Single-Event Multi-Level Surgery in Cerebral Palsy: A Bibliometric Analysis.

Background and Objectives: Single-Event Multi-Level Surgery (SEMLS) is a complex surgical programme in which soft tissue contractures and bony torsional deformities at the ankle, knee and hip, in both lower limbs are surgically corrected during a single operative session, requiring one hospital admission and one period of rehabilitation. The aim of SEMLS is to improve gait and function in ambulant children with cerebral palsy. Utilisation of the SEMLS concept can reduce the number of surgical events, hospital inpatient stays and reduce rehabilitation requirements to a single intensive episode. Three-dimensional gait analysis is a pre-requisite to plan intervention at multiple anatomic levels to correct fixed deformities and to improve gait and function. Materials and Methods: This study was a bibliometric analysis of SEMLS in cerebral palsy using the Clarivate Web of Science Core Collection database from 1900 to 29 May 2023. Results: A total of 84 studies met the inclusion criteria. The most highly cited article was "Correction of severe crouch gait in patients with spastic diplegia with use of multilevel orthopaedic surgery" by Rodda et al. (2006) with 141 citations. The most productive institutions by number of articles were the Royal Children's Hospital Melbourne (Australia), Murdoch Children's Research Institute (Australia) and University of Melbourne (Australia). The most productive author by number of citations was HK Graham (Australia). Conclusions: The literature base for SEMLS consists largely of retrospective cohort studies. The aforementioned three institutes in Melbourne, Australia, which frequently collaborate together, have contributed the greatest number of studies in this field.

Understanding skeletal muscle in cerebral palsy: a path to personalized medicine?

Until recently, there has been little interest in understanding the intrinsic features associated with the pathomorphology of skeletal muscle in cerebral palsy (CP). Coupled with emerging evidence that challenges the role of spasticity as a determinant of gross motor function and in the development of fixed muscle contractures, it has become increasingly important to further elucidate the underlying mechanisms responsible for muscle alterations in CP. This knowledge can help clinicians to understand and apply treatment modalities that take these aspects into account. Thus, the inherent heterogeneity of the CP phenotype allows for the potential of personalized medicine through the understanding of muscle pathomorphology on an individual basis and tailoring treatment approaches accordingly. This review aims to summarize recent developments in the understanding of CP muscle and their relationship to musculoskeletal manifestations, in addition to proposing a treatment paradigm that incorporates this new knowledge.

Three-Dimensional Gait Analysis in Children Undergoing Gastrocsoleus Lengthening for Equinus Secondary to Cerebral Palsy.

Background and Objectives: Equinus is the most common deformity in children with cerebral palsy, and surgical lengthening of the gastrocsoleus muscle-tendon unit is the most commonly performed operation for children with cerebral palsy. Treatment outcomes of orthopaedic surgery can be measured objectively with three-dimensional gait analysis. This study examined the quality of evidence for gastrocsoleus lengthening surgery based on objective measures. Materials and Methods: A search was performed with Medline, Embase and PubMed from 1990 to 25 August 2020 using the keywords "cerebral palsy", "equinus", "surgery" and "gait analysis". Only studies of gastrocsoleus lengthening surgery using three-dimensional gait analysis were included, yielding 34 studies. Results: Fourteen studies reported swing phase kinematics and all studies reported a significant improvement. Rates of recurrent equinus and calcaneus were reported in 21 studies and varied widely based on follow-up period and surgical technique. Conclusions: Poor study quality and marked variability in study samples and interventions made comparison difficult. Future studies should consider prospective design, controls or comparison groups and more detailed breakdowns of outcomes by cerebral palsy subtype, sagittal gait pattern, and equinus type in order to allow more rigorous treatment recommendations to be made.

Hairless regulates p53 target genes to exert tumor suppressive functions in glioblastoma.

