Added value of electromyography in the diagnosis of myopathy: A consensus exercise.

OBJECTIVE: Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies. METHODS: One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres. Each patient was given three different consensus diagnoses: (1) the EDX diagnosis solely based on EDX results, (2) the pure clinical diagnosis based on all available information except EDX results, and (3) the final diagnosis including EDX and all additional information. The myopathies were grouped as muscular dystrophy (45), inflammatory myopathy (46), other aetiology (36) or unknown aetiology (67). RESULTS: Higher diagnostic probabilities for myopathy were seen in the final diagnosis compared to the pure clinical diagnosis (p<0.001). Adding EDX information increased the diagnostic probability of myopathy in 67 patients (34.4%). The greatest increase was seen for myopathies of unknown aetiology. CONCLUSIONS: EDX has a major impact in the diagnosis of myopathies of unknown aetiology. In genetically or biopsy proven myopathies, EDX generally supports the diagnosis. SIGNIFICANCE: EDX is still a useful tool in the diagnostic work-up of most patients with suspected myopathy.

Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset. CONCLUSION: The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.

Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'.

The properties of neuromuscular junctions (NMJs) were studied in motor-point biopsy samples from eight patients with congenital myasthenic syndromes affecting primarily proximal limb muscles ['limb-girdle myasthenia' (LGM)]. All had moderate to severe weakness of the proximal muscles, without short-term clinical fatigability but with marked variation in strength over periods of weeks or months, with little or no facial weakness or ptosis and no ophthalmoplegia. Most had a characteristic gait and stance. All patients showed decrement of the compound muscle action potential (CMAP) on repetitive stimulation at 3 Hz, and increased jitter and blocking was detected by SFEMG, confirming the presence of impaired neuromuscular transmission. None of the patients had serum antibodies against acetylcholine receptors (AChRs). Two of the patients had similarly affected siblings. Intracellular recording from isolated nerve-muscle preparations revealed that the quantal content (the number of ACh quanta released per nerve impulse) was only approximately 50% of that in controls. However, the quantal size (amplitude of miniature end-plate currents) and the kinetic properties of synaptic potentials and currents were similar to control values. The area of synaptic contact and extent of post-synaptic folding were approximately 50% of control values. Thus, the quantal content per unit area of synaptic contact was normal. The number of AChRs per NMJ was also reduced to approximately 50% of normal, so the local AChR density was normal. Immunolabelling studies revealed qualitatively normal distributions and abundance of each of 14 proteins normally concentrated at the NMJ, including components of the basal lamina, post-synaptic membrane and post-synaptic cytoskeleton. DNA analysis failed to detect mutations in the genes encoding any of the following proteins: AChR subunits, rapsyn, ColQ, ChAT or muscle-specific kinase. Response of these patients to treatment was varied: few showed long-term improvement with pyridostigmine and some even deteriorated with treatments, while others had intolerable side-effects. Several patients showed improvement with 3,4-diaminopyridine, but this was generally only transient. Ephedrine was helpful in half of the patients. We conclude that impaired neuromuscular transmission in these LGM patients results from structural abnormalities of the NMJ, including reduced size and post-synaptic folding, rather from any abnormality in the immediate events of neuromuscular transmission.

Treatment of stiff person syndrome with rituximab.

This case report is about the novel use of the anti-CD20 antibody, rituximab, in the treatment of a 41 year old woman with stiff person syndrome. She was admitted to hospital as an emergency with prolonged and painful extensor spasms affecting the neck and back, arms, and legs. The disease had progressed despite a favourable initial response to conventional treatment with intravenous immunoglobulin and cytotoxics. Treatment with rituximab induced a lasting clinical remission.

Variation in the classification of polyneuropathies among European physicians.

