Compound muscle action potentials during repetitive nerve stimulation

When using repetitive nerve stimulation to examine neuromuscular transmission, the change in compound muscle action potential (CMAP) size is usually assessed by measurement of negative-peak or peak-to-peak amplitude. Technological developments now allow automatic measurement of CMAP area, but some patients show increment of CMAP amplitude and decrement of CMAP area. This study systematically analyzed the changes in these CMAP parameters in 23 neurologically healthy subjects. CMAPs were recorded when the ulnar nerve was stimulated at frequencies of 1, 2, 5, 10, 20, 30, and 50 HZ (five pulses per train). CMAP amplitude showed significant increment within a train when stimulus frequency was above 5 HZ (probably due to increased muscle-fiber conduction velocity), whereas CMAP area hardly changed at any frequencies. Measurement of CMAP area produces less ambiguous results than amplitude measurement in repetitive nerve stimulation studies.     

Muscle fiber recovery functions studied with double pulse stimulation

Direct electrical stimulation with paired pulses at varied intervals was used to study the propagation velocity and action potential amplitude recovery functions (VRF and ARF) of single muscle fibers. Following a subnormal period with slowed conduction, most of the muscle fibers tested in healthy subjects showed a period of supernormal propagation velocity starting at 3 to 12 ms, with a peak between about 5 and 15 ms, a mean increase of 7%, and an approximately logarithmic decay toward 1 second. The onset of supernormality was earlier in muscle fibers from patients with muscular dystrophy and significantly delayed in those from denervated muscles. Denervated muscle fibers also had a significantly longer refractory period.     

Jitter in the muscle fibre.

Direct stimulation of muscle fibres with a regular 10 Hz rate, three computer generated random rhythms and a sequence of voluntary discharges was used to quantify the interdischarge interval (IDI) dependent jitter due to velocity recovery function (VRF). This jitter was found to depend on conduction time and strength of VRF, but not on propagation velocity. The results suggest that in the usual jitter study in voluntarily activated muscle fibre pairs, with moderately irregular discharge rate and interpotential intervals below 3 ms the IDI dependent jitter contributes on average less than 10 microseconds, but can be so large as to produce false abnormal values at more irregular rates, longer interpotential intervals and pronounced differences in VRF. It can be effectively removed by mathematical algorithms or, better still, by using electrical stimulation.     

Effect of muscle-fiber velocity recovery function on motor unit action potential properties in voluntary contractions

Measurements of muscle-fiber conduction velocity during voluntary contractions have been used in the diagnosis of neuromuscular diseases. However, the velocity of propagation of action potentials depends on the interspike interval of activation due to the velocity recovery function (VRF) of muscle fibers. The comparison of muscle-fiber conduction velocity estimates between individuals may thus be influenced by differences in motor unit discharge rate. This study investigates action potential properties of motor units of the sternocleidomastoid muscle during voluntary modulation of discharge rate with the purpose of assessing the effect of the VRF on motor unit properties in voluntary contractions. Nineteen healthy men trained to control a target motor unit with feedback of surface multichannel electromyographic (EMG) signals. The subjects performed three 30-s contractions of cervical flexion/rotation modulating the discharge rate of the target motor unit from 6.6 +/- 1.6 pps to 28.0 +/- 6.4 pps. Action potential conduction velocity was correlated to instantaneous discharge rate (R = 0.38 +/- 0.21). Action potential conduction velocity, peak-to-peak amplitude, and duration varied between minimum and maximum discharge rate (P < 0.01; percent change 12.3 +/- 5.0, -11.8 +/- 9.9, and -12.9 +/- 7.3). Thus, the properties of surface motor unit action potentials vary with modulation of discharge rate. This has implications for the use of conduction velocity values measured during voluntary contractions to differentiate patient populations from healthy individuals and for the development of normative data.     

A congenital myasthenic syndrome refractory to acetylcholinesterase inhibitors.

