eMedicine - EMG Evaluation of the Motor Unit: The Electrophysiologic Biopsy : Article by Paul E Barkhaus

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EMG Evaluation of the Motor Unit: The Electrophysiologic Biopsy

Article Last Updated: Jan 23, 2008

The motor unit (MU) is a part of the neuromuscular system that contains an anterior horn cell, its axon, and all of the muscle fibers (MFs) that it innervates, including the axon's specialized point of connection to the MFs, the neuromuscular junction. The neuromuscular system also includes upper motor neuron inputs to the lower motor neuron as well as afferent inputs from the periphery such as position receptors in joints, Golgi tendon organs, and muscle spindles. The result is the ability of the muscle to make various patterns of contraction under the control of the upper motor neurons in the central nervous system (CNS).

In routine needle-electrode examination (ie, electromyography [EMG]) of voluntary muscle contraction, the electrodiagnostic consultant assesses the signature electrical signal generated by the MUs, termed the MU action potential (MUAP). In addition, signals generated by individual or non-MU groups of MFs, termed insertion activity (IA) and spontaneous activity (SA), are assessed. These are patterns of random or rogue sub-MUAP activity that may yield important clues in the interpretation of the EMG signal. In electrodiagnosis, consideration of all data is important. The focus of this article is on MUs and the MUAPs they generate, particularly in neuromuscular disorders in which remodeling of the MU may occur. To place these concepts in perspective, some review of basic clinical neurophysiologic concepts is necessary. This discussion also is predicated on the assumption that the reader has some basic understanding of EMG.

Beginning with the pioneering work of Professor Fritz Buchthal and colleagues in the 1950s, the technique of EMG in MUAP analysis has undergone much refinement. In the last 2 decades, the advent of computers in EMG and variations in needle electrodes and instrumentation have given greater capability to the electrodiagnostic consultant. This has created a renaissance in clinical studies of the MU, particularly with the work of Professor Erik Stalberg.

The formal analysis or quantitation of the MUAP signal, termed quantitative analysis (QA), is currently not as cumbersome and time-consuming as in the past. It involves a discipline of quantitating the various features of the MUAPs. However, electrodiagnostic consultants have become accustomed to the expedient of subjective assessment of the EMG signal in routine analysis. A general trend also exists toward underutilization of new technology in instrumentation.

QA is not necessarily needed in every study, but careful analysis of the MUAP signal is essential. So why is an understanding of at least the principles of QA important? QA forms the foundation upon which routine subjective assessment of the MUAP waveforms is made.

Over the decades, clinicians have become immured with a closed-mindedness that reflexively links the diagnosis to the waveforms (eg, myopathic MUAP, neurogenic MUAP, BSAPs [brief, small, abundant potentials]). Daube expostulated this terminologic approach long ago.¹ The EMG signal should be assessed in the context of all electrodiagnostic data. A diagnostic impression should not be intended to bias the referring clinician against other reasonable possibilities.

In every routine EMG study, therefore, a more formal or objective approach to MUAP analysis should be made. This is accomplished by the electrodiagnostician training his or her eye to truly measure the size, complexity, and stability of the waveforms. This means not being a passive observer of the waveforms as they race across the screen but reaching out and manipulating the EMG instrument's settings to extract more information from this same signal (ie, interacting with the instrument). The authors refer to this approach as objective-interactive EMG, a practical compromise to traditional QA.^{2, 3}

The term MU, as defined by Sherrington, still is considered the anterior horn cell or alpha motoneuron (MN), its axon, and all the MFs it innervates, including the neuromuscular junctions. It remains the basic functional element of a skeletal muscle. Conversely, a muscle may be considered a grouping of MUs. Media file 1 schematically illustrates 2 MUs in a muscle.

Although 1 MN supplies or innervates 1 MF, the reverse is obviously not true. One MN may supply from 6-10 MFs in extraocular muscle to hundreds of MFs in a large proximal limb muscle such as the biceps brachii. The result is a remarkable expansion from controlling unit (ie, MN) to the endpoint of its apparatus (ie, MFs), in both anatomic and physiologic terms. In addition to the function of the MU in motor control, the MN also has a trophic effect in maintaining the integrity of the MFs at its endplate.

The endplate is that specialized region between the motor nerve terminal and the MF that mediates neuromuscular transmission (see Media file 1, region x). Therefore, the endplate region on the MFs contains the acetylcholine (ACh) receptors. When these receptors are activated successfully, the result is an endplate potential. Consequent to the endplate potential, an action potential (AP) is generated that spreads electrotonically down the length of the MF. As the AP travels down the MF membrane, the contractile apparatus is activated in turn.

The endplate zone in a healthy muscle is fairly homogeneous in that the endplates are usually at the mid portion along the length of the MFs (see Media file 1). This may vary depending on the shape of the muscle. Such positioning of the endplates allows greater efficiency in the bidirectional spread of the AP along the length of the MF membrane.

Minimal data are available on MF in humans. Knowing how MF length was assayed experimentally and differentiating between anatomic length and functional length are also important.⁴ MFs may vary considerably in length from approximately a few centimeters in the biceps brachii to less than 2 cm in smaller distal limb muscles. The configuration of a muscle is complicated further by the spatial arrangement of its MFs (eg, pinnate vs staggered). MFs have AP propagation velocities of 2-6 m/s (mean value 3.7 m/s).

The composition of a muscle by MF types (see Table 1) depends in part on the functional demands on that muscle. The gastrocnemius, which has more of a role in static postural maintenance, tends to be represented more heavily with type S (ie, slow twitch, fatigue-resistant) alpha MNs (see Table 1). In contrast, the first dorsal interosseous muscle (ie, of the hand) participates in more rapid, phasic movements and has more type FF (ie, fast twitch, fast to fatigue) MNs. Different classification schemes have been offered for MNs and MFs, which also may have some interspecies differences (see Table 1).

The MU territory (MUT) is defined as "the area in a muscle over which the MFs belonging to an individual MU are distributed".⁵ In humans, MUTs vary in size in different muscles. In a larger proximal limb muscle such as the biceps brachii, the MUT has an estimated diameter of 5-10 mm (ie, cross-section) based on scanning EMG studies.⁶ Data from animals suggest greater dispersion of the MUT in a muscle that also may change in size along the length of the muscle.⁴

SFEMG Fiber-density measurements in healthy muscle suggest that MFs (see Media file 2, electrode C) often are separated by 300 µm. Since the mean diameter of a healthy MF is 50-60 µm, the inference is that MFs from other MUs separate MFs within the same MU as in a mosaic pattern.

In a low-power histologic cross-section of muscle containing approximately 100 MFs, approximately 20-25 MUs are represented, with approximately 1-5 MFs per MU (see Media file 1B). This reflects the extensive interspersion of MFs from different MUs. Although an MU is homogeneous for the histochemical type of MF it contains, on routine histologic cross-section of muscle those MFs belonging to individual MUs still cannot be discerned. Newer techniques in quantitative histochemistry suggest a possible diversity in histochemical and biochemical properties even within the MFs of the same MU.

