Functional assessment of stretch hyperreflexia in children with cerebral palsy using treadmill perturbations

Background: As hyperactive muscle stretch reflexes hinder movement in patients with central nervous system disorders, they are a common target of treatment. To improve treatment evaluation, hyperactive reflexes should be assessed during activities as walking rather than passively. This study systematically explores the feasibility, reliability and validity of sudden treadmill perturbations to evoke and quantify calf muscle stretch reflexes during walking in children with neurological disorders. Methods: We performed an observational cross-sectional study including 24 children with cerebral palsy (CP; 6–16 years) and 14 typically developing children (TD; 6–15 years). Short belt accelerations were applied at three different intensities while children walked at comfortable speed. Lower leg kinematics, musculo-tendon lengthening and velocity, muscle activity and spatiotemporal parameters were measured to analyze perturbation responses. Results: We first demonstrated protocol feasibility: the protocol was completed by all but three children who ceased participation due to fatigue. All remaining children were able to maintain their gait pattern during perturbation trials without anticipatory adaptations in ankle kinematics, spatiotemporal parameters and muscle activity. Second, we showed the protocol’s reliability: there was no systematic change in muscle response over time (P = 0.21–0.54) and a bootstrapping procedure indicated sufficient number of perturbations, as the last perturbation repetition only reduced variability by ~ 2%. Third, we evaluated construct validity by showing that responses comply with neurophysiological criteria for stretch reflexes: perturbations superimposed calf muscle lengthening (P < 0.001 for both CP and TD) in all but one participant. This elicited increased calf muscle activity (359 ± 190% for CP and 231 ± 68% for TD, both P < 0.001) in the gastrocnemius medialis muscle, which increased with perturbation intensity (P < 0.001), according to the velocity-dependent nature of stretch reflexes. Finally, construct validity was shown from a clinical perspective: stretch reflexes were 1.7 times higher for CP than TD for the gastrocnemius medialis muscle (P = 0.017). Conclusions: The feasibility and reliability of the protocol, as well as the construct validity—shown by the exaggerated velocity-dependent nature of the measured responses—strongly support the use of treadmill perturbations to quantify stretch hyperreflexia during gait. We therefore provided a framework which can be used to inform clinical decision making and treatment evaluation.Biomechatronics & Human-Machine Contro

Muscle synergies in response to biofeedback-driven gait adaptations in children with cerebral palsy

Background: Children with cerebral palsy (CP) often show impaired selective motor control (SMC) that induces limitations in motor function. Children with CP can improve aspects of pathological gait in an immediate response to visual biofeedback. It is not known, however, how these gait adaptations are achieved at the neural level, nor do we know the extent of SMC plasticity in CP. Aim: Investigate the underlying SMC and changes that may occur when gait is adapted with biofeedback. Methods: Twenty-three ambulatory children with CP and related (hereditary) forms of spastic paresis (Aged: 10.4 ± 3.1, 6–16 years, M: 16/F: 9) were challenged with real-time biofeedback to improve step length, knee extension, and ankle power while walking on an instrumented treadmill in a virtual reality environment. The electromyograms of eight superficial muscles of the leg were analyzed and synergies were further decomposed using non-negative matrix factorization (NNMF) using 1 to 5 synergies, to quantify SMC. Total variance accounted for (tVAF) was used as a measure of synergy complexity. An imposed four synergy solution was investigated further to compare similarity in weightings and timing patterns of matched paired synergies between baseline and biofeedback trials. Results: Despite changes in walking pattern, changes in synergies were limited. The number of synergies required to explain at least 90% of muscle activation increased significantly, however, the change in measures of tVAF1 from baseline (0.75 ± 0.08) were less than ±2% between trials. In addition, within-subject similarity of synergies to baseline walking was high (>0.8) across all biofeedback trials. Conclusion: These results suggest that while gait may be adapted in an immediate response, SMC as quantified by synergy analysis is perhaps more rigidly impaired in CP. Subtle changes in synergies were identified; however, it is questionable if these are clinically meaningful at the level of an individual. Adaptations may be limited in the short term, and further investigation is essential to establish if long term training using biofeedback leads to adapted SMC.Biomechatronics & Human-Machine Contro

