stimulation. RESULTS: By the end of the training program, the primary outcome, walking speed, improved by 0.13 m/s (p < 0.001). Secondary outcomes of walking endurance, balance, and functional gait also improved as measured by the 6-Minute Walk Test (47 m, p < 0.001), Berg Balance Scale (2.93 points, p < 0.001), and Functional Gait Assessment (1.80 points, p < 0.001). Daily step count significantly improved with and average increase of 1,750 steps per day (p < 0.001). There was a 35% increase in detectable lower limb motor evoked potentials and a significant decrease in the active motor threshold in the medial gastrocnemius (-5.7, p < 0.05) after training with the device. CONCLUSIONS: Gait training with the GEMS-H exoskeleton showed significant improvements in walking speed, walking endurance, and balance in persons with chronic stroke. Day-to-day activity also improved as evidenced by increased daily step count. Additionally, corticomotor excitability changes suggest that training with this device may help correct interhemispheric imbalance typically seen after stroke. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT04285060).

Understanding corticomotor mechanisms for activation of non-target muscles during unilateral isometric contractions of leg muscles after stroke.

PURPOSE: Muscle activation often occurs in muscles ipsilateral to a voluntarily activated muscle and to a greater extent after stroke. In this study, we measured muscle activation in non-target, ipsilateral leg muscles and used transcranial magnetic stimulation (TMS) to provide insight into whether corticomotor pathways contribute to involuntary activation. MATERIALS AND METHODS: Individuals with stroke performed unilateral isometric ankle dorsiflexion, ankle plantarflexion, knee extension, and knee flexion. To quantify involuntary muscle activation in non-target muscles, muscle activation was measured during contractions from the ipsilateral tibialis anterior (TA), medial gastrocnemius (MG), rectus femoris (RF), and biceps femoris (BF) and normalized to resting muscle activity. To provide insight into mechanisms of involuntary non-target muscle activation, TMS was applied to the contralateral hemisphere, and motor evoked potentials (MEPs) were recorded. RESULTS: We found significant muscle activation in nearly every non-target muscle during isometric unilateral contractions. MEPs were frequently observed in non-target muscles, but greater non-target MEP amplitude was not associated with greater non-target muscle activation. CONCLUSIONS: Our results suggest that non-target muscle activation occurs frequently in individuals with chronic stroke. The lack of association between non-target TMS responses and non-target muscle activation suggests that non-target muscle activation may have a subcortical or spinal origin. Non-target muscle activation has important clinical implications because it may impair torque production, out-of-synergy movement, and muscle activation timing.

Motor overflow in the lower limb after stroke: Insights into mechanisms.

Motor overflow (involuntary muscle activation) is common after stroke, particularly in the non-paretic upper limb. Two potential cortical mechanisms are as follows: (1) The contralesional hemisphere controls both limbs, and (2) inhibition from the ipsilesional to the contralesional hemisphere is diminished. Few studies have differentiated between these hypotheses or investigated motor overflow in the lower limb after stroke. To investigate these potential mechanisms, individuals with chronic stroke performed unilateral isometric and dynamic dorsiflexion. Motor overflow was quantified in the contralateral, resting (non-target) ankle. Transcranial magnetic stimulation (TMS) was applied, and responses were measured in both legs. Relations between motor overflow, excitability of ipsilateral motor pathways, and interhemispheric inhibition were assessed. Non-target muscle activity (motor overflow) was greater during isometric and dynamic conditions than rest in both legs (p ≤ 0.001) and was higher in the non-paretic than the paretic leg (p = 0.03). Some participants (25%) had motor overflow >4SD above the group mean in the non-paretic leg. Greater motor overflow in the non-paretic leg was associated with lesser inhibition from the ipsilesional to the contralesional hemisphere (p = 0.04). In both legs, non-target TMS responses were greater during the isometric and dynamic than the rest condition (p ≤ 0.01) but not when normalized to background muscle activity. Overall, motor overflow occurred in both legs after stroke, suggesting a common bilateral mechanism. Our correlational results suggest that alterations in interhemispheric inhibition may contribute to motor overflow. Furthermore, the lack of differences in non-target motor evoked potentials MEPs between rest, isometric, and dynamic conditions suggests that subcortical and/or spinal pathways may contribute to motor overflow.

