Overview and Description
Electrodiagnosis (EDX) is an integral part of physical medicine and rehabilitation practice. A referral for electrodiagnostic studies is indicated when the clinician is uncertain about the etiology of neuromuscular symptoms, diagnosing and/or confirming a clinical picture, or seeking prognostic information. The electrodiagnostic study can often help to clarify these situations. It is essential for an electrodiagnostician to understand the basic physiological principles of nerve conduction studies (NCS) and needle electromyography (EMG). This article reviews and outlines these principles.
Relevance to Clinical Practice
The cell membranes of both the nerve and muscle regulate the interchange of substances between exterior and interior. It allows certain ions to pass freely but restricts the diffusion of others. This results in an unequal distribution of charged ions across the membrane. The difference in charge between outside and inside is referred to as resting potential. The integrity of the muscle and nerve cell membrane is an important factor in maintaining this resting potential.
The intracellular fluid of a nerve and muscle cell is high in potassium (K+) and low in sodium (Na+) and chloride (Cl–) ions. In the extracellular fluid, Na+ and Cl– are high, while K+ is low. A sodium-potassium ATPase uses energy to move both Na+ and K+ across their concentration gradients, resulting in extracellular fluid with a large concentration of Na+ ions and the intracellular fluid with a large concentration of K+ ions. The membrane is selectively more permeable to K+, allowing K+ to freely leak into the extracellular space (moving down the concentration gradient) leading to further accumulation of positively charged ions outside the cell membrane. This net movement of positive charges outside of the cell results in a polarized cell membrane.
In a steady state, equilibrium of electrical charges is maintained, so that influx exactly matches the efflux. During the state of electro-chemical equilibrium, net movement of ions across the membrane is zero. The calculated resting potential is derived by using the Nernst equation. With K+, for example,
where R is the gas constant, T the temperature in Kelvin (K), z is the ion charge, F is Faraday’s constant (~96,500 coulombs/mol), [K+]e is the extracellular concentration of the ion and [K+]i is the intracellular concentration of the ion. The equation results in -97 mV potential for K+.
To determine the membrane resting potential for any cell, the collective Nernst equations of K+, Na+ and Cl– must be combined using the Goldman–Hodgkin–Katz equation (also called the Goldman Equation)
where Vm is the membrane potential, R is the gas constant, T the temperature in K, F is Faraday’s constant, Pion is the membrane permeability of K+, Na+ and Cl– ions and [ion]e and [ion]i are the respective extracellular and intracellular concentrations of the ion. K+ is mainly responsible for the resting potential since Na+ concentration is much lower inside the cell and because anions have poor membrane permeability. The combination of resting potentials for all three ions (K+, Na+, Cl–) leads to a resting potential of approximately -75 mV in nerve and -80 mV in muscle.
A resting potential is continuously maintained across the membrane of normal nerve and muscle fibers. The resting potential is the result of the separation of electrical charges, which results in a net negative charge inside the cell membrane and a net positive charge outside the membrane.
A rapid change in cell membrane electric potential followed by a return to the membrane’s resting potential is called an action potential (AP). Cells where APs can be triggered are called excitable. If the nerve or muscle cell is given enough electrical current or otherwise stimulated to change the trans-membrane potential close to neutral, an AP is generated that depolarizes a neuron or myocyte and propagates along the cellular membrane. However, this current must be of a certain strength and of a certain duration to achieve depolarization. Every time the current exceeds 10-30 mV above the resting potential, also known as the threshold potential, it creates an AP.
In order for depolarization to occur, the voltage of the membrane must increase enough to change the membrane permeability to Na+ ions in the extracellular space. Voltage-gated Na+ channels are molecular pores, which have gates that open and close in response to membrane potentials. When threshold potential has been reached, voltage sensors in the Na+ channels respond and open the channel, allowing Na+ to enter the axon. As further depolarization continues and more Na+ channels open, a second channel, voltage-gated K+ channels, opens, increasing the membrane permeability to K+ and causing K+ efflux from the cell. When the voltage gradient has reversed and there is greater positive charge within the cell, a second Na+ gate, called the inactivation gate, closes the Na+ channels. Once the inactivation gate closes, the membrane becomes unexcitable. The time period in which the membrane is unexcitable is referred to as the refractory period.
The AP is an all-or-none response and propagates within 1-2 ms and is moving away from the stimulation site. The conduction velocity (CV) of this propagated signal depends on several factors including the diameter, insulation, and temperature of the axon. Larger axons conduct the action potential more rapidly than smaller diameter fibers.