We studied 4 siblings (3 men and 1 woman), ages 22 to 43 years, with congenital ptosis, external ophthalmoplegia, proximal muscle weakness and fatigability unresponsive to acetylcholinesterase (AChE) inhibitors. Repetitive nerve stimulation showed a significant compound muscle action potential (CMAP) area decrement at 2 or 3 Hz. Nerve conduction studies and concentric needle electromyography were normal, and repetitive CMAPs to single nerve stimulation were not observed. Voluntary single fiber electromyography (SFEMG) showed increased jitter and blocking. Assessment of individual end-plates using SFEMG with intramuscular axonal microstimulation showed no uniform relationship between jitter and the rate of stimulation, consistent with a postsynaptic defect of neuromuscular transmission. Edrophonium eliminated the decremental response to repetitive nerve stimulation, but caused no significant clinical improvement, suggesting an additional mechanism for weakness in these patients.     

Compound sensory action potentials evoked by tactile and by electrical stimulation in normal median and sural nerves

The compound sensory action potential evoked by electrical stimulation provides a measure of the number and physiological properties of myelinated fibers in the nerve but does not allow evaluation of the most distal part of the sensory nerve. This study compares the compound sensory action potential, evoked by electrical and tactile stimuli, and recorded through needle electrodes placed close to the median and sural nerves of 22 normal males aged 16–51 years. The tactile probe, with a slight preindentation, delivered an indentation of the skin of 200 μm at a rate of 400 μ/ms at the tip of digit III and the dorsolateral side of the foot. The responses were recorded from the median nerve at wrist and elbow and from the sural nerve at the lateral malleolus and midcalf. The amplitudes of the responses averaged 0.5 μV and 0.7 μV in the sural and the median nerves (P < 0.02), respectively, which was only 5–10% of the amplitude evoked by electrical stimulation. The mean maximal conduction velocity determined by tactile stimulation was 54 m/s in the sural nerve compared with 65 m/s in the median nerve and similar to that calculated after electrical stimulation. In the median nerve the sensory conduction velocity was 8% faster than the motor conduction velocity. These findings indicated that only a fraction of the fibers in the nerve were activated by the probe and that the response was conducted along large myelinated sensory fibers. The latency of the tactile response was longer than that of the electrically evoked response due to the receptor delay and conduction along thin distal fiber portions. The delay at the mechanoreceptors was about 1 ms in the sural and 0.65 ms in the median nerve (P < 0.01). © 1994 John Wiley & Sons, Inc.     

Compound sensory action potential in normal and pathological human nerves

The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers in different polyneuropathies. In this review, different factors that characterize sensory fibers and set the SNAP apart from the CMAP are discussed to emphasize the supplementary and complementary information that can be obtained from sensory conduction studies. Sensory conduction studies require particular effort and attention to theory and practical detail that may be time consuming.     

Compressive bilateral peroneal neuropathy: serial electrophysiologic studies and pathophysiological remarks

A case of bilateral common peroneal neuropathy following prolonged squatting is reported. Serial peroneal conduction velocities with analysis of compound muscle action potential (CMAP) amplitude, area and duration performed at Days 1, 2, 5, 7, 14, 21, 37, 80 showed conduction block localized at the fibular head which lasted 14 days and paralleled clinical conditions. Axonal loss coexisted as indicated by amplitude reduction of CMAP from peroneal nerve stimulation at the ankle which reached the lowest values at Day 7. Excessive temporal dispersion, as indicated by abnormal increased duration of the CMAP from stimulation above the fibular head, was never detected. Conduction velocity in the segment across the fibular head was reduced as long as conduction block was present, due to preferential block of large diameter, fast conducting, fibers. The rapid resolution of conduction block and the absence of temporal dispersion suggest that compressive conduction block is not necessarily due to demyelination. Mechanical factors or ischemic-metabolic mechanisms might play a role.     

