Silent Muscle Research Articles

Plateau potentials contribute to myotonia in mouse models of myotonia congenita.

It has long been accepted that myotonia (muscle stiffness) in patients with muscle channelopathies is due to myotonic discharges (involuntary firing of action potentials). In a previous study, we identified a novel phenomenon in myotonic muscle: development of plateau potentials, transient depolarizations to near -35mV lasting for seconds to minutes. In the current study we examined whether plateau potentials contribute to myotonia. A recessive genetic model (ClCadr mice) with complete loss of muscle chloride channel (ClC-1) function was used to model severe myotonia congenita with complete loss of ClC-1 function and a pharmacologic model using anthracene-9-carboxylic acid (9AC) was used to model milder myotonia congenita with incomplete loss of ClC-1 function. Simultaneous measurements of action potentials and myoplasmic Ca2+ from individual muscle fibers were compared to recordings of whole muscle force generation. In ClCadr muscle both myotonia and plateau potentials lasted 10s of seconds to minutes. During plateau potentials lasting 1-2min, there was a gradual transition from high to low intracellular Ca2+, suggesting a transition in individual fibers from myotonia to flaccid paralysis in severe myotonia congenita. In 9AC-treated muscles, both myotonia and plateau potentials lasted only a few seconds and Ca2+ remained elevated during the plateau potentials, suggesting plateau potentials contribute to myotonia without causing weakness. We propose, that in myotonic muscle, there is a novel state in which there is contraction in the absence of action potentials. This discovery provides a mechanism to explain reports of patients with myotonia who suffer from electrically silent muscle contraction lasting minutes.

Clinical, Kinematic and Muscle Assessment of Bilateral Coordinated Upper-Limb Movements Following Cervical Spinal Cord Injury.

Cervical spinal cord injury (cSCI) often results in bilateral impairment of the arms, leading to difficulties in performing daily activities. However, little is known about the neuromotor alterations that affect the ability of individuals with cSCI to perform coordinated movements with both arms. To address this issue, we developed and tested a functional assessment that integrates clinical, kinematic, and muscle activity measures, including the evaluation of bilateral arm movements. Twelve subjects with a C5-C7 spinal lesion and six unimpaired subjects underwent an evaluation that included three tests: the Manual Muscle Test, Range Of Motion test and Arm stabilisation test, a subsection of the "Van Lieshout arm/hand function test". During the latter, we recorded kinematic and muscle activity data from the upper-body during the execution of a set of movements that required participants to stabilize both arms against gravity at different configurations. Analytical methods, including muscle synergies, spinal maps, and Principal Component Analysis, were used to analyse the data. Clinical tests detected limitations in shoulder abduction-flexion of cSCI participants and alterations in elbows-wrists motor function. The instrumented assessment provided insight into how these limitations impacted the ability of cSCI participants to perform bilateral movements. They exhibited severe difficulty in performing movements involving over-the-shoulder motion and shoulder internal rotation due to altered patterns of activity of the scapular stabilizer muscles, latissimus dorsi, pectoralis, and triceps. Our findings shed light on the bilateral neuromotor changes that occur post-cSCI addressing not only motor deficits, but also the underlying abnormal, weak, or silent muscle activations.

Magnetic resonance imaging with diffusion-weighted imaging in the evaluation of thyroid-associated orbitopathy: getting below the tip of the iceberg

To compare extraocular muscles (EOMs) T2, post-contrast T1 (T1Gad) signal intensity ratios (SIRs) and normalized-apparent diffusion coefficient (n-ADC) values in patients with thyroid-associated orbitopathy (TAO) at different phases of activity and severity and correlate MRI modifications to clinical evolution during follow-up. A total of 74 TAO patients were classified as active or inactive on the basis of the clinical activity score (CAS). Severity of EOM impairment was evaluated by assigning a functional score to each rectus. T2, T1Gad SIRs and n-ADC of EOMs were compared in patients with active inflammation, those with inactive disease and 26 healthy controls, and correlated with clinical scores. MRI parameter variation was correlated with clinical modifications during follow-up. All MRI parameters in TAO EOMs were significantly higher than in healthy subjects and correlated with muscle dysfunction and CAS. EOMs of active patients showed higher T2 and T1Gad SIRs than those with inactive disease. The T2 SIR and n-ADC of normally functioning TAO EOMs were higher than those of healthy controls. SIRs decreased in clinically improved and clinically stable EOMs after therapy. T2 SIR, T1Gad SIR and n-ADC are objective measures of activity and severity of EOMs in TAO patients. MRI shows clinically silent muscle involvement and modifications. • MRI and DWI measures are objective, quantitative parameters of TAO activity and severity • MRI and DWI measures significantly correlate with clinical scores in TAO patients • MRI and DWI can identify clinically silent inflammation of deep orbital structures • MRI and DWI can depict subclinical modifications during follow-up • MRI and DWI may aid clinicians in choosing the most appropriate treatment.

