Collagen architecture and biomechanics of gracilis and adductor longus muscles from children with cerebral palsy.

Cerebral palsy (CP) describes some upper motoneuron disorders due to non-progressive disturbances occurring in the developing brain that cause progressive changes to muscle. While longer sarcomeres increase muscle stiffness in patients with CP compared to typically developing (TD) patients, changes in extracellular matrix (ECM) architecture can increase stiffness. Our goal was to investigate how changes in muscle and ECM architecture impact muscle stiffness, gait and joint function in CP. Gracilis and adductor longus biopsies were collected from children with CP undergoing tendon lengthening surgery for hamstring and hip adduction contractures, respectively. Gracilis biopsies were collected from TD patients undergoing anterior cruciate ligament reconstruction surgery with hamstring autograft. Muscle mechanical testing, two-photon imaging and hydroxyproline assay were performed on biopsies. Corresponding data were compared to radiographic hip displacement in CP adductors (CPA), gait kinematics in CP hamstrings (CPH), and joint range of motion in CPA and CPH. We found at matched sarcomere lengths muscle stiffness and collagen architecture were similar between TD and CP hamstrings. However, CPH stiffness (R2 = 0.1973), collagen content (R2 = 0.5099) and cross-linking (R2 = 0.3233) were correlated to decreased knee range of motion. Additionally, we observed collagen fibres within the muscle ECM increase alignment during muscular stretching. These data demonstrate that while ECM architecture is similar between TD and CP hamstrings, collagen fibres biomechanics are sensitive to muscle strain and may be altered at longer in vivo sarcomere lengths in CP muscle. Future studies could evaluate the impact of ECM architecture on TD and CP muscle stiffness across in vivo operating ranges. KEY POINTS: At matched sarcomere lengths, gracilis muscle mechanics and collagen architecture are similar in TD patients and patients with CP. In both TD and CP muscles, collagen fibres dynamically increase their alignment during muscle stretching. Aspects of muscle mechanics and collagen architecture are predictive of in vivo knee joint motion and radiographic hip displacement in patients with CP. Longer sarcomere lengths in CP muscle in vivo may alter collagen architecture and biomechanics to drive deficits in joint mobility and gait function.

Muscle satellite cells and fibro-adipogenic progenitors from muscle contractures of children with cerebral palsy have impaired regenerative capacity.

AIM: To evaluate the mechanosensitivity of muscle satellite cells (MuSCs) and fibro-adipogenic progenitors (FAPs) in cerebral palsy (CP) and the efficacy of the drug verteporfin in restoring cells' regenerative capacity. METHOD: Muscle biopsies were collected from six children with CP and six typically developing children. MuSCs and FAPs were isolated and plated on collagen-coated polyacrylamide gels at stiffnesses of 0.2 kPa, 8 kPa, and 25 kPa. Cells were treated with verteporfin to block mechanosensing or with dimethyl sulfoxide as a negative control. MuSC differentiation and FAP activation into myofibroblasts were measured using immunofluorescence staining. RESULTS: Surprisingly, MuSC differentiation was not affected by stiffness; however, stiff substrates resulted in large myonuclear clustering. Across all stiffnesses, MuSCs from children with CP had less differentiation than those of their typically developing counterparts. FAP activation into myofibroblasts was significantly higher in children with CP than their typically developing peers, but was not affected by stiffness. Verteporfin did not affect differentiation or activation in either cell population, but slightly decreased myonuclear clustering on stiff substrates. INTERPRETATION: Cells from children with CP were less regenerative and more fibrotic compared to those of their typically developing counterparts, with MuSCs being sensitive to increases in stiffness. Therefore, the mechanosensitivity of MuSCs and FAPs may represent a new target to improve differentiation and activation in CP muscle.

Legg-Calvé-Perthes Disease: Diagnosis, Decision Making, and Outcome.

ABSTRACT: Legg-Calvé-Perthes disease (LCPD), or idiopathic avascular necrosis of the proximal capital femoral epiphysis in children, has a variable presentation and can result in significant femoral head deformity that can lead to long-term functional deficits. Plain radiographic imaging is crucial in diagnosing LCPD and guiding treatment. Although the etiology of LCPD remains unknown, the evolution of the disease has been well characterized to include the phases of ischemia, revascularization, and reossification. The mechanical weakening during these phases of healing place the femoral head at high risk of deformity. Treatment of LCPD, therefore, focuses on minimizing deformity through operative and nonoperative strategies to reduce the risk of premature osteoarthritis. Advanced imaging using perfusion MRI may refine surgical decision making in the future, and biological treatments to improve femoral head healing are on the horizon.

HipScreen mobile app for the measurement of hip migration percentage in children with cerebral palsy: Accuracy, reliability, and discriminatory ability.

