Electrodiagnostic Evaluation of Myopathy

Anatomy and Physiology

Skeletal muscle consists of multiple muscle fascicules, and each fascicule is composed of multiple muscle fibers. A muscle fiber is a multinucleated cell containing myofibrils, structures responsible for muscle contraction, and an enfolding plasma membrane (sarcolemma). There are also 3 layers of associated connective tissues: endomysium surrounding each muscle fiber, perimysium between different muscle fascicules, and epimysium (the outermost layer) covering all fascicules. The epimysium is connected to tendon or aponeurosis that attaches muscle to the bone or occasionally to the skin or connective tissue.

The motor unit is a motor neuron (or anterior horn cell), its axon with all branches, neuromuscular junctions, and innervated muscle fibers. This is the basic anatomical structure from which signals are recorded during EMG. The number of muscle fibers within 1 motor unit varies from muscle to muscle. Usually, muscles with high precision control (hand muscles, extraocular muscles) have a high innervation ratio (fewer muscle fibers per motor unit), while low, precise control muscles (quadriceps, gastrocnemius) have a low ratio. The number of motor units, the density of fibers in a single unit, and their special distribution throughout the muscle contribute to needle electrode recordings during electrodiagnostic studies.[5]

At rest, the normal muscle membrane has only resting potential; therefore, resting muscle EMG is "electrically silent." Small normal endplate potentials can be recorded only when the needle electrode is close to the neuromuscular junction.

The action potential travels along the nerve when a motor neuron is activated. It arrives at the neuromuscular junction, where muscle fiber depolarization occurs after a series of electrochemical processes. The action potential propagates along the sarcolemma by shifts in sodium and potassium ion-driven currents, generating a depolarizing electrical field and adjacent membrane segments. Thus, activation of each motor neuron generates a motor unit action potential, consisting of the summation of individual muscle fiber action potentials within a single motor unit. An essential part of needle EMG evaluation is assessing motor unit action potential parameters.[6]

Indications

Electrodiagnostic studies must be considered in a patient presenting with a weakness to confirm the presence of muscle disease and rule out alternative diagnoses and myopathy mimickers. Additionally, this study can reduce differential diagnoses and point towards specific types or groups of myopathies.[1] The test may also help identify suitable sites for biopsy, as it can detect affected muscle that is not clinically weak and identify muscles to be avoided for biopsy due to end-stage denervation changes.[3] Electrodiagnostic testing is important in investigating patients with suspected myopathy, excepting hereditary myopathies with positive family history, where proceeding directly to genetic testing is reasonable and preferable.[1][4] 

Contraindications

In general, electrical stimuli applied during routine NCS are safe. However, in patients with external pacers, microcurrents can trigger dangerous arrhythmias, and therefore, nerve conduction studies should not be performed until external pacer wires are removed. Implantable pacemakers, defibrillators, and central lines are safe. Reasonable caution should be taken with proximal stimulation near these internal devices.[7]

There are no absolute contraindications for needle EMG. Anticoagulation poses potential risks and represents a relative contraindication. Safety measures should be taken to avoid hemorrhagic complications.[8]

Equipment

Modern electrodiagnostic equipment combines a hardware unit with a stimulator, amplifier, control panel, and computer containing special signal processing and storage software.[9] Various quantitative analysis tools have been introduced in recent years to enhance and complement the visual analysis of recorded signals. Quantitative EMG is used extensively for research purposes and in some clinical situations. Equipment components that contact the patient include surface electrodes and needle electrodes.

• Surface electrodes for NCS are usually made from silver-silver chloride, platinum, or stainless steel and require an appropriate coupling medium (gel, adhesive, paste, or saline) to ensure electrical contact.
• Only disposable needle electrodes are currently used for needle EMG to prevent transmission of infectious diseases (hepatitis, HIV, prion disease). Two main types of needle electrodes are used for routine EMG.
  • The monopolar electrode has a sharpened pointed tip that serves as an active electrode, and another surface electrode placed on the skin serves as a reference.
  • The concentric needle has a central insulated wire within the cannula; the tip is an active electrode, while the cannula shaft is a reference. This allows close positioning of active and reference electrodes, minimizing noise.