The MN exerts a trophic influence on the MFs and exhibits plasticity. Cross-innervation experiments have demonstrated that MFs may change their histochemical type. Fast MUs also may be changed experimentally to slow MUs by constant electrical stimulation, thymectomy, and castration. Exercise training in rats did not change the proportion of MN subtypes (see Table 1), which under usual conditions is fixed.

Subsequent to early development in animals, fast MUs may change to slow MUs with increasing age and body size, presumably in response to increased body weight and hence the need for more type S or tonic MUs. By selective training in which force is generated, MFs may hypertrophy, particularly the type II MFs. Endurance training alone (eg, running) generally does not result in MF hypertrophy. The exact mechanism of force generation in muscle and the functional connections of the MFs to the extracellular matrix are still incompletely understood.

Aging produces effects on the MU. Elderly individuals typically experience decrease in muscle bulk. This is probably due to generalized atrophy of individual MFs rather than to a decrease in the total number of MFs. Type II MF atrophy is a frequent change noted in aging. Muscle biopsy of healthy elderly individuals also exhibited evidence of MU remodeling. This was based on the findings of targeted MFs and mild degrees of MF type grouping.

Electrophysiologic evidence of MU remodeling in elderly individuals comes from 3 observations. First, the concentric needle (CN) MUAP demonstrates an increase in duration with increased age, though not to any significant degree until the individual is older than 60 years. Second, the (muscle) fiber density as measured in SFEMG increases after the sixth decade. This is the electrophysiologic analogue to MF type grouping but is based on the MU discharge rather than histochemical grouping. Third, macro-EMG MUAP amplitude in the vastus lateralis and anterior tibial muscles becomes larger after the sixth decade.

These specialized EMG techniques are discussed in Recording of the EMG signal. They collectively demonstrate changes in the MU compatible with reinnervation as suggested by the MF type grouping on muscle biopsy. Hence, these quantitative EMG and histologic findings imply a drop out of MNs as senescence proceeds beyond the fifth decade. Data from investigators counting motor axons in anterior roots support the concept of MN loss, though dying back of motor axons cannot be excluded.

The alpha MNs are arranged somatotopically into groups in the ventral horn according to myotomes and, in turn, the muscles that they supply. A group of alpha MNs supplying a given muscle is organized in a vertical column within the ventral horn such that the rostral MNs supply the superficial and proximal MUs of the muscle and the more caudal MNs supply the deeper and more caudal MUs. Knight and Kamen reported that superficial MUs were large relative to deep MUs, as studied by using macro EMG. In humans, almost all muscles are supplied by more than 1 root, allowing some protective effect in a single-level radiculopathy.⁷ The percent proportion of supply of a given muscle by a specific root may vary among individuals and between sides in the same individual.⁸

Homogeneity is found in the MFs supplied by a given alpha MN. Hence, a type I (ie, S alpha MN) has only histochemical type I MFs in its MU (see Media file 1). If an MF is orphaned (eg, denervated), it assumes the characteristics of the MN subsequently reinnervating it. Therefore, under such conditions, a histochemical type I MF may become a type II, or vice versa. During development, 1 neuron supplies a terminal axon to 1 MF. Whether any polyneuronal innervation of MFs occurs in the normal state is doubtful. Polyneuronal innervation exists in early development but disappears in rats and kittens by the age of 6 weeks. A similar phenomenon may occur transiently in reinnervation after denervation.

Recruitment is defined as "the successive activation of the same and additional MUs with increasing strength of voluntary muscle contraction".⁵ It is a complex process that is under CNS control. MU recruitment results in a strong efficient muscle contraction. Patterns of recruitment may differ between various types of motor activation (eg, slow isometric muscle contraction vs ballistic movement). The former pattern is used in routine clinical EMG assessment of MUAPs (see Media file 3A); hence, a bias exists toward examination of the lower threshold, type S MUs. In healthy muscle, a programmed pattern of activation of MUs is under central control, depending on the type of activation needed (eg, slow postural movement vs rapid phasic movement).

The size principle refers to alpha MN size relative to its order of recruitment in a population of MUs that comprises the fundamental organizational units of a muscle. The soma of alpha MNs vary in size, accounting for some of the differences between MU types I and II. Definite differences exist in other properties (see Table 1). Dendritic volume (ie, number of excitatory synapses on the neuronal soma) is constant in the 2 types of alpha MNs. Therefore, smaller type I MNs have relatively greater excitatory input given their smaller membrane size. In contrast, type II alpha MNs have a larger membrane, but given the same number of excitatory inputs, they have a lower excitatory potential.

Critical firing level (CFL) is a specific property of a particular MU that means an MN has a precise and reliable level or threshold of excitation at which it discharges. It ceases to discharge when input drive to the MN pool drops below the CFL. This also may be termed functional threshold. This has a narrow range of approximately 1-3% as demonstrated by varying input stimulation.

Although recruitment gradation refers to the number of alpha MNs being activated, rate gradation refers to the discharge frequency of a specific MN. In a smooth, graded isometric contraction (ie, ramp), a muscle must be capable of prolonged activation that is relatively resistant to fatigue. This is achieved by the size principle, in that the small type I MNs are activated initially. A single MU is activated first. With further effort, an increased rate gradation occurs within that particular MN before central input to a second MN (ie, recruitment gradation) reaches its CFL and begins to discharge. This continues until the larger type II MNs reach their CFLs and are activated. This pattern makes sense in that the type II MNs are activated later, as they are less resistant to fatigue.

To correlate with routine EMG needle examination, bias exists in assessing the waveforms of type I MNs. This is because the recording is made at low levels of activation (ie, voluntary muscle effort). MUAP amplitudes are relatively lower than at higher levels of activation. At maximal levels of voluntary effort, MUAP amplitudes increase, reflecting activation of the larger type II MUs. Special studies such as precision decomposition have demonstrated that in healthy human muscle, MUs may discharge at rates approaching 50 Hz at maximal effort.⁹

In practical application, however, MUAP amplitude reflects the size and distance of the closest MF to the recording surface of the needle electrode (see Media file 4A). Therefore, this does not necessarily reflect MU size. As force is increased, some recruited MUs have MFs close to the needle electrode. Their MUAPs are recognized easily by their large size. Conversely, some MUs that are distant have smaller amplitude MUAPs (eg, second recruited MUAP in Media file 3A is smaller than initially recruited MUAP). Thus, the size principle is not demonstrated in CN EMG recordings.¹⁰

In most modern EMGs, the myogenic or EMG signal is amplified by using a high-quality digital differential amplifier and then displayed on a digital screen (usually a computer monitor). A differential amplifier has 3 inputs: active, reference, and ground. Most of the new-generation EMGs are computer based. Some are based in smaller notebook-type computers yet still have powerful analysis capability compared with that of older-generation analog EMGs. The EMG signal is concurrently fed into an audio amplifier.

