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Electrophysiology of Myopathy Approach to the Patient with Myopathy in the EMG Laboratory

Electrophysiology of Myopathy Approach to the Patient with Myopathy in the EMG Laboratory

20 of Approach to the Patient With Myopathy in the EMG Laboratory

Nithi S. Anand and David Chad

Summary The myopathic disorders represent a heterogeneous group of diseases with a variety of causes. Although electrodiagnostic testing rarely allows an entirely specific diagnosis to be made, such testing can be extremely helpful in first confirming the presence of myopathy and therefore helping to appropriately categorize it. Standard motor conduction studies generally do not demon- strate substantial abnormalities, except occasional reductions in compound motor potential ampli- tude in severe cases or where predominantly distal disease is present. Needle EMG remains the most important part of neurophysiological examination. In most myopathic conditions, sponta- neous activity is increased, although it is most prominently increased in inflammatory or necrotizing myopathic processes. The presence of myotonic discharges can be very helpful in limiting the dif- ferential diagnosis. Complex repetitive discharges, which are present in myopathic conditions, are nonspecific. potentials in myopathy are generally of low-amplitude and short duration, except in very chronic conditions, in which the motor unit potentials can actually become of long duration and high amplitude. Finally, it is critical to remember that an entirely normal EMG does not exclude the presence of myopathy.

Key Words: ; fibrillation potential; myopathy; myositis; myotonic discharge; ; .

1. INTRODUCTION The term myopathy is used to denote diseases of the striated muscle. Diseases of muscle are common in neurological practice, and EMG has an important role in their diagnosis and management. We suggest that most patient encounters in the EMG laboratory start with a brief history. This is performed to ascertain the mode of onset, progression, pattern of mus- cle involvement, and to inquire about relevant medical history, including medications (e.g., statin drugs, coumadin). The history is followed by a focused neurological examination to identify the weak muscle groups and confirm the pattern of muscle involvement. In gen- eral, the pattern of muscle involvement in myopathy is proximal more than distal, although there are exceptions to this general rule. In this context, it is useful to have in mind a clas- sification of muscle diseases (Table 1). It is worth remembering that lesions in other parts of the nervous system, such as watershed cerebral infarctions, motor diseases, neu- romuscular junction (NMJ) disorders, and motor neuropathies might mimic the clinical picture of myopathy. It is also useful to remember key clinical findings of common

From: The Primer Edited by: A. S. Blum and S. B. Rutkove © Humana Press Inc., Totowa, NJ

325 326 Anand and Chad

Table 1 Classification of Muscular dystrophies Duchenne Becker muscular dystrophy Emery–Dreifuss muscular dystrophy Limb girdle muscular dystrophy Facioscapulohumeral muscular dystrophy Oculopharyngeal muscular dystrophy Myotonic muscular dystrophy Proximal myotonic myopathy Congenital Congenital fiber type disproportion Nemaline rod myopathy Central core myopathy Metabolic Glycolytic pathway myopathy (acid maltase deficiency, McArdle’s, and Taruis) Lipid storage myopathy (carnitine palmitoyltransferase deficiency and carnitine deficiency) (chronic progressive external ophthalmoplegia, Kearn–Sayre syndrome, mitochondrial encephalopathy with lactic acidosis, and epilepsy with ragged red fibers) Ion Periodic paralyses (hypokalemic and hyperkalemic) congenita Malignant hyperthermia Inflammatory Polymyositis Dermatomyositis Connective-tissue disorders Infections Toxic Chloroquine Colchicine Statins ICU related Endocrine Corticosteroid excess Hypothyroid Hyperthyroid myopathies because these distinguishing features provide important clues to the final diag- nosis (Table 2). Although EMG plays an important role in the diagnosis of myopathic dis- orders, it should always be considered as an extension of the clinical examination. The final diagnosis of myopathy rests not only on the EMG findings but also on patient’s history, the clinical examination, laboratory tests, such as creatine kinase, and . Before delving into details of EMG testing, it is helpful to review the anatomy and physiology of normal and myopathic muscle. Electrophysiology of Myopathy 327

Table 2 Clinical Patterns in Myopathy Myopathies with ocular palsies (ptosis and ophthalmoparesis) Myotonic dystrophy (ptosis only) Facioscapulohumeral muscular dystrophy (FSHD) (ptosis only) Mitochondrial myopathies Oculopharyngeal muscular dystrophy Grave’s diseasea Myasthenia gravisa Myopathies with facial weakness Myotonic dystrophy FSHD Congenital myopathies Congenital facial diplegia (Mobius syndrome)a Myopathies with dysarthria/dysphagia/dysphonia Myotonic dystrophy Inflammatory myopathies Oculopharyngeal muscular dystrophy myopathya Myopathies with hypertrophied muscles Duchenne’s and Becker’s dystrophy Limb–girdle dystrophy Hypothyroid myopathy Cysticercosisa Malignant hyperpyrexiaa Myopathies with muscle pain and tenderness Polymyositis and dermatomyositis Myopathies with connective-tissue disease Polymyalgia rheumaticaa Acute rhabdomyolysisa Infection (influenza, trichinosis) Myopathies with notable distal weakness Myotonic dystrophy (mainly type 1 but also type 2) Inclusion body myositis Distal myopathies Scapuloperoneal syndromes Miscellaneous patterns “Popeye arms” and inverted axillary folds in FSHD Skin rash and Gottron’s papules in dermatomyositis Lymphadenopathy in malignancy, infection, and sarcoidosisa Episodic hypoglycemia/encephalopathy in carnitine deficiencya aConditions not primarily diseases of the muscle.

2. NORMAL MUSCLE ANATOMY, HISTOLOGY, PHYSIOLOGY, AND THE ORIGIN OF THE NORMAL ELECTRICAL ACTIVITY OF MUSCLE 2.1. Anatomy/Histology Muscle fibers in adults are approx 50 µm in size. They are polygonal in shape and are bun- dled into fascicles (Fig. 1). Each fascicle contains approx 20 to 60 muscle fibers, and each 328 Anand and Chad

