Botulinum Toxin Type A Versus Placebo for Idiopathic Clubfoot: A Two-Center, Double-Blind, Randomized Controlled Trial.

BACKGROUND: Congenital idiopathic clubfoot is a condition that affects, on average, approximately 1 in 1,000 infants. One broadly adopted method of management, described by Ponseti, is the performance of a percutaneous complete tenotomy when hindfoot stall occurs. The use of onabotulinum toxin A (BTX-A) along with the manipulation and cast protocol described by Ponseti has been previously reported. Our goal was to compare the clinical outcomes between BTX-A and placebo injections into the gastrocnemius-soleus muscle at the time of hindfoot stall in infants with idiopathic clubfoot treated with the Ponseti method of manipulation and cast changes. METHODS: This was a double-blind, placebo-controlled, parallel-group study with balanced randomization. RESULTS: At 6 weeks after the study injection (T1), 66% of the 32 feet in the BTX-A arm and 63% of the 30 in the placebo arm responded to the treatment (i.e., obtained ≥15° of dorsiflexion). Seven of the 11 patients in the BTX-A arm and all of the 11 in the placebo arm who had not responded at T1 responded to a rescue BTX-A injection at 12 weeks after the first injection (T2). The combined response rate at T2, which included the first-time responders as well as the patients who did not respond at T1 but did at T2, was 88% in the BTX-A arm and 100% in the placebo arm, culminating in a 94% response rate at T2. At T3 (2 years of age), 89% of the feet continued to respond and there was an 8% surgical rate. CONCLUSIONS: There was no difference in outcomes between the BTX-A and placebo groups when the injection was performed at the time of hindfoot stall. Overall, 92% of the clubfeet in this study responded to a manipulation and cast protocol alone, with or without BTX-A injection, by 12 weeks after hindfoot stall, or we can say that 92% of the clubfeet did not require percutaneous Achilles tendon lengthening by 2 years of age. The need for tenotomy is limited to those who have not responded to treatment at this point, and the need for surgery is limited to those for whom all attempts at treatment with sequential casts, BTX-A, and percutaneous Achilles tendon lengthening have failed. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Early ultrasonographic evaluation of idiopathic clubfeet treated with manipulations, casts, and Botox(®): a double-blind randomized control trial.

BACKGROUND: The manipulations, casts, and Botox(®) method for treating idiopathic clubfoot is an alternative non-surgical treatment method. Botox(®)-induced reversible muscle paralysis of the gastrocsoleus enables a physician to manipulate and cast the clubfoot in greater dorsiflexion. Ultrasound is incorporated during the early treatment stages to monitor the underlying physiology of the muscle-tendon unit following Botox(®). METHODS: Ultrasonographic evaluation was performed parallel to a double-blind randomized control trial administering Botox(®) or placebo to correct clubfoot. Patients underwent two-dimensional ultrasound to monitor the length changes to the gastrocsoleus and Achilles tendon unit at two time points: pre-injection (baseline) and 6 weeks post-blinded injection. Gastrocsoleus and Achilles tendon length measurements were analyzed among placebo, Botox(®) and contralateral controls using repeated measures ANOVA. RESULTS: The baseline gastrocsoleus length of the clubfoot (322.4 pixels) before blinded injection appears shorter than controls (337.5 pixels), but fails to reach significance (p = 0.05). The complex length within each of the three treatment groups displayed no significant change between baseline and 6 weeks. The complex-tendon ratio and muscle-tendon ratio of the Botox(®) treatment group was significantly decreased compared to controls (p = 0.049 and 0.042, respectively). Briefly, when expressed as a proportion, an increase in Achilles tendon length and decrease in gastrocsoleus is observed when clubfeet are treated with Botox(®). CONCLUSIONS: Only in the Botox(®) treatment cohort did the muscle shrink to uncover tendon (seen as a decreased complex-tendon ratio and muscle-tendon ratio) over the 6-week interval to effectively increase tendon length with respect to the unit as a whole.

Classification of midfoot break using multi-segment foot kinematics and pedobarography.

