Discriminant classification of motor unit potentials (MUPs) successfully separates neurogenic and myopathic conditions. A comparion of multi- and univariate diagnostical algorithms for MUP analysis

Multivariate statistical methods may be more appropriate for the multidimensional material of quantitative motor unit potential (MUP) analysis than the multiple univariate tests of the conventional Buchthal analysis. Buchthal analysis was slightly modified before it was used as the gold standard for new multivariate diagnostical algorithms, based on principal component analysis and on MUP discriminant classification: muscle means of continuous variables were related to tolerance limits after adequate transformation. Chi-square tests were used for dichotomized variables, e.g., polyphasia. Sensitivity and specificity of the uni- and multivariate algorithms were compared for 539 muscles from patients with motor neuron diseases, neuropathies and myopathies and for 91 biceps brachii, rectus femoris and tibialis anterior control muscles. False positive results accumulated less than expected by repeat univariate tests for single MUP parameters, due to high correlation. Combination of single parameters to factor scores did not improve specificity. One advantage of factor analysis was that factor matrix and factor scores matched those of previous studies in spite of different input parameters, which may facilitate multicenter comparisons. Discriminant classification successfully separated neurogenic and myopathic conditions, even in myositic muscles and motor neuron diseases, where myopathic and neuropathic MUPs frequently intermingle. Discriminant classification may support expert decisions and add weight to EMG differential diagnosis.     

Reinnervation of anal sphincter muscle by low and high-threshold motor neurones.

The external anal sphincter (EAS) has continuously active low-threshold and recruitable high-threshold motor units (MUs), the latter being 'larger'. On performing concentric needle electromyography (EMG) of the EAS, the high-threshold MUs seemed to reveal more neuropathic changes than the low-threshold MUs. To verify this hypothesis, low- and high-threshold motor unit potentials (MUPs) were compared in patients with neuropathic EAS and controls. Fifteen subjects without pelvic disorders and 29 patients with sequela after cauda equina lesions were studied. In patients, only muscles ipsilateral to severe perianal sensory loss were included. MUPs were sampled using multi-MUP analysis during relaxation ('low-threshold'), and on activation ('high-threshold' MUs). MUP parameters of low- and high-threshold MUs from controls and patients were compared, as was the sensitivity and specificity with which MUPs were classified as normal or pathological (using discriminant analysis). MUP changes due to reinnervation, and the sensitivity and specificity in classifying MUPs as normal or pathological were not significantly different between the low- and high-threshold MUPs. Stronger activation of EAS does not improve discrimination between neuropathic and normal MUPs. New EMG techniques for sampling sphincter MUPs at higher activation levels would seem not to yield additional information.     

"Satellite potentials" and the duration of motor unit potentials in normal, neuropathic and myopathic muscles.

Time-locked activity in the EMG was studied in normal, neuropathic and myopathic muscles, using the averaging technique. Normal and neuropathic muscles seemed in most cases not to differ with regard to the frequency nor the quality of "satellite signals", i.e. small and short potentials joining the main component of the MUP with a constant interval, up to 26 ms in duration. In normal muscles 10% of the MUPs and in neuropathic muscles 12% had a satellite, which, when studied, showed no signs of blocking. However, in 2 patients with an apparent old spinal affection both an increased number and an increased latency of satellite signals were found. In the different myopathies studied 45% of the MUPs recorded consecutively were preceded or followed by an often increased number of tiny satellites. Sometimes the satellites joining the myopathic MUP formed a long (up to 60 ms) "tail" after the triggering component. On the basis of our results we conclude that in myopathies the total duration of MUPs is in certain cases pathologically incrased rather than decreased.     

Comparison of quantitative techniques in anal sphincter electromyography.

