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.

Short-Term Effects of Botulinum Toxin-A Injection on the Medial Gastrocnemius Histological Features in Ambulant Children with Cerebral Palsy: A Longitudinal Pilot Study.

Botulinum toxin-A (BoNT-A) injection is known to exert beneficial effects on muscle tone, joint mobility and gait in children with cerebral palsy (CP). However, recent animal and human studies have raised the concern that BoNT-A might be harmful to muscle integrity. In CP-children, the impact of BoNT-A on muscle structure has been poorly studied, and inconsistent results have been reported. This study was aimed at determining the time course effect of a single BoNT-A administration on medial gastrocnemius (MG) morphology in CP-children. MG microbiopsies from 12 ambulant and BoNT-A-naïve CP-children (age, 3.4 (2.3) years, ranging from 2.5 to 7.8 years; seven boys and five girls; GMFCS I = 5, II = 4 and III = 3) were collected before and 3 and 6 months after BoNT-A treatment to analyze the fiber cross-sectional area (fCSA) and proportion; capillarization; and satellite cell (SC) content. Compared with the baseline, the fCSA decreased at 3 months (-14%, NS) and increased at 6 months (+13%, NS). Fiber size variability was significantly higher at 3 months (type I: +56%, p = 0.032; type IIa: +37%, p = 0.032) and 6 months (type I: +69%, p = 0.04; type IIa: +121%, p = 0.032) compared with the baseline. The higher type I proportion seen at 3 months was still present and more pronounced at 6 months (type I: +17%, p = 0.04; type IIx: -65%, p = 0.032). The capillary fiber density was reduced at 3 months (type I: -43%, NS; type II: -44%, p = 0.0320) but normalized at 6 months. There was a non-significant increase in SC/100 fibers at 3 months (+75%, NS) and 6 months (+40%, NS) compared with the baseline. These preliminary data suggest that BoNT-A induced alterations in the MG of children with CP, which were still present 6 months after BoNT-A injection but with signs of muscle recovery.

Histological analysis of the gastrocnemius muscle in preschool and school age children with cerebral palsy compared with age-matched typically developing children.

Inconsistent alterations in skeletal muscle histology have been reported in adolescents with cerebral palsy (CP) and whether alterations are present in young children and differ from older children is not yet known. This study aimed to define histological alterations in the medial gastrocnemius (MG) of ambulant CP (gross-motor classification system, GMFCS I-III) stratified in two age groups (preschool children, PS: 2-5 and school age children, SA: 6-9-yr old) compared with age-matched typically developing (TD) children. We hypothesized that alterations in muscle microscopic properties are already present in PS-CP and are GMFCS level specific. Ultrasound guided percutaneous microbiopsies were collected in 46 CP (24-PS) and 45 TD (13-PS) children. Sections were stained to determine fiber cross-sectional area (fCSA) and proportion, capillary, and satellite cell amount. Average absolute and normalized fCSA were similar in CP and TD, but a greater percentage of smaller fibers was found in CP. Coefficient of variation (CV) was significantly larger in PS-CP-GMFCS I-II and for type I fiber. In SA-CP, all fiber types contributed to the higher CV. Type IIx proportion was higher and type I was lower in PS-CP-GMFCS-III and for all SA-CP. Reduced capillary-to-fiber ratio was present in PS-CP-GMFCS II-III and in all SA-CP. Capillary fiber density was lower in SA-CP. Capillary domain was enhanced in all CP, but capillary spatial distribution was maintained as was satellite cell content. We concluded that MG histological alterations are already present in very young CP but are only partly specific for GMFCS level and age.NEW & NOTEWORTHY Inconsistent histological alterations have been reported in children with cerebral palsy (CP) but whether they are present in very young and ambulant CP children and differ from those reported in old CP children is not known. This study highlighted for the first time that enhanced muscle fiber size variability and loss of capillaries are already present in very young CP children, even in the most ambulant ones, and these alterations seem to extend with age.

Digital mucous cysts of the finger without osteoarthritis: optimizing outcome of long needle trajectory aspiration and injection.

Digital mucous cysts are common, benign and highly recurrent tumors of the distal interphalangeal joints of the fingers and often associated with osteoarthritis. Multiple treatment modalities have been described, but still no consensus is stated. In the absence of degenerative changes, we promote a novel non-surgical approach. The aim of this study was to examine all patients with digital mucous cysts without underlying osteoarthritis, undergoing this injection technique and to assess outcome and complications of this procedure. This was a single center study (2018-2019) of 17 patients who received a long needle trajectory aspiration and injection for treatment of digital mucous cysts. Exclusion criteria were prior surgical treatment, post-traumatic cyst formation and the presence of radiographic distal interphalangeal joint osteophytosis. A total of 15 patients were found eligible for inclusion. The patient reports were retrospectively analyzed with a follow-up of 6 months. The primary study outcome was resolution of the cyst; secondary outcomes were complications of the procedure. Twelve (80%) resolved completely and three (20%) had limited local recurrence at 6 months. No complications were reported. None of the patients with limited recurrence desired further treatment. We believe that this technique offers a non-invasive, low-cost treatment option for digital mucous cysts, particularly in the subset of patients with ample evidence of degenerative articular changes in the distal interphalangeal joint. The described technique can be performed in an office-based setting and avoids typical surgical as well as aspiration-associated complications.

Upper-extremity spasticity and functionality after selective dorsal rhizotomy for cerebral palsy: a systematic review.