OBJECTIVE: Considerable debate still exists regarding the classification of polyneuropathies (PNPs) into predominantly demyelinating, predominantly axonal loss, mixed or unclassified. This study was designed to determine the variation among physicians in the classification of PNPs by using the European Standardized Telematic tool to Evaluate Electromyography knowledge-based systems and Methods (ESTEEM) multicenter database. METHODS: Seven physicians from 6 laboratories in Europe sent a total of 156 prospectively collected cases of PNP with electromyography (EMG) data including diagnosis (examination diagnosis) to the database. Each physician interpreted the electrophysiological data from all cases (interpretation diagnosis) and a final diagnosis was given at the consensus meetings of the group (consensus diagnosis). RESULTS: Comparison of each physician's examination diagnosis with his/her interpretation diagnosis, i.e. intra-physician variation, showed a change towards less classified PNPs (P < 0.05). Interpretation diagnoses showed large inter-physician variation in the classification of PNPs. The consensus group was more cautious than individual physicians in classifying PNPs as mixed and axonal. The probability of the consensus diagnosis increased with increasing number of abnormal motor and sensory segments tested. CONCLUSIONS: Recognition of variation in classification of PNP as shown in this study and suggesting standards of good clinical practice developed by a consensus group may increase the quality of EMG practice.

Is decreased treatment time in hemodialysis patients harmful if solute clearance is maintained?

An association between decreased duration of hemodialysis and increased morbidity and mortality in patients has been suggested. Whether this is due only to decreased solute clearance is unclear. In this prospective randomised study the effect of reducing treatment time whilst maintaining constant solute clearance was examined in fourteen patients. The study lasted for a period of 36 weeks (3x12 week study periods) and used a crossover design. The patients dialysis prescription (KW) was not changed on entering the study and was maintained during short (150 minutes) and long dialysis (240 minutes) by varying blood flow, dialysate flow and dialyzer surface area. The delivered KW was kinetically assessed. Fractional urea clearance was also measured during each treatment period by measurement of urea concentration in spent dialysate and total body water using 3H2O. At the end of each treatment period a full biochemical and hematological profile, nutritional intake and status, 24 h ambulatory blood pressure, nerve conduction studies, and quality of life questionnaire were performed. Within patients the delivered single pool KW was uniform throughout the 3 treatment periods and fractional urea clearance did not vary. However, Kt/W assessed using equilibrated models (Daugardis and Smye) was significantly lower in the short dialysis period. No differences between short and long dialysis sessions were noted in any of the measured variables. Thus, over a 36 week period there is no evidence to suggest that hemodialysis patients are adversely affected by decreased duration of treatment provided that solute clearance is maintained.

A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci.

We describe a novel autosomal dominant myopathy presenting in mid-adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct.

Variation in diagnostic strategy of the EMG examination--a multicentre study.

OBJECTIVES: In order to improve the universal quality of the EMG examination, knowledge about the variation among physicians is needed. METHODS: The variation among physicians in diagnostic strategy or criteria for diagnosing was analysed from a multicentre database with 940 EMG examinations sampled by seven physicians from six laboratories in Europe. RESULTS: For the whole group of patients as well as for the subgroup of patients with polyneuropathy, variation among physicians in examination techniques, number of examined structures per patient and number of abnormal structures per patient required for a diagnosis was found. Some of the variation may be explained by use of different techniques, which showed differences in sensitivity, while some of the variation may be due to differences in diagnostic strategy and criteria for diagnosing. CONCLUSIONS: The study indicates a need for development and revision of international guidelines for EMG practice although implementation of standards requires caution.

Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies.

Congenital myasthenic syndromes are a heterogeneous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the neuromuscular junction. We describe four new cases of AChR deficiency, characterized by a reduction in both miniature endplate potential amplitude and AChR abundance accompanied by elongation of the neuromuscular junction and some decrease in postsynaptic folding. A number of cytoplasmic proteins are normally associated with the postsynaptic membrane and may contribute to the clustering of AChRs at the neuromuscular junction. We therefore investigated the expression of several of these proteins in these AChR-deficiency patients. In each patient, immunolabelling of the neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form of beta-spectrin was strong but that for utrophin was markedly reduced or absent. This suggested that a defect in utrophin expression might underlie the congenital AChR deficiency. However, a reduction in utrophin labelling was also seen in three patients with adult acquired autoimmune myasthenia gravis in whom AChR loss results directly from the extracellular binding of autoantibodies. We conclude that the loss of AChRs in AChR deficiency does not result from the absence of rapsyn or beta-dystroglycan and that reduction of utrophin is probably secondary to the loss of AChRs. The possible role of AChRs and/or utrophin in determining the extent of postsynaptic folding is discussed.

Electromyography in myopathy.