The basic (or routine) technique of recording the EMG signal uses intramuscular needle electrodes. The 2 basic types are monopolar (MON) and CN needle electrodes. The MON needle electrode is fabricated by grinding a Teflon-coated metal wire to a sharp conical tip (see Media file 5). This is the recording surface of the MON electrode. Two additional surface electrodes serve as a reference and ground.

The CN needle electrode is constructed from a fine metal wire inserted through a larger diameter metal cylinder, termed the cannula. The inner core is insulated from the cannula. The tip of this electrode is ground to a 15° angle to expose the inner wire's surface (150 X 580 µm) as an ellipse. The core of the CN is the recording surface, with the cannula serving as the reference. (In some images in this article, a short solid line is shown as the recording surface; this is meant to represent the CN recording surface in side view.) A third surface electrode is used for the ground input to the amplifier, similar to the recording montage of the MON electrode.

The size of the recording surface affects the recording characteristics of the needle electrode. Although the recording surfaces of these 2 electrodes differ (MON is 0.24 mm², whereas CN is 0.07 mm²), they are similar compared to other needle electrodes used in QA (see Media file 6). The SFEMG electrode is the most selective, with a recording surface of 0.0003 mm², and it can differentiate reliably the APs generated by single MFs (see Media file 2).

At the other end of the spectrum is the macro-EMG needle electrode, with a recording surface of 27 mm², which makes it the least selective recording needle electrode. It is used to record the electrical signal generated by the entire MU, a useful technique in looking at changes in MU size and in monitoring certain neuromuscular disorders. Collectively, these techniques provide complementary information to supplement the routine needle EMG.

Although the MON and CN needle electrodes have similar recording surfaces and both have intermediate selectivity, they differ from each other in the waveforms they generate (eg, MON-recorded MUAPs tend to have higher amplitude values and more phases), which are based on the inherent physical properties of these needle electrodes. The electrodiagnostic consultant must be aware of these differences when using these electrodes.

A further caveat involves use of the so-called facial (or pediatric) CN needle electrode. This electrode has a smaller recording surface than the standard CN (approximately 0.019 mm², which may vary among manufacturers) and is shorter in length (25 mm), making it appealing for those trying to compromise between use of a CN and greater patient comfort. Because of its smaller recording surface, some differences might be expected in MUAP metrics as reported by Barkhaus, Roberts, and Nandedkar.¹¹ Its length limits its use in sampling MUs in larger muscle.

Although this article emphasizes MUAPs, a brief review of the EMG signal may be helpful because signals are occasionally difficult to identify or because they may overlap each other (Barkhaus and Nandedkar, 1999). Examination of the EMG signal can initially be divided into 2 parts on routine assessment: involuntary and voluntary activity (see Examination of the EMG signal).

Two further categories are found under involuntary activity: IA and SA. IA results from mechanical irritation of the muscle as the needle electrode passes through the muscle and is velocity dependent with respect to electrode movement. Hence, a slow-moving electrode generates little to no IA in healthy muscle, whereas fast movements, particularly "pogo-sticking" the electrode at various sites, tend to elicit more IA. Use of the latter technique should be judicious from the standpoint of patient comfort and interpretation.

The 2 basic categories of IA are random (ie, bursts of spikes of varying shape and duration) and patterned (eg, complex repetitive discharges, myotonic discharges, trains of positive sharp waves, fibrillation potentials).

SA is described while the needle electrode is held in a fixed position in rested muscle. In healthy muscle, the baseline of the signal should be smooth and uninterrupted. In pathological conditions, patterned signals may appear similar to those that may have been recorded on IA assessment. Therefore, SA and IA are different in that they record APs generated spontaneously or by mechanical movement, respectively. Most of these signals are derived from single MFs or groups of MFs below the organizational level of the MUAP.

Examples of SA may occur at the MUAP organizational level, including fasciculation potentials that are the spontaneous random discharge of single MUs. Another example may be resting tremor, which represents periodic bursts of MUAP discharges as a result of abnormal central output from upper MNs (eg, Parkinson disease). Identification and classification of IA and SA, particularly the rogue sub-MUAP and MUAP discharges, are essential in making a comprehensive assessment of the EMG signal.

The second portion in the generation and assessment of the EMG signal includes 2 parts: the assessment of individual MUAPs and their patterns of activation. Individual MUAP measurement is made by having the patient slowly and minimally activate the muscle. The EMG signal should contain only the discharges of a few MUAPs with adequate baseline between discharges to enable full identification of their size and shape. The bias in the routine assessment of MUAPs is that they represent the signals generated by low-threshold type I (S) MUs. At low levels of activation, a presumed MUAP should be visualized 3 times before finally accepting it as a MUAP because of frequent superimposition between discharging MUAPs. These superimpositions may result in bizarre waveforms that may imply a pathological process in an otherwise normal study (see Media file 7).

The final portion of the assessment of the MUAPs lies in their activation pattern. The patient gradually increases the force of contraction, resulting in greater recruitment of MUs (see Media file 3) until full activation is achieved (ie, IP; see article on Inclusion Body Myositis, Image 4). This second portion of the assessment is the focus of this article and is how the MUAP relates to pathological changes in the MUs. Comprehensive assessment is not possible without considering other information such as IA, SA, and other electrophysiologic studies such as motor and sensory nerve conductions.

Before starting a study, the electrodiagnostic consultant must decide on a strategy of which muscles to sample. In presumed diffuse processes, the pattern of muscles most likely affected is based on clinical examination (eg, distal in most polyneuropathies vs proximal in most myopathies). In focal processes (eg, radiculopathy, mononeuropathy), segmental anatomy or myotomes and their potential variations must be considered.⁸

Acquisition of the EMG signal with attention to sampling of MUAPs is based on knowledge of the MU and the MUT as already described. To acquire MUAPs, the patient minimally activates the muscle after the needle electrode is inserted through the skin to the surface of the muscle. The needle electrode then is advanced in a linear track or corridor perpendicular to the long axis of the MFs. This ensures that the needle electrode passes through the maximum number of MFs proportionate to the length of the electrode that is in the muscle.

Scanning EMG studies demonstrate that the MUAP may vary considerably depending on where it is recorded in the MUT (see Media file 8). This variability is even more marked in neuromuscular disorders in which the normal mosaic distribution of the MFs in the MU is altered due to changes in the MFs or their distribution in the MUT. Sampling different MUAPs from different MUs may exhibit wide variation (see Media file 9). To ensure that a different MUAP is sampled at a given site, advancing the needle electrode the distance of the diameter of the MUT (eg, 5-10 mm in the biceps brachii) may be necessary.

To enter a different corridor once the needle electrode is at full depth of penetration, it is withdrawn to the surface of the muscle. The electrode then is angled approximately 30-45° medial or lateral to the axis of the first perpendicular corridor, and the electrode again is advanced, sampling MUAPs at each site. Three corridors are generally sufficient to sample a large limb muscle by using an electrode of suitable length (50 mm). With CN electrodes, the depth of sampling may affect amplitude because of the influence of the cannula on the signal. If more corridors are needed in the same muscle, the electrode is moved to a new skin insertion site at a suitable distance medial or lateral to the previous site and the long axis of the MFs.¹²

Reviewing the mathematical aspects of QA is beyond the scope of this article. In general, a sampling of 20 MUAPs is considered adequate. No matter which QA technique is used, the standard protocol for that technique must be followed carefully to ensure accurate measurement. For instance, MUAP duration typically is measured at a sensitivity setting of 100-200 µV per division, and polyphasic MUAPs are not included when mean duration is measured. MUAPs must be measured at the same instrumentation settings as the reference data.

