Muscle fiber conduction velocity at different states of isotonic contraction.

Conduction velocity (CV), relative twitch force (RTF) and contraction time (CT) of single muscle fibers (SF) and small muscle fiber bundles (FB) were measured at different states of isotonic contraction with double impulse stimuli at varying interstimulus intervals (ISI) from 0 to 1000 ms in the biceps brachii muscle in vivo. During an isotonic contraction, muscle fibers conducted the action potential on average 0.18 m/s faster along the muscle fiber membrane than did relaxed muscle fibers. This difference was statistically significant (P < 0.001). There was a significant positive correlation between the degree of isotonic contraction and fiber bundle conduction velocity (FBCV) with a first peak at the maximum RTF at an ISI of 9 ms and a second peak at the maximum CT at an ISI of 100 ms.     

Pharmacologic and genetic therapy for childhood muscular dystrophies

The outstanding advances in the molecular characterization of muscle diseases, including muscular dystrophies, inflammatory myopathies, and ion channel disorders, have resulted in the identification of potential targets for pharmacologic and genetic therapy in the best characterized of these diseases. The most common myopathy in children, Duchenne muscular dystrophy (DMD), is the focus of active pharmacologic clinical trials. Genetic transfer therapy research for this and other dystrophies is rapidly moving forward. However, as new approaches for treatment are being actively investigated, the current modality of treatment for all myopathies is still in the realm of physical medicine and rehabilitation. The focus of this review is on the advances in pharmacologic and genetic therapy research in DMD and limb girdle muscular dystrophies.     

Augmentation of the contraction force of human thenar muscles by and during brief discharge trains

We investigated the influence of the history of activity on the contractile properties of abductor pollicis brevis (APB) to define how the forces produced by individual stimuli change within a stimulus train, with a view to clarifying the optimal discharge frequency for force production in brief trains. Supramaximal electrical stimuli were delivered to the median nerve at the wrist singly or in trains of 2-5 at various interstimulus intervals (ISIs). The force and electromyographic (EMG) responses to trains of n stimuli were defined by online subtraction of the responses to n - 1 stimuli. The force attributable to the nth stimulus was normalized to that produced by a single stimulus. The contraction force produced by 2 stimuli exceeded the force expected with linear summation of 2 single twitches by 30-40% at ISIs of 2-100 ms. Increasing the number of stimuli resulted in less augmentation of the force produced by the last stimulus in the train for ISIs up to 20 ms, but greater augmentation for ISIs of 50-100 ms. At ISIs of less than 10 ms, the time to peak force produced by the last stimulus in a 5-pulse train was delayed by approximately 100 ms, the peak force produced by that stimulus was less than that produced by a single stimulus, and it occurred on the falling phase of the overall contraction. These properties are best explained by the catchlike property of muscle. This implies that the augmentation of contraction force due to this property can increase throughout a stimulus train, and is not restricted to the doublet discharges that have conventionally been studied. We conclude that, with brief discharge trains, maximal forces occur at ISIs of 56-75 ms, intervals that are longer than those conventionally associated with the catchlike property. Discharge rates of 15-20 HZ appear to be optimal for force generation by APB during steady contractions.     

Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency

Idiopathic inflammatory myopathies are a group of acquired, heterogeneous, systemic diseases commonly regarded as autoimmune disorders. Differential diagnosis includes muscular dystrophies, especially the dysferlin-deficiency myopathy. We report a case of a patient diagnosed with polymyositis and with associated autoimmune diseases that finally turned out to be a dysferlin deficiency (limb girdle muscular dystrophy type 2B). A possible link between dysferlin deficiency an autoimmunity is discussed.     

Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique ultrastructural feature

Rimmed vacuoles (RV) are a characteristic pathological feature in inclusion body myositis, but may also occur in other neuromuscular disorders, such as distal myopathies, oculopharyngeal myopathy, polymyositis, rigid spine syndrome, congenital myopathies, and some limb girdle muscular dystrophies, as well as in various neurogenic diseases. We describe a patient with RV in familial facioscapulohumeral muscular dystrophy (FSHD) associated with an FSHD-typical deletion on chromosome 4q35. Thus, FSHD should be included in the differential diagnosis of neuromuscular disorders with RV.     