Immediate effects of immersive biofeedback on gait in children with cerebral palsy

Objective: To investigate the immediate response to avatar-based biofeedback on 3 clinically important gait parameters: step length, knee extension, and ankle power in children with cerebral palsy (CP). Design: Repeated measures design. Setting: Rehabilitation clinic. Participants: Children with spastic paresis (N=22; 10.5±3.1y), able to walk without assistive devices. Intervention: Children walked on a treadmill with a virtual reality environment. Following baseline gait analysis, they were challenged to improve aspects of gait. Children visualized themselves as an avatar, representing movement in real time. They underwent a series of 2-minute trials receiving avatar-based biofeedback on step length, knee extension, and ankle power. To investigate optimization of biofeedback visualization, additional trials in which knee extension was visualized as a simple bar with no avatar; and avatar alone with no specific biofeedback were carried out. Main Outcome Measures: Gait pattern, as measured by joint angles, powers, and spatiotemporal parameters, were compared between baseline and biofeedback trials. Results: Participants were able to adapt gait pattern with biofeedback, in an immediate response, reaching large increases in ankle power generation at push-off (37.7%) and clinically important improvements in knee extension (7.4o) and step length (12.7%). Biofeedback on one parameter had indirect influence on other aspects of gait. Conclusion: Children with CP show capacity in motor function to achieve improvements in clinically important aspects of gait. Visualizing biofeedback with an avatar was subjectively preferential compared to a simplified bar presentation of knee angle. Future studies are required to investigate if observed transient effects of biofeedback can be retained with prolonged training to test whether biofeedback-based gait training may be implemented as a therapy tool.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this workBiomechatronics & Human-Machine Contro

Early Development of Locomotor Patterns and Motor Control in Very Young Children at High Risk of Cerebral Palsy, a Longitudinal Case Series

The first years of life might be critical for encouraging independent walking in children with cerebral palsy (CP). We sought to identify mechanisms that may underlie the impaired development of walking in three young children with early brain lesions, at high risk of CP, via comprehensive instrumented longitudinal assessments of locomotor patterns and muscle activation during walking. We followed three children (P1–P3) with early brain lesions, at high risk of CP, during five consecutive gait analysis sessions covering a period of 1 to 2 years, starting before the onset of independent walking, and including the session during the first independent steps. In the course of the study, P1 did not develop CP, P2 was diagnosed with unilateral and P3 with bilateral CP. We monitored the early development of locomotor patterns over time via spatiotemporal gait parameters, intersegmental coordination (estimated via principal component analysis), electromyography activity, and muscle synergies (determined from 11 bilateral muscles via nonnegative matrix factorization). P1 and P2 started to walk independently at the corrected age of 14 and 22 months, respectively. In both of them, spatiotemporal gait parameters, intersegmental coordination, muscle activation patterns, and muscle synergy structure changed from supported to independent walking, although to a lesser extent when unilateral CP was diagnosed (P2), especially for the most affected leg. The child with bilateral CP (P3) did not develop independent walking, and all the parameters did not change over time. Our exploratory longitudinal study revealed differences in maturation of locomotor patterns between children with divergent developmental trajectories. We succeeded in identifying mechanisms that may underlie impaired walking development in very young children at high risk of CP. When verified in larger sample sizes, our approach may be considered a means to improve prognosis and to pinpoint possible targets for early intervention.Biomechatronics & Human-Machine Contro

Applying Stretch to Evoke Hyperreflexia in Spasticity Testing: Velocity vs. Acceleration