Fig. 1. Schematic diagram of the connective tissue sheaths of muscle. Muscle fibers are bundled into fascicles bordered by perimysial connective tissue. From DeGirolami and Smith, 1982 with permission. muscle fiber consists of 50 to 100 myofibrils (Fig. 2). The myofibrils are divided into sarcom- eres, which are the smallest contractile units. The sarcomere is that portion of the myofibril that extends from Z band to Z band (Fig. 3). The sarcomere consists of two filaments, the thick (myosin) filaments alternating with the thin (actin) filaments. The four major contrac- tile proteins that are present in a myofilament are actin, myosin, troponin, and tropomyosin. The T tubules (Fig. 2) are located near the junction of the A and I bands and transmit the ini- tial depolarization at the motor end plate. They are opposed on each side by the terminal cis- terns of the sarcoplasmic reticulum. The terminal cisterns act as the storage space for calcium ions. This sarcoplasmic reticulum-T tubule-sarcoplasmic reticulum complex is called the “triad” and is responsible for converting electrical signals (membrane action potentials) to chemical signals (calcium release). In a normal muscle, the muscle fibers are organized into functional groups called motor units. The term “motor unit,” first used by Liddell and Sherrington in 1929, refers to a single lower and the muscle fibers it innervates. One motor neuron innervates multi- ple muscle fibers, but each muscle fiber is innervated by only one motor neuron. The average number of muscle fibers in a motor unit determines the innervation ratio of the muscle. This ratio varies greatly from one muscle to another and is related to the degree of dexterity required of that muscle. For instance, the innervation ratio of the external ocular muscles is approx 10 muscle fibers to 1 motor neuron, that of intrinsic hand muscles is approx 100 mus- cle fibers to 1 motor neuron, and that of gastrocnemius is approx 2000 muscle fibers to 1 motor neuron. The muscle fibers belonging to a motor unit are typically distributed widely, reaching over as many as 100 fascicles. They are randomly distributed over a circular or oval Electrophysiology of Myopathy 329

Fig. 2. Structure of a single muscle fiber cut both horizontally and longitudinally. Individual myofib- rils are surrounded and separated by sarcoplasmic reticulum. T tubules are continuous with extracellular fluid and interdigitate with sarcoplasmic reticulum. Note the regular association of T tubule with sar- coplasmic reticulum to form membranous triads. Note the location of myonuclei at the periphery of the muscle fiber and the presence of many mitochondria. From Westmoreland et al., 1994 with permission. region that can reach approx 20 to 30% of the muscle’s cross sectional area, with an average diameter of 5 to 10 mm. In general, there is a mosaic pattern of as many as 20 to 50 overlap- ping motor units in the same muscle, although a slightly higher density of muscle fibers belonging to the same motor unit is observed at the center of the motor unit.

2.2. Physiology occurs as a result of a series of steps. The process starts with an traveling along the motor nerve axon and reaching the axon terminal (Fig. 4). This (presynaptic) depolarization opens voltage-gated calcium channels, which increases calcium conductance and leads to release of acetylcholine (ACh) into the synaptic cleft. The ACh receptors (ligand-gated channels) at the postsynaptic membrane bind to this ACh, resulting in an end-plate potential, which, when reaching threshold, triggers opening of the adjacent mus- cle fiber voltage-gated sodium channels (Fig. 4). This ionic flow induces a voltage change, producing an action potential that initiates the excitation-contraction coupling. With this outline in mind, let us now consider each step in more detail. In the resting state, small fluctuations in membrane potentials occur at the end-plate region called miniature end- plate potentials. The miniature end-plate potentials are produced by the spontaneous release of quanta of ACh from the motor nerve ending that are not sufficient to produce an action 330 Anand and Chad

Fig. 3. Organization of protein filaments in a myofibril. (A) Longitudinal section through one sarcomere (Z disc to Z disc) showing the overlap of actin and myosin. (B) Cross section through the A band, where the thin actin filaments interdigitate with the thick myosin filaments in a hexagonal formation. (C) Location of specific proteins in the sarcomere. From Westmoreland et al., 1994 with permission. potential. An action potential is generated if this end-plate potential reaches sufficient ampli- tude. Postsynaptic depolarization causes the action potential to travel along the muscle fiber in both directions at a velocity of approx 4 m/s and to come in contact with the terminal cis- ternae of the sarcoplasmic reticulum, thus, gaining entry into the contractile apparatus. The T tubules transmit this action potential inward, penetrating the triad complex (sar- coplasmic reticulum-T tubule-sarcoplasmic reticulum complex). This results in a signal transduction through ryanodine receptors releasing calcium ions. The calcium ions then bind to the troponin subunits, causing a conformational change in the tropomyosin and the actin helix configuration. Sliding of the thin actin filaments over the thick myosin filaments pro- duces muscle contraction. The shortening of the sarcomeres and the I band during contrac- tion is not caused by any change in the absolute length of the filaments but rather by the sliding of the filaments themselves. Contraction ceases when calcium is removed from the sarcoplasmic reticulum by active transport.

2.3. EMG Correlates of Normal Muscle Physiology In muscle at rest, the advancing needle records discharges described as insertional activity and the stationary needle electrode records discharges described as spontaneous activity. When the muscle is voluntarily activated, the needle electrode records groups of individual motor unit action potentials (MUAPs). Electrophysiology of Myopathy 331

Fig. 4. The binding of acetylcholine (ACh) at transmitter-gated channels opens channels perme- able to both Na+ and K+. The flow of these ions into and out of the depolarizes the cell mem- brane, producing the end-plate potential. This depolarization opens neighboring voltage-gated Na+ channels. To elicit an action potential, the depolarization produced by the end-plate potential must open sufficient Na+ channels to reach the threshold for initiating the action potential. From Kandel et al., 1995 with permission.

2.3.1. Insertional Activity In normal muscle, the act of inserting the needle electrode generally evokes only a brief discharge that lasts a little longer than the actual movement of the needle. 2.3.2. Spontaneous Activity Physiological spontaneous activity is usually restricted to the end-plate regions, observed as end-plate noise and spikes. A more prolonged discharge can occur when the needle elec- trode is in the end-plate zone (Fig. 5). 2.3.3. Motor Unit Action Potential The standard concentric needle electrode used in EMG practice has an active recording surface of approx 150 × 600 µm. This recording surface captures activity of muscle fibers that 332 Anand and Chad