Symmetry Is Associated With Interlimb Coordination During Walking and Pedaling After Stroke.

BACKGROUND AND PURPOSE: Asymmetry during walking may be explained by impaired interlimb coordination. We examined these associations: (1) propulsive symmetry with interlimb coordination during walking, (2) work symmetry with interlimb coordination during pedaling, and (3) work symmetry and interlimb coordination with clinical impairment. METHODS: Nineteen individuals with chronic stroke and 15 controls performed bilateral, lower limb pedaling with a conventional device and a device with a bisected crank and upstroke assistance. Individuals with stroke walked on a split-belt treadmill. Measures of symmetry (%Propulsionwalk, %Workped) and interlimb phase coordination index (PCIwalk, PCIped) were computed. Clinical evaluations were the lower extremity Fugl-Meyer (FMLE) and walking speed. Associations were assessed with Spearman's rank correlations. RESULTS: Participants with stroke displayed asymmetry and impaired interlimb coordination compared with controls (P ≤ 0.001). There were significant correlations between asymmetry and impaired interlimb coordination (walking: R2 = 0.79, P < 0.001; pedaling: R2 = 0.62, P < 0.001) and between analogous measures across tasks (%Workped, %Propulsionwalk: R2 = 0.41, P = 0.01; PCIped, PCIwalk: R2 = 0.52, P = 0.003). Regardless of task, asymmetry and interlimb coordination were correlated with FMLE (R2 ≥ 0.48, P ≤ 0.004) but not walking speed. There was larger within group variation for %Propulsionwalk than %Workped (Z = 2.6, P = 0.005) and for PCIped than PCIwalk (Z = 3.6, P = 0.003). DISCUSSION AND CONCLUSIONS: Pedaling may provide useful insights about walking, and impaired interlimb coordination may contribute to asymmetry in walking. Pedaling and walking provide distinct insights into stroke-related impairments, related to whether the task allows compensation (walking > pedaling) or compels paretic limb use (pedaling > walking). Pedaling a device with a bisected crank shaft may have therapeutic value.Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A365).

Ipsilateral motor pathways to the lower limb after stroke: Insights and opportunities.

Stroke-related damage to the crossed lateral corticospinal tract causes motor deficits in the contralateral (paretic) limb. To restore functional movement in the paretic limb, the nervous system may increase its reliance on ipsilaterally descending motor pathways, including the uncrossed lateral corticospinal tract, the reticulospinal tract, the rubrospinal tract, and the vestibulospinal tract. Our knowledge about the role of these pathways for upper limb motor recovery is incomplete, and even less is known about the role of these pathways for lower limb motor recovery. Understanding the role of ipsilateral motor pathways to paretic lower limb movement and recovery after stroke may help improve our rehabilitative efforts and provide alternate solutions to address stroke-related impairments. These advances are important because walking and mobility impairments are major contributors to long-term disability after stroke, and improving walking is a high priority for individuals with stroke. This perspective highlights evidence regarding the contributions of ipsilateral motor pathways from the contralesional hemisphere and spinal interneuronal pathways for paretic lower limb movement and recovery. This perspective also identifies opportunities for future research to expand our knowledge about ipsilateral motor pathways and provides insights into how this information may be used to guide rehabilitation.

Motor evoked potential latency and duration from tibialis anterior in individuals with chronic stroke.

Ipsilateral motor pathways from the contralesional hemisphere to the paretic limbs may be upregulated to compensate for impaired function after stroke. Onset latency and duration of motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) provide insight into compensatory pathways but have been understudied in the lower limb. This study assessed MEP onset latency and duration in the lower limb after stroke, and compared ipsilateral and contralateral MEPs in the paretic and non-paretic limb. We hypothesized that: (1) onset latency would be longer for ipsilateral than contralateral MEPs and longer for the paretic than the non-paretic limb, and (2) duration would be shorter for ipsilateral than contralateral MEPs and longer for the paretic than the non-paretic limb. Data were collected as a part of a pre-test of a randomized controlled trial. TMS was applied to the ipsilateral and contralateral hemisphere of the paretic and non-paretic limb. MEP onset latency and duration were calculated from the tibialis anterior. Thirty-five participants with chronic stroke were included in the final analysis. Onset latency was longer in the paretic than the non-paretic limb (~ 6.0 ms) and longer after ipsilateral than contralateral stimulation (~ 1.8 ms). Duration was longer in the paretic than the non-paretic limb (~ 9.2 ms) and longer after contralateral than ipsilateral stimulation (~ 5.2 ms). Ipsilateral MEPs may be elicited through ipsilateral pathways with fewer fibers with a higher activation threshold and/or greater spinal branching. MEPs from the paretic limb may reflect slower central motor conduction, peripheral changes, or changes in motor pathway.

