Intensive Therapy of the Lower Limbs and the Trunk in Children with Bilateral Spastic Cerebral Palsy: Comparing a Qualitative Functional and a Functional Approach.

Few studies have examined the effect of intensive therapy on gross motor function and trunk control in children with cerebral palsy (CP). This study evaluated the effects of an intensive burst of therapy on the lower limbs and trunk by comparing qualitative functional and functional approaches. This study was designed as a quasi-randomized, controlled, and evaluator-blinded trial. Thirty-six children with bilateral spastic CP (mean age = 8 y 9 mo; Gross Motor Function Classification II and III) were randomized into functional (n = 12) and qualitative functional (n = 24) groups. The main outcome measures were the Gross Motor Function Measure (GMFM), the Quality Function Measure (QFM), and the Trunk Control Measurement Scale (TCMS). The results revealed significant time-by-approach interaction effects for all QFM attributes and the GMFM's standing dimension and total score. Post hoc tests showed immediate post-intervention gains with the qualitative functional approach for all QFM attributes, the GMFM's standing and walking/running/jumping dimension and total score, and the total TCMS score. The qualitative functional approach shows promising results with improvements in movement quality and gross motor function.

Reliability of 3D freehand ultrasound to assess lower limb muscles in children with spastic cerebral palsy and typical development.

This study investigated the reliability of 3-dimensional freehand ultrasound (3DfUS) to quantify the size (muscle volume [MV] and anatomical cross-sectional area [aCSA]), length (muscle length [ML], tendon length [TL], and muscle tendon unit length [MTUL]), and echo-intensity (EI, whole muscle and 50% aCSA), of lower limb muscles in children with spastic cerebral palsy (SCP) and typical development (TD). In total, 13 children with SCP (median age 14.3 (7.3) years) and 13 TD children (median age 11.1 (1.7) years) participated. 3DfUS scans of rectus femoris, semitendinosus, medial gastrocnemius, and tibialis anterior were performed by two raters in two sessions. The intra- and inter-rater and intra- and inter-session reliability were defined with relative and absolute reliability measures, that is, intra-class correlation coefficients (ICCs) and absolute and relative standard error of measurement (SEM and SEM%), respectively. Over all conditions, ICCs for muscle size measures ranged from 0.818 to 0.999 with SEM%s of 12.6%-1.6%. For EI measures, ICCs varied from 0.233 to 0.967 with SEM%s of 15.6%-1.7%. Length measure ICCs ranged from 0.642 to 0.999 with SEM%s of 16.0%-0.5%. In general, reliability did not differ between the TD and SCP cohort but the influence of different muscles, raters, and sessions was not constant for all 3DfUS parameters. Muscle length and muscle tendon unit length were the most reliable length parameters in all conditions. MV and aCSA showed comparable SEM%s over all muscles, where tibialis anterior MV was most reliable. EI had low-relative reliability, but absolute reliability was better, with better reliability for the distal muscles in comparison to the proximal muscles. Combining these results with earlier studies describing muscle morphology assessed in children with SCP, 3DfUS seems sufficiently reliable to determine differences between cohorts and functional levels. The applicability on an individual level, for longitudinal follow-up and after interventions is dependent on the investigated muscle and parameter. Moreover, the semitendinosus, the acquisition, and processing of multiple sweeps, and the definition of EI and TL require further investigation. In general, it is recommended, especially for longitudinal follow-up studies, to keep the rater the same, while standardizing acquisition settings and positioning of the subject.

Morphological Medial Gastrocnemius Muscle Growth in Ambulant Children with Spastic Cerebral Palsy: A Prospective Longitudinal Study.

