Calf Muscle Volume Research Articles

FGF‐Mimicking Triphen[3]arene Peptide Self‐Assembly to Accelerate Muscle Regeneration and Repair

AbstractBioactive peptides play crucial roles in the biomedicine fields including cancer therapy and regenerative medicine due to their favorable biocompatibility, low immunogenicity, and excellent biological activity. However, their low stability greatly limits their clinical application. Herein, a novel bioactive peptide delivery strategy is reported that utilizes triphen[3]arene polyvalent‐conjugated bioactive peptides to induce self‐assembly and form nanofibers to enhance the in vivo stability and bioactivity of bioactive peptides. Specifically, a water‐soluble triphen[3]arene (WTP3(YRSRK)6, Comp. 2) containing six FGF‐mimicking peptides, primarily comprising two components: triphen[3]arene serves as a skeleton molecule and an assembly motif with multiple customizable sites, while YRSRK is a pentapeptide with fibroblast growth factor 2 (FGF‐2) biological activity. Despite the presence of the inhibitor dexamethasone (Dex), Comp. 2 continued to enhance cell proliferation by 15% and rescued 17% of cells from apoptosis. The administration of Comp. 2 resulted in improved restoration of skeletal muscle atrophy and functional damage in mice. The mean grip strength increased by 42%, and the calf muscle volume increased by 17%. This innovative approach of utilizing macrocycle polyvalent conjugated bioactive peptides offers a universal method for enabling bioactive peptides to produce sustained and efficient biological effects, potentially advancing the development of promising peptide‐based nanomedicines.

Vigeo Promotes Myotube Differentiation and Protects Dexamethasone-Induced Skeletal Muscle Atrophy via Regulating the Protein Degradation, AKT/mTOR, and AMPK/Sirt-1/PGC1α Signaling Pathway In Vitro and In Vivo.

Sarcopenia, a condition caused by an imbalance between muscle growth and loss, can severely affect the quality of life of elderly patients with metabolic, inflammatory, and cancer diseases. Vigeo, a nuruk-fermented extract of three plants (Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK)) has been reported to have anti-osteoporotic effects. However, evidence of the effects of Vigeo on muscle atrophy is not available. Here, in the in vivo model of dexamethasone (Dex)-induced muscle atrophy, Vigeo treatment significantly reversed Dex-induced decreases in calf muscle volume, gastrocnemius (GA) muscle weight, and histological cross-section area. In addition, in mRNA and protein analyses isolated from GA muscle, we observed that Vigeo significantly protected against Dex-induced mouse muscle atrophy by inhibiting protein degradation regulated by atrogin and MuRF-1. Moreover, we demonstrated that Vigeo significantly promoted C2C12 cell line differentiation, as evidenced by the increased width and length of myotubes, and the increased number of fused myotubes with three or more nuclei. Vigeo alleviated the formation of myotubes compared to the control group. Vigeo also significantly increased the mRNA and protein expression of myosin heavy chain (MyHC), MyoD, and myogenin compared to that in the control. Vigeo treatment significantly reduced the mRNA and protein expression of muscle degradation markers atrogin-1 and muscle RING Finger 1 (MuRF-1) in the C2C12 cell line in vitro. Vigeo also activated the AMP-activated protein kinase (AMPK)/silent information regulator 1 (Sirt-1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) mitochondrial biogenesis pathway and the Akt/mTOR protein synthesis signaling pathway in Dex-induced myotube atrophy. These findings suggest that Vigeo may have protective effects against Dex-induced muscle atrophy. Therefore, we propose Vigeo as a supplement or potential therapeutic agent to prevent or treat sarcopenia accompanied by muscle atrophy and degeneration.

