Prolonged-release fampridine in multiple sclerosis: Improved ambulation effected by changes in walking pattern.

BACKGROUND: Prolonged-release fampridine (PR-fampridine, 4-aminopyridine) increases walking speed in the timed 25-foot walk test (T25FW) in some patients (timed-walk responders) with multiple sclerosis (MS). OBJECTIVE: To explore the effects of PR-fampridine on different aspects of walking function and to identify associated gait modifications in subjects with MS. METHODS: In this prospective, randomized, placebo-controlled, double-blind, phase II study (FAMPKIN; clinicaltrials.gov, NCT01576354), subjects received a 6-week course of oral placebo or PR-fampridine treatment (10 mg, twice daily) before crossing over. Using 3D-motion-analysis, kinematic and kinetic parameters were assessed during treadmill walking (primary endpoint). Clinical outcome measures included T25FW, 6-minute walk test (6MWT), and balance scales. Physical activity in everyday life was measured with an accelerometer device. RESULTS: Data from 55 patients were suitable for analysis. Seventeen subjects were timed-walk responders under PR-fampridine. For the total study population and for responders, a significant increase in walking speed (T25FW) and distance (6MWT) was observed. Gait pattern changes were found at the single-subject level and correlated with improvements in the T25FW and 6MWT. Physical activity was increased in responders. CONCLUSION: PR-fampridine improves walking speed, endurance, and everyday physical activity in a subset of subjects with MS and leads to individual modifications of the gait pattern.

Characterizing cognitive-motor impairments in patients with myotonic dystrophy type 1.

Myotonic Dystrophy Type 1 (DM1) is the most frequent hereditary, adult-onset muscular dystrophy. Nevertheless, DM1-associated cognitive-motor impairments have not been fully characterized so far. This study aimed at profiling cognitive and locomotor dysfunctions in these patients. In addition, cognitive-motor interactions were assessed using a dual-task paradigm. Comprehensive cognitive-motor impairment profiles were generated for 19 patients with DM1 and 19 healthy subjects by thorough clinical, biomechanical and neuropsychological examinations. Detailed gait analysis was performed using a 3D motion capture system, whereas cognitive function was assessed using a standardized neuropsychological test battery. Patients with DM1 showed impaired functional mobility, gait velocity and endurance. DM1-related gait pathology was mainly characterized by enhanced dynamic instability, gait variability, and restricted ankle dorsiflexion. Patients' cognitive impairments particularly concerned attentional functions. Dual-task conditions induced gait deviations that slightly differed between patients and controls. DM1-associated cognitive impairments correlated with reduced functional mobility and impaired ankle dorsiflexion. Patients with DM1 revealed significant impairments of walking function, balance and cognitive performance. Differential cognitive-motor interference and significant interactions between cognitive and motor dysfunctions point towards a prominent role of cognition in gait performance of patients with DM1.

Familiarization with treadmill walking: How much is enough?

Treadmill-based gait analysis is widely used to investigate walking pathologies and quantify treatment effects on locomotion. Differential sensorimotor conditions during overground vs. treadmill walking necessitate initial familiarization to treadmill walking. Currently, there is no standardized treadmill acclimatization protocol and insufficient familiarization potentially confounds analyses. We monitored initial adaptations to treadmill walking in 40 healthy adults. Twenty-six walking parameters were assessed over 10 minutes with marker-based kinematic analysis and acclimatization profiles were generated. While 16 walking parameters demonstrated initial acclimatization followed by plateau performance, ten parameters remained stable. Distal lower limb control including ankle range of motion, toe trajectory and foot clearance underwent substantial adaptations. Moreover, intralimb coordination and gait variability also demonstrated acclimatization, while measures of symmetry and interlimb coordination did not. All parameters exhibiting a plateau after acclimatization did so within 6-7 minutes (425 strides). Older participants and those naïve to treadmill walking showed adaptations with higher amplitudes but over similar timescales. Our results suggest a minimum of 6 minutes treadmill acclimatization is required to reach a stable performance, and that this should suffice for both older and naïve healthy adults. The presented data aids in optimizing treadmill-based gait analysis and contributes to improving locomotor assessments in research and clinical settings.

Cooperative hand movements: task-dependent modulation of ipsi- and contralateral cortical control.