Electrically Silent Muscle Visible by Ultrasound

A 65-year-old woman with multiple chronic cranial neuropathies had spinal accessory innervated muscles that were virtually invisible to electromyography. Ultrasound imaging revealed the extensive atrophy and increased echogenicity that corresponded to the thinness of the muscles and their loss of insertional activity. In patients with severe atrophy of trapezius or sternocleidomastoid muscles, ultrasound may help in identify chronically denervated muscle.

Role of MRI in the diagnosis of neuromuscular disorders

Recently, the assessment of the muscles using limb MRI and whole body MRI has become widely available and more frequent. In cases of muscular dystrophies it may help to select the optimal muscles for biopsy, because the severely atrophic and degenerated muscles are not suitable for histological tests. It is also known that the pattern of muscle involvement is characteristic for a certain neuromuscular disease, and clinically silent muscle damage can be visualized, as well. Therefore, imaging of muscles is helpful in neuromuscular differential diagnosis and planning genetic tests.

Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation

Suv39h1 is a histone H3 lysine-9 (H3-K9) specific methyltransferase (HMT) that is associated with gene silencing through chromatin modification. The transition from proliferation into differentiation of muscle cell is accompanied by transcriptional activation of previously silent muscle genes. I report Suv39h1 interaction with myogenic regulator MyoD in proliferating muscle cells and its HMT activity, which is associated with MyoD, diminishes as differentiation proceeds. The Suv39h1-MyoD complex was detected on the chromatin regulatory regions of a silent differentiation signal muscle gene myogenin and that Suv39h1 presence correlated with H3-K9 methylation. Increased Suv39h1 expression repressed MyoD-dependent muscle gene expression and this property required its HMT activity. This repression required Suv39h1 association with MyoD as well as sustained methylation of H3-K9 on myogenin promoter. Suv39h1 was required for muscle gene repression because its abrogation by siRNA activates these gene expressions by MyoD. These findings suggest that Suv39h1 presence in association with MyoD on the promoter of muscle genes silences gene transcription, providing a necessary checkpoint between proliferation and differentiation.

Evoked pain in the motor endplate region of the brachial biceps muscle: an experimental study.

Spontaneous electrical activity, interpreted as motor endplate activity, has been reported at muscle trigger points. This study examined whether the motor endplate region, identified by electromyography, is more sensitive to noxious stimuli than other muscle sites. We induced pain in the brachial biceps muscles of 21 healthy subjects by injecting capsaicin (30 microg/0.1 ml) and NaCl (5%/0.2 ml) in the motor endplate region and at electrically silent muscle sites. Needle and evoked pain were measured by a visual analogue scale (VAS) (0-10) and the short form of the McGill Pain Questionnaire. The needle pain in the motor endplate region differed both in intensity and quality from that at other sites. The maximal pain after NaCl 5% was higher, and the VAS area-under-the-curve for NaCl 5% and capsaicin were larger, in the motor endplate region than in other sites. A higher density of muscle nociceptors in the vicinity of the motor endplate region may account for the observed differences in pain. These findings may have clinical implications for the treatment of musculoskeletal pain conditions.

Diagnosis and Differential Diagnosis of Muscle Cramps: A Clinical Approach

Muscle cramps are one of the most frequently occurring neuromuscular features. They occur normally in healthy persons, can be the manifestation of one of several cramp syndromes, but can also be the expression of various underlying neuromuscular disorders. We review the various types and boundaries of cramps, ranging from true muscle cramps to electromyographic silent muscle contractures (for example, Brody's disease) and cramps associated with dystrophinopathies. In addition, we delineate true muscle cramp from muscle stiffness and muscle twitching. Finally, we propose a workup in a patient suspected of having muscle cramps.

Rippling muscle disease: a review.

Rippling muscle disease (RMD) is a benign myopathy with symptoms and signs of muscular hyperexcitability. The typical finding is electrically silent muscle contractions provoked by mechanical stimuli and stretch. After the first description in 1975, there have been several publications on this disorder. Although RMD most often is reported with autosomal dominant inheritance, some sporadic cases are found, and an association with other diseases such as myasthenia gravis has also been reported. The pathophysiological mechanism is still not clarified. Abnormalities in calcium homeostasis in the sarcoplasmic reticulum have been proposed as the most probable causes. However, recent genetic studies make a primary channelopathy unlikely. In this article, a review of this curious disease is presented.

