Magnetic resonance imaging of the anterior compartment of the lower leg is a biomarker for weakness, disability, and impaired gait in childhood Charcot-Marie-Tooth disease.

INTRODUCTION: Biomarkers of disease severity in Charcot-Marie-Tooth disease (CMT) are required to evaluate early responses to treatment. In this study we used magnetic resonance imaging (MRI) to evaluate the relationship between muscle volume and intramuscular fat accumulation with weakness, disability, and impaired gait in affected children and adolescents. METHODS: Fifty-five participants underwent MRI of the anterior compartment of the lower leg. Muscle and fat volumes were calculated. Strength was measured using hand-held dynamometry, disability using the CMT Pediatric Scale, and 3-dimensional gait analysis using an 8-camera Vicon Nexus motion capture system. RESULTS: Lower muscle volume was significantly associated with reduced dorsiflexion strength, increased disability, impaired gait profile score, and foot drop. Intramuscular fat accumulation was associated with reduced dorsiflexion strength and impaired gait profile score. DISCUSSION: The MRI protocol described was feasible, reliable, and sensitive to the magnitude of weakness, disability, and walking difficulties in children with CMT. Muscle Nerve 59:213-217, 2019.

Clinimetric properties of hip abduction strength measurements obtained using a handheld dynamometer in individuals with a lower extremity amputation.

INTRODUCTION: Suitable handheld dynamometer (HHD)-techniques to test hip abduction strength in individuals with a lower extremity amputation, irrespective of their amputation level are absent. The aim of this study was to optimise a HHD-technique and to test its reproducibility and validity. METHODS: This study involved three phases, in which two techniques were evaluated. Both HHD-techniques used a lever-arm of 22 centimetre. HHD-technique 1 used a break-technique. After obtaining within-session test-retest reproducibility (phase 1) we optimised the HHD-technique by adding a fixation-belt and using a make-technique (HHD-technique 2). We tested the within-session test-retest and inter-rater reproducibility (phase 2) and the validity (phase 3) of HHD-technique 2 using an isokinetic dynamometer. New cohorts of participants were recruited for each phase. RESULTS: Phase 1: we tested HHD-technique 1 in 26 participants with a lower extremity amputation. It was test-retest reproducible (ICC3.1agreement: 0.80-0.92, standard error of measurement (SEM): 3.1-4.4 Nm and smallest detectable change (SDC): 8.6-12.3 Nm). There were questions regarding the validity of the measurement, because the mean muscle torque of the residual limb and sound limb were similar, which is uncommon. Phase 2: reproducibility of HHD-technique 2 was tested in 44 participants with a lower extremity amputation. It was test-retest reproducible (ICC3.1agreement: 0.96-0.97, SEM: 3.9-4.7 Nm and SDC: 10.9-12.9 Nm) but not inter-rater reproducible despite having good reliability (ICC3.1agreement: 0.92, SEM: 6.9-7.6 Nm and SDC: 19.2-21.2 Nm). Systematic bias and bias related to the magnitude of the muscle torque was suspected. Phase 3: the concurrent validity was established in 30 healthy participants (r = 0.84). Systematic bias in measurement error was present, including a consistent overestimation of the muscle torque of 28% using the HHD. CONCLUSION: HHD-technique 2 is a test-retest reproducible and valid measuring technique The technique may be further optimised by the use of an external device to stabilise the HHD.

Safety and efficacy of progressive resistance exercise for Charcot-Marie-Tooth disease in children: a randomised, double-blind, sham-controlled trial.

