Botulinum neurotoxin type A responders among children with spastic cerebral palsy: Pattern-specific effects.

AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.

Single-event multilevel surgery, but not botulinum toxin injections normalize joint loading in cerebral palsy patients.

BACKGROUND: Many patients with cerebral palsy present a pathologic gait pattern, which presumably induces aberrant musculoskeletal loading that interferes with natural bone growth, causing bone deformations on the long term. Botulinum toxin interventions and single-event multilevel surgeries are used to restore the gait pattern, assuming that a normal gait pattern restores musculoskeletal loading and thus prevents further bone deformation. However, it is unknown if these interventions are able to restore musculoskeletal loading. Hence, we investigated the impact of botulinum toxin injections and single-event multilevel surgery on musculoskeletal loading. METHODS: Gait data collected in 93 children with bilateral cerebral palsy, which included pre- and post multi-level botulinum toxin (49 children) and single-event multilevel surgery (44 children) assessments, and 15 typically developing children were retrospectively processed using a musculoskeletal modelling workflow to calculate joint angles, moments, muscle and joint contact force magnitudes and orientations. Differences from the typically developing waveform were expressed by a root-mean square difference were compared using paired t-tests for each intervention separately (alpha <0.05). FINDINGS: Botulinum toxin induced significant changes in the joint angles, but did not improve the muscle and joint contact forces. Single-event multilevel surgery induced significant kinematic and kinetic changes, which were associated with improved muscle and joint contact forces. INTERPRETATION: The present results indicate that botulinum toxin injections were not able to restore normal gait kinematics nor musculoskeletal loading, whereas single-event multilevel surgery did successfully restore both. Therefore, single-event multilevel surgery might be protective against the re-occurrence of bone deformation on the longer term.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

BACKGROUND AND PURPOSE: To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. METHODS: During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. RESULTS: The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. CONCLUSIONS: A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.

An evaluator-blinded randomized controlled trial evaluating therapy effects and prognostic factors for a general and an individually defined physical therapy program in ambulant children with bilateral spastic cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is characterized by a heterogeneous nature with a variety of problems. Therefore, individualized physical therapy might be more appropriate to address the needs for these children. AIM: The first aim was to compare the effectiveness of an individually-defined therapy program (IT) and a general therapy program (GT) on gait and gross motor function in children with CP. The second aim was to evaluate interaction-effects, time-effects, treatment with botulinum toxin A, age, gross Motor Function Classification Scale (GMFCS), treatment frequency and quality as factors influencing outcome. DESIGN: An evaluator-blinded, randomized controlled trial. SETTING: Outpatient rehabilitation unit. POPULATION: Forty ambulant children with spastic bilateral CP (mean age 6 years 1 month). METHODS: All children were randomly assigned to receive either IT or GT over a 10 week period. Nineteen of these children were enrolled into a second and/or third program, resulting in 60 interventions. Primary outcome was assessed with the Goal Attainment Scale (GAS) for gross motor function goals and z-scores for goals based on specific 3D gait parameters. Secondary outcome included the Gross Motor Function Measure-88 (GMFM-88) scores, time and distance gait parameters, Gait Profile Score, Movement Analysis Profiles and time needed to complete Timed-Up-and-Go and Five-Times-Sit-To-Stand tests. RESULTS: There were higher, but non-significant GAS and z-score changes following the IT program compared to the GT program (GAS: 46.2 for the IT versus 42.2 for the GT group, P=0.332, ES 0.15; z-score: 0.135 for the IT compared to 0.072 for the GT group, P=0.669, ES 0.05). Significant time-effects could be found on the GAS (P<0.001) and the GMFM-88 total score (P<0.001). Age was identified as a predictor for GAS and GMFM-88 improvement (P=0.023 and P=0.044). CONCLUSION: No significant differences could be registered between the effects of the IT and the GT. The favorable outcome after the IT program was only a trend and needs to be confirmed on larger groups and with programs of longer duration. CLINICAL REHABILITATION IMPACT: Both programs had a positive impact on the children's motor functioning. It is useful to involve older children more actively in the process of goal setting.

Identification of the neural component of torque during manually-applied spasticity assessments in children with cerebral palsy.