Only cross-sectional studies have demonstrated muscle deficits in children with spastic cerebral palsy (SCP). The impact of gross motor functional limitations on altered muscle growth remains unclear. This prospective longitudinal study modelled morphological muscle growth in 87 children with SCP (age range 6 months to 11 years, Gross Motor Function Classification System [GMFCS] level I/II/III = 47/22/18). Ultrasound assessments were performed during 2-year follow-up and repeated for a minimal interval of 6 months. Three-dimensional freehand ultrasound was applied to assess medial gastrocnemius muscle volume (MV), mid-belly cross-sectional area (CSA) and muscle belly length (ML). Non-linear mixed models compared trajectories of (normalized) muscle growth between GMFCS-I and GMFCS-II&III. MV and CSA growth trajectories showed a piecewise model with two breakpoints, with the highest growth before 2 years and negative growth rates after 6-9 years. Before 2 years, children with GMFCS-II&III already showed lower growth rates compared to GMFCS-I. From 2 to 9 years, the growth rates did not differ between GMFCS levels. After 9 years, a more pronounced reduction in normalized CSA was observed in GMFCS-II&III. Different trajectories in ML growth were shown between the GMFCS level subgroups. These longitudinal trajectories highlight monitoring of SCP muscle pathology from early ages and related to motor mobility. Treatment planning and goals should stimulate muscle growth.

Associations between muscle morphology and spasticity in children with spastic cerebral palsy.

INTRODUCTION: Due to the heterogeneous clinical presentation of spastic cerebral palsy (SCP), which makes spasticity treatment challenging, more insight into the complex interaction between spasticity and altered muscle morphology is warranted. AIMS: We studied associations between spasticity and muscle morphology and compared muscle morphology between commonly observed spasticity patterns (i.e. different muscle activation patterns during passive stretches). METHODS: Spasticity and muscle morphology of the medial gastrocnemius (MG) and semitendinosus (ST) were defined in 74 children with SCP (median age 8 years 2 months, GMFCS I/II/III: 31/25/18, bilateral/unilateral: 46/27). Using an instrumented assessment, spasticity was quantified as the difference in muscle activation recorded during passive stretches at low and high velocities and was classified in mixed length-/velocity-dependent or pure velocity-dependent activation patterns. Three-dimensional freehand ultrasound was used to assess muscle morphology (volume and length) and echogenicity intensity (as a proxy for muscle quality). Spearman correlations and Mann-Whitney-U tests defined associations and group differences, respectively. RESULTS: A moderate negative association (r = -0.624, p < 0.001) was found between spasticity and MG muscle volume, while other significant associations between spasticity and muscle morphology parameters were weak. Smaller normalized muscle volume (MG p = 0.004, ST p=<0.001) and reduced muscle belly length (ST p = 0.015) were found in muscles with mixed length-/velocity-dependent patterns compared to muscles with pure velocity-dependent patterns. DISCUSSION: Higher spasticity levels were associated with smaller MG and ST volumes and shorter MG muscles. These muscle morphology alterations were more pronounced in muscles that activated during low-velocity stretches compared to muscles that only activated during high-velocity stretches.

A comprehensive normative reference database of muscle morphology in typically developing children aged 3-18 years-a cross-sectional ultrasound study.

During childhood, muscle growth is stimulated by a gradual increase in bone length and body mass, as well as by other factors, such as physical activity, nutrition, metabolic, hormonal, and genetic factors. Muscle characteristics, such as muscle volume, anatomical cross-sectional area, and muscle belly length, need to continuously adapt to meet the daily functional demands. Pediatric neurological and neuromuscular disorders, like cerebral palsy and Duchenne muscular dystrophy, are characterized by impaired muscle growth, which requires treatment and close follow-up. Nowadays ultrasonography is a commonly used technique to evaluate muscle morphology in both pediatric pathologies and typically developing children, as it is a quick, easy applicable, and painless method. However, large normative datasets including different muscles and a large age range are lacking, making it challenging to monitor muscle over time and estimate the level of pathology. Moreover, in order to compare individuals with different body sizes as a result of age differences or pathology, muscle morphology is often normalized to body size. Yet, the usefulness and practicality of different normalization techniques are still unknown, and clear recommendations for normalization are lacking. In this cross-sectional cohort study, muscle morphology of four lower limb muscles (medial gastrocnemius, tibialis anterior, the distal compartment of the semitendinosus, rectus femoris) was assessed by 3D-freehand ultrasound in 118 typically developing children (mean age 10.35 ± 4.49 years) between 3 and 18 years of age. The development of muscle morphology was studied over the full age range, as well as separately for the pre-pubertal (3-10 years) and pubertal (11-18 years) cohorts. The assumptions of a simple linear regression were checked. If these assumptions were fulfilled, the cross-sectional growth curves were described by a simple linear regression equation. Additional ANCOVA analyses were performed to evaluate muscle- or gender-specific differences in muscle development. Furthermore, different scaling methods, to normalize muscle morphology parameters, were explored. The most appropriate scaling method was selected based on the smallest slope of the morphology parameter with respect to age, with a non-significant correlation coefficient. Additionally, correlation coefficients were compared by a Steiger's Z-test to identify the most efficient scaling technique. The current results revealed that it is valid to describe muscle volume (with exception of the rectus femoris muscle) and muscle belly length alterations over age by a simple linear regression equation till the age of 11 years. Normalizing muscle morphology data by allometric scaling was found to be most useful for comparing muscle volumes of different pediatric populations. For muscle lengths, normalization can be achieved by either allometric and ratio scaling. This study provides a unique normative database of four lower limb muscles in typically developing children between the age of 3 and 18 years. These data can be used as a reference database for pediatric populations and may also serve as a reference frame to better understand both physiological and pathological muscle development.