Glioblastoma (GBM) is the most common malignant brain tumor and is associated with a poor prognosis, with most patients living less than a year after diagnosis. Given that GBM nearly always recurs after conventional treatments, there is an urgent need to identify novel molecular targets. Hairless (HR) is a nuclear factor enriched in the skin and has been previously implicated in hair cycling. HR is also highly expressed in the brain, but its significance is unknown. We found that human hairless gene (HR) expression is significantly decreased in all GBM subtypes compared with normal brain tissue and is predictive of prognosis, which suggests that loss of HR expression can contribute to GBM pathogenesis. HR was recently discovered to bind to and regulate p53 responsive elements, and thus we hypothesized that HR may have a tumor suppressive function in GBM by modulating p53 target gene expression. We found that HR indeed regulates p53 target genes, including those implicated in cell cycle progression and apoptosis in the GBM-derived U87 cell line, and restoring HR expression triggered G2/M arrest and apoptosis. An analysis of sequenced genomes from patients with GBM revealed 10 HR somatic mutations in patients with glioma, two of which are located in the histone demethylase domain of HR. These two mutations, P996S and K1004N, were reconstructed and found to have impaired p53 transactivating properties. Collectively, the results of our study suggest that HR has tumor suppressive functions in GBM, which may be clinically relevant and a potential avenue for therapeutic intervention.

Injection frequency of botulinum toxin A for spastic equinus: a randomized clinical trial.

AIM: We compared two botulinum toxin A (BoNT-A) injection frequency regimens, 12-monthly versus 4-monthly, for spastic equinus in a randomized clinical trial. The primary outcome measure was passive ankle dorsiflexion. METHOD: Forty-two ambulant children with spastic equinus, secondary to cerebral palsy (23 males and 19 females; mean age 3y 6mo, SD 13mo; GMFCS levels I [n=20], II [n=19], III [n=3]) were randomized to receive either 12-monthly or 4-monthly BoNT-A injections to the calf, over a 26-month period. Twenty-one children had spastic hemiplegia, 21 children had spastic diplegia. A fixed 6U/kg dose of Botox was injected into the gastrocnemius muscle of both limbs in children with diplegia and the gastrocsoleus of the affected limb in children with hemiplegia, under mask anaesthesia. RESULTS: Forty-two children entered the trial with 21 participants randomized to each group. There were three withdrawals and two children received serial casting midway through the trial. There was no significant difference in passive dorsiflexion between 12-monthly and 4-monthly regimens (p=0.41). There were also no significant between group differences on secondary outcome measures. There were no serious adverse events - the rate was 1.2 adverse events per child per year in the 12-monthly group and 2.2 adverse events per child per year in the 4-monthly group. Subgroup analysis revealed a significant difference in passive dorsiflexion between children with hemiplegia and diplegia (p=0.01). INTERPRETATION: There was no significant difference between 12-monthly and 4-monthly injection regimens on passive dorsiflexion or secondary outcome measures. BoNT-A injections for spastic equinus may be recommended on a 12-monthly basis.

Cross-sectional study to investigate the health-related quality of life in children with severe lower limb trauma in Victoria.

AIMS: The aim of this study is to investigate the health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury and to assess patient and injury characteristics in association with the health-related quality of life scores. METHODS: All children in the state of Victoria, who were 18 years of age or younger, suffering from severe lower limb injury before 2006 were studied. Patient and injury characteristics were abstracted from medical records. The health-related quality of life (HRQOL) scores were obtained using the Paediatric Quality of Life Inventory. RESULTS: Thirty-two out of 64 eligible patients participated in this study. All aspects of health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury were significantly poorer compared with non-affected children, particularly in the physical health domain (difference: -12.51 ± 7.43: P < 0.05). It was observed that bilateral limb involvement and the need for soft tissue management were related to poor physical functioning (P < 0.05). Other characteristics such as traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not affect the overall HRQOL scores (P > 0.05). CONCLUSIONS: The HRQOL in children with severe lower limb trauma was significantly impaired even after 12 months post-injury, notably in patient group with bilateral limb involvement and need for soft tissue management. Traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not have an impact on quality of life.