Clinical assessment of spasticity is compromised by the difficulty to distinguish neural from non-neural components of increased joint torque. Quantifying the contributions of each of these components is crucial to optimize the selection of anti-spasticity treatments such as botulinum toxin (BTX). The aim of this study was to compare different biomechanical parameters that quantify the neural contribution to ankle joint torque measured during manually-applied passive stretches to the gastrocsoleus in children with spastic cerebral palsy (CP). The gastrocsoleus of 53 children with CP (10.9 ± 3.7 y; females n = 14; bilateral/unilateral involvement n = 28/25; Gross Motor Functional Classification Score I-IV) and 10 age-matched typically developing (TD) children were assessed using a manually-applied, instrumented spasticity assessment. Joint angle characteristics, root mean square electromyography and joint torque were simultaneously recorded during passive stretches at increasing velocities. From the CP cohort, 10 muscles were re-assessed for between-session reliability and 19 muscles were re-assessed 6 weeks post-BTX. A parameter related to mechanical work, containing both neural and non-neural components, was compared to newly developed parameters that were based on the modeling of passive stiffness and viscosity. The difference between modeled and measured response provided a quantification of the neural component. Both types of parameters were reliable (ICC > 0.95) and distinguished TD from spastic muscles (p < 0.001). However, only the newly developed parameters significantly decreased post-BTX (p = 0.012). Identifying the neural and non-neural contributions to increased joint torque allows for the development of individually tailored tone management.

Instrumented assessment of the effect of Botulinum Toxin-A in the medial hamstrings in children with cerebral palsy.

This study examined the sensitivity of an instrumented spasticity assessment of the medial hamstrings (MEH) in children with cerebral palsy (CP). Nineteen children received Botulinum Toxin type A (BTX-A) injections in the MEH. Biomechanical (position and torque) and electrophysiological (surface electromyography, EMG) signals were integrated during manually-performed passive stretches of the MEH at low, medium and high velocity. Signals were examined at each velocity and between stretch velocities, and compared pre and post BTX-A (43 ± 16 days). Average change between pre and post BTX-A was interpreted in view of the minimal detectable change (MDC) calculated from previously published reliability results. Improvements greater than the MDC were found for nearly all EMG-parameters and for torque parameters at high velocity and at high versus low velocity (p<0.03), however large inter-subject variability was noted. Moderate correlations were found between the improvement in EMG and in torque (r=0.52, p<0.05). Biomechanical and electrophysiological parameters proved to be adequately sensitive to assess the response to treatment with BTX-A. Furthermore, studying both parameters at different velocities improves our understanding of spasticity and of the physiological effect of selective tone-reduction. This not only provides a clinical validation of the instrumented assessment, but also opens new avenues for further spasticity research.

Three-dimensional head and trunk movement characteristics during gait in children with spastic diplegia.

This study uses a recently developed trunk model to determine which head and trunk kinematic parameters differentiate children with spastic diplegia from typically developing (TD) children while walking. Differences in head and trunk parameters in relation to the severity of the motor involvement (GMFCS levels) were additionally examined. The trunk model consisted of five segments (pelvis, thorax, head, shoulder line, spine). Discrete kinematic parameters (ROM, mean position) and angular waveforms were compared between 20 children with spastic diplegia (age 9.8 years±2.9 years; GMFCS I: n=10, GMFCS II: n=10) and 20 individually age-matched TD children (9.7 years±3 years). A new measure for overall trunk pathology, the trunk profile score (TPS), was proposed and included in the comparative analysis. Compared to TD children, children with GMFCS II showed a significantly higher TPS and increased ROM for pelvis tilt, for thorax and head in nearly all planes, and the angle of kyphosis. In children with GMFCS I, only ROM of thorax lateral bending was significantly increased. Sagittal ROM differentiated best between GMFCS levels, with higher ROM found in children with GMFCS II. Current results provide new insights into head and trunk kinematics during gait in children with spastic diplegia.

Reliability of head and trunk kinematics during gait in children with spastic diplegia.

This study describes the reliability of a clinically oriented model for three-dimensional movement analysis of head and trunk movements in children with spastic diplegia. The model consists of five rigid segments (head, thorax, pelvis, shoulder line, spine) and includes a detailed analysis of spinal segmental movements. Within and between session reliability during gait was tested in 10 children with spastic diplegia (6-14yrs). Reliability of discrete parameters was assessed with the intraclass correlation coefficient (ICC) and similarity of thorax and pelvis waveforms with the coefficient of multiple correlation (CMC). Measurement errors were calculated for all parameters (SEM, σ). Results indicated acceptable within and between session reliability of discrete parameters for thorax, pelvis, shoulder line, angle of kyphosis and the majority of the spinal segmental angles, reflected by low SEMs (<4°) and most ICCs>0.60. Within and between session waveform errors were below 4°. CMCs ranged from poor to very good, with highest values for movements in the frontal and transversal planes. The angle of lordosis showed lower between session reliability for several discrete parameters, although waveform errors were still below 5°. Head parameters showed lower overall reliability. The results of this study support the reliability of the proposed model. Head kinematic parameters should be interpreted with caution, due to difficulties in standardization. Accurate palpation of the spinal markers, especially the lumbar spine, is critical and demands thorough training of the assessor.

