Patients with poor upper limb motor recovery after stroke are likely to develop increased resistance to passive wrist extension, i.e., wrist hyper-resistance. Quantification of the underlying neural and non-neural elastic components is of clinical interest. This cross-sectional study compared two methods: a commercially available device (NeuroFlexor®) with an experimental EMG-based device (Wristalyzer) in 43 patients with chronic stroke. Spearman's rank correlation coefficients (r) between components, modified Ashworth scale (MAS) and range of passive wrist extension (PRoM) were calculated with 95% confidence intervals. Neural as well as elastic components assessed by both devices were associated (r = 0.61, 95%CI: 0.38-0.77 and r = 0.53, 95%CI: 0.28–0.72, respectively). The neural component assessed by the NeuroFlexor® associated significantly with the elastic components of NeuroFlexor® (r = 0.46, 95%CI: 0.18–0.67) and Wristalyzer (r = 0.36, 95%CI: 0.06–0.59). The neural component assessed by the Wristalyzer was not associated with the elastic components of both devices. Neural and elastic components of both devices associated similarly with the MAS (r = 0.58, 95%CI: 0.34–0.75 vs. 0.49, 95%CI: 0.22–0.69 and r = 0.51, 95%CI: 0.25–0.70 vs. 0.30, 95%CI: 0.00–0.55); elastic components associated with PRoM (r = -0.44, 95%CI: -0.65- -0.16 vs. -0.74, 95%CI: -0.85- -0.57 for NeuroFlexor® and Wristalyzer respectively). Results demonstrate that both methods perform similarly regarding the quantification of neural and elastic wrist hyper-resistance components and have an added value when compared to clinical assessment with the MAS alone. The added value of EMG in the discrimination between neural and non-neural components requires further investigation.@en

Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods. A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results. Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P @en

Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods. A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results. Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P @en

Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods. A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results. Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P @en

Background and Objective. Favorable prognosis of the upper limb depends on preservation or return of voluntary finger extension (FE) early after stroke. The present study aimed to determine the effects of modified constraint-induced movement therapy (mCIMT) and electromyography-triggered neuromuscular stimulation (EMG-NMS) on upper limb capacity early poststroke. Methods. A total of 159 ischemic stroke patients were included: 58 patients with a favorable prognosis (>10° of FE) were randomly allocated to 3 weeks of mCIMT or usual care only; 101 patients with an unfavorable prognosis were allocated to 3-week EMG-NMS or usual care only. Both interventions started within 14 days poststroke, lasted up until 5 weeks, focused at preservation or return of FE. Results. Upper limb capacity was measured with the Action Research Arm Test (ARAT), assessed weekly within the first 5 weeks poststroke and at postassessments at 8, 12, and 26 weeks. Clinically relevant differences in ARAT in favor of mCIMT were found after 5, 8, and 12 weeks poststroke (respectively, 6, 7, and 7 points; P @en

Background: Orthostatic hypotension (OH), a blood pressure drop after postural change, is associated with impaired standing balance and falls in older adults. This study aimed to assess the association between blood pressure (BP) and a measure of quality of standing balance, i.e. Center of Pressure (CoP) movement, after postural change from supine to standing position in geriatric outpatients, and to compare CoP movement between patients with and without OH. Methods: In a random subgroup of 75 consecutive patients who were referred to a geriatric outpatient clinic, intermittent BP measurements were obtained simultaneously with CoP measurements in mediolateral and anterior-posterior direction directly after postural change during 3 min of quiet stance with eyes open on a force plate. Additional measurements of continuous BP were available in n = 38 patients. Associations between BP change during postural change and CoP movement were analyzed using Spearman correlation. Mann-Whitney-U tests were used to compare CoP movement between patients with OH and without OH, in which OH was defined as a BP drop exceeding 20 mmHg of systolic BP (SBP) and/or 10 mmHg of diastolic BP (DBP) within 3 min after postural change. Results: OH measured intermittently was found in 8 out of 75 (11%) and OH measured continuously in 22 out of 38 patients (57.9%). BP change did not associate with CoP movement. CoP movement did not differ significantly between patients with and without OH. Conclusions: Results do not underpin the added value of CoP movement measurements in diagnosing OH in a clinical setting. Neither could we identify the role of CoP measurements in the understanding of the relation between OH and impaired standing balance.@en