Personnel

The American Association of Electrodiagnostic Medicine set up requirements for the qualifications of an electrodiagnostic physician. An appropriately trained physician must perform all needle EMGs. A trained assistant can perform Nerve conduction studies under that physician’s supervision.[10]

Preparation

No special preparation is necessary for electrodiagnostic studies. Patients should avoid applying lotions, creams, or oils to the skin a few days before or at least on the day of the procedure.

Technique or Treatment

Electrodiagnostic studies for evaluating myopathies include NCS and needle EMG.

NCS

Routine nerve conduction studies include sensory and motor studies, analyzing distal latencies, amplitudes, and conduction velocities for tested nerves. Sensory nerve action potentials (SNAPs) are usually normal in disorders of muscles unless there is a superimposed sensory polyneuropathy or disorder affecting muscle and nerve simultaneously (critical illness neuropathy/myopathy, amyloidosis). Compound muscle action potentials (CMAPs) are normal in proximal myopathies but abnormal in distal myopathies when significant muscle atrophy is present.[2]

EMG

Electromyography can be performed using a needle electrode or surface electrode.

• Only EMG needles are used to assess myopathy, allowing analysis of individual MUAPs as the needle is positioned close to the muscle membrane.[5] Surface EMG, while non-invasive, picks up electrical signals from a distance, where intervening tissues distort potentials. It is used primarily in rehabilitation to assess gross muscle function and fatigue and to assess movement disorders. It has a promising potential for use as a natural interface in robotic limb control.
• Needle electrode recording of muscle electrical activity is performed at rest and with muscle activation. The exact muscles studied are chosen based on the clinical picture and patient-related limitations. In myopathies, clinically weak muscles must be tested. If a muscle biopsy is considered, a search for moderately affected muscles rather than normal or severely affected ones should be performed to identify suitable muscle biopsy targets. EMG can guide the identification of affected muscle that is not clinically apparent. In such cases, needle EMG should be performed only on 1 side, leaving the nondominant side for biopsy.
• The needle electrodes have a small recording area that can pick up several motor unit action potentials. It is recommended that several sites in the muscle be sampled and at least 20 MUAPs recorded for analysis. 

EMG analysis includes assessing spontaneous activity, motor unit potential configuration, and a recruitment pattern.

Spontaneous Activity

There is no spontaneous activity in normal muscle, excluding potentials that could be recorded if the needle is positioned near a neuromuscular junction (end-plate noise and spikes). The most common abnormal spontaneous potentials seen in myopathic disorders include fibrillations, positive sharp waves, complex repetitive discharges, and myotonic discharges.[11] The presence of these discharges provides additional clues to the diagnosis.

• Fibrillation potentials and positive sharp waves are potentials that individual muscle fibers generate. They are usually associated with denervation but can be present in myopathies, which are thought to be due to segmental necrosis and inflammation of the muscle fibers separating it from the end-plate zone. They have a rhythmical firing pattern, and their sound is described as a "ticking clock."
• Complex repetitive discharges are initiated in 1 muscle fiber and then spread through the ephaptic transmission to neighboring muscle fibers, generating complexes of spikes that fire in a rhythmical fashion, producing a sound resembling a "jackhammer." They can be seen in chronic neuropathic and myopathic conditions.[6]
• Individual muscle fibers also generate myotonic discharges and can be triggered by the movement of the needle or tapping of the muscle. They have a distinct sound, described as a “dive bomber” sound, and are characterized by a typical waxing and waning amplitude change and frequency of spontaneous spikes. Electrical myotonia can be seen with and without clinical myotonia.[6]

Configuration of MUAPs and Motor Unit Recruitment

• With volitional activation, MUAPs can be recorded and several parameters calculated, including amplitude, duration, number of phases, and firing rate. With minimal contraction, only a few motor units are usually activated. With increased force, more motor units are recruited orderly as a function of increasing firing rate. With maximal contraction, the numerous MUAPs fill the baseline, which is called full recruitment.
• In myopathies, the number of motor units remains the same. However, the number of normally functioning muscle fibers is reduced, causing MUAPs to become small in duration and amplitude. The asynchronous firing of affected fibers creates a polyphasic appearance. Many motor units are activated earlier than expected to generate force with minimal volitional contraction. This is an early or rapid recruitment pattern typical for myopathic processes.