A clinical measurement to quantify spasticity in children with cerebral palsy by integration of multidimensional signals.

Most clinical tools for measuring spasticity, such as the Modified Ashworth Scale (MAS) and the Modified Tardieu Scale (MTS), are not sufficiently accurate or reliable. This study investigated the clinimetric properties of an instrumented spasticity assessment. Twenty-eight children with spastic cerebral palsy (CP) and 10 typically developing (TD) children were included. Six of the children with CP were retested to evaluate reliability. To quantify spasticity in the gastrocnemius (GAS) and medial hamstrings (MEH), three synchronized signals were collected and integrated: surface electromyography (sEMG); joint-angle characteristics; and torque. Muscles were manually stretched at low velocity (LV) and high velocity (HV). Spasticity parameters were extracted from the change in sEMG and in torque between LV and HV. Reliability was determined with intraclass-correlation coefficients and the standard error of measurement; validity by assessing group differences and correlating spasticity parameters with the MAS and MTS. Reliability was moderately high for both muscles. Spasticity parameters in both muscles were higher in children with CP than in TD children, showed moderate correlation with the MAS for both muscles and good correlation to the MTS for the MEH. Spasticity assessment based on multidimensional signals therefore provides reliable and clinically relevant measures of spasticity. Moreover, the moderate correlations of the MAS and MTS with the objective parameters further stress the added value of the instrumented measurements to detect and investigate spasticity, especially for the GAS.

Increased mechanical cost of walking in children with diplegia: the role of the passenger unit cannot be neglected.

Gait efficiency in children with cerebral palsy is decreased. To date, most research did not include the upper body as a separate functional unit when exploring these changes in gait efficiency. Since children with spastic diplegia often experience problems with trunk control, they could benefit from separate evaluation of the so-called 'passenger unit'. Therefore, the aim of the current study was to improve insights in the role of the passenger unit in decreased gait efficiency in children with diplegia. Mechanical cost of walking was investigated by calculating work by the integrated joint power approach in 18 children with diplegia and 25 age-related typical developing controls. The total mechanical work in children with diplegia was 1.5 times higher than in typical children. In children with diplegia work at the lower limbs was increased by 37% compared to typical children. Substantially higher increases, up to 222%, were noted at the passenger unit. Trunk and head were the main contributors to the increased work of the passenger unit, but the role of the arms cannot be neglected. Due to these disproportional increases in locomotor and passenger unit, the demands of the passenger unit in pathological gait can no longer be considered minor, as in typical gait. Therefore, the role of the passenger unit must be recognized in the decrease of gait efficiency in children with spastic diplegia and should be part of the evaluation of gait efficiency in clinical practice.

To what extent is mean EMG frequency during gait a reflection of functional muscle strength in children with cerebral palsy?

The aim of the current paper was to analyze the potential of the mean EMG frequency, recorded during 3D gait analysis (3DGA), for the evaluation of functional muscle strength in children with cerebral palsy (CP). As walking velocity is known to also influence EMG frequency, it was investigated to which extent the mean EMG frequency is a reflection of underlying muscle strength and/or the applied walking velocity. Surface EMG data of the lateral gastrocnemius (LGAS) and medial hamstrings (MEH) were collected during 3DGA. For each muscle, 20 CP children characterized by a weak and 20 characterized by a strong muscle (LGAS or MEH) were selected. A weak muscle was defined as a manual muscle testing score <3; a strong muscle was defined as a manual muscle testing score ≥4. Patient selection was based on the following inclusion criteria: (a) predominantly spastic type of CP (3-15 years old), (b) either (near) normal muscle strength or muscle weakness in at least one of the studied lower limb muscles, (c) no lower limb Botulinum Toxin-A treatment within 6 months prior to the 3DGA, (d) no history of lower limb surgery, and (e) high-quality noise-free EMG-data. For each muscle, twenty age-related typically developing (TD) children were included as controls. In both muscles a consistent pattern of increasing mean EMG frequency with decreasing muscle strength was observed. This was significant in the LGAS (TD versus weak CP). Walking velocity also had a significant effect on mean EMG frequency in the LGAS. Furthermore, based on R(2) and partial correlations, it could be concluded that both walking velocity and muscle strength have an impact on EMG, but the contribution of muscle strength was always higher. These findings underscore the potential of the mean EMG frequency recorded during 3DGA, for the evaluation of functional muscle strength in children with CP.