Background: Orthostatic hypotension (OH) is common in older adults and associated with increased morbidity and mortality, loss of independence and high health-care costs. Standing up slowly is a recommended non-pharmacological intervention. However, the effectiveness of this advice has not been well studied. Objectives: The aim of this study was to investigate whether standing up slowly antagonises posture-related blood pressure (BP) decrease in a clinically relevant population of geriatric outpatients. Methods: In this cross-sectional study, 24 community-dwelling older adults referred to a geriatric outpatient clinic and diagnosed with OH were included. BP was measured continuously during 3 consecutive transitions from supine to standing position during normal, slow and fast transition. Results: The relative BP decrease at 0-15 s after slow transition was significantly lower than after normal transition (p = 0.003 for both systolic BP and diastolic BP) and fast transition (p = 0.045 for systolic BP; diastolic BP: non-significant). The relative diastolic BP decrease at 60-180 s after normal transition was significantly lower than after fast transition (p = 0.029). Conclusion: Standing up slowly antagonises BP decrease predominantly during the first 15 s of standing up in a clinically relevant population of geriatric outpatients diagnosed with OH. Results support the non-pharmacological intervention in clinical practice to counteract OH.@en

Purpose: Loss of selective muscle activation after stroke contributes to impaired arm function, is difficult to quantify and is not systematically assessed yet. The aim of this study was to describe and validate a technique for quantification of selective muscle activation of wrist flexor and extensor muscles in a cohort of post-stroke patients. Patterns of selective muscle activation were compared to healthy volunteers and test-retest reliability was assessed. Materials and methods: Activation Ratios describe selective activation of a muscle during its expected optimal activation as agonist and antagonist. Activation Ratios were calculated from electromyography signals during an isometric maximal torque task in 31 post-stroke patients and 14 healthy volunteers. Participants with insufficient voluntary muscle activation (maximal electromyography signal <3SD higher than baseline) were excluded. Results: Activation Ratios at the wrist were reliably quantified (Intraclass correlation coefficients 0.77–0.78). Activation Ratios were significantly lower in post-stroke patients compared to healthy participants (p < 0.05). Conclusion: Activation Ratios allow for muscle-specific quantification of selective muscle activation at the wrist in post-stroke patients. Loss of selective muscle activation may be a relevant determinant in assigning and evaluating therapy to improve functional outcome.Implications for Rehabilitation Loss of selective muscle activation after stroke contributes to impaired arm function, is difficult to quantify and is not systematically assessed yet. The ability for selective muscle activation is a relevant determinant in assigning and evaluating therapy to improve functional outcome, e.g., botulinum toxin. Activation Ratios allow for reliable and muscle-specific quantification of selective muscle activation in post-stroke patients.@en

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception. Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke. Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke. Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke. Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.@en

Background: The positive relationship between cognitive and physical performance has been widely established. The influence of brain structure on both domains has been shown as well. Objective: We studied whether the relationship between brain structure and physical performance is independent of cognitive performance. Methods: This was a cross-sectional analysis of 297 middle-aged to older adults (mean age ± SD 65.4 ± 6.8 years). Memory function, executive function and physical performance measured by the Tandem Stance Test, Chair Stand Test, 4-meter walk and 25-meter walk were assessed. Magnetic resonance imaging was available in 237 participants and used to determine the (sub)cortical gray matter, white matter, hippocampal and basal ganglia volumes and the presence of cerebral small-vessel disease, i.e. white matter hyperintensities, cerebral microbleeds (CMBs) and lacunar infarcts (LIs). Regression analysis was used adjusting for age, gender, education and whole-brain volume. A Bonferroni correction was applied considering p values <0.017 as statistically significant. Results: Poor memory function was associated with a slower 4-meter walking speed (p < 0.01). No association was found between brain structure and cognitive performance. The presence of CMBs and LIs was associated with a slower 25-meter walking speed (p < 0.001). This result did not change after additional adjustment for cognitive performance. Conclusions: In middle-aged to older adults, CMBs and LIs are associated with walking speed independent of cognitive performance. This emphasizes the clinical relevance of identifying each of the possible underlying mechanisms of physical performance, which is required for the development of timely and targeted therapies.@en