AIM: To assess the accuracy, reliability, and discriminatory ability of a mobile app for measurement of migration percentage in hip surveillance radiographs of children with cerebral palsy (CP). METHOD: The free mobile app HipScreen (www.hipscreen.org) was utilized by a diverse group of users to measure the migration percentage of 40 hips at two time points after completing an online tutorial and competency test. The mean absolute error (MAE) was calculated against the reference standard obtained on a radiology workstation. Statistical analyses included linear regression, intraclass correlation coefficient (ICC), and area under receiver-operating characteristic curve (AUC). RESULTS: Thirty-seven users completed the study, with 30 having a healthcare professional background, but only 15 with x-ray interpretation expertise. The overall MAE of migration percentage measurement using the HipScreen app was 5.72% (95% confidence interval [CI]: 5.38-6.06), with good reliability between time points (ICC = 0.83). With a migration percentage less than 30% considered as a positive case, the HipScreen app had a sensitivity of 94% (95% CI: 87-97), specificity of 66% (95% CI: 61-77), and an AUC of 0.92 (95% CI: 0.88-0.96). INTERPRETATION: Users from a broad range of backgrounds can utilize the HipScreen app to measure hip surveillance radiographs with clinically acceptable accuracy, reliability, and discriminatory ability. WHAT THIS PAPER ADDS: The HipScreen app can accurately and reliably measure migration percentage. As a screening tool, HipScreen has excellent sensitivity and discriminatory ability. A broad range of HipScreen users achieve clinically acceptable performance.

Surgical Management of Severe Equinus Deformity in Ambulatory Children With Cerebral Palsy.

BACKGROUND: Tendo Achilles lengthening (TAL) for the management of equinus contractures in ambulatory children with cerebral palsy (CP) is generally not recommended due to concerns of over-lengthening, resulting in weakness and plantar flexor insufficiency. However, in some cases, surgical correction of severe equinus deformities can only be achieved by TAL. The goal of this study is to assess the outcomes following TAL in these cases. METHODS: A retrospective cohort study of children with CP with severe equinus contractures (ankle dorsiflexion with the knee extended of -20 degrees or worse) who underwent TAL as part of a single event multilevel surgery, with preoperative and postoperative gait analysis studies. Continuous data were analyzed by paired t test, and categorical data by McNemar Test. RESULTS: There were 60 subjects: 42 unilateral, 18 bilateral CP; 41 GMFCS II, 17 GMFCS I; mean age at surgery was 10.6 years, mean follow-up was 1.3 years. Ankle dorsiflexion with the knee extended improved from -28 to 5 degrees (P<0.001). The ankle Gait Variable Score improved from 34.4 to 8.6 (P<0.001). The ankle moment in terminal stance improved from 0.43 to 0.97 Nm/kg (P<0.001). Significant improvements (P<0.001) were seen in radiographic measures of foot alignment following surgery. There were few significant differences in the outcome parameters between subjects with unilateral versus bilateral CP (eg, only the bilateral group showed improved but persistent increased knee flexion in mid-stance). CONCLUSIONS: The outcomes following TAL for the management of severe equinus deformity in ambulatory children with CP were favorable 1 year after surgery, with significant improvements in all domains measured. SIGNIFICANCE: This study does not advocate for the widespread use of TAL to correct equinus deformity in children with CP. However, it does show that good short-term outcomes following TAL are possible in properly selected subjects with severe contractures when the dosing of the surgery is optimal (correction of contracture to between 0 and 5 degrees of dorsiflexion with the knee extended) and the procedure is performed in the setting of single event multilevel surgery with subsequent proper orthotic management and rehabilitation.

Neuraxial anesthesia for post-operative pain control after hip surgery in children with cerebral palsy and pre-existing intrathecal baclofen pumps.

PURPOSE: The purpose of this study is to describe the efficacy and adverse events of neuraxial anesthesia for post-operative pain control in non-ambulatory children with cerebral palsy with pre-existing intrathecal baclofen (ITB) pumps undergoing hip reconstructive or palliative surgery. METHODS: Twelve children (mean age 11.25 years) were included in the study with the following neuraxial anesthesia methods: indwelling epidural catheter (8 patients), neuraxial opioids administered through the side port of the ITB pump (3 patients), and single injection spinal anesthetic (1 patient). Observational pain scores and opioid requirements were quantified for all patients. RESULTS: There were no ITB pump or surgical complications at a mean follow-up of 2.2 years. The average length of stay was 6 days. Patients had good post-operative pain control with a mean observational pain score of 0.7 and mean morphine equivalent use of 0.26mg/kg/day. Four patients required anti-emetics to control nausea and three patients had urinary retention requiring repeat catheterization, but all medical complications resolved prior to discharge. CONCLUSION: Neuraxial anesthesia can effectively control post-operative pain in children with a pre-existing ITB pump. Utilizing the side port of the ITB pump for administration of neuraxial opioids is an option when epidural or spinal anesthesia is not possible.