Rhabdomyolysis as a complication of canine babesiosis

Rhabdomyolysis was diagnosed in two dogs with babesiosis. The first animal presented with muscle pain and caramel-coloured urine, and had markedly elevated serum myoglobin and muscle enzymes. Acute renal failure complicated the clinical picture. The second dog exhibited muscle pain and tremors, together with neurological signs and pulmonary oedema, and died soon after admission. Muscle necrosis and haemorrhage were found at necropsy. In human malaria, a disease clinically similar to canine babesiosis, rhabdomyolysis is unusual, but clinically silent muscle damage appears to be common. Likewise, biochemical evidence of muscle damage is readily found in experimental bovine babesiosis. Muscle enzymes were mildly elevated in three dogs with severe babesiosis and pigmenturia but there was no obvious muscle damage, indicating that this might also apply to canine babesiosis. The pathogenesis of infection-associated rhabdomyolysis and acute renal failure remains unclear, but inflammatory cytokines and nitric oxide could play an important role.

A myopathy associated with muscle hypertonicity in the Cavalier King Charles Spaniel

Clinical signs of electrically silent muscle hypertonicity are described in five Cavalier King Charles dogs. Biopsies of the biceps femoris and triceps muscles, when examined with the electron miscroscope, revealed evidence of sarcotubular and mitochondrial abnormalities. These included enlargement of the sarcoplasmic reticulum, hydropic degeneration of mitochondria, tubular proliferations in the vicinity of the triads and vacuolar invagination of mitochondria. The exact nature of these findings is not clear and it is suggested that utilization of tracer techniques would help to explain them.

Electrically silent muscle contractions, myoedema and myopathy

Electrically silent muscle contractions, myoedema and myopathy

5-Azacytidine permits gene activation in a previously noninducible cell type.

We previously reported that silent muscle genes in fibroblasts could be activated following fusion with muscle cells to form heterokaryons. This activation did not require changes in chromatin structure involving significant DNA synthesis. We report here that muscle gene activation was never observed when HeLa cells were used as the nonmuscle fusion partner. However, if HeLa cells were treated with 5-azacytidine (5-aza-CR) prior to fusion, muscle gene expression was induced in the heterokaryons. The genes for both an early (5.1H11 cell surface antigen) and a late (MM-creatine kinase) muscle function were activated, but were frequently not coordinately expressed. These results suggest that the expression of two muscle genes, which is usually sequential, is not interdependent. Furthermore, changes induced by 5-aza-CR, presumably in the level of DNA methylation, are required for muscle genes in HeLa cells to be expressed in response to putative trans-acting regulatory factor(s) present in muscle cells.

High energy phosphate depletion in a model of defective muscle glycolysis.

AbstractAn animal model of defective muscle glycolysis can be produced by intra‐aortic injection of iodoacetate which blocks the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase. The animals show exercise‐induced, electrically silent muscle cramps and postexercise rhabdomyolysis. Exercised, cramped soleus and extensor digitorum longus muscles from these animals show marked depletion of the high energy compounds adenosine triphosphate (ATP) and creatine phosphate and accumulation of fructose‐1, 6‐diphosphate. This finding supports the hypothesis that exercise‐induced muscle contracture and cell damage in disorders of muscle glycolysis/glycogenolysis are the result of depletion of high energy molecules in the muscle cells.

Studies on the origin and the pattern of the miniature electrical oscillation in the insect muscle.

1. The miniature electrical oscillation of the tymbal muscle of the cicada was investigated with the following species: Terpnosia vacua, Platypleura kaempferi, Cryptotympana japonensis, Graptopsaltria nigrofuscata, Tanna japo-nensis, Oncotympana maculaticollis and Meimna opalifera.2. The miniature electrical oscillation was observed not only in the silent muscle but also in the shrilling muscle. It was observed either in situ or in isolated preparation.3. The miniature electrical oscillation was not affected by motor innervation but originated myogenically.4. The pattern of oscillation was usually irregular but sometimes changed to be regular, waxing and waning.5. The frequencies of two sources which were supposed to compose the beating oscillation were approximately equal to that which was found when the wave was regular.6. The frequencies of regular and beating discharges were quite comparable to that of the action potentials of respective species in singing.7. The cause of the transition of the pattern of oscillation was discussed and its similarity to the electrocardiogram of the fibrillation was noticed.