Blood Flow Restriction Combined with Electrical Stimulation Attenuates Thigh Muscle Disuse Atrophy.

PURPOSE: This study aimed to investigate the effects of blood flow restriction (BFR) combined with electrical muscle stimulation (EMS) on skeletal muscle mass and strength during a period of limb disuse. METHODS: Thirty healthy participants (22 ± 3 yr; 23 ± 3 kg·m-2) were randomly assigned to control (CON; n = 10), BFR alone (BFR; n = 10), or BFR combined with EMS (BFR + EMS; n = 10). All participants completed unloading of a single leg for 14 d, with no treatment (CON), or while treated with either BFR or BFR + EMS (twice daily, 5 d·wk-1). BFR treatment involved arterial three cycles of 5-min occlusion using suprasystolic pressure, each separated by 5 min of reperfusion. EMS (6 s on, 15 s off; 200 µs; 60 Hz; 15% maximal voluntary contraction [MVC]) was applied continuously throughout the three BFR cycles. Quadriceps muscle mass (whole-thigh lean mass via dual-energy x-ray absorptiometry and vastus lateralis [VL] muscle thickness via ultrasound) and strength (via knee extension MVC) were assessed before and after the 14-d unloading period. RESULTS: After limb unloading, whole-thigh lean mass decreased in the control group (-4% ± 1%, P < 0.001) and BFR group (-3% ± 2%, P = 0.001), but not in the BFR + EMS group (-0.3% ± 3%, P = 0.8). VL muscle thickness decreased in the control group (-4% ± 4%, P = 0.005) and was trending toward a decrease in the BFR group (-8% ± 11%, P = 0.07) and increase in the BFR + EMS group (+5% ± 10%, P = 0.07). Knee extension MVC decreased over time (P < 0.005) in the control group (-18% ± 15%), BFR group (-10% ± 13%), and BFR + EMS group (-18% ± 15%), with no difference between groups (P > 0.5). CONCLUSION: Unlike BFR performed in isolation, BFR + EMS represents an effective interventional strategy to attenuate the loss of muscle mass during limb disuse, but it does not demonstrate preservation of strength.

Diffusion tensor imaging and diffusion modeling: Application to monitoring changes in the medial gastrocnemius in disuse atrophy induced by unilateral limb suspension.

BACKGROUND: Diffusion tensor imaging (DTI) assesses underlying tissue microstructure, and has been applied to studying skeletal muscle. Unloading of the lower leg causes decreases in muscle force, mass, and muscle protein synthesis as well as changes in muscle architecture. PURPOSE: To monitor the change in DTI indices in the medial gastrocnemius (MG) after 4-week unilateral limb suspension (ULLS) and to explore the feasibility of extracting tissue microstructural parameters based on a two-compartment diffusion model. STUDY TYPE: Prospective cohort study. SUBJECTS: Seven moderately active subjects (29.1 ± 5.7 years). FIELD STRENGTH/SEQUENCE: 3T, single-shot fat-suppressed echo planar spin echo sequence. ASSESSMENT: Suspension-related changes in the DTI indices (eigenvalues: λ1 , λ2 , λ3 , fractional anisotropy; coefficient of planarity) were statistically analyzed. Changes in model-derived tissue parameters (muscle fiber circularity and diameter, intracellular volume fraction, and residence time) after suspension are qualitatively discussed. STATISTICAL TESTS: Changes in the DTI indices of the MG between pre- and postsuspension were assessed using repeated-measures two-way analysis of variance (ANOVA). RESULTS: All the eigenvalues (λ1 : P = 0.025, λ2 : P = 0.035, λ3 : P = 0.049) as well as anisotropic diffusion coefficient (P = 0.029) were significantly smaller post-ULLS. Diffusion modeling revealed that fibers were more circular (circularity index increased from 0.55 to 0.95) with a smaller diameter (diameter decreased from 82-60 µm) postsuspension. DATA CONCLUSION: We have shown that DTI indices change with disuse and modeling can relate these voxel level changes to changes in the tissue microarchitecture. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf.

OBJECTIVE: Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment. MATERIALS AND METHODS: We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward. RESULTS: Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm2; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm2 (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (rs = -0.86, p < 0.01). CONCLUSIONS: The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

Relationship of changes in strain rate indices estimated from velocity-encoded MR imaging to loss of muscle force following disuse atrophy.

