Muscle ultrasonography and electromyography correlation for evaluation of floppy infants

Floppiness in an infant may have a number of different etiologies from disorders of the brain to spinal cord lesions, neuropathies, neuromuscular junction disorders and myopathies.In this study we aimed to investigate the correlation of muscle ultrasonography (US) and electromyography (EMG) in the diagnosis of floppy infants.The study encompassed 41 floppy infants aged 2-24 months. The muscle US and EMG examinations were performed without awareness of the clinical diagnosis. The final diagnosis was established by molecular genetic tests or muscle/nerve biopsy. The neurogenic group consisted of 16 infants according to their US and EMG findings. Fifteen of them had spinal muscular atrophy proven by genetic analysis and one had polyneuropathy diagnosed by nerve biopsy. Six infants were in the myopathic group according to their muscle US and EMG results. All of them underwent muscle biopsy and microscopic examination revealed five congenital muscular dystrophy and one glycogen storage disease. In two infants the US and EMG data conflicted. Their biopsies were also insufficient for the diagnosis. Seventeen infants had normal US and EMG findings but pathologic cranial magnetic resonance imaging or metabolic/genetic tests. They were considered in the group of central hypotonia.Our results suggest a high concordance of US and EMG findings in the diagnostic work-up of neurogenic and myopathic disorders.     

Muscular dystrophies and related skeletal muscle disorders in an Indian population--a prospective correlative study.

Since most centers in developing countries have limited facilities for investigation of patients with muscular dystrophies and similar disorders, this study was conducted with the aim of assessing the correlation between clinical, electromyographic (EMG) and histopathological findings in this group. We included 100 patients with muscular dystrophy and clinically similar disorders and subjected them to detailed clinical, electrophysiological and histopathological as well as immunohistochemical evaluation. Sensitivity, specificity, positive and negative predictive values and concordance rates for clinical and EMG diagnosis compared to diagnosis after histopathological examination were analyzed. With histopathology as standard, clinical diagnosis and a concordant EMG have very high sensitivity and negative predictive value (100%), but low specificity (33.3%). We conclude that detailed histopathological evaluation with immunohistochemical analysis is essential for the work-up of patients with suspected muscular dystrophies, since occasionally treatable muscle disorders like inflammatory myopathies can be detected when not suspected clinically. Muscle biopsies should only be conducted at major centers where full histochemical facilities are available.     

Correlation between specific histological and electromyographic findings in neuromuscular disorders

An attempt was made to find a correlation between specific electromyography (EMG) abnormalities with histological findings in muscle biopsies (MB) in 100 patients with neuromuscular disorders. Quantified EMG and MB with histochemistry was made in the same muscle, but on the opposite side, within a period of 3 weeks. The isolated findings of EMG and MB were analysed with a computer through a chi-square test. A statistical relation (p less than 0.01) was found between the isolated findings of MB and EMG in only 6.99% (39 in 558 attempts) of the abnormalities expected to occur in myopathy and denervation. Also was found 2.51% (14 in 558 attempts) of inconsistences with the current literature.     