BACKGROUND: Exercise is potentially therapeutic for neuromuscular disorders, but a risk of harm exists due to overwork weakness. We aimed to assess the safety and efficacy of progressive resistance exercise for foot dorsiflexion weakness in children with Charcot-Marie-Tooth disease. METHODS: We did this randomised, double-blind, sham-controlled trial across the Sydney Children's Hospitals Network (NSW, Australia). Children aged 6-17 years with Charcot-Marie-Tooth disease were eligible if they had foot dorsiflexion weakness (negative Z score based on age-matched and sex-matched normative reference values). We randomly allocated (1:1) children, with random block sizes of 4, 6, and 8 and stratification by age, to receive 6 months (three times per week on non-consecutive days; 72 sessions in total) of progressive resistance training (from 50% to 70% of the most recent one repetition maximum) or sham training (negligible non-progressed intensity), using an adjustable exercise cuff to exercise the dorsiflexors of each foot. The primary efficacy outcome was the between-group difference in dorsiflexion strength assessed by hand-held dynamometry (expressed as a Z score) from baseline to months 6, 12, and 24. The primary safety outcome was the between-group difference in muscle and intramuscular fat volume of the anterior compartment of the lower leg assessed by MRI (expressed as a scaled volume) from baseline to 6 months and 24 months. Participants, parents, outcome evaluators, and investigators other than the treatment team were masked to treatment assignment. Analysis was by intention to treat. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613000552785. FINDINGS: From Sept 2, 2013, to Dec 11, 2014, we randomly assigned 60 children to receive progressive resistance exercise (n=30) or sham training (n=30), and 55 (92%) children completed the trial. ANCOVA-adjusted Z score differences in dorsiflexion strength between groups were 0 (95% CI -0·37 to 0·42; p=0·91) at 6 months, 0·3 (-0·23 to 0·81; p=0·27) at 12 months, and 0·6 (95% CI 0·03 to 1·12; p=0·041) at 24 months. Scaled muscle and fat volume was comparable between groups at 6 months (ANCOVA-adjusted muscle volume difference 0, 95% CI -0·03 to 0·10, p=0·24; and fat volume difference 0, 95% CI -0·01 to 0·05, p=0·25) and 24 months (0, -0·08 to 0·12, p=0·67; and 0, -0·05 to 0·03, p=0·58). No serious adverse events were reported. INTERPRETATION: 6 months of targeted progressive resistance exercise attenuated long-term progression of dorsiflexion weakness without detrimental effect on muscle morphology or other signs of overwork weakness in paediatric patients with Charcot-Marie-Tooth disease. FUNDING: Muscular Dystrophy Association and Australian National Health and Medical Research Council.

1000 Norms Project: protocol of a cross-sectional study cataloging human variation.

BACKGROUND: Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or 'normal' values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. METHODS/DESIGN: In 2012 the 1000 Norms Project Consortium defined the concept of 'normal', established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype ('gene for speed'). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. DISCUSSION: This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures.

Systematic review of exercise for Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a slowly progressive hereditary degenerative disease and one of the most common neuromuscular disorders. Exercise may be beneficial to maintain strength and function for people with CMT, however, no comprehensive evaluation of the benefits and risks of exercise have been conducted. A systematic review was completed searching numerous electronic databases from earliest records to February 2015. Studies of any design including participants of any age with confirmed diagnosis of CMT that investigated the effects of exercise were eligible for inclusion. Of 13,301 articles identified following removal of duplicates, 11 articles including 9 unique studies met the criteria. Methodological quality of studies was moderate, sample sizes were small, and interventions and outcome measures used varied widely. Although the majority of the studies identified changes in one or more outcome measurements across exercise modalities, the majority were non-significant, possibly due to Type II errors. Significant effects described included improvements in strength, functional activities, and physiological adaptations following exercise. Despite many studies showing changes in strength and function following exercise, findings of this review should be met with caution due to the few studies available and moderate quality of evidence. Well-powered studies, harmonisation of outcome measures, and clearly described interventions across studies would improve the quality and comparability of the evidence base. The optimal exercise modality and intensity for people with CMT as well as the long-term safety of exercise remain unclear.

Diagnostic accuracy of clinical tests for ankle syndesmosis injury.