Cooperative hand movements are known to be controlled by a task-specific neural coupling associated with an involvement of the respective ipsilateral hemispheres. The aim of this study was to explore in how far this neural control applies to and is modulated during various, fine and gross, cooperative hand movements required during activities of daily living. Somatosensory evoked potentials and contralateral electromyographic reflex responses to unilateral ulnar nerve stimulation were simultaneously recorded in healthy participants during three different cooperative hand movement tasks and a resting condition. Amplitude ratio (ipsi-/contralateral) of the somatosensory evoked potentials, which is a measure for the involvement of the ipsilateral hemisphere in movement control, was higher in all three movement tasks compared to resting. This ratio was highest during the fine cooperative movement studied here. Contralateral reflex responses, as a measure for the functional coupling of the arms, were elicited following stimulation of both arms during gross cooperative movements. However, such a response could only be elicited in the dominant arm during fine movement. It is concluded that the neural coupling and thus enhancement of ipsilateral cortical control is preserved through different cooperative hand movement tasks, independently whether fine or gross motor tasks are performed. However, modulation of cortical control can be observed as ipsilateral cortical control is stronger during fine movements and functional coupling of the arms more focused to the dominant hand compared to gross cooperative tasks.

Short Trail Running Race: Beyond the Classic Model for Endurance Running Performance.

PURPOSE: This study aimed to examine the extent to which the classical physiological variables of endurance running performance (maximal oxygen uptake (V˙O2max), %V˙O2max at ventilatory threshold (VT), and running economy (RE)) but also muscle strength factors contribute to short trail running (TR) performance. METHODS: A homogeneous group of nine highly trained trail runners performed an official TR race (27 km) and laboratory-based sessions to determine V˙O2max, %V˙O2max at VT, level RE (RE0%) and RE on a +10% slope, maximal voluntary concentric and eccentric knee extension torques, local endurance assessed by a fatigue index (FI), and a time to exhaustion at 87.5% of the velocity associated with V˙O2max. A simple regression method and commonality analysis identifying unique and common coefficients of each independent variable were used to determine the best predictors for the TR race time (dependent variable). RESULTS: Pearson correlations showed that FI and V˙O2max had the highest correlations (r = 0.91 and r = -0.76, respectively) with TR performance. The other selected variables were not significantly correlated with TR performance. The analysis of unique and common coefficients of relative V˙O2max, %V˙O2max at VT, and RE0% provides a low prediction of TR performance (R = 0.48). However, adding FI and RE on a +10% slope (instead of RE0%) markedly improved the predictive power of the model (R = 0.98). FI and V˙O2max showed the highest unique (49.8% and 20.4% of total effect, respectively) and common (26.9% of total effect) contributions to the regression equation. CONCLUSIONS: The classic endurance running model does not allow for meaningful prediction of short TR performance. Incorporating more specific factors into TR such as local endurance and gradient-specific RE testing procedures should be considered to better characterize short TR performance.

Profiling walking dysfunction in multiple sclerosis: characterisation, classification and progression over time.

Gait dysfunction is a common and relevant symptom in multiple sclerosis (MS). This study aimed to profile gait pathology in gait-impaired patients with MS using comprehensive 3D gait analysis and clinical walking tests. Thirty-seven patients with MS walked on the treadmill at their individual, sustainable speed while 20 healthy control subjects walked at all the different patient's paces, allowing for comparisons independent of walking velocity. Kinematic analysis revealed pronounced restrictions in knee and ankle joint excursion, increased gait variability and asymmetry along with impaired dynamic stability in patients. The most discriminative single gait parameter, differentiating patients from controls with an accuracy of 83.3% (χ2 test; p = 0.0001), was reduced knee range of motion. Based on hierarchical cluster and principal component analysis, three principal pathological gait patterns were identified: a spastic-paretic, an ataxia-like, and an unstable gait. Follow-up assessments after 1 year indicated deterioration of walking function, particularly in patients with spastic-paretic gait patterns. Our findings suggest that impaired knee/ankle control is common in patients with MS. Personalised gait profiles and clustering algorithms may be promising tools for stratifying patients and to inform patient-tailored exercise programs. Responsive, objective outcome measures are important for monitoring disease progression and treatment effects in MS trials.

Modulating Arm Swing Symmetry with Cognitive Load: A Window on Rhythmic Spinal Locomotor Networks in Humans?