Electromyography (EMG) accuracy compared to muscle biopsy in childhood

Reports show wide variability of electromyography (EMG) in detecting pediatric neuromuscular disorders. The study's aim was to determine EMG/nerve conduction study accuracy compared to muscle biopsy and final clinical diagnosis, and sensitivity for myopathic motor unit potential detection in childhood. Of 550 EMG/nerve conduction studies performed by the same examiner from a pediatric neuromuscular service, 27 children (ages 6 days to 16 years [10 boys; M:F, 1:1.7]) with muscle biopsies and final clinical diagnoses were compared retrospectively. Final clinical diagnoses were congenital myopathies (5 of 27,18%), nonspecific myopathies (biopsy myopathic, final diagnosis uncertain; 6 of 27, 22%), congenital myasthenic syndrome (3 of 27, 11%), juvenile myasthenia gravis (1 of 27, 4%), arthrogryposis multiplex congenita (2 of 27, 7%), hereditary motor and sensory neuropathy (1 of 27, 4%), bilateral peroneal neuropathies (1 of 27, 4%), and normal (8 of 27, 30%). There were no muscular dystrophy or spinal muscular atrophy patients. EMG/nerve conduction studies had a 74% agreement with final clinical diagnoses and 100% agreement in neurogenic, neuromuscular junction, and normal categories. Muscle biopsies concurred with final diagnoses in 87%, and 100% in myopathic and normal categories. In congenital myasthenic syndrome, muscle biopsies showed mild variation in fiber size in 2 of 3 children and were normal in 1 of 3. EMG sensitivity for detecting myopathic motor unit potentials in myopathies was 4 of 11 (36%), greater over 2 years of age (3 of 4, 75%), compared to infants less than 2 years (1 of 7, 14%), not statistically significant (P = .0879). EMGs false-negative for myopathy in infants < 2 years of age were frequently neurogenic (3 of 6, 50%). In congenital myopathies EMG detected myopathic motor unit potentials in 40%, with false-negative results neurogenic (20%) or normal (40%). Because our study has no additional tests for active myopathies, for example Duchenne muscular dystrophy genetic testing, our sensitivity for myopathies is lower than if we used a more global view. In conclusion, EMG detection rate of myopathic motor unit potentials at a young age was low, improving in children over 2 years of age. In neurogenic and neuromuscular junction disorders, the EMG has a very high detection rate. In children with mild to moderate neurogenic EMG findings and normal nerve conduction, a myopathy should always be considered.     

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.     

Myofibrillar myopathies

Myofibrillar myopathies represent a group of muscular dystrophies with a similar morphologic phenotype. They are characterized by a distinct pathologic pattern of myofibrillar dissolution associated with disintegration of the Z-disk, accumulation of myofibrillar degradation products, and ectopic expression of multiple proteins and sometimes congophilic material. The clinical features of myofibrillar myopathies are more variable. These include progressive muscle weakness, that often involves or begins in distal muscles but limb-girdle or scapuloperoneal distributions can also occur. Cardiomyopathy and peripheral neuropathy are frequent associated features. EMG of the affected muscles reveals myopathic motor unit potentials and abnormal irritability often with myotonic discharges. Rarely, neurogenic motor unit potentials or slow nerve conductions are present. The generic diagnosis of myofibrillar myopathies is based on muscle biopsy findings in frozen sections. To date, all myofibrillar myopathy mutations have been traced to Z-disk-associated proteins, namely, desmin, αB-crystallin, myotilin, ZASP, filamin C and Bag3. However, in the majority of the myofibrillar myopathy patients the disease gene awaits discovery.     

Clinical forms of inclusion body myositis: 12 cases

Inclusion body myositis is now a well-known disease but its incidence is underestimated. We report 12 cases with clinical heterogeneity. Three groups of patients could be described. The first one corresponded to asymmetrical muscle involvement and distribution with a slow clinical course (4 cases). The second was characterized by a polymyositis-like syndrome (3 cas), but steroid therapy was ineffective. The last group mimicked a chronic spinal muscular atrophy (4 cases). One patient showed a scapuloperoneal syndrome. Both myopathic and neurogenic EMG patterns were present in 6 patients; a neurogenic pattern was found in 4 cases and a myopathic pattern in 2 cases. In all patients, muscle biopsies showed rimmed vacuoles with eosinophilic inclusions. In 9 cases ultrastructural studies displayed abnormal filaments of 15-18 nm in diameter in the vacuoles. Intranuclear filaments were rarely observed. The significance of the filaments is unknown and their specificity is doubtful because they are present in other myopathies with rimmed vacuoles (some distal myopathies and oculopharyngeal muscular dystrophies). Finally a rich inflammatory exudate was present in 8 patients only.     