In neurological diseases, muscles often become hyper-resistant to stretch due to hyperreflexia, an exaggerated stretch reflex response that is considered to primarily depend on the muscle's stretch velocity. However, there is still limited understanding of how different biomechanical triggers applied during clinical tests evoke these reflex responses. We examined the effect of imposing a rotation with increasing velocity vs. increasing acceleration on triceps surae muscle repsonse in children with spastic paresis (SP) and compared the responses to those measured in typically developing (TD) children. A motor-operated ankle manipulator was used to apply different bell-shaped movement profiles, with three levels of maximum velocity (70, 110, and 150°/s) and three levels of maximum acceleration (500, 750, and 1,000°/s2). For each profile and both groups, we evaluated the amount of evoked triceps surae muscle activation. In SP, we evaluated two additional characteristics: the intensity of the response (peak EMG burst) and the time from movement initiation to onset of the EMG burst. As expected, the amount of evoked muscle activation was larger in SP compared to TD (all muscles: p < 0.001) and only sensitive to biomechanical triggers in SP. Further investigation of the responses in SP showed that peak EMG bursts increased in profiles with higher peak velocity (lateral gastrocnemius: p = 0.04), which was emphasized by fair correlations with increased velocity at EMG burst onset (all muscles: r > 0.33–0.36, p ≤ 0.008), but showed no significant effect for acceleration. However, the EMG burst was evoked faster with higher peak acceleration (all muscles p < 0.001) whereas it was delayed in profiles with higher peak velocity (medial gastrocnemius and soleus: p < 0.006). We conclude that while exaggerated response intensity (peak EMG burst) seems linked to stretch velocity, higher accelerations seem to evoke faster responses (time to EMG burst onset) in triceps surae muscles in SP. Understanding and controlling for the distinct effects of different biological triggers, including velocity, acceleration but also length and force of the applied movement, will contribute to the development of more precise clinical measurement tools. This is especially important when aiming to understand the role of hyperreflexia during functional movements where the biomechanical inputs are multiple and changing.Biomechatronics & Human-Machine Contro

Gastrocnemius Medialis Muscle Geometry and Extensibility in Typically Developing Children and Children With Spastic Paresis Aged 6–13 Years

Gait of children with spastic paresis (SP) is frequently characterized by a reduced ankle range of motion, presumably due to reduced extensibility of the triceps surae (TS) muscle. Little is known about how morphological muscle characteristics in SP children are affected. The aim of this study was to compare gastrocnemius medialis (GM) muscle geometry and extensibility in children with SP with those of typically developing (TD) children and assess how GM morphology is related to its extensibility. Thirteen children with SP, of which 10 with a diagnosis of spastic cerebral palsy and three with SP of unknown etiology (mean age 9.7 ± 2.1 years; GMFCS: I–III), and 14 TD children (mean age 9.3 ± 1.7 years) took part in this study. GM geometry was assessed using 3D ultrasound imaging at 0 and 4 Nm externally imposed dorsal flexion ankle moments. GM extensibility was defined as its absolute length change between the externally applied 0 and 4 Nm moments. Anthropometric variables and GM extensibility did not differ between the SP and TD groups. While in both groups, GM muscle volume correlated with body mass, the slope of the regression line in TD was substantially higher than that in SP (TD = 3.3 ml/kg; SP = 1.3 ml/kg, p < 0.01). In TD, GM fascicle length increased with age, lower leg length and body mass, whereas in SP children, fascicle length did not correlate with any of these variables. However, the increase in GM physiological cross-sectional area as a function of body mass did not differ between SP and TD children. Increases in lengths of tendinous structures in children with SP exceeded those observed in TD children (TD = 0.85 cm/cm; SP = 1.16 cm/cm, p < 0.01) and even exceeded lower-leg length increases. In addition, only for children with SP, body mass (r = −0.61), height (r = −0.66), muscle volume (r = − 0.66), physiological cross-sectional area (r = − 0.59), and tendon length (r = −0.68) showed a negative association with GM extensibility. Such negative associations were not found for TD children. In conclusion, physiological cross-sectional area and length of the tendinous structures are positively associated with age and negatively associated with extensibility in children with SP.Biomechatronics & Human-Machine Contro