The effect of different physiotherapy interventions in post-BTX-A treatment of children with cerebral palsy.

AIM: To distinguish the effects of different physiotherapeutic programs in a post BTX-A regime for children with Cerebral Palsy (CP). DESIGN: Retrospective, controlled intervention study. PARTICIPANTS AND INTERVENTIONS: A group of 38 children (X¯ = 7y7m, GMFCS I-III, 27 bilateral, 11 unilateral CP) receiving an individually defined Neurodevelopment Treatment (NDT) program, was matched and compared to a group of children with the same age, GMFCS and diagnosis, receiving more conventional physiotherapy treatment. All patients received selective tone-reduction by means of multilevel BTX-A injections and adequate follow-up treatment, including physiotherapy. OUTCOME MEASURES: Three-dimensional gait analyses and clinical examination was performed pre and two months post-injection. Treatment success was defined using the Goal Attainment Scale (GAS). RESULTS: Both groups' mean converted GAS scores were above 50. The average converted GAS score was higher in the group of children receiving NDT than in the group receiving conventional physiotherapy (p < 0.05). In the NDT group, overall treatment success was achieved in 76% of the goals, compared to 67% of the goals defined for the conventional physiotherapy group. Especially for the goals based on gait analyses (p < 0.05) and in the group of children with bilateral CP (p < 0.05), treatment success was higher in the NDT group. CONCLUSION: In a post-BTX-A regime, the short-term effects of an NDT approach are more pronouncedthan these from a conventional physiotherapy approach.

A systematic review of arm activity measures for children with hemiplegic cerebral palsy.

OBJECTIVE: To identify psychometrically sound and clinically feasible assessments of arm activities in children with hemiplegic cerebral palsy for implementation in research and clinical practice. DATA SOURCES: PubMed, CINAHL, Cochrane Library, Web of Science and reference lists of relevant articles were searched. REVIEW METHODS: A systematic search was performed based on the following inclusion criteria: (1) evaluative tools at the activity level according to the International Classification of Functioning, Disability and Health; (2) previously used in studies including children with hemiplegic cerebral palsy aged 2-18 years; (3) at least one aspect of reliability and validity in children with cerebral palsy should be established. Descriptive information, psychometric properties and clinical utility were reviewed. RESULTS: Eighteen assessments were identified of which 11 met the inclusion criteria: eight functional tests and three questionnaires. Five functional tests were condition-specific, three were generic. All functional tests measure different aspects of activity, including unimanual capacity and performance during bimanual tasks. The questionnaires obtain information about the child's abilities at home or school. The reliability and validity have been established, though further use in clinical trials is necessary to determine the responsiveness. CONCLUSIONS: To obtain a complete view of what the child can do and what the child actually does, we advise a capacity-based test (Melbourne Assessment of Unilateral Upper Limb Function), a performance-based test (Assisting Hand Assessment) and a questionnaire (Abilhand-Kids). This will allow outcome differentiation and treatment guidance for the arm in children with cerebral palsy.

Botulinum toxin assessment, intervention and after-care for lower limb spasticity in children with cerebral palsy: international consensus statement.

Botulinum neurotoxin type-A (BoNT-A) has been used in association with other interventions in the management of spasticity in children with cerebral palsy (CP) for almost two decades. This consensus statement is based on an extensive review of the literature by an invited international committee. The use of BoNT-A in the lower limbs of children with spasticity caused by CP is reported using the American Academy of Neurology Classification of Evidence for therapeutic intervention. Randomized clinical trials have been grouped into five areas of management, and the outcomes are presented as treatment recommendations. The assessment of children with CP and evaluation of outcomes following injection of BoNT-A are complex, and therefore, a range of measures and the involvement of a multidisciplinary team is recommended. The committee concludes that injection of BoNT-A in children with CP is generally safe although systemic adverse events may occur, especially in children with more physical limitations (GMFCS V). The recommended dose levels are intermediate between previous consensus statements. The committee further concludes that injection of BoNT-A is effective in the management of lower limb spasticity in children with CP, and when combined with physiotherapy and the use of orthoses, these interventions may improve gait and goal attainment.

The effect of individually defined physiotherapy in children with cerebral palsy (CP).