If a laboratory uses published reference data, the electrodiagnostic consultant must confirm these by comparing his or her own reference data before using them. Use of the term reference data is deliberate in lieu of normal. What is normal? In collecting reference data in asymptomatic subjects, finding abnormality that is not clinically significant is always possible. Collective reference data involve the decision as to whether a subject should be included. Such a decision may be purely subjective. In assuming a gaussian distribution of values, the range within ±2 standard deviations should include 95% of tested subjects. Based on this, the chance always exists that a healthy subject may have an "abnormal" measurement. Mean values of MUAP features such as amplitude and duration traditionally have been used in QA, along with percent polyphasic MUAPs.

In routine EMG or subjective analysis, the strategy is different. The electrodiagnostic consultant looks for MUAPs with features that would not be observed in normal muscle (eg, increased amplitude, long duration, increased number of phases). Stalberg et al have designated these MUAPs as outliers. They defined upper and lower limit values for MUAP features such as amplitude. A muscle may have no more than 10% outlier recordings. Assuming a typical study sample of 20 MUAPs, the study becomes abnormal when the third outlier is encountered. At this point, the testing of that particular muscle has reached diagnostic significance, and the study can be extended to another muscle or concluded. This approach allows a greater economy of time yet still requires the examiner to quantify the MUAP signal.

A further point is that the patterns of abnormality should be consistent. In other words, the duration values in a muscle should not be abnormal by being both below and above the reference ranges. This occasionally happens, often resulting in the unsuitable terms mixed findings or neuromyopathy. Careful scrutiny of all data generally reveals a predominant trend in abnormality in key MUAP features. Thus, in neuromuscular disorders, look for a pattern or gestalt to help arrive at an interpretation or diagnostic impression. Media file 9 in this article and Image 1 in the article on Inclusion Body Myositis show composites of different MUAPs recorded from the biceps brachii in myopathy. Note the wide range in MUAP features (see Electrophysiologic Measurements of the Motor Unit), particularly amplitude.

To perform QA, a standardized methodology or protocol is necessary. The main methodologies in QA are described in Table 2. For a more extensive review, the reader is referred to Nandedkar and Barkhaus.^{2, 13} If an electrodiagnostic consultant is using commercially available software for analysis, he or she is obliged to understand the algorithm in how it makes measurements. In CN electrode analysis, the authors' protocol excludes polyphasic MUAPs from duration measurement, and they do not accept CN-recorded MUAPs less than 50 µV in amplitude for analysis.

Although trigger delay is a QA technique, its intermittent use (ie, interacting with instrumentation) to confirm waveforms may be essential during a study (see Media file 7). Trigger delay also may be used to examine other waveforms such as iterative discharges (eg, myotonic discharges, complex repetitive discharges) in performing a study. Moreover, this instrumentation adjustment is necessary to study MUAP stability.

The blanket principle (or "poor-person's" SFEMG) is as follows: In 1978, Payan used the example of a blanket covering a statue to describe how an electrode of intermediate selectivity such as the CN or MON electrode could be changed to one of higher selectivity by altering the instrumentation.¹⁸ To change the example, imagine standing in a precisely fixed position within a forest and wishing to take a picture of a tree that is directly in front. Acquisition is being made using a single lens reflex camera with an intermediate use lens of 55 mm. The photographer would like to refocus to appreciate closer details on the tree but cannot change position. Therefore, stopping and breaking the fixed focus with the camera to change to a separate, close-up lens is not possible.

Modern photography has provided the zoom lens, and in an analogous manner, modern EMGs have provided better instrumentation to zoom without breaking position (ie, losing the waveform of interest). This is achieved by increasing the low-frequency filter from the 2- to 20-Hz standard setting for routine MUAP acquisition to 500-1000 Hz. This removes surrounding low-frequency components of the MUAP signal, leaving only those APs of MFs very close to the recording surface of the needle electrode.

Increasing the low-frequency filter reduces the electrode's recording territory by removing generally the contribution of the MFs between those contributing to turns and phases and those contributing to the duration measure at filter standard settings (see Media file 10A). In other words, increasing the low-frequency filter reduces the electrode's recording territory by attenuating the contribution of the MFs beyond those contributing to turns and phases at filter standard settings; see Media file 6A). Therefore, the blanket (ie, low-frequency components of the signal) covering the statue is removed, and the inherent detail can be appreciated.

In the case of MUAP, most of the microarchitecture of the MU can be observed immediately near the recording surface of the electrode to appreciate its "spikiness" (not the same as fiber-density measure in SFEMG) and stability (analogous to jitter on SFEMG). Despite change in filter settings and other changes in instrumentation, a CN or MON electrode cannot substitute completely for the highly selective SFEMG electrode. The spikes or APs observed may represent single MFs or more than 1 MF. By increasing the sweep speed (0.5-1.5 ms per division), stability of the MU may be appreciated readily in a subjective manner by superimposing successive sweeps of the signal. Therefore, in addition to making quantitative assessments of the MUAPs, the electrodiagnostic consultant now is interacting with the EMG (see Media files 10-11).

Various strategies are available for measuring recruitment and IP. See Nandedkar and Barkhaus for details.^{13, 19}

In summary, QA requires a discipline in acquisition and recording that may be time-consuming. Because it is not needed in the majority of studies, it may be considered superfluous by many electrodiagnostic consultants. However, QA is the foundation upon which current understanding of EMG is based. Therefore, understanding at least the basics is essential so that, in turn, disease processes are better understood.

From assessing the routine EMG signal in a subjective manner to retraining the eyes to the graticules on the screen to make objective measures of the signals is a small step. Therefore, a qualitative description such as "large amplitude" becomes quantitative (eg, > 2 mV in amplitude). This is termed objective EMG. By interacting with the instrument, more data are extracted in a time-efficient manner. Taken together, this approach is termed objective-interactive EMG. We feel that this yields a more thoughtful interpretation of the EMG signal. Changes in the MUAP waveforms allow inferences to be made with respect to the integrity of the MFs and their MNs. The authors consider this to be an "electrophysiologic biopsy" of the MU (see Electrophysiologic Biopsy), analogous to the traditional morphologic muscle biopsy.

When the MN discharges, all of the MFs respond by generating an AP. Collectively, these single MF APs summate to form the MUAP (see Media file 12). The AP from a single MF recorded extracellularly is triphasic in shape when recorded away from the endplate zone. The shape of the MUAP varies considerably depending on from where it is recorded within the MUT, as demonstrated by scanning EMG studies (see Media file 8). Although the typical MUAP is also thought to be triphasic, it easily may be polyphasic or exhibit increased turns if phase interaction occurs between its component single MF APs (see Media file 12C-D).