Calpain-3 gene defect causing limb gird muscular dystrophy in a Hungarian family

Limb gird muscular dystrophies (LGMD2) are a clinically and genetically heterogeneous group of hereditary diseases with autosomal recessive trait, characterized by progressive atrophy and weakness predominantly in the proximal limb muscles. The authors present clinical, histological, immunohistochemical and immunoblot results of two sisters suffering from so far unclassified autosomal recessive limb girdle muscular dystrophy. Haplotype analysis for genes possibly involved in autosomal recessive limb girdle muscular dystrophies was performed in the genetically informative family. All of the results pointed to a molecular genetic defect of the calpain-3 (CAPN3) gene. Direct sequencing of the CAPN3 gene revealed compound heterozygous state for two mutations previously described in association with limb girdle muscular dystrophy, proving pathogenicity. The authors would like to emphasize the importance of the above described combined strategy in diagnosing limb girdle muscular dystrophies.     

Diagnostic value of in situ muscle fiber conduction velocity measurements in myopathies

In situ studies on muscle fiber conduction velocity (MFCV) were performed in 54 patients with histologically and biochemically defined myopathies. MFCV was measured over a 10 cm segment of the rectus femoris muscle by intramuscular stimulation and recording. Muscle disorders included muscular dystrophies, myotonic dystrophy, inflammatory myopathies, metabolic myopathies, endocrine myopathies, and congenital myopathies with structural abnormalities. Ten healthy volunteers served as controls. MFCV was significantly reduced in all patients except those with a defect in glycolysis and those that had recovered from acute myositis. MFCV did not vary with either sex, age or the duration of the disease. This shows that MFCV slowing is an unspecific finding in most myopathies. However, in some patients with normal needle electromyography, MFCV provided additional information in diagnosing muscle disease.     

Muscle biopsy correlated with electromyography. Study of 100 cases

To find what the correlation is and verify if it is possible to avoid extensive electromyographic examination, studying only one muscle, 100 patients with neuromuscular disorders (58 primary myopathies, 32 neurogenic disorders and 10 myotonic dystrophies) were submitted to quantified electromyography (EMG) and muscle biopsy (MB) with fresh-frozen section plus histochemistry in the same muscle, but on the opposite side. The EMG was abnormal in 98% and MB in 93% of the cases. EMG and MB had a concordance of 84.3% in the neurogenic disorders and 84.77% in the primary myopathies. A correlation of 80% was obtained between all MB and EMG (including the cases of myotonic dystrophies), regarding the origin of the pathogenic process (p less than 0.01). The EMG had 5% inconsistencies and the MB 11%, with respect to the pathogenic process. When the myotonic dystrophy was separated from the primary myopathies and from the denervation disorders, a complete concordance was found in all MB and had only 3.4% inconsistencies in the denervation disorders and 3.1% in the primary myopathies.     

Muscle function in patients with primary hyperparathyroidism

The muscle contraction of the anterior tibial muscle was investigated by measurements of electrically stimulated and computer-analyzed muscle twitches in 18 unselected patients with primary hyperparathyroidism (HPT) and in 20 healthy control persons. The HPT patients had a lower muscle twitch tension (TT) at single stimulation, compared with the control group [76 +/- 24 N (SD) and 99 +/- 33 N respectively, P less than 0.05]. At high-frequency stimulation the difference in muscle force increased, and at 20 Hz stimulation the force in the HPT patients was 73% of that in the controls (P less than 0.01). There were no differences between the HPT patients and the control persons in neither contraction time nor half relaxation time at single muscle twitch nor in twitch potentiation after 20 and 90 seconds maximal voluntary contraction. The results indicate that patients with primary HPT have an impaired muscle function of probable importance for their symptoms of weakness and generalized fatigue.     