Midfoot break (MFB) is a foot deformity that can occur when ankle dorsiflexion is restricted due to muscle spasticity or contractures, causing abnormal increased motion through the midfoot. MFB has been previously described in terms of forefoot (FF) and hindfoot (HF) motion in the sagittal plane. The purpose of this study was to further classify MFB by describing FF and HF motion in the coronal and transverse planes along with plantar pressures, with the goal of optimizing treatment of this deformity. Three-dimensional foot kinematics were assessed using a multi-segment foot model in children with MFB (n=30) and children with no foot or gait abnormalities (n=30). The MFB group was subdivided into three categories: (1) Pronated MFB, (2) Supinated MFB and (3) Flat Foot MFB. Unique patterns of plantar pressures and foot kinematics were identified for each MFB group. The Pronated MFB group had increased medial midfoot pressures, increased forefoot pronation, and increased external forefoot rotation (forefoot abductus). The Supinated MFB group had increased lateral midfoot pressures, increased forefoot supination, and increased internal forefoot rotation (forefoot adductus). In the Flat Foot MFB group, midfoot pressures were increased and distributed uniformly between the medial and lateral sides, forefoot pronation was increased, and internal forefoot rotation was present. By combining this new information with previously reported methods of measuring sagittal plane kinematics of MFB, it is now possible to characterize midfoot break in terms of severity and foot-floor contact pattern.

Onabotulinumtoxin A injections: a safety review of children with clubfoot under 2 years of age at BC Children's Hospital.

BACKGROUND: Pediatric indications for Onabotulinumtoxin A extend beyond treatment of skeletal muscle conditions. Each of the indications for Onabotulinumtoxin A use have adverse events reported in the past. The aim of this study was to review dverse events in children less than 2 years of age who were treated with Onabotulinumtoxin A injections as part of equinus foot deformity, in the setting of clubfoot at British Columbia's Children Hospital. METHODS: A retrospective review of all clubfoot patients at British Columbia's Children Hospital, less than 2 years of age, who received a Onabotulinumtoxin A injection for equinus correction, between September 2000 and December 2012 was conducted. Data collected included demographics, clinical diagnosis, treatment history, ankle range of motion and any adverse event noted by the clubfoot team or reported by the families. RESULTS: A total of 239 eligible subjects (361 feet) had received 523 Onabotulinumtoxin A injections before the age of 2 years. There was only one adverse event reported out of the 523 Onabotulinumtoxin A injections (adverse events rate of 0.19%) given at British Columbia's Children Hospital. However, this adverse event was not found related to the Onabotulinumtoxin A injection. CONCLUSIONS: Onabotulinumtoxin A appears to be safe with respect to the adverse events, for use in children under 2 years of age with the diagnosis of clubfoot when dosed at 10 units per kilogram. However, the dose of Onabotulinumtoxin A and underlying diagnosis should always be kept in mind.

A kinematic description of dynamic midfoot break in children using a multi-segment foot model.

Midfoot break (MFB) is a foot deformity that occurs most commonly in children with cerebral palsy (CP), but may also affect children with other developmental disorders. Dynamic MFB develops because the muscles that cross the ankle joint are hypertonic, resulting in a breakdown and dysfunction of the bones within the foot. In turn, this creates excessive motion at the midfoot. With the resulting inefficient lever arm, the foot is then unable to push off the ground effectively, resulting in an inadequate and painful gait pattern. Currently, there is no standard quantitative method for detecting early stages of MFB, which would allow early intervention before further breakdown occurs. The first step in developing an objective tool for early MFB diagnosis is to examine the difference in dynamic function between a foot with MFB and a typical foot. Therefore, the main purpose of this study was to compare the differences in foot motion between children with MFB and children with typical feet (Controls) using a multi-segment kinematic foot model. We found that children with MFB had a significant decrease in peak ankle dorsiflexion compared to Controls (1.3 ± 6.4° versus 8.6 ± 3.4°) and a significant increase in peak midfoot dorsiflexion compared to Controls (15.2 ± 4.9° versus 6.4 ± 1.9°). This study may help clinicians track the progression of MFB and help standardize treatment recommendations for children with this type of foot deformity.

Health-related quality of life in people with hereditary multiple exostoses.