术中神经电生理监测和刺激尺神经治疗肘管综合征

目的 评估尺神经松解前置术结合术中超强电刺激治疗肘管综合征的治疗效果.方法 30例中重度肘管综合征患者首先进行尺神经松解前置术,测定并记录松解后小指展肌复合肌肉动作电位(CMAP)的潜伏期及波幅;然后给予尺神经超强电刺激治疗(80 mA,2Hz,10 min),按照同样的方法再次记录小指展肌CMAP的潜伏期及波幅,并将刺激前后的数据进行统计学分析.结果 患者尺神经外膜松解后与超强电刺激后小指展肌CMAP的波幅分别为(2.5±0.4) mV和(6.2±0.8)mV,潜伏期分别为(12.0±0.6)ms和(10.3±0.3)ms,经比较有统计学意义(P＜0.05).超强电刺激后小指展肌CMAP的潜伏期较前平均缩短15.7％,波幅平均增大约2倍.结论 术中超强电刺激对肘管综合征患者的尺神经功能恢复具有辅助治疗作用.     

The cause of slowed forearm median conduction velocity in carpal tunnel syndrome.

OBJECTIVES: Attempting to answer a debate concerning the etiopathogenesis of the decreased forearm median motor conduction velocity (FMMCV), we tried to use proximal stimulation at the wrist, elbow, mid-arm and axillary regions to determine segmental median motor conduction velocity (MMCV). We also correlated the FMMCV with median motor distal latency (MMDL) and compound muscle action potential (CMAP) amplitudes of the abductor pollicis brevis (APB) muscle in order to assess whether the conduction block of large myelinating fibers or retrograde axonal atrophy was the major cause of the decreased FMMCV. BACKGROUND: The cause of the decreased FMMCV resulting from either the conduction block of the large myelinating fibers at the wrist or distal compression with retrograde axonal atrophy remains an unresolved issue at the moment. Animal models have supported the hypothesis that the retrograde axonal atrophy might also occur in humans. Other authors believe the standard FMMCV is calculated by subtracting the distal latency which may not represent an exact assessment of FMMCV but rather the velocity of small fibers that persist through the carpal tunnel. SUBJECTS AND METHODS: Patients with the clinical symptoms and signs of carpal tunnel syndrome (CTS) confirmed using standard electrodiagnosis were included. The patients were arbitrarily divided into two groups based on the FMMCV, one with reduced FMMCV (n = 20, FMMCV < 50 m/s) and the other with normal FMMCV (n = 35, FMMCV> or =50 m/s). Age-matched volunteers served as controls. We explored motor conduction proximally at wrist, elbow, mid-arm and axillary stimulation, and recorded at the APB muscles. Based on the latency differences, we calculated the FMMCV, distal arm MMCV (DAMMCV) and proximal arm MMCV (PAMMCV), and compared the conduction velocity (CV) differences of DAMMCV-FMMCV, PAMMCV-FMMCV and PAMMCV-DAMMCV in the two patient groups and the control. Furthermore, we correlated FMMCV with MMDL and CMAP amplitudes of APB muscle because MMDL and CMAP amplitudes might reflect the integrity of the large myelinating fibers. RESULTS: CMAP amplitudes of APB muscle at wrist stimulation and MMDL were not correlated with FMMCV in either of the two patient groups; however, the CMAP amplitude was markedly decreased and MMDL was significantly prolonged when compared with normal controls. The significant increase of CV gradient of DAMMCV-FMMCV and PAMMCV-FMMCV without an equal increase of CV gradient of PAMMCV-DAMMCV only occurred in the reduced FMMCV patient group, suggesting that the conduction block is not the primary cause. The CV gradient of DAMMCV-FMMCV and PAMMCV-DAMMCV did not show any significant difference between patients with the normal FMMCV and the control group. CONCLUSION: The retrograde axonal atrophy, not selective damage of the large fibers at the wrist, was the direct cause of the decreased FMMCV.     

Critical illness myopathy: further evidence from muscle-fiber excitability studies of an acquired channelopathy

Recent studies have demonstrated acquired muscle inexcitability in critical illness myopathy (CIM) and have used direct muscle stimulation (DMS) techniques to distinguish neuropathy from myopathy as a cause of weakness in the critically ill. The mechanisms underlying weakness in CIM are incompletely understood and DMS is only semiquantitative. We report results from a series of 32 patients with CIM and demonstrate significant slowing of muscle-fiber conduction velocity (MFCV) and muscle-fiber conduction block during the acute phase of CIM, which correlates with prolonged compound muscle action potential (CMAP) duration, clinical severity, and course. We also used a paired stimulation technique to explore the excitability of individual muscle fibers in vivo. We demonstrate altered muscle-fiber excitability in CIM patients. Serial studies help define the course of these pathophysiological changes. Parallels are made between CIM and hypokalemic periodic paralysis. Our findings provide further evidence for muscle membrane dysfunction being the principal underlying abnormality in CIM.     

