SMA

The EDX features of the proximal SMAs I to IV, as classified by Dubowitz, are determined by the rate of anterior horn cell degeneration and the stage in the course of the disease. SMA I, or Werdnig-Hoffmann disease, presents in utero or in infancy, is rapidly progressive and generally leads to death before 2 years of age if ventilatory support and manual or mechanical airway clearance (ie, cough assist) is not provided. SMA II has an age of onset between 6 and 18 months. Children usually achieve independent sitting but not independent ambulation and often survive into adulthood. Cranial nerve innervated muscles are less likely to be involved in SMA II. SMA III, or Kugelberg-Welander disease, has an insidious onset between 3 and 30 years of age and is slowly progressive, with ambulation possible for 10 to 30 years after disease onset.

Sensory NCS are normal in all forms of SMA. CMAPs are decreased in proportion to the degree of muscle atrophy. Motor velocities are most likely to be abnormally slow in SMA I because of the extensive loss of large myelinated axons and slower baseline conduction velocities in children younger than 5 years. Motor conduction velocity slowing is usually no more than 25% less than the lower limit of normal.

The most profound loss of MUAPs is seen in SMA I. With maximal effort, only a few MUAPs may fire at a rapid rate. Small MUAPs are common because reinnervation cannot compensate for the rapid loss of anterior horn cells. Myopathic-appearing, low-amplitude, polyphasic, short-duration MUAPs also may be seen because of muscle fiber degeneration. In the other types of SMA, large-amplitude MUAPs (up to 10–15 mV) may be observed because the number of muscle fibers per motor unit increases as reinnervation occurs. These large units may be polyphasic with increased duration. Satellite potentials appear as remodeling occurs.

On NEE in SMA I, fibrillation potentials and PSWs are diffuse and seen in many muscles, including the paraspinals. Fasciculation potentials are uncommon and are found in less than 35% of children with SMA1. Spontaneously firing MUAPs at 5 to 15 Hz, even during sleep, are a unique EDX feature of both SMA I and II. In more chronic forms of SMA, fibrillation potentials and PSWs are even more common and increase in frequency as age increases. CRDs are often seen in SMA II and III, and fasciculations are more common than in SMA I.

Kennedy disease

Kennedy disease, also known as X-linked bulbospinal muscular atrophy, is a slowly progressive X-linked recessive motor neuron disease characterized by proximal limb and bulbar weakness, tongue atrophy, and prominent muscle cramping and fasciculations. In addition, it is associated with diabetes, gynecomastia, and testicular atrophy because of an androgen receptor defect. Although patients generally do not have sensory complaints, absence or reduction of SNAPs is a common finding. Motor NCS are normal or may show a reduction in amplitude. NEE shows large-amplitude and long-duration MUAPs consistent with an indolent neurogenic disease course. Fibrillation potentials and PSWs may be prominent and present in all muscles examined. Fasciculation potentials are also abundant in limb, facial, and tongue muscles.

Adult nonhereditary motor neuron disease

The most common form of adult nonhereditary motor neuron disease is ALS. Less common forms of adult nonhereditary motor neuron disease include progressive muscular atrophy (PMA) with lower motor neuron findings only, progressive lateral sclerosis (PLS) with upper motor neuron findings only, and progressive bulbar palsy (PBP) with only lower motor neuron bulbar muscle involvement. Over time, individuals initially diagnosed with PMA, PLS, or PBP often develop ALS. Approximately 10% of patients with ALS have familial ALS that can be inherited either as an autosomal dominant or recessive trait. Clinical and electrodiagnostic features of these patients are no different from those with sporadic ALS.