Cortical priming strategies for gait training after stroke: a controlled, stratified trial.

BACKGROUND: Stroke survivors experience chronic gait impairments, so rehabilitation has focused on restoring ambulatory capacity. High-intensity speed-based treadmill training (HISTT) is one form of walking rehabilitation that can improve walking, but its effectiveness has not been thoroughly investigated. Additionally, cortical priming with transcranial direct current stimulation (tDCS) and movement may enhance HISTT-induced improvements in walking, but there have been no systematic investigations. The objective of this study was to determine if motor priming can augment the effects of HISTT on walking in chronic stroke survivors. METHODS: Eighty-one chronic stroke survivors participated in a controlled trial with stratification into four groups: 1) control-15 min of rest (n = 20), 2) tDCS-15 min of stimulation-based priming with transcranial direct current stimulation (n = 21), 3) ankle motor tracking (AMT)-15 min of movement-based priming with targeted movements of the ankle and sham tDCS (n = 20), and 4) tDCS+AMT-15 min of concurrent tDCS and AMT (n = 20). Participants performed 12 sessions of HISTT (40 min/day, 3 days/week, 4 weeks). Primary outcome measure was walking speed. Secondary outcome measures included corticomotor excitability (CME). Outcomes were measured at pre, post, and 3-month follow-up assessments. RESULTS: HISTT improved walking speed for all groups, which was partially maintained 3 months after training. No significant difference in walking speed was seen between groups. The tDCS+AMT group demonstrated greater changes in CME than other groups. Individuals who demonstrated up-regulation of CME after tDCS increased walking speed more than down-regulators. CONCLUSIONS: Our results support the effectiveness of HISTT to improve walking; however, motor priming did not lead to additional improvements. Upregulation of CME in the tDCS+AMT group supports a potential role for priming in enhancing neural plasticity. Greater changes in walking were seen in tDCS up-regulators, suggesting that responsiveness to tDCS might play an important role in determining the capacity to respond to priming and HISTT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03492229. Registered 10 April 2018 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03492229 .

Motor unit activity in biceps brachii of left-handed humans during sustained contractions with two load types.

The purpose of the study was to compare the discharge characteristics of single motor units during sustained isometric contractions that required either force or position control in left-handed individuals. The target force for the two sustained contractions (24.9 ± 10.5% maximal force) was identical for each biceps brachii motor unit (n = 32) and set at 4.7 ± 2.0% of maximal voluntary contraction (MVC) force above its recruitment threshold (range: 0.5-41.2% MVC force). The contractions were not sustained to task failure, but the duration (range: 60-330 s) was identical for each motor unit and the decline in MVC force immediately after the sustained contractions was similar for the two tasks (force: 11.1% ± 13.7%; position: 11.6% ± 9.9%). Despite a greater increase in the rating of perceived exertion during the position task (task × time interaction, P < 0.006), the amplitude of the surface-recorded electromyogram for the agonist and antagonist muscles increased similarly during the two tasks. Nonetheless, mean discharge rate of the biceps brachii motor units declined more during the position task (task × time interaction, P < 0.01) and the variability in discharge times (coefficient of variation for interspike interval) increased only during the position task (task × time interaction, P < 0.008). When combined with the results of an identical study on right-handers (Mottram CJ, Jakobi JM, Semmler JG, Enoka RM. J Neurophysiol 93: 1381-1392, 2005), the findings indicate that handedness does not influence the adjustments in biceps brachii motor unit activity during sustained submaximal contractions requiring either force or position control.

Reliability and Validity of Ratings of Perceived Exertion in Persons With Multiple Sclerosis.