Subtalar fusion for pes valgus in cerebral palsy: results of a modified technique in the setting of single event multilevel surgery.

BACKGROUND: We studied the use of cortico-cancellous circular allograft combined with cannulated screw fixation for the correction of dorsolateral peritalar subluxation in a series of children with bilateral spastic cerebral palsy undergoing single event multilevel surgery. METHODS: Forty-six children who underwent bilateral subtalar fusion between January 1999 and December 2004 were retrospectively reviewed. Gait laboratory records, Gross Motor Function Classification System (GMFCS) levels, Functional Mobility Scale (FMS) scores, and radiographs were reviewed. The surgical technique used an Ollier type incision with a precut cortico-cancellous allograft press-fit into the prepared sinus tarsi. One or two 7.3 mm fully threaded cancellous screws were used to fix the subtalar joint. Radiographic analysis included preoperative and postoperative standing lateral radiographs measuring the lateral talocalcaneal angle, lateral talo-first metatarsal angle, and navicular cuboid overlap. Fusion rate was assessed with radiographs >12 months after surgery. RESULTS: The mean patient age was 12.9 years (range, 7.8 to 18.4 y) with an average follow-up of 55 months. Statistically significant improvement postoperatively was found for all 3 radiographic indices: lateral talocalcaneal angle, mean improvement 20 degrees (95% CI, 17.5-22.1; P<0.001); lateral talo-first metatarsal angle, mean improvement 21 degrees (95% CI, 19.2-23.4; P<0.001); and navicular cuboid overlap, mean improvement 29% (95% CI, 25.7%-32.6%; P<0.001). FMS improved across all patients, with Gross Motor Function Classification System III children experiencing a 70% improvement across all 3 FMS distances (5, 50, and 500 m). All 3 radiographic measures improved significantly (P<0.001). Fusion was achieved in 45 patients and there were no wound complications. CONCLUSIONS: With this study, we demonstrate significant improvement in radiographic segmental alignment and overall function outcome with this modified subtalar fusion technique. We conclude that this technique is an effective complement for children with dorsolateral peritalar subluxation undergoing single event multilevel surgery. LEVEL OF EVIDENCE: Level IV.

Hip Surgery in Cerebral Palsy: A Bibliometric Analysis.

Hip dislocation in cerebral palsy can lead to pain, pressure sores and difficulty with perineal hygiene. Hip surveillance programs have been implemented to identify patients who might benefit from early intervention and preventive strategies. Surgical techniques used to treat hip dislocation include soft tissue procedures, guided growth, osteotomies and salvage procedures. A search was conducted using Clarivate Web of Science Core Collection on 18 October 2022, to identify all studies of bony or soft tissue surgery for hip pathology in children with cerebral palsy. Fifty-nine original studies and reviews with at least 20 citations were included in this bibliometric analysis. We found that there has been an increase in studies over the decades, with the most studies being published in the Journal of Pediatric Orthopaedics. The United States of America was the most productive country, with Boston Children's Hospital and Harvard University publishing the most articles. The Methodological Index for Non-randomized Studies (MINORS) scoring system was used to analyse the methodological quality of included cohort studies, with the median score being 11 out of 18; many studies had no prospective calculation of study size and lacked control groups. Overall, the literature on this topic appears to be preferentially published in the Journal of Pediatric Orthopaedics, and influential papers by Hagglund 2005 and 2014 continue to be highly cited.

Foot drop after gastrocsoleus lengthening for equinus deformity in children with cerebral palsy.