Data comparing results and utility of different quantitative electromyographic (EMG) techniques are limited. In the present study, we analyzed the EMG signal from the external anal sphincter (EAS) muscle using three techniques of motor unit potential (MUP) analysis, and a technique of interference pattern (IP) analysis. We examined 56 patients with damage to the cauda equina or conus medullaris, and 64 control subjects. Using manual-MUP and multi-MUP analysis about 20 MUPs, using a single-MUP technique about 10 MUPs, and using turn/amplitude (T/A) analysis about 20 IP samples were obtained. The sensitivities of these techniques in distinguishing neuropathic from control muscles were calculated. The single-MUP technique detected 63%, manual-MUP 57%, and multi-MUP analysis 62% of neuropathic muscles, and MUP parameters obtained by each of these differed significantly from the other. The sensitivity of T/A analysis of IP was 29%. Our results confirm the need for separate MUP normative data for each of the MUP analysis techniques, and favor them over the IP analysis technique. The normative data presented for the EAS muscle should improve and promote quantitative EMG in patients.     

Diagnostic accuracy of clinical data, quantitative electromyography and histochemistry in neuromuscular disease. A study of 105 cases

One hundred and five (105) cases of muscle weakness were reviewed in order to evaluate the reliability of clinical diagnosis, quantitative EMG, and muscle histochemistry in neuromuscular disorders. Patients were grouped into 3 categories: group I, disorders which could be diagnosed by clinical observation alone (38 patients); group II, disorders in which the EMG and biopsy were necessary for delineation (63 patients); disorders in which it was not possible to make a diagnosis because the clinical and laboratory studies were contradictory (4 patients). In group I, only one patient showed an inconsistency between clinical and laboratory data. In group II, the EMG and biopsy were concordant in all but 4 cases of Kugelberg-Welander syndrome with neuropathic EMG and myopathic biopsy. In group III, 4 patients had a myopathic EMG and neuropathic biopsy.The overall concordance of EMG and histochemistry was greater than 90%. The laboratory studies also discerned 2 different categories of disease, “neuropathic” and “myopathic”. The consistency in EMG and histochemistry correlation suggests that a true division between neuropathic and myopathic disorders exists.     

Turn and phase counts of individual motor unit potentials: correlation and reliability.

Different turn algorithms are used for quantitative motor unit potential (MUP) analysis. To compare their retest reliability, 420 myopathic and neuropathic MUPs were recorded twice and the turn count of the first registration was correlated with that of the second. Reliability was best for the algorithm according to Willison as compared to the conventionally used algorithms based on amplitude criteria for 2 or 3 successive relative extrema. As demonstrated by discriminant analysis, an amplitude limit of 25 microV yielded more useful turn counts than a limit of 50 microV if myopathic MUPs had to be discriminated from normal MUPs. For this discrimination the turn count was superior to the phase count which did not further improve the discriminant model. This was different for the discrimination between normal and neuropathic MUPs. In this case, both parameters measured partly independent features of the MUP and had to be considered together.     

Electromyographic evidence of subclinical myopathy in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is due to a number of mutations of contractile protein genes such as beta-cardiac myosin, myosin binding protein-C, and troponin-T. Unlike troponin-T, beta-myosin is a constituent of slow skeletal muscle and its mutations generally have a better prognosis. In order to investigate the usefulness of electromyography in detecting skeletal muscle involvement in HCM, 46 patients were examined using both conventional electromyography (EMG) and quantitative electromyography (QEMG) methods. The QEMG involved motor unit potential (MUP) analysis, turns/amplitude (TAA) analysis, and power spectrum analysis of the interference pattern. Using conventional EMG, myopathic findings were demonstrated in 13 patients (28%). Receiver operating characteristic (ROC) analysis of the results of a discriminant function extracted using QEMG values, identified correctly 10 out of 11 normal controls and all 9 myopathic control patients, and displayed a 15% presence of myopathy (7 patients) among the cardiomyopathy group. The duration of MUPs was the most sensitive among the quantitative parameters in differentiating normal from myopathic subjects. Since skeletal muscle involvement may be due to distinct gene mutations, normal and myopathic EMG findings may reflect HCM subpopulations with a different genetic substrate.     