OBJECTIVE: Lumbosacral selective dorsal rhizotomy is a neurosurgical treatment option to reduce spasticity in the lower extremities in children with cerebral palsy. Surprisingly, concomitant improvement of spasticity in the upper extremities and functionality of the hands has been sporadically reported postoperatively. In this systematic review, the authors aimed to quantify the postoperative improvement in upper-extremity spasticity and functionality, identify predictors, and discuss underlying mechanisms. METHODS: The authors searched the MEDLINE and Embase databases for studies reporting upper-extremity outcomes in cerebral palsy patients after selective dorsal rhizotomy that reported one or more of the following clinical scales: the Ashworth Scale (AS), the Modified AS (MAS), the fine motor skills domain of the Peabody Developmental Motor Scales (PDMS), the Quality of Upper Extremity Skills Test (QUEST), the self-care domain of the Functional Independence Measure for Children (WeeFIM), or the self-care domain of the Pediatric Evaluation of Disability Inventory (PEDI). The authors arbitrarily divided postoperative follow-up into short-term (< 6 months), medium-term (6-24 months), and long-term (> 24 months) follow-up. A 1-point change in MAS score has been reported as clinically significant. To assess bias, the Cochrane Collaboration's tool and ROBINS-I tool were used. RESULTS: The authors included 24 articles describing 752 patients. Spasticity reduction of the upper extremities ranged from 0.30 to 0.55 (AS) and between 0 and 2.9 (MAS) at medium-term follow-up. This large variability may partially be attributed to a floor effect since patients with normal upper-extremity function would not be expected to have further improvement. QUEST improvement ranged from 2.7% to 4.5% at medium-term follow-up. The mean improvements in functional skills of the self-care domain of the PEDI were 4.3 at short-term and 7 at medium-term follow-ups and ranged from 10.8 to 34.7 at long-term follow-up. There are insufficient data to draw meaningful conclusions regarding the PDMS fine motor skills and the WeeFIM self-care domains. CONCLUSIONS: The literature suggests that a pronounced postoperative spasticity reduction in the lower extremities and a moderately severe preoperative upper-extremity spasticity may positively predict postoperative reduction in upper-extremity spasticity. There are at least 5 hypotheses that may explain the postoperative reduction in upper-extremity spasticity and functionality: 1) a somatosensory cortex reorganization favoring the hand region over the leg region, 2) a decrease in abnormal electrical transmission throughout the spinal cord, 3) an indirect result of improved posture due to improved truncal and leg stability, 4) an indirect consequence of occupational/physical therapy intensification, and 5) a maturation effect. However, all remain unproven to date.

Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions.

Botulinum neurotoxin type-A (BoNT) injections are commonly used as spasticity treatment in cerebral palsy (CP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised, and the BoNT effect on muscle stem cells remains not well defined. This study aims at clarifying the impact of BoNT on growing muscles (1) by analyzing the in vitro effect of BoNT on satellite cell (SC)-derived myoblasts and fibroblasts obtained from medial gastrocnemius microbiopsies collected in young BoNT-naïve children (t0) compared to age ranged typically developing children; (2) by following the effect of in vivo BoNT administration on these cells obtained from the same children with CP at 3 (t1) and 6 (t2) months post BoNT; (3) by determining the direct effect of a single and repeated in vitro BoNT treatment on neuromuscular junctions (NMJs) differentiated from hiPSCs. In vitro BoNT did not affect myogenic differentiation or collagen production. The fusion index significantly decreased in CP at t2 compared to t0. In NMJ cocultures, BoNT treatment caused axonal swelling and fragmentation. Repeated treatments impaired the autophagic-lysosomal system. Further studies are warranted to understand the long-term and collateral effects of BoNT in the muscles of children with CP.

Functional recovery in the surgical treatment of tennis elbow: side-to-side vs. tendon-to-bone attachment using a knotless suture anchor: a randomized controlled trial.

BACKGROUND: Lateral epicondylitis of the elbow sometimes does not respond to conservative treatment and requires surgical intervention. Many different surgical techniques have been described. The aim of this randomized study was to compare functional outcomes of open side-to-side suturing of the tendon and tendon-to-bone fixation with a knotless suture anchor. METHODS: In total, 68 patients were included (4 were lost to follow-up) and were randomized into either the side-to-side tendon group or the suture anchor group. Demographic data consisted of age, sex, body mass index, affected arm, dominant arm, previous treatments, and symptom duration. Professional and sports activities were noted. Preoperative values of the Mayo Elbow Performance Index (MEPI) score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, and Numeric Pain Rating Scale (NRS) score were noted. Clinical features consisted of range of motion in flexion and extension, grip strength, and wrist flexion and extension strength. All measurements were noted at 6 weeks, 3 months, and 1 year postoperatively. RESULTS: The MEPI and NRS scores did not differ between the 2 groups, but there was a significant improvement in the MEPI score at 6 weeks vs. preoperatively in both the suture group (from 70.6 to 87.4) and the anchor group (from 68 to 86.5). The NRS scores showed no difference at each time point in both groups. The QuickDASH and QuickDASH-Sport scores showed a faster improvement between 6 weeks and 3 months in the anchor group compared with the suture group. Grip and extension strength also showed a slightly faster improvement at 6 weeks postoperatively in the anchor group. No significant difference in the number of weeks required to return to work was found between the groups (10.4 weeks in both groups). CONCLUSION: Our results of side-to-side tendon repair compared with bone-tendon interface restoration by a suture anchor showed no significant differences in functional outcomes. Patients who received a suture anchor did have faster rehabilitation at 6 weeks postoperatively in terms of both functional outcome scores and grip and wrist extension strength measures.

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.