Patella Alta in Ambulatory Children With Cerebral Palsy: Prevalence and Functional Significance.

BACKGROUND: Gait dysfunction associated with patella alta (PA) in subjects with cerebral palsy (CP) has been presumed but not objectively established clinically or through biomechanical modeling. It is hypothesized that PA is associated with increasing level of motor impairment, increasing age, obesity, and worse stance phase knee kinematics and kinetics in children with CP. METHODS: Retrospective case series of 297 subjects with CP studied in our Motion Analysis Center. Data analyzed included patient demographics (age, body mass index, CP classification), patella height (Koshino-Sugimoto Index), and knee kinematics and kinetics. RESULTS: PA was present in 180 of 297 subjects (61%), in 68 of the 146 (47%) with unilateral CP, and 112 of 151 subjects (74%) with bilateral CP. For unilateral CP, the prevalence of PA was not significantly different between Gross Motor Function Classification System (GMFCS) I and II (P=0.357). For bilateral CP, the prevalence of PA in GMFCS III was significantly greater than in GMFCS I and II (P=0.02). Regression analysis showed a significant trend between increasing age and PA in unilateral and bilateral groups (P<0.001 and 0.001, respectively). The prevalence of PA was not significantly different across body mass index categories for either unilateral or bilateral groups. There were only 2 of 10 significant correlations between PA and gait parameters for subjects with unilateral CP functioning at the GMFCS I and II levels. There were 8 of 12 significant correlations between PA and gait parameters for subjects with bilateral CP functioning at the GMFCS I, II, and III levels. CONCLUSIONS: PA is common in ambulatory children with CP across topographic types and motor functional levels. PA is well tolerated with respect to gait dysfunction in unilateral CP, but may contribute to crouch gait in bilateral CP. Gait dysfunction cannot be inferred from the radiographic assessment of patellar height, and radiographic evidence of PA by itself does not justify surgical correction with patellar tendon advancement or shortening. LEVEL OF EVIDENCE: Level III-prognostic, retrospective series.

Proximal Femoral Deformity Following Threaded Prophylactic Fixation for Slipped Capital Femoral Epiphysis: Risk Stratification Using the Modified Oxford Score.

BACKGROUND: This study assesses the effect of skeletal maturity on the development of iatrogenic proximal femoral deformity following threaded prophylactic screw fixation in patients presenting with unilateral slipped capital femoral epiphysis (SCFE). METHODS: Children who underwent threaded screw prophylaxis of the uninvolved hip (Group P) and those who were observed with no prophylaxis (Group N) on presentation with unilateral SCFE were compared. Skeletal maturity was assessed with the Modified Oxford Score (MOS). Proximal femoral morphology was characterized by femoral neck length, femoral neck width, neck shaft angle, and trochanteric femoral head overlap percentage (TFHOP). Femoral head deformity at final follow-up was characterized as spherical (Type 1), mildly aspherical (Type 2), or ovoid (Type 3). Analysis of variance and t test were used to compare the groups. RESULTS: Thirty-eight patients in Group P and 17 patients in Group N met inclusion criteria. The average follow-up was 2.6 years. Group P was younger than Group N by an average of 9.6 months (P=0.04), but the MOS for skeletal maturity was not different between groups (P=0.15). Group P had significantly diminished neck length (P=0.008) and significantly increased relative trochanteric overgrowth as evidenced by increased trochanteric femoral head overlap percentage (P<0.001), but there was no difference between groups in neck shaft angle and neck width. No patient in Group N developed femoral head deformity (all Type 1). In Group P, 14 patients (37%) developed Types 2 and 3 deformity. In patients with MOS 16 in Group P, 60% (3/5) developed Type 2 deformity and 40% (2/5) developed Type 3 deformity. In patients with MOS 17 in Group P, 45% (5/11) had Type 2 deformity. CONCLUSIONS: Skeletally immature patients with an MOS of 16 and 17 are at high risk for developing the triad of relative trochanteric overgrowth, coxa breva, and femoral head asphericity with prophylactic threaded screw fixation for SCFE. When prophylactic surgery is indicated, consideration should be given to growth friendly fixation strategies to avoid iatrogenic proximal femoral deformity. LEVELS OF EVIDENCE: Level III-therapeutic retrospective comparative study.

Quantitative Assessment of Knee Progression Angle During Gait in Children With Cerebral Palsy.