Complications

Electrodiagnostic studies are safe and generally well tolerated by patients. Iatrogenic side effects are very rare. Transdermal electrical stimulation produces a theoretical risk for electrical complications in nerve conduction studies. Needle EMG carries the potential complications of any needle insertion, including infection, hemorrhage, tissue injury, and pneumothorax.

• Electrical complications. The electrical current that stimulates the nerve may pose a risk for some patients. Modern equipment has built-in electrical insulation to prevent potential electric injury during an electrodiagnostic study. Maintaining equipment regularly and using ground electrodes and grounded outlets is essential. Nerve conduction studies are safe in patients with peripheral and central intravenous lines, modern implantable pacemakers, and defibrillators with bipolar leads.[12] Studies performed in the ICU settings require more caution, as the presence of external wires and other electrical equipment makes patients sensitive to microcurrents. Electrodiagnostic studies should be avoided in patients with external temporary pacemakers.
• Pneumothorax. The most dangerous iatrogenic complication of needle EMG is pneumothorax. Even though this complication is rare, examining particular muscles - serratus anterior, diaphragm, thoracic, lower cervical paraspinal muscles, rhomboid, and suprascapular muscles - carries increased risk. The best strategy is to avoid sampling these muscles on routine studies.[13] In situations when testing of high-risk muscles is necessary, ultrasound guidance of needle placement can be used.[12]
• Hemorrhage. Bleeding complications during needle EMG are extremely rare.[8][14][15] Studies of muscles using magnetic resonance imaging and ultrasound after needle EMG showed that the risk of clinically symptomatic hematoma is very low, even in patients on anticoagulation or antiplatelet therapy.[14][15][14] It is recommended that anticoagulation and antiplatelet medications should not be held before needle EMG.[12] Special strategies to reduce the risk of hemorrhage include using the smallest gauge needle, limiting the number of needle passes, avoiding deep muscles that cannot be externally compressed, and not testing muscles located near large vessels.[5]
• Infections. Since the use of disposable needles, this potential complication has not been reported. Clean technique and reasonable caution are recommended for the procedure.  Infected areas of the skin should be avoided.[16]

Clinical Significance

Electrodiagnostic studies are an integral part of the core investigations in patients with suspected myopathy. These studies can help establish a diagnosis of myopathy and, in some cases, point towards etiology and guide the selection of muscle when a biopsy is considered.

• Nerve conduction studies are usually normal in myopathies, except for severe distal weakness and muscle atrophy in distal myopathies when CMAP can be reduced. Another unique and specific feature is prolonged CMAP duration in critical illness myopathies.[17] Recognition of this pattern can facilitate the diagnosis of this condition.
• Typical myopathic features on needle EMG include short duration, low amplitude, and polyphasic motor unit potentials with rapid recruitment. Reduced spike duration is considered the most reliable sign of myopathy.[2]
• These findings are non-specific and can be seen not only in myopathies but also in neuromuscular junction disorders. Therefore, more detailed testing, including repetitive nerve stimulation and single-fiber EMG, must be performed when a neuromuscular junction disorder is suspected.[2]
• Some features of needle EMG can point towards the etiology of myopathy. These features include spontaneous activity and the topographical distribution of involved muscles. 

