Electrophysiological study of neuromuscular system involvement in mitochondrial cytopathy.

OBJECTIVES: To define the neuromuscular involvement in 'mitochondrial' patients with clinical evidence of a neuromuscular disorder, and to evaluate if the proposed electrophysiological protocol was suitable to reveal a subclinical neuropathy or myopathy in 'mitochondrial' patients with no clinical sign of a neuromuscular disturbance. METHODS: Quantitative concentric needle electromyography (CNEMG), single fiber electromyography (SFEMG) and nerve conduction studies (NCS) were performed in 33 patients with mitochondrial cytopathies. Lastly, we studied 9 clinically unaffected relatives. RESULTS: NCS were abnormal in 18% of patients, with CNEMG and SFEMG in 58% of cases, but there was not a complete overlapping of the positivity of the different techniques. No asymptomatic relatives showed abnormalities of the electrophysiological studies. CONCLUSIONS: Electrophysiological findings did not correlate with any specific biochemical or genetic defect, but were consistent with clinical diagnosis in almost all of the patients with clinical signs of myopathy and/or neuropathy. Increase of both SFEMG jitter and fiber density was significantly tied to a neuropathic process. CNEMG and SFEMG were altered in about 30% of subjects without clinical signs of myopathy or neuropathy and were therefore able to reveal a subclinical involvement of neuromuscular system in some patients who had external ophthalmoplegia or retinitis only.     

EMG of reinnervated motor units: a simulation study

Using computer simulation techniques, reinnervation of motor units (MUs) was studied by increasing the number of muscle fibers in the MU without changing the MU territory. The fiber density (FD) measured by single fiber EMG electrodes, the amplitude, area and number of turns of concentric needle (CN) EMG motor unit action potentials (MUAPs) and the amplitude of macro EMG MUAPs were most affected by partial reinnervation changes. The values of these features increased during simulated advanced reinnervation, as did the number of CNEMG MUAPs that had increased numbers of phases or turns and the mean CNEMG MUAP duration. The increase in macro EMG MUAP amplitude, FD and CNEMG MUAP area were proportional to the increase in the number of muscle fibers in the MU. When loss of muscle fibers due to so-called MU fractionation was simulated, values of all EMG features fell, but were still increased compared to normal. Two patterns of change in SFEMG and macro EMG values were identified that may distinguish between recordings made from reinnervated low force threshold MUs and those from higher force threshold MUs.     

Simulation of the normal concentric needle electromyogram by using a muscle model.

OBJECTIVES: To study the correlation between anatomical parameters and EMG signals by means of simulations. METHODS: A mathematical model of the electrical activity from muscle fibres and motor units has been developed. The electrical fields around the muscle fibres are simulated using a line source model. The model permits the simulation of single muscle fibre action potentials obtained by SFEMG, concentric and Macro EMG electrodes. By using appropriate anatomical parameters EMG recordings with these electrodes can be simulated. The model is flexible and permits a number of anatomical parameters to be changed such as; number of muscle fibres in a motor unit, fibre diameter distribution, and motor end-plate geometry. Some physiological parameters can be optionally varied; firing rate, threshold for recruitment, jitter. RESULTS: In this study, simulations of CNEMG are performed and the influence of a number of parameters on the CNEMG signal is studied. It is shown that the model produces motor unit potentials reasonably well resembling those from live recordings. More important is however the relative change in MUP parameters when certain conditions are changed; number of muscle fibres in a motor unit, recording position, muscle fibre diameters and some special effects of the recording conditions. CONCLUSIONS: The simulated muscle and corresponding EMG recording can be used both as a research tool and for teaching.     

Comparison between concentric needle EMG and macro EMG in patients with a history of polio.