Factors affecting the stability of the spike-triggered averaged force in the human first dorsal interosseus muscle

The reproducibility of motor unit twitches obtained using spike-triggered averaging (STA) was examined in the human first dorsal interosseus. For each motor unit (30 total) a series of STA twitches was derived using a 30 s averaging window. Within each averaging window, eight independent measures characterizing motor unit discharge and whole muscle force properties were recorded. These included the mean and standard deviation (S.D.) of the interspike interval (ISI), the mean and S.D. of pre and post-trigger ISIs used in averaging, and mean and S.D. of whole muscle force. To determine the relative importance of the independent variables on twitch reproducibility, the variables were used in a multiple regression analysis performed on STA twitch peak force (PF), time to peak force (TTP) and time of half-force decay (HFD). It was found that PF was significantly correlated to the mean and S.D. of whole muscle force, and mean post-trigger ISI. TTP was significantly correlated to the S.D. of the post-trigger ISI and mean whole muscle force while HFD was related to the mean and S.D. of the pre-trigger ISI and the mean post-trigger ISI. It was concluded that by minimizing whole muscle force variability and the mean and S.D. of acceptable ISIs used in the STA process, the reproducibility of the STA twitch is improved.     

Single muscle fiber contractile properties in adults with muscular dystrophy treated with MYO‐029

Myostatin inhibitors are being investigated as treatments for myopathies. We assessed single muscle fiber contractile properties before and after 6 months of study drug in 6 patients with facioscapulohumeral, Becker, and limb‐girdle muscular dystrophy. Five of the patients received MYO‐029, a myostatin inhibitor, and 1 received placebo. The chemically skinned single muscle fiber preparation was used to measure single fiber force, specific force, maximum unloaded shortening velocity, power, and specific power in type I and IIa fibers from each subject. In 4 of 5 patients who received MYO‐029, improvement was seen in single muscle fiber contractile properties; thus, there may be a beneficial effect of myostatin inhibition on muscle physiology at the cellular level. No improvement was seen in the patient who received placebo. This finding may be clinically relevant in spite of the fact that quantitative muscle strength measurements in our patients did not improve. Further studies of myostatin inhibition as a treatment for muscular dystrophy are warranted, and single muscle fiber contractile studies are a useful assay for muscle function at the cellular level. Muscle Nerve 39: 3–9, 2009     

Muscle contractile properties in children with spastic diplegia

The aim of the present study was to evaluate contractile properties of the plantarflexor muscles in children with spastic diplegia (SD) in comparison of age-matched healthy children. Twelve prepubertal children with SD aged 11-12 years (6 girls and 6 boys) and 12 age- and gender-matched healthy control children (6 girls and 6 boys) participated in this study. Subjects were seated in a custom-made dynamometric chair with the dominant leg flexed 90 degrees at the knee and ankle joints. Twitch contraction characteristics of the plantarflexor muscles were measured by supramaximal electrical stimulation of posterior tibial nerve in popliteal fossa using square-wave pulses of 1 ms duration at rest and after a brief (5 s) isometric maximal voluntary contraction (MVC), i.e., during post-activation potentiation (PAP). Children with SD had significantly lower (p<0.05) MVC force, twitch contraction peak force (PF), PAP of twitch force, and twitch maximal rates of force development and relaxation compared to control group. Twitch contraction PF:MVC force ratio was higher (p<0.05) in children with SD than in the control group. However, no significant differences in twitch contraction and half-relaxation times were observed between the measured groups. It was concluded that prepubertal children with SD in comparison of normal children are characterized by markedly reduced isometric voluntary and electrically evoked twitch contraction maximal force, capacity for twitch PAP, and rates of twitch force production and relaxation of the plantarflexor muscles. The time-course characteristics of isometric twitch contraction were similar in children with SD and normal children.     

Contractile properties of muscles in myotonic dystrophy.