OBJECTIVE: To test the reliability and validity of using the Borg rating of perceived exertion (RPE) scale (ratings 6-20) in persons with multiple sclerosis (PwMS). DESIGN: Nonrandomized repeated measures. SETTING: Research laboratory. PARTICIPANTS: Volunteer sample (N=27) comprised of 16 PwMS (10 women) and 11 age-matched persons without multiple sclerosis (MS) (6 women). Clinical measures included symptomatic fatigue, depression, and MS functional capacity. INTERVENTIONS: A submaximal cycling test was performed to estimate maximal capacity. Participants then pedaled for 2 minutes at 50% and 60% of predicted maximal oxygen consumption per unit time (V˙o2), and physiological measures and RPE were obtained (week 1: response protocol). One week later, participants replicated the prescribed V˙o2 using the RPE range from week 1 (week 2: reproduction protocol). V˙o2, heart rate, and respiratory quotient were measured continuously; RPE and workload were measured every minute; and blood lactate and mean arterial pressure were measured after exercise. MAIN OUTCOME MEASURES: RPE, workload, V˙o2, and heart rate from week 1 to week 2. RESULTS: PwMS had greater fatigue (P<.01) and disability (P<.001). Baseline measures were similar between groups and weeks. During exercise, RPE, workload, V˙o2, and heart rate were similar between groups. Both groups had an intraclass correlation coefficient >.86 for RPE, workload, and V˙o2. The intraclass correlation coefficient was comparatively lower for heart rate for both groups (MS group: .72, non-MS group: .83). RPE was highly correlated with V˙o2 (r=.691, P<.001) and workload (r=.700, P<.001) for the MS group. CONCLUSIONS: Results suggest that RPE can be reliably reproduced, is valid, and may be used in exercise prescription in mildly to moderately impaired PwMS during cycling exercise.

Barriers to Enrollment in a Post-Stroke Neuromodulation and Walking Study: Implications for Recruiting Women.

BACKGROUND: Women have a higher risk of stroke and related disability than men but are underrepresented in stroke clinical trials. Identifying modifiable recruitment and enrollment barriers for women can improve study generalizability, statistical power, and resource utilization. OBJECTIVE: In a post-stroke neuromodulation study, we determined the impact of sex on the occurrence of exclusion criteria and compared the sex distribution of screened and enrolled individuals with a broader stroke-affected population. METHODS: A total of 335 individuals with chronic stroke were screened for a study examining how neuromodulation and high-intensity treadmill training affect walking speed and corticomotor excitability. Demographics and exclusions were retrospectively gathered as a secondary dataset. Exclusion criteria consisted of 6 categories (not target population, unable to do treadmill protocol, unable to do non-invasive brain stimulation, insufficient ankle motion and disinterest, and cognitive impairment). Incidence of each exclusion criterion was compared between women and men. The sex distribution was compared to a dataset from Chicago primary stroke centers. RESULTS: A total of 81 individuals were enrolled and 254 were not. The percentage of women excluded was significantly greater than that of men (P = .04). No individual exclusion criterion or categories excluded women more frequently than men. Screened and enrolled individuals had a lower proportion of women and younger age than a representative stroke population (P < .001). CONCLUSIONS: We identified exclusion criteria (ie, headaches, cognitive scores, and age) that are modifiable barriers to enrollment of women in this post-stroke neuromodulation study. Addressing underrepresentation of women in stroke research is pivotal for enhancing generalizability, achieving statistical power, and optimizing resources.

The association of interlimb coordination and temporal symmetry with walking function and motor impairment after stroke.

OBJECTIVE: Interlimb coordination during walking is impaired after stroke, with unknown effects on walking function. This cross-sectional study determined associations of interlimb coordination and temporal symmetry with walking function and motor impairment. DESIGN: During walking, participants wore wireless sensors to detect heel strikes. We calculated interlimb coordination as the phase coordination index and temporal symmetry as the ratio of contralesional (i.e., paretic) to ipsilesional (i.e., non-paretic) stance times. Associations with walking speed (10-meter walk test), walking endurance (6-minute walk test), dynamic balance (Mini Balance Evaluation Systems Test), and motor impairment (Fugl Meyer Lower Extremity assessment) were assessed. RESULTS: 56 individuals with chronic stroke were tested. Worse interlimb coordination was correlated with slower comfortable (R = -0.38, p = 0.004) and maximal (R = -0.36, p = 0.006) walking speed and worse motor function (R = -0.45, p = 0.001). Worse temporal symmetry was correlated with worse motor function (R = 0.39, p = 0.004). Interlimb coordination had stronger associations than temporal symmetry with comfortable (R: -0.38 vs. 0.08) and maximal walking speeds (R: -0.36 vs. 0.12). CONCLUSION: Poor interlimb coordination was associated with slow walking and motor impairment and had stronger associations with walking speeds than temporal symmetry did. Interlimb coordination may provide unique insights into walking function and a target for walking rehabilitation after stroke.