In healthy subjects, changes in arm swing symmetry while walking are observed when a cognitive dual task is added, with a tendency toward left-dominant arm swing as cognitive load increases. We applied a modified Stroop word/color naming paradigm to investigate this effect in spinal cord injured (SCI) patients. Six patients with cervical SCI (cSCI), 6 with thoracic injuries (tSCI; all 12 patients American Spinal Injury Association [ASIA] Injury Score [AIS]D), and 12 healthy, matched controls underwent three-dimensional 3D gait analysis while walking normally at a comfortable speed (NW) and when performing an additional congruent (CS) and incongruent (IS) Stroop task. An arm swing symmetry index (ASI)-in which positive values indicate proportionally more movement on the left and vice versa-was calculated. Even in the baseline NW condition, all three subject groups showed larger arm movements on the left. In controls, ASI increased (NW, 13.7 ± 6.3; CS, 16.6 ± 6.4; IS, 19.6 ± 7.8) as the task became more demanding. A larger shift in tSCI patients (NW, 15.8 ± 6.0; CS, 23.4 ± 3.8; IS, 30.7 ± 4.4) was driven by a significant reduction in right wrist trajectory (p = 0.014), whereas cSCI patients showed a small reduction in mean ASI with high variability (NW, 14.2 ± 10.7; CS, 9.3 ± 13.5; IS, 6.0 ± 12.9). The effect of the IS task on ASI compared to baseline (NW) was significantly different between tSCI (+12.5 ± 6.3) and cSCI (-8.2 ± 6.0) patients (p = 0.011). Disruption of the long propriospinal connections coordinating arm and leg movements during walking may explain the heightened sensitivity to manipulation of cognitive load in tSCI, whereas the more robust automaticity in cSCI may be attributed to impaired supraspinal inputs in the context of preserved intraspinal pathways.

Effects of circadian cortisol on the development of a health habit.

OBJECTIVE: Given the impact of individuals' habits on health, it is important to study how behaviors can become habitual. Cortisol has been well documented to have a role in habit formation. This study aimed to elucidate the influence of the circadian rhythm of cortisol on habit formation in a real-life setting. METHOD: Forty-eight students were followed for 90 days during which they attempted to adopt a health behavior (psoas iliac stretch). They were randomly assigned to perform the stretch either upon waking in the morning, when cortisol concentrations are high, or before evening bedtime, when cortisol levels approach the nadir. A smartphone application was used to assess the Self-Report Behavioural Automaticity Index every day and to provide reminders for salivary measurements every 30 days. The speed of the health habit formation process was calculated by modeling the learning curves. RESULTS: Extrapolation of the curves indicated that the morning group achieved automaticity at an earlier time point (105.95 days) than did the evening group (154.01 days). In addition, the cortisol level during the performance of the health behavior was identified as a significant mediator of the time point when the health behavior became habitual. CONCLUSION: The present findings suggest that the time course of the development of healthy habits depends on the time of the day and that the effect is mediated through diurnal variation in cortisol levels. Future studies are now needed to determine to what extent cortisol rhythmicity can help individuals to adopt new health behaviors. (PsycINFO Database Record

Increasing cognitive load attenuates right arm swing in healthy human walking.

Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

Minimum toe clearance: probing the neural control of locomotion.

Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait cycle and is associated with the highest risk of unintentional contact with obstacles or the ground. Age, cognitive function, attention and visual feedback affect foot clearance but how these factors interact to influence MTC control is not fully understood. We measured MTC in 121 healthy individuals aged 20-80 under four treadmill walking conditions; normal walking, lower visual field restriction and two Stroop colour/word naming tasks of two difficulty levels. Competition for cognitive and attentional resources from the Stroop task resulted in significantly lower mean MTC in older adults, with the difficult Stroop task associated with a higher frequency of extremely low MTC values and subsequently an increased modelled probability of tripping in this group. While older adults responded to visual restriction by markedly skewing MTC distributions towards higher values, this condition was also associated with frequent, extremely low MTC values. We reveal task-specific, age-dependent patterns of MTC control in healthy adults. Age-related differences are most pronounced during heavy, distracting cognitive load. Analysis of critically-low MTC values during dual-task walking may have utility in the evaluation of locomotor control and fall risk in older adults and patients with motor control deficits.

Pushing to the limits: the dynamics of cognitive control during exhausting exercise.