BACKGROUND: Abnormal hip rotation is a common deviation in children with cerebral palsy (CP). Clinicians typically assess hip rotation during gait by observing the direction that the patella points relative to the path of walking, which is referred to as the knee progression angle (KPA). Two kinematic methods for calculating the KPA are compared with each other. Video-based qualitative assessment of KPA is compared with the quantitative methods to determine reliability and validity. METHODS: The KPA was calculated by both direct and indirect methods for 32 typically developing (TD) children and a convenience cohort of 43 children with hemiplegic type CP. An additional convenience cohort of 26 children with hemiplegic type CP was selected for qualitative assessment of KPA, performed by 3 experienced clinicians, using 3 categories (internal, >10 degrees; neutral, -10 to 10 degrees; and external, >-10 degrees). RESULTS: Root mean square (RMS) analysis comparing the direct and indirect KPAs was 1.14+0.43 degrees for TD children, and 1.75+1.54 degrees for the affected side of children with CP. The difference in RMS among the 2 groups was statistically, but not clinically, significant (P=0.019). Intraclass correlation coefficient revealed excellent agreement between the direct and indirect methods of KPA for TD and CP children (0.996 and 0.992, respectively; P<0.001).For the qualitative assessment of KPA there was complete agreement among all examiners for 17 of 26 cases (65%). Direct KPA matched for 49 of 78 observations (63%) and indirect KPA matched for 52 of 78 observations (67%). CONCLUSIONS: The RMS analysis of direct and indirect methods for KPA was statistically but not clinically significant, which supports the use of either method based upon availability. Video-based qualitative assessment of KPA showed moderate reliability and validity. The differences between observed and calculated KPA indicate the need for caution when relying on visual assessments for clinical interpretation, and demonstrate the value of adding KPA calculation to standard kinematic analysis. LEVEL OF EVIDENCE: Level II-diagnostic test.

The pediatric polytrauma patient: current concepts.

Understanding the pediatric response to polytrauma is essential for the orthopaedic surgeon. The physiologic effects of multisystem injury that manifest in a child have important implications for coordination of treatment, particularly in relation to the timing and incidence of organ failure. The orthopaedic surgeon plays an important role in managing hemodynamic instability, vascular insult, and neurologic damage in the child with multiple injuries. Indications for surgery and postoperative immobilization in the pediatric polytrauma patient differ from those in the patient with an isolated injury. Further research is needed to determine the most appropriate method of management for extremity fractures in the pediatric polytrauma patient, particularly regarding the timing of fixation and management of open fractures.

Septic arthritis associated with closed intra-articular fracture: a case series.

BACKGROUND: Osteomyelitis in the setting of closed fractures is a recognized association in the literature, but to our knowledge, septic arthritis after a closed intra-articular fracture has not yet been reported. METHODS: We conducted a retrospective review of 3 cases of septic arthritis after closed intra-articular fractures of the proximal phalanx of the great toe, distal tibia, and distal humerus. RESULTS: The patients presented with fever, erythema, pain, and elevated infectious indices. All patients had a delay in diagnosis of up to 10 days. On diagnosis, all patients underwent open irrigation and debridement and were treated with organism-specific antibiotics for Staphylococcus aureus or Streptococcus pneumoniae. One patient required metatarsophalangeal joint arthrodesis, whereas the other 2 patients returned to full function after a prolonged treatment course. CONCLUSIONS: Septic arthritis after closed intra-articular fracture is a rare clinical condition and requires prompt diagnosis and treatment. LEVEL OF EVIDENCE: Level IV.

Novel biomechanical quantification methodology for lumbar intraforaminal spinal nerve adhesion in a laminectomy and disc injury rat model.

Spinal nerve fibrosis following injury or surgical intervention may play an important role in the pathophysiology of chronic back pain. In this current study, we demonstrate the role of biomechanical quantification of lumbar intraforaminal spinal nerve adhesion and tethering in the analysis of the post-laminectomy condition and describe a direct methodology to make this measurement. Twenty age-matched Sprague-Dawley male rats were divided into operative and non-operative (control) groups. Operative animals underwent a bilateral L5-L6 laminectomy with right-side L5-6 disc injury, a post-laminectomy pain model previously published by this lab. At eight weeks, animals were sacrificed and the strength of adhesion of the L5 intraforaminal spinal nerve to surrounding structures was quantified using a novel biomechanical methodology. Operative animals were found to have a significantly greater load to displace the intact right L5 spinal nerve through the intervertebral foramen when compared to control animals. The findings show that the post-laminectomy condition creates quantifiable fibrosis of the spinal nerve to surrounding structures and supports the conclusion that this fibrosis may play a role in the post-laminectomy pain syndrome.