The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

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.

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.

Medial gastrocnemius volume and echo-intensity after botulinum neurotoxin A interventions in children with spastic cerebral palsy.

AIM: This cross-sectional investigation evaluated whether recurrent botulinum neurotoxin A (BoNT-A) interventions to the medial gastrocnemius have an influence on muscle morphology, beyond Gross Motor Function Classification System (GMFCS) level. METHOD: A cohort of typically developing children (n=67; 43 males, 24 females; median age 9y 11mo [range 7y 10mo-11y 6mo]), a cohort of children with spastic cerebral palsy (CP) naive to BoNT-A interventions (No-BoNT-A; n=19; 10 males, nine females; median age 9y 3mo [range 8y 5mo-10y 10mo]) and a cohort of children with spastic CP with a minimum of three recurrent BoNT-A interventions to the medial gastrocnemius (BoNT-A; n=19; 13 males, six females; median age 9y 8mo [range 7y 3mo-10y 7mo]) were recruited. Three-dimensional freehand ultrasound was used to estimate medial gastrocnemius volume normalized to body mass and echo-intensity. RESULTS: Normalized medial gastrocnemius volume and echo-intensity significantly differed between the two spastic CP cohorts (p≤0.05), with the BoNT-A cohort having larger alterations. Associations between normalized medial gastrocnemius volume and echo-intensity were highest in the No-BoNT-A cohort, followed by the BoNT-A cohort. Multiple regression analyses revealed that both GMFCS level and BoNT-A intervention history were significantly associated with smaller normalized medial gastrocnemius volume and higher echo-intensity. INTERPRETATION: Recurrent BoNT-A interventions may induce alterations to medial gastrocnemius volume and echo-intensity beyond the natural history of the spastic CP pathology. WHAT THIS PAPER ADDS: In spastic cerebral palsy, medial gastrocnemius volumes are smaller and echo-intensities higher compared with typical development. Alterations after botulinum neurotoxin A intervention (BoNT-A) are larger than in no BoNT-A intervention. Gross Motor Function Classification System level and BoNT-A history significantly associate with medial gastrocnemius and echo-intensity alterations.

VOLUMEN DEL MÚSCULO GASTROCNEMIUS MEDIAL E INTENSIDAD DE LA ECOGRAFÍA DESPUÉS DE LA COLOCACIÓN DE NEUROTOXINA BOTULÍNICA (TIPO A), EN NIÑOS CON PARÁLISIS CEREBRAL ESPÁSTICA (PC): OBJETIVO: Esta investigación de corte transversal evaluó si la colocación recurrente de neurotoxina botulínica tipo A (BoNT-A) en el músculo gastrocnemius medial tienen una influencia en la morfología muscular, más allá del nivel del Sistema de Clasificación de la Función Motora Gruesa (GMFCS, siglas en ingles). MÉTODO: Una cohorte de niños con desarrollo tipico (n = 67; 43 varones, 24 mujeres; mediana de edad 9 años 11 meses [rango 7 años 10 meses -11 años 6 meses]), otra cohorte de niños con parálisis cerebral espástica (PC) que no habían recibido intervenciones de BoNT-A ( n = 19; 10 hombres, nueve mujeres; mediana de edad 9 años 3 meses [rango 8 años 5 meses -10 años 10 meses]) y una cohorte de niños con PC espástica con un mínimo de tres administraciones recurrentes de BoNT-A en el músculo gastrocnemius medial (BoNT-A; n = 19; 13 varones, seis mujeres; mediana de edad 9 años 8 meses [rango 7 años 3 meses - 10 años 7 meses]) fueron reclutados. Se usó ultrasonido tridimensional a mano alzada para estimar el volumen del músculo gastrocnemius medial normalizado a la masa corporal y la intensidad del eco. RESULTADOS: El volumen del músculo gastrocnemius medial normalizado y la intensidad del eco difirieron significativamente entre las dos cohortes de PC espástica (p≤0,05), la cohorte BoNT-A tuvo alteraciones mayores. Las asociaciones entre el volumen músculo gastrocnemius medial normalizado y la intensidad del eco fueron más altas en la cohorte No-BoNT-A, seguidas de la cohorte BoNT-A. Los análisis de regresión múltiple revelaron que tanto el nivel de GMFCS como el antecedente de intervención de BoNT-A se asociaron significativamente con un volumen del músculo gastrocnemius medial normalizado más pequeño y una mayor intensidad de eco. INTERPRETACIÓN: La colocación recurrentes de BoNT-A pueden inducir alteraciones en el volumen del músculo gastrocnemius medial y en la intensidad del eco más allá de la historia natural de la patología por PC espástica.