For years, Lambert’s criteria were the standard for the electromyographic diagnosis of ALS. The following 4 criteria must be met to make a definite diagnosis of ALS : (1) positive sharp waves or fibrillation potentials in 3 of 5 limbs, counting the head as a limb (For a limb to be considered affected, at least 2 muscles innervated by different peripheral nerves and roots should show active denervation. ); (2) normal sensory nerve conduction studies ; (3) normal motor conduction studies (However, if the CMAP amplitude is very low, the conduction velocity may decrease as low as 70% of the lower limit of normal. ); and (4) reduced recruitment of MUAPs on needle examination. The EDX findings in PMA are identical to those in ALS; the distinction between the two diagnoses is made by the presence or absence of upper motor neuron signs on physical examination. By definition, the EDX examination is normal in PLS. In PBP, active denervation is found only in the muscles of the head and neck.

In 1990, a special task force of the World Federation of Neurology developed the El Escorial Criteria for diagnosing ALS in response to the stringency of the Lambert criteria. The EDX portion of the criteria differs somewhat from Lambert’s criteria. The criteria stated that electrodiagnostic findings must be present in at least 2 of 4 regions (bulbar, cervical, thoracic, and lumbar) for a diagnosis of ALS. Electrophysiologic features required to define clinically definite disease include the following: (1) reduced recruitment, (2) large MUAPs, and (3) fibrillations potentials. The revised El Escorial Criteria was developed in 2000 and categorizes patients into 4 levels of certainty : clinically definite ALS, clinically probable ALS, clinically probable laboratory–supported ALS, and clinically possible ALS. For electromyogram (EMG) findings to support a diagnosis of ALS, there must be signs of chronic and active denervation in at least 2 muscles in the cervical and lumbosacral regions and 1 muscle in the brainstem and thoracic regions.

In December 2006, an International Federation of Clinical Neurophysiology-sponsored consensus conference was convened on Awaji Island, Japan to consider how clinical neurophysiology could be used more effectively to facilitate early diagnosis. An evidence-based approach was used and consensus recommendations were made ( Box 3 ). They concluded that because needle EMG is essentially an extension of the clinical examination in detecting features of denervation and reinnervation, the finding of neurogenic EMG changes in a muscle should have the same diagnostic significance as clinical features of neurogenic change in an individual muscle. Specific EMG features suggestive of ALS were found to be the following: (1) chronic neurogenic change (MUAPs of increased amplitude and duration, usually with an increased number of phases, as assessed by qualitative or quantitative studies); (2) decreased motor unit recruitment, defined by rapid firing of a reduced number of motor units; (3) presence of unstable and complex MUAPs using a narrow band pass filter (500 Hz to 5 kHz); (4) fibrillations and PSWs recorded in strong, nonwasted muscles; and (5) fasciculation potentials (preferably of complex morphology) are equivalent to fibrillations and PSWs in their clinical significance (see Box 3 ).

Early in the progression of ALS, many patients with a suspected clinical diagnosis of ALS do not meet the electrodiagnostic criteria for a definite diagnosis. A repeat study several months later will often fulfill the EDX criteria for diagnosis. On the other hand, some patients who do not fulfill the clinical criteria for diagnosis because of the limited distribution of muscle weakness may have evidence of widespread denervation on EDX, allowing a diagnosis of ALS to be made based on the Awaji-shima consensus. This diagnosis is important when determining eligibility for clinical trial participation.

NCS changes in ALS are characterized by decreased CMAP amplitudes. The mild slowing of motor conduction velocity and the prolongation of F-wave latencies is attributed to the loss of the fastest conducting fibers. An interesting phenomenon observed in many patients is that of the split hand whereby CMAP amplitudes are decreased to a greater degree on the radial side of the hand than on the ulnar side. CMAPs obtained from the abductor pollicis brevis and first dorsal interosseous are much lower than those obtained from the abductor digit minimi. More than 2 stimulation sites should be used in the evaluation of motor nerves to exclude the presence of CB because MMN with CB occasionally can be misdiagnosed as ALS. The ulnar nerve can be stimulated easily at the wrist, below and above the elbow, in the axilla and in the supraclavicular fossa. In limbs with upper motor neuron signs, H reflexes may be elicited from muscles in which they normally cannot be obtained. SNAP amplitudes may be abnormal in a small percentage of patients with otherwise typical ALS. There have been case reports of concomitant sporadic ALS and a sensory neuropathy for which alternative causes could not be identified. Repetitive stimulation studies may show decrement in CMAP with stimulation at 3 Hz. This decrement is caused by the instability of neuromuscular transmission in collateral nerve terminal sprouts. Some degree of decrement occurs in more than half of patients with ALS, and the amplitude decrement is usually less than 10%.