Muscle CT, biopsy and EMG in diagnosis of neuromuscular diseases

The diagnostic value of EMG and muscle biopsy has been compared with muscle CT in 53 patients with neuromuscular diseases. CT concordance with clinical diagnosis was found in 62% of myopathies and was highest in Duchenne PMD and scapulo-peroneal myopathy and very low in metabolic and inflammatory myopathies. In neurogenic diseases muscle CT agreed with clinical diagnosis in 63% of patients: the highest concordance was found in acquired polyneuropathies.

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Sommario Il valore diagnostico dell' EMG e della biopsia muscolare viene confrontato con quello della TC muscolare in 53 pazienti affetti da malattie neuromuscolari. La TC muscolare concorda con la diagnosi clinica nel 62% delle miopatie, con un massimo nelle distrofie di Duchenne e nella miopatia scapolo-peroneale, mentre è di scarsa utilità nelle miopatie metaboliche ed infiammatorie. Nelle malattie neurogene la TC muscolare è in concordanza con la diagnosi clinica nel 63% dei casi, con un massimo nelle neuropatie acquisite.

     

Neuromuscular diseases 2: muscular dystrophies (MD)

Traditionally, muscular dystrophies (MDs) are progressive, hereditary, and primarily degenerative myopathies. Nowadays, due to molecular biology, MDs are looked upon as clinically and genetically heterogeneous myopathies characterized by protein defects of muscle tissue resulting most often in muscle weakness. They are caused by gene mutations leading to a decrease of structural proteins or enzymes. The site of the primary defect and the protein function are different. The disorders are defined according to the underlying protein defect (dystrophinopathy, calpainopathy, and others). The gene or gene product are not yet known in all forms of MD (for example, facioscapulohumeral muscular dystrophy). Therefore, the nomenclature based on the protein defects and the term MD are used concurrently. Clinical symptoms, pathogenesis, diagnosis, therapy, prognosis, and possible prevention of the more frequent MDs are discussed: dystrophinopathies (Duchenne, Becker type), Emery-Dreifuss syndrome (3 forms), facioscapulohumeral MD, limb-girdle MD (17 forms), myotonic dystrophies (2 forms), and congenital MD (11 forms). This article highlights the significance of molecular analyses and the possible multisystemic symptoms in these myopathies.     

Congenital myopathies with secondary neuromuscular transmission defects; A case report and review of the literature

Congenital myopathies are a clinically and genetically heterogeneous group of disorders characterized by early onset hypotonia, weakness and characteristic, but not pathognomonic, structural abnormalities in muscle fibres. The clinical features overlap with muscular dystrophies, myofibrillar myopathies, neurogenic conditions and congenital myasthenic syndromes. We describe a case of cap myopathy with myasthenic features due to a mutation in the TPM2 gene that responded to anticholinesterase therapy. We also review other published cases of congenital myopathies with neuromuscular transmission abnormalities. This report expands the spectrum of congenital myopathies with secondary neuromuscular transmission defects. The recognition of these cases is important since these conditions can benefit from treatment with drugs enhancing neuromuscular transmission.     

NCAM, vimentin and neonatal myosin heavy chain expression in human muscle diseases

The intermediate filament protein vimentin, the neonatal isoform of the myosin heavy chain gene (MHCn), and the neural cell adhesion molecule (NCAM) are developmentally and/or neurally regulated molecules that reappear transiently after the induction of necrosis, or denervation. Immunostaining using antibodies against these molecules helps to identify regenerating and/or denervated muscle fibres even if they are not recognized by conventional staining procedures. This study examined the expression of vimentin, MHCn, and NCAM using immunohistochemistry in 82 biopsy specimens from muscular dystrophies, inflammatory myopathies, and neurogenic atrophies. Anti-vimentin labelled significantly more fibres than anti-MHCn staining in the inflammatory myopathies (P<0.03) but not in the muscular dystrophies (P=0.58) and neurogenic atrophies (P=0. 58). The fraction of NCAM+ fibres was always more elevated than vimentin+ or MHCn+ fibres. In the necrotizing myopathies, most NCAM+ fibres were regenerating ones (co-expressing vimentin). In neurogenic atrophies, half the NCAM+ fibres were regenerating and half of them were NCAM+/vimentin- and thus were considered to be denervated. Taken together, anti-vimentin staining detects a broader spectrum of regenerating fibres than anti-MHCn, at least in the inflammatory myopathies. The number of anti-NCAM labelled fibres in the necrotizing myopathies is similar, but not identical, to the number of regenerating fibres. Co-staining with anti-vimentin (or anti-MHCn) and anti-NCAM identifies a subset of fibres that is considered to be denervated.     