Abnormal Spontaneous Activity

• It has been shown that fibrillation potentials, positive sharp waves, complex repetitive discharges, and myotonic discharges are more typical for myopathies with intramuscular structural changes, including protein accumulation, vacuoles, inflammatory infiltrates, fiber necrosis, and fiber splitting.[11][18][19]
• Polymyositis, dermatomyositis, and necrotizing myopathies are typically associated with prominent fibrillation potentials and positive sharp waves in affected muscles.[20][21][22]
• Fibrillation potentials also can be seen in some muscular dystrophies and other inherited myopathies.[3]
• Myotonic discharges can be seen not only in myotonic disorders with clinical myotonia (myotonic dystrophy type 1 and type 2, myotonia congenita, Schwartz–Jampel syndrome), and with clinical paramyotonia (paramyotonia congenita, hyperkalemic periodic paralysis), but also in disorders where electrical myotonia can be detected without clinical myotonia (acid maltase deficiency).[23]

Topographical Distribution of Affected Muscles in Different Myopathies

The most typical pattern for most myopathies is predominantly proximal muscle involvement. The comprehensive electrodiagnostic evaluation should also include neck extensor, distal, and facial muscles to assess less typical patterns.[24]

• In inclusion, body myositis, proximal muscles of the lower extremities, and distal muscles of the upper extremities usually are preferentially affected, with asymmetric weakness early in the disease course. The flexor group of the forearms (flexors digitorum and flexor carpi radialis) are commonly tested muscles to pick up myopathic changes.[21]
• Distal predominant muscle involvement is seen in myotonic dystrophy type 1, myofibrillar myopathy, distal muscular dystrophies, and toxic neuromyopathies.
• Facial and oropharyngeal involvement is seen in myotonic dystrophy type 1, oculopharyngeal muscular dystrophy, mitochondrial myopathies, and congenital myopathy.
• The scapulo-peroneal pattern of involvement is seen in facioscapulohumeral muscular dystrophy, scapulo-peroneal dystrophy, Emery-Dreifuss dystrophy, and limb-girdle muscular dystrophy (LGMD) 1B and 2A.
• Neck extensor myopathy (head drop) can be seen in isolated neck extensor myopathy, myotonic dystrophy type 2, adult rod body myopathy, and amyloidosis.

In some myopathies, electrodiagnostic testing can be normal. For example, in steroid myopathy cases, the most common drug-induced myopathy, NCS, and EMG are usually normal.[25] Steroid myopathy affects predominantly type IIb fibers, while EMG assesses predominantly type 1 muscle fibers. Steroid myopathy is commonly used to treat dermatomyositis and polymyositis. Still, the worsening of weakness can be due to exacerbation or undertreatment of inflammatory myopathy or the development of steroid myopathy. Lack of abundant spontaneous activity facilitates this distinction and can point towards steroid myopathy.

EMG also has a low yield in disorders that alter mechanical but not electrical properties of the muscle, as seen in some metabolic and congenital myopathies.[2]

Enhancing Healthcare Team Outcomes

Electrodiagnostic testing is a valuable technique for evaluating a suspected myopathy patient. The standard test usually includes nerve conduction studies and needle EMG examination. The care of patients with disorders of muscle often involves different specialties, including neurologists, rheumatologists, orthopedic surgeons, primary care providers, physical and occupational therapists, speech pathologists, cardiologists, and others.

The traditional approach to diagnosis has evolved in the era of molecular genetics and neuroimaging breakthroughs. It requires a tailored approach to each patient where an electrodiagnostic study is required. Enhancing knowledge about electrodiagnostic studies and their role in diagnosing neuromuscular disorders among different healthcare providers improves the appropriateness of referrals and yield of the tests.[26] Proper patient selection and appropriate techniques can guide further diagnostic investigations, including genetic testing, muscle biopsy, and treatment strategies.

Overall, electrodiagnostic testing is safe and well-tolerated by most patients. However, sometimes, it can cause sufficient patient discomfort, leading to aborted studies or inconclusive results. It has been shown that a lack of information or incorrect information about the test is associated with higher anticipated pain and test failure in some patients.[12][26][12] Studies also showed that needle EMG is less painful than expected, and patients who underwent electrodiagnostic studies are willing to repeat the test if necessary.[12][27] Anticoagulation is only a relative contraindication for needle EMG, usually requiring careful planning and approach, but studies have shown the procedure to be safe.

Improving communications and expanding knowledge of the electrodiagnostic evaluation's principles, indications, and limitations, as well as its role in the patient workup and further management, help make timely clinical decisions and improve treatment outcomes.