BACKGROUND: Hereditary multiple exostoses (HME) is a rare genetic disorder, which can be associated with severe complications that may significantly affect the health-related quality of life (HRQL). Our primary objective was to describe the baseline HRQL in HME individuals at the British Columbia's Children's Hospital HME clinic and the Multiple Hereditary Exostoses Coalition compared with relevant Canadian and US population norms. This is the first study to explore the HRQL among adults and children with HME. METHODS: Previously validated instruments Short Form-36 version 2, Short form-6D, and Child Health Questionnaire Parent Form 50 were used to assess the HRQL of individuals with HME. The scores from these instruments were compared with the relevant population norms. The British Columbia's Children's Hospital and Multiple Hereditary Exostoses coalition populations were also compared with each other. RESULTS: The study sample consisted of 100 participants including 57 adults and 43 children. The mean age for Short Form 36 version 2 survey was 40.10±13.01 years and for Child Health Questionnaire Parent Form 50 was 9.93±3.48 years. Adult HME population had lower scores than both the US and Canadian general population in all domains except for emotional role limitations. Short Form -6D utility scores (0.65) indicates the quality of life for some individuals is near death and for others it is comparable or better than individuals with rheumatoid arthritis. Children with HME scored less than the US general population; particularly lower scores were seen in bodily pain (51.2 vs. 81.7) and emotional self-esteem (52.0 vs. 79.8). CONCLUSIONS: HME population has lower HRQL than the general population. These data provide a benchmark for individuals with HME. From such data, future research on HME disease progression and effectiveness of treatments/interventions can be tracked over time. LEVEL OF EVIDENCE: Level II, This is a prognostic, prospective study with participants enrolled at different points in their disease.

Recurrent viral-induced compartment syndrome.

UNLABELLED: Rhabdomyolysis and compartment syndrome are rare but a limb-threatening complication of viral myositis. Because of the potential for severe consequences of compartment syndrome, clinicians should maintain a high index of suspicion when examining children with rhabdomyolysis due to viral myositis. We report a case of recurrent bilateral thigh compartment syndrome in a patient with influenza A, subtype pandemic H1N1-2009. CASE: An 8-year-old girl with a history of rhabdomyolysis, acute renal failure, and compartment syndrome secondary to parainfluenza infection that resulted in release of her lower limb compartments presented with a 3-day history of flu symptoms and increasing bilateral thigh pain. Compartment syndrome was confirmed by intracompartmental pressure measurements and comparison of intracompartmental pressure measurements to diastolic blood pressure. The compartments were released. She also experienced acute renal failure, which was treated by continuous renal replacement therapy and hemodialysis. At her most recent orthopedic follow-up, she was doing well. CONCLUSIONS: This is the first reported case of recurrent rhabdomyolysis and compartment syndrome as a complication of viral myositis. This case highlights the importance of maintaining a high index of suspicion for compartment syndrome in the child with viral myositis.

Segond fractures: not necessarily pathognemonic of anterior cruciate ligament injury in the pediatric population.

Initially described following cadaveric studies in the late 19th century by Dr. Paul Segond, the Segond fracture is now widely accepted as a pathognemonic radiographic marker of anterior cruciate ligament injury. This fracture in a skeletally immature 16-year-old was not seen with an anterior cruciate ligament injury, but with a Salter-Harris type IV fracture of the tibial plateau. A nonweightbearing knee immobilizer with the leg in full extension was used for 6 weeks. Recovery was uncomplicated, and range of motion and weightbearing began at 6 weeks.

The use of botulinum type A toxin in the treatment of idiopathic clubfoot: 5-year follow-up.

BACKGROUND: Continued monitoring and reporting of outcomes in clubfoot patients are important for providing an indicator of functional outcomes and surveillance and treatment for problems or recurrences. The purpose of this study is to report the 5-year outcomes of the updated cohort of 44 patients with 65 idiopathic clubfeet treated with manipulation, casting, and Botulinum toxin A (BTX-A). METHODS: As part of the original study, the patients underwent the corrective treatment phase of manipulation and casting followed with BTX-A injection and then the maintenance phase of bracing. The patients were seen at regular intervals and a detailed clinical history was maintained for each patient including ankle range of motion, recurrences, and interventions for recurrences. RESULTS: Mean values for range of motion at the 5-year visit were 22.3 and 17.1 degrees for dorsiflexion with the knee in flexion and extension, respectively. Overall, 48% (31 of 65 clubfeet) successfully responded to a single BTX-A injection and experienced no recurrence over the follow-up period. At least 1 repeat BTX-A injection was required in 34 clubfeet, for an overall recurrence rate of 52%. Surgery was required in 10 clubfeet, and the overall surgical rate was 15.4%. CONCLUSIONS: Idiopathic clubfeet treated with BTX-A continued to show good outcomes at 2 to 5-year follow-up. The experience with this cohort provides support for the effectiveness of BTX-A in the initial correction and continued management of idiopathic clubfoot. LEVEL OF EVIDENCE: Levels III to IV. This is a prospective, nonexperimental clinical study investigating efficacy of an innovative treatment.

Evaluation of the anatomic burden of patients with hereditary multiple exostoses.