PURPOSE: This study explores changes in strain rate (SR) (rate of regional deformation) parameters extracted from velocity-encoded MRI and their relationship to muscle force loss following 4-week unilateral lower limb suspension in healthy humans. METHODS: Two-dimensional SR maps were derived from three directional velocity-encoded MR phase-contrast images of the medial gastrocnemius in seven subjects. Atrophy-related and regional differences in the SR eigenvalues, angle between the SR and muscle fiber (SR-fiber angle), and strain rates in the fiber basis were statistically analyzed using analysis of variance and linear regression. RESULTS: During isometric contraction, SR in the fiber cross section (SRin-plane ) was significantly lower, and the SR-fiber angle was significantly higher postsuspension (P < 0.05). On multiple variable regression analysis, the volume of medial gastrocnemius, SRin-plane , and SR-fiber angle were significantly associated with force and changes in the, and the SR eigenvalues and shear SR were significantly associated with change in force with disuse. CONCLUSIONS: Changes in SR-fiber angle, SRin-plane , and shear SR as well as their ability to predict force and force changes may reflect the role of remodeling of the extracellular matrix in disuse atrophy and its functional consequence in reducing lateral transmission of force. Magn Reson Med 79:912-922, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography.

The objective of this study was to determine alteration of corticospinal tract in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal controls, and then ALS were divided into two subgroups according to their clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5. The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were significantly reduced compared with normal controls, and SBMA patients. On the other hand, the mean diffusivity (MD) values were not significantly different among normal controls and the three disease groups. The rate of disease progression (ΔFRS-R) of ALS patients was significantly correlated with FA values and central motor conduction time (CMCT). In conclusion, the present study demonstrated a significant reduction of FA values in ALS patients, and the ΔFRS-R of ALS patients showed distinct regressions with FA values and CMCT, suggesting that this DTT analysis could be useful for detecting disease progression of ALS patients.

Rotator cuff muscle degeneration and tear severity related to myogenic, adipogenic, and atrophy genes in human muscle.

Large rotator cuff tear size and advanced muscle degeneration can affect reparability of tears and compromise tendon healing. Clinicians often rely on direct measures of rotator cuff tear size and muscle degeneration from magnetic resonance imaging (MRI) to determine whether the rotator cuff tear is repairable. The objective of this study was to identify the relationship between gene expression changes in rotator cuff muscle degeneration to standard data available to clinicians. Radiographic assessment of preoperative rotator cuff tear severity was completed for 25 patients with varying magnitudes of rotator cuff tears. Tear width and retraction were measured using MRI, and Goutallier grade, tangent (tan) sign, and Thomazeau grade were determined. Expression of myogenic-, adipogenic-, atrophy-, and metabolism-related genes in biopsied muscles were correlated with tear width, tear retraction, Goutallier grade, tan sign, and Thomazeau grade. Tear width positively correlated with Goutallier grade in both the supraspinatus (r = 0.73) and infraspinatus (r = 0.77), along with tan sign (r = 0.71) and Thomazeau grade (r = 0.68). Decreased myogenesis (Myf5), increased adipogenesis (CEBPα, Lep, Wnt10b), and decreased metabolism (PPARα) correlated with radiographic assessments. Gene expression changes suggest that rotator cuff tears lead to a dramatic molecular response in an attempt to maintain normal muscle tissue, increase adipogenesis, and decrease metabolism. Fat accumulation and muscle atrophy appear to stem from endogenous changes rather than from changes mediated by infiltrating cells. Results suggest that chronic unloading of muscle, induced by rotator cuff tear, disrupts muscle homeostasis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2808-2814, 2017.

The effects of hibernation and forced disuse (neurectomy) on bone properties in arctic ground squirrels.

Bone loss is a well-known medical consequence of disuse such as in long-term space flight. Immobilization in many animals mimics the effects of space flight on bone mineral density. Decreases in metabolism are also thought to contribute to a loss of skeletal mass. Hibernating mammals provide a natural model of disuse and metabolic suppression. Hibernating ground squirrels have been shown to maintain bone strength despite long periods of disuse and decreased metabolism during torpor. This study examined if the lack of bone loss during torpor was a result of the decrease in metabolic rate during torpor or an evolutionary change in these animals affording protection against disuse. We delineated changes in bone density during natural disuse (torpor) and forced disuse (sciatic neurectomy) in the hind limbs of the arctic ground squirrel (AGS) over an entire year. We hypothesized that the animals would be resistant to bone loss due to immobilization and disuse during the winter hibernation season when metabolism is depressed but not the summer active season. This hypothesis was not supported. The animals maintained bone density (dual-energy X-ray absorptiometry) and most bone structural and mechanical properties in both seasons. This was observed in both natural and forced disuse, regardless of the known metabolic rate increase during the summer. However, trabecular bone volume fraction (microcomputed tomography) in the distal femur was lower in neurectomized AGS at the study endpoint. These results demonstrate a need to better understand the relationship between skeletal load (use) and bone density that may lead to therapeutics or strategies to maintain bone density in disuse conditions.

Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse.

Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. µCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin-neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading.

Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.

Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat-K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK-KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast-phenotype-related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse-induced bone mass reduction.

Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy.

OBJECTIVES: The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats. METHODS: Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed. RESULTS: Direct ES significantly reduced the disuse-induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups. CONCLUSIONS: These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone.

Additive effect of PTH (1-34) and zoledronate in the prevention of disuse osteopenia in rats.

Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia. Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1-34) (80µg/kg) was given 5days/week and Zln (100µg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, µCT, dynamic bone histomorphometry, and mechanical testing. BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (-25%, p<0.05), lower tibial trabecular bone formation rate (BFR/BS) (-29%, p<0.05), and lower bone strength (Fmax) at the distal femur (-19%, p<0.001) compared with Ctrl. BTX+PTH resulted in higher femoral BV/TV (+31%, p<0.05), higher tibial trabecular BFR/BS (+297%, p<0.05), and higher Fmax at the distal femur (+11%, p<0.05) compared with BTX. BTX+Zln resulted in higher femoral BV/TV (+36%, p<0.05), lower tibial trabecular BFR/BS (-93%, p<0.05), and higher Fmax at the distal femur (+10%, p<0.05) compared with BTX. BTX+PTH+Zln resulted in higher femoral BV/TV (+70%, p<0.001), higher tibial trabecular BFR/BS (+59%, p<0.05), and higher Fmax at the distal femur (+32%, p<0.001) compared with BTX. In conclusion, BTX-induced immobilization led to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl.

Moderate intensity resistive exercise improves metaphyseal cancellous bone recovery following an initial disuse period, but does not mitigate decrements during a subsequent disuse period in adult rats.

Spaceflight provides a unique environment for skeletal tissue causing decrements in structural and densitometric properties of bone. Previously, we used the adult hindlimb unloaded (HU) rat model to show that previous exposure to HU had minimal effects on bone structure after a second HU exposure followed by recovery. Furthermore, we found that the decrements during second HU exposure were milder than the initial HU cycle. In this study, we used a moderate intensity resistance exercise protocol as an anabolic stimulus during recovery to test the hypothesis that resistance exercise following an exposure to HU will significantly enhance recovery of densitometric, structural, and, more importantly, mechanical properties of trabecular and cortical bone. We also hypothesized that resistance exercise during recovery, and prior to the second unloading period, will mitigate the losses during the second exposure. The hypothesis that exercise during recovery following hindlimb unloading will improve bone quality was supported by our data, as total BMC, total vBMD, and cancellous bone formation at the proximal tibia metaphysis increased significantly during exercise period, and total BMC/vBMD exceeded age-matched control and non-exercised values significantly by the end of recovery. However, our results did not support the hypothesis that resistance exercise prior to a subsequent unloading period will mitigate the detrimental effects of the second exposure, as the losses during the second exposure in total BMC, total vBMD, and cortical area at the proximal tibia metaphysis for the exercised animals were similar to those of the non-exercised group. Therefore, exercise did not mitigate effects of the second HU exposure in terms of pre-to-post HU changes in these variables, but it did produce beneficial effects in a broader sense.

The effect of electrical muscle stimulation on the prevention of disuse muscle atrophy in patients with consciousness disturbance in the intensive care unit.