Background. The mechanism and time course of increased wrist joint stiffness poststroke and clinically observed wrist flexion deformity is still not well understood. The components contributing to increased joint stiffness are of neural reflexive and peripheral tissue origin and quantified by reflexive torque and muscle slack length and stiffness coefficient parameters. Objective. To investigate the time course of the components contributing to wrist joint stiffness during the first 26 weeks poststroke in a group of patients, stratified by prognosis and functional recovery of the upper extremity. Methods. A total of 36 stroke patients were measured on 8 occasions within the first 26 weeks poststroke using ramp-and-hold rotations applied to the wrist joint by a robot manipulator. Neural reflexive and peripheral tissue components were estimated using an electromyography-driven antagonistic wrist model. Outcome was compared between groups cross-sectionally at 26 weeks poststroke and development over time was analyzed longitudinally. Results. At 26 weeks poststroke, patients with poor recovery (Action Research Arm Test [ARAT] ≤9 points) showed a higher predicted reflexive torque of the flexors (P <.001) and reduced predicted slack length (P <.001) indicating shortened muscles contributing to higher peripheral tissue stiffness (P <.001), compared with patients with good recovery (ARAT ≥10 points). Significant differences in peripheral tissue stiffness between groups could be identified around weeks 4 and 5; for neural reflexive stiffness, this was the case around week 12. Conclusions. We found onset of peripheral tissue stiffness to precede neural reflexive stiffness. Temporal identification of components contributing to joint stiffness after stroke may prompt longitudinal interventional studies to further evaluate and eventually prevent these phenomena.@en

Human standing balance is a complex of systems, like the muscles, nervous system and sensory systems, interacting with each other in a closed loop to maintain upright stance. With age, disease and medication use these systems deteriorate, which could result in impaired balance. In this paper, it is demonstrated that multi-input-multi-output closed loop system identification techniques (MIMO-CLSIT) can be used to assess the underlying systems involved in standing balance and guide possible therapeutic options. In this study, mechanical and sensory perturbations were combined and applied simultaneously using a Balance test Room. The results demonstrate the value of MIMO-CLSIT to assess the underlying systems involved in standing balance and therefore to improve diagnosis of impaired standing balance.@en

Human standing balance is a complex of systems, like the muscles, nervous system and sensory systems, interacting with each other in a closed loop to maintain upright stance. With age, disease and medication use these systems deteriorate, which could result in impaired balance. In this paper, it is demonstrated that multi-input-multi-output closed loop system identification techniques (MIMO-CLSIT) can be used to assess the underlying systems involved in standing balance and guide possible therapeutic options. In this study, mechanical and sensory perturbations were combined and applied simultaneously using a Balance test Room. The results demonstrate the value of MIMO-CLSIT to assess the underlying systems involved in standing balance and therefore to improve diagnosis of impaired standing balance.@en