The NEE is the most important part of the EDX in suspected ALS. Fasciculation potentials are seen in most patients with ALS but they are not necessary to meet diagnostic criteria. The significance of fasciculations depends on the company they keep and are pathologic only when accompanied by fibrillation potentials, PSWs, or the appropriate neurogenic MUAP changes. In patients with advanced disease, fibrillations potentials and PSWs are prominent in most muscles but they may be sparse early in the course of the disease when collateral sprouting can keep up with denervation. Occasionally, CRDs and doublets or triplets are seen in patients with ALS but these are not typical findings. The thoracic paraspinals should be examined on NEE because they are typically spared in cervical and lumbar spinal stenosis. The primary NEE finding in ALS in involved muscles is decreased recruitment. If the disease is progressing slowly, MUAP amplitudes and durations become increased as a result of collateral sprouting. If the disease course is rapid, denervation outpaces reinnervation and enlarged MUAPs do not develop. The density and distribution of fasciculations and fibrillations does not correlate with the disease course or prognosis. Serial EDX are not useful for monitoring disease progression once a definite diagnosis has been made.

Polio

Acute poliomyelitis is an acquired disease of the anterior horn cells that most electromyographers likely will not encounter. However, the sequelae of previous polio frequently are encountered in the EMG laboratory and make the diagnosis of any superimposed neuromuscular problem difficult. In both acute and old polio, the NCS findings are similar to those of other motor neuron diseases: normal sensory studies, normal motor conduction velocities, and low CMAP amplitudes in atrophic muscles. Patients with postpolio frequently have superimposed entrapment neuropathies, such as median or ulnar mononeuropathies, from years of using assistive ambulatory devices.

The NEE in acute polio will begin to show fibrillation potentials and PSWs in affected muscles 2 to 3 weeks after the onset of weakness. Fasciculation potentials may appear before fibrillation potentials. Initially, the recruitment pattern is decreased, but MUAP size is normal because remodeling of the motor units has not yet had time to occur. As time passes, collateral sprouting and motor unit remodeling occur, creating giant MUAPs with amplitudes up to 20 mV. Fibrillation potentials may persist indefinitely but are small (<100 uV) in chronic polio.

When patients with a history of polio are examined 20 to 30 years later, reduced recruitment, giant MUAPs, and fibrillation potentials may be seen diffusely, not just in muscles clinically involved in the acute polio episode. For this reason, superimposed neuromuscular disorders can be impossible to diagnose by EDX. A superimposed neuropathy may be diagnosed if sensory conduction studies are abnormal, but one cannot distinguish accurately between a pure sensory and a sensorimotor neuropathy. SFEMG studies in patients with chronic polio show increased jitter, blocking, and fiber density.

Fifteen percent to 80% of patients with a history of polio develop postpolio syndrome years after their acute illness. Halstead’s criteria for a diagnosis of postpolio syndrome include: (1) history of acute polio; (2) a period of at least 15 years of neurologic and functional stability before the onset of new problems; (3) gradual or abrupt onset of new neurogenic weakness; and (4) no apparent medical, orthopedic, or neurologic cause for the new weakness. EDX is not useful in differentiating between chronic polio with and without postpolio syndrome because both groups have similar findings of NEE and SFEMG studies. The only useful role of EDX in diagnosing postpolio syndrome is to confirm that patients did indeed have polio in the past.