VOLUME E ECO-INTENSIDADE DO MÚSCULO GASTROCNÊMIO MEDIAL APÓS INTERVENÇÕES COM NEUROTOXINA BOTULÍNICA A EM CRIANÇAS COM PARALISIA CEREBRAL ESPÁSTICA: OBJETIVO: Esta investigação transversal avaliou se intervenções recorrentes com neurotoxina botulínica A (NTBo-A) no músculo gastrocnêmio medial têm influência na morfologia muscular, além do nível segundo o Sistema de Classificação da Função Motora Grossa (GMFCS). MÉTODO: Uma coorte de crianças com desenvolvimento típico (n=67; 43 do sexo masculino, 24 do sexo feminino; idade mediana 9a 11m [variação 7a 10m-11a 6m]), uma coorte de crianças com paralisia cerebral espástica (PC) que nunca recebeu intervenções com NTBo-A (No-NTBo-A; n=19; 10 do sexo masculino, nove do sexo feminino; idade mediana 9a 3m [variação 8a 5m-10a 10m]) e uma coorte de crianças com PC espástica com no mínimo três intervenções de NTBo-A no músculo gastrocnêmio medial (NTBo-A; n=19; 13 do sexo mascuino, seis do sexo feminino; idade mediana 9a 8m [variação 7a 3m-10a 7m]) foram recrutadas. Ultrassom tridimensional foi usado para estimar o volume do gastrocnêmio normalizado para a massa corporal e eco-intensidade. RESULTADOS: O volume normalizado e eco-intensidade do músculo gastrocnêmio medial diferiu significantemente entre as duas coortes de PC espástica (p≤0,05), com a coorte NTBo-A tendo maiores alteracões. Associações entre o volume normalizado do gastrocnêmio e eco-intensidade foram maiores na coorte No-NTBo-A, seguida pela coorte NTBo-A. Análises de regressão múltipla revelaram que tanto o nível GMFCS quanto a história de intervenção com NTBo-A foram significativamente associadas com menor volume normalizado do músculo gastrocnêmio medial e maior eco-intensidade. INTERPRETAÇÃO: Intervenções recorrentes com NTBo-A podem induzir alterações no volume e eco-intensidade do músculo gastrocnêmio medial, além da história natural da patologia da PC espástica.

Estimating medial gastrocnemius muscle volume in children with spastic cerebral palsy: a cross-sectional investigation.