Concurrent validity of walking speed measured by a wearable sensor and a stopwatch during the 10-meter walk test in individuals with stroke.

BACKGROUND: Walking speed is often measured with a stopwatch throughout stroke recovery. Wearable sensors also have been used recently to measure walking speed and provide information about spatiotemporal characteristics of walking. RESEARCH QUESTION: Do walking speeds measured with stopwatch and APDM wearable sensors have concurrent validity? METHODS: Individuals with chronic stroke (n = 62) performed the 10-meter walk test at comfortable and maximal speeds. Walking speeds were measured with a stopwatch and APDM Opal wireless wearable sensors (3-unit). Tests of concurrent validity between stopwatch and APDM (Bland-Altman plots, systematic and proportional bias, and intraclass correlations) and test-retest reliability between trials (intraclass correlations, standard error of measurement, and minimal detectable change) were performed. RESULTS: Walking speeds measured with APDM were ∼0.07 m/s slower than those measured with stopwatch (systematic bias; t ≥ 13.1, p < 0.001). Intraclass correlations ranged from poor to excellent. There were greater differences in walking speeds between APDM and stopwatch for individuals with faster walking speeds (proportional bias). Test-retest reliability was excellent for both APDM and stopwatch (intraclass correlation≥0.94). Standard error of measurement ranged from 0.04 to 0.07 m/s and minimal detectable change ranged from 0.10 to 0.19 m/s. SIGNIFICANCE: It may be inappropriate to use walking speed measurements from APDM sensors and stopwatch interchangeably in individuals with chronic stroke. Differences in walking speeds may reflect stopwatch error or the derivation of walking speed from wearable sensors. Test-retest reliability was excellent for both stopwatch and APDM, but minimal detectable change values were large. Large changes in walking speed may be required to be confident that the change is a true and clinically meaningful change and not measurement error. The validity and reliability of measuring walking speed with wearable sensors in individuals with chronic stroke has important implications for determining community ambulation, assessing improvements after rehabilitation, and developing exercise prescriptions.

Functional connectivity of proximal and distal lower limb muscles and impact on gait variability in stroke.

BACKGROUND: Higher gait variability after stroke increases risk of falls and compromises safe community ambulation. Corticomotor connectivity plays an important role in walking after stroke, however, its relation to gait variability remains unknown. RESEARCH QUESTION: Do corticomotor characteristics of the proximal and distal lower limb muscles predict gait variability in individuals with chronic stroke? METHODS: Retrospective analysis of data from 30 individuals with chronic stroke was conducted. Corticomotor characteristics were measured in the paretic and non-paretic tibialis anterior (TA, distal muscle) and rectus femoris (RF, proximal muscle) using transcranial magnetic stimulation. We calculated corticomotor excitability ratio of paretic TA and RF (CMETA/RF), corticomotor excitability symmetry (CMEsym) between hemispheres for the TA and RF, and ipsilateral corticomotor excitability (ICE) of the paretic TA. Gait variability was quantified as the coefficient of variation of the paretic step length (spatial) and step time (temporal) during comfortable walking. Relations between corticomotor characteristics and gait variability were tested with multiple linear regression. RESULTS: CMETA/RF and CMEsym of RF were significant predictors of spatial gait variability. Greater corticomotor input to the paretic RF compared to the paretic TA and greater symmetry of RF were related to higher spatial gait variability. There were no significant predictors of temporal gait variability. SIGNIFICANCE: Corticomotor inputs to the proximal RF may be important for spatial gait variability, reflecting a compensatory role of RF in walking after stroke. Stroke survivors with relatively greater corticomotor input to the paretic RF may adopt compensatory strategy to enhance propulsion and achieve foot clearance, but it may also increase spatial gait variability, particularly when combined with impaired motor control of the paretic TA. These findings may provide novel rehabilitative targets to decrease gait variability and promote safe ambulation in individuals with stroke.