OBJECTIVE: Our aim was to investigate the diagnostic accuracy of the clinical presentation of ankle syndesmosis injury and four common clinical diagnostic tests. DESIGN: Cross-sectional diagnostic accuracy study. SETTING: 9 clinics in two Australian cities. PARTICIPANTS: 87 participants (78% male) with an ankle sprain injury presenting to participating clinics within 2 weeks of injury were enrolled. METHODS: Clinical presentation, dorsiflexion-external rotation stress test, dorsiflexion lunge with compression test, squeeze test and ankle syndesmosis ligament palpation were compared with MRI results (read by a blinded radiologist) as a reference standard. Tests were evaluated using diagnostic accuracy, sensitivity, specificity and likelihood ratios (LRs). A backwards stepwise Cox regression model determined the combined value of the clinical tests. RESULTS: The clinical presentation of an inability to perform a single leg hop had the highest sensitivity (89%) with a negative LR of 0.37 (95% CI 0.13 to 1.03). Specificity was highest for pain out of proportion to the apparent injury (79%) with a positive LR of 3.05(95% CI 1.68 to 5.55). Of the clinical tests, the squeeze test had the highest specificity (88%) with a positive LR of 2.15 (95% CI 0.86 to 5.39). Syndesmosis ligament tenderness (92%) and the dorsiflexion-external rotation stress test (71%) had the highest sensitivity values and negative LR of 0.28 (95% CI 0.09 to 0.89) and 0.46 (95% CI 0.27 to 0.79), respectively. Syndesmosis injury was four times more likely to be present with positive syndesmosis ligament tenderness (OR 4.04, p=0.048) or a positive dorsiflexion/external rotation stress test (OR 3.9, p=0.004). CONCLUSIONS: Although no single test is sufficiently accurate for diagnosis, we recommend a combination of sensitive and specific signs, symptoms and tests to confirm ankle syndesmosis involvement. An inability to hop, syndesmosis ligament tenderness and the dorsiflexion-external rotation stress test (sensitive) may be combined with pain out of proportion to injury and the squeeze test (specific).

Effectiveness of a single platelet-rich plasma injection to promote recovery in rugby players with ankle syndesmosis injury.

AIMS: To determine whether a single ultrasound-guided platelet-rich plasma (PRP) injection into the anterior inferior tibiofibular ligament (AITFL) reduces the time for rugby athletes to return to function and match play following MRI confirmed ankle syndesmosis injury. METHODS: Cohort controlled pilot study. 10 Rugby Union players were recruited during the 2014 season, and consented to receive a single autologous PRP injection into the AITFL within 14 days of MRI confirmed ankle syndesmosis injury. A historical control group included 11 comparable Rugby Union players between 2011 and 2013 who were treated conservatively with the same inclusion criteria and rehabilitation protocol as the intervention group. Participants followed a standardised rehabilitation protocol involving simple milestones for progression. Early functional tests were performed 2 weeks after the removal of the CAM (controlled ankle motion) boot. Time to return to play was recorded. Repeat functional testing occurred within 1 week of return to play. RESULTS: Groups were comparable in anthropometrics, playing position and MRI injury severity. Time to return to play was significantly less in the intervention group (p=0.048). Following return to play, athletes in the intervention group showed higher agility (p=0.002) and vertical jump (p=0.001). There was a lower level of fear avoidance associated with rugby in the intervention group (p=0.014). CONCLUSIONS: This pilot study shows that, following ankle syndesmosis injury, a single autologous PRP injection may accelerate safe and successful return to Rugby Union, with improved functional capacity and reduced fear avoidance. It demonstrates the feasibility of a randomised controlled trial to further assess this therapy. TRIAL REGISTRATION NUMBER: ANZCTRN12614000055606.

Design and reliability of a novel heel rise test measuring device for plantarflexion endurance.