Standardization of anal sphincter electromyography: utility of motor unit potential parameters.

Advanced electromyography systems offer quantitative analysis of a number of motor unit potential (MUP) parameters. However, only limited data are available on the diagnostic usefulness of these parameters. In the present study, we compared the sensitivities of MUP parameters in revealing "neuropathic" changes in the external anal sphincter (EAS) muscles in 56 patients examined 5-240 months after damage to the cauda equina or conus medullaris. Using multi-MUP analysis, 20 MUPs were obtained from patients' EAS muscles. Their MUP parameters were compared with normative data from 64 controls. The diagnostic sensitivities of mean values/"outliers" of MUP parameters for detecting neuropathic EAS muscles were calculated (area 25%/30%; number of turns 18%/29%; size index 13%/24%; thickness 18%/18%; amplitude 17%/17%; spike duration 20%/9%; duration 15%/12%; number of phases 15%/11%; and their combination 51%/52%). Altogether, the cumulative sensitivity of multi-MUP analysis using both mean values and "outliers" was 62%. The combination of MUP parameters improves the diagnostic yield of MUP analysis, but the influence on specificity remains unknown.     

Size of motor unit potential sample

In quantitative electromyography (EMG), a sample size of 20 motor unit potentials (MUPs) is standard. The effect of increase in the number of MUPs above 20 is not known, although advanced MUP analysis techniques make such samples practical. In the present study, using multi-MUP analysis, pools of 3,720 neuropathic and 2,526 control MUPs were obtained from external anal sphincter muscles. From each pool, 10,000 random samples of 5, 10, 15, 20, 30, 40, 50, and 100 MUPs were obtained by a computer. For each sample size, 95% normative limits for mean values, SDs, and "outliers," and sensitivities were calculated for eight MUP parameters. As the magnitude of MUP samples increased, normative limits narrowed and sensitivities increased (at 5: 20-30%; at 20: 30-55%; at 100: 80-100%) for all statistics of all MUP parameters. Our results demonstrated a substantial increase in sensitivity by increasing the MUP sample to more than 20. This option deserves consideration in an attempt to improve the usefulness of quantitative EMG.     

Probabilistic muscle characterization using QEMG: Application to neuropathic muscle

Clinicians who use electromyographic (EMG) signals to help determine the presence or absence of abnormality in a muscle often, with varying degrees of success, evaluate sets of motor unit potentials (MUPs) qualitatively and/or quantitatively to characterize the muscle in a clinically meaningful way. The resulting muscle characterization can be improved using automated analysis. As such, the intent of this study was to evaluate the performance of automated, conventional Means/Outlier and Probabilistic methods in converting MUP statistics into a concise, and clinically relevant, muscle characterization. Probabilistic methods combine the set of MUP characterizations, derived using Pattern Discovery (PD), of all MUPs detected from a muscle into a characterization measure that indicates normality or abnormality. Using MUP data from healthy control subjects and patients with known neuropathic disorders, a Probabilistic method that used Bayes' rule to combine MUP characterizations into a Bayesian muscle characterization (BMC) achieved a categorization accuracy of 79.7% compared to 76.4% using the Mean method (P > 0.1) for biceps muscles and 94.6% accuracy for the BMC method compared to 85.8% using the Mean method (P < 0.01) for first dorsal interosseous muscles. The BMC method can facilitate the determination of “possible,” “probable,” or “definite” levels for a given muscle categorization (e.g., neuropathic) whereas the conventional Means and Outlier methods support only a dichotomous “normal” or “abnormal” decision. This work demonstrates that the BMC method can provide information that may be more useful in supporting clinical decisions than that provided by the conventional Means or Outlier methods. Muscle Nerve, 2010     

Criteria for neuropathic abnormality in quantitative anal sphincter electromyography