Instrumented strength assessment in typically developing children and children with a neural or neuromuscular disorder: A reliability, validity and responsiveness study.

The aim of this study was to determine the clinimetric properties, i.e., reliability, validity and responsiveness of an instrumented strength assessment in typically developing (TD) children and children with cerebral palsy (CP) and Duchenne muscular dystrophy (DMD). Force (N), torque (Nm) and normalized torque (Nm/kg) were defined for maximal voluntary isometric contractions (MVICs) of the lower limb muscles using a pre-established protocol. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimal detectable change (MDC) of TD children (n = 14), children with CP (n = 11) and DMD (n = 11) were used to evaluate intra-rater reliability for the three cohorts and the inter-rater intersession as well as inter-rater intrasession reliability for TD children. Construct validity was assessed by comparing MVICs in TD children (n = 28) to children with CP (n = 26) and to children with DMD (n = 30), using the Kruskal Wallis and post-hoc Mann-Whitney U tests. Responsiveness was investigated by assessing changes in MVICs following a strength intervention in CP (n = 26) and a 1 and 2 year follow-up study in DMD (n = 13 and n = 6, respectively), using the Wilcoxon Signed-Rank test. The overall intra-rater reliability, was classified as good to excellent for 65.1%, moderate for 27.0% and poor for 7.9% of the measures (47.6%, 76.2%, and 66.7% good-excellent; 28.6%, 23.8%, and 33.7% moderate; 23.8%, 0%, and 0% poor in TD, CP, and DMD, respectively), while ICC values for TD children were slightly lower for inter-rater intrasession reliability (38.1% good-excellent, 33.3% moderate and 26.6% poor) and for inter-rater intersession reliability (47.6% good-excellent, 23.8% moderate and 28.6% poor). Children with CP and DMD were significantly weaker than TD children (p < 0.001) and the majority of these strength differences exceeded the MDC. Children with CP significantly improved strength after training, with changes that exceeded the SEMs, whereas only limited strength decreases over time were observed in the DMD cohort. In conclusion, the investigated instrumented strength assessment was sufficiently reliable to confirm known-group validity for both cohorts and could detect the responsiveness of children with CP after a strength intervention. However, more research is necessary to determine the responsiveness of this assessment in children with DMD regarding their natural decline.

Progressive resistance training for children with cerebral palsy: A randomized controlled trial evaluating the effects on muscle strength and morphology.