OBJECTIVES: Acute poliomyelitis causes degeneration of anterior horn cells, followed by denervation. Reinnervation and muscle fibre hypertrophy are mechanisms that compensate this loss of neurones. Concentric needle EMG (CNEMG) and macro EMG are two methods to assess the magnitude of initial involvement and the compensatory reinnervation. The aim of this study is to explore the difference between CNEMG and macro EMG describing the status of the motor unit in patients previously affected by polio. METHODS: Macro and concentric needle EMG investigations were performed in 261 muscles in 121 patients with a remote history of polio. RESULTS: CNEMG was abnormal in 211 muscles, macro EMG was abnormal in 246 muscles. The macro amplitude was 3-4 times 'more abnormal' than CNEMG amplitude relative to the reference values. CNEMG duration was less abnormal and showed only weak correlation with macro amplitudes. The most likely explanation for the difference in magnitude of deviation from reference values for CNEMG and macro EMG, is a more pronounced 'phase cancellation' between single fibre action potentials in CNEMG. This is supported by simulation studies reported here. CONCLUSIONS: In conclusion macro EMG better reflects the size of the motor unit than the CNEMG. For detection of concomitant disorders, CNEMG is the method of choice.     

Electrophysiological spectrum of inclusion body myositis

We present electrodiagnostic data on 30 patients with inclusion body myositis (IBM) in order to better delineate its electrophysiological features. Comprehensive electromyography (EMG) and nerve conduction studies (NCS) were performed in all cases. Twelve patients had single fiber electromyography (SFEMG). EMG showed abundant short-small motor unit potentials (MUP) with fibrillations and positive sharp waves in 56.6% of patients, and a mixed pattern of large and small MUP in 36.7%. In 6.7%, only "neurogenic" features were seen. NCS were slow in 33.3%. SFEMG revealed a mildly abnormal jitter and a slightly increased fiber density. IBM demonstrates a heterogeneous EMG profile. A pattern of large and small MUP is highly suggestive of IBM but is seen in only about one third of cases.     

Motor unit potential abnormalities in multiple sclerosis: further evidence for a peripheral nervous system defect.

We have recently reported abnormalities of single fibre EMG in patients with multiple sclerosis. The present study applies quantitative electrophysiological techniques to the same group of patients. The number of motor units in the extensor digitorum brevis muscle was measured and their characteristics recorded. Also the shortest distal motor latency and fastest motor conduction velocities were estimated. Abnormalities suggesting a patchy denervating/reinnervating process due to pathology in the intramuscular nerve network or at the endplate were found in a number of patients. There was a good correlation between patients with abnormal motor unit potentials and those with abnormal single fibre EMG "jitter".     

The single-fiber EMG in chronic demyelinating neuropathy

Various parameters of single- fiber electromyography (SFEMG) were studied in 19 patients with electrophysiologically and histologically proven chronic demyelinating neuropathy. The mean duration of disease at the time of testing was four years. Motor nerve conduction in the median nerve was abnormal in all patients, whereas sensory nerve conduction was abnormal in all but one. Needle EMG in the extensor digitorum communis (EDC) muscle showed rare fibrillations and fasciculations and some abnormal motor unit potentials in most of patients. SFEMG in the EDC muscle showed an increased fiber density in seven cases (37%) and minimally abnormal jitter in 14 cases (74%). Single-fiber action potentials were stable, whereas blocking was rare. Fiber density was significantly increased in patients with fibrillation in the conventional needle EMG. Our study showed that the SFEMG is mildly abnormal in many patients with demyelinating neuropathy and that this test is useful in detecting and quantitating axonal degeneration in demyelinating neuropathy.     

A useful electrophysiological test for diagnosis of minimal conduction block.

OBJECTIVE: To evaluate the usefulness, sensitivity and specificity of a new neurophysiological test for partial conduction block. METHODS. In 17 patients (17 nerves) with clinical pictures strongly suggesting the presence of motor conduction block and 20 healthy subjects (40 nerves), motor nerve conduction studies were performed with the conventional surface technique and with a new technique developed by us: the single fiber EMG (SFEMG) conduction block test. Moreover, we also evaluated patients with other neurological diseases. The recent American Association of Electrodiagnostic Medicine (AAEM) consensus criteria for partial conduction block were used for the standard conduction block tests. RESULTS: According to AAEM consensus criteria, 5/17 cases presented 'definite' partial conduction block and 6 presented 'probable' partial conduction block. In contrast, 16/17 cases (94%) presented evidence of conduction block at the SFEMG conduction block test. The 5/6 cases that did not fulfill in the AAEM criteria and that presented abnormal findings at SFEMG nerve conduction test could be considered affected by minimal conduction block. The sensitivity of this new test was greater than conventional test. The specificity was 100% (no abnormal findings in healthy subjects or patients with diseases other than neuropathy). CONCLUSIONS: The SFEMG conduction block test is a sensitive, complementary, technique for diagnosis of minimal conduction block in patients with normal findings in standard nerve conduction studies.     