BACKGROUND: Plantarflexion results from the combined action of the soleus and gastrocnemius muscles in the calf. The heel rise test is commonly used to test calf muscle endurance, function, and performance by a wide variety of professionals; however, no uniform description of the test is available. This paper aims to document the construction and reliability of a novel heel rise test device and measurement protocol that is suitable for the needs of most individuals. METHODS: This device was constructed from compact and lightweight materials and is fully adjustable, enabling the testing of a wide variety of individuals. It is easy to assemble and disassemble, ensuring that it is portable for use in different settings. FINDINGS: We tested reliability on 40 participants, finding excellent interrater reliability (ICC2,1 0.97, 95% CI: 0.94 to 0.98). Limits of agreement were less than two repetitions in 90% of cases and the Bland-Altman plot showed no bias. INTERPRETATION: We have designed a novel, standardized, simple, and reliable device and measurement protocol for the heel rise test which can be used by researchers and clinicians in a variety of settings.

Randomised controlled trial protocol of foot and ankle exercise for children with Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited neuromuscular diseases--there is no effective treatment. Foot and ankle weakness is a major problem for children with CMT, thus interventions that focus on maintaining and increasing strength may provide a solution. RESEARCH QUESTION: Is progressive resistance strength training an effective and safe intervention to improve strength, disability, gait and quality of life of children with CMT? PARTICIPANTS AND SETTING: Sixty children (6 to 17 years) with confirmed CMT who reside in Sydney, Australia will be recruited via referral from a paediatric neurologist, advertisements or the Australasian Paediatric CMT Registry. INTERVENTION: Participants will be randomised to undergo a 24-week, thrice weekly, high-intensity progressive resistance foot and ankle exercise programme (HIGH) or low-intensity foot and ankle exercise control programme (LOW). MEASUREMENTS: Out-come measures will be conducted at baseline, 6, 12 and 24 months.The primary outcome is isometric dorsiflexion strength measured by hand-held dynamometry. Secondary outcomes include disability, gait, quality of life, functional ankle instability and muscle volume and fatty infiltration of the anterior compartment of the lower leg (determined by MRI). PROCEDURE: Randomisation and allocation will be by a computer-generated algorithm, maintained and assigned by an external phone-based system, concealed to the investigators. Participants, parents and the outcome assessors will be blinded to group assignment. ANALYSIS: Treatment effect between groups is by intention-to-treat with a linear regression approach to analysis of covariance using 95% CI and p < 0.05. DISCUSSION: This study is the first randomised controlled trial to evaluate the risks and benefits of strengthening the affected muscles in children with CMT. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12613000552785.

Predictive factors for ankle syndesmosis injury in football players: a prospective study.

OBJECTIVES: Up to 25% of all ankle injuries involve the ankle syndesmosis and factors that increase risk have yet to be investigated prospectively. This study aimed to identify predictors of ankle syndesmosis injury in football players. DESIGN: A prospective study. METHODS: Rugby Union and Australian Football League players were recruited during 2010. Rugby League and different Rugby Union players were recruited during 2011. Baseline data collection included: age, body size, flexibility, strength and balance. Bivariate correlations were performed between all predictors. Variables with r ≥ 0.7 had only one variable entered in further analysis. Remaining predictor variables were analysed for association with the presence/absence of ankle syndesmosis injury. Variables with non-significant association with injury (p>0.2) were included in a backward step-wise Cox regression model. RESULTS: 202 male participants aged 21 ± 3.3 years (mean ± SD) were recruited of whom 12 (5.9%) sustained an ankle syndesmosis injury. The overall incidence rate was 0.59/1000 h sport participation for Rugby Union and Rugby League. Australian Football League training data was not available. No significant predictors were identified; however, participants who sustained an injury during the season performed a higher vertical jump (63.6 ± 8.2 cm) and greater Star Excursion Balance Test reach (80.5 ± 5.3 cm), than participants who did not sustain an injury: 59.1 ± 7.8 cm for Vertical Jump and 77.9 ± 6.1 cm for Star Excursion Balance Test. This was normalised for height. CONCLUSIONS: Variables such as age, body size, foot posture, flexibility and muscle strength did not increase risk of ankle syndesmosis injury. Jump height and balance performance may play a role in predicting ankle syndesmosis sprains.