Fig. 5. Normal spontaneous activity in the end-plate region. Electrical activity recorded from the muscle at rest after insertional activity has subsided, and there is no voluntary muscle contraction. From Daube, 1991 with permission. are located within a 10-mm diameter. The electrical activity of a motor unit recorded by a needle electrode represents the summation of action potentials of muscle fibers that are fir- ing near the electrode. Approximately 8 to 20 muscle fibers belonging to the same motor unit contribute to the recorded MUAP. It is important to appreciate that the MUAP represents the summated activity of some muscle fibers in a motor unit but not activity of all fibers of a motor unit. Type I muscle fibers are primarily responsible for the generation of the MUAP because low-threshold small motor are preferentially activated on initial minimal voluntary contraction. Normally, there is some variation of size and form of the MUAPs in a single muscle and of the average size and form of action potential in different muscles. The morphology of the MUAPs is influenced by a number of technical and physiological factors, such as type of nee- dle electrode used, patient’s age, muscle temperature, and so on. In general, MUAP duration is shorter in proximal than in distal muscles and their size is larger in adults than in children. MUAPs recorded in normal muscles of the extremities are commonly diphasic or triphasic waves, and they produce a thumping or knocking sound over the loudspeaker. A variety of parameters define the MUAP (Fig. 6). The amplitude is primarily derived from the muscle fiber action potentials of the motor unit residing within 500 µm of the active recording surface and usually measures between 100 µV and 2 mV. It is influenced by the number and diameter of fibers involved, proximity of the needle electrode to motor units, and the synchronicity of their action potentials. The rise time is measured from the ini- tial positive peak to the subsequent negative peak, and is an indicator of the distance between the recording tip of the electrode and the depolarizing muscle fibers. The rise time should be less than 500 µs before a MUAP is accepted as a genuine near-field MUAP. A short rise time is characterized by a sharp, crisp sound. If the MUAP is associated with a dull sound, the electrode should be adjusted until MUAPs with sharp and crisp sounds are detected. The amplitude and rise time are inversely proportional to the distance between the electrode and the muscle fibers. The duration of the MUAP depends on the depolarization of many muscle fibers that are both away from and close to the tip of the needle. It best reflects the number of muscle fibers Electrophysiology of Myopathy 333

Fig. 6. A schematic motor unit potential with characteristics that can be measured. The motor unit potential (also known as the motor unit action potential) is the compound action potential of a single motor unit whose muscle fibers lie within the recording range of an electrode. From Daube, 1991 with permission. in a motor unit, and typically measures approx 5 to 15 ms. It is the time from the initial deflection away from the baseline to its final return to the baseline. It varies with the muscle tested, patient’s age, and the muscle temperature. The initial deflection reflects the arrival of the fastest muscle fiber action potential and, thus, the arrival time of various action potentials determine the final duration of that particular MUAP. Factors that influence the arrival time of various action potentials include length of individual terminal nerve branches, the distance of individual NMJs from the recording electrode, the diameter of individual muscle fibers, and the conduction velocity along individual muscle fibers (Fig. 7). Thus, unlike the ampli- tude, the duration of the MUAP is significantly affected by the distant muscle fibers. The number of phases in the MUAP depends on the synchrony of depolarization of the muscle fibers, that is, the extent to which the muscle fibers within a motor unit fire at the same time. MUAPs with more than four phases are called polyphasic. Polyphasia may be observed nor- mally, and up to 12% polyphasic MUAPs has been described in normal muscles. 2.3.4. Recruitment in Normal Muscle Motor unit recruitment refers to the successive activation of the same and additional motor units with increasing strength of voluntary muscle contraction. The Henneman size principle refers to the orderly successive activation of motor units during an increasing voluntary mus- cle activation, with the activation of small, weak (type 1) motor units first in an early contrac- tion, and the sequential addition of larger, stronger (type 2) motor units to provide a smooth increase in muscle power. Recruitment frequency refers to the firing rate of a MUAP when a different MUAP appears during gradually increasing voluntary muscle contraction. Recruitment interval refers to the time elapsed between consecutive discharges of a MUAP when a different MUAP first appears during gradually increasing muscle contraction. 334 Anand and Chad

Fig. 7. Schematic representation of motor unit action potential generation and recording by a con- centric needle electrode. Individual muscle fiber action potentials numbered one through six arrive at the recording electrode at different times, depending on factors such as terminal nerve branch length, distance between the muscle fiber’s and the recording electrode, diameter of the individual muscle fiber, and the conduction velocity of muscle fiber action potentials along indi- vidual muscle fibers. From Ball 1985 with permission.

In the EMG laboratory, motor unit recruitment is commonly assessed with the rule of fives. Let us consider a situation in which the first motor unit begins to fire at 5 Hz. A new MUAP is recruited when the first motor unit reaches a firing frequency of 10 Hz. Subsequent new motor units are added as the previous motor units reach their maximal firing frequency. For instance, if the MUAPs are firing at 25 Hz, there should be at least five different MUAPs on the EMG monitor. If the ratio exceeds six, this indicates that few motor units are present and those are firing rapidly, at more than the usual frequency of 5 Hz. Each muscle also has a characteristic maximal MUAP recruitment frequency. For instance, the facial muscles have high maximal recruitment frequencies (20–30 Hz) in contrast to the extremity muscles, which have maximal recruitment frequencies in the 10- to 12-Hz range. The other commonly used term for recruitment in the EMG laboratory is interference pat- tern. A full interference pattern implies that no individual MUAP can be clearly identified. In healthy individuals, one would expect a full interference pattern on voluntary muscle contrac- tion. A reduced interference pattern is one in which some of the individual MUAPs may be identified, whereas other individual MUAPs cannot be identified because of superimposition of waveforms. The importance of early or increased recruitment observed in myopathy will be discussed in Section 3.2.4. If documenting recruitment pattern or the interference pattern, it is important to specify the force of muscle contraction associated with that pattern.

3. MYOPATHIC MUSCLE: HISTOPATHOLOGY AND THE ORIGIN OF ABNORMAL ELECTRICAL ACTIVITY DETECTED BY EMG 3.1. Histopathology Myopathic states result in a variety of structural alterations in the muscle. Muscle fiber atrophy is typically produced by denervation, although it can be observed in the late stages of severe myopathies (Fig. 8). Muscle fiber hypertrophy (Fig. 8) is observed in chronic muscle diseases, notably in the muscular dystrophies and in other longstanding disorders (e.g., hypothyroid myopathy). Muscle fiber necrosis results in disruption and fragmentation Electrophysiology of Myopathy 335