The role of different EMG methods in evaluating myopathy.

For the diagnosis of myopathy, EMG may have an important role along with blood tests, muscle biopsies and genetic testing. This review evaluates different EMG methods in the diagnosis of myopathy. These include manual analysis of individual motor unit potentials and multi-motor unit potential analysis sampled at weak effort. At high effort, turns-amplitude analyses such as the cloud analysis and the peak ratio analysis have a high diagnostic yield. The EMG can seldom be used to differentiate between different types of myopathy. In the channelopathies, myotonia, exercise test and cooling of the muscle are helpful. Macro-EMG, single-fibre EMG and muscle fibre conduction velocity analysis have a limited role in myopathy, but provide information about the changes seen. Analysis of the firing rate of motor units, power spectrum analysis, as well as multichannel surface EMG may have diagnostic potential in the future. EMG is of great importance in the diagnosing of patients with myopathy, preferably a needle electrode and quantitative analyses should be used. A combination of a method at weak effort as well as a method at stronger effort seems optimal.     

Single fibre electromyography in various processes affecting the anterior horn cell

SFEMG recordings were carried out in patients with amyotrophic lateral sclerosis, progressive muscular atrophy, familial spinal muscular atrophy and syringomyelia. The fibre density was increased in all conditions, especially in progressive muscular atrophy indicating marked collateral sprouting. The duration of the action potential was increased indicating a mixture of hypertrophic and atrophic fibres and slowly conducting newly formed nerve sprouts. The action potentials were unstable with varying degree of impulse blocking especially in the more progressive cases (ALS), representing recent re-innervation. The SFEMG method is used to characterize the functional status of the motor unit and helps in diagnosis and in predicting prognosis. In addition, SFEMG recordings reveal abnormalities in clinically and electromyographically normal muscles.     

Vulnerability of lower brachial myotomes in motor neurone disease: A clinical and single fibre EMG study

Single fibre EMG was used to study the motor unit fibre density in the right biceps brachii, extensor digitorum communis and first dorsal interosseous muscles of 15 patients with motor neurone disease, with different patterns of initial weakness. There was an inverse relationship between strength and fibre density in these muscles. Abnormalities were more marked in patients whose initial symptom was arm weakness, but collateral reinnervation was not as effective as in other neurogenic disorders. These findings are consistent with a hypothesis that motor neurone disease begins segmentally, or at a discrete level within the motor system, before becoming generalised. The single fibre EMG fibre density is a useful quantitative technique for sequential assessment of patients with neurogenic disorders.     

Single-fiber electromyography in sporadic inclusion body myopathy.

OBJECTIVE: To report the SFEMG findings in sporadic inclusion body myopathy (S-IBM). METHODS: We have analyzed the SFEMG data in 25 patients (mean age: 63; 16 males) with S-IBM which was diagnosed by the presence of classical rimmed vacuoles in the muscle biopsy together with clinical, laboratory, and electrophysiological findings. RESULTS: All patients had fibrillations, positive sharp waves, and small-amplitude short-duration motor unit potentials (MUPs) in the needle EMG. High-amplitude MUPs were observed in eight (32%) patients, two of whom had long-duration MUPs. SFEMG was abnormal in 17 (68%) cases: mean "mean consecutive difference (MCD)" was increased beyond the age-adjusted normal limit in 16 cases, and more than 10% of potential pairs (PP) had MCD longer than the upper normal limit of an individual MCD in one case. Mean fiber density (FD) was 2.16, with maximum FD being 4.15. Increased FD was noted in 11 (44%) cases. In four cases, more than 10% of PP had blocking, but there was no neurogenic blocking in any PP. As expected, MCD increased linearly (r=0.85) with the percentage of PP beyond the normal upper limit. CONCLUSIONS: The SFEMG findings in S-IBM are typical of the classical pattern of myopathy. SIGNIFICANCE: Our findings support the consensus that S-IBM is a myopathy.     