Some nerve fibers are encased in an insulating material called myelin. Myelin is laid down in concentric spirals and supported by Schwann cells in the peripheral nervous system. Segments of nerve covered by myelin are known as internodes. Between the internodes, the axons are exposed. These unmyelinated portions are known as the nodes of Ranvier and are about 1-2 mm in length. Depolarization occurs only at the nodes of Ranvier and the action potential is propagated by way of saltatory conduction, where ‘saltatory’ is Latin for ‘leaping’ or ‘bounding’. After depolarizing one node the AP jumps to the next and continues. The CV of the action potential slower in unmyelinated fibers, since the entire nerve fiber needs to be depolarized in order to propagate the signal. CV for unmyelinated axons ranges from 0.2-1.5 m/s. In contrast, myelinated human nerve fibers conduct at 35-75 m/s which is approximately 50 times faster. During remyelination of damaged nerves, the number of nodes of Ranvier increase, thus decreasing the conduction velocity of the action potential.1
A motor unit consists of an anterior horn cell, its axon and all the muscle fibers that axon innervates. Activation of this motor unit via a stimulus will produce a motor unit action potential (MUAP). Motor nerve cell bodies of the peripheral nervous system begin in the anterior horn of the spinal cord and extend into the periphery, with the axon gradually dividing into many branches before ending at the neuromuscular junction (NMJ). The NMJ is essentially an electrochemical link between the nerve and muscle where the nerve terminal ends, and the muscle begins. As the nerve AP reaches the presynaptic side of the NMJ, voltage-gated channels are activated, allowing influx of calcium ions (Ca2+). Ca2+ influx causes presynaptic vesicles called quanta to fuse with the cell membrane, releasing acetylcholine (ACh) into the synaptic cleft. Some quanta also fuse with the membrane spontaneously, resulting in miniature end-plate potentials (MEPPs). The MEPPs are too small to trigger a normal AP.
The post-synaptic membrane contains several folds lined with ACh receptors. As ACh diffuses across the synaptic cleft, it binds to post-synaptic ACh receptors, triggering influx of Na+ and the start of muscle depolarization. When a muscle fiber membrane depolarizes at the end plate, the signal is transmitted along the membrane through the transverse tubular system, which then travels deeper into the muscle fibers. Muscle fibers contain bundles of myofibrils, which in turn are composed of many filaments. Two of these filaments, actin and myosin, overlap and form a sarcomere, or the basic contractile unit of the muscle. Each sarcomere is separated by Z lines. Actin is a thin filament that inter-digitates with myosin, a thicker filament. In the resting state, the binding sites on actin are covered by tropomyosin.
During depolarization of the muscle fiber, Ca2+ is released from the sarcoplasmic reticulum into the muscle cell. Ca2+ then binds to troponin, causing tropomyosin to change configuration and expose the binding sites for myosin. The myosin heads then use ATP to cause a muscle shortening contraction and generation of force. When a muscle contracts, the sarcomere becomes shorter because thin filaments move together. In relaxed state, the thin filaments move apart. Skeletal muscle contains many thousands of muscle fibers that act in synchrony to produce force that results in muscle contraction.
How are these potentials recorded?
Electrodiagnosis utilizes tools to record intracellular changes in the extracellular space. Surface electrodes record potentials transmitted to the skin during NCSs, whereas needle electrodes record EMG potentials as the intracellular potentials are transmitted through tissue to the electrodes. When potentials are recorded close to their source generation, they are called near-field potentials. These potentials produce a triphasic response, or wave form, as the advancing AP approaches, passes under, and then away from the recording electrode. The electrical correlate is an initial positive, then a negative, and then a trailing positive phase. If a volume conducted near-field potential is directly under the recording electrode, then an initial negative phase is seen.2 The potential is biphasic and seen at the end plate. Examples of near-field potentials are compound motor action potential (CMAP), nerve action potential (NAP), sensory nerve action potential (SNAP) and motor unit action potentials (MUAPs).
Far-field potentials are routinely used in somatosensory evoked potential (SSEP) recordings. Two recording electrodes are used – one closer and the other farther from the source, both which see the source at the same time.2 Far-field potentials have the potential to superimpose on near-field activity during NCSs.3 SSEPs can be used in surgical cases to detect electrophysiological changes in nerve conduction that may predict nerve injury.4,5
Cutting Edge/ Unique Concepts/ Emerging Issues
Over the past two decades significant improvements occurred in computer software, allowing better signal averaging. Automatic calculations of different parameters of NCSs by the computer are now possible. Some machines provide software that assists the diagnostician in generating reports and have the capacity to interface with electronic medical records.