Instrumented assessment of motor function in dyskinetic cerebral palsy: A systematic review

Background: In this systematic review we investigate which instrumented measurements are available to assess motor impairments, related activity limitations and participation restrictions in children and young adults with dyskinetic cerebral palsy. We aim to classify these instrumented measurements using the categories of the international classification of functioning, disability and health for children and youth (ICF-CY) and provide an overview of the outcome parameters. Methods: A systematic literature search was performed in November 2019. We electronically searched Pubmed, Embase and Scopus databases. Search blocks included (a) cerebral palsy, (b) athetosis, dystonia and/or dyskinesia, (c) age 2-24 years and (d) instrumented measurements (using keywords such as biomechanics, sensors, smartphone, and robot). Results: Our search yielded 4537 articles. After inspection of titles and abstracts, a full text of 245 of those articles were included and assessed for further eligibility. A total of 49 articles met our inclusion criteria. A broad spectrum of instruments and technologies are used to assess motor function in dyskinetic cerebral palsy, with the majority using 3D motion capture and surface electromyography. Only for a small number of instruments methodological quality was assessed, with only one study showing an adequate assessment of test-retest reliability. The majority of studies was at ICF-CY function and structure level and assessed control of voluntary movement (29 of 49) mainly in the upper extremity, followed by assessment of involuntary movements (15 of 49), muscle tone/motor reflex (6 of 49), gait pattern (5 of 49) and muscle power (2 of 49). At ICF-CY level of activities and participation hand and arm use (9 of 49), fine hand use (5 of 49), lifting and carrying objects (3 of 49), maintaining a body position (2 of 49), walking (1 of 49) and moving around using equipment (1 of 49) was assessed. Only a few methods are potentially suitable outside the clinical environment (e.g. inertial sensors, accelerometers). Conclusion: Although the current review shows the potential of several instrumented methods to be used as objective outcome measures in dyskinetic cerebral palsy, their methodological quality is still unknown. Future development should focus on evaluating clinimetrics, including validating against clinical meaningfulness. New technological developments should aim for measurements that can be applied outside the laboratory.Biomechatronics & Human-Machine Contro

Exergaming improves balance in children with spastic cerebral palsy with low balance performance: results from a multicenter controlled trial

Purpose: Previous studies investigating the effectiveness of exergame balance-training (using video-games) in children with cerebral palsy (CP) yielded inconsistent results that could be related to underpowered studies. Therefore, in this multicenter intervention study, we investigated whether exergaming improves balance clinically in spastic CP. Materials and methods: In total, 35 children with unilateral or bilateral spastic CP (GMFCS-level I–II) were included (age-range: 7–16 years); 16 at VUMC (trial: NTR6034), 19 at UHG (trial: NCT03219112). All participants received care as usual. The intervention group (n = 24) additionally performed exergame-training; 6–8 weeks home-based X-box One Kinect training focused on balance. Balance performance was assessed with the pediatric balance scale (PBS) and two subscales of the Bruininks–Oseretsky Test of Motor Proficiency-2nd edition (“balance” [BOTbal] and “running speed and agility” [BOTrsa]). Mixed model ANOVAs with between and within factors were used to test differences between and within groups. Results: On group level, no post-intervention differences were found between the intervention and control group (PBS: p = 0.248, ηp2 = 0.040; BOTbal: p = 0.374, ηp2 = 0.024; BOTrsa: p = 0.841, ηp2 = 0.001). Distribution of CP-symptoms (unilateral versus bilateral) did not affect training (PBS: p = 0.373, ηp2 = 0.036; BOTbal: p = 0.127, ηp2 = 0.103; BOTrsa: p = 0.474, ηp2 = 0.024). Children with low baseline balance performance (based on PBS) in the intervention group showed improvements in balance performance after training (PBS: p = 0.003, ηp2 = 0.304; BOTbal: p = 0.008, ηp2 = 0.258), whereas children with high baseline balance performance did not. Conclusions: This exergame-training resulted in balance improvements for the current population of CP that had a low baseline function.IMPLICATIONS FOR REHABILITATION Exergame-training (training using video-games) shows mixed results in children with cerebral palsy (CP). Children with spastic CP (GMFCS level I–II) with a high baseline balance-level did not show functional balance improvements after this home-based exergame-training, suggesting that these children should not be enrolled in this type of exergame-training protocol. Children with spastic CP (GMFCS level I–II) with a low baseline balance-level showed clinically relevant functional balance improvements after this home-based exergame-training, suggesting that these children can benefit from enrolment in this type of exergame-training protocol to improve their balance. The distribution of CP-symptoms did not affect the effectiveness of this balance exergame-training in children with spastic CP with GMFCS-level I and II.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Biomechatronics & Human-Machine Contro