GCPII Inhibition in Macrophages Delays Age-related Muscle Atrophy in Mice

Age-related loss of muscle mass and strength (Sarcopenia) significantly impairs quality of life in the elderly, yet lacks effective treatments. We previously demonstrated that inhibition of GCPII delayed muscle function decline and neuromuscular junction (NMJ) denervation in an amyotrophic lateral sclerosis (ALS) animal model. As sarcopenia shares NMJ deterioration with ALS, we tested the potent GCPII inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) in aging mice, and found that it also preserved muscle function and NMJ integrity. By immunofluorescent staining, we demonstrated that aged mice muscles were associated with GCPII-positive infiltrating macrophages. We next developed a macrophage-targeting GCPII inhibitor delivery system by covalently attaching 2-PMPA to 4th-generation polyamidoamine (G4-PAMAM) dendrimers (D-2-PMPA). The D-2-PMPA was found to inhibit GCPII with IC50= 3.50±0.05 nM. Aged mice muscle showed increased GCPII activity specifically in CD11b+ enriched macrophage cells (138.6±3.0 vs. 336.6±52.9; p<0.05) but not in CD11b− cells. Systemic D-2-PMPA therapy (20 mg/kg 2-PMPA equivalent; IP 3 × /week) completely inhibited the elevated GCPII activity (336.5±52.8 vs. 21.8±9.2 fmol/mg/h; p<0.001). 5-months of D-2-PMPA therapy initiated with 15-month-old mice significantly preserved calf muscle volume (95.0±0.8% vs. 90.4±0.7%; p <0.001), enhanced isometric force (230.2±13.3 vs. 184.0±9.0 mN, female p<0.05; 257.3±21.0 vs. 189.7±19.3 mN, male p<0.05), improved grip strength (96.1±1.6 vs. 90.2±2.2 % of maximum p<0.001) and increased rotarod latency (119.0±6.6 vs. 93.5±9.3 s, female p<0.05; 104.5±5.2 vs. 79.3±4.2 s, male p<0.001). Age-related decline of nerve signal conductivity to muscles was also delayed with D-2-PMPA as observed by improved compound muscle action potential (CMAP) latency (1.28±0.02 vs. 1.38±0.04 ms; p< 0.05) and amplitude (15.2±0.5 vs. 1.27±0.6 mV; p<0.01). Furthermore, NMJ integrity was preserved with treatment as demonstrated by single fiber jitter (5.4±0.3 vs. 7.5±0.5 μs; p<0.01). Overall, our current results support that excessive GCPII activity in muscle macrophages is associated with age-related muscle atrophy, which is improved by GCPII inhibition. This study highlights GCPII inhibition in macrophages as a new therapeutic approach to delay sarcopenia. R01AG078181, R01AG068130, R01NS093416. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Whey Peptide Alleviates Muscle Atrophy by Strongly Regulating Myocyte Differentiation in Mice.

Background and Objectives: Muscle atrophy occurs when protein degradation exceeds protein synthesis, resulting in imbalanced protein homeostasis, compromised muscle contraction, and a reduction in muscle mass. The incidence of muscle atrophy is increasingly recognized as a significant worldwide public health problem. The aim of the current study was to evaluate the effect of whey peptide (WP) on muscle atrophy induced by dexamethasone (DEX) in mice. Materials and Methods: C57BL/6 mice were divided into six groups, each consisting of nine individuals. WPs were orally administered to C57BL/6 mice for 6 weeks. DEX was administered for 5-6 weeks to induce muscle atrophy (intraperitoneal injection, i.p.). Results: Microcomputer tomography (CT) analysis confirmed that WP significantly increased calf muscle volume and surface area in mice with DEX-induced muscle atrophy, as evidenced by tissue staining. Furthermore, it increased the area of muscle fibers and facilitated greater collagen deposition. Moreover, WP significantly decreased the levels of serum biomarkers associated with muscle damage, kidney function, and inflammatory cytokines. WP increased p-mTOR and p-p70S6K levels through the IGF-1/PI3K/Akt pathway, while concurrently decreasing protein catabolism via the FOXO pathway. Furthermore, the expression of proteins associated with myocyte differentiation increased noticeably. Conclusions: These results confirm that WP reduces muscle atrophy by regulating muscle protein homeostasis. Additionally, it is believed that it helps to relieve muscle atrophy by regulating the expression of myocyte differentiation factors. Therefore, we propose that WP plays a significant role in preventing and treating muscle wasting by functioning as a supplement to counteract muscle atrophy.

Quantitative Assessment of Calf Muscle Volume, Strength, and Quality After Achilles Tendon Rupture Repair: A 1-Year Prospective Follow-up Study

Background: A number of studies have reported that calf muscle atrophy is a common long-term problem after Achilles tendon repair; however, there is still a lack of data concerning early postoperative morphological changes in the calf muscle after surgery. Purpose: To investigate changes over time in calf muscle volume and fatty degeneration during 1 year after Achilles tendon repair. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective 1-year serial magnetic resonance imaging study was carried out with 20 patients who underwent tendon repair for unilateral acute Achilles tendon rupture. The magnetic resonance imaging assessment in addition to clinical and functional evaluations was performed at 1, 3, 6, and 12 months after surgery. The muscle volume of the medial and lateral gastrocnemius, soleus, and flexor hallucis longus (FHL) and fatty degeneration of the medial and lateral gastrocnemius and soleus were measured for the calf muscles, and the relative volume and fatty degeneration changes in the affected leg compared with the healthy contralateral leg were calculated as a percentage ([injured/healthy control] × 100) to assess structural changes over time. Results: Muscle volumes of the medial gastrocnemius, lateral gastrocnemius, soleus, and FHL were 92.3%, 92.8%, 84.6%, and 95.9% at 12 months after surgery, respectively. Medial and lateral gastrocnemius and FHL muscle volumes improved over time and recovered to almost equal to that of the healthy side at 12 months after surgery. The soleus muscle volume did not recover significantly over time and was statistically significantly smaller than that of the healthy side at 12 months (P = .029). Fatty degeneration rates of the medial gastrocnemius, lateral gastrocnemius, and soleus were 118.2%, 113.9% and 121.1% at 12 months after surgery, respectively. Fatty degeneration of the medial and lateral gastrocnemius did not change significantly, but there was a statistically significant increase in fatty degeneration of the soleus over time (P < .001). Conclusion: Within the triceps surae muscle, the soleus was the most negatively affected by injury and repair for both muscle volume and fatty degeneration. Postoperative management to recover the soleus muscle function before a return to sporting activities should be considered in the future.