Fig. 8. Chronic myopathic changes (Emery–Dreifuss muscular dystrophy). Cross-section demon- strating pronounced variation in muscle fiber size with enlarged (hypertrophic) and small (atrophic) fibers. Additionally, there are prominent internalized myonuclei, fiber splitting (arrows), and an excess of connective tissue. This increase in fiber size variation compared with healthy muscle contributes to the temporal dispersion of muscle fiber action potentials arriving at the recording electrode and, hence, to the polyphasic MUAP of myopathic disorders [see Fig. 7]. By creating two fibers from one, fiber splitting has the effect of increasing MUAP amplitude. H&E stain. of the sarcoplasm and loss of normal cross striations (Fig. 9). Regenerating fibers stain dark blue with hematoxylin stain because of their increased RNA content. Segmental necrosis may result in separation of a portion of a muscle fiber from the NMJ, resulting in denerva- tion of the detached portion of the muscle fiber. Interstitial mononuclear cell infiltrates (Fig. 10) are important markers for inflammatory muscle disease, such as polymyositis. Vacuolar degeneration may be observed in a number of myopathies, including glycogen and lipid storage disorders, IBM (Fig. 11), and hypokalemic . By electron microscopy, the vacuoles may contain normal or abnormal material and fluid. Various structural changes may be observed with congenital myopathies, such as nemaline rod myopathy, centronuclear myopathy (Fig. 12), and . Additionally, mito- chondrial abnormalities (Fig. 13) are observed in a variety of myopathies, including the Kearns-Sayre syndrome. 3.2. EMG Correlates of Myopathic Muscle 3.2.1. Insertional Activity in Myopathic Muscle A marked reduction of insertional activity occurs if muscle fibers are severely atrophied or replaced by fibrous tissue or fat, or if they become unexcitable, for example, during severe paralysis in familial periodic paralysis. An increase in insertional activity is the first EMG clue to the presence of abnormal spontaneous potentials in the muscle (Fig. 14). 3.2.2. Spontaneous Activity in Myopathic Muscle The general rule of thumb is that any spontaneous potential with an initial positive deflec- tion should be regarded as abnormal. It is also important to pause and allow sufficient time 336 Anand and Chad

Fig. 9. Muscle fiber necrosis. Longitudinal section showing a necrotic muscle fiber segment (arrows) with disruption/fragmentation of the sarcoplasm and loss of normal cross striations. Myonuclei (arrowheads), with prominent nucleoli of a regenerating muscle fiber (open arrowheads) are also noted. Such a pathological state may be associated with fibrillation potential activity because still healthy muscle fiber segments may have become separated from the muscle end-plate region by segmental fiber necrosis. H&E stain.

(≥1–2 s) between each needle electrode advancement to look for abnormal spontaneous potentials. The four abnormal spontaneous potentials to look for in a patient with myopathy comprise: fibrillation potentials, positive sharp waves (PSWs), myotonic potentials, and com- plex repetitive discharges (CRDs). Fibrillation potentials are the most common abnormal insertional/spontaneous activity observed in myopathies. They seem to arise spontaneously from either a single muscle fiber or a few muscle fibers and are not associated with visible contractions. They are biphasic or triphasic waves with an initial positive deflection (Fig. 15). They are usually 1 to 2 ms in duration and less than 100 µV in amplitude. They are identified by their regular frequency, with a typical sound on the loudspeaker that is likened to “raindrops on tin roof.” PSW, as the name implies, are biphasic waves with an initial PSW followed by a long negative wave. They are usually 30 ms in duration, with amplitudes of 50 µV to 1 mV. They are regular in fre- quency and are identified by their “dull thud” or “ticking of clock” sounds on the loud- speaker. Fibrillation potentials in myopathic disorders were described as early as 1949 by Electrophysiology of Myopathy 337

Fig. 10. Mononuclear cell infiltration and excessive muscle fiber size variation in . The inflammation surrounds small vessels (*) and spills out into the endomysium to sur- round some muscle fibers. H&E stain.

Fig. 11. Vacuolated muscle fiber in the setting of inclusion body myositis. The vacuoles are lined or “rimmed” with granular material. H&E stain.

Kugelberg. They are thought to result from segmental necrosis of muscle fibers, in which the necrosis leaves a distal muscle fiber segment separated from the part carrying the motor plate. Both fibrillation potentials and PSWs have the same clinical significance and can be observed with both neurogenic and myopathic disorders. However, when observed in excess in a myo- pathic illness, the muscle biopsy almost always shows some necrotizing features. Myotonic discharges are the second most common abnormal insertional/spontaneous activity observed in myopathies. They are the EMG hallmark of myotonia and are often asso- ciated with clinical myotonia. When observed diffusely on needle examination, the patient is considered to have a myotonic disorder unless proven otherwise. They are generated by single 338 Anand and Chad

Fig. 12. Centronuclear myopathy. Instead of their normal peripheral location, muscle nuclei are located in the central regions of the muscle fibers. H&E stain.

Fig. 13. Mitochondrial myopathy in the context of Kearns-Sayre syndrome. Note the accumula- tion of darkly staining material in the subsarcolemmal regions that prove by electron microscopy to be abnormal mitochondria. H&E stain. muscle fibers and can occur either spontaneously, by stimulation of the supplying the recorded muscle, by voluntary MUAP activation, or by mechanical stimulation. Cold is thought to enhance myotonic discharges in most conditions; the one exception to this rule is , in which prolonged cooling will lead to complete electrical silence of the muscle. The frequency of their discharge ranges between 15 and 150 Hz, and their amplitude ranges between 10 µV and 1 mV. Their waxing and waning amplitudes and the “dive-bomber sound” on the loudspeaker are characteristic (Fig. 16). Although the precise Electrophysiology of Myopathy 339

Fig. 14. Insertion activity. Top, normal insertion activity. Bottom, increased insertion activity. From Daube, 1991 with permission.

Fig. 15. Fibrillation potentials. Top, spike form. Center, positive waveform. Bottom, development of a positive wave form (serial photographs taken after insertion of needle electrode). From Daube, 1991 with permission. mechanism of myotonia is unclear, it is thought to be secondary to a defect in ion channels on the muscle membrane (the chloride channel in myotonia congenita, and the sodium chan- nel in paramyotonia and hyperkalemic periodic paralysis). CRDs are repetitive discharges of polyphasic or serrated action potentials characterized by their uniform frequency, shape, and amplitude, with abrupt onset, cessation, or change in con- figuration (Fig. 17). In contrast to myotonic discharges, CRDs do not wax and wane in ampli- tude or frequency. Formerly referred to as “bizarre high-frequency waves” or the confusing 340 Anand and Chad

Fig. 16. Myotonic discharge. Note that the potentials wax and wane in amplitude and frequency. From Daube, 1991 with permission.