AIM: This prospective double blind intervention study aims to evaluate the effectiveness of an individually defined physiotherapy program on the function and gait pattern of 16 children with diplegia (age 3-12 year, GMFCS I-II). METHOD: A 6 weeks general training program was followed by a specific training program based on individual goals determined by the results of 3D gait analyses, GMFM-88 and a clinical evaluation. Goal attainment scores were used for the evaluation of the achievement of individual goals. RESULTS: After the general training program, 6.7% of the children achieved the treatment goals, 33.3% stayed at the same level and 60% worsened and this in comparison to 40, 33.3 and 26.6% of the children respectively after the individually defined training program. The improvement for walking, running and jumping of the GMFM-88 was significantly more pronounced after the individually defined (p < 0.05), compared to the general training program. Whereas ankle dorsiflexion, spasticity of the hamstrings (p < 0.01), selectivity of hip abductors, knee extensors and ankle dorsiflexors significantly improved over the complete period of study (p < 0.01), hip extension, step length, stride length, ankle power generation and all hip parameters changed specifically after the individually defined training program (p < 0.01). CONCLUSION: A quantified effect is manifest with the application of an individually defined training program over a six weeks period.

Upper limb motor and sensory impairments in children with hemiplegic cerebral palsy. Can they be measured reliably?

PURPOSE: To establish interrater and test-retest reliability of a clinical assessment of motor and sensory upper limb impairments in children with hemiplegic cerebral palsy aged 5-15 years. METHOD: The assessments included passive range of motion (PROM), Modified Ashworth Scale (MAS), manual muscle testing (MMT), grip strength, the House thumb and Zancolli classification and sensory function. Interrater reliability was investigated in 30 children, test-retest reliability in 23 children. RESULTS: For PROM, interrater reliability varied from moderate to moderately high (correlation coefficients 0.48-0.73) and test-retest reliability was very high (>0.81). For the MAS and MMT, total score and subscores for shoulder, elbow, and wrist showed a moderately high to very high interrater reliability (0.60-0.91) and coefficients of >0.78 for test-retest reliability. The reliability for the individual muscles varied from moderate to high. The Jamar dynamometer was found to be highly reliable. The House thumb classification showed a substantial reliability and the Zancolli classification an almost perfect reliability. All sensory modalities had a good agreement. CONCLUSIONS: For all motor and sensory assessments, interrater and test-retest reliability was moderate to very high. Test-retest reliability was clearly higher than interrater reliability. To improve interrater reliability, it was recommended to strictly standardize the test procedure, refine the scoring criteria and provide intensive rater trainings.

Comparison of the Melbourne Assessment of Unilateral Upper Limb Function and the Quality of Upper Extremity Skills Test in hemiplegic CP.

This study investigated interrater reliability and measurement error of the Melbourne Assessment of Unilateral Upper Limb Function (Melbourne Assessment) and the Quality of Upper Extremity Skills Test (QUEST), and assessed the relationship between both scales in 21 children (15 females, six males; mean age 6y 4mo [SD 1y 3mo], range 5-8y) with hemiplegic CP. Two raters scored the videotapes of the assessments independently in a randomized order. According to the House Classification, three participants were classified as level 1, one participant as level 3, eight as level 4, three as level 5, one participant as level 6, and five as level 7. The Melbourne Assessment and the QUEST showed high interrater reliability (intraclass correlation 0.97 for Melbourne Assessment; 0.96 for QUEST total score; 0.96 for QUEST hemiplegic side). The standard error of measurement and the smallest detectable difference was 3.2% and 8.9% for the Melbourne Assessment and 5.0% and 13.8% for the QUEST score on the hemiplegic side. Correlation analysis indicated that different dimensions of upper limb function are addressed in both scales.

Clinical value of botulinum toxin in neurological indications.

Botulinum toxin type-A (BoNT-A) prevents the release of acetylcholine at cholinergic junctions, thereby causing temporary muscle weakness lasting 3-4 months. It is now widely used to treat a broad range of clinical disorders characterized by muscle hyperactivity. BoNT-A has proved effective in the management of several neurological conditions and, in particular, in the management of movement disorders (e.g. blepharospasm, cervical dystonia, laryngeal dystonia, limb dystonia, hemifacial spasm, focal tics, tremor and other hyperkinetic disorders). As a treatment of spasticity, BoNT-A can improve mobility and dexterity as well as preventing the development of distressing and costly secondary complications. In cerebral palsy, BoNT-A is of value, being able to delay or even avoid surgery until motion patterns have become established.