Children with spastic cerebral palsy often present with muscle weakness, resulting from neural impairments and muscular alterations. While progressive resistance training (PRT) improves muscle weakness, the effects on muscle morphology remain inconclusive. This investigation evaluated the effects of a PRT program on lower limb muscle strength, morphology and gross motor function. Forty-nine children with spastic cerebral palsy were randomized by minimization. The intervention group (nparticipants = 26, age: 8.3 ± 2.0 years, Gross Motor Function Classification System [GMFCS] level I/II/III: 17/5/4, nlegs = 41) received a 12-week PRT program, consisting of 3-4 sessions per week, with exercises performed in 3 sets of 10 repetitions, aiming at 60%-80% of the 1-repetition maximum. Training sessions were performed under supervision with the physiotherapist and at home. The control group (nparticipants = 22, age: 8.5 ± 2.1 year, GMFCS level I/II/III: 14/5/3, nlegs = 36) continued usual care including regular physiotherapy and use of orthotics. We assessed pre- and post-training knee extension, knee flexion and plantar flexion isometric strength, rectus femoris, semitendinosus and medial gastrocnemius muscle morphology, as well as functional strength, gross motor function and walking capacity. Data processing was performed blinded. Linear mixed models were applied to evaluate the difference in evolution over time between the control and intervention group (interaction-effect) and within each group (time-effect). The α-level was set at p = 0.01. Knee flexion strength and unilateral heel raises showed a significant interaction-effect (p ≤ 0.008), with improvements in the intervention group (p ≤ 0.001). Moreover, significant time-effects were seen for knee extension and plantar flexion isometric strength, rectus femoris and medial gastrocnemius MV, sit-to-stand and lateral step-up in the intervention group (p ≤ 0.004). Echo-intensity, muscle lengths and gross motor function showed limited to no changes. PRT improved strength and MV in the intervention group, whereby strength parameters significantly or close to significantly differed from the control group. Although, relative improvements in strength were larger than improvements in MV, important effects were seen on the maintenance of muscle size relative to skeletal growth. In conclusion, this study proved the effectiveness of a home-based, physiotherapy supervised, PRT program to improve isometric and functional muscle strength in children with SCP without negative effects on muscle properties or any serious adverse events. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03863197.

The Short-Term Impact of Botulinum Neurotoxin-A on Muscle Morphology and Gait in Children with Spastic Cerebral Palsy.

Children with spastic cerebral palsy (SCP) are often treated with intramuscular Botulinum Neurotoxin type-A (BoNT-A). Recent studies demonstrated BoNT-A-induced muscle atrophy and variable effects on gait pathology. This group-matched controlled study in children with SCP compared changes in muscle morphology 8-10 weeks post-BoNT-A treatment (n = 25, median age 6.4 years, GMFCS level I/II/III (14/9/2)) to morphological changes of an untreated control group (n = 20, median age 7.6 years, GMFCS level I/II/III (14/5/1)). Additionally, the effects on gait and spasticity were assessed in all treated children and a subgroup (n = 14), respectively. BoNT-A treatment was applied following an established integrated approach. Gastrocnemius and semitendinosus volume and echogenicity intensity were assessed by 3D-freehand ultrasound, spasticity was quantified through electromyography during passive muscle stretches at different velocities. Ankle and knee kinematics were evaluated by 3D-gait analysis. Medial gastrocnemius (p = 0.018, -5.2%) and semitendinosus muscle volume (p = 0.030, -16.2%) reduced post-BoNT-A, but not in the untreated control group, while echogenicity intensity did not change. Spasticity reduced and ankle gait kinematics significantly improved, combined with limited effects on knee kinematics. This study demonstrated that BoNT-A reduces spasticity and partly improves pathological gait but reduces muscle volume 8-10 weeks post-injections. Close post-BoNT-A follow-up and well-considered treatment selection is advised before BoNT-A application in SCP.

Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy.

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and -3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.

The Contribution of Decreased Muscle Size to Muscle Weakness in Children With Spastic Cerebral Palsy.