Possible neurogenic factor in muscular dystrophy: its similarity to denervation atrophy

Muscle biopsy specimens from 179 cases of muscular dystrophies and from 140 cases of anterior horn cell disorders (from a total of 1,348 biopsied patients) were examined histologically. There were 72 cases of Duchenne type muscular dystrophy (DMD), five of Becker type MD, four girls with myopathy resembling DMD, 40 with limb-girdle, 10 with facioscapulohumeral, seven with late onset, 13 with congenital, and 28 with unclassifiable muscular dystrophies. Groups of small atrophied muscle fibres were encountered in 42 (23%) of the cases in this group, most frequently in patients with limb-girdle, facioscapulohumeral, and least frequently with DM dystrophy. In the second group there were 25 cases of infantile, 38 of juvenile, and 39 of adult spinal muscular atrophy (SMA); there were 21 patients with motor neurone disease (MND), six with poliomyelitis, and 11 with an unclassifiable type of anterior horn cell disorder. Pseudomyopathic changes were encountered in 43 (30%) of all cases in this group. They were most frequently present among patients with juvenile and adult SMA and in those with MND. The presence of group atrophy in muscular dystrophy is considered significant myopathological evidence of a denervation process. On the other hand, pseudomyopathic changes, variation in fibre size, rounding, central nuclei, and increase in connective tissue occurring in various anterior horn cell disorders are seen not to be specific `myopathic'' changes. Thus there was an overlap of pathological reactions in muscles from the dystrophies and the neurogenic atrophies. Comparably atrophied fibres (much less than 2 SDs below the normal mean diameter) and hypertrophied fibres (much more than 2 SDs above the normal mean diameter) were encountered in both dystrophy and neurogenic atrophy, considering the large muscles of the limb. Likewise, the mean fibre diameters were comparable in DMD and in juvenile SMA. The fourth evidence of a neurogenic factor in muscular dystrophy was derived from an examination of SDH preparations of muscle. There was a preponderance of type I muscle fibres in dystrophic muscles compared with specimens from controls, suggesting depletion of type II fibres. It appears that the concept of muscular dystrophy as a primary muscle disease needs to be re-examined.     

Concentric-needle versus macro EMG. II. Detection of neuromuscular disorders.

OBJECTIVE: Little is known about the relation and sensitivity of macro-EMG (MA-EMG) compared with concentric-needle EMG (CN-EMG) in the detection of neuromuscular disorders. METHODS: CN-EMGs and MA-EMGs were recorded from the right brachial biceps muscle of 40 healthy subjects, aged 17-83 years, 20 patients with neurogenic disorders, aged 25-75 years, and 20 patients with myopathy, aged 18-76 years. Motor unit action potentials (MUAPs) were examined. RESULTS: In patients with neurogenic disorders CN-MUAP duration, CN-MUAP amplitude, percent polyphasia, MA-MUAP amplitude, MA-MUAP area and fibre density were significantly increased. In patients with myopathy, only fibre density was significantly increased. In patients with neurogenic disorders, the sensitivity of CN-EMG was 80%, and that of MA-EMG 85%. In myopathies, the sensitivity was 50% for each technique. Pooling the results of both EMG techniques, the sensitivity increased to 90% in patients with neurogenic disorders, and to 65% in myogenic disease. CONCLUSIONS: MA-EMG has a similar sensitivity in the detection of neuromuscular disorders as CN-EMG. Particularly when myopathy is suspected, both techniques should be applied if one is unrevealing.     