Fig. 17. Complex repetitive discharges. These are the action potentials of groups of muscle fibers discharging in near synchrony at high rates. Note that they are characterized by abrupt onset and ces- sation. From Daube, 1991 with permission. term “pseudomyotonic discharges,” they are indicative of a hyperirritable muscle membrane with a group of muscle fibers firing in near synchrony. CRDs are observed in both neurogenic and myopathic disorders. Their presence is suggestive of a more chronic or longstanding process. They may be found in patients with muscular dystrophy, hyperkalemic periodic paralysis, glycogen storage disorders, and hypothyroid myopathy, but also in chronic dener- vating diseases. Clinically, are visible muscle twitches and they represent the spontaneous contractions of a group of muscle fibers belonging to a single motor unit. The electrical activ- ity associated with the twitch is called a potential, and it has the configuration of a MUAP. Although fasciculation potentials generally arise in the wake of an underlying neurogenic process, rarely, they are observed in myopathies, such as and inclusion body myositis (IBM). Even in such rare instances, an underlying neurogenic component may be the cause of fasciculations. Likewise, myokymic potentials are not usually observed in diseases of the muscle in the absence of a coexisting or underlying neurogenic process. In fact, the presence of fasciculations or myokymia should prompt the clinician to rethink the diagnosis of a primary muscle disease. 3.2.3. MUAP Changes in Myopathic Muscle In myopathy, there is a reduction in the average number of functional muscle fibers per motor unit. Some of the fibers within a motor unit may be nonfunctional because of muscle fiber necrosis and, hence, the electrode may be less likely to record activity from distant fibers. The initial and terminal portions of the MUP are not recorded, thereby producing short-duration MUAPs. The shortening does not depend on the type of myopathy but is greater in patients with weakness that is more advanced, and is more likely to be found in Electrophysiology of Myopathy 341

Fig. 18. Normal and abnormal motor unit action potential (MUAP) configurations. (A) Normal MUAPs. (B) Myopathic MUAPs. Short-duration, low-to-moderate amplitude, “spikey” and polypha- sic MUAPs. The reduced number of muscle fibers per motor unit leads to a MUAP that is shorter in duration and lower in amplitude than normal. Because of the increased variation in size of remaining muscle fibers, there is less synchronous firing of individual muscle fibers, leading to increased polyphasia. (C) Large-amplitude, long-duration (including satellite potentials), polyphasic MUAPs, as observed in neurogenic disorders. Time marker, 10 ms; voltage marker, 200 µV. From Bromberg and Albers, 1988 with permission. proximal than distal muscles. If the number of active fibers lying close to the electrode is also reduced, the mean amplitude of the potentials may also be diminished because of loss of con- tributions of fibers that have disappeared. In adult limb muscles, MUAPs of shorter than 6 ms are considered to be short in duration. Short-duration MUAPs are usually also low in ampli- tude (<500 µV) and recruited early (see below) (an inappropriately large number of MUAPs in the face of a weak voluntary muscle contraction). Thus, small-amplitude, short-duration (SASD) MUAPs are the EMG hallmarks of myopathy (Fig. 18). There are likened to “news- paper rubbing between two fingers” on the loudspeaker. These potentials (SASDs) are often referred to as “myopathic.” As discussed below, it is important to remember that the so-called “myopathic” potentials are not diagnostic of myopathy and can be observed with a number of other conditions. In chronic or end-stage myopathies, some MUAPs may be increased rather than decreased in amplitude and duration. These alterations in MUAP appearance, observed mostly in necro- tizing myopathies (Fig. 9), probably result from reinnervation of previously denervated mus- cle fiber segments by secondary collateral sprouts, fiber splitting, and from the increase in numbers of hypertrophic fibers (Fig. 8). An additional point to keep in mind is that in severe, 342 Anand and Chad

Fig. 19. Pattern of motor unit action potential (MUAP) recruitment at low levels of muscle force. (A) Normal recruitment with 3 MUAPs recruited. (B) Myopathy (myositis). Early recruitment with many short duration polyphasic MUAPs despite low level of force. Because each motor unit contains fewer muscle fibers, it generates less force than normal. To develop a given level of force, an increased number of MUAPs is required compared with normal. (C) Decreased recruitment with only one high-amplitude MUAP firing rapidly, as observed in neurogenic disorders. Time marker, 10 ms; voltage marker, 200 µV. From Bromberg and Albers, 1988 with permission. end-stage disease, the process of recruitment (see next section) may actually be reduced (Fig. 19) rather than early or increased because the extensive loss of muscle fibers leads to the functional equivalent of a loss of motor units. 3.2.4. Recruitment Pattern in Myopathic Muscle In myopathic disorders, individual muscle fibers drop out of the motor unit without affect- ing the integrity of the motor unit’s connection with the central nervous system. Accordingly, the number of functional motor units remains unaltered until an advanced stage of the dis- ease. Because each motor unit contains fewer functioning muscle fibers, it generates less force than normal. As a result, more motor units than normal are required to generate a cer- tain level of force; this phenomenon is called early recruitment (Fig. 19). Hence, in myo- pathic diseases, an inappropriately large number of MUAPs is firing in the face of muscle contractions that generate only weak force. In this situation, the interference pattern remains full (but compared with normal, the amplitude is reduced because the pattern is generated by SASD MUAPs). Because activation, a central nervous system process—the ability to fire motor units faster—is unaffected in myopathy, the ratio of firing frequency to number of MUAPs will typically be less than normal (<5). 3.2.5. Clinical Significance and Differential Diagnosis of “Myopathic” MUAPs Overall, just as fibrillation potentials are indicative of the disease activity, MUAP changes are indicative of disease severity. Of the various MUAP alterations, an increased proportion of polyphasic MUAP is often reported to be the earliest recognizable change with myopathies. Decreased MUAP duration and early recruitment are considered the most reliable Electrophysiology of Myopathy 343

Fig. 20. Differential diagnosis of the short duration MUAP. Schematic representation of the motor unit and specific targets of disease processes that lead to failure to generate muscle fiber action poten- tials. From Ferrante and Wilbourn, 2000 with permission. changes. Decreased MUAP amplitude is considered least reliable, because it is dependent on various needle electrode factors. In addition to myopathies, short-duration MUAPs can also be observed in NMJ disorders such as , Lambert-Eaton myasthenic syndrome (LEMS), and (Fig. 20). In these cases, the “myopathic” MUAP occur because of the failure of action poten- tial generation secondary to a defect in the NMJ. SASD MUAPs may also be observed with nascent motor units after denervation and reinnervation. However, nascent MUAPs reveal markedly reduced recruitment in contrast to the early recruitment observed in myopathies.