A cognitive task, deep breathing, and static stretching reduce variability of motor evoked potentials during subsequent transcranial magnetic stimulation.

BACKGROUND: Motor evoked potentials (MEPs) induced via transcranial magnetic stimulation (TMS) demonstrate trial-to-trial variability limiting detection and interpretation of changes in corticomotor excitability. This study examined whether performing a cognitive task, voluntary breathing, or static stretching before TMS could reduce MEP variability. METHODS: 20 healthy young adults performed no-task, a cognitive task (Stroop test), deep breathing, and static stretching before TMS in a randomized order. MEPs were collected in the non-dominant tibialis anterior muscle at 130% active motor threshold. Variability of MEP amplitude was quantified as coefficient of variation (CV). RESULTS: MEP CV was greater after no-task (25.4 ± 7.0) than after cognitive task (23.3 ± 7.2; p < 0.05), deep breathing (20.1 ± 6.3; p < 0.001), and static stretching (20.9 ± 6.0; p = 0.004). MEP CV was greater after cognitive task than after deep breathing (p = 0.007) and static stretching (p = 0.01). There was no effect of condition on MEP amplitude. CONCLUSIONS: Performing brief cognitive, voluntary breathing, and stretching tasks before TMS can reduce MEP variability with no effect on MEP amplitude in the tibialis anterior of healthy, young adults. Similar tasks could be incorporated into research and clinical settings to improve detection of changes, normative data, and clinical predictions.

Changes in Walking Speed After High-Intensity Treadmill Training Are Independent of Changes in Spatiotemporal Symmetry After Stroke.

Objectives: Decreased walking speeds and spatiotemporal asymmetry both occur after stroke, but it is unclear whether and how they are related. It is also unclear whether rehabilitation-induced improvements in walking speed are associated with improvements in symmetry or greater asymmetry. High-intensity speed-based treadmill training (HISTT) is a recent rehabilitative strategy whose effects on symmetry are unclear. The purpose of this study was to: (1) assess whether walking speed is cross-sectionally associated with spatiotemporal symmetry in chronic stroke, (2) determine whether HISTT leads to changes in the spatiotemporal symmetry of walking, and (3) evaluate whether HISTT-induced changes in walking speed are associated with changes in spatiotemporal symmetry. Methods: Eighty-one participants with chronic stroke performed 4 weeks of HISTT. At pre, post, and 3-month follow-up assessments, comfortable and maximal walking speed were measured with the 10-meter walk test, and spatiotemporal characteristics of walking were measured with the GAITRite mat. Step length and swing time were expressed as symmetry ratios (paretic/non-paretic). Changes in walking speed and symmetry were calculated and the association was determined. Results: At pre-assessment, step length and swing time asymmetries were present (p < 0.001). Greater temporal symmetry was associated with faster walking speeds (p ≤ 0.001). After HISTT, walking speeds increased from pre-assessment to post-assessment and follow-up (p ≤ 0.002). There were no changes in spatiotemporal symmetry (p ≥ 0.10). Change in walking speed was not associated with change in spatial or temporal symmetry from pre- to post-assessment or from post-assessment to follow-up (R2 ≤ 0.01, p ≥ 0.37). Conclusions: HISTT improves walking speed but does not systematically improve or worsen spatiotemporal symmetry. Clinicians may need to pair walking interventions like HISTT with another intervention designed to improve walking symmetry simultaneously. The cross-sectional relation between temporal symmetry and walking speed may be mediated by other factors, and not be causative.

Ipsilateral Motor Pathways and Transcallosal Inhibition During Lower Limb Movement After Stroke.