Muscle weakness is a common clinical symptom in children with spastic cerebral palsy (SCP). It is caused by impaired neural ability and altered intrinsic capacity of the muscles. To define the contribution of decreased muscle size to muscle weakness, two cohorts were recruited in this cross-sectional investigation: 53 children with SCP [median age, 8.2 (IQR, 4.1) years, 19/34 uni/bilateral] and 31 children with a typical development (TD) [median age, 9.7 (IQR, 2.9) years]. Muscle volume (MV) and muscle belly length for m. rectus femoris, semitendinosus, gastrocnemius medialis, and tibialis anterior were defined from three-dimensional freehand ultrasound acquisitions. A fixed dynamometer was used to assess maximal voluntary isometric contractions for knee extension, knee flexion, plantar flexion, and dorsiflexion from which maximal joint torque (MJT) was calculated. Selective motor control (SMC) was assessed on a 5-point scale for the children with SCP. First, the anthropometrics, strength, and muscle size parameters were compared between the cohorts. Significant differences for all muscle size and strength parameters were found (p ≤ 0.003), except for joint torque per MV for the plantar flexors. Secondly, the associations of anthropometrics, muscle size, gross motor function classification system (GMFCS) level, and SMC with MJT were investigated using univariate and stepwise multiple linear regressions. The associations of MJT with growth-related parameters like age, weight, and height appeared strongest in the TD cohort, whereas for the SCP cohort, these associations were accompanied by associations with SMC and GMFCS. The stepwise regression models resulted in ranges of explained variance in MJT from 29.3 to 66.3% in the TD cohort and from 16.8 to 60.1% in the SCP cohort. Finally, the MJT deficit observed in the SCP cohort was further investigated using the TD regression equations to estimate norm MJT based on height and potential MJT based on MV. From the total MJT deficit, 22.6-57.3% could be explained by deficits in MV. This investigation confirmed the disproportional decrease in muscle size and muscle strength around the knee and ankle joint in children with SCP, but also highlighted the large variability in the contribution of muscle size to muscle weakness.

Reliability of Processing 3-D Freehand Ultrasound Data to Define Muscle Volume and Echo-intensity in Pediatric Lower Limb Muscles with Typical Development or with Spasticity.

This investigation assessed the processer reliability of estimating muscle volume and echo-intensity of the rectus femoris, tibialis anterior and semitendinosus. The muscles of 10 typically developing children (8.15 [1.40] y) and 15 children with spastic cerebral palsy (7.67 [3.80] y; Gross Motor Function Classification System I = 5, II = 5, III = 5) were scanned with 3-D freehand ultrasonography. For the intra-processer analysis, the intra-class correlations coefficients (ICCs) for muscle volume ranged from 0.943-0.997, with relative standard errors of measurement (SEM%) ranging from 1.24%-8.97%. For the inter-processer analysis, these values were 0.853 to 0.988 and 3.47% to 14.02%, respectively. Echo-intensity had ICCs >0.947 and relative SEMs <4% for both analyses. Muscle volume and echo-intensity can be reliably extracted for the rectus femoris, semitendinosus and tibialis anterior in typically developing children and children with cerebral palsy. The need for a single processer to analyze all data is dependent on the size of the expected changes or differences.

Muscle Characteristics in Pediatric Hereditary Spastic Paraplegia vs. Bilateral Spastic Cerebral Palsy: An Exploratory Study.

Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9-17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP (p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass (p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups.

Joint and Muscle Assessments of the Separate Effects of Botulinum NeuroToxin-A and Lower-Leg Casting in Children With Cerebral Palsy.

Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 ± 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon levels were performed using Spearman correlation coefficients (p < 0.05). Increased joint resistance, measured during slow ankle rotations, was not significantly reduced after either treatment. Additional joint resistance assessed during fast rotations only reduced in the BoNT-A group (-37.6%, p = 0.013, effect size = 0.47), accompanied by a reduction in MG stretch reflexes (-70.7%, p = 0.003, effect size = 0.56). BoNT-A increased the muscle length measured at the resting ankle angle (6.9%, p = 0.013, effect size = 0.53). Joint angles shifted toward greater dorsiflexion after casting (32.4%, p = 0.004, effect size = 0.56), accompanied by increases in tendon length (5.7%, p = 0.039, effect size = 0.57; r = 0.40). No associations between the changes in muscle or tendon lengths and the changes in the stretch reflexes were found. We conclude that intramuscular BoNT-A injections reduced stretch reflexes in the MG accompanied by an increase in resting muscle belly length, whereas casting resulted in increased dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle.