Marked Muscle Atrophy Research Articles

Predicting muscle function and mass with electrical impedance myography: A study in rat analogs of micro- and partial gravity

IntroductionSpaceflight results in marked muscle atrophy and a corresponding loss in muscle strength. Methods to evaluate spaceflight-induced changes to muscle size and strength are difficult to achieve within the tight confines of spacecrafts. Therefore, convenient methods to non-invasively monitor muscle that are predictive of actual muscle function are critical for future missions to ensure the health and safety of crew members. PurposeEvaluate the ability of non-invasive in vivo electrical impedance myography (EIM) combined with statistical models to predict muscle size and strength in rodent models of micro- and partial gravity. MethodsMale and female Fisher rats (N = 120), half gonadectomized, were divided into three different weightbearing (WB) conditions of 40 animals each, including 0%WB (0 % of weight-bearing, simulated microgravity), 40%WB (40 % of weight-bearing, simulated Martian gravity), and 100%WB (100 % of weight-bearing, full weight-bearing controls). Rats remained in designated interventions for 28 days. Afterward, rats underwent a series of musculoskeletal strength assessments and measurement of EIM. Rats were then euthanized and gastrocnemius tissues collected. Machine-learning (ML) algorithms were applied to full spectrum EIM data to predict various muscle parameters. Results40%WB and 0%WB rats had lower grip strength and plantar flexion compared to 100%WB. Correspondingly, 40%WB and 0%WB also had reduced gastrocnemius mass compared to 100%WB. EIM resistance values demonstrated a dose-dependency response, with greater resistance values associated with reduced gravitational load. ML-enhanced EIM yielded strong predictions of muscle plantar flexion force and muscle mass, with root mean squared errors of 18.4 % of 22.0 %, and R2 values of 0.87 an 0.88, respectively. ConclusionML-enhanced EIM may be a helpful tool to non-invasively monitor muscle changes predictive of muscle force production and mass during exposure to reduced gravity.

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice.

Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.

Transcapillary PO2 Gradients in Contracting Muscles of Type I Diabetic Rats.

This study aimed to clarify the effect of Type I diabetes (DIA) on transcapillary PO2 gradients, which are oxygen-driving factors between the blood and the interstitium, in the contracting muscle of rats. Wistar male rats were divided into the diabetic (streptozocin i.p.) and sham groups. Microvascular and interstitial PO2 were measured in the extensor digitorum longus muscle during electrical stimulation-induced muscle contraction, using the phosphorescence quenching method. Transcapillary PO2 gradient, ΔPO2, was calculated as microvascular minus interstitial PO2. Resting microvascular PO2 was higher in the diabetic group than in the sham group (6.3 ± 1.7 vs. 4.7 ± 0.9 mmHg, p < 0.05) and remained for 180 s. Interstitial PO2 from rest to muscle contraction did not differ between the groups. The ΔPO2 was higher in the diabetic group than in the sham group at rest and during muscle contraction (4.03 ± 1.42 vs. 2.46 ± 0.90 mmHg at rest; 3.67 ± 1.51 vs. 2.22 ± 0.65 mmHg during muscle contraction, p < 0.05). Marked muscle atrophy was observed in the diabetic group. DIA increased microvascular and transcapillary PO2 gradients in the skeletal muscle. The enhanced PO2 gradients were maintained from rest to muscle contraction in diabetic muscle.

Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 ‍IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

Traumatic injury of left femoral nerve causing unilateral hindlimb lameness in a cat

AbstractA 1‐year‐old, female, domestic shorthair cat was referred for orthopaedic evaluation of acute‐onset, non‐progressive left pelvic limb lameness of 2.5‐week duration. Orthopaedic examination revealed an abnormal gait with impaired ability to support weight on the left pelvic limb. There was marked atrophy of the quadriceps muscles. Neurological examination revealed an absent patellar reflex and decreased sensation in the cutaneous zone of the saphenous nerve of the left pelvic limb. Magnetic resonance imaging showed T2‐weighted/short‐tau inversion recovery hyperintensity and contrast enhancement in the area of the femoral nerve and within muscles innervated by this nerve. Findings were deemed consistent with traumatic nerve injury and denervation/traumatic myopathy or myositis/neuritis. Electromyography of the quadriceps muscles revealed fibrillation potentials and positive sharp waves. Follow‐up over the next 9 months revealed no changes in the neurological deficits. This was deemed to be consistent with either partial axonotmesis or partial neurotmesis of the left femoral nerve.

Bone Lesions in a Young Dog and a NEEM (Azadirachta indica) Spray as the Only Preventive Measure against Leishmaniasis: A Case Report

As the spread of canine leishmaniasis (CanL) is increasing throughout the world, the need for effective agents to prevent its transmission has intensified. In this case report, an intact 1.5-year-old male French bulldog was presented for treatment of severe, sudden, and constant lameness on his right hindlimb, which had started approximately four months previously and was unresponsive to routine nonsteroidal anti-inflammatory drugs. A Neem oil-based product was sprayed three times a week on the dog’s coat for about fourteen months as the only prophylactic measure against CanL. The orthopedic examination revealed grade 3–4 lameness and marked atrophy of the thigh muscles with swollen and painful right stifle joint. The radiological investigation showed polyostotic periosteal proliferation at both hindlimbs. The diagnosis of CanL was established by examination of fine-needle aspiration of lymph nodes (left prescapular, right and left popliteal) and immunofluorescence antibody testing. A leishmanicidal therapeutic protocol was prescribed. Within ten days of starting the therapy, the dog was significantly less lame, and eight months later radiographic examination revealed complete regression of the bone lesions. Some owners resort to a naturalistic approach for CanL prevention, also using products that have not been clinically evaluated. Neem oil is thought to prevent sandfly bites in dogs. Some laboratory and field studies have identified Neem oil as a possible alternative herbal drug that is repellent to sandflies. However, the clinical, laboratory, and radiographic findings clearly show that the Neem oil spray formulation used in this case report was not an effective means of CanL prevention. There is no clinical evidence in support of Neem oil-based products for the protection of dogs against CanL transmission. As Neem oil has previously been shown to be somewhat volatile, this case report suggests that even though it is a very effective repellent against sandflies, in practice, its effect on the dogs’ coat was only short-lived.

Improvement of Motor Nerve Regeneration Using the Nanofibrils Technique in Adult Mongrel Dogs

The dog was selected as the experimental animal due to the fact that the larger the animal, the higher the regenerative power which depends mainly on the size of the nerve in use. Nine adult mongrel dogs were included in this study which aimed at evaluating motor nerve regeneration using nanofibrils technique for the purpose of developing a rationale for a minimal morbidity. A one and half cm gap was made in the common peroneal nerve by the direct cutting of both sides (proximal cut and then distal to avoid the double shock). The nanofibrils were used to fill the space and cover the two fixed ends in six of the dogs and another three animals were used as control. The nerve was cut and the space in between the two fixed ends was left without nanofibrils. Four months after surgery, the regenerated nerves were evaluated by macroscopic and microscopic examination. Normal segments of the deep peroneal nerve (D.P.N.) were taken to compare the changes. All animals with implanted nanofibrils used their limbs successfully at 3-4 weeks, the animal gait returned to its normal condition without any remarkable symptoms of lameness and the joints angles displayed its normal posture. Dogs in the control group showed lameness and flexion of the upper joints all-over during the time of the experiment with marked atrophy of the limb muscles. Better organized histological structures of nanofibre in treated nerve samples than the untreated control one were noted. More compartmentation of well-differentiated myelinated nerve fibers into several small nerve bundles in nanofibre treated nerve trunks compared with fewer bundles in the untreated control group. Connective tissue stroma (epineurium, perineurium and endoneurum) were more prominent with relatively higher numbers of small blood vessels compared with the untreated control group. Thus we concluded that nanofibres can be regarded as an efficient regeneration enhancing material in peripheral nerve injuries.

Craniomandibular Osteopathy in Mixed Breed Dogs

Background: Craniomandibular osteopathy (CMO) is a degenerative, osteopetrotic, and self-limiting bone disease that is rare in the canine species. The most affected bones and joints are the branches of the mandible, tympanic bulla, and temporomandibular joint (TMJ) with generalized thickening of the bone trabeculae, increased lines of bone cementation, and bone proliferation. The aim of the present study was to evaluate 2 cases of CMO in mixed-breed dogs belonging to the same litter sent to the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD / FV / UFPel).Cases: Three canines (mixed-breed, 2 female and 1 male) belonging to the same litter presented at eight months of age with increases in volume and pain in the face, difficulties in moving the jaw, anorexia, and sialorrhea. The 2 female dogs were euthanized and sent to LRD / FV / UFPel for necropsy. The animals underwent radiography of the left and right lateral and dorsoventral lateral projections in the imaging sector of the Hospital de Clínicas Veterinária (HCV) at UFPel. During the necropsy, fragments of organs from the abdominal and thoracic cavities, as well as the central nervous system and head bones, were collected and fixed in 10% buffered formalin. The tissue samples were cleaved, processed routinely, embedded in paraffin, cut into sections of 3 µm thickness, and stained using hematoxylin and eosin (HE). The bone fragments were decalcified in a 50/50 solution of 8% hydrochloric acid and 8% formic acid and subsequently cleaved and stained with HE. The head and jaw of one of the animals was dissected and subjected to maceration in water at room temperature. Radiographic examination of the two remaining animals showed irregular and exuberant bone proliferation in the mandible and temporomandibular region. In the tympanic bullae, occipital bone, and zygomatic process, thickening of the structures was observed with increased opacity. On necropsy, the animals were cachectic with marked muscle atrophy and increased volume of the mandibular branches and head bones, in addition to marked edema in the adjacent subcutaneous tissue. The regional lymph nodes were enlarged, and in one of the animals, bilateral lesions in the femurs were also observed. In the head subjected to biological maceration, areas of bone proliferation and rarefaction were observed, with increased volume and destruction of the TMJ. On histopathological evaluation of the ventral portion of the mandibular bodies, a network of bony trabeculae was observed, composed of a chondroid matrix with different degrees of mineralization. The cortical portion of the bones exhibited loss of lamellar compactness, with greater spread of the bone trabeculae. The bone trabeculae were perpendicular to the long axis of the cortical of the mandible and were distributed in the medullary spaces, presenting some dense foci of inflammatory infiltrates composed predominantly of neutrophils, lymphocytes, and plasma cells.Discussion: The breeds most predisposed to developing CMO are the West Highland White Terrier and Scottish Terrier; however, the disease has also been described in other non-Terriers. Nevertheless, there are no descriptions in the literature of mixed-breed animals (SRD), with this report being the first of CMO in SRD dogs. The bones most frequently affected in CMO are those of the head. In Terrier dogs, the TMJ is also affected. In the cases of this study, severe CMO occurred, affecting both the head bones and TMJ, and in 1 of the animals, it also affected the femurs. Although CMO has not previously been reported in SRD dogs, the condition can seriously affect these animals, and differential diagnosis should always be made.Keywords: degenerative bone disease, bone proliferation, lion jaw, TMJ.Título: Osteopatia craniomandibular em cães sem raça definidaDescritores: doença óssea degenerativa, proliferação óssea, mandíbula de leão, ATM.

Infiltrative Lipoma Causing Lumbar Nerve Root Compression in a Dog

Background: Lipomas are benign soft tissue mesenchymal neoplasms composed of adipose cells and are usually found in the subcutaneous tissue. Occasionally, lipomas may invade muscles or grow between them, in which case they are characterized as infiltrative lipomas. Clinical signs resulting from an intermuscular lipoma compressing peripheral nerves are rarely encountered in dogs. This case report aims to describe the neurological signs, diagnosis, and clinical evaluation of a dog diagnosed with infiltrative lipoma compressing a lumbar spinal nerve root.Case: A 12-year-old neutered male Fox Paulistinha, weighing 10.5 kg, was presented with difficulties in walking for the past 15 days with no previous history of trauma. On physical examination, the presence of three cutaneous nodules was noted in the ventral thoracic region, with onset of one year and slow and progressive growth. A cytological evaluation of the nodules was performed, and lipoma was diagnosed. At the neurological examination, the patient presented ambulatory paraparesis with marked motor deficit and atrophy of the quadriceps muscles of the left pelvic limb. Conscious proprioceptive deficit, the absence of patellar reflex, and diminished withdrawal reflex were observed in the left hind limb, in addition to diffuse pain on epaxial palpation of the lumbar region. Electroneuromyography showed increased insertion activity in the left gastrocnemius muscle and moderate spontaneous activity (fibrillation). Persistence of 10% was observed in the F-wave study of the left tibial nerve. These findings indicate partial involvement of the roots of the left sciatic-tibial nerve. Magnetic resonance imaging (MRI) showed the presence of a mass measuring 3.18 × 1.04 × 1.4 cm, interspersed with the paravertebral muscles, and located adjacent to the L2 and L3 spinous processes. An ultrasound-guided fine needle aspiration biopsy of the mass was performed and the findings of the cytopathological analysis of the collected material were considered consistent with lipoma. In view of these findings, surgical removal was recommended. However, the owner chose to attempt conservative treatment to control pain. Thus, the patient was treated with gabapentin, tramadol hydrochloride, carprofen, dipyrone, omeprazole, and physiotherapy. The animal exhibited a good response to conservative treatment, regaining its hind limb mobility in approximately 30 days.Discussion: Infiltrative lipomas compressing nerve roots are rarely described, with only one report of infiltrative lipoma in the lumbar region causing nerve root compression in dogs found in the literature. MRI was beneficial in this case, since it helped in determine the shape, location, and extent of the mass causing compression of the left L2 nerve root. The history and neurological examination findings in the patient described in this report were accounted for by the presence of an infiltrative lipoma compressing the left nerve root of L2. Surgical excision is the treatment of choice for intramuscular lipomas in most cases since conservative treatment elicits only a limited response. In contradiction to the literature, the dog in this report experienced a good response to conservative treatment, returning to normal mobility approximately 30 days after starting treatment. After six months of follow-up, the dog had not experienced a recurrence of the clinical signs. However, since the tumor has not been removed, clinical relapse is expected to occur in the future. Thus, despite the good response to conservative treatment in this case, we recommend the surgical excision of the tumor in order to decompress the affected nerve root. Although infiltrative lipomas compressing nerve roots are rare, clinicians should consider them as differential diagnosis when there is a presence of subcutaneous lipomas and neurologic signs of radiculopathy.

The clinical case of limb-girdle muscle dystrophy 2Q associated with myasthenic syndrome and lung damage

Limb-girdle muscle dystrophy 2Q is one of the rarest forms of plectinopathies and is represented by an isolated muscular dystrophic syndrome, according to two previously described literature reports. There are five forms of plectinopathies, including limb-girdle muscle dystrophy 2Q, are caused by mutations in the PLEC gene, the alternative splicing of which determines the synthesis of 9 isoforms of the plectin protein (1, 1a, 1b, 1c, 1d, 1e, 1f, 1g, 3) performing cytolinker function in the neuronal, epithelial and muscle tissue. The article describes the family observation of three sick siblings with the limb-girdle muscle dystrophy 2Q phenotype due to the presence of a new homozygous mutation (NM_201378.3:c.58G&gt;T, NP_958780.1:p.Glu20Ter) in the isoform 1f PLEC revealed by whole-exome sequencing. Clinical, electromyography, visualization and histopathological features of limb-girdle muscle dystrophy 2Q were analyzed in detail. The onset of clinical manifestations in all the described siblings was observed in early childhood with moderate weakness mainly in the pelvic girdle muscles and proximal lower limbs with minimal involvement of the muscles of the shoulder girdle. A distinctive aspect is the stagnation of the myodystrophic process until 20—21 years, followed by the progression and development of episodes of respiratory failure, as well as the formation of rigidity of the cervical, thoracic spine and moderate contracture of the Achilles tendons. Typical features are marked atrophy of paravertebral muscles with the formation of pterygoid scapula and the presence of hypertrophy m. gastrocnemius, m. quadriceps femoris, m. deltoideus and m. triceps brachii. Histopathological examination m. vastus lateralis revealed myodystrophic process without inflammatory infiltration, muscle fiber cytoskeleton disorganization resulted from the plectin loss. Electrocardiography signs of the early repolarization syndrome, focal cardiosclerosis and sinus tachycardia are described. For the first time, involvement in the pathological process of pulmonary tissue in the form of noninfectious bronchiolitis, atelectasis, and the development of the myasthenic syndrome causing episodes of respiratory failure resulted in the death of two described siblings aged 29 and 31 years. Discussed pathogenetic role of PLEC 1f isoform in the development of described syndromes, expands understanding of rare nosology limb-girdle muscle dystrophy 2Q.

Negative Effects of Long-duration Spaceflight on Paraspinal Muscle Morphology

Prospective case series. Determine the extent of paraspinal muscle cross-sectional area (CSA) and attenuation change after long-duration spaceflight and recovery on Earth. Determine association between in-flight exercise and muscle atrophy. Long-duration spaceflight leads to marked muscle atrophy. However, another negative consequence of disuse is intramuscular fatty infiltration. Notably, few studies have investigated the effects of spaceflight on intramuscular fatty infiltration, or how muscle atrophy is associated with in-flight exercise. We analyzed computed tomography scans of the lumbar spine (L1/L2) from 17 long-duration astronauts and cosmonauts to determine paraspinal muscle CSA and attenuation. Computed tomography scans were collected preflight, postflight, 1-year postflight, and, in a subset, 2 to 4 years postflight. We measured CSA (mm) and attenuation (Hounsfield Units) of the erector spinae (ES), multifidus (MF), psoas (PS), and quadratus lumborum (QL) muscles. We used paired t tests to compare muscle morphology at each postflight time point to preflight values and Pearson correlation coefficients to determine the association between muscle changes and in-flight exercise. ES, MF, and QL CSA and attenuation were significantly decreased postflight compared with preflight (-4.6% to -8.4% and -5.9% to -8.8%, respectively, p < 0.05 for all). CSA of these muscles equaled or exceeded preflight values upon Earth recovery, however QL and PS attenuation remained below preflight values at 2 to 4 years postflight. More resistance exercise was associated with less decline in ES and MF CSA, but greater decline in PS CSA. Increased cycle ergometer exercise was associated with less decline of QL CSA. There were no associations between in-flight exercise and muscle attenuation. Both CSA and attenuation of paraspinal muscles decline after long-duration spaceflight, but while CSA returns to preflight values within 1 year of recovery, PS and QL muscle attenuation remain reduced even 2 to 4 years postflight. Spaceflight-induced changes in paraspinal muscle morphology may contribute to back pain commonly reported in astronauts. 4.

P84-T Neuromyositis associated with cytomegalovirus infection in an immunocompetent patient with antineutrophil cytoplasmic antibodies-associated vasculitis

The role of CMV in ANCA-positive vasculitis is controversial. A 40-year-old man, with an unremarkable medical history, presented with progressive muscle weakness of all four limbs, accompanied by diffuse myalgia, arthralgia, and a 10 kg weight loss 2 months before admission to the Neurology Department of our hospital. Clinical examination revealed a flaccid tetraparesis with absent reflexes on the lower limbs and marked muscle atrophy. Electrophysiological investigations were consistent with a demyelinating motor polyradiculoneuropathy. Laboratory data showed AST = 1137 IU/L (normal < 37 IU/L), ALT = 582 IU/L (normal < 41 IU/L), C-reactive protein (CRP) = 19 mg/L (normal < 8 mg/L), CPK = 13779 IU/L (normal < 397). and LDH = 911 IU/L (normal < 192). CMV ELISA (serum) was strongly positive and CMV DNA by polymerase chain reaction (PCR) in blood and CSF also was positive. Immunologic screening revealed positive anti-myeloperoxidase antibodies anti-MPO = 56,9 IU/mL (normal < 9 IU/mL; ELISA). The inflammatory process involving the vessel walls and muscle fibers was histologically found in biopsy specimen of the muscle, with positive staining for CMV. The patient was treated initially with corticosteroids and intravenous immunoglobulins, but these therapies had very poor effect. Immunosuppressive therapy was instituted, resulting in a progressive partial recovery of all four limb weakness without relapses. We hypothesize that the CMV infection triggered an ANCA-positive vasculitis and its particular severe neurological involvement. An awareness of the association between CMV infection and vasculitis may have important therapeutic consequences.

Functional Improvement of Upper and Lower Extremity After Decompression and Neurolysis and Nerve Transfer in a Pediatric Patient with Acute Flaccid Myelitis

Patient: Female, 5Final Diagnosis: Enterovirus infectionSymptoms: Weakness in all 4 limbsMedication: —Clinical Procedure: Nerve decompression • neurolysis and nerve transferSpecialty: NeurosurgeryObjective:Rare diseaseBackground:Acute flaccid myelitis is an emerging polio-like illness mostly affecting young children, characterized by rapid onset of extremity weakness and paralysis in 1 or more limbs. Certain viruses, including enteroviruses such as EV-68, EV-71, poliovirus, and West Nile virus, can cause this disorder. The largest known outbreak of EVD68 in the United States was in the summer of 2014, causing severe respiratory illness and acute flaccid myelitis, mainly in young children. Furthermore, the US Centers for Disease Control and Prevention noted an increase in the number of patients with clinical symptoms of acute flaccid myelitis in 2018, and 134 confirmed cases by December 2018 were reported in the USA.Case Report:The patient in our present study was a 5-year-old female who had significant weakness and paralysis in all 4 extremities due to acute flaccid myelitis. EV-D68 had caused this disorder in this patient in August 2014. Conservative management had not helped her condition. Specific areas of concern were both shoulders and biceps, and the femoral and peroneal nerves in both sides. Of these, the right shoulder function was the worst, at less than grade 3. The patient also had marked atrophy and weakness of the right quadricep muscles. The patient underwent surgical treatment and had steady improvements in all 4 extremity functional movements.Conclusions:We demonstrated that decompression, neurolysis, and nerve transfer surgical procedures can be used successfully to correct the paralyzed upper and lower extremity movements in acute flaccid myelitis patients.

RNA-sequencing reveals altered skeletal muscle contraction, E3 ligases, autophagy, apoptosis, and chaperone expression in patients with critical illness myopathy

BackgroundCritical illness myopathy (CIM) is associated with severe skeletal muscle wasting and impaired function in intensive care unit (ICU) patients. The mechanisms underlying CIM remain incompletely understood. To elucidate the biological activities occurring at the transcriptional level in the skeletal muscle of ICU patients with CIM, the gene expression profiles, potential upstream regulators, and enrichment pathways were characterized using RNA sequencing (RNA-seq). We also compared the skeletal muscle gene signatures in ICU patients with CIM and genes perturbed by mechanical loading in one leg of the ICU patients, with an aim of reducing the loss of muscle function.MethodsRNA-seq was used to assess gene expression changes in tibialis anterior skeletal muscle samples from seven critically ill, immobilized, and mechanically ventilated ICU patients with CIM and matched control subjects. We also examined skeletal muscle gene expression for both legs of six ICU patients with CIM, where one leg was mechanically loaded for 10 h/day for an average of 9 days.ResultsIn total, 6257 of 17,221 detected genes were differentially expressed (84% upregulated; p < 0.05 and fold change ≥ 1.5) in skeletal muscle from ICU patients with CIM when compared to control subjects. The differentially expressed genes were highly associated with gene changes identified in patients with myopathy, sepsis, long-term inactivity, polymyositis, tumor, and repeat exercise resistance. Upstream regulator analysis revealed that the CIM signature could be a result of the activation of MYOD1, p38 MAPK, or treatment with dexamethasone. Passive mechanical loading only reversed expression of 0.74% of the affected genes (46 of 6257 genes).ConclusionsRNA-seq analysis revealed that the marked muscle atrophy and weakness observed in ICU patients with CIM were associated with the altered expression of genes involved in muscle contraction, newly identified E3 ligases, autophagy and calpain systems, apoptosis, and chaperone expression. In addition, MYOD1, p38 MAPK, and dexamethasone were identified as potential upstream regulators of skeletal muscle gene expression in ICU patients with CIM. Mechanical loading only marginally affected the skeletal muscle transcriptome profiling of ICU patients diagnosed with CIM.

Emaciation and Sporadic Mortality in Older Laying Hens Caused by Intussusception of the Proventriculus

Laying hens (n = 2267) ranging in age from 2 to 4 yr in a study evaluating ovarian cancer prevention were necropsied. Those that died or were culled during the 2-yr study (n = 1591) were necropsied weekly to determine the most probable cause of death or culling and cancer status. Hens surviving until the end of the study (n = 676) were euthanized and necropsied. Hens necropsied before and after a hen with proventricular intussusception served as cohorts (n = 38). Nineteen hens (13 dead, 6 culled) had intussusceptions of the proventriculus into the ventriculus. Mean age of affected hens was 154 wk (range 110-204 wk). None of the hens in the study had an intestinal intussusception, and none of the hens euthanized at the end of the study had a proventricular intussusception. Hens with proventricular intussusceptions were severely emaciated; mean body weights were 1040 and 1736 g for affected and cohort hens, respectively. Necropsy findings included prominent keel, marked muscle atrophy, generalized serous atrophy of fat, no visible proventriculus, esophagus directly entering the ventriculus, and an enlarged, spherical, firm ventriculus, which contained an invaginated, swollen, diffusely ulcerated proventriculus. Eighteen affected hens were anovulatory (94.7%) compared to 27 cohorts (71.1%). Severe, diffuse necrosis and ulceration of the proventricular mucosa was confirmed microscopically, but no etiologic agent was identified. In conclusion, proventricular intussusception of undetermined etiology was identified as a cause of sporadic emaciation, culling, and mortality in older laying hens.

Diagnostic sensitivity of electrophysiology and ultrasonography in ulnar neuropathies of different severity

ObjectiveTo assess the diagnostic performance of electrophysiology and nerve ultrasound in ulnar neuropathies of varying clinical severity in 135 consecutive patients. MethodsClinical severity of ulnar neuropathy was graded on a 4 point scale from very mild (symptoms only) to severe (marked atrophy of intrinsic hand muscles). Sensitivity and localization ability of electrophysiology and nerve ultrasound were assessed for each point of the scale. ResultsUltrasound had higher sensitivity than electrophysiology in clinically very mild (20% and 3% for ultrasound and electrophysiology, respectively) and mild (62% and 47% for ultrasound and electrophysiology, respectively) neuropathies, had greater localizing ability in axonal ulnar neuropathies, and identified nerve hypermobility.Ultrasound nerve cross-sectional area had strong positive correlation with both clinical and electrophysiological severity scores, but with significant overlap across the severity groups. ConclusionThe diagnostic work-up of ulnar neuropathies was improved by using both electrophysiology and ultrasound at all levels of clinical severity. Ultrasound increased the diagnostic yield in very mild and mild neuropathies, localized all the ulnar neuropathies with abnormal non-localizing electrophysiology and identified nerve hypermobility. SignificanceThis is the first detailed analysis of the diagnostic performance of electrophysiology and ultrasound in ulnar neuropathies of varying severity.

Effects of mesenchymal stromal cells on type 1 diabetes mellitus rat muscles.

Type 1 diabetes mellitus (DM) causes marked skeletal muscle atrophy. Mesenchymal stromal cells (MSC) are an attractive therapy to avoid diabetic complications because of their ability to modify the microenvironment at sites of tissue injury. The objective of this study was to evaluate the effects of MSC transplantation on muscle adaptation caused by diabetes. DM was induced by streptozotocin (STZ), and the diabetic animals received systemic MSC transplantation. The von Frey test and footprint analysis were used to assess sensation and sensory motor performance, respectively. Tibialis anterior muscles were investigated by morphology; molecular markers atrogin-1/muscle RING-finger protein-1, nuclear factor κB/p38 mitogen-activated protein kinase, tumor necrosis-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, myostatin, myogenic differentiation 1, and insulin-like growth factor 1 were also assessed. MSC transplantation improved sensation and walking performance and also decreased muscle fibrosis in DM rats by modulating atrogenes but did not prevent muscle atrophy. MSCs can reduce muscle and functional complications that result from type 1 DM in rats. Muscle Nerve 58: 583-591, 2018.

P.192 - Muscle fiber dysfunction contributes to clinical muscle weakness in inclusion body myositis

Inclusion body myositis (IBM) is the most common acquired muscle disorder in adults over 50 years old. It is characterized by progressive muscle weakness and marked muscle atrophy, most prominent in the finger flexors and quadriceps muscle. In addition to atrophy, fatty replacement of muscle tissue contributes to clinical muscle weakness and functional decline. This study aims to investigate the contractile performance of residual muscle tissue. We included 8 participants with IBM and 12 healthy controls. We measured individual health related quality of life, functional performance and muscle strength. In all participants, muscle contractile capacity was measured both in vivo, using quantitative muscle testing and MRI imaging, and ex vivo, using single fiber studies of the vastus lateralis as well as tibialis anterior muscle biopsies. Quadriceps specific force was calculated by correcting the voluntary maximum force (N) for the contractile cross-sectional area (CCSA). CCSA was calculated by multiplying the total cross-sectional area by the muscle fraction on MRI. Voluntary maximum force generation of the quadriceps muscle was significantly reduced in IBM participants (216.9 ± 57.6 N vs. 572.1 ± 53.1 N, p < .001). Quadriceps specific force was reduced in IBM participants. Muscle fiber specific force was also reduced in IBM patients compared to healthy controls (type 1 fibers: 158.3 ± 4.1 mN/mm2 in IBM vs. 178.9 ± 3.4 in controls, type 2 fibers: 180.3 ± 7.2 mN/mm2 in IBM vs. 213.7 ± 4.2 in controls, p = .036). Reduced muscle fiber specific force was equally present in vastus lateralis and tibialis anterior muscles. Contractile performance of residual muscle tissue is impaired in IBM patients, both in vivo and ex vivo. We conclude that sarcomeric dysfunction contributes to clinical muscle weakness in IBM.

Exome sequencing reveals independent SGCD deletions causing limb girdle muscular dystrophy in Boston terriers

BackgroundLimb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked muscle weakness and atrophy in the shoulder and hips during puppyhood.MethodsFollowing clinical evaluation, the identification of the dystrophic histological phenotype on muscle histology, and demonstration of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome sequencing was performed on five Boston terriers: one affected dog and its three family members and one unrelated affected dog.ResultsWithin sarcoglycan-δ (SGCD), a two base pair deletion segregating with LGMD in the family was discovered, and a deletion encompassing exons 7 and 8 was found in the unrelated dog. Both mutations are predicted to cause an absence of SGCD protein, confirmed by immunohistochemistry. The mutations are private to each family.ConclusionsHere, we describe the first cases of canine LGMD characterized at the molecular level with the classification of LGMD2F.

Lumbosciatalgia Due to Pyramidal Syndrome

Piriformis syndrome is a poorly known cause of sciatica and there are few cases reported in the international literature where sciatica is the form of presentation. It is caused by compression or entrapment of the sciatic nerve due to piriformis muscle pathology. A 65-year-old Caucasian man was admitted in Department of Neurology because he suffered from sciatica and weakness of the left lower limb, so initially a disc herniation was suspected. Upon physical examination, he presented marked gluteal muscle atrophy, mild quadriceps muscle atrophy and paresis of the left lower extremity with distal dominance. Electroneuromyography provided evidence of left sciatic nerve injury of severe intensity and profuse signs of active denervation present. MRI lumbar plexus revealed asymmetrical enlargement of the left piriformis muscle that obliterated the ipsilateral greater sciatic foramen, compressing the left sciatic nerve. As a result, secondary atrophy of the gluteus maximus and medius can be observed on this side. Due to the severity of the symptoms, surgery was performed to release the nerve. Piriformis syndrome rarely occurs as sciatica. The diagnosis is usually delayed because of the absence of further pathognomic testing and established diagnostic criteria, which are based on clinical manifestations. This syndrome is often confused with lumbar-sacral or hip disease. So, in a disease such as the case presented, the piriformis syndrome should be considered. We think that it is very interesting to know that a piriformis syndrome can debut as a lumbosciatalgia and it can be confused with lumbar disc pathology, so this may delay the diagnosis and cause further suffering to the patient. J Med Cases. 2016;7(6):248-251 doi: http://dx.doi.org/10.14740/jmc2503w