4. THE WORKUP FOR MYOPATHY 4.1. Advantages of Electrodiagnosis EMG provides a much wider source of sampling than other diagnostic procedures, such as muscle biopsy. EMG also helps enormously in the differential diagnosis of weakness, distin- guishing myopathic disorders from diseases of peripheral nerve/anterior horn cell or NMJ. For example, IBM and amyotrophic lateral sclerosis may share clinical features of asymmet- ric muscle atrophy and weakness, but the former would be more likely to demonstrate SASD MUAPs and early recruitment. EMG is also useful in identifying certain electrophysiological abnormalities, such as myotonic discharges, that may not have a clinical counterpart, thereby providing an important clue for the diagnostic process. In addition, EMG findings may pro- vide important information that helps in the selection of a muscle for biopsy. For example, a muscle involved by an inflammatory myopathy might be expected to reveal needle electrode findings of fibrillation potentials and SASD MUAPs. Finally, EMG findings may be the only objective evidence of motor unit dysfunction and is especially useful in the early stages of a disease or if the disease is mild. For example, early in the course of an inflammatory myopathy, 344 Anand and Chad

Table 3 Recommended Electrodiagnostic Studies for the Patient With a Suspected Myopathya Recommended nerve conduction studies for myopathy: At least one motor and one sensory conduction, with corresponding F-wave from the arm (e.g., median sensory and motor, median F-wave) At least one motor and one sensory conduction, with corresponding F-wave from the leg (e.g., sural sensory and tibial motor, tibial F-wave) (if generalized decrease in CMAP, proceed with workup for neuromuscular junction disorders) Recommended needle electrode examination for myopathy (perform examination on muscles on one side of the body, leaving the other side for muscle biopsy, if needed): At least two proximal and two distal muscles in the lower extremity (e.g., tibialis anterior, gastrocnemius, vastus lateralis, and iliopsoas) At least two proximal and two distal muscles in the upper extremity (e.g., first dorsal interosseus, flexor carpi radialis, biceps, and deltoid) At least one paraspinal muscle aAdapted from Preston and Shapiro. when weakness is minimal and limited, fibrillation potential activity might be mild but wide- spread, including paraspinal muscles.

4.2. Limitations of Electrodiagnosis The findings of EMG are not diagnostic of any one illness. No waveforms are pathogno- monic of a specific disease. The EMG findings are diverse; some disorders, such as congen- ital or endocrine myopathies, do not produce extensive EMG changes (probably because they mainly affect the contractile properties of the muscle fibers without modifying their electri- cal activity), whereas others, such as inflammatory myopathy, may produce striking findings. The EMG appearance may differ depending on the stages of the disease. A coexisting neuro- genic disorder also limits the usefulness of the EMG. Therefore, before arriving at a specific diagnosis, EMG results should be integrated with the clinical findings.

4.3. Planning the EMG Study Just before the EMG examination we explain the purpose of the EMG and the procedure itself to the patient. We tailor testing conditions to patient’s comfort, ensuring that the room temperature is warm and the patient appropriately clothed. Once the clinical impression of a myopathy is confirmed, it is reasonable to proceed with the first of the two-part EMG, the (NCS) (Table 3). It is a common practice to perform the NCS before the needle examination. 4.3.1. Nerve Conduction Studies in Myopathy

4.3.1.1. NERVE CONDUCTION STUDIES Because most myopathies tend to be characterized by proximal more than distal muscle involvement, the results of routine motor studies recording from distal small muscles are usu- ally normal, unless the myopathy is severe. Proximal and intermediate muscles (deltoid, biceps, and tibialis anterior) certainly may be evaluated, and some reductions in compound muscle action potentials (CMAPs) may be found more readily in those muscles. The reduction in CMAP amplitude is explained by the fact that the CMAP is a summation of individual muscle Electrophysiology of Myopathy 345 action potentials. More importantly, a generalized reduction in the CMAP amplitudes should alert the electromyographer to the possibility of disorders involving either the presynaptic portion of the NMJ, motor polyradiculopathies, or motor neuron diseases. It is then essential to perform repetitive nerve stimulation (RNS) testing and postactivation facilitation testing to look for LEMS. Another reason to perform RNS in the workup of a myopathy is that myasthenia gravis may simulate myopathy in some patients if it presents with proximal muscle weakness without symptomatic cranial nerve signs. Late responses, such as H-reflexes and F-waves, are usually normal in myopathies. They may be rarely reduced if the recorded muscles are severely affected. Sensory NCS results are generally normal in myopathy and when attenuated or absent suggest a coexisting neuropa- thy that may be part of a systemic disease. 4.3.1.2. REPETITIVE NERVE STIMULATIONS RNS are generally expected to be normal in disease of the muscle alone. The usefulness of RNS in myopathies is mainly to differentiate myopathies from diseases such as myasthenia gravis, especially when it presents with proximal muscle weakness alone without any ocular or bulbar symptoms, or LEMS. A few points regarding RNS in myopathies are worth noting: • A decremental response may be observed with the myotonic disorders. However, it is more prominent, with repetition rates of 5 Hz, rather than the usual 2-Hz repetition rate. • An incremental response may be observed during attacks of periodic paralysis (where a low- amplitude CMAP increases with repetitive rates of 10 Hz). • Both decremental and incremental responses have been reported with polymyositis. • Decremental responses have also been noted with myophosphorylase deficiency (McArdle’s disease). 4.3.2. Needle Electrode Examination in Myopathy The NCS is followed by the needle electrode examination (NEE). Here, a monopolar or concentric bipolar needle is inserted into selected muscles to assess the insertional activity, spontaneous activity, and the motor unit morphology on voluntary activity. Certain key points are worth remembering during the needle examination, taking inflammatory muscle disease as an example. In this regard, we find the approach of Dr. Wilbourn very useful. The most proximal muscles, such as iliacus, glutei, and paraspinal muscles, are the ones most likely to show abnormalities, rather than biceps, deltoid, and the vasti. Certain mid-limb muscles, par- ticularly brachioradialis and tibialis anterior, more often show abnormalities than muscles that are more proximal, such as the vasti. In addition, whenever possible, the needle exami- nation should be confined to one side of the body, leaving the other for a muscle biopsy, if needed. It is important to avoid any needle-induced muscle fiber trauma that could potentially influence the muscle biopsy results. 4.3.3. Single-Fiber EMG in Myopathy Single-fiber EMG is not commonly pursued in the evaluation of myopathy. However, abnormal jitter and blocking will be identified because these findings are the result of non- specific damage to the end terminal.