BACKGROUND: Stroke rehabilitation may be improved with a better understanding of the contribution of ipsilateral motor pathways to the paretic limb and alterations in transcallosal inhibition. Few studies have evaluated these factors during dynamic, bilateral lower limb movements, and it is unclear whether they relate to functional outcomes. OBJECTIVE: Determine if lower limb ipsilateral excitability and transcallosal inhibition after stroke depend on target limb, task, or number of limbs involved, and whether these factors are related to clinical measures. METHODS: In 29 individuals with stroke, ipsilateral and contralateral responses to transcranial magnetic stimulation were measured in the paretic and nonparetic tibialis anterior during dynamic (unilateral or bilateral ankle dorsiflexion/plantarflexion) and isometric (unilateral dorsiflexion) conditions. Relative ipsilateral excitability and transcallosal inhibition were assessed. Fugl-Meyer, ankle movement accuracy, and walking characteristics were assessed. RESULTS: Relative ipsilateral excitability was greater during dynamic than isometric conditions in the paretic limb (P ≤ .02) and greater in the paretic than the nonparetic limb during dynamic conditions (P ≤ .004). Transcallosal inhibition was greater in the ipsilesional than contralesional hemisphere (P = .002) and during dynamic than isometric conditions (P = .03). Greater ipsilesional transcallosal inhibition was correlated with better ankle movement accuracy (R2 = 0.18, P = .04). Greater contralateral excitability to the nonparetic limb was correlated with improved walking symmetry (R2 = 0.19, P = .03). CONCLUSIONS: Ipsilateral pathways have increased excitability to the paretic limb, particularly during dynamic tasks. Transcallosal inhibition is greater in the ipsilesional than contralesional hemisphere and during dynamic than isometric tasks. Ipsilateral pathways and transcallosal inhibition may influence walking asymmetry and ankle movement accuracy.

Genetic polymorphisms for BDNF, COMT, and APOE do not affect gait or ankle motor control in chronic stroke: A preliminary cross-sectional study.

Background: Motor deficits after stroke are a primary cause of long-term disability. The extent of functional recovery may be influenced by genetic polymorphisms. Objectives: Determine the effect of genetic polymorphisms for brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), and apolipoprotein E (APOE) on walking speed, walking symmetry, and ankle motor control in individuals with chronic stroke. Methods: 38 participants with chronic stroke were compared based upon genetic polymorphisms for BDNF (presence [MET group] or absence [VAL group] of a Met allele), COMT (presence [MET group] or absence [VAL group] of a Met allele), and APOE (presence [ε4+ group] of absence [ε4- group] of ε4 allele). Comfortable and maximal walking speed were measured with the 10-m walk test. Gait spatiotemporal symmetry was measured with the GAITRite electronic mat; symmetry ratios were calculated for step length, step time, swing time, and stance time. Ankle motor control was measured as the accuracy of performing an ankle tracking task. Results: No significant differences were detected (p ≥ 0.11) between the BDNF, COMT, or APOE groups for any variables. Conclusions: In these preliminary findings, genetic polymorphisms for BDNF, COMT, and APOE do not appear to affect walking speed, walking symmetry, or ankle motor performance in chronic stroke.

Walking test procedures influence speed measurements in individuals with chronic stroke.

BACKGROUND: Walking speed measurements are clinically important, but varying test procedures may influence measurements and impair clinical utility. This study assessed the concurrent validity of walking speed in individuals with chronic stroke measured during the 10-m walk test with variations in 1) the presence of an electronic mat, 2) the speed measurement device, and 3) the measurement distance relative to the total test distance. METHODS: Twenty-five individuals with chronic stroke performed walking tests at comfortable and maximal walking speeds under three conditions: 1) 10-m walk test (without electronic mat) measured by stopwatch, 2) 10-m walk test (partially over an electronic mat) measured by software, and 3) 10-m walk test (partially over an electronic mat) measured by stopwatch. Analyses of systematic bias, proportional bias, and absolute agreement were performed to determine concurrent validity between conditions. FINDINGS: Walking speeds were not different between measurements (P ≥ 0.11), except maximal walking speed was faster when speed was measured with software vs. stopwatch (P = 0.002). Absolute agreement between measurements was excellent (ICC ≥ 0.97, P < 0.001). There was proportional bias between software vs. stopwatch (R2 ≥ 0.19, P ≤ 0.03) and between tests with vs. without the electronic mat (R2 = 0.27, P = 0.008). Comparisons between conditions revealed that walking speed and concurrent validity may be influenced by walking test distance, presence of an electronic mat, speed measurement device, and relative measurement distance. INTERPRETATION: Walking test procedures influence walking speed and concurrent validity between measurements. Waking test procedures should be as similar as possible with normative data or between repeated measurements to optimize validity.

Feasibility and Safety of Transcranial Direct Current Stimulation in an Outpatient Rehabilitation Setting After Stroke.