Neuromuscular control before and after independent walking onset in children with cerebral palsy

Early brain lesions which produce cerebral palsy (CP) may affect the development of walking. It is unclear whether or how neuromuscular control, as evaluated by muscle synergy analysis, differs in young children with CP compared to typically developing (TD) children with the same walking ability, before and after the onset of independent walking. Here we grouped twenty children with (high risk of) CP and twenty TD children (age 6.5–52.4 months) based on their walking ability, supported or independent walking. Muscle synergies were extracted from electromyography data of bilateral leg muscles using non-negative matrix factorization. Number, synergies’ structure and variability accounted for when extracting one (VAF1 ) or two (VAF2 ) synergies were compared between CP and TD. Children in the CP group recruited fewer synergies with higher VAF1 and VAF2 compared to TD children in the supported and independent walking group. The most affected side in children with asymmetric CP walking independently recruited fewer synergies with higher VAF1 compared to the least affected side. Our findings suggest that early brain lesions result in early alterations of neuromuscular control, specific for the most affected side in asymmetric CP.Biomechatronics & Human-Machine Contro

Home‐Based Measurements of Dystonia in Cerebral Palsy Using Smartphone‐Coupled Inertial Sensor Technology and Machine Learning: A Proof‐of‐Concept Study

Accurate and reliable measurement of the severity of dystonia is essential for the indication, evaluation, monitoring and fine‐tuning of treatments. Assessment of dystonia in children and adolescents with dyskinetic cerebral palsy (CP) is now commonly performed by visual evaluation either directly in the doctor’s office or from video recordings using standardized scales. Both methods lack objectivity and require much time and effort of clinical experts. Only a snapshot of the severity of dyskinetic movements (i.e., choreoathetosis and dystonia) is captured, and they are known to fluctuate over time and can increase with fatigue, pain, stress or emotions, which likely happens in a clinical environment. The goal of this study was to investigate whether it is feasible to use home‐based measurements to assess and evaluate the severity of dystonia using smartphonecoupled inertial sensors and machine learning. Video and sensor data during both active and rest situations from 12 patients were collected outside a clinical setting. Three clinicians analyzed the videos and clinically scored the dystonia of the extremities on a 0–4 scale, following the definition of amplitude of the Dyskinesia Impairment Scale. The clinical scores and the sensor data were coupled to train different machine learning models using cross‐validation. The average F1 scores (0.67 ± 0.19 for lower extremities and 0.68 ± 0.14 for upper extremities) in independent test datasets indicate that it is possible to detected dystonia automatically using individually trained models. The predictions could complement standard dyskinetic CP measures by providing frequent, objective, real‐world assessments that could enhance clinical care. A generalized model, trained with data from other subjects, shows lower F1 scores (0.45 for lower extremities and 0.34 for upper extremities), likely due to a lack of training data and dissimilarities between subjects. However, the generalized model is reasonably able to distinguish between high and lower scores. Future research should focus on gathering more high‐quality data and study how the models perform over the whole day.Biomechatronics & Human-Machine Contro