Halothane-caffeine contracture testing in neuromuscular diseases

The association of malignant hyperthermia (MH) with neuromuscular disorders has been recognized since 1970. These disorders include central core disease, Duchenne muscular dystrophy, myotonia congenita, myotonic dystrophy, nonspecific myopathies, and King-Denborough syndrome. In order to assess the anesthetic risk of MH in the neuromuscular population, we performed halothane and caffeine contracture testing for MH susceptibility on biopsied muscle removed from 25 consecutive neuromuscular patients during diagnostic evaluation. Positive contracture tests were found in 7 of 18 patients with myopathic disorders and 3 of 7 patients with neurogenic disorders. Two of our patients had anesthetic events suggesting MH. These findings suggest that myopathic and neuropathic disorders share pathogenic mechanisms with MH, resulting in positive contracture tests and possibly leading to clinical events during anesthesia. Although there is controversy regarding the interpretation of a positive contracture test, contracture testing remains the most widely accepted test for MH susceptibility. Thus, a variety of neuromuscular disorders may be associated with MH susceptibility, and caution should be exercised during anesthesia in this group of patients.     

Comparison of electrophysiological and histochemical methods for assessing the spatial distribution of muscle fibres of a motor unit within muscle

The spatial distribution of muscle fibres of a motor unit has been examined in patients with a variety of neuromuscular disorders using the fibre density (FD) technique of single fibre EMG and the enclosed fibre count (EFC) method, and the results of the two approaches compared. Agreement between the findings occurred in 64% of cases; an increase in both parameters was seen only in neurogenic conditions. FD was found to be more sensitive to minor disturbances of motor unit architecture as seen in myopathies and mild neurogenic states, and this factor together with sampling differences accounted for most of the discrepancies between the two methods. The finding of normal FD and EFC values in the presence of fibre type disproportion helped to exclude reinnervation as the cause by confirming the predominantly diffuse distribution of muscle fibres.     

Apoptosis and muscle fibre loss in neuromuscular disorders

The past decade has witnessed increasing evidence that besides necrosis, apoptotic cell death mechanisms contribute to muscle fibre loss in various neuromuscular conditions, including the muscular dystrophies, metabolic myopathies, and cases of denervation. The up-regulation of bax and bcl-2, both members of the bcl-2 family, indicate that the predominant effectors involve permeability transition pores in the mitochondrial membrane and subsequent caspase activation which confers the typical morphological and biochemical features of apoptosis such as DNA-fragmentation. It is likely that apoptotic degradation of nuclei and contractile elements is a localized event in muscle fibre segments leading to muscle fibre atrophy and finally loss in these disorders. Essential triggers of apoptosis seem to be homeostatic dysregulation as well as oxidative stress, with increased generation of free oxygen radicals and nitric oxide. In the absence of effective primary treatments, there is hope that interventions in muscle fibre apoptosis will bear promising therapeutic strategies.     

Evoked isometric muscle contractions in myopathies: analysis of pathophysiological properties by different stimulus patterns