5. PUTTING IT ALL TOGETHER Now that we have an understanding of the muscle physiology in myopathy and its electrical correlates, it is time to make the final diagnosis. Again, as we mentioned in Section 1., EMG is 346 Anand and Chad

Table 4 Electrodiagnostic Clues to the Diagnosis of Specific Myopathies Myopathies that may present with normal EMG Metabolic myopathies Endocrine myopathies Hypokalemic periodic paralysis (in between attacks) Myopathy with fiber type disproportion Myopathies that may present with fibrillation potentials only Inflammatory myopathies Chloroquine myopathy Acute Myopathies that may present with myotonia Myotonic dystrophy Myotonia congenita (MUAPs normal) Proximal myotonic myopathy Paramyotonia congenita Colchicine myopathy Acid maltase Deficiency Hyperkalemic periodic paralysis (in between attacks) Centronuclear myopathy Myopathies with denervating features (fibrillation potentials and positive sharp waves) Inflammatory myopathies Muscular dystrophies Congenital myopathies Metabolic myopathies Toxic myopathies Infectious myopathy only one part of the puzzle. We have to blend the clinical history and physical examination findings with the EMG results to arrive at a final diagnosis. Although the examiner is generally expected to wear the “electromyographer hat” during the study, taking care not to be biased with the available clinical information, the final report should be formulated after considering all of the technical factors and the inherent subjective nature of analyzing the MUAPs on the EMG monitor. Some caveats are worth remembering when interpreting abnormal EMG findings in a patient with suspected myopathy. • Small MUAPs in the early stages of reinnervation after severe denervation may be misinter- preted as caused by myopathy. • Individual MUAPs may have a normal or even high amplitude in patients with mild myopathies or in clinically unaffected muscles from patients with myopathy; for instance, if the needle electrode is close to normal or hypertrophic muscle fibers (as a compensatory reaction in early stages). • EMG mainly reflects activity of type I fibers (diseases of the adrenal or pituitary glands as well as steroid-related myopathy show type 2 atrophy without degenerative change). • The spike duration may sometimes seem extremely prolonged because of late satellite potentials. (In Duchenne’s dystrophy, polyphasic MUAPs with prolonged spike duration are rather typical (Fig. 6). It is also important to remember that although EMG is useful in the diagnosis of myopathies, there are a number of diseases of muscle that may present as challenges to the electromyographer (Table 4). Metabolic and endocrine myopathies may not have abnormal EMG findings. Electrophysiology of Myopathy 347

Fig. 21. The cycle of needle electrode examination changes that can be observed during the various stages of a reversible necrotizing myopathy, such as polymyositis. Fibs, fibrillation potentials; MUPs, motor unit potential. From Wilbourn, 1993 with permission.

Fibrillation potentials may be the only abnormal findings in the early stages of necrotizing myopathies, such as inflammatory myopathies. Likewise, myotonic discharges may be the only abnormal EMG finding in a number of myotonic myopathies.

6. EMG IN SELECTED MYOPATHIES Before concluding, we highlight a few important features (and EMG caveats) of some important groups of muscle diseases. Inflammatory myopathies are important because some are eminently treatable. EMG plays a critical role not only in their diagnosis but also for monitoring the activity of the disease and its response to treatment. Although IBM is not responsive to immunosuppressive therapies, unlike polymyositis and dermatomyositis, it is considered here because it may simulate clinically, and EMG plays an essential roll in establishing the correct diagnosis. Certain myopathies with myotonia are often missed clinically because of the absence of clinical myotonia. Endocrine and congen- ital myopathies may have a normal EMG and it is important for the electromyographer to be aware of these possibilities. 6.1. Polymyositis/Dermatomyositis • Characterized by abundant fibrillation potentials and PSW, CRD, and MUAPs of short duration and low amplitude. • Serial EMG studies during treatment showing a reduction in fibrillation potential activity is con- sidered a marker of disease improvement (Fig. 21). 6.2. Inclusion Body Myositis • A mixed pattern of high-amplitude, long-duration MUAPs and SASD MUAPs accompanied by abnormal spontaneous activity is highly suggestive of this condition. • Approximately 15 to 30% of patients with IBM may have an associated axonal neuropathy. 348 Anand and Chad

6.3. Myotonic Myopathies • Myotonic discharges on needle examination is characteristic. • Myotonic discharges may be restricted to paraspinal muscles in patients with adult-onset acid mal- tase deficiency and to intrinsic hand muscles in asymptomatic patients with myotonic dystrophy. • MUAP changes may be more prominent in distal muscles than in proximal muscles. Hence, several distal limb muscles must be assessed in addition to proximal muscles.

6.4. Acute Illness/ICU Myopathy • Generalized low-amplitude or absent CMAPs and normal sensory nerve action potentials on NCS. • Widespread fibrillation potentials on NEE (this is found variably). • “Myopathic MUAPs” if voluntary activity possible. • RNS necessary to exclude NMJ disorders. • Post-tetanic facilitation (for LEMS) unreliable because muscles too weak.

6.5. Endocrine Myopathies • Fasciculation potentials and myokymic discharges may be the only spontaneous activity in . • Hyperkalemic periodic paralysis may be associated with increased fibrillation potentials (myotonic discharges and CRDs are found between attacks). • EMG in familial hypokalemic periodic paralysis is often normal between attacks. • Steroid myopathy is a misnomer, because, in the absence of denervation, steroids do not cause histological signs of myopathy but, rather, a selective atrophy of type 2 muscle fibers.

6.6. Congenital Myopathies • A normal EMG does not exclude a . • Scant fibrillation potentials and short-duration MUAPs are observed. • Among all congenital myopathies, centronuclear myopathy has the most prominent changes in spon- taneous activity (fibrillations, PSW, CRD, and myotonia), sometimes mimicking myotonic dystrophy.

SUGGESTED READING Aminoff MJ. in Clinical Practice, 3rd ed. Churchill Livingstone, New York, NY, 1998. Ball RD. Basics of needle electromyography. An AAEE Workshop. AAEM, 1985, Rochester, MN. Bromberg MD, Albers JW. Electromyography in idiopathic myositis. Mt Sinai J Med 1988;55(6): 459–464. Daube JR. AAEM minimonograph #11: needle examination in electromyography. Muscle Nerve 1991;14:685–700. Daube JR. Electrodiagnosis of muscle disorders. In: Myology (Engel AG, Franzini-Armstrong C, eds.). McGraw-Hill, New York, NY, 1994. DeGirolami U, Smith TW. Pathology of . Am J Pathol 1982;107:235–276. Dumitru D. Myopathies. In: Electrodiagnostic (Dumitru D, ed). Hanley and Belfus, Philadelphia, PA 1994. Ferrante MA, Wilbourn AJ. In: Comprehensive Clinical Neurophysiology (Levin K, Luders H, eds.). WB Saunders, Philadelphia, PA, 2000, pp. 268–280. Kandel ER, Schwartz JH, Jessell TM. Essentials of Neural Science and Behavior. Appleton and Lange, Stamford, CT, 1995, pp. 212. Katirji B. Electromyography in Clinical Practice. St. Louis, Mosby, 1998. Kimura J. Electrodiagnosis in Diseases of Nerve and Muscle: Principles and Practice. Oxford University Press, New York, NY, 2001. WB Saunders, Philadelphia, 19. Oh SJ. Principles of Electromyography. Williams and Wilkins, Baltimore, MD, 1998. Electrophysiology of Myopathy 349

Phillips LH, Litchy WJ, Auger RG, et al. AAEM Glossary of terms in electrodiagnostic medicine. Muscle Nerve 2001;Suppl 10. Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders. Clinical–Electrophysiological Correlations. Butterworth-Heinemann, Boston, MA, 1998. Westmoreland BE, Benarroch EE, Daube JR, Reagan TJ, Sandok BA. Medical Neurosciences. An Approach to Anatomy, Pathology and Physiology by Systems and Levels. Little Brown and Co., Boston, MA, 1994, pp. 353. Wilbourn AJ. The electrodiagnostic examination with myopathies. J Clin Neurophysiol 1993; 10:132–148.