Effect of the Copenhagen Achilles Rupture Treatment Algorithm (CARTA) on Calf Muscle Volume and Tendon Elongation After Acute Achilles Tendon Rupture: A Predefined Secondary Analysis of the First 60 Patients in a Randomized Controlled Trial.

Surgical treatment of acute Achilles tendon rupture (ATR) lowers the risk of rerupture and may reduce calf atrophy and elongation of the Achilles tendon. The Copenhagen Achilles Rupture Treatment Algorithm (CARTA) was developed to provide individualized treatment selection based on ultrasonographic evaluation of the rupture. In a randomized setup, the present study aimed to investigate whether treatment selection using the CARTA could reduce atrophy and tendon elongation compared with (1) patients treated surgically and (2) patients treated nonsurgically. Randomized controlled trial; Level of evidence, 2. A total of 60 patients with an acute ATR were randomly assigned to receive treatment based on the CARTA (intervention), surgical treatment (control), or nonsurgical treatment (control) in a 1 to 1 to 1 ratio. After 1 year, magnetic resonance imaging of both calves was performed, and muscle volume and Achilles tendon length were measured. Results were presented as the ratio between the affected and the unaffected limbs (ie, limb symmetry index; %). A total of 156 patients were assessed for eligibility, 60 patients were randomized, and 54 patients provided data for the study-19 patients received treatment based on the CARTA (intervention group), 17 patients received nonsurgical treatment (control), and 18 patients received surgical treatment (control). No statistically significant differences were found between the intervention group and the 2 control groups regarding muscle volume and tendon length. No statistically significant differences were found between patients treated surgically and patients treated nonsurgically. Comparison between the affected and the unaffected limb showed statistically significant muscle atrophy (24%-30%) and tendon elongation (soleus, 59%-76%; gastrocnemius, 8%-14%) in the affected limb in all 3 groups. Individualized treatment of acute ATR using an ultrasonographic selection algorithm did not reduce calf muscle atrophy or tendon elongation when compared with surgical and nonsurgical treatment. Surgical treatment did not reduce calf muscle atrophy or tendon elongation compared with nonsurgical treatment.

One-Year Serial MRI Study of the Calf Muscle Volume and Fatty Degeneration after Achilles Tendon Repair

One-Year Serial MRI Study of the Calf Muscle Volume and Fatty Degeneration after Achilles Tendon Repair

3-D Ultrasonographic Quantification of Hand and Calf Muscle Volume: Statistical Shape Modeling Approach.

Accurate acquisition and segmentation of muscles are essential in 3-D freehand ultrasonography (US) to estimate in vivo muscle volume, but the source of segmentation inaccuracy in shape variation has never been the focus. This study was aimed at investigating reliability of 3-D US in the acquisition and segmentation for muscle volume of two muscles of different sizes and in identifying a primary source of measurement difference. The lateral gastrocnemius and flexor pollicis brevis of 12 healthy adults were assessed using freehand 3-D US scans. The motion-tracking data of the probe were synchronized with the B-mode ultrasound scan to reconstruct 3-D muscle volume. Statistical shape modeling was used to provide a spatial segmentation volume difference that further explains the variation around segmentation repeatability. The absolute difference of the flexor pollicis brevis was 3.5 percentage points greater than that for the lateral gastrocnemius. The highest measurement differences were observed when for inter-acquirer analysis. Statistical shape modeling revealed that the primary segmentation volume differences were at the muscle ends and edges, where the muscle interfaces with the surrounding muscles. Three-dimensional US is a reliable tool in the clinical setting, but care must be taken to ensure that acquisition and segmentation are consistent, particularly in a small muscle that interfaces with tendons and other soft tissues.