Hereditary multiple exostosis (HME) is an autosomal dominant condition resulting predominantly from mutations in the exostosin 1 (EXT1) and exostosin 2 (EXT2) genes. We asked two questions in our study: first, what is the anatomic burden of subjects with HME; second, is there a difference in anatomic burden in subjects with EXT 1 versus EXT 2. The anatomic burden experienced by HME patients was defined according to three domains: (1) lesion quality; (2) limb malalignment and deformity; and (3) limb segment lengths and percentile height. Seventy-nine subjects with HME were included in this study. Of these 79 phenotypes were completed. Forty-eight genotypes were confirmed leaving 48 complete genotype-phenotype profiles for analysis. Analysis of the coding and flanking intronic regions of EXT1 and EXT2 was performed in each patient by direct sequencing of PCR-amplified genomic DNA. All three domains of anatomic burden showed a wide range of presentation in the HME study sample. More lesions and greater tendency to flat bone occurrence was associated with EXT1. EXT1 patients were shorter. All limb segments tended to be shorter for EXT1 subjects. EXT1 subjects showed more anatomic burden with respect to lesion quality and height.

Treatment of idiopathic clubfoot utilizing botulinum A toxin: a new method and its short-term outcomes.

A pivotal point in most clubfoot management protocols is Achilles tendon lengthening or tenotomy to address hindfoot deformity. The effectiveness of botulinum A toxin (BTX-A) in attenuating the function of the triceps surae muscle complex as an alternative to tenotomy was investigated. Fifty-one patients with 73 idiopathic clubfeet were recruited. Outcome measures included surgical rate, Pirani clubfoot score, ankle dorsiflexion with knee in flexion and extension, and recurrences. Patients were divided according to age: group 1 (<30 days old) and group 2 (>30 days and <8 months old). Ankle dorsiflexion in knee flexion and extension remained above 20 degrees and 15 degrees, respectively, and Pirani scores below 0.5 following BTX-A injection for both groups. One of the 51 patients required limited posterior release and 9 patients required repeat manipulation and casting plus or minus BTX-A injection. The use of BTX-A as an adjunctive therapy in the noninvasive approach of manipulation and casting in idiopathic clubfoot is a safe and effective treatment.

A prospective, double-blind, randomized clinical trial comparing subacromial injection of betamethasone and xylocaine to xylocaine alone in chronic rotator cuff tendinosis.

BACKGROUND: Rotator cuff tendinosis is a common problem with significant health and economic effects. Nonoperative management includes the widespread use of subacromial steroid injections despite the lack of evidence of its efficacy. HYPOTHESIS: A subacromial injection of betamethasone will be more effective than xylocaine alone in improving the quality of life, impingement sign, and range of motion in patients who have chronic rotator cuff tendinosis or partial rotator cuff tears. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: Patients with rotator cuff tendinosis or partial cuff tear with symptoms longer than 6 months, with failure of 6 weeks of physical therapy and 2 weeks of nonsteroidal anti-inflammatory drugs, who were older than 30 years of age, and who showed >50% improvement with the Neer impingement test were stratified for Workplace Safety and Insurance Board status and previous injection. Outcome measures--the Western Ontario Rotator Cuff Index; American Shoulder and Elbow Surgeons standardized form; Disabilities of the Arm, Shoulder and Hand; active forward elevation; active internal rotation; active external rotation; and the Neer impingement sign--were assessed at 2, 6, 12, and 24 weeks after injection. The injection into the subacromial space contained either 5 mL of 2% xylocaine alone or 4 mL of 2% xylocaine and 1 mL (6 mg) of betamethasone in an opaque syringe. RESULTS: In 58 patients (betamethasone group, n = 30; xylocaine group, n = 28), the authors found no statistically significant difference between the 2 treatment groups for all outcomes and time intervals. The scores for the Western Ontario Rotator Cuff Index at 3 months were xylocaine = 45.4% +/- 13% and betamethasone = 56.3% +/- 17% (P = .13). At 6 months, the scores were xylocaine = 51% +/- 32% and betamethasone = 59% +/- 26% (P = .38). All other outcomes showed similar values. As well, similar results were found for 2 and 6 weeks after injection. Both groups showed improvement from baseline in all outcomes. CONCLUSIONS: With the numbers available for this study, the authors found betamethasone to be no more effective in improving the quality of life, range of motion, or impingement sign than xylocaine alone in patients with chronic rotator cuff tendinosis for all follow-up time intervals evaluated.