Electrodiagnosticians increasingly, are utilizing ultrasound while performing NCSs and needle EMG. A recent study shows that CMAPs for specific nerves improved when utilizing ultrasound guidance for electrode placement instead of landmark guidance.6 Ultrasound (US) can detect and isolate pathologies that may not be recognized without direct visualization of the muscle or nerve.7 Recent studies demonstrates a correlation between pathologic appearance of peripheral nerves on ultrasonography and EMG-NCSs.8,9 A recent pilot study shows that US may also be useful in motor unit scanning EMG.10 In addition, use of peripheral nerve stimulation in conjunction with US-guided EMG allows for improved sensitivity and earlier detection of motor unit potentials after traumatic nerve lesions.11 Use of US allows another dimension of understanding into neuromuscular pathology by visualizing the neuromuscular architecture under US.
Magnetic resonance imaging (MRI) is another imaging modality that correlates well with electrodiagnostic findings, as noted by a growing body of evidence. Notably, these diagnostic tools can provide complementary information in certain pathologies.12,13
A number of neuromuscular complications have resulted from the global pandemic from COVID-19. Cases of small-fiber neuropathy,14,15 dysautonomia,14 and Parsonage Turner syndrome16 have been reported in patients following COVID-19 vaccination. Viral infection can lead to small fiber neuropathy which may be implicated in some of the clinical manifestations of long COVID.17,18 It is important to note that small fiber neuropathy cannot be appreciated on standard EMG/NCS but should remain on the differential in patients have characteristic paresthesias and/or dysautonomia. More study is needed to determine the pathophysiologic mechanism behind the vaccine/virus and its impact on the neuromuscular system.
Gaps in Knowledge/ Evidence Base
- It is not completely understood how nerve conduction abnormalities are related to genetic conditions.
- The effects of medication on remyelination are still poorly understood.
- Due to limitations in sensitivity of signal processing as well as the size of the thinnest nerves, electromyography remains unable to detect pathologies in small fiber polyneuropathies, like diabetes-induced polyneuropathy.
- More research is needed to understand the effects of COVID-19 and vaccinations on the peripheral nervous system.
- Sherman DL, Brophy PJ. Mechanisms of axon ensheathment and myelin growth. Nat Rev Neurosci. Sep 2005;6(9):683-90. doi:10.1038/nrn1743
- Kimura J. Volume conduction, waveform analysis, and near- and far-field potentials. Handb Clin Neurol. 2019;160:23-37. doi:10.1016/B978-0-444-64032-1.00002-3
- Kimura J. Principles and pitfalls of nerve conduction studies. Annals of neurology. 1984;4:415-429. doi:10.1002/ana.410160402
- Lueders H, Gurd A, Hahn J, Andrish J, Weiker G, Klem G. A new technique for intraoperative monitoring of spinal cord function: multichannel recording of spinal cord and subcortical evoked potentials. Spine (Phila Pa 1976). 1982;7(2):110-5. doi:10.1097/00007632-198203000-00004
- Epstein NE, Danto J, Nardi D. Evaluation of intraoperative somatosensory-evoked potential monitoring during 100 cervical operations. Spine (Phila Pa 1976). May 1993;18(6):737-47. doi:10.1097/00007632-199305000-00011
- Wei KC, Chiu YH, Wu CH, Liang HW, Wang TG. Ultrasound guidance may have advantages over landmark-based guidance for some nerve conduction studies. Muscle Nerve. Apr 2021;63(4):472-476. doi:10.1002/mus.27165
- Gentile L, Coraci D, Pazzaglia C, et al. Ultrasound guidance increases diagnostic yield of needle EMG in plegic muscle. Clin Neurophysiol. Feb 2020;131(2):446-450. doi:10.1016/j.clinph.2019.10.012
- Domkundwar S, Autkar G, Khadilkar SV, Virarkar M. Ultrasound and EMG-NCV study (electromyography and nerve conduction velocity) correlation in diagnosis of nerve pathologies. J Ultrasound. Jun 2017;20(2):111-122. doi:10.1007/s40477-016-0232-3
- Toia F, Gagliardo A, D’Arpa S, Gagliardo C, Gagliardo G, Cordova A. Preoperative evaluation of peripheral nerve injuries: What is the place for ultrasound? J Neurosurg. Sep 2016;125(3):603-14. doi:10.3171/2015.6.JNS151001
- Maitland S, Hall J, McNeill A, Stenberg B, Schofield I, Whittaker R. Ultrasound-guided motor unit scanning electromyography. Muscle Nerve. Dec 2022;66(6):730-735. doi:10.1002/mus.27720
- Padua L, Fusco A, Erra C, et al. Ultrasound-guided-electromyography in plegic muscle: Usefulness of nerve stimulation. Muscle Nerve. Mar 2023;67(3):204-207. doi:10.1002/mus.27727