Electromyography (EMG) is the most common procedure for screening patients with myopathies and remains the most important technique for assessing the course of the disease over time. Fibrillation potentials, positive sharp waves, myotonic or complex repetitive discharge, as well as polyphasic potentials are non specific and can occur in both myopathic and neurogenic lesions. The most sensitive and specific parameter for myopathy in conventional EMG is the decreased duration of motor unit potentials (MUP), but this can also be seen in disorders of the terminal motor fibers or the neuromuscular junction. More advanced techniques such as single fiber EMG, macro EMG, scanning EMG and turns/amplitude analysis have opened additional possibilities for analysis of the motor unit and the interference pattern, by which both the sensitivity to early changes and specificity for myopathic alterations is increased. The importance of combining different techniques to improve diagnostic yield and specificity is stressed.

Neuromuscular effects of Papuan Taipan snake venom.

Snakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single-fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.

Repetitive nerve stimulation of anconeus in the assessment of neuromuscular transmission disorders.

Repetitive nerve stimulation of the anconeus muscle is described. Control studies showed the test to be reliable and well tolerated over a range of stimulus frequencies and train lengths. Sixty-one patients with primary disorders of neuromuscular transmission were tested. Repetitive nerve stimulation of anconeus was abnormal in 2 of 21 patients with ocular myasthenia, but showed a significant decrementing response in 16 of 30 patients with generalized myasthenia gravis. In comparison with other muscles, repetitive nerve stimulation of anconeus was more sensitive than abductor digiti minimi, but equally sensitive as deltoid. The test may also be used to help characterize other disorders of neuromuscular transmission such as congenital myasthenia or the Lambert-Eaton myasthenic syndrome. Compared with single fibre EMG on extensor digitorum communis, repetitive stimulation of anconeus was usually, but not always, a less sensitive method of detecting a neuromuscular transmission disorder.

KANDID--an EMG decision support system--evaluated in a European multicenter trial.

KANDID is an advanced EMG decision support system dedicated to the support of the clinical neurophysiologist during EMG examinations. It has facilities for test planning, automatized and structured data interpretation, EMG diagnosis, explanation, and reporting. In a prospective European multicenter field trial, the agreement levels between clinical neurophysiologists and KANDID's diagnostic statements were measured under ordinary clinical EMG practice. KANDID was assessed in 159 individual patient EMG examinations by nine clinical neurophysiologists at seven different EMG laboratories. The reasoning of KANDID was considered understandable for the examiners in 80-90% of cases. The agreement level for the electrophysiological states of muscles and nerves between KANDID and the individual examiners was, on average, 81%. The corresponding diagnostic agreement with KANDID was, on average, 61%. A pronounced interexaminer variation in the agreement level related to the different EMG centers was observed. All Danish and Belgian examiners agreed with KANDID in more than 50% of their cases with regard to the EMG diagnosis, while the English examiners were in agreement with KANDID in 50% or less of their cases. These differences were possibly due to differences in epidemiology, examination techniques, control material, and examination planning strategies. It is concluded that it is possible to transfer systems like KANDID out of their development sites and apply them successfully if they can be locally customized by the clinical end users via editors.

Electromyographic abnormalities in the urethral and anal sphincters of women with idiopathic retention of urine.

Previous concentric needle studies of the urethral sphincter in women with idiopathic urinary retention have found evidence of denervation and reinnervation as well as abnormal patterns of muscle fibre discharge--complex repetitive discharges (CRDs). In order to test the hypothesis that these abnormalities represented a more widespread disease process of pelvic floor function, we carried out an electromyographic (EMG) study of both anal and urethral sphincters in 18 women with idiopathic urinary retention. The urethral sphincter EMG was abnormal in 15 patients. These abnormalities included polyphasic and long duration potentials. Complex repetitive discharges were identified in 8 women. However, abnormalities of the anal sphincter were found in 14 of the 15 patients with abnormal urethral sphincter EMGs, polyphasic and abnormally long duration potentials being found in the anal sphincters of all 14 patients. In addition, 7 of the 8 women who had complex repetitive discharges in the urethral sphincters had similar complex repetitive discharges in their anal sphincters. Women with complex repetitive discharges had a significantly greater proportion of abnormal potentials than women with no such repetitive discharges. These results support the previous findings of electromyographic urethral sphincter abnormalities in women with idiopathic urinary retention, but also suggest that these abnormalities reflect a widespread disease process involving the pelvic floor in such patients.

Structure and function of neuromuscular junctions in the vastus lateralis of man. A motor point biopsy study of two groups of patients.