Background: Cognitive and physical impairment frequently co-occur in older people. The aim of this study was to assess the temporal order of these age-related changes in cognitive and physical performance and to assess whether a relationship was different across specific cognitive and physical domains and age groups. Methods: Cognitive domains included global, executive, and memory function; physical domains included gait speed and handgrip strength. These domains were assessed in two population-based longitudinal cohorts covering the age ranges of 55-64, 65-74, 75-85, and 85-90 years with a follow-up of 5-12 years. Cross-lagged panel models were applied to assess the temporal relationships between the different cognitive and physical domains adjusting for age, sex, education, comorbidity, depressive symptoms, and physical activity. Results: Over all age groups, poorer executive function was associated with a steeper decline in gait speed (p < .05). From the age of 85 years, this relationship was found across all cognitive and physical domains (p < .02). From the age of 65 years, slower gait speed and/or weaker handgrip strength were associated with steeper declines in global cognitive function (p < .02), with statistically significant results across all cognitive domains in the age group of 75-85 years (p < .04). Conclusions: The temporal relationship between cognitive and physical performance differs across domains and age, suggesting a specific rather than a general relationship. This emphasizes the importance of repeated measurements on different domains and encourages future research to the development of domain-and age-specific interventions.@en

Background: Cognitive and physical impairment frequently co-occur in older people. The aim of this study was to assess the temporal order of these age-related changes in cognitive and physical performance and to assess whether a relationship was different across specific cognitive and physical domains and age groups. Methods: Cognitive domains included global, executive, and memory function; physical domains included gait speed and handgrip strength. These domains were assessed in two population-based longitudinal cohorts covering the age ranges of 55-64, 65-74, 75-85, and 85-90 years with a follow-up of 5-12 years. Cross-lagged panel models were applied to assess the temporal relationships between the different cognitive and physical domains adjusting for age, sex, education, comorbidity, depressive symptoms, and physical activity. Results: Over all age groups, poorer executive function was associated with a steeper decline in gait speed (p < .05). From the age of 85 years, this relationship was found across all cognitive and physical domains (p < .02). From the age of 65 years, slower gait speed and/or weaker handgrip strength were associated with steeper declines in global cognitive function (p < .02), with statistically significant results across all cognitive domains in the age group of 75-85 years (p < .04). Conclusions: The temporal relationship between cognitive and physical performance differs across domains and age, suggesting a specific rather than a general relationship. This emphasizes the importance of repeated measurements on different domains and encourages future research to the development of domain-and age-specific interventions.@en

Proper understanding of motor control requires insight into the extent and manner in which task performance and control strategy are influenced by various aspects of visual information. We therefore systematically manipulated the visual presentation (i.e., scaling factor and optical flow density) of a visuomotor tracking task without changing the task itself, and investigated the effect on performance, effort, motor control strategy (i.e., anticipatory or corrective steering) and underlying neuromechanical parameters (i.e., intrinsic muscle stiffness and damping, and proprioceptive and visual feedback). Twenty healthy participants controlled the left-right position of a virtual car (by means of wrist rotations in a haptic robot) to track a slightly curved virtual road (presented on a 60” LED screen), while small torque perturbations were applied to the wrist (1.25–20 Hz multisine) for quantification of the neuromechanical parameters. This visuomotor tracking task was performed in conditions with low/medium/high scaling factor and low/high optical flow density. Task performance was high in all conditions (tracking accuracy 96.6%–100%); a higher scaling factor was associated with slightly better performance. As expected, participants did adapt their control strategy and the use of proprioceptive and visual feedback in response to changes in the visual presentation. These findings indicate that effects of visual representation on motor behavior should be taken into consideration in designing, interpreting and comparing experiments on motor control in health and disease. In future studies, these insights might be exploited to assess the sensory-motor adaptability in various clinical conditions.@en