The radial distance to the nearest MF determines the amplitude, which is high if the radial distance is less than 500 µm but lower when recorded from a distance of 2000-2500 µm (see Media file 12; compare the positions of MFs 3 versus 1 and 6 in Image 12B and their corresponding APs in Media file 12C). When the MUAP is recorded 2 cm or more from the endplate region, the electrodes are roughly equidistant from the endplates. Thus, the initial and terminal slow components are the same for all the MFs (see Media file 12).

An exception is a MUAP recorded from the endplate zone (see Media file 1A, position x). Because the recording is made at the endplate, no initial wave of positivity or depolarization occurs, as when the single MF APs are recorded away from the endplate. The MUAP recorded here is typically biphasic with an initial negative-going phase (see Media file 1C). Endplate noise on the baseline may be noted.

The positive-to-negative-going spike of the AP is not synchronous, signifying variable arrival times of the single MFs at the electrode (see Media file 12). This variation in time is termed temporal dispersion and is the result of many inherent physiologic characteristics of the MU. Temporal dispersion is inherently lower in muscles with shorter MF lengths. Some inherent variation also exists in neuromuscular transmission at the endplates. Therefore, the normal biologic system always has some variability, and the formal quantification of this is termed jitter in SFEMG. This is approximated in routine EMG by assessing the stability of the MUAPs or the instability when increased (see Media files 10-11A).

Therefore, the true MUAP from an MU in a larger limb muscle is a theoretical ideal. Why? As stated already, the needle electrodes used to record the MUAPs have limitations and distort the ideal MUAP waveform signal. The CN electrode MUAP recorded in the biceps brachii has a recording area of approximately 2500 µm (this defines the MUAP duration feature as discussed below). Therefore, it does not record the contributions of all the MFs within the MUT (estimated to be 5- to 10-mm diameter). Furthermore, the size of the individual MF AP it records is heavily dependent on the distance of the MF from the electrode. While anatomic cross-section of healthy muscle reveals an appearance of homogeneity and equality in size and shape, great physiologic disparity is found in the electrical activities of the APs of single MFs as they formulate the MUAP.

Most of this discussion covers the CN because less is known about the physical characteristics of the MON electrode. The formidable-sounding macro-EMG needle electrode is the least selective needle electrode (see Media file 2). Although it has the largest recording area, it records waveforms that are actually much lower in amplitude than the routine CN MUAP. This brings us back to the prefatory quote of this article. The measuring device (ie, needle electrode) is of the user's construction, and the MUAP as recorded is not nature itself but that signal that the operator exposes, and to some degree distorts, by the method of questioning, namely the EMG procedure.

Rise time is not a feature of the MUAP but rather a criterion for MUAP quality when accepting MUAPs for measurement. Rise time is defined as the time interval between the maximum initial positive peak to the maximum negative peak. This is uncomplicated when one deals with simple triphasic waves (see Media file 13, time interval between the first 2 arrows denoting turns). The traditional rise time value should be less than 0.5 milliseconds.

However, when dealing with pathologic conditions, the traditional value cannot be used since very few MUAPs in chronic reinnervation processes can be accepted. Highly complex waveforms (see Media file 11D) may have 2 or more turns or phases between the maximum initial positive peak and maximum negative peak, making the measurement points problematic. Some automated algorithms do not select MUAPs on rise time but rather on slope. Even otherwise high-quality simple triphasic MUAPs may have rise times slightly greater than 0.5 millisecond. Therefore, the authors have proposed relaxing this criterion.²⁰

Data from simulation studies indicate that the CN MUAP peak-to-peak amplitude is determined by the MFs within 0.5 mm of the recording tip as shown in Media file 6 (particularly on the distance to and diameter of the closest MF). Thus, the most obvious feature of the MUAP is recorded from few MFs (typically 2-3) and from a disproportionately small area of the MUT. Not surprisingly, minor movement of the electrode's recording tip may significantly alter MUAP amplitude.²²

The main spike component of the MUAP depends on the temporal dispersion of the MF APs within 1 mm of the recording electrode tip. This is estimated to comprise 5-10 MFs. The number of phases and turns and main spike duration define and characterize the main spike. As temporal dispersion increases so do the values of these features.

Area is determined by the MFs of an MU within 2.0 mm of the electrode tip and duration by those MFs within 2.5 mm of the electrode tip (see Media file 6). Since the MUT may measure upward of 10 mm, only a portion of the total MFs of the MU are being reflected in what is termed the CN MUAP. This assumption also does not take into consideration that the recording surface of the needle electrode actually may be central or eccentric in its location within the MUT. A quip exists: "The map is not the territory." To make a bit of a pun for emphasis, one might say, "The MUAP is not the (MU) territory." The MON electrode has a recording area similar to that of the CN (see Media file 6). MUAP duration values are similar for both electrodes.

In healthy muscle, each MN discharge results in generation of an AP in all of the MFs of its MU. If, on repeated discharges, sporadic delay or failure in AP generation occurs in 1 or more muscle MFs, the waveform varies in shape from 1 discharge to the next. This delay is analogous to the increased jitter and blocking quantified in SFEMG (see Media file 11). This may be subtle or unappreciated on standard filter and sweep speed settings (see Media file 11D).

By using the blanket principle (ie, increasing the low-frequency filter to 500 Hz and increasing the sweep speed to 0.5-2 ms per division), instability may be observed easily, as well as any increase in spikiness of the main spike component. The latter suggests subtle changes in the microarchitecture of the MU in the form of abnormal increase or dispersion of the MFs closest to the recording tip of the CN or MON electrode (see Remodeling of the MU in Neuromuscular Disorders, Electrophysiologic Biopsy).

The MU may remodel in neuromuscular disorders in 2 basic ways. The first relates to changes in the MFs. The second is the way in which they are distributed, or rather redistributed, within the MUT. Other morphologic change may occur but does not have direct electrophysiologic implications on the MUAP per se (eg, accumulation of storage products, presence of inflammatory cells).

Table 4 shows that similar electrophysiologic findings may be encountered in both myopathic and neurogenic disease processes. An example is MUAP amplitude, which may be increased in both myopathic and neurogenic processes. However, the key to proper interpretation is to look at all of the MUAP features collectively to make the correct assessment. Although MUAP amplitude may be increased in myopathic processes, it is rarely accompanied by any commensurate increase in area and certainly not in duration of simple (ie, noncomplex) MUAPs (see Media file 9).

Table 4 gives the electrophysiologic correlates relating to these pathologic changes in morphologic restructuring. Note that no single MUAP feature is pathognomonic for a particular disease process. This implies some overlap in both morphologic (eg, MF hypertrophy) and physiologic (eg, instability) features in both myopathic and neurogenic processes. Therefore, the constellation of findings, considering all electrophysiologic features, offers optimal interpretation as to the actual pathologic process.