The properties of neuromuscular junctions (NMJs) in the vastus lateralis of man have been studied in motor point biopsy samples and compared with those reported for lower vertebrates (frogs and mice). The patients studied had no convincing evidence of a primary disturbance of neuromuscular transmission or other neurogenic component. Morphological studies were made using a variety of methods at the light- and electron-microscope levels. The size of the presynaptic nerve terminal and the area of postsynaptic specialization were smaller, relative to the size of the muscle fibres, than in the lower vertebrates. In contrast, the extent of postsynaptic folding was greater. Intracellular recordings from single muscle fibres showed that the duration of synaptic currents was longer than in most other vertebrates so far studied and that the number of transmitter 'quanta' released by a single nerve impulse, about 20, was lower, probably reflecting the small size of the presynaptic terminals. The hypothesis is discussed that in man, a relatively weak effect of transmitter on the muscle fibre surface is amplified by voltage-dependent sodium channels which have been shown in the rat to be concentrated in the depths of the synaptic folds. The implications of this hypothesis for the interpretation of pathological findings in myasthenic syndromes are also discussed.

Familial infantile myasthenia: a diagnostic problem.

The authors report the diagnostic difficulties experienced with two siblings presenting with recurrent apnoeic attacks caused by the rare condition, familial infantile myasthenia. Standard repetitive nerve stimulation studies were normal in both cases, while changes typical of a subacute neurogenic condition were noted on concentric needle electromyography in one. A 14-day course of pyridostigmine did not elicit any clinical improvement in the elder sibling, in whom tracheomalacia was diagnosed by chest fluoroscopy and bronchoscopy. This infant died at the age of 11 months with hypoxic brain-damage after a severe apnoeic episode. For the second sibling, a positive decremental response was obtained in the hypothenar muscles only after two minutes continuous 10 Hz stimulation of the ulnar nerve. This child has responded well to treatment with pyridostigmine.

Artificial neural nets in computer-aided macro motor unit potential classification.

The use of macro electromyography to obtain a macro motor unit potential (MMUP) is described. At least 20 potentials are measured from a single muscle to obtain a reasonable estimate of the parameters of an average motor unit potential. The MMUP data are analyzed by means of the peak-to-peak amplitude and the integral of the central 50 ms of the signal. The possibility of using artificial neural networks (ANNs) to analyze the macro data in a way that makes no assumptions about the relationships between the parameters and without recourse to conventional modeling methods is discussed. The results of an analysis carried out on 820 MMUPs recorded from 41 subjects who were classified on the basis of a clinical opinion and the appearance of a muscle biopsy are presented and discussed.

The quadriceps femoris muscle in 20-70-year-old subjects: relationship between knee extension torque, electrophysiological parameters, and muscle fiber characteristics.

Comparisons have been made between torque (isometric and isokinetic), electrophysiological (SFEMG, Macro EMG), and muscle fiber characteristics in the vastus lateralis muscle of both legs in healthy subjects aged between 20 and 70 years. Torque was greater in males and decreased with age in both sexes. Multifactorial analysis showed a positive correlation between torque, body surface area, and mean fiber area. These variables explained only about 30-40% of the torque changes. The electrophysiological parameters (Marco EMG amplitudes and fiber density) revealed evidence of reinnervation, indicating preceeding denervation and therefore loss of motor units. It was concluded that this fall out of motor units also contributes to the reduction in torque, when compensatory reinnervation begins to fall. Other factors, such as reduction in muscle fiber contractility, metabolic factors, and central factors, may also play a role in age-related reduction in torque.

Demyelinating neuropathy due to primary IgM kappa B cell lymphoma of peripheral nerve.

A 53-year-old man presented with a painful, demyelinating sensorimotor peripheral neuropathy with lymphomatous infiltration on sural nerve biopsy, but no evidence of systemic lymphoma. The neuropathy responded to cytotoxic therapy. Seven years later he developed generalized lymphadenopathy due to B cell lymphoplasmacytoid lymphoma, with a subpopulation of cells expressing a monoclonal pattern of IgM kappa. The lymphomatous infiltrate in the original nerve biopsy showed similar monoclonal IgM kappa reactivity. The mechanism of demyelination of the peripheral nerves may be similar to that described in patients with IgM kappa monoclonal gammopathies.