BACKGROUND: Gastrocsoleus lengthening (GSL) is the most common surgical procedure to treat equinus deformity in ambulant children with cerebral palsy (CP). Foot drop, where the ankle remains in plantarflexion during swing phase, can persist in some children post-operatively. There is currently limited understanding of which children will demonstrate persistent foot drop after GSL. RESEARCH QUESTION: Which children develop persistent foot drop after GSL surgery for equinus? METHODS: We conducted a retrospective cohort study on ambulant children with CP who had GSL surgery for fixed equinus deformity. The aims of the study were: to determine the frequency of persistent foot drop post-operatively and to compare outcome parameters from physical examination and three-dimensional gait analysis for children with hemiplegia or diplegia. RESULTS: One hundred and ten children functioning at GMFCS Levels I/II/III of 28/75/7 met the inclusion criteria for this study. There were 71 boys and mean age was 9.1 years at time of GSL surgery. The overall frequency of persistent foot drop was 25%, with a higher frequency of persistent foot drop in children with hemiplegia (42%) than children with diplegia (19%). There were significant improvements in dorsiflexor strength and in selective motor control in children with diplegia but not in children with hemiplegia. Mean (SD) pre-operative mid-swing ankle dorsiflexion for children with hemiplegia was - 14.0° (9.9°) and improved post-operatively to - 1.6° (5.5°). For children with diplegia, the pre-operative mid-swing ankle dorsiflexion was - 12.1° (12.9°) and improved post-operatively to + 4.2° (6.9°). SIGNIFICANCE: Foot drop is present following GSL surgery for fixed equinus deformity in a significant number of children with hemiplegia and to a lesser extent in children with diplegia, which may reflect a difference in the central nervous system lesion between these groups. New management approaches are required for this important and unsolved problem.

Hip Surveillance and Management of Hip Displacement in Children with Cerebral Palsy: Clinical and Ethical Dilemmas.

Hip displacement is the second most common musculoskeletal deformity in children with cerebral palsy. Hip surveillance programs have been implemented in many countries to detect hip displacement early when it is usually asymptomatic. The aim of hip surveillance is to monitor hip development to offer management options to slow or reverse hip displacement, and to provide the best opportunity for good hip health at skeletal maturity. The long-term goal is to avoid the sequelae of late hip dislocation which may include pain, fixed deformity, loss of function and impaired quality of life. The focus of this review is on areas of disagreement, areas where evidence is lacking, ethical dilemmas and areas for future research. There is already broad agreement on how to conduct hip surveillance, using a combination of standardised physical examination measures and radiographic examination of the hips. The frequency is dictated by the risk of hip displacement according to the child's ambulatory status. Management of both early and late hip displacement is more controversial and the evidence base in key areas is relatively weak. In this review, we summarise the recent literature on hip surveillance and highlight the management dilemmas and controversies. Better understanding of the causes of hip displacement may lead to interventions which target the pathophysiology of hip displacement and the pathological anatomy of the hip in children with cerebral palsy. We have identified the need for more effective and integrated management from early childhood to skeletal maturity. Areas for future research are highlighted and a range of ethical and management dilemmas are discussed.

Arthrodesis of the first metatarsophalangeal joint for severe hallux valgus in adolescents with cerebral palsy: A retrospective comparison study of three surgical techniques.

Purpose: We compared the outcomes of arthrodesis of the first metatarsophalangeal joint for severe hallux valgus in 31 adolescents with cerebral palsy, using three different methods of fixation: K-wires, non-locking plates, and locking plates. Methods: Clinical outcomes included time to weight-bearing, fusion rates and surgical complications. Radiographic assessment included comparing pre- and post-operative hallux valgus angles, intermetatarsal angles, interphalangeal angles, and lateral metatarsophalangeal angles. Patient-reported outcomes included pre- and post-operative visual analogue scales addressing bunion pain and concerns, difficulties with wearing shoes and braces, and difficulties with foot hygiene. Results: Of the 31 adolescents (16 male), 10 patients had K-wire fixation, 11 had a non-locking dorsal plate, and 10 had fixation with a dorsal locking plate. Mean age at surgery was 16 years (12-18 years) and mean follow-up was 4 years (2.7-6.5 years). Patients with K-wire fixation had delayed weight-bearing and had more complications than those managed by dorsal plating. There were significant improvements in radiographic parameters (except interphalangeal angle) and in patient-reported outcomes, in all groups (p < 0.001). However, radiographic and clinical outcomes were better in the dorsal plating groups compared to the K-wire group. Conclusion: Arthrodesis of the first metatarsophalangeal joint gave good correction of deformity with improvements in symptoms and radiographic parameters in adolescents with cerebral palsy. We recommend dorsal plating that allowed early weight-bearing and had fewer complications with better clinical and radiographic outcomes, than K-wire fixation. Level of evidence: IV: Retrospective case series.