AIM: This cross-sectional investigation evaluates the reliability of estimating medial gastrocnemius anatomical cross-sectional area (aCSA) in typically developing and spastic cerebral palsy (SCP) cohorts. It verifies whether muscle volume estimations based on aCSA improve when aCSA is multiplied by muscle-tendon unit (MTU) or muscle length, and whether the resulting errors in volume estimations are smaller than changes after intervention. METHOD: Fifteen typically developing children (mean age 8y 2mo [SD 1y 5mo], six males, nine females) and 30 children with SCP (mean age 9y 2mo [SD 2y 5mo], 22 males, eight females, Gross Motor Function Classification System [GMFCS] level I=15, II=15) participated in the investigation. The SCP cohort was divided according to GMFCS level. A three-dimensional freehand ultrasound technique was used to estimate medial gastrocnemius aCSA, muscle volume, MTU, and muscle length. Estimated muscle volume (aCSA×MTU or muscle length) was compared with the measured muscle volume. RESULTS: Anatomical cross-sectional area, muscle volume, and muscle length significantly differed between the typically developing and two SCP cohorts (p≤0.050). aCSA multiplied by either MTU or muscle length improved estimations of medial gastrocnemius volume. Leave-one-out cross-validation revealed an absolute difference with measured muscle volume of 3.77 ml (SD 2.90). INTERPRETATION: This investigation revealed that medial gastrocnemius muscle volume can be reliably estimated in a clinically feasible manner in typically developing children and those with SCP. WHAT THIS PAPER ADDS: Medial gastrocnemius anatomical cross-sectional area (aCSA) can be reliably estimated in children with spastic cerebral palsy. The location of the anatomical cross-section should be taken with respect to muscle and not bone length. Medial gastrocnemius volume can be reliably estimated by multiplying aCSA and muscle length. The errors in volume estimations are smaller than reported differences after interventions.

Safety of dry needling in stroke patients: a scoping review.

INTRODUCTION: Spasticity is a common problem in stroke patients. Treatments of spasticity often have side effects or are insufficiently effective. Dry needling (DN) has been proposed as a potential additional option to consider in the multimodal treatment of post-stroke spasticity, although questions about its safety remain. The goal of this study is to assess the safety of DN in stroke patients. EVIDENCE ACQUISITION: A systematic search in Medline, Embase, The Cochrane Library, Web of Science, CIHNAL and PEDro was conducted in June 2023. Two reviewers independently screened abstracts according to the eligibility criteria. EVIDENCE SYNTHESIS: Twenty-five articles were included in this review. Only six studies reported adverse events, all of which were considered minor. None of the included studies reported any serious adverse events. In four of the included studies anticoagulants were regarded as contra-indicative for DN. Anticoagulants were not mentioned in the other included studies. CONCLUSIONS: There is a paucity of literature concerning the safety of DN in stroke patients. This review is the first to investigate the safety of DN in stroke patients and based on the results there is insufficient evidence regarding the safety of DN in stroke patients. CLINICAL REHABILITATION IMPACT: Although DN could be a promising treatment in post-stroke spasticity, further research is indicated to investigate its mechanism of action and its effect on outcome. However, before conducting large clinical trials to assess outcome parameters, the safety of DN in stroke patients must be further investigated.

Defining tibial anterior muscle morphology in first-ever chronic stroke patients using three-dimensional freehand ultrasound.

BACKGROUND: Drop foot is common post-stroke, elevating fall risks and mobility limitations. It is caused by weakness and lack of control of the tibialis anterior muscle (TA), for which various rehabilitation treatments are used. A reliable objective estimate of changes in TA muscle morphology and composition can enhance treatment optimization. OBJECTIVES: We aimed to ascertain 3D freehand ultrasound (3DfUS) reliability in measuring TA muscle volume, length, and echo intensity in stroke patients and healthy controls and its validity by comparing these features across legs, between patients and controls, and between clinical subgroups (i.e. patients with and without ankle contracture, spastic muscle overactivity, and foot dorsiflexor paresis). METHODS: We included 9 stroke patients and 9 healthy controls to define reliability and 26 stroke patients and 28 healthy controls to define validity. For reliability, data were collected and processed by 2 different operators and processors. For inter- and intra-rater reliability, intra-class correlation coefficient (ICC) and standard error of measurement (SEM) were used. For validity, Wilcoxon-Signed-Ranked and Mann-Whitney U tests were used for comparisons between groups and subgroups. RESULTS: All measurements showed good to excellent inter- and intra-rater reliability (ICC: 0.816 to 0.997, SEM: 0.5% to 7.8%). Comparison analyses revealed no differences in muscle features among legs, groups, or subgroups. CONCLUSION: While the 3DfUS is a reliable method to define TA morphology and composition, its clinical validity needs further investigation into factors influencing muscle property changes across various age groups and post-stroke time points. MESH TERMS: Stroke; Skeletal muscle morphology; muscle composition; 3D freehand ultrasonography, Anterior Tibial Muscle.