REVIEW QUESTIONS 1. Which one of the following structures comprises the essential contractile unit of a muscle fiber? A. Sarcomere. B. Myosin. C. Actin. D. Myofibril. 2. All of the following statements regarding the motor unit are true except: A. One motor unit innervates multiple muscle fibers. B. Each muscle fiber is innervated by only one motor unit. C. Muscle fibers belonging to a motor unit are contiguous. D. The innervation ratio varies with each muscle. 3. Essential steps involved in the process of muscle contraction include all of the following except: A. Depolarization induced opening of voltage gated calcium channels. B. Signal transduction of ryanodine receptors. C. Sliding of actin and myosin filaments. D. Decrease in absolute length of thick and thin filaments. 4. Which one of the following statements regarding the MUAP is false: A. MUAP amplitude depends on number and size of the muscle fibers closest to the recording electrode. B. The presence of any polyphasic MUAPs is generally indicative of an underlying pathological process. C. Duration depends both on fibers close to and away from the recording electrode. D. Rise time should ideally be shorter than 500 µs. 5. Match the following: A. Fibrillation potentials i. Waxing and waning amplitudes B. Myotonic discharges ii. “Raindrops on roof” C. Complex repetitive discharges iii. Thyrotoxic myopathy D. Fasciculation potentials iv. Normally found in Iliacus 6. EMG findings most consistent with the diagnosis of myopathy are: A. Absent motor responses on NCS, fibrillation potentials, and SASD MUAPs. B. Fibrillation potentials, fasciculation potentials, and large-duration MUAPs. C. Fibrillation potentials, complex repetitive potentials, and SASD MUAPs. D. Normal EMG. 7. All statements regarding NEE findings in myopathy are true EXCEPT: A. Decreased MUAP amplitude is the most reliable finding. B. MUAP findings indicate disease severity. C. Increased or early recruitment is characteristic. D. Fibrillation potentials indicate disease activity. 8. A generalized reduction in CMAP amplitudes in NCS may indicate all EXCEPT: A. Presynaptic defect of the NMJ. B. Motor polyradiculopathies. C. Motor neuron disease. D. Myopathy in early stages. 350 Anand and Chad

9. Myopathies that may present with “denervating features” on EMG include all EXCEPT: A. Inflammatory myopathies. B. Muscular dystrophies. C. Corticosteroid myopathy. D. Toxic myopathies. 10. All of the following myopathies may present with myotonic discharges EXCEPT: A. Myotonia congenita. B. The myopathy of intensive care. C. Colchicine myopathy. D. Paramyotonia congenita.

REVIEW ANSWERS 1. The correct answer is A. The sarcomere is the smallest contractile unit in a myofibril. It extends from Z band to Z band. The sarcomere consists of two filaments, the thick (myosin) filaments alternating with the thin (actin) filaments. The four major contractile proteins that are present in a myofilament are actin, myosin, troponin, and tropomyosin. 2. The correct answer is C. The term “motor unit” refers to a single and the muscle fibers it innervates. One motor neuron innervates multiple muscle fibers but each mus- cle fiber is innervated by only one motor neuron. The muscle fibers belonging to a motor unit are typically distributed widely, extending over as many as 100 fascicles. Muscle fibers are ran- domly distributed over a circular or oval region that can reach approx 20 to 30% of the muscle’s cross-sectional area, with an average diameter of 5 to 10 mm. 3. The correct answer is D. Sliding of the thin actin filaments over the thick myosin filaments pro- duces muscle contraction. The shortening of the sarcomeres and the I band during contraction is not caused by any change in the absolute length of the filaments but rather by the sliding of the filaments themselves. 4. The correct answer is B. MUAPs with more than four phases are referred to as polyphasic. Up to 12% of recorded MUAPs in normal muscles are polyphasic. 5. The audio-amplified correlate of fibrillation potentials have been likened to the sound of “raindrops on a tin roof.” Complex repetitive potentials may be found in the iliacus muscle of healthy individ- uals and, hence, should not be considered abnormal if restricted to that muscle. Fasciculations may be observed in thyrotoxic myopathy. Electrical myotonia (waxing and waning of discharges) is characteristically observed in myotonic myopathies. 6. The correct answer is C. Fibrillation potentials are usually observed in necrotizing myopathies. SASD MUAPs are not specific for myopathies (they are also observed in neurogenic disorders and diseases of the NMJ). Motor responses on NCS are expected to be normal in diseases of muscle, unless it is end-stage disease. Although CRDs are nonspecific, they may occur in myopathies. The EMG may be normal in some myopathies—those that are endocrine or meta- bolic in nature. 7. The correct answer is A. Just as fibrillation potentials are indicative of disease activity,MUAP changes are indicative of disease severity. Of the various MUAP alterations, an increased pro- portion of polyphasic MUAP is often reported to be the earliest recognizable change with myopathies. Decreased MUAP duration and early or increased recruitment are considered the most reliable changes. Decreased MUAP amplitude is considered the least reliable, because it is dependent on various needle electrode factors. 8. The correct answer is D. A generalized reduction in the CMAP amplitudes should alert the elec- tromyographer to the possibility of disorders involving either the presynaptic portion of the NMJ, motor polyradiculopathies, or motor neuron diseases. Early stage myopathies generally do not present such an EMG profile. 9. The correct answer is C. “Denervating features” on EMG generally refer to a mixture of high- amplitude, long-duration MUAPs accompanied by abnormal spontaneous activity. Inflammatory Electrophysiology of Myopathy 351

myopathies, IBM, muscular dystrophies, and toxic myopathies may all produce such an EMG picture. Corticosteroids usually produce a rather selective atrophy of type 2 muscle fibers and do not cause denervation. 10. The correct answer is B. Myotonic discharges are characterized by the waxing and waning of amplitude and frequency on EMG. These discharges are found in myopathies with defects in the sarcolemma. They are not observed in the myopathy of intensive care, a disorder characterized by loss of myosin filaments with sparing of the sarcolemmal membrane.

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