Electrophysiologic biopsy is a concept introduced to emphasize that concordance should exist between the electrophysiologic findings and findings on traditional muscle biopsy in various disease processes (not that conventional biopsy actually is performed in muscles affected by a focal structural process such as a radiculopathy). The authors do this to take their formalized method of analysis (ie, objective-interactive EMG) to the next step of analysis. This is done to comprehensively look at the electrophysiologic data to make inferences as to how the MU is remodeled in a particular disease process. This serves as a reminder of the responsibility to carefully analyze the data to accurately represent the underlying disease process.

EMG differs from other electrophysiologic studies, such as EEG. The latter is a physiologic analysis of central neuronal signal generators. The MUAP waveform is unique in that it carries morphologic implications by way of how the MU is remodeled in disease.

Sampling is critical, since the normal mosaic distribution of the MFs in the MU is altered in many neuromuscular disorders. Also, as shown in Media file 8, needle electrode position within the MUT influences the MUAP waveform. The electrophysiologic biopsy approach samples not only multiple biopsy sites within a muscle but performs biopsy on other muscles as needed. This makes it an excellent tool to sample adequate sites when pathology is minimal in severity or patchy in distribution and to scout optimal sites for conventional muscle biopsy.

Beyond the MUAP waveform, patterns of MUAP activation (recruitment) should be evaluated, as well as other data such as IA, SA, and nerve conductions. Recruitment of MUs is not covered in detail in this section. It requires special evaluation, and interpretation may be difficult. The reader is referred to the article by Nandedkar and Barkhaus for further discussion of pathophysiology in MU recruitment.² The major categories of basic disease processes (ie, myopathy, neuropathy, disorders of neuromuscular transmission) are described in this section.

Myopathic disorders

The quintessential process in myopathies is the dysfunction, alteration, or loss of MFs, resulting in abnormal muscle function (see Media files 14-15). In most situations, such abnormality is reflected in changes in the myogenic signal. In muscle that is affected significantly by the disease process, MUAP amplitude is reduced, particularly if the electrode tip is in an area of MF atrophy (see Media file 8B, Media file 16B).

In the converse, MUAP amplitude may be normal if the recording tip is near even 1 functioning MF and may be increased if the MF is hypertrophied (if we assume normal membrane function), as shown in Media file 16C. MUAP area is reduced and, in simple MUAPs, duration also may be reduced. In some myopathic processes, the myogenic signal may not be altered if the process involves primarily the subsarcolemmal structures (eg, contractile mechanism).

Loss of MFs per se does not result in polyphasic or serrated MUAPs. MF diameter variability produces increases in phases or turns by desynchronizing the main spike signal (see Media file 8B, Media file 16E). These in turn may increase the MUAP duration. MF hypertrophy may result in MF splitting. MUAPs of increased complexity and duration are not correlated with chronicity of the process. Besides MF variability, other possible causes for complexity in myopathic processes include innervation of regenerating satellite cells and possibly reinnervation of MFs that had lost their endplate area to segmental necrosis. Instability in MUAPs may occur in myopathic processes but is uncommon (see Media file 7B, Media file 17A).

If MF loss occurs, the APs from more distant MFs that contribute to the initial and terminal components of the MUAP are lost, and duration becomes shortened (see Media file 16). MUAP duration has the inherently lower limit of the duration of a single MF AP, ie, a fibrillation potential. In simulation studies, a temporal dispersion of 1-2 milliseconds can easily produce an MUAP with a duration of 4-5 milliseconds in an MU containing 5-15 MFs. The latter is observed in some healthy small muscles. A healthy larger muscle such as the biceps brachii, which has more than 200 MFs in its MUs, has a duration of 10-12 milliseconds. In simulation studies, 100-200 MFs generated the normal MUAP duration. Hence, the relationship between the number of MFs in a MU and MUAP duration is nonlinear. Smaller muscles having shorter durations (eg, distal hand muscles, laryngeal muscles) are particularly unsuitable in assessing myopathy.

Recruitment in myopathic processes may be particularly difficult to assess. The central drivers (ie, lower MNs) are unaffected. In some myopathies, the first-order neurons controlling the early activated MUs are not observed because of severe MF loss (see Media file 4C, Media file 17A, and Media file 2 in Inclusion Body Myositis). Thus the second-order and third-order neurons controlling the higher threshold MUs appear to be earlier in onset of activation. The result is the apparent recruitment of the first 2 MUs, showing a spurious pattern of reduced number of MUs firing rapidly for effort. This may be observed in moderately to severely affected muscles. The electrodiagnostic consultant must be cautious in describing neurogenic recruitment or IPs in the setting of MUAP waveforms that suggest a myopathic process.
For further discussion, see the article by Nandedkar and Barkhaus, 2002².

In summary, increased MUAP complexity (ie, increased phases, turns, or linked components) may be observed as a sensitive but nonspecific finding of abnormality in early or mild myopathy. Abnormalities specific for myopathy include shortened MUAP duration or reduced area, particularly area-to-amplitude ratio (ie, thinning of the main spikes of the MUAP). Although MUAP amplitude may be decreased in myopathy, it may be normal or even increased.^{23, 24, 15}

In a serial quantitative EMG study of sporadic inclusion body myositis, the more selective concentric needle electrode was useful in detecting remodeling of the MUs but was not useful in correlating with clinical strength of the muscle studied (biceps brachii).²³ The macro-EMG MUAPs recorded by the less selective macro-EMG electrode correlated better with change in clinical strength between patients and over time. The latter observation makes sense in that the macro-EMG MUAP reflects the contribution of more MFs to its MUAP signal than that of the more selective (ie, smaller recording surface) concentric electrode MUAP.

Neurogenic disorders

In this process, MUs are lost by virtue of loss of MNs or their axons. In processes such as polyneuropathies of axonal type, partial losses of MUs may occur transiently as an axon degenerates; in such processes, however, the axons generally degenerate or die back in segments, making total loss of the MU more likely. The severity in dropout of MUs in a muscle may range from partial to complete loss. In general, the MU uses 2 basic compensatory mechanisms to regain function. One is MF hypertrophy, and the second is reinnervation of orphaned MFs that have lost their controlling MNs. This is accomplished by other surviving MUs, the MFs of which are interspersed within their original MUT (see Media file 18).

For general categorization, neurogenic processes can be divided into 2 basic types that share common characteristics but different patterns on EMG: acute-onset monophasic denervation followed by reinnervation that may range from partial to complete MU loss (eg, radiculopathy) and ongoing processes with variable rates of progression exhibiting concurrent denervation and reinnervation (eg, amyotrophic lateral sclerosis). Because of shared characteristics in the denervation and/or reinnervation process, the electrodiagnostic consultant must rely heavily on the history, examination, and other electrophysiologic data such as nerve conductions to help decide which pattern is most likely.

Acute onset monophasic partial loss of MUs may occur with partial trauma to a nerve trunk or root. The motor axons involved fail to propagate from their central MNs past the site of the lesion. Assuming actual acute axonal loss (vs temporary block from compression, which is a transient lesion), MU structure initially is unchanged. Between onset and 7-10 days after onset, degeneration of the distal axon occurs. Before this time, the compound muscle action potential (CMAP) evoked distal to the lesion is normal despite clinical weakness. Increase in IA supervenes after several days, and SA such as fibrillation potentials occur at 21 days, somewhat sooner in axons of shorter length (eg, facial nerve).