Muscle fiber conduction velocity at different states of isotonic contraction.

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

A new method to measure the distribution of motor conduction velocity in man.

A new method of measuring the distribution of conduction velocities in human motor fibers is described. In this method, a modification of Kimura's collision technique is combined with Hopf's technique. This enabled us to determine the collision end-point in Hopf's technique, from which the minimum velocity is derived. The size of the distorted compound muscle action potential (CMAP) measured with Hopf's technique is corrected using the CMAP size with the modified Kimura technique. This resolves the problem of CMAP distortion due to transient change in muscle conduction in Hopf's technique. In addition, a new equation to correct for the refractory period was developed. This can be applied even if there is stimulus spread. Using our method, one can clearly determine the maximum and minimum velocities. The former corresponds to the motor conduction velocity as measured by the conventional method.     

Electrophysiological characteristics of motor units and muscle fibers in trained and untrained young male subjects

We hypothesized that the amplitudes of compound muscle action potentials (CMAPs) and interference pattern analysis (IPA) would be larger in trained subjects compared with untrained subjects, possibly due to hypertrophy of muscle fibers and/or increased central drive. Moreover, we hypothesized that the untrained muscle is less excitable compared with the trained muscle. An electromyographic (EMG) needle electrode was used to record the IPA at maximal voluntary effort. The CMAP was obtained by stimulating the musculocutaneous nerve and recording the brachial biceps muscle using surface electrodes. CMAPs were obtained by direct muscle stimulation (DMS) with two stainless‐steel subdermal electrodes placed subcutaneously in the distal third of the muscle. Amplitudes of CMAP and IPA were significantly larger in trained subjects compared with untrained subjects. We found no differences between trained and untrained subjects in IPA power spectrum and turns per second or amplitude of the CMAPs obtained by DMS. Muscle fiber hypertrophy and/or altered central drive may account for our results, but there was no indication of changes in muscle fiber excitability. Muscle Nerve, 2010     

A novel stimulation pattern improves performance during repetitive dynamic contractions

The purpose of this study was to determine the effect of three different stimulation patterns on repetitive knee movements. Each subject's quadriceps femoris was stimulated with: (1) a constant-frequency train (CFT) with an interpulse interval (IPI) of 50 ms; (2) a variable-frequency train (VFT)-similar to the CFT, except with an initial doublet with an IPI of 5 ms; and (3) a doublet-frequency train (DFT) with multiple doublets (doublet IPI 5 ms) separated by 50 ms, while the muscle was resisted by a load equal to 10% of the muscle's maximum voluntary isometric contraction. The muscle was stimulated while the knee moved through a 50 degrees arc of motion (90 degrees to 40 degrees of flexion). Testing was stopped when the subject failed to reach the target three consecutive times. Results showed that DFTs reached the target (mean +/- SD) 36.4 +/- 14.4 times, followed by VFTs (25.4 +/- 17.9) and CFTs (17.4 +/- 11.9). The DFT was the best pattern for producing shortening contractions. The results suggest that DFTs may have significant benefits during clinical functional electrical stimulation.     

Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques

ObjectiveTo determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans.MethodsA collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1–5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time.ResultsCompound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve.ConclusionsThe conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test.SignificanceWe provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.     

