Histological analysis of the medial gastrocnemius muscle in young healthy children.

Introduction: Histological data on muscle fiber size and proportion in (very) young typically developing (TD) children is not well documented and data on capillarization and satellite cell content are also lacking. Aims: This study investigated the microscopic properties of the medial gastrocnemius muscle in growing TD children, grouped according to age and gender to provide normal reference values in healthy children. Methods: Microbiopsies of the medial gastrocnemius (MG) muscle were collected in 46 TD boys and girls aged 2-10 years subdivided into 4 age groups (2-4, 4-6, 6-8 and 8-10 years). Sections were immunostained to assess fiber type cross-sectional area (fCSA) and proportion, the number of satellite cells (SC), capillary to fiber ratio (C/F), capillary density for type I and II fiber (CFD), capillary domain, capillary-to-fiber perimeter exchange index (CFPE) and heterogeneity index. fCSA was normalized to fibula length2 and the coefficient of variation (CV) was calculated to reflect fCSA intrasubject variability. Results: Absolute fCSA of all fibers increased with age (r = 0.72, p < 0.001) but more in boys (+112%, p < 0.05) than in girls (+48%, p > 0.05) Normalized fCSA, CV and fiber proportion did not differ between age groups and gender. C/F was strongly correlated with age in boys (r = 0.83, p < 0.001), and to a lesser extent in girls (r = 0.37, p = 0.115), while other capillary parameters as well as the number of SC remained stable with increasing age in boys and girls. Discussion: This study provides reference values of histological measures in MG according to age in normally growing boys and girls. These data may be used as a reference to determine disease impact and efficacy of therapeutic approach on the muscle.

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.

Bone marrow oedema syndrome of the foot and ankle in a paediatric population: a retrospective case series with serial MRI evaluation.

PURPOSE: By means of a case series we wanted to describe and correlate the clinical and imaging features of bone marrow oedema syndrome (BMOS) of the foot and ankle in children. METHODS: A retrospective data study was performed on patients born on or after 01 January 2001 who underwent multiple MRI scans of the foot and ankle for pain symptoms. Six patients who presented with increased signal intensity on T2-weighted MR imaging without any underlying causes or concomitant pathology were included. RESULTS: All patients, three boys and three girls with a mean age of 11 years (8 to 14), displayed patchy areas of increased signal intensity on T2-weighted and turbo inversion recovery magnitude (TIRM) images. On average, six tarsal bones were involved (4 to 8). In all patients, treatment consisted of rest and/or protected weight-bearing. The mean time for symptoms to improve during treatment was 6 months (1 to 16). The mean duration of treatment was nine months (3 to 16). In all patients clinical and imaging symptoms were strongly correlated and regressed in time. CONCLUSION: BMOS as a pathological entity should be considered in paediatric patients with foot and ankle pain without a clear underlying cause, and characteristic T2-weighted and TIRM signal intensity increase on MRI images. As BMOS is transient and self-limiting, conservative treatment is advised while the oedema regresses. An early diagnosis of this pathology could prevent unnecessary diagnostic investigations and invasive treatments. LEVEL OF EVIDENCE: IV.

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking. Therefore, it remains difficult to understand the early onset and trajectory of altered muscle properties in growing CP children. Because muscle stem cells are responsible for postnatal growth, repair and remodeling, multiple adult stem cell populations from young CP children could play a role in altered muscle development. To this end, new methods for studying muscle samples of young children, valid to delineate the features and to elucidate the regenerative potential of muscle tissue, are necessary. Using minimal invasive muscle microbiopsy, which was applied in young subjects under general anaesthesia for the first time, we aimed to isolate and characterize muscle stem cell-derived progenitors of TD children and patients with CP. Data of 15 CP patients, 3-9 years old, and 5 aged-matched TD children were reported. The muscle microbiopsy technique was tolerated well in all participants. Through the explant technique, we provided muscle stem cell-derived progenitors from the Medial Gastrocnemius. Via fluorescent activated cell sorting, using surface markers CD56, ALP, and PDGFRa, we obtained SC-derived progenitors, mesoangioblasts and fibro-adipogenic progenitors, respectively. Adipogenic, skeletal, and smooth muscle differentiation assays confirmed the cell identity and ability to give rise to different cell types after appropriate stimuli. Myogenic differentiation in CP SC-derived progenitors showed enhanced fusion index and altered myotube formation based on MYOSIN HEAVY CHAIN expression, as well as disorganization of nuclear spreading, which were not observed in TD myotubes. In conclusion, the microbiopsy technique allows more focused muscle research in young CP patients. Current results show altered differentiation abilities of muscle stem cell-derived progenitors and support the hypothesis of their involvement in CP-altered muscle growth.

Role of femoral derotation on gait after selective dorsal rhizotomy in children with spastic cerebral palsy.