Proper understanding of motor control requires insight into the extent and manner in which task performance and control strategy are influenced by various aspects of visual information. We therefore systematically manipulated the visual presentation (i.e., scaling factor and optical flow density) of a visuomotor tracking task without changing the task itself, and investigated the effect on performance, effort, motor control strategy (i.e., anticipatory or corrective steering) and underlying neuromechanical parameters (i.e., intrinsic muscle stiffness and damping, and proprioceptive and visual feedback). Twenty healthy participants controlled the left-right position of a virtual car (by means of wrist rotations in a haptic robot) to track a slightly curved virtual road (presented on a 60” LED screen), while small torque perturbations were applied to the wrist (1.25–20 Hz multisine) for quantification of the neuromechanical parameters. This visuomotor tracking task was performed in conditions with low/medium/high scaling factor and low/high optical flow density. Task performance was high in all conditions (tracking accuracy 96.6%–100%); a higher scaling factor was associated with slightly better performance. As expected, participants did adapt their control strategy and the use of proprioceptive and visual feedback in response to changes in the visual presentation. These findings indicate that effects of visual representation on motor behavior should be taken into consideration in designing, interpreting and comparing experiments on motor control in health and disease. In future studies, these insights might be exploited to assess the sensory-motor adaptability in various clinical conditions.@en

The dynamic behavior of the wrist joint is governed by nonlinear properties, yet applied mathematical models, used to describe the measured input-output (perturbation-response) relationship, are commonly linear. Consequently, the linearly estimated model parameters will depend on properties of the applied perturbation properties (such perturbation amplitude and velocity). We aimed to systematically address the effects of perturbation velocity on linearly estimated neuromechanical parameters. Using a single axis manipulator ramp and hold perturbations were applied to the wrist joint. Effects of perturbation velocity (0.5, 1 and 3 rad/s) were investigated at multiple background torque levels (0, 0.5 and 1 N·m). With increasing perturbation velocity, estimated joint stiffness remained constant, while damping and reflex gain decreased. This variation in model parameters is dependent on background torque levels, i.e. muscle contraction. These observations support the future development of nonlinear models that are capable of describing wrist joint behavior over a larger range of loading conditions, exceeding the restricted range of operation that is required for linearization.@en

The dynamic behavior of the wrist joint is governed by nonlinear properties, yet applied mathematical models, used to describe the measured input-output (perturbation-response) relationship, are commonly linear. Consequently, the linearly estimated model parameters will depend on properties of the applied perturbation properties (such perturbation amplitude and velocity). We aimed to systematically address the effects of perturbation velocity on linearly estimated neuromechanical parameters. Using a single axis manipulator ramp and hold perturbations were applied to the wrist joint. Effects of perturbation velocity (0.5, 1 and 3 rad/s) were investigated at multiple background torque levels (0, 0.5 and 1 N·m). With increasing perturbation velocity, estimated joint stiffness remained constant, while damping and reflex gain decreased. This variation in model parameters is dependent on background torque levels, i.e. muscle contraction. These observations support the future development of nonlinear models that are capable of describing wrist joint behavior over a larger range of loading conditions, exceeding the restricted range of operation that is required for linearization.@en

Background: About half of all chronic stroke patients experience loss of arm function coinciding with increased stiffness, reduced range of motion and a flexed wrist due to a change in neural and/or structural tissue properties. Quantitative assessment of these changes is of clinical importance, yet not trivial. The goal of this study was to quantify the neural and structural properties contributing to wrist joint stiffness and to compare these properties between healthy subjects and stroke patients. Methods: Stroke patients (n = 32) and healthy volunteers (n = 14) were measured using ramp-and-hold rotations applied to the wrist joint by a haptic manipulator. Neural (reflexive torque) and structural (connective tissue stiffness and slack lengths and (contractile) optimal muscle lengths) parameters were estimated using an electromyography driven antagonistic wrist model. Kruskal-Wallis analysis with multiple comparisons was used to compare results between healthy subjects, stroke patients with modified Ashworth score of zero and stroke patients with modified Ashworth score of one or more. Findings: Stroke patients with modified Ashworth score of one or more differed from healthy controls (P <0.05) by increased tissue stiffness, increased reflexive torque, decreased optimal muscle length and decreased slack length of connective tissue of the flexor muscles. Interpretation: Non-invasive quantitative analysis, including estimation of optimal muscle lengths, enables to identify neural and non-neural changes in chronic stroke patients. Monitoring these changes in time is important to understand the recovery process and to optimize treatment.@en