A study has been made of the contractile properties of plantarflexor and dorsiflexor muscles in 25 patients with myotonic dystrophy and in the same number of closely-matched control subjects. As anticipated, the mean torques developed during maximal voluntary contraction and during the isometric twitch were significantly reduced in the patient population, as were the mean amplitudes of the respective maximum muscle compound action potentials (M-waves). There was considerable variation in weakness between patients, however, and in some there was a striking discrepancy between the results for the plantarflexor and dorsiflexor muscles. It was also found that, in both muscle groups, the mean twitch contraction times were significantly shorter in patients than in controls, but no differences could be demonstrated in relation to fatiguability and post-activation of the twitch. Some patients had great difficulty in obtaining full activation of plantarflexor motor units but there was improvement with repeated effort.     

The floppy infant: contribution of genetic and metabolic disorders

The floppy infant syndrome is a well-recognized entity for pediatricians and neonatologists. The condition refers to an infant with generalized hypotonia presenting at birth or in early life. The diagnostic work up in many instances is often complex, and requires multidisciplinary assessment. Advances in genetics and neurosciences have lead to recognition of newer diagnostic entities (several congenital myopathies), and rapid molecular diagnosis is now possible for several conditions such as spinal muscular atrophy (SMA), congenital muscular dystrophies (CMD), several forms of congenital myopathies and congenital myotonic dystrophy. The focus of the present review is to describe the advances in our understanding in the genetic, metabolic basis of neurological disorders, as well as the investigative work up of the floppy infant. An algorithm for the systematic evaluation of infants with hypotonia is suggested for the practicing pediatrician/neonatologist.     

External recording of twitch time course in cat ankle muscles

In chronic experiments concerning the activity-dependent plasticity of muscle properties, a simple and noninvasive method was used for monitoring changes of twitch speed in conscious adult cats. The animals had been provided with implanted electrodes for nerve stimulation, and a hand-held force transducer was pressed against the fully extended ankle joint while single test pulses were delivered to the common peroneal nerve. In the present report, this technique for the recording of ankle twitches is subjected to critical analysis and evaluation. The measurements were highly reproducible with respect to contraction time (time-to-peak) but less so for half-relaxation time and twitch amplitude; other methods should be used for the long-term monitoring of contractile force. The total force (torque) of the ankle twitch was mainly produced by tibialis anterior (about 45%), peroneus longus (PerL; 27%) and extensor digitorum longus (23%). The ankle twitch produced by PerL alone had about the same contraction time as that of all the muscles together. Among muscles that had become changed as a result of long-term electrical stimulation there was, in general, a good correspondence between the contraction times from simple external recordings of ankle twitches and those separately measured for PerL under general anesthesia (force transducer then directly connected to PerL tendon).     

Distribution of skeletal muscle involvement in myotonic dystrophy--a computed tomographic study

The computed tomography (CT) scan was performed on 8 myotonic dystrophy (MD) and 3 congenital myotonic dystrophy (CMD) patients on the following seven levels; the jaw, the neck, the shoulder girdle, the abdomen, the pelvic girdle, the thigh and the lower leg. Muscle atrophy was shown as low density areas or a reduction in the cross-sectional area of the muscles. The earliest finding in the disease was severe atrophy of the sternocleidomastoid and mild atrophy of the masseter and the pterygoid medialis. In addition, spinal, abdominal wall and lower leg muscles were involved. The distal muscles were more markedly affected than the proximal in the lower limbs. These changes were characteristically observed in cases without apparent muscle symptoms. Levator scapulae, psoas major, rectus femoris, peroneal longus et brevis and tibialis posterior were relatively well preserved and were even hypertrophic in some cases. The shoulder girdle muscles were more markedly affected than the pelvic girdle muscles. There was no substantial difference in the CT findings between MD and CMD.     

Properties of motor units in the first deep lumbrical muscle of the cat's foot.