For the external anal sphincter muscle, both normative values and an optimal set of motor unit potential (MUP) parameters have been defined. However, criteria for the diagnosis of neuropathic conditions have not yet been validated. Therefore, in this study, sensitivity was examined in 86 patients with cauda equina lesions (227 muscles), and specificity in 77 controls (119 muscles), using multi-MUP analysis. Six previously defined diagnostic criteria (mean values and outliers for MUP area, duration, and number of turns) were used. An increase in the number of diagnostic criteria required for muscle abnormality (two and three instead of one), and the application of more stringent normative limits resulted in a progressive increase in specificity from 74% to 99% (controls), and a decrease in sensitivity from 70% to 21% (patients). The data suggest that no single cut-off diagnostic criterion has both satisfactory sensitivity and specificity. Introduction of the diagnostic categories of "possible," "probable," and "definite" neuropathic abnormalities into quantitative electromyographic analysis is proposed.     

EMG power spectrum, turns-amplitude analysis and motor unit potential duration in neuromuscular disorders

The diagnostic value of power spectrum analysis of the needle EMG pattern at a force of 30% of maximum was compared to that of turns-amplitude analysis and to that of manual measurements of motor unit potential (MUP) duration in the brachial biceps muscle of 20 patients with myopathy and 11 patients with neurogenic disorders. In myopathy the power spectrum analysis had the same diagnostic value as the turns-amplitude analysis and MUP duration measurements and the 3 methods supplemented each other. In patients with neurogenic disorders the diagnostic value of the power spectrum analysis as well as that of the turns-amplitude analysis were lesser than that of MUP duration measurement. In diseased muscles the amount of high frequencies increased with increasing ratio of turns to mean amplitude while there was no relation between the power spectrum and the MUP changes. The results suggest that the power spectrum analysis of EMG can be used as a diagnostic tool in patients with neuromuscular disorders.     

Predictive power of motor unit potential parameters in anal sphincter electromyography

The diagnostic utility of motor unit potential (MUP) parameters is usually based exclusively on their diagnostic sensitivity, disregarding specificity. In the present study, advanced statistical methods were used to determine MUP parameters with the highest predictive power for the separation of neuropathic and normal external anal sphincter (EAS) muscles. Using multi-MUP analysis, 3,720 MUPs from 138 muscles of 52 patients with cauda equina lesion and 2,526 from 112 muscles of 64 controls were obtained. Only two principal components (PCs), which put weight on the MUP area and amplitude, were needed to explain all the data variability. On logistic and probit regression analyses, MUP area, duration, and number of turns gave results identical to all MUP parameters. Our results suggest that only these three MUP parameters are needed, and that they are as effective as PCs, in MUP analysis of chronic neuropathic EAS muscles. Reduced number of MUP parameters is expected to simplify MUP analysis and increase its specificity.     

Sensitivity of motor unit potential analysis in facioscapulohumeral muscular dystrophy

Template-operated motor unit potential (MUP) analysis has made quantitative electromyography (EMG) feasible, even in busy laboratories, but validation of this approach is still necessary. In the present study, the utility of multi-MUP analysis was assessed in patients with a molecular genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD). Manual assessment of muscle strength and concentric-needle EMG of the biceps brachii and vastus lateralis muscles were performed. The sensitivity for diagnosing myopathy (mean values and outliers) was tested for eight MUP parameters and four of their combinations. The group comprised 31 patients. Elbow flexion and knee extension strength was normal in 45% and 52% of patients, respectively. The most sensitive MUP parameter was thickness, followed by duration. A combination of three MUP parameters (thickness, amplitude, and duration/area) was needed for maximal sensitivity. The study demonstrated a high sensitivity of multi-MUP analysis in FSHD. Myopathic abnormalities were demonstrated in all weak biceps brachii muscles, and in 77% of biceps brachii muscles with normal strength.     