P062 31P MRS and MRI phenotyping of muscle metabolic quality in IBD fatigue

Abstract Background Fatigue perception and exercise intolerance are common in inflammatory bowel disease (IBD). The mechanisms are unknown, although physical deconditioning is greater in fatigued relative to non-fatigued patients, suggesting an aetiological role for deconditioning. To assess peripheral muscle quality in Crohn’s disease (CD), we quantified the time-course of muscle phosphocreatine (PCr) recovery, which is wholly mitochondrial dependent, following ischaemic high-intensity exercise in fatigued CD and HV. Methods Participant body mass and regional body composition was assessed by DEXA. All MR data was collected using a 3T Philips Achieva scanner and a 14cm 31P coil on the medial gastrocnemius muscle. 1H mDIXON scans were acquired to image the calf prior to ischaemic plantar flexion exercise at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using jMRUI Beta 6.0 using the AMARES function with prior knowledge. Cytosolic pH was estimated using the chemical shift difference between Pi and PCr peaks. Post exercise PCr recovery was quantified after reinstating limb blood flow. PCr recovery was expressed relative to baseline (non-ischaemic) signal amplitude and fit to a mono-exponential function in GraphPad prism. (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t)) where t is the time from the start of non-ischaemic recovery, PCrinitial and PCrend is the PCr signal at the initial and end of recovery phases. An FSL and Matlab pipeline was used to obtain calf muscle volume and fat fraction from 1H mDIXON images. Results 13 quiescent CD patients (7 female, HBI 1±2, CRP &amp;lt;5) and 9 HVs (4 female) were matched for age (P = 0.986) and BMI (P = 0.845). General fatigue score was greater in CD (13 ± 4) relative to HV (8 ± 3) (t19=3.08, P = 0.006) (Table 1.) End-exercise muscle PCr depletion (%) (85.25 ± 10.12 vs 83.28 ± 7.8%, P = 0.639) and estimated end-exercise muscle pH (6.6 ± 0.2 vs 6.5 ± 0.2, P = 0.320) was consistent between HV and CD. The mean rate constant of PCr resynthesis (kPCr min-1) in CD (0.76 ± 0.23) was significantly less (t20 = 2.6, P = 0.016) than HV (1.03 ± 0.23). PCr recovery curves were well described using a mono-exponential function in CD (R2=0.98 ± 0.01, R2value) and HV (R2=0.96 ± 0.03) (Table 3). Conclusion The PCr resynthesis rate following intensity matched ischemic exercise was less in fatigued CD patients relative to HV. This points to peripheral muscle deconditioning and associated loss of mitochondrial mass as a driver of exercise intolerance in IBD. This may be amenable to exercise training intervention.

Effect of Blood Flow Restriction Therapy Following Achilles Rupture and Repair: A Randomized Controlled Trial

Category:Sports; OtherIntroduction/Purpose:Blood flow restriction (BFR) therapy involves the use of a tourniquet to partially occlude blood flow to the affected limb, creating an anaerobic environment during exercise. This is thought to stimulate growth and recovery by increasing the body's anabolic response. BFR therapy can be initiated shortly after surgery since it allows for significant muscle activation with limited load bearing. To date, no existing study has evaluated the effect of using BFR therapy for recovery following Achilles tendon rupture and repair, after which patients often experience significant losses in calf strength and girth. This is a randomized controlled trial designed to study whether BFR can minimize loss of calf strength and muscle volume after Achilles rupture compared to a conventional physical therapy protocol.Methods:Patients presenting with an acute Achilles tendon rupture were randomized into the BFR or control group. Patients in the control group performed at-home exercises and began in-person physical therapy at 6 weeks postoperatively, as is the standard of care in our practice. The exercises were standardized across groups with BFR the isolated variable. The primary outcome studied was ankle plantarflexion strength as measured during isokinetic strength testing 3 months after surgical repair. We also tested knee strength during flexion and extension. All strength tests were performed at two rotational speeds. Calf atrophy was assessed by measuring the circumference of both calves 15 cm below the joint line at the time of operation and at 2 weeks, 6 weeks, 3 months, and 6 months postoperatively. Finally, Patient-Reported Outcome Measurement Information System (PROMIS) scores were collected pre- and postoperatively.Results:The study enrolled 43 patients, 24 of whom were assigned to the BFR group. 30 patients completed strength testing at 3 months and 26 at 6 months. Calf measurements through 3 months were completed for 39 patients and 6 month measurements were completed for 32 patients. Results for ankle plantarflexion strength at 3 months are displayed in Table 1, showing that patients in the BFR group demonstrated greater absolute strength in the operative calf compared to the control group, but no significant advantage in strength relative to the uninvolved calf. We failed to detect a significant difference in strength between groups for ankle dorsiflexion, knee extension, or knee flexion. Our model of calf circumference over time showed that BFR had a positive but insignificant correlation to calf circumference (p = 0.59). The only factors that demonstrated a significant (p<0.05) positive relationship to calf circumference were male sex and BMI.Conclusion:We have observed significant advantages in the BFR group when analyzing absolute calf strength metrics when compared to a randomized control group. This indicates that, when used during rehabilitation following Achilles rupture, BFR therapy may increase the strength of the operative leg and may facilitate recovery and outcome.

Branched-Chain Amino Acid Supplementation Does Not Preserve Lean Mass or Affect Metabolic Profile in Adults with Overweight or Obesity in a Randomized Controlled Weight Loss Intervention

