Gait classification for growing children with Duchenne muscular dystrophy.

Classifying gait patterns into homogeneous groups could enhance communication among healthcare providers, clinical decision making and clinical trial designs in boys with Duchenne muscular dystrophy (DMD). Sutherland's classification has been developed 40 years ago. Ever since, the state-of-the-art medical care has improved and boys with DMD are now longer ambulatory. Therefore, the gait classification requires an update. The overall aim was to develop an up-to-date, valid DMD gait classification. A total of 137 three-dimensional gait analysis sessions were collected in 30 boys with DMD, aged 4.6-17 years. Three classes were distinguished, which only partly aligned with increasing severity of gait deviations. Apart from the mildly affected pattern, two more severely affected gait patterns were found, namely the tiptoeing pattern and the flexion pattern with distinct anterior pelvic tilt and posterior trunk leaning, which showed most severe deviations at the ankle or at the proximal segments/joints, respectively. The agreement between Sutherland's and the current classification was low, suggesting that gait pathology with the current state-of-the-art medical care has changed. However, overlap between classes, especially between the two more affected classes, highlights the complexity of the continuous gait changes. Therefore, caution is required when classifying individual boys with DMD into classes.

Longitudinal trajectory of medial gastrocnemius muscle growth in the first years of life.

AIM: To define the longitudinal trajectory of gastrocnemius muscle growth in 6- to 36-month-old children with and without spastic cerebral palsy (SCP) and to compare trajectories by levels of gross motor function (Gross Motor Function Classification System, GMFCS) and presumed brain-lesion timing. METHOD: Twenty typically developing children and 24 children with SCP (GMFCS levels I-II/III-IV = 15/9), were included (28/16 females/males; mean age at first scan 15.4 months [standard deviation 4.93, range 6.24-23.8]). Three-dimensional freehand ultrasound was used to repeatedly assess muscle volume, length, and cross-sectional area (CSA), resulting in 138 assessments (mean interval 7.9 months). Brain lesion timing was evaluated with magnetic resonance imaging classification. Linear mixed-effects models defined growth rates, adjusted for GMFCS levels and presumed brain-lesion timing. RESULTS: At age 12 months, children with SCP showed smaller morphological muscle size than typically developing children (5.8 mL vs 9.8 mL, p < 0.001), while subsequently no differences in muscle growth were found between children with and without SCP (muscle volume: 0.65 mL/month vs 0.74 mL/month). However, muscle volume and CSA growth rates were lower in children classified in GMFCS levels III and IV than typically developing children and those classified in GMFCS levels I and II, with differences ranging from -56% to -70% (p < 0.001). INTERPRETATION: Muscle growth is already hampered during infancy in SCP. Muscle size growth further reduces with decreasing functional levels, independently from the brain lesion. Early monitoring of muscle growth combined with early intervention is needed.

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.

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.

Longitudinal Alterations in Gait Features in Growing Children With Duchenne Muscular Dystrophy.

Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Three-dimensional gait analysis (3DGA) could provide sensitive parameters to study the efficacy of clinical trials aiming to preserve ambulation. However, quantitative descriptions of the natural history of gait features in DMD are first required. The overall goal was to provide a full delineation of the progressive gait pathology in children with DMD, covering the entire period of ambulation, by performing a so-called mixed cross-sectional longitudinal study. Firstly, to make our results comparable with previous literature, we aimed to cross-sectionally compare 31 predefined gait features between children with DMD and a typically developing (TD) database (1). Secondly, we aimed to explore the longitudinal changes in the 31 predefined gait features in growing boys with DMD using follow-up 3DGA sessions (2). 3DGA-sessions (n = 124) at self-selected speed were collected in 27 boys with DMD (baseline age: 4.6-15 years). They were repeatedly measured over a varying follow-up period (range: 6 months-5 years). The TD group consisted of 27 children (age: 5.4-15.6 years). Per measurement session, the spatiotemporal parameters, and the kinematic and kinetic waveforms were averaged over the selected gait cycles. From the averaged waveforms, discrete gait features (e.g., maxima and minima) were extracted. Mann-Whitney U tests were performed to cross-sectionally analyze the differences between DMD at baseline and TD (1). Linear mixed effect models were performed to assess the changes in gait features in the same group of children with DMD from both a longitudinal (i.e., increasing time) as well as a cross-sectional perspective (i.e., increasing baseline age) (2). At baseline, the boys with DMD differed from the TD children in 17 gait features. Additionally, 21 gait features evolved longitudinally when following-up the same boys with DMD and 25 gait features presented a significant cross-sectional baseline age-effect. The current study quantitatively described the longitudinal alterations in gait features in boys with DMD, thereby providing detailed insight into how DMD gait deteriorates. Additionally, our results highlight that gait features extracted from 3DGA are promising outcome measures for future clinical trials to quantify the efficacy of novel therapeutic strategies.

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.

The effect of hip muscle weakness and femoral bony deformities on gait performance.