Distal femoral extension osteotomy and patellar tendon advancement or shortening in ambulatory children with cerebral palsy: A modified Delphi consensus study and literature review.

Purpose: In children with cerebral palsy, flexion deformities of the knee can be treated with a distal femoral extension osteotomy combined with either patellar tendon advancement or patellar tendon shortening. The purpose of this study was to establish a consensus through expert orthopedic opinion, using a modified Delphi process to describe the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. A literature review was also conducted to summarize the recent literature on distal femoral extension osteotomy and patellar tendon shortening/patellar tendon advancement. Method: A group of 16 pediatric orthopedic surgeons, with more than 10 years of experience in the surgical management of children with cerebral palsy, was established. The group used a 5-level Likert-type scale to record agreement or disagreement with statements regarding distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening. Consensus for the surgical indications for distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening was achieved through a modified Delphi process. The literature review, summarized studies of clinical outcomes of distal femoral extension osteotomy/patellar tendon shortening/patellar tendon advancement, published between 2008 and 2022. Results: There was a high level of agreement with consensus for 31 out of 44 (70%) statements on distal femoral extension osteotomy. Agreement was lower for patellar tendon advancement/patellar tendon shortening with consensus reached for 8 of 21 (38%) of statements. The literature review included 25 studies which revealed variation in operative technique for distal femoral extension osteotomy, patellar tendon advancement, and patellar tendon shortening. Distal femoral extension osteotomy and patellar tendon advancement/patellar tendon shortening were generally effective in correcting knee flexion deformities and extensor lag, but there was marked variation in outcomes and complication rates. Conclusion: The results from this study will provide guidelines for surgeons who care for children with cerebral palsy and point to unresolved questions for further research. Level of evidence: level V.

Assessment of foot alignment and function for ambulatory children with cerebral palsy: Results of a modified Delphi technique consensus study.

Purpose: The purpose of this study was to establish consensus for the assessment of foot alignment and function in ambulatory children with cerebral palsy, using expert surgeon's opinion through a modified Delphi technique. Methods: The panel used a five-level Likert-type scale to record agreement or disagreement with 33 statements regarding the assessment of foot alignment and function. Consensus was defined as at least 80% of responses being in the highest or lowest of two of the five Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest two ratings. There was no agreement if neither threshold was reached. Results: Consensus was achieved for 25 (76%) statements, general agreement for 4 (12%) statements, and lack of consensus for 4 (12%) of the statements. There was consensus that the functional anatomy of the foot is best understood by dividing the foot into three segments and two columns. Consensus was achieved concerning descriptors of foot segmental alignment for both static and dynamic assessment. There was consensus that radiographs of the foot should be weight-bearing. There was general agreement that foot deformity in children with cerebral palsy can be classified into three levels based on soft tissue imbalance and skeletal malalignment. Conclusion: The practices identified in this study can be used to establish best care guidelines, and the format used will be a template for future Delphi technique studies on clinical decision-making for the management of specific foot segmental malalignment patterns commonly seen in children with cerebral palsy. Level of Evidence: V.

Finding consensus for hamstring surgery in ambulatory children with cerebral palsy using the Delphi method.