Branched-chain amino acid (BCAA) supplementation has been shown to increase muscle mass or prevent muscle loss during weight loss. We aimed to investigate the effects of a BCAA-supplemented hypocaloric diet on lean mass preservation and insulin sensitivity. A total of 132 Chinese adults (63 men and 69 women aged 21-45 y, BMI 25-36kg/m2) were block randomly assigned by gender and BMI into 3 hypocaloric diet (deficit of 500kcal/d) groups: standard-protein (14%) with placebo (control, CT) or BCAA supplements at 0.1g·kg-1 body weight·d-1 (BCAA) or high-protein (27%) with placebo (HP). The subjects underwent 16 wk of dietary intervention with provision of meals and supplements, followed by 8 wk of weight maintenance with provision of supplements only. One-way ANOVA analysis was conducted to analyze the primary (lean mass and insulin sensitivity) and secondary outcomes (anthropometric and metabolic parameters) among the 3 groups. Paired t-test was used to analyze the change in each group. The 3 groups demonstrated similar significant reductions in body weight (7.97%), fat mass (13.8%), and waist circumference (7.27%) after 16 wk of energy deficit. Lean mass loss in BCAA (4.39%) tended to be lower than in CT (5.39%) and higher compared with HP (3.67%) (P=0.06). Calf muscle volume increased 3.4% in BCAA and intramyocellular lipids (IMCLs) decreased in BCAA (17%) and HP (18%) (P<0.05) over 16 wk. During the 8 wk weight maintenance period, lean mass gain in BCAA (1.03%) tended to be lower compared with CT (1.58%) and higher than in HP (-0.002%) (P=0.04). Lean mass gain differed significantly between CT and HP (P=0.03). Insulin sensitivity and metabolic profiles did not differ among the groups throughout the study period. BCAA supplementation does not preserve lean mass or affect insulin sensitivity in overweight and obese adults during weight loss. A higher protein diet may be more advantageous for lean mass preservation.

Water Extract of Lotus Leaf Alleviates Dexamethasone-Induced Muscle Atrophy via Regulating Protein Metabolism-Related Pathways in Mice.

Muscle atrophy is an abnormal condition characterized by loss of skeletal muscle mass and function and is primarily caused by injury, malnutrition, various diseases, and aging. Leaf of lotus (Nelumbo nucifera Gaertn), which has been used for medicinal purposes, contains various active ingredients, including polyphenols, and is reported to exert an antioxidant effect. In this study, we investigated the effect of water extract of lotus leaf (LL) on muscle atrophy and the underlying molecular mechanisms of action. Amounts of 100, 200, or 300 mg/kg/day LL were administered to dexamethasone (DEX)-induced muscle atrophy mice for 4 weeks. Micro-computed tomography (CT) analysis revealed that the intake of LL significantly increased calf muscle volume, surface area, and density in DEX-induced muscle atrophy mice. Administration of LL recovered moving distance, grip strength, ATP production, and body weight, which were decreased by DEX. In addition, muscle damage caused by DEX was also improved by LL. LL reduced the protein catabolic pathway by suppressing gene expression of muscle atrophy F-Box (MAFbx; atrogin-1), muscle RING finger 1 (MuRF1), and forkhead box O (FoxO)3a, as well as phosphorylation of AMP-activated kinase (AMPK). The AKT-mammalian target of the rapamycin (mTOR) signal pathway, which is important for muscle protein synthesis, was increased in LL-administered groups. The HPLC analysis and pharmacological test revealed that quercetin 3-O-beta-glucuronide (Q3G) is a major active component in LL. Thus, Q3G decreased the gene expression of atrogin-1 and MuRF1 and phosphorylation of AMPK. This compound also increased phosphorylation levels of mTOR and its upstream enzyme AKT in DEX-treated C2C12 cells. We identified that LL improves muscle wasting through regulation of muscle protein metabolism in DEX-induced muscle atrophy mice. Q3G is predicted to be one of the major active phenolic components in LL. Therefore, we propose LL as a supplement or therapeutic agent to prevent or treat muscle wasting, such as sarcopenia.

Validity and reliability of a freehand 3D ultrasound system for the determination of triceps surae muscle volume in children with cerebral palsy.

This study assessed the validity, intra-rater and inter-rater reliability of segmentation of invivo medial gastrocnemius (MG), lateral gastrocnemius (LG) and soleus (SOL) muscle volume measurement using a single sweep freehand 3D ultrasound (3DUS) in children with cerebral palsy (CP). The MG, LG and SOL of both limbs of 18 children with CP (age 8years 4months±1year 10months, 11 males, unilateral CP=9, bilateral CP=9, Gross Motor Functional Classification System I=11, II=7) were scanned using freehand 3DUS and magnetic resonance imaging (MRI). All freehand 3DUS and MRI images were segmented and volumes rendered by two raters. Validity was assessed using limits of agreement method. Intra-rater and inter-rater reliability was assessed using intra-class correlation (ICC), coefficient of variance (CV) and minimal detectable change (MDC). Freehand 3DUS overestimated muscle volume of the MG and LG by <0.3mL (1%) and underestimated SOL by <1.3mL (1.5%) compared with MRI. ICCs for intra-rater reliability of the segmentation process for the freehand 3DUS system and MRI for muscle volume were >0.98 and 0.99, respectively, for all muscles. ICCs for inter-rater reliability of the segmentation process for freehand 3DUS and MRI volumes were >0.96 and 0.98, respectively, for all muscles. MDCs for single rater freehand 3DUS and MRI were <4.0mL (14%) and 3.2mL (11%), respectively, in all muscles. Freehand 3DUS is a valid and reliable method for the measurement of lower leg muscle volume that can be measured with a single sweep in children with CP invivo. It can be used as an alternative to MRI for the detection of clinically relevant changes in calf muscle volume as the result of growth and interventions.