Neuromuscular junction disorders

Disorders of the neuromuscular junction (NMJ) may be classified as presynaptic (Lambert-Eaton myasthenic syndrome [LEMS] and botulism) or postsynaptic (myasthenia gravis [MG]) depending on the location of the defect. NMJ transmission disorders may also be acquired or inherited (congenital myasthenic syndromes). Presynaptic or postsynaptic dysfunction influences the electrophysiologic response to repetitive nerve stimulation (RNS), a technique developed to assist in the EDX of NMJ disorders. In general, findings on routine NCS and NEE in the NMJ disorders are similar to the findings in myopathies. Motor and sensory NCS are normal, with the exception of reduced CMAP amplitudes in presynaptic disorders. MUAPs in affected muscles are either normal or polyphasic with low amplitudes or decreased duration. Small MUAPs are caused by decreased neuromuscular transmission and are not truly myopathic. A unique feature of NMJ disorders is that cooling the muscle may minimize abnormalities seen with RNS and may cause an increase in duration and amplitude in myopathic-appearing MUAPs. Recruitment pattern is full with a submaximal muscle contraction. Moment-to-moment amplitude variation, unstable motor unit, is seen on NEE when a single MUAP is isolated. Fibrillation potentials are seen only in severe disease with complete disintegration of the NMJ. Table 3 outlines the EDX findings in various disorders of the NMJ transmission.

RNS studies are a technique for evaluating the safety factor of the NMJ. The safety factor refers to the number of acetylcholine receptors (AChRs) that must be opened to generate an end plate potential large enough to depolarize the muscle membrane and produce muscle contraction. In healthy individuals, the safety factor can be reduced by exercise or repetitive nerve activation but not to a degree large enough to prevent the generation of an endplate potential. In presynaptic disorders, acetylcholine release is diminished, resulting in too few postsynaptic AChRs opening, thus decreasing the safety factor. In postsynaptic disorders, a normal amount of acetylcholine is released but too few AChRs are available for binding and the safety factor is again reduced.

RNS studies generally are performed at 2 stimulation rates: slow (2–3 Hz) and fast (20–30 Hz). With slow stimulation, each successive stimulus results in fewer vesicles of acetylcholine being released. In individuals with NMJ disorders, the safety factor is reduced. In patients with a baseline low safety factor, the safety factor is reduced to the extent that NMJ block occurs in some single muscle fibers so that fewer fibers contribute to the overall CMAP, thus reducing the CMAP amplitude. To perform slow RNS, a train of 5 supramaximal stimuli is delivered. A decrement in CMAP amplitude of greater than 10% is abnormal. When a decrement occurs, it should be greatest between the first and second recorded stimuli. The patient is then asked to exercise or maximally contract the target muscle for 10 to 20 seconds in the setting of a decrement and 30 to 60 seconds in the setting of no decrement. The normal response is up to a 15% increase in CMAP amplitude immediately following exercise. The train of 5 supramaximal stimuli is repeated immediately after exercise, at 30 seconds and at 1, 2, 3, and 4 minutes after exercise. Patients with defects in NMJ transmission may demonstrate complete or partial repair of the decrement immediately after exercise (postexercise facilitation); after 3 to 4 minutes, the decrement worsens (postactivation exhaustion). If the patient is too weak to exercise or is unable to follow directions concerning exercise, fast repetitive stimulation (20–30 Hz) of 1 or 2 seconds may be substituted for the exercise to produce the same result.

SFEMG is the gold standard for the electrodiagnosis of disorders involving the NMJ when repetitive stimulation studies are negative or nonrevealing. Jitter is increased in both presynaptic and postsynaptic NMJ disorders but is nonspecific because it is also increased in motor neuron diseases, myopathies, and neuropathies in which immature NMJs are present. An SFEMG is most commonly performed in the extensor digitorum communis muscle because it is easy to isolate single MUAPs in this muscle. Twenty pairs of MUAPs are recorded, and the study is considered abnormal if the mean jitter of all pairs is increased, if 2 or more individual pairs have jitter greater than a given parameter (based on age), or if frequent blocking occurs. Blocking of neuromuscular transmission begins to occur when jitter reaches 80 microseconds.