Probabilistic muscle characterization using quantitative electromyography: Application to facioscapulohumeral muscular dystrophy

Based on quantitative electromyography, a muscle can be categorized as normal or affected by a neuromuscular disorder. The objective of this work was to compare the utility of probabilistic to conventional means and outlier methods of categorization of myopathic and normal muscles. Various sets of motor unit potential (MUP) features detected in biceps brachii muscles of control subjects and patients with facioscapulohumeral muscular dystrophy were used to categorize them as normal or myopathic based on conventional means and outlier categorization (CMC) as well as a new probabilistic muscle categorization (PMC). The sensitivity, specificity, and accuracy provided by each categorization method were compared. The categorizations made using PMC were significantly more accurate (by at least 10%) compared with CMC (P < 10^?10) for muscles evaluated in this study. Area, duration, and thickness were highly discriminative MUP features. Muscle Nerve, 2010     

Electromyography in congenital nemaline myopathy

To clarify the discrepancies between earlier reports of electromyography (EMG) in congenital nemaline myopathy (CNM), conventional electromyography was done on 13 patients with CNM, and results were compared with those of 18 earlier EMG examinations of the same patients. Fiber density was measured in 10 patients with a computerized method and neuromuscular jitter in 3 with single-fiber EMG. With age, the EMG abnormality progressed, and "neuropathic" EMG features developed in distal muscles. In 9 of 10 patients fiber density was higher than normal. In two of three patients jitter was abnormal. Motor (13 of 13 patients) and sensory (3 of 3 patients) nerve conduction velocities were normal. Our results seem to explain the conflicting reports of EMG in CNM. We conclude that active degeneration and regeneration of muscle fibers takes place in CNM and suggest that the "neuropathic" motor unit potentials seen in our patients may be secondary to myopathic disease activity.     

Effects of the amplitude threshold on the separability of neuropathic and myopathic from normal EMG using parameters of the turns/amplitude analysis.

OBJECTIVE: In this study, the relationship between the amplitude threshold used for the determination of the turns of the electromyographic (EMG) interference pattern and the parameters of the turns/amplitude analysis was examined. It was investigated whether the discrimination of myopathic and neuropathic from normal muscles could be optimized by an appropriate amplitude threshold. METHODS: The interference patterns of the tibialis anterior muscle of 15 patients with myopathies, 30 patients with neuropathies and 56 controls were recorded, using concentric needle electrodes. A computer program performed the Willison analysis, systematically varying the amplitude threshold between 10 microV and 200 microV. RESULTS: Amplitudes as well as the number of turns per second were non-linearly related to the amplitude threshold. The reduction of the amplitude threshold to 30 microV resulted in a clearly better separation of the distributions of the number of turns of neuropathic, myopathic and normal EMG, compared to the traditional threshold value of 100 microV. The distributions of amplitude values, however, were not affected. The distance between the turns parameter distributions of neuropathic patients and controls and between the distributions of myopathic patients and controls, expressed by the Kolmogoroff-Smirnov distance, had a maximum at 30 microV. CONCLUSIONS: For the turns/amplitude analysis of the tibialis anterior muscle an amplitude threshold of 30 microV should be selected.     

Myopathic changes detected by quantitative electromyography in patients with MuSK and AChR positive myasthenia gravis

Myopathic changes are frequent a electrophysiological finding in patients with muscle specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). The aim of this study was to explore the importance of quantitative electromyography (EMG) in the detection of myopathic changes in MuSK MG patients. Classical and quantitative EMG were performed in 31 MuSK and 28 acetylcholine receptor (AChR) positive MG patients, matched by sex, age, disease duration and severity. Classical EMG revealed the presence of myopathic changes more frequently in MuSK MG compared to AChR MG patients, especially in the facial muscles. Quantitative EMG registered myopathic lesions more frequently than classical EMG, but the frequency was similar between MuSK and AChR MG patients. Quantitative EMG revealed myopathic changes in the majority of both MuSK and AChR positive MG patients. This examination is sensitive, but it cannot be used to differentiate between MG patients belonging to the different disease groups. It should not be used in isolation. Rather, it should complement classical EMG in the detection of myopathic changes.     

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.