This study aimed at investigating concurrent changes in cognitive control and cerebral oxygenation (Cox) during steady intense exercise to volitional exhaustion. Fifteen participants were monitored using prefrontal near-infrared spectroscopy and electromyography of the thumb muscles during the completion of an Eriksen flanker task completed either at rest (control condition) or while cycling at a strenuous intensity until exhaustion (exercise condition). Two time windows were matched between the conditions to distinguish a potential exercise-induced evolutive cognitive effect: an initial period and a terminal period. In the initial period, Cox remained unaltered and, contrary to theoretical predictions, exercise did not induce any deficit in selective response inhibition. Rather, the drop-off of the delta curve as reaction time lengthened suggested enhanced efficiency of cognitive processes in the first part of the exercise bout. Shortly before exhaustion, Cox values were severely reduced - though not characteristic of a hypofrontality state - while no sign of deficit in selective response inhibition was observed. Despite this, individual's susceptibility to making fast impulsive errors increased and less efficient online correction of incorrect activation was observed near exhaustion. A negative correlation between Cox values and error rate was observed and is discussed in terms of cerebral resources redistribution.

Reproducibility of performance and fatigue in trail running.

OBJECTIVES: This study aimed to test the reproducibility of running performance, neuromuscular fatigue markers and indirect muscle damage indicators in a field-based trail time-trial. DESIGN: Running performance and changes in classical physiological parameters were analysed in 11 experienced trail runners before and in the days following four bouts of outdoor trail running (15.6 km), 7 days apart. METHODS: Heart rate, running time and lactate concentration were monitored in each running bout. Maximal voluntary contraction torque, counter movement jump height, plasma creatine kinase activity and muscle soreness were assessed before and 1, 24 and 48 h post-race. Within-bout changes were elucidated using a two-way repeated measures ANOVA. Inter-repetition reproducibility was examined using an intraclass correlation coefficient (R) and the mean intra-subject coefficient of variation at each measurement time point. RESULTS: Running time was longer (p<0.05) for the first bout compared with the other three bouts. Magnitude and time course of changes in counter movement jump height, creatine kinase activity and muscle soreness were similar among all four bouts (overall peak means: -17%, +35% and 54/100mm respectively). The acute reduction in maximal voluntary contraction torque (peak mean: -17%) was attenuated exclusively in the fourth bout (p<0.05). The two middle bouts showed good reproducibility (intraclass correlation coefficient and coefficient of variation) for running time, maximal voluntary contraction torque and counter movement jump height, but low to moderate for creatine kinase activity, muscle soreness, blood lactate and rate of perceived exertion. CONCLUSIONS: A short outdoor trail run is a reliable model for investigations of fatigue and muscle damage, but certain methodological precautions should be respected.

The influence of ice slushy on voluntary contraction force following exercise-induced hyperthermia.

This study aimed to investigate the effect of exercise-induced hyperthermia on central fatigue and force decline in exercised and nonexercised muscles and whether ingestion of ice slushy (ICE) ameliorates fatigue. Eight participants (5 males, 3 females) completed 45 s maximal voluntary isometric contractions (MVIC) with elbow flexors and knee extensors at baseline and following an exercise-induced rectal temperature (Trec) of 39.3 ± 0.2 °C. Percutaneous electrical muscle stimulation was superimposed at 15, 30 and 44 s during MVICs to assess muscle activation. To increase Trec to 39.3 °C, participants cycled at 60% maximum power output for 42 ± 11 min in 40 °C and 50% relative humidity. Immediately prior to each MVIC, participants consumed 50 g of ICE (-1 °C) or thermoneutral drink (38 °C, CON) made from 7.4% carbohydrate beverage. Participants consumed water (19 °C) during exercise to prevent hypohydration. Voluntary muscle force production and activation in both muscle groups were unchanged at Trec 39.3 °C with ICE (knee extensors: 209 ± 152 N) versus CON (knee extensors: 255 ± 157 N, p = 0.19). At Trec 39.3 °C, quadriceps mean force (232 ± 151 N) decreased versus baseline (302 ± 180 N, p < 0.001) and mean voluntary activation was also decreased (by 15% ± 11%, p < 0.001). Elbow flexor mean force decreased from 179 ± 67 N to 148 ± 65 N when Trec was increased to 39.3 °C (p < 0.001) but mean voluntary activation was not reduced at 39.3 °C (5% ± 25%, p = 0.79). After exercise-induced hyperthermia, ICE had no effect on voluntary activation or force production; however, both were reduced from baseline in the exercised muscle group. Peripheral fatigue was greater than the central component and limited the ability of an intervention designed to alter central fatigue.