High serum levels of creatine kinase: asymptomatic prelude to distal myopathy

Two brothers and an unrelated man had serum creatine kinase values of 3000-8000 units when they were asymptomatic, and there was no weakness on examination. EMG and muscle biopsy showed changes indicative of myopathy. Years later, all three developed weakness that was limited to the gastrocnemius. Because siblings were affected, the disorder can be regarded as a form of muscular dystrophy. The distribution of weakness, serum enzyme changes, and histologic changes resembled an autosomal recessive distal myopathy first described by Miyoshi and differed from many other reported cases of distal myopathy. Our cases also indicate that myopathy may be asymptomatic.     

Electrophysiological studies in the post-viral fatigue syndrome.

Single fibre electromyography (SFEMG) was studied in 40 patients with the post-viral fatigue syndrome. These patients were also assessed clinically, serologically, virologically and immunologically. About 75% of the patients had definitely abnormal SFEMG results. This was regarded as evidence of abnormality in the peripheral part of the motor unit. The muscle fibre was the likely site of involvement.     

Single fibre electromyography in multifocal motor neuropathy with persistent conduction blocks

OBJECTIVE—To study theprocess of denervation-reinnervation in multifocal motor neuropathywith persistent conduction blocks in clinically affected and unaffected muscles.
METHOD—Volitionalsingle fibre electromyography (SFEMG) was performed in the extensordigitorum communis (EDC) of seven patients. The jitter, the fibredensity, and the mean interpotential interval were determined. Theresults before and after treatment with intravenous immunoglobulin(IVIg) between the unaffected EDC and affected EDC examined during thesame SFEMG session were also compared. In addition the values ofjitter, fibre density, and mean interpotential interval were analysedfor correlation with the strength score on the MRC scale, the durationof the neuropathy, the number of IVIg treatment periods, and the radialnerve conduction block values.
RESULTS—Mean jitter,percentage of jitters>60 µs, and impulse blocking percentage, werehigher than normal in both the affected EDCs and to a lesser degree inunaffected EDCs. Jitter decreased significantly after IVIg andcorrelated only with the MRC score. Fibre density and meaninterpotential interval were higher than normal equally in the affectedEDC and unaffected EDCs, but no correlation was found with strength,duration of the neuropathy, number of treatment periods, and conductionblock values.
CONCLUSION—The majorfinding is the presence of SFEMG abnormalities in clinically unaffectedEDCs. This shows a process of denervation-reinnervation even in theabsence of clinical symptoms, probably more frequent than commonlysupposed in this neuropathy. The rapid clinical improvement after IVIginfusions could be due to remyelination after demyelination and to aninterference of IVIg with the blocking effect of antibodies on theNa⁺ channels at the motor nerve endings.

     

Fasciculations in motor neuron disease: discharge rate reflects extent and recency of collateral sprouting.

Single fibre EMG recordings were made from 152 fasciculating motor units in 17 patients with motor neuron disease. All recordings showed abnormal jitter, many (75%) displayed intermittent blocking, and most had abnormal fibre density (mean 4.3), demonstrating considerable degrees of collateral sprouting supported by the fasciculating motor units, and varying degrees of functional immaturity of the new axonal twigs and the motor end plates. The SFEMG abnormalities reflecting both the degree and the recency of collateral reinnervation correlated with the mean interdischarge interval, suggesting that the properties of the generator site depend on the functional state of the fasciculating motor unit as a whole.     

Single fibre EMG in 6 cases of botulism

ABSTRACT- In 6 cases of mild botulinum intoxication, conventional EMG and single fibre EMG (SFEMG) were performed on admission to our ward (about 15 days after ingestion of the toxin) and 4, 8 and 14 weeks after admission.
In 4 cases, conventional EMG resulted in abnormal findings; and they normalized 4 weeks later. On the first examination, SFEMG revealed in all cases but one the occurrence of potential pairs with abnormal jitter (above 50 μs). The % of the potential pairs with abnormal jitter ranged in different cases from 17% to 44%. Some of the potential pairs with abnormal jitter showed blockings; the occurrence of blockings was not strictly related to jitter value. Mean jitter value and % of potential pairs with abnormal jitter became progressively reduced with increasing time after intoxication. Nevertheless, in 4 cases slightly abnormal findings were still present after 4 months.
The data obtained in the basal condition are in agreement with those reported by others. SFEMG findings relate fairly well to conventional EMG data and clinical status. SFEMG has proved to be a very sensitive method for studying the neuromuscular transmission defect in botulism and in obtaining further information on the course of the syndrome.     