Calf Muscle Atrophy and Achilles Tendon Elongation After Acute Achilles Tendon Rupture

Calf muscle atrophy and Achilles tendon elongation seems to be the principal structural explanations for calf muscle strength deficit at short and long term follow up and also explain surgery related greater plantar flexion strength compared conservative treatment after acute Achilles tendon rupture. Despite good clinical results of surgery and conservative treatment for acute Achilles tendon rupture (ATR), surgery may result in 10-18% better calf muscle strength. However, 12-18% strength deficit compared to the unaffected leg usually remains even in long-term follow up. We aimed to assess whether Achilles tendon elongation and calf muscle volume changes could explain the difference in calf muscle strength between conservative treatment and surgery and side-to side strength deficit of calf muscle for patients with operatively treated ATR in long term follow-up. Group 1; 60 patients with acute ATRs were randomized to surgery or conservative treatment. Conservative treatment and post operative treatments were identical; cast immobilization for one week, followed by functional orthosis for 6 weeks, which allowed full weight bearing after week 1 and active plantar flexion after week 5 post injury. At 18 months, MRI was used to evaluate the volume of calf muscles and the length of the affected Achilles tendon. Group 2; 60 patients with acute ATRs were randomized to simple end-to-end repair or augmented repair, both with postoperative bracing allowing free active plantar flexion for 3 weeks. After follow-up of =13 years, 55 patients (28 non-augmented, 27 augmented) were re-examined and MRI was used to evaluate the volume of calf muscles, and the length of the Achilles tendons for both legs. Group 1; At 18 months, the mean differences between healthy and affected soleus muscle volumes were 83.2 cm3 (17.7%) after surgery and 115.5 cm3 (24.8%) after conservative treatments (difference between means: 33.1 cm3, 95% CI: 1.3 to 65.0, p = 0.042). Achilles tendon length from calcaneal insertion to soleus muscle MTJ for affected leg was 18.7mm longer for conservative treatment compared operative treatment (95% CI: 8.5 to 28.8, p<0.001). All patients in group 1 suffered up to 21% calf muscle atrophy for affected leg, which was compensated by 11% hypertrophy in flexor hallucis longus (FHL) (p=0.001 in all). Group 2; At 14 years patients in group 2 suffered up to 12% calf muscle atrophy for affected leg which was compensated by 5.4% hypertrophy in flexor halluces longus (FHL) (p=0.001 in all). Achilles tendon length from calcaneal insertion to medial gastrocnemius muscle MTJ for affected leg was 12.1mm longer compared healthy tendon (95% CI, 8.6 to 15.6, p<0.001). At 18 months ATR conservative treatment with a functional rehabilitation protocol resulted in greater soleus muscle atrophy and 19 mm longer calcaneus to soleus MTJ length to surgical treatment. At 14 years ATR operative treatment resulted up to 12% calf muscle atrophy and 12mm longer Achilles tendon of the affected leg. Calf muscle atrophy in the affected leg was compensated with hypertrophy of the FHL both in short and long term follow-up. Achilles tendon elongation may be the principal structural explanation of calf muscle atrophy and muscle strength deficit at short and long term follow-up after ATR.

Tendon Length, Calf Muscle Atrophy, and Strength Deficit After Acute Achilles Tendon Rupture: Long-Term Follow-up of Patients in a Previous Study.

In this prospective study, we used magnetic resonance imaging (MRI) to assess long-term Achilles tendon length, calf muscle volume, and muscle fatty degeneration after surgery for acute Achilles tendon rupture. From 1998 to 2001, 60 patients at our center underwent surgery for acute Achilles tendon rupture followed by early functional postoperative rehabilitation. Fifty-five patients were reexamined after a minimum duration of follow-up of 13 years (mean, 14 years), and 52 of them were included in the present study. Outcome measures included Achilles tendon length, calf muscle volume, and fatty degeneration measured with MRI of both the affected and the uninjured leg. The isokinetic plantar flexion strength of both calves was measured and was correlated with the structural findings. The Achilles tendon was, on average, 12 mm (95% confidence interval [CI] = 8.6 to 15.6 mm; p < 0.001) longer (6% longer) in the affected leg than in the uninjured leg. The mean volumes of the soleus and medial and lateral gastrocnemius muscles were 63 cm (13%; p < 0.001), 30 cm (13%; p < 0.001), and 16 cm (11%; p < 0.001) lower in the affected leg than in the uninjured leg, whereas the mean volume of the flexor hallucis longus (FHL) was 5 cm (5%; p = 0.002) greater in the affected leg, indicating FHL compensatory hypertrophy. The median plantar flexion strength for the whole range of motion ranged from 12% to 18% less than that on the uninjured side. Finally, the side-to-side difference in Achilles tendon length correlated substantially with the strength deficit (ρ = 0.51, p < 0.001) and with medial gastrocnemius (ρ = 0.46, p = 0.001) and soleus (ρ = 0.42, p = 0.002) muscle atrophy. Increased Achilles tendon length is associated with smaller calf muscle volumes and persistent plantar flexion strength deficits after surgical repair of Achilles tendon rupture. Strength deficits and muscle volume deficits are partly compensated for by FHL hypertrophy, but 11% to 13% deficits in soleus and gastrocnemius muscle volumes and 12% to 18% deficits in plantar flexion strength persist even after long-term follow-up. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Severe Equinus Deformity After Radiofrequency-Induced Calf Muscle Reduction