The voluntary activity in the EMG in this initial period demonstrates a decrease in recruitment, roughly reflecting the severity of the lesion. In turn, the IP is reduced. The MUAP amplitude is defined by MFs within 0.5 mm of the electrode tip. If the MU activated has no MF within this area, it does not contribute to the measurement of the IP. For the electrodiagnostic consultant, if it is out of range of the electrode (though it may be activated at a distance), it does not exist for recording purposes. The area near the electrode tip normally is represented by MFs from approximately 20 MUs. Assuming a normal firing rate of 20 Hz at full effort (IP), this results in 400 spikes per second (assuming a spike duration of 5 ms at a lower sensitivity setting on the amplifier). This is adequate to fill the display screen to show a full IP (ie, >500 ms of a 1-s baseline epoch).

Thus, assume a 50% loss of MUs. By using the same values, more than half the baseline will still remain full. Therefore, a reduced pattern of baseline may not be seen until more than half of the MUs are lost. MUAP waveforms are normal during this period in uncomplicated cases as they represent the unaffected MUs prior to the reinnervation phase.

Several weeks after the acute insult, the MUAPs begin to exhibit changes in the waveform reflecting the reinnervation process. This is achieved by collateral sprouting from terminal axons of the surviving MUs. These terminal axons are responding to the trophic effects of the denervated or orphaned MFs from the lost MUs. This requires development of new collateral branches to the MFs and the establishment of new synapses (see Media files 14-15). The once relatively narrow, well-defined endplate zone of the surviving MU adopting these MFs now becomes more diffuse. The once denervated, orphaned MFs also begin to increase in diameter as reinnervation is established.

Viewed from the perspective of the MUAP, the waveform may begin to show increased complexity (ie, increased phases, turns, or linked components), an early but nonspecific finding. This reflects the variability in MF diameter as in Media file 18B (skinny orphans newly joining a family of otherwise healthy MFs of normal diameter so that a spectrum exists in the conduction velocities along the MFs), dispersion of the endplate zone, and the new terminal collateral sprouts having variable lengths and conduction times.

Another early finding is instability of the MUAP, reflecting the reinnervation process as the terminal sprouts from new synapses on the orphaned MFs (see Media file 11B-C, Media file 19C; in the latter, the successively discharging MUAP changes in shape even with standard filter settings). Instability persists until the synapses mature (ie, weeks to months).

As the reinnervating MU acquires more MFs, MUAP amplitude increases but with an associated increase in area. This is particularly apparent in the main spike, indicating increase in focal rearrangement of the MFs in the MUT within 0.5 mm of the recording electrode tip. This is reflected as MF type grouping on muscle biopsy. MUAP duration also increases. These changes in the MUAP waveform are specific to neurogenic processes. As reinnervation proceeds successfully, IA and SA decrease. IP remains decreased because MUs are not replaced per se; rather, the remaining MUs are enlarged (see Media file 4B, Media file 17B). Hence, increase in spike amplitude may occur in IP. A recent study suggests that experimental partial peripheral motor nerve lesions may induce some changes in axon conduction properties of the surviving MNs.²⁵

Several months later to upward of a year after onset, reinnervation becomes complete in that it reaches its maximum. This depends on a number of variables but predominantly on the degree of original MU loss. This is reflected secondarily in the size of the surviving MUs that have provided reinnervation to the orphaned MFs (see Media file 18C; note the calibration). Successful reinnervation is reflected by enlarged but stable MUAPs with minimal to no fibrillation potentials.

Acute complete loss of MUs (eg, initial complete transection of a nerve trunk or nerve root) demonstrates the same changes in the temporal sequence of loss of the distal portions of the axons as they degenerate (as discussed in Acute onset monophasic partial loss of MUs). The difference lies in the complete loss of clinical function despite a normal evoked CMAP in the early postonset period as already discussed. The timing of increases in IA and SA is also the same except that it is more prominent, reflecting the complete loss of MUs. Since all MUs are lost, no voluntary activation occurs, and only baseline is recorded on voluntary activation with the needle electrode.

A major difference in the reinnervation process here is the source of the reinnervating axons. In this situation, the key to any recovery is successful regrowth of the axons from the proximal side of the lesion through the area of lesion, then distally along the path of the original axon. Many factors affect this, including the distance of the lesion to the muscle (regrowth of axons is approximately 1 mm/d) and how much the lesion has disrupted the path for the axons to regrow to the orphaned MFs in the muscle.

Assuming successful regrowth, the axon sends sprouts to innervate the MFs in a manner analogous to that already described. In this setting, no "normally" sized MUs are present at the beginning, thus the reinnervation process forms MUs de novo (see Media file 19). These MUs have abnormal architecture from the beginning of their formation. As the number of successfully innervated MFs for such an MU increases, the MUAP in turn becomes more enlarged. The reinnervating MUAP ultimately may become more enlarged for that particular muscle.

Thus, these MUs initially are characterized as normal-to-reduced amplitude, complex, short-duration MUAP waveforms. Because these MUAPs are formed de novo from a completely denervated muscle, they sometimes are termed nascent MUAPs (see Media file 19C). Viewed in isolation when the details of the disease process are unknown, they may resemble superficially a MUAP from a myopathic process. The exception is that they are highly unstable in the setting of prominent IA and SA. Note in Media file 19C how the configuration of the spikes varies on successive occurrences of the reinnervating MUAP. While the latter may be observed in myopathy (eg, inflammatory myopathy), MUAP instability is not prominent in myopathy.

Depending on the number of successful axons regrowing into the muscle, the MUs enlarge to variable degrees compared to those observed in partial lesions, as already described. In this setting, the topography of the MFs in the newly formed MUT is quite different with respect to size of the original MUT. Usually, the reinnervated MFs cluster by a single terminal axon to a greater degree (see Media file 19B).

The changes in the MUAP waveform in the early period reflect the variability in size and dispersion of the endplates (ie, MUAP complexity), relatively fewer MFs in the initially formed MU (ie, reduced MUAP area and duration), and instability (ie, immature terminal sprouts and synapses). As additional MFs are reinnervated, MUAP amplitude, area, and duration increase to reflect the addition of their APs to the MUAP. When reinnervation reaches its maximum, which is not necessarily equivalent to a complete functional recovery, the MUAPs become stable and SA becomes minimal.

Ongoing processes of denervation have ongoing concomitant reinnervation. These are typically diffuse processes such as polyneuropathies and motor neuron disorders but also may be focal, such as progressive radiculopathy secondary to spondylosis. The process is characterized by ongoing MU loss with compensatory reinnervation. In this pattern, dating the onset is difficult because typically no precipitating event has occurred.