Isometric contractions of single motor units were studied in the first deep lumbrical muscle of the cat's hind-foot. Motor units with short twitch contraction times (15-20 msec) generally differed from those with longer ones (23-50 msec; contraction time measured in unpotentiated twitches) in showing (1) a greater maximum tetanic tension, (2) a smaller resistance to fatigue, (3) more post-tetanic potentiation of twitch tension, and (4) no post-tetanic occurrence of repetitive activity in response to single nerve stimuli (such "post-tetanic repetitive activity" was seen in several of the slower units). The ratio between unpotentiated twitch tension and maximum tetanic tension was similar for units with brief and long contraction times. The peak-to-peak amplitude of a single motor unit spike, recorded with gross electrodes, tended to be directly proportional to the maximum tetanic tension of the same motor unit.     

Myotonic syndromes

PURPOSE OF REVIEW: To highlight recent advances in understanding the clinical manifestations and molecular genetics of myotonic syndromes, with particular emphasis on the myotonic dystrophies. RECENT FINDINGS: Myotonic syndromes include the non-dystrophic myotonias, caused by mutations in genes encoding the chloride or sodium channels that are specific to skeletal muscle, and the myotonic dystrophies. Previous studies have shown that myotonic dystrophy type 1 is caused by the expansion of a CTG repeat in the gene. Recently, it was discovered that myotonic dystrophy type 2 (proximal myotonic myopathy) is also caused by a DNA expansion mutation. In both types of myotonic dystrophy the expanded repeat is transcribed and the RNA produced from the mutant allele is retained in nuclear inclusions. Recent studies suggest that the mutant RNA has a toxic effect on muscle fibers by interfering with the essential functions of the myonucleus, such as RNA processing. SUMMARY: It now appears likely that myotonic dystrophy is the first instance of a genetic disease in which the harmful effect of a mutation involves the production of a pathogenic RNA. However, the exact mechanism is not understood, and it is unclear whether this RNA-mediated disease process is also responsible for the manifestations of myotonic dystrophy in non-muscle tissues.     

DNAJB6基因突变致显性遗传性肌病一家系并文献复习

目的总结常染色体显性遗传性DNAJB6基因突变所致肌病的临床表型和基因突变特点。方法回顾分析一家系2例DNAJB6基因突变所致肌病患者的临床表现、实验室、肌肉影像学、神经电生理学、肌肉病理学和基因检测结果,并进行文献复习。结果先证者主要表现为四肢远近端肌无力,下肢重于上肢、近端重于远端,其父呈姿势异常,上楼需扶持。二者血清肌酸激酶水平正常,MRI表现为不同程度肌肉脂肪化,组织病理学可见肌营养不良样改变,部分肌纤维内镶边空泡形成,核内移增多或个别肌纤维再生。基因检测提示先证者及其父均携带DNAJB6基因c.161A>C(p.Glu54Ala)杂合突变,为中国大陆首次报道,分别为肢带型肌营养不良症D1型(LGMD?D1型)和远端型肌病型,该家系明确为常染色体显性遗传性DNAJB6基因突变所致肌病家系。结合文献提示DNAJB6基因突变所致肌病临床表现存在异质性,同一家系可表现为不同的临床亚型。结论DNAJB6基因突变可导致肢带型肌营养不良症和远端型肌病两种表型,肌肉病理均呈现镶边空泡和肌营养不良样改变。该家系进一步扩展了DNAJB6基因突变的表型谱。     

Firing and contractile properties of human lower lip motor units during sustained isometric contractions

Human subjects were taught to generate constant forces with their lips by contracting across a pair of hooks which held the corners of the mouth fixed in place. The force was measured with a strain gauge attached to one of the hooks. The activity of single motor units was recorded during production of small to near maximal levels of force. The recruitment and firing patterns of each unit were observed, and in vivo contractile properties of each unit were estimated using spike-triggered averaging of the high-gain force record. Recruitment of units was observed at all levels of force and recruitment level varied from trial to trial for each unit. Interspike interval variability was high at all levels of force. The twitch tensions of the units were all less than 10 g; the contraction times ranged from 16 to 90 ms. It is hypothesized that the differences between lip and limb motor unit properties in this task reflect the mechanical, anatomic, and neurophysiologic differences between these systems.