Radiofrequency-induced calf muscle volume reduction is a commonly used method for cosmetic shaping of the lower leg contour. Functional disabilities associated with the use of the radiofrequency (RF) technique, with this procedure targeting the normal gastrocnemius muscle, still have not been reported. However, the authors have experienced several severe ankle equinus cases after RF-induced calf muscle volume reduction. This study retrospectively reviewed 19 calves of 12 patients who showed more than 20° of fixed equinus even though they underwent physical therapy for more than 6months. All were women with a mean age of 32years (range, 23-41years). Of the 12 patients, 7 were bilateral. All the patients received surgical Achilles lengthening for deformity correction. To evaluate the clinical outcome, serial ankle dorsiflexion was measured, and the American Orthopedic Foot and Ankle Society (AOFAS) score was evaluated at the latest follow-up visit. The presence of soleus muscle involvement and an ongoing lesion that might affect the postoperative results of preoperative magnetic resonance imaging (MRI) were investigated. Statistical analysis was conducted to analyze preoperative factors strongly associated with patient clinical outcomes. The mean follow-up period after surgery was 18.6months (range, 12-28months). At the latest follow-up visit, the mean ankle dorsiflexion was 9° (range, 0-20°), and the mean AOFAS score was 87.7 (range, 80-98). On preoperative MRI, 13 calves showed soleus muscle involvement. Seven calves had ongoing lesions. Five of the ongoing lesions were muscle edema, and the remaining two lesions were cystic mass lesions resulting from muscle necrosis. Ankle dorsiflexion and AOFAS scores at the latest follow-up evaluation were insufficient in the ongoing lesions group. Although RF-induced calf muscle reduction is believed to be a safer method than conventional procedures, careful handling is needed because of the side effects that may occur in some instances. The slow progression of fibrosis could be observed after RF-induced calf reduction. Therefore, long-term follow-up evaluation is needed after the procedure. Therapeutic case series.

Magnetic resonance imaging measurement reproducibility for calf muscle and adipose tissue volume

To describe a new semiautomated method for segmenting and measuring the volume of the muscle, bone, and adipose (subcutaneous and intermuscular) tissue in calf muscle compartments using magnetic resonance (MR) images and determine the intrarater and interrater reproducibility of the measures. Proton-density weighted MR images were acquired from the right calf of 21 subjects. Three raters segmented and measured the volumes of bones, adipose tissue, and five individual muscle compartments. Two raters repeated the segmentations. The intra- and interrater reproducibility of the measures (intraclass correlation coefficients; ICC) were determined using generalizability theory. All ICC values were greater than 0.96. The average standard error of the mean (SEM) of all measures was 1.21 cm(3) and none were greater than 2.3 cm(3) . Essentially all variation (≥97% for all measures) was due to subject differences, indicating low error in the measurements. The volumetric measurements for the bones, adipose tissue, and muscle in each of the compartments using MRI were highly reproducible. MRI can provide quantitative, reproducible volumetric measures of bone, adipose tissue, and individual muscle compartments in the calf. We believe these methods can be used to quantify specific muscle or adipose volumetric measures for other clinical or research purposes.

Muscle volume and motor development in spastic cerebral palsy

describe volumetric deficits in the medial gastrocnemiiof young children (2–5y) with spastic CP of 22%. Their paperis important because it challenges a prevalent view that thedevelopment of musculoskeletal deformity is associated withthe older child. The age range of the participants in this paperis such that the authors come tantalizingly close to answeringa fundamental question of muscular deformity and develop-ment in spastic CP: ‘Is delayed muscle development causedsolely by disuse secondary to the delayed acquisition of com-promised motor skills or is lack of muscle development moredirectly related to the superposition of cerebral injuries on adeveloping motor system?’ If the latter, then lack of plantar-flexor muscle growth in infancy may be an important factor tothe delayed acquisition of motor milestones and even, in part,responsible for the persistent toe-walking pattern observed inthis group.How can deficits in calf muscle volume contribute to thedevelopment of a toe-walking pattern? The members of theplantarflexor muscle group are essential to the maintenance ofstanding balance and, in gait, to the support and progressionof the body. In the typically developing, these muscles appearto work at close to 50% of their capacity during heel-toe walk-ing.

What are the long-term consequences of botulinum toxin injections in spastic cerebral palsy?