Isometric twitches of the adductor pollicis muscle following ulnar nerve stimulation were investigated in healthy subjects (n = 35) and patients with different types of myopathies (myotonic dystrophy, n = 19; limb girdle muscular dystrophy, n = 10; metabolic myopathy, n = 6). The changes within the rising part (i.e. within the contraction time, CT) of the isometric twitches after single stimuli were similar in myotonic and limb girdle dystrophies: the first part of CT, which lasts until the maximal contraction rate is achieved, was shortened, whereas the following second part of CT, which lasts until the maximal twitch force is achieved, was normal. In metabolic myopathies the first part was normal, whereas the second part was prolonged. The relaxation was prolonged in all types of myopathies, particularly in metabolic myopathies. Using double stimuli with short interstimulus intervals (ISI), the absolute refractory period of the muscle contraction (healthy subjects: 1.35 +/- 0.16 ms) was shortened in patients with myotonic dystrophy (1.02 +/- 0.11 ms). In the other types of myopathies, the absolute refractory period was only shortened provided that the single twitch force was clearly reduced. A similar dependence on a reduced single twitch force was also found with regard to the maximal force development with two stimuli and the corresponding ISI: the force contributed by a second stimulus was pathologically enhanced if the single twitch force was clearly reduced. The ISI related to the maximal force with two stimuli was shifted towards very short values (healthy subjects: 10.5 ms, myotonic dystrophy: 4.6 ms, limb girdle dystrophies: 5.0 ms). Our results can be attributed to altered kinetics of calcium release and uptake by the sarcoplasmic reticulum in myopathies.     

Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies.

Satellite cells are responsible for the formation of postnatal muscle fibers. The number, mitotic activity, and differentiation potential of satellite cells and the muscle fiber diameter are tightly regulated events in normal muscle. The signal that induces satellite cells to stop proliferation once the determined muscle fiber size has been reached in normal growth is not known. The aim of the present study was to determine whether a correlation exists between satellite cell frequency and muscle fiber diameter in human muscle disease. Muscle biopsies from 7 cases of Duchenne muscular dystrophy (DMD), 8 other muscular dystrophies, 23 cases of inflammatory myopathy, and 22 cases of neurogenic atrophy were examined. The satellite cell number was elevated in DMD and neurogenic atrophy but not in other muscular dystrophies or inflammatory myopathies. Nevertheless, in all the diseased muscles, but not in normal controls, there was a significantly higher relative frequency of satellite cells with increasing fiber diameter. It has been shown before that satellite cells show ultrastructural and autoradiographic signs of activation and proliferation in myopathic and neurogenic conditions. We assume that we are dealing with activated, not quiescent, satellite cells in diseased muscle and that under these conditions the fiber diameter does not represent a stop signal for satellite cells to proliferate. The data suggest that not only the number of satellite cells matters in diseased muscle, as has been shown before, but that it is their behavior that influences, at least in part, progress and severity of muscle diseases.     

Evaluation of an automated method for analysing the electromyogram.

An automated system, incorporating the ANOPS-101 mini-computer, has been used to analyse the EMG. The vastus medialis (VM) and biceps brachii (BB) muscles were studied in 28 controls, 16 patients with myopathies, and in 26 patients with denervating disorders. For each muscle mean values were computed for the durations and numbers of phases of muscle action potentials; the mean density and amplitude of the deflections in the interference pattern were also measured. A higher incidence of abnormalities could be detected in myopathic than in neuropathic disorders; for both conditions the incidence was significantly greater in BB than in VM. For the diagnosis of denervation the most useful measurement was that of potential duration; for the detection of myopathies amplitude determinations were also very useful. The present results have been compared with those of other published studies in which automatic EMG analysis has been employed.     

98例神经肌肉病的临床、肌电图与病理研究

目的 探讨肌电图（EMG），肌活检对神经肌肉病的诊断价值。比较EMG，肌活检及初始临床诊断3者之间的关系。方法 将98例神经肌肉病分成肌病。重症肌无力和运动神经元病3组进行研究。结果 肌病组（80例），68.8%(55/80)肌活检，75%（60/80）EMG呈肌源性损害；重症肌无力组（10例）；针极EMG（不包括重视频率电刺激）及肌活检均未显示特异性改变；运动神经元病组（8例），75?/8）肌活检，100%（8/8）EMG呈神经源性损害。结论 肌活检对肌病明确诊断可提供直接信息。对运动神经元病只能做出神经源性损害结果。缺乏特异性。EMG对神经肌肉病只能做出分类诊断；单纯凭借初始临床资料易导致该类疾病误诊。