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.

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.

Reliability of Isokinetic Strength Assessments of Knee and Hip Using the Biodex System 4 Dynamometer and Associations With Functional Strength in Healthy Children.

Background: This study aimed to analyze the reliability of concentric isokinetic strength assessments (knee and hip) using the Biodex System 4 in healthy children and assess the association with functional strength tests (sit-to-stand [STS], lateral-step-up [LSU]). Methods: 19 children (6-12 years) were included. Knee and hip flexion and extension, and hip abduction and adduction were tested at 60 and 90°/s. Results: Relative and absolute reliability at 60°/s tended to show better results compared to those at 90°/s. Intra class correlations (ICCs) of knee flexion and extension at 60°/s were good (0.79-0.89). For hip flexion, extension, abduction and adduction at 60°/s ICCs were moderate to good (0.53-0.83). The smallest detectable change (SDC) values (expressed in %) were highly variable. The SDC% for knee flexion and extension and hip abduction at 60°/s were around 50%. Positive associations were found between hip extension and abduction isokinetic strength and the STS test. Conclusion: Concentric isokinetic strength assessments in healthy children using the Biodex System 4 were found reliable for knee flexion and extension and hip abduction. Limited associations were found between concentric isokinetic strength tests and functional strength tests.

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.

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.

Reliability of functional tests of the lower limbs and core stability in children and adolescents with cerebral palsy.

BACKGROUND: Muscle weakness in children and adolescents with cerebral palsy (CP) can affect daily life activities, even more if functional capabilities are poor. Also, core stability plays an important role in distal force generation. AIM: The main purpose of this study was to investigate the reliability of functional tests of the lower limbs and the core stability in children and adolescents with bilateral spastic CP with Gross Motor Function Classification System (GMFCS) levels II and III. Secondary, associations within the functional tests and between the functional tests and gait capacity were analyzed. DESIGN: Cross-sectional study. SETTING: CP reference center at Ghent University Hospital, pediatric physiotherapists and schools for children and adolescents with motor impairments. POPULATION: Twenty-four children and adolescents with CP (11.4±2.5 yrs, GMFCS II/III:13/11) participated in this study. METHODS: Functional tests of the lower limbs (GMFCS II: sit-to-stand [STS], lateral step-up [LSU], bilateral heel rise [BHR], high jump [HJ], long jump [LJ]; GMFCS III: STS, LSU) and core stability (bridging and rolling like a ball [RLB]) were tested twice. On the second test occasion, gait capacity (1-minute walk test [1MWT] and modified timed up and go [mTUG]) were also assessed. RESULTS: Relative reliability of the functional tests ranged from good to excellent (Intraclass Correlation Coefficients (ICC), 0.88 - 0.96). Absolute reliability showed large variability with acceptable results for the BHR, HJ, LJ and RLB (Minimal Detectable Change % (MDC%) <40%). Strong associations were found of the RLB test and the mTUG with the BHR, HJ and LJ tests. CONCLUSIONS: The functional tests of the lower limbs and core stability were found reliable. To measure change over time, the BHR, the HJ and LJ can be used for children and adolescents with GMFCS level II. The RLB test can be used for both GMFCS levels. Associations between the BHR, HJ and LJ tests showed strong associations with the RLB test and with the mTUG. CLINICAL REHABILITATION IMPACT: The study highlighted the importance of developing functional tests for children and adolescents with lower motor function capacities and to integrate core stability tests in routine clinical assessments.

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.

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.