Transcranial direct current stimulation (tDCS) has strong potential for outpatient clinical use, but feasibility and safety of tDCS has only been evaluated in laboratory and inpatient clinical settings. The objective of this study was to assess feasibility and safety of tDCS for stroke in an outpatient clinical setting. Individuals with stroke in outpatient therapy received tDCS during physical therapy sessions. Feasibility was assessed with screening, enrollment, withdrawal, and adherence numbers, tDCS impressions, and perceived benefits and detriments of tDCS. Acute changes in fatigue and self-reported function and pre-post changes in fatigue were also assessed. Safety was assessed as adverse events and side effects. In total, 85 individuals were screened, and 10 were enrolled. Most exclusions were unrelated to clinical feasibility. In total, 3 participants withdrew, so 7 participants completed 2 sessions/week for 5-6 weeks with 100% adherence. In total, 71% reported positive impressions of tDCS. tDCS setup decreased to 5-7 min at end of study. There was one adverse event unrelated to tDCS. Mild to moderate side effects (tingling, itching, pinching, and fatigue) were experienced. In total, 86% of participants recounted benefits of tDCS. There were acute improvements in function and energy. Results support the feasibility and safety of tDCS in an outpatient clinical setting.

Determinants of low bone mineral density in people with multiple sclerosis: Role of physical activity.

BACKGROUND: People with multiple sclerosis (PwMS) have reduced bone mineral density (BMD), but the causes are unclear. Some factors that may cause reduced BMD in PwMS have been understudied, including physical activity, inflammation, cortisol, symptomatic fatigue, and depression. The aim of this study was to investigate factors that may uniquely contribute to reduced BMD in PwMS as compared to people without MS. We hypothesized that physical activity would be the primary determinant of low BMD in PwMS, with additional contributions from inflammation and sympathetic nervous system activation. METHODS: We tested 23 PwMS (16 women; median EDSS: 2) and 22 control participants (16 women). BMD was measured from the femoral neck and lumbar spine with dual x-ray absorptiometry. Disability was measured with the Expanded Disability Status Scale, and functional capacity was measured with the Multiple Sclerosis Functional Composite. Questionnaires measured symptomatic fatigue and depression. A blood draw was used to measure calcium, phosphate, vitamin D, N-terminal telopeptide, osteopontin, and cytokine markers of inflammation. Physical activity was measured with accelerometry. Salivary cortisol and cardiac heart rate variability also were obtained. All outcome variables were compared between groups with independent samples t-tests. Variables that were different between groups and significantly correlated (Pearson product-moment) with femoral neck BMD, were included in a theoretical model to explain femoral neck BMD. The expected direction of relations in the theoretical model were developed based upon the results of previous research. A Bayesian path analysis was used to test the relations of predictive variables with femoral neck BMD and interrelations among predictive variables, as detailed in the theoretical model. RESULTS: PwMS had lower BMD at the femoral neck than controls (p = =0.04; mean difference: -0.09; 95% CI: -0.2, -0.004; Cohen's d = =0.65), and there was a smaller, statistically non-significant difference in BMD at the lumbar spine (p = =0.07; mean difference: -0.08; 95% CI: -0.17, 0.007; Cohen's d = =0.59). PwMS also had lower functional capacity (p ≤ 0.001; Cohen's d = =1.50), greater fatigue (p<0.001; Cohen's d = =1.88), greater depression (p<0.001; d = =1.31), and decreased physical activity (p = =0.03; Cohen's d = =0.62). Using path analysis to test our theoretical model, we found that disability (standardized estimate= -0.17), physical activity (standardized estimate=0.39), symptomatic fatigue (standardized estimate= -0.36), depression (standardized estimate= -0.30), and inflammatory markers (standardized estimate=0.27) explained 51% of the variance in femoral neck BMD. Inflammatory markers were also predictive of disability (standardized estimate=0.44) and physical activity (standardized estimate= -0.40). Symptomatic fatigue and depression were correlated (r = =0.64). CONCLUSION: Physical activity, symptomatic fatigue, depression, disability, and inflammation all contributed independently to decreased femoral neck BMD in PWMS. Bone metabolism in PwMS is complex. Efforts to increase physical activity and address symptomatic fatigue and depression may improve bone mineral density in PwMS. Future research should investigate the mechanisms through which symptomatic fatigue and depression contribute to reduced BMD in PwMS.