In such chronic processes, denervation may be insidious such that compensatory reinnervation occurs in step with MU loss. Therefore, patients do not appreciate any early change in strength. This compensatory reinnervation process is so successful that as many as half of the MUs in a muscle may be lost before the reinnervation mechanism begins to fail and clinical weakness becomes manifest.

Meriggioli and Rowin reported a case of Kennedy disease that manifested as fatigue but normal clinical strength.²⁶ The expected chronic reinnervation changes were found on routine EMG, with the added presence of increased jitter on single fiber EMG. The authors believed that the latter finding of impaired neuromuscular transmission explained the patient's fatigue. In macro-EMG studies in such processes, macro-EMG MUAPs may reach sizes approximately 20 times normal, implying an extraordinary ability to reinnervate and add MFs to a MU (see Media file 18C). Sandberg and Stalberg reported a serial macro EMG study in old polio, showing a differential change in macro MUAP size between the biceps brachii and the anterior tibial muscles.²⁷

This compensatory mechanism eventually fails, and the reinnervated enlarged MU also begins to fail. This process is called fractionation of the MU (see Media file 18D-E). This has been demonstrated on macro-EMG studies in which the recording is made from an area exceeding that of the MUT (ie, greater recording area than that using an intermediate selective CN or MON electrode). Fractionation therefore is not appreciated on CN or MON electrode studies. It is the process whereby enlarged MUAPs, as a result of reinnervation, become relatively less enlarged due to loss of MFs within the reinnervated MU.

Does this loss represent sporadic loss of MFs within the MUT or, more likely, selective loss of terminal branches (much like losing a limb on a tree to disease rather than a patchy loss of leaves)? Because the (muscle) fiber-density measurements (by SFEMG study) remain unchanged (analogous to the highly localized measure of the leaves), loss of limbs seems most likely.

The electrophysiologic changes in the MUAP have similarities to the reinnervation process already described but with some important distinguishing characteristics. On initial study, the MUAPs already are enlarged to varying degrees (ie, MUAP amplitude, area, and duration with variable complexity). The patient may assert that onset of weakness was recent, but clearly the changes recorded imply chronicity (ie, months).

IA and SA are increased. The presence of fibrillation potentials indicates duration of at least 21 days, whereas enlarged MUAPs imply a chronicity of at least months. These alone do not indicate an active process. As already discussed, SA in the form of fibrillation potentials can occur in the setting of an acute lesion and take many months or longer to resolve. The concomitant presence of MUAP instability suggests a lesion is active. Therefore, electrophysiologic evidence exists for both denervation and reinnervation.

To summarize, nonspecific changes in MUAP waveforms such as increased complexity and increased amplitude may be sensitive markers for abnormality but are nonspecific overall because these changes also may occur in myopathic processes. The specific changes in MUAP waveform that characterize a chronic neurogenic process are increases in duration of MUAPs with concurrent increases in amplitude and area. Mean amplitude that is more than twice the upper limit also is considered a specific abnormality for neuropathy. Instability in such MUAPs indicates ongoing reinnervation.

Recruitment is said to be decreased, that is, the number of high-amplitude spikes firing rapidly for effort is reduced. Such patterns may be observed in myopathy as described in Myopathic disorders (see Media file 4C, Media file 17A).

To distinguish neurogenic processes, the spikes representing MUAP waveforms are of increased amplitude and area (see Media file 4B, Media file 17B). Ostensible dropout of MUs must be interpreted with caution in that the location of the recording electrode determines the number of MUs being recorded (see Media file 4). This emphasizes the importance of electrodeposition and sampling of adequate sites in assessing MU loss.

Media file 20 summarizes how the increasing presence of fibrillation potentials relates to stability of the MUAPs. Under normal circumstances, MUAPs are normal in size and no fibrillation potentials are seen. If enlarged stable MUAPs are noted but without fibrillation potentials, then this suggests either completed reinnervation or, possibly, a very slowly progressive process. In the opposite situation (prominent fibrillation potentials and marked instability of typically mildly enlarged or enlarged MUAPs), active denervation with ongoing reinnervation is present in a relatively rapidly progressive process (eg, focal, such as radiculopathy; diffuse, such as motor neuron disease).

The presence of fibrillation potentials without MUAP instability suggests recent onset of a neurogenic process or, if the MUAPs are enlarged, recent progression in a previously stable/reinnervated process. The presence of unstable enlarged MUAPs in the absence of fibrillation potentials suggests some ongoing reinnervation without concomitant denervation. If the MUAPs are relatively normal in size, then a disorder of neuromuscular transmission should be suspected. These relationships can be interpreted properly only after consideration of other variables, such as MUAP size and, of course, clinical history.

Disorders of neuromuscular transmission

Two important points must be considered in this category. The first is that these disorders generally are not picked up passively on routine testing, but must be suspected. Special techniques may be required to detect them. The second point is that neuromuscular transmission disorders are not detected readily on routine needle electrode examination because they typically do not change the architecture of the MU, as already discussed. Their pathology lies in the functional dynamics of the neuromuscular system (ie, MUAP stability) rather than the morphology (ie, MUAP waveform size or complexity). This further emphasizes the importance of the electrophysiologic biopsy as a comprehensive assessment of the MUAP signal.

Occasionally, the variation in the MUAP waveform at standard settings is so florid that the correct interpretation is made very quickly.

In mild to moderately severe disorders (eg, myasthenia gravis), the variability is not observed easily. Hence, the electrodiagnostic consultant must interact with the instrumentation to convert the intermediate level selectivity of the recording electrode (CN, MON) to a highly selective one (ie, increasing the low-frequency filter to 500-1000 Hz and increasing sweep speed to 0.5-2 ms per division). By trigger delaying and superimposing successive sweeps, instability or intermittent blocking is observed readily in most instances, particularly when clinical weakness exists (see Media file 10, Media file 11E-F). Blocking is usually incomplete; if it is complete, it cannot be appreciated since no APs are recorded. The latter situation may occur in severe disorders of neuromuscular transmission.

This change in electrode selectivity is analogous to performing a semiquantitative SFEMG study. The complete details and differences between the 2 is beyond the scope of this discussion. A confirmatory electrophysiologic study for a disorder of neuromuscular transmission should rely on a more detailed quantitative study (eg, SFEMG). An SFEMG electrode is more selective than a CN or MON needle electrode, either of which may permit underestimation of jitter or instability.

MUAP instability may be observed in both myopathic and neurogenic disorders. In the former, instability

EMG Evaluation of the Motor Unit: The Electrophysiologic Biopsy

AUTHOR AND EDITOR INFORMATION

INTRODUCTION AND MOTOR UNIT ANATOMY

PHYSIOLOGY OF THE MU - ACTIVATION AND CONTROL OF MU DISCHARGES

EMG SIGNAL

QUANTITATIVE ANALYSIS

ELECTROPHYSIOLOGIC MEASUREMENTS OF THE MU

REMODELING OF THE MU IN NEUROMUSCULAR DISORDERS

ELECTROPHYSIOLOGIC BIOPSY

Myopathic disorders

Neurogenic disorders

Disorders of neuromuscular transmission