BACKGROUND: Children with cerebral palsy (CP) present with a pathological gait pattern due to musculoskeletal impairments, such as muscle weakness and altered bony geometry. However, the effect of these impairments on gait performance is still unknown. Research aim:This study aimed to explore the effect of hip muscle weakness and femoral deformities on the gait performance of CP and typical developing (TD) subjects. METHODS: 6400 musculoskeletal models were created by weakening the hip extensors, abductors, adductors and flexors from 0% to 75 % and increasing the femoral anteversion angle (FAA) and neck shaft angle (NSA) from 20° to 60° and 120° to 160°, respectively. One TD and five CP gait patterns were imposed to each model and muscle forces were calculated. The effect of weakness and bony deformities on the capability gap (CG) at the hip, i.e. the lack in hip moment generating capacity to perform the gait pattern, was investigated using regression analysis. RESULTS: The CG of apparent equinus, stiff knee gait, TD gait, jump gait and true equinus increased with 0.080, 0.038, 0.015, 0.023 and 0.005 Nm/kg per 10 percent hip abductor weakness increase, with 0.211, 0.130, 0.056, 0.045 and 0.011 Nm/kg per 10 degrees FAA increase and with 0.163, 0.080, 0.036, 0.043 and 0.011 Nm/kg per 10 degrees NSA increase, respectively. Combined weakness and bony deformities explained 96 %, 85 %, 82 %, 65 %, 40 % and 35 % of the variance in the CG of apparent equinus, TD gait, stiff knee gait, jump gait, true equinus and crouch gait, respectively. SIGNIFICANCE: The results suggest that surgical correction of femoral deformities is more likely to be effective than strength training of hip muscles in enhancing CP gait performance. Jump gait, true equinus and especially crouch were more robust, while apparent equinus and stiff knee gait were limited by hip weakness and femoral deformities.

Muscle weakness has a limited effect on motor control of gait in Duchenne muscular dystrophy.

AIM: Our aim was to determine if synergy weights and activations are altered in Duchenne muscular dystrophy (DMD) and if these alterations could be linked to muscle weakness. METHODS: In 22 children with DMD and 22 typical developing (TD) children of a similar age, surface electromyography (sEMG) of the gluteus medius, rectus femoris (REF), medial hamstrings, tibialis anterior, and medial gastrocnemius (GAS) were recorded during gait. Muscle weakness was assessed with maximal voluntary isometric contractions (MVIC). Synergies were calculated with non-negative matrix factorization. The number of synergies explaining ≥90% of the variance in the sEMG signals (N90), were extracted and grouped with k-means cluster analysis. We verified differences in weights with a Mann-Whitney U test. Statistical non-parametric mapping (Hotelling's T2 test and two-tailed t-test) was used to assess group differences in synergy activations. We used Spearman's rank correlation coefficients and canonical correlation analysis to assess if weakness was related to modifications in weights and activations, respectively. RESULTS: For both groups, average N90 was three. In synergy one, characterized by activity at the beginning of stance, the DMDs showed an increased REF weight (p = 0.001) and decreased GAS weight (p = 0.007). Synergy activations were similar, with only a small difference detected in mid-swing in the combined activations (p<0.001). Weakness was not associated with these differences. CONCLUSION: Despite the apparent weakness in DMD, synergy weights and activations were similar between the two groups. Our findings are in line with previous research suggesting non-neural alterations have limited influence on muscle synergies.

Systematic review on gait classifications in children with cerebral palsy: An update.

BACKGROUND: Gait classification systems (GCSs) aim to aid clinicians and researchers in categorizing the gait of pathological populations, with the intent to improve the communication between them, to support treatment planning and enable the evaluation of patients over time. Throughout the years, various GCSs have been defined for children with cerebral palsy (CP), which were first summarized in a systematic review published in 2007. RESEARCH QUESTION: The current systematic review aimed to: a) identify GCSs that have been more recently developed, b) appraise their methodological quality and c) specify the most commonly used multiple joint gait patterns for children with CP reported in literature. METHODS: Four databases (Medline, EMBASE, CINAHL, Web of Science) were searched until July 2017. Several forms of validity and the reliability of these studies were assessed according to the principles of the consensus-based standards for the selection of health measurement instruments checklist or criteria defined in the original review. All published GCSs were also scrutinized in order to identify multiple joint patterns that have reached a predefined level of consensus. RESULTS: Thirty-six studies were considered in this review, 15 of them being GCSs that were not included in the original review. The validity, reliability and clinical applicability of all GCSs was reported, including 3 studies from the original review. Six multiple joint patterns for children with CP reached a consensus in literature. CONCLUSION: Since the previous review, obvious progress has been made in the field of GCSs for CP, resulting in improved methodological quality of the majority of published GCSs. This encouraged the applicability of GCSs in clinical or research settings. The six reliable, valid and commonly used multiple joint patterns, emerging from this systematic review, may aid clinical and research applications and create a common language among healthcare providers.