Prognosis of ankle syndesmosis injury.

PURPOSE: Ankle syndesmosis injury has been associated with persistent pain and prolonged recovery; however, no predictors of prolonged recovery have been identified. The aims of this study were to establish prognosis for ankle syndesmosis injury compared with a lateral ankle sprain and to explore factors associated with prolonged recovery. METHODS: Participants (n = 63) age 21 ± 3.2 yr, with acute ankle ligament injuries (diagnosed through magnetic resonance imaging), were recruited from 10 sport clubs and sports medicine and physiotherapy clinics in two Australian cities. Follow-up was until full recovery and with preinjury activity level. Time to return to play was compared between injury types using Kaplan-Meier survival curves. Secondary analysis investigated putative factors that increased risk of prolonged recovery. For this analysis, participants unrecovered at 2 wk completed the following: Fear Avoidance Beliefs Questionnaire (FABQ); Star Excursion Balance Test, weight-bearing lunge, and vertical jump (VJ). These variables were correlated with time to recovery using bivariate Pearson's r correlation coefficient. RESULTS: The median recovery time for conservatively treated ankle syndesmosis injury was 62 and 15 d for lateral sprain. The sport-specific subscale scores of the FABQ were significantly higher (P = 0.017) for the ankle syndesmosis group, whereas vertical jump height was lower for this group, (P = 0.052). No baseline variables were strong predictors (r ≥ 0.6) of recovery. Moderate correlations were found for VJ (r = -0.471, P = 0.004) and the sport-specific subscale of the FABQ (r = 0.463, P = 0.004). CONCLUSIONS: Conservatively treated ankle syndesmosis injuries took four times longer to recover than lateral ankle sprain. Tests such as VJ and FABQ may identify individuals at risk of prolonged recovery and allow health professionals to determine realistic and appropriate time to recovery.

Diagnostic accuracy of clinical tests for diagnosis of ankle syndesmosis injury: a systematic review.

OBJECTIVES: To determine the value of clinical tests for accurate diagnosis of ankle syndesmosis injury. DESIGN: Systematic review. DATA SOURCES: An electronic database search was conducted (to 6 August 2012) of databases such as: MEDLINE, CINAHL, EMBASE, PubMed and Cochrane Databases. References from identified articles were examined and seven authors of eligible studies were contacted for additional information. STUDY SELECTION: Studies of any design, without language restriction, were included; however, systematic reviews were excluded. Eligible studies included participants with a suspected ankle syndesmosis injury but without fracture. Reliability studies compared one or more clinical tests and studies of test accuracy compared the clinical test with a reference standard. RESULTS: The database search resulted in 114 full text articles which were assessed for eligibility. Three studies were included in the review and raw data of these studies were retrieved after contacting the authors. Eight clinical diagnostic tests were investigated; palpation of the tibiofibular ligaments, external rotation stress test, squeeze, Cotton, fibula translation, dorsiflexion range of motion (ROM) and anterior drawer tests. Two studies investigated diagnostic accuracy and both investigated the squeeze test by with conflicting results. Likelihood ratios (LR) ranging from LR+1.50 to LR-1.50 were found for other tests. High intra-rater reliability was found for the squeeze, Cotton, dorsiflexion ROM and external rotation tests (83-100% close agreement). Inter-rater reliability was good for the external rotation test (ICC2,1>0.70). Fair-to-poor reliability was found for other tests. CONCLUSIONS: This is the first systematic review to investigate the reliability and accuracy of clinical tests for the diagnosis of ankle syndesmosis injury. Few studies were identified and our findings show that clinicians cannot rely on a single test to identify ankle syndesmosis injury with certainty. Additional diagnostic tests, such as MRI, should be considered before making a final diagnosis of syndesmosis injury.