Muscle spasticity, defined as a velocity dependent resistance to stretch, is the primary impairment of spastic cerebral palsy (CP) and is neural in origin. However, spastic muscle also undergoes significant morphological and structural alterations secondary to spasticity which contribute to muscle weakness, muscle stiffness, restricted joint range of motion, and skeletal deformity. These secondary alterations can progress with age and contribute to a gradual loss of functional capacity during development, including the ability to ambulate independently. There is consensus that intra-muscular botulinum toxin A (BoNT-A) injections can be effective in the management of lower limb spasticity in children with spastic CP. BoNT-A injections can improve gait and delay and reduce the requirement for surgical interventions to treat musculoskeletal deformities when combined with conservative treatments. The study by Alhusaini et al. is one of the first that begins to address the important clinical question of how BoNT-A injections influence the secondary effects of spasticity on joint-level mechanical properties in children with spastic CP. An attractive feature of the study was that the authors assessed ankle joint stiffness and not just joint range of motion. Alhusaini et al. showed that BoNT-A has relatively minor effects on passive mechanical properties of the ankle plantar-flexor muscles at 6-weeks post injection in children with spastic CP aged 4– 10 years with high ankle joint stiffness. This study therefore does not support the efficacy of BoNT-A for treating contractures. What remains unclear at the present time is how BoNT-A might influence other structural and neuro-mechanical properties of the muscle and ⁄or tendon, especially in the longer term. For example, how does BoNT-A affect muscle size, strength, force-length-velocity behaviour, moment arms, co-activation, and tendon compliance? Of increasing concern is evidence from animal studies that intra-muscular BoNT-A injections adversely influence muscle growth in the injected muscle as well as muscles remote from the injection site. For example, Fortuna et al. recently reported up to 95% reductions in rabbit hind limb quadriceps muscle strength following 6 months of repeated BoNT-A injections, which was accompanied by up to 60% reductions in muscle mass. Reductions in strength and mass were also reported for quadriceps muscles in the contralateral limb. These findings point to the possibility that the short-term functional benefits of BoNT-A injections reported in clinical studies in spastic CP may be offset by accelerated structural weakening of muscle. This is important because children aged 2–5 years with spastic CP that have not undergone orthopaedic surgery or commenced BoNT-A injections already have significantly lower calf muscle volume relative to their typically developed peers. BoNT-A is routinely administered to children in this age group and is often repeated over many cycles. Further muscle weakening by BoNT-A would therefore be expected to adversely influence functional capacity. BoNT-A acts to weaken overactive muscles through chemical blockade of the neuromuscular junction. It might be expected that any associated muscle atrophy could contribute to observed improvements in gait following BoNT-A injections. However, during maturation in childhood and adolescence, muscles must increase in size to cope with the increased mechanical loading associated with motor function in activities such as gait. Muscle weakening from BoNT-A could therefore be beneficial in the short-term but detrimental in the longerterm because of impeded muscle growth. Aside from the study by Alhusaini et al., to our knowledge no detailed in vivo studies of the effects of BoNT-A on the active and passive mechanical properties of muscle in children with spastic CP have been conducted. In spite of the widespread use of BoNT-A injections in children with spastic CP for almost two decades, the long-term efficacy of this treatment for improving functional outcomes in children with spastic CP remain relatively unknown. In using a short-term solution we may be creating a long-term problem which could lead to increased costs of care in spastic CP. Long-term trials of the structural and neuro-mechanical responses of muscle to BoNT-A and their consequences for motor function in spastic CP are required. New developments in musculoskeletal modeling and simulation may prove fruitful in linking muscletendon adaptation with gait function in spastic CP.

Effectiveness of Exercise Countermeasures for Protecting Muscle on the International Space Station (ISS)

These investigators document(ed) the exercise program used by crewmembers aboard the ISS and examine(d) its effectiveness for preserving skeletal muscle size and function. Participants were 10 American and Russian ISS crewmembers with mission durations of 161 to 192 days. A treadmill, cycle ergometers, and a resistance exercise device were available on the ISS and programs were individualized for each subject. Countermeasure performance varied widely among the subjects. The study concentrated on the calf muscles because they atrophy more than other leg or upper body muscles with spaceflight. After missions, soleus muscles had atrophied more than gastrocnemius muscles, with great variation among crewmembers. All measured muscle performance variables were reduced after flight and the muscles also showed changes, and individual variation, in myosin heavy chain fiber types. Analyses of caloric intake and individual exercise indicated the caloric intake was 17 to 23% below the predicted caloric need. The investigators conclude that the exercise program did not completely protect the calf muscle. They identified four factors in addition to the microgravity environment contributed to muscle loss: 1) calf muscle volume before spaceflight; 2) volume of treadmill exercise; 3) treadmill mode (passive mode may protect better); and 4) inadequate caloric intake. In addition to providing evidence the current exercise countermeasure program does not fully protect human skeletal muscle in spaceflight, this research provides valuable information for future monitoring and for the development of an effective countermeasure program.