Macro EMG

A new EMG recording technique called macro EMG is described. The recording electrode is the cannula of the modified single fiber electromyography (SFEMG) electrode. By means of spike triggered averaging, the contribution from all muscle fibers in a motor unit is extracted. The resulting signal reflects the number and size of muscle fibers in one motor unit. This paper presents the details of the technique, the neurophysiological basis for generation of the macro EMG signal, and the typical findings in normal and diseased muscles. Finally, examples are given of the additional information that can be obtained by combining investigations with SFEMG, conventional EMG, and macro EMG in the same muscles.     

Origin of ICU acquired paresis determined by direct muscle stimulation

BACKGROUND: Acquired diffuse paresis in an intensive care unit (ICU) can result from critical illness myopathy or polyneuropathy. Clinical examination and conventional neurophysiological techniques may not distinguish between these entities. OBJECTIVE: To assess the value of direct muscle stimulation (DMS) to differentiate myopathic from neuropathic process in critically ill patients with diffuse severe muscle weakness. METHODS: 30 consecutive patients with ICU acquired diffuse motor weakness were studied. Responses of the right deltoid and tibialis anterior muscles to DMS and to motor nerve stimulation (MNS) were studied and compared with results of conventional nerve conduction studies and concentric needle electromyography (EMG). An original algorithm was used for differential diagnosis, taking into account first the amplitude of the responses to DMS, then the MNS to DMS amplitude ratio, and finally the amplitude of the sensory nerve action potentials recorded at the lower limbs. RESULTS: Evidence of neuropathy and myopathy was found in 57% and 83% of the patients, respectively. Pure or predominant myopathy was found in 19 patients. Other results were consistent with neuromyopathy (n = 5) and pure or predominant neuropathy (n = 2). Four patients had normal results with stimulation techniques, but spontaneous EMG activity and raised plasma creatine kinase suggesting necrotic myopathy. CONCLUSIONS: A neurophysiological approach combining DMS and conventional techniques revealed myopathic processes in a majority of ICU patients. Reduced muscle fibre excitability may be a leading cause for this. The diagnosis of myopathy in ICU acquired paralysis can be established by a combination of DMS, needle EMG, and plasma creatine kinase.     

Single-fiber electromyography in hyperCKemia: the value of fiber density

Although persistently raised serum creatine kinase (sCK), or hyperCKemia, is considered the biological hallmark of neuromuscular diseases, pauci- or asymptomatic- or isolated-hyperCKemia can often be found. Single-fiber electromyography (SFEMG) is an electrophysiological technique of great value in the assessment of neuromuscular, neuropathic and myopathic disorders. We hypothesize that SFEMG fiber density (FD) evaluation is able to detect subclinical electrophysiological abnormalities indicating a myopathic process in subjects with hyperCKemia. Nineteen subjects with hyperCKemia without evident clinical signs of muscle involvement and 15 healthy controls were studied. Electrophysiological investigations including nerve conduction studies (NCS), quantitative EMG (QEMG), SFEMG with focus on FD measurements, and muscle biopsy were performed. NCS, QEMG, SFEMG were normal in all controls. In subjects with hyperCKemia, NCS were normal; QEMG was abnormal in 5, while both SFEMG and muscle biopsy disclosed abnormalities in 12 subjects. The mean FD value was 2.6 ± 0.5 in the control and 4 ± 1.4 (p = 0.003) in the hyperCKemia group. SFEMG revealed subclinical changes in the majority of subjects with hyperCKemia. To the best of our knowledge, this is the first study demonstrating that SFEMG FD evaluation is able to detect the presence of muscle diseases, which are in a subclinical phase and would remain unidentified otherwise. SFEMG may be used to distinguish hyperCKemia associated to asymptomatic muscle disorders from idiopathic hyperCKemia. We believe that SFEMG FD evaluation should be added to the routine examinations in the screening of idiopathic hyperCKemia.