Neuromuscular response in man to repetitive nerve stimulation

Paired stimulation has been used extensively in clinical neuropathysiology. We studies change in the sizes of compound muscle action potencial (CNAPs) in humans after a single electrical stimulus to the peripheral nerve. When the interstimulus intervals were varied, the second potentials underwent refractoriness and then were facilitated up to 20–30 ms, thereafter being depressed for 160–200 ms. When intensities were graded at fixed intervals for motor fibers the maximal effects was obtained with liminal stimulation, but was no longer observed at supramaximal stimulation. When the intrensity used to obtain M-resposes was half the maximum, maximal facilitations were 35% (CNAP) and 17% (CMAP) of the first potential, the respective maximal depressions being 13% and 42%. When the sizes of the two CNARs were equalized by adjusting the second stimuli, the CMAP was facilitated (26%) up to 65 ms, thereafter being depressed (13%). These results must be taken into account when making clinical examinations that use paired stimulation. © 1993 John Wiley & Sons, Inc.     

Repetitive nerve stimulation: effects of recording site and the nature of 'pseudofacilitation'.

OBJECTIVES: To describe changes in the waveform of the compound muscle action potential (CMAP) during repetitive nerve stimulation for various recording sites. METHODS: Responses to trains of 10 stimuli given at 0.1, 1, 3, 5, 10 and 30 Hz to the ulnar nerve were recorded simultaneously from 8 hand sites in 15 healthy subjects. Percentile changes of amplitude, duration and area of both negative and positive phases were analyzed. RESULTS: Duration consistently decreased during the trains. At 30 Hz, the mean amplitude of the negative phase increased on 5 sites but decreased on 3. Area consistently decreased, but least for hypothenar sites. Repeated stimulation causes an alteration in the waveform of the CMAP that consists of 4 elements: (1) shorter duration; (2) changed amplitude of the negative phase (up or down); (3) merging of bifid peaks; (4) changes were more pronounced for positive than negative phases. CONCLUSIONS: As the term 'pseudofacilitation' implies an increase in amplitude, it is often not appropriate. Increased muscle fiber conduction velocity can explain most of the waveform alterations. Movement and shortening of muscles may play additional roles. Consequences for diagnostic yield await a comparison with disease groups.     

Differentiation between axonal and demyelinating neuropathies: Identical segments recorded from proximal and distal muscles

The presence of significant slowing of motor nerve conduction velocity is considered one of the electrodiagnostic hallmarks of demyelinating neuropathies; however, slowing of conduction velocity may also accompany severe axonal loss. When compound muscle action potential (CMAP) amplitudes are markedly reduced, it is frequently difficult to determine if conduction velocity slowing is due to axonal loss with dropout of the fastest conducting fibers or demyelination. To evaluate the relationship between conduction velocity and axonal dropout, we compared conduction velocities through the same segment of nerve recording from distal and proximal peroneal muscles in patients with chronic neuropathies, in patients with motor neuron disease, and in control subjects. In controls and patients with motor neuron disease, conduction velocities were normal with no significant difference between proximal and distal sites. In patients with axonal neuropathies, conduction velocities were preferentially slowed when recording from distal muscles and relatively normal when recording from proximal sites. Patients with demyelinating neuropathies showed marked slowing of conduction at both sites. We conclude that comparing conduction velocity obtained from proximal versus distal muscle recordings provides a simple, reliable aid for differentiating between chronic axonal and demyelinating polyneuropathies, especially in cases with conduction velocity slowing and low CMAP amplitudes. © 1995 John Wiley & Sons, Inc.     

Motor neuron firing range,axonal conduction velocity,and muscle fiber histochemistry in neuromuscular diseases

The voluntary discharge properties and axonal conduction velocity of single motor units were studied in patients with neuromuscular diseases with retained differentiation of the muscle fibers into type 1 and type 2, and in patients with late-onset hereditary distal myopathy in which muscle fibers have only intermediate histochemical properties. In the patients with muscle fiber differentiation, the findings were similar to those in normal subjects; that is, there was a continuum between motor units which fired tonically at low rates and had a low axonal conduction velocity, and motor units which fired phasically at high rates and had a high axonal conduction velocity. In the patients without muscle fiber differentiation, all motor units had intermediate firing properties and a low axonal conduction velocity. It is suggested that in chronic pathologic states, the differentiation of the muscle fiber histochemistry remains only as long as the differentiation of the motor neurons remains.