AIM: To evaluate the long-term outcome of selective dorsal rhizotomy (SDR) on gait and the influence of previous femoral derotation osteotomy (FDO). METHOD: In a retrospective cohort study of 29 children (16 females, 13 males) with spastic diplegic cerebral palsy, 14 children received FDO before SDR, whereas 15 children with moderate or near-normal internal femoral rotation during gait received only SDR. Three-dimensional gait data were obtained pre-FDO, pre-SDR, 1 year post-SDR, and 3 to 5 years post-SDR, to study the Gait Profile Score (GPS), pelvic tilt, and knee and hip kinematics. A mixed analysis of variance with the repeated measure 'time' was performed between different time points for each group. RESULTS: Children who first underwent FDO and then SDR started with a more complex gait pathology but showed fewer gait deviations 3 to 5 years post-SDR, compared to children who only underwent SDR. This was reflected by a lower GPS and pelvic tilt, as well as less knee flexion in stance. INTERPRETATION: The effect of SDR on gait is only significant in the mid- to long-term if the bony lever arms are also corrected. Thus, the clinical outcome after SDR is dependent on good proximal alignment. WHAT THIS PAPER ADDS: Pelvic tilt remains stable after femoral derotation osteotomy (FDO)+selective dorsal rhizotomy (SDR). But pelvic tilt deteriorates after SDR only. Hip and knee extension is better after FDO+SDR than after SDR only. Spasticity reduction (by SDR) combined with bony lever arm correction (by FDO) improves gait.

PAPEL DE LA DESROTACION FEMORAL EN LA MARCHA DESPUES DE UNA RIZOTOMIA SELECTIVE POSTERIOR EN NIÑOS CON PARÁLISIS CEREBRAL: OBJETIVO: Evaluar el resultado a largo plazo de la rizotomía selective posterior (RSP) sobre la marcha y la influencia de la osteotomía femoral desrotadora (OFD) previa. METODO: Estudio de cohorte retrospectivo de 29 niños (13 mujeres, 16 varones) con parálisis cerebral subtipo diplejia espástica, 14 niños recibieron OFD antes de la RSP, mientras que 15 niños con rotación femoral interna moderada o casi normal durante la marcha recibieron solo RSP. Se obtuvieron datos tridimensionales de la marcha pre-OFD, pre-RSP, 1 año post-RSP y 3 a 5 años post-RSP, para estudiar la puntuación del perfil de la marcha (Gait Profile Score. GPS, sigla en inglés), inclinación pélvica y cinemática de rodilla y cadera. Se realizó un análisis mixto de varianza con la medida repetida "tiempo" entre diferentes puntos de tiempo para cada grupo. RESULTADOS: Los niños que primero se sometieron a OFD y luego RSP comenzaron con una patología de la marcha más compleja, pero mostraron menos desviaciones de la marcha de 3 a 5 años después de la RSP, en comparación con los niños que solo se sometieron a RSP. Esto se reflejó por una menor GPS e inclinación pélvica, así como una menor flexión de la rodilla durante el apoyo. INTERPRETACIÓN: El efecto de la RSP en la marcha solo es significativo a medio o largo plazo si los brazos de palanca óseos también se corrigen. Por lo tanto, el resultado clínico después de la RSP depende de una buena alineación proximal.

PAPEL DA DERROTAÇÃO FEMORAL NA MARCHA APÓS RIZOTOMIA DORSAL SELETIVA EM CRIANÇAS COM PARALISIA CEREBRAL ESPÁSTICA: OBJETIVO: Avaliar o resultado em longo prazo da rizotomia dorsal seletiva (RDS) na marcha e a influência da osteotomia derrotativa femoral (ODF). MÉTODO: Em um estudo de coorte retrospectivo com 29 crianças (13 do sexo feminino, 16 do sexo masculino) com paralisia cerebral diplégica espástica, 14 crianças receberam ODF antes da RDS, enquanto 15 crianças com rotação femoral interna moderada ou quase normal durante a marcha receberam apenas RDS. Dados tridimensionais de marcha foram obtidos pré ODF, pré RDS, 1 ano pós RDS, e 3 a 5 anos após RDS, para estudar o Escore do Perfil da Marcha (EPM), inclinação pélvica, e cinemática de joelho e quadril. Uma análise mista de variância com a medida repetida 'tempo' foi realizada entre os diferentes pontos para cada grupo. RESULTADOS: Crianças que primeiro passaram por ODF e depois pela RDS começaram com patologia de marcha mais complexa, mas tiveram menos desvios na marcha 3 a 5 anos após RDS, comparadas com crianças que receberam apenas RDS. Isso foi refletido por menor escore EMG e inclinação pélvica, assim como menos flexão do joelho na fase de apoio. INTERPRETAÇÃO: O efeito da RDS na marcha apenas é significativo no médio a longo prazo se os braços de alavanca ósseos também são corrigidos. Assim, o resultado clínico após RDS depende de bom alinhamento proximal.