MG

MG is the most commonly encountered NMJ disorder and is a model for the electrophysiologic findings of all postsynaptic NMJ disorders. Other postsynaptic disorders include a subset of postsynaptic congenital myasthenic syndromes, organophosphate poisoning, and poisoning with curarelike compounds. Routine sensory and motor NCS are normal, with the exception of low CMAPs from the most severely weak muscles. When weakness is fairly severe in the muscle from which a CMAP is being recorded, a strong initial stimulus should be delivered to the nerve to avoid the necessity of multiple stimuli, which may result in NMJ fatigue and an even lower CMAP than would be recorded otherwise. A motor NCS should be conducted for every planned repetitive stimulation study. The abductor pollicis brevis and abductor digit minimi are the easiest to study with repetitive stimulation because they can be immobilized more easily than proximal muscles. However, in mild disease, proximal muscles are more likely to show an abnormal response to repetitive stimulation. The slow repetitive stimulation protocol outlined previously is used in an attempt to elicit the classic triad of findings characteristic of MG: (1) CMAP decrement with slow repetitive stimulation, (2) repair of decrement immediately after exercise, and (3) worsening of the decrement 2 to 4 minutes after exercise. If the RNS study of a distal muscle is negative, a proximal muscle should be evaluated; the nasalis and trapezius are commonly used proximal muscles. In patients with ocular myasthenia, it may be necessary to perform repetitive stimulation of the orbicularis oculi muscle. The most significant finding on NEE is MUAP moment-to-moment amplitude variation. This variation must be studied by isolating a single MUAP and observing its morphology over time. Amplitude variation is the needle electrode equivalent of the decrement seen on RNS studies. A small number of patients with severe, chronic disease have fibrillation potentials and PSWs in the weakest muscles because the muscles are functionally denervated at the NMJ. The dropout of single muscle fibers can decrease the amplitude and duration of MUAPs, giving them a myopathic appearance, which occurs more frequently than the presence of fibrillation potentials and PSWs.

Single fiber EMG is necessary only when repetitive nerve stimulation studies fail to show a decrement, NEE does not show moment-to-moment amplitude variation in affected muscles and AChR antibody testing is negative. Generally, the extensor digitorum communis is examined first. If this study is normal, then a single fiber EMG is performed in the frontalis muscle. Single fiber EMG may be performed without stopping anticholinesterase medications because jitter is usually abnormal even while taking medication. Anticholinesterase medication must be discontinued 12 hours before repetitive nerve stimulation studies in order for accurate and valid assessment of obtained results.

LEMS

LEMS is the most commonly encountered presynaptic disorder of neuromuscular transmission. Botulism, tetanus, and some forms of congenital myasthenia are also presynaptic disorders. Sensory NCS are normal in pure LEMS. Because more than 50% of patients with LEMS have a malignancy, most commonly small cell carcinoma, a concomitant paraneoplastic sensory or sensorimotor neuropathy is common. Motor NCS are characterized by a low CMAP, often only a few 100 μV. After 10 to 20 seconds of exercise (isometric muscle contraction), the CMAP amplitude will increase by more than 100% because of the accumulation of calcium in the presynaptic terminal, which increases ACh release. If exercise is performed for longer than 20 seconds, this facilitation may be replaced by postexercise exhaustion in which no increase in amplitude is seen. Low RNS will produce a decrement similar to that seen in MG except that repair of the decrement following exercise is much pronounced and accompanied by a large increase in amplitude as previously described. This response lasts 20 to 30 seconds and is then once again replaced by a low CMAP, which decreases with repetitive nerve stimulation. In all patients with low CMAPs, a brief period of exercise should be given and another CMAP elicited to look for a presynaptic neuromuscular transmission defect. In severely weak patients who are unable to exercise, rapid repetitive stimulation may be applied for 1 to 2 seconds to generate an increment in CMAP amplitude. In LEMS, an increment in CMAP with exercise usually can be detected in any muscle examined. Once the increment has been demonstrated, there is no need to repeat the study in additional muscles. In mild early cases, an increment may be isolated to proximal muscles.