Purpose: There is marked variation in indications and techniques for hamstring surgery in children with cerebral palsy. There is particular uncertainty regarding the indications for hamstring transfer compared to traditional hamstring lengthening. The purpose of this study was for an international panel of experts to use the Delphi method to establish consensus indications for hamstring surgery in ambulatory children with cerebral palsy. Methods: The panel used a five-level Likert-type scale to record agreement or disagreement with statements regarding hamstring surgery, including surgical indications and techniques, post-operative care, and outcome measures. Consensus was defined as at least 80% of responses being in the highest or lowest two of the five Likert-type ratings. General agreement was defined as 60%-79% falling into the highest or lowest two ratings. There was no agreement if neither of these thresholds was reached. Results: The panel reached consensus or general agreement for 38 (84%) of 45 statements regarding hamstring surgery. The panel noted the importance of assessing pelvic tilt during gait when considering hamstring surgery, and also that lateral hamstring lengthening is rarely needed, particularly at the index surgery. They noted that repeat hamstring lengthening often has poor outcomes. The panel was divided regarding hamstring transfer surgery, with only half performing such surgery. Conclusion: The results of this study can help pediatric orthopedic surgeons optimize decision-making in their choice and practice of hamstring surgery for ambulatory children with cerebral palsy. This has the potential to reduce practice variation and significantly improve outcomes for ambulatory children with cerebral palsy. Level of evidence: level V.

Indications for gastrocsoleus lengthening in ambulatory children with cerebral palsy: a Delphi consensus study.

PURPOSE: Equinus is the most common deformity in cerebral palsy (CP) and gastrocsoleus lengthening (GSL) is the most commonly performed surgery to improve gait and function in ambulatory children with CP. Substantial variation exists in the indications for GSL and surgical technique. The purpose of this study was to review surgical anatomy and biomechanics of the gastrocsoleus and to utilize expert orthopaedic opinion through a Delphi technique to establish consensus for surgical indications for GSL in ambulatory children with CP. METHODS: A 17-member panel, of Fellowship-trained paediatric orthopaedic surgeons, each with at least 9 years of clinical post-training experience in the surgical management of children with CP, was established. Consensus for the surgical indications for GSL was achieved through a standardized, iterative Delphi process. RESULTS: Consensus was reached to support conservative Zone 1 surgery in diplegia and Zone 3 surgery (lengthening of the Achilles tendon) was contraindicated. Zone 2 or Zone 3 surgery reached general agreement as a choice in hemiplegia and under-correction was preferred to any degree of overcorrection. Agreement was reached that the optimum age for GSL surgery was 6 years to 10 years and should be avoided in children aged under 4 years. Physical examination measures with the child awake and under anaesthesia were important in decision making. Gait analysis was supported both for decision making and for assessing outcomes, in combination with patient reported outcomes (PROMS). CONCLUSIONS: The results from this study may encourage informed practice evaluation, reduce practice variability, improve clinical outcomes and point to questions for further research. LEVEL OF EVIDENCE: V.

Establishing surgical indications for hamstring lengthening and femoral derotational osteotomy in ambulatory children with cerebral palsy.

PURPOSE: Surgical procedures, such as medial hamstring lengthening (MHL) and femoral derotational osteotomy (FDO), can improve the gait of children with cerebral palsy (CP); however, substantial variation exists in the factors that influence the decision to perform surgery. The purpose of this study was to use expert surgeon opinion through a Delphi technique to establish consensus for indications in ambulatory children with CP. METHODS: A 15-member panel, all established experts with at least nine years' experience in the surgical management of children with CP, was created (mean of 20.81 years' experience). All panel members also had expertise of the use of movement analysis for the assessment of gait disorders in children with CP. The group initially focused on two of the most commonly performed procedures, MHL and FDO, in an attempt to gain consensus (> 80%). This was obtained through a standardized, iterative Delphi process. RESULTS: For MHL, a total of 59 questions were surveyed: 41 indication questions and 18 outcome questions, for which there was consensus on ten indication questions and seven outcomes. For FDO, a total of 55 questions were surveyed: 43 indication questions and 12 outcome questions, for which there was consensus on 29 indication questions and eight outcomes. CONCLUSION: This study is the first to use an expert panel to identify best-practice indications for common surgical procedures of children with CP. The results from this study will allow for more informed evaluation of practice and form the basis for future improvement efforts to standardize surgical recommendations internationally. LEVEL OF EVIDENCE: Level IV.