PURPOSE: Disuse atrophy of the lower limbs of patients with consciousness disturbance has often been recognized as "an unavoidable consequence," such that the mechanism was not investigated diligently. In this study, we examined the preventive effects of electrical muscle stimulation (EMS) against disuse atrophy of the lower limbs in patients in coma after stroke or traumatic brain injury in the intensive care unit. MATERIALS AND METHODS: We evaluated changes in cross-sectional area of lower limb muscles weekly with computed tomography in 6 control group patients and 9 EMS group patients. Electrical muscle stimulation was performed daily from day 7 after admission. We evaluated the anterior thigh muscle compartment, posterior thigh muscle compartment, anterior leg muscle compartment, and posterior leg muscle compartment. RESULTS: In the control group, the decrease in cross-sectional area progressed in all compartments every week (P < .0001). Cross-sectional areas of all compartments at day 14 were significantly decreased in the control group compared with those in the EMS group at day 7 (P < .001). We were able to limit the rate of muscle atrophy as measured in the cross-sectional areas to within 4% during the period of EMS (days 7-42) in 5 patients. The difference between the control and the EMS groups was statistically significant (P < .001). CONCLUSION: Electrical muscle stimulation is effective in the prevention of disuse muscle atrophy in patients with consciousness disorder.

Frontal dysfunctions of ALS-PBP patients in relation to their bulbar symptoms and rCBF decline.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by progressive degeneration of spinal and bulbar motor neurons. However up to 50% ALS patients may also have cognitive dysfunction which has not been fully examined. METHODS: 35 ALS patients [23 patients presenting with limb-type ALS (ALS-limb) and 12 patients presenting with primary bulbar palsy (PBP)-type ALS (ALS-PBP)] and 5 Spinal and Bulbar Muscular Atrophy (SBMA) patients have participated. To assess cognitive function mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), and frontal assessment battery (FAB) were performed. Additionally the time to complete card flipping with a computerized touch panel-type screening test was also examined. To investigate regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) using a (99m)Tc labeled ethyl cysteinate dimer ((99m)Tc-ECD) were performed. Statistical image analysis was performed using the easy Z-score imaging system (eZIS). RESULTS: HDS-R and FAB scores were significantly lower in the ALS-PBP group than in age- and gender-matched control subjects or ALS-limb groups (p<0.01). The time to complete card flipping was significantly longer in the ALS-PBP group than in the control and ALS-limb groups (p<0.01). Although MMSE, HDS-R and FAB scores and the time to complete card flipping had no correlation with ALS functional rating scale-revised (ALSFRS-R) or Norris-limb scale scores, FAB score (r=0.63, p <0.01) and the time to complete card flipping (r=-0.66, p<0.01) were strongly correlated with Norris-bulbar score. The eZIS showed that rCBF of the frontal lobe was more severely declined in ALS-PBP patients than in ALS-limb patients (p<0.05). CONCLUSION: These results suggest a selective decline of frontal cerebral functions in the ALS-PBP group in relation to their bulbar symptoms and rCBF decline.

Monochromatic synchrotron radiation muCT reveals disuse-mediated canal network rarefaction in cortical bone of growing rat tibiae.

The purpose of this study was to demonstrate the ability of computed microtomography based on monochromatic synchrotron radiation (SRmuCT) in microstructural analysis of cortical bone. Tibial diaphyses of growing rats (14 wk, n = 8) undergoing unilateral sciatic neurectomy 8 wk before study were imaged with spatial volume resolution of 5.83 x 5.83 x 5.83 microm3 by SRmuCT (20 keV) at the synchrotron radiation facility (SPring-8). Reconstructed image data were translated into local mineral densities by using a calibrated linear relationship between linear absorption coefficients and concentrations of homogeneous K2HPO4 solution. Pure bone three-dimensional images, produced by simple thresholding at a bone mineral density of 0.82 g/cm3, were analyzed for macro- and microscopic structural properties. In neurectomized hindlimbs, cortical canal network rarefaction as well as bone atrophy were found. The former was characterized by 30% smaller porosity, 11% smaller canal density in transverse section, and 38% smaller canal connectivity density than those in contralateral bone. On the other hand, no difference was found in bone mineral density between neurectomized and intact hindlimbs (1.37 vs. 1.36 g/cm3). In conclusion, SRmuCT is a promising method for the three-dimensional analysis of cortical microstructure and the degree of mineralization in small animals.

Unilateral fibroadipose degeneration of the masticatory muscles.

A unique case of fatty replacement of the masticatory muscles, causing progressive limitation of mouth opening, is presented. Both CT and MRI revealed an almost total substitution of the masticatory muscles with fatty tissue, confirmed by the histopathology at surgery. Myotomy of masseter and internal pterygoid muscles and coronoidotomy improved his symptoms. There is no known cause of fibroadipose replacement of muscle fibres.