The hallmark of NEE in patients with LEMS is moment-to-moment amplitude variation in all muscles examined, independent of clinical weakness. Because only a few muscle fibers per motor unit may fire, the MUAPs may be short in duration, low amplitude, and polyphasic, with a myopathic appearance. With sustained voluntary contraction, MUAPs may increase in amplitude and duration, losing their myopathic appearance. This feature can help distinguish them from the firing pattern seen in myopathies. Fibrillation potentials and PSWs are not present. SFEMG shows markedly increased jitter and blocking in all muscles, unlike MG whereby jitter is increased in only the most severely affected muscles. In LEMS, both jitter and blocking decrease as firing rate increases.

Botulism

The EXD findings in botulism are similar to those seen in LEMS with a few key differences. The CMAP amplitude is not as severely reduced, and the incremental response to exercise is somewhat less dramatic but should be at least 40%. The increase in CMAP amplitude persists much longer than in LEMS, often for as long as 4 minutes. In infants, it may last up to 20 minutes. In severe cases of botulism, rapid RNS may not result in facilitation because of the complete block of ACh release by the toxin. In these cases, the endplates break down because of the lack of ACh and functional denervation occurs resulting in the presence of fibrillation potentials and PSWs. Unlike LEMS, only clinically weak muscles show EMG changes. Bulbar muscles should be examined in mild cases because they are usually affected first and most severely.

Progressive muscular dystrophies

With the availability of molecular genetic testing for the identification of increasing numbers of progressive muscular dystrophies, the role of EDX examination is decreasing. In all of the progressive muscular dystrophies, the needle feel on insertion and the ease of needle advancement changes as the muscle is replaced by fat and connective tissue. The muscle develops a gritty feel and physical resistance to needle movement develops over time. The EDX findings in the muscular dystrophies are similar to those found in other myopathies, with a few unique characteristics. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), fibrillation potentials and PSWs are widespread, although they are somewhat less prominent in BMD. Occasionally, CRDs and myotonic discharges are present but they are not prominent. In addition to myopathic-appearing MUAPs, large-amplitude and increased-duration MUAPs may be seen. These MUAPs are a result of muscle fiber hypertrophy or increased fiber density motor units caused by remodeling following muscle degeneration. In facioscapulohumeral muscular dystrophy (FSHD), fibrillation potentials and PSWs may or may not be present. When they are present, they are less abundant than in DMD. Unlike DMD, large-amplitude, long-duration motor units are not seen. The earliest muscles involved are facial muscles, but NEE is often not helpful because typical facial muscle MUAPs may seem myopathic when compared with limb muscles. Other affected muscles that may be tested are the scapular stabilizers, biceps, and triceps. The tibialis anterior is the first muscle affected in the lower limbs. Similar findings can be seen in individuals with limb girdle muscular dystrophies (LGMDs) in clinically weak muscles. The main difference between FSHD and LGMD is that MUAPs amplitudes tend to be larger in the latter. The NEE findings in Emery-Dreifuss muscular dystrophy are similar those found in other progressive muscular dystrophies, with a mixed pattern of small and large MUAPs. A unique characteristic of Emery-Dreifuss is more severe involvement of biceps and triceps than more proximal upper extremity muscles.

Myotonic muscular dystrophy has unique EDX features, including the presence of myotonic discharges and response to high-rate RNS. At low-rate RNS, no CMAP decrement is present. However, at high-rate RNS, a progressive decrement is seen. Myotonic potentials are induced by both needle movement and voluntary muscle contraction. They are most notable in the distal muscles and may not be present in all of the muscles examined. Fibrillation potentials are present and may be caused by spontaneous discharges of innervated single muscle fibers or by denervation. An accompanying peripheral neuropathy has been detected in some individuals with myotonic dystrophy.

Congenital myopathies

The most common congenital myopathies are central core disease, multicore disease, nemaline myopathy, centronuclear myopathy (also called myotubular myopathy), and congenital fiber-type disproportion. In general, the congenital myopathies have nonspecific myopathic changes on EDX. However, a normal examination can be seen with congenital fiber-type disproportion. Abnormal spontaneous activity is uncommon except in centronuclear myopathy, which often has fibrillation potentials, PSWs, CRDs, and occasionally myotonic discharges (Hawkes). A concomitant defect in NMJ transmission has been described in a few patients with centronuclear myopathy.

Mitochondrial myopathies

Mitochondrial myopathies also have nonspecific EDX findings. In mild cases, the EDX can be normal. Despite the common complaint of activity-induced fatigue, RNS studies are normal. Some individuals with mitochondrial disease have EDX findings showing a concomitant peripheral neuropathy.

Metabolic myopathies

The metabolic myopathies include disorders of glycogen metabolism, lipid metabolism, and myoadenylate deaminase deficiency (MADD). There are 5 known glycogen metabolism disorders that have EDX abnormalities: glycogen storage disease (GSD) type II (acid maltase deficiency, Pompe disease), GSD type III (debranching enzyme deficiency), GSD type IV (branching enzyme deficiency), GSD type V (myophosphorylase deficiency, McArdle disease), and type VII (phosphofructokinase deficiency, Tarui disease). Acid maltase deficiency is unique in that it produces profuse spontaneous activity, including fibrillations, PSWs, CRDs, and myotonic discharges. Spontaneous activity is most prominent in the paraspinal muscles. Findings of myotonic discharges in the paraspinal muscles of an adult with proximal limb and respiratory weakness suggest Pompe disease/acid maltase deficiency. Debranching enzyme deficiency (GSD type III) can be distinguished by a concomitant peripheral neuropathy in some patients. They may also have fibrillation potentials and CRDs, although to a lesser degree than GSD type II. Myotonic discharges are not a common finding with debranching enzyme deficiency. Patients diagnosed with McArdle disease experience frequent muscle cramping and contracture. On NEE, muscle contracture is electrically silent despite obvious prolonged muscle contractions. At the onset of a contracture, the interference pattern amplitude declines as does the number of MUAPs firing. Gradually over minutes, electrical silence occurs. In many patients, the NEE is normal when they are not experiencing muscle cramping. When the disease is severe enough to cause permanent weakness, myopathic-appearing MUAPs can be seen. Patients with late-onset disease are likely to have fibrillation potentials, PSWs, and CRDs. An abnormal response to low-rate and high-rate RNS has been reported in some patients with McArdle disease, suggesting a concomitant defect in neuromuscular transmission. Data on the EDX findings in Tarui disease are minimal but may be similar to those found in McArdle disease in some patients.

The EDX findings in lipid metabolism disorders that result in weakness, carnitine deficiency, and carnitine palmitoyltransferase deficiency (CPT) are nonspecific and not well described. In most cases of carnitine deficiency, myopathic-appearing MUAPs are seen. In severe disease, extremely weak muscles show fibrillation potentials, PSWs, and CRDs. A superimposed sensorimotor peripheral neuropathy has also been reported in patients with CPT. The EDX is normal in MADD.

Inflammatory myopathies

Although clinical features and muscle biopsy findings of polymyositis and dermatomyositis can distinguish the two disorders, their electrodiagnostic findings are identical. NEE of proximal muscles and paraspinals at multiple levels should be examined. In some cases, findings are only seen in the paraspinal muscles. Abnormal findings on NEE may be patchy in distribution necessitating multiple needle insertions within the same muscle. If no abnormalities are detected in a clinically weak muscle, then a second or even third insertion site should be evaluated. Fibrillation potentials and PSWs are common and their quantity may be reflective of the severity of disease, although no correlative studies have been done. However, serial EDX studies are not recommended to evaluate the response to treatment. The EDX can be used to help distinguish between exacerbation of the inflammatory myopathy and the progression of weakness as a result of steroid myopathy in those individuals receiving treatment with corticosteroids. CRDs are common in chronic stages of the disease, and the muscle may have a gritty feel on needle insertion because of the replacement of muscle tissue with connective tissue. MUAP morphology changes are similar to those seen in other myopathies. In chronic stages of the disease, there may be some large-amplitude MUAPs among the typical myopathic motor units that are small with polyphasia.

Inclusion body myositis (IBM) may be distinguished from polymyositis by its pattern of muscle weakness, clinic course, EDX findings, and distinctive features on muscle biopsy. EDX findings are similar to those found in polymyositis and dermatomyositis; however, fibrillation potentials and PSWs are more prominent in IBM and may be found in almost every muscle examined. CRDs, myotonic discharges, and fasciculations may also be more prominent in IBM. MUAPs vary in amplitude and duration depending on the chronicity of the illness and may seem myopathic, neuropathic, or mixed. In addition to proximal muscle involvement, distal muscles, including the forearm flexors, hand intrinsics, and tibialis anterior, are involved. The quadriceps muscles are typically involved as seen by NEE, whereas the glutei are often spared.

Channelopathies

The ion channel disorders encompass both myotonic disorders and the periodic paralyses. Myotonic dystrophy involves abnormalities in the sodium channel and calcium-activated potassium channel. Myotonia congenita is a chloride channel disorder, hypokalemic periodic paralysis is a calcium channel disorder, and hyperkalemic periodic paralysis and paramyotonia congenital are sodium channel disorders.

There are 2 variants of myotonia congenita. Thomsen disease is autosomal dominant and Becker disease is autosomal recessive. In both forms, diffuse myotonic discharges are seen in most muscles and may prevent the assessment of individual MUAPs. MUAPs seem normal with Thomsen disease but may be short in duration and amplitude with long-standing Becker disease. Amplitude decrement with rapid RNS is seen in Thomsen disease, whereas a similar decrement is seen with both rapid and slow rates of RNS with Becker disease.

Clinically, paramyotonia congenita and myotonia congenita are often confused. On EDX evaluation, there are distinct differences. In paramyotonia congenita, a decrement in CMAP occurs either after cooling the muscle or immediately after several minutes of forceful exercise and the CMAP amplitude does not return to baseline for more than 1 hour. In myotonia congentia, a smaller decrement is seen following exercise and it often recovers within a few minutes after stopping exercise. On NEE, cooling the limb with ice water or exercising the limb can cause decreased recruitment that approaches an electrically silent contracture in some individuals with paramyotonia congenita. Between episodes of muscle stiffness, MUAPs are normal but may be difficult to assess because of the persistent and diffuse myotonia, particularly in the distal limb muscles. Fibrillation potentials, PSWs, and increased myotonic discharges may be observed during episodes of weakness, before the onset of complete electrical silence. Abnormal spontaneous activity is not observed during asymptomatic periods.

Attacks of hyperkalemic periodic paralysis are triggered by rest following cold exposure, exercise, immobilization, fasting, and heavy meals. After exercise, a CMAP decrement is noted. It is preceded by a CMAP increment and gradually reaches its nadir by 20 minutes following exercise. Clinical and electrical myotonia may or may not be present. Patients may only display electrical myotonia, which is usually present in all muscles on NEE, even during asymptomatic periods. At the beginning of an attack, complete electrical silence may occur. Some affected individuals eventually develop mild weakness, and myopathic-appearing MUAPs are present on NEE between attacks.

Attacks of hypokalemic periodic paralysis are triggered by rest following carbohydrate loading, strenuous exercise, and stress. During attacks, the muscle membrane becomes unexcitable. CMAP amplitudes decline severely or disappear altogether. While the CMAP is in the process of declining, rapid (10 Hz) RNS can be used to reverse the decline in amplitude. As an attack progresses, recruitment and MUAP amplitude and duration decreases. Eventually at the nadir of the attack, electrical silence occurs. Fibrillation potentials and PSWs may be observed between the onset of the attack and electrical silence. Myotonic potentials are not seen. In most patients, the NEE is normal between attacks. A few patients with permanent weakness have myopathic-appearing MUAPs and fibrillation potentials.