Excerpt from EMG Evaluation of the Motor Unit: The Electrophysiologic Biopsy

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Since the measuring device has been constructed by the observer . . . we have to remember that what we observe is not nature itself but nature exposed to our method of questioning.

Werner Karl Heisenberg (Physics and Philosophy, 1958)

Introduction

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}

A list of the abbreviations used in this article is provided in the Summary.

Anatomy and types of MUs

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).

Table 1. Types of Alpha MNs and Their Corresponding MF Type*

ATPase = adenosine triphosphatase; NA = not applicable.

*Although related, alpha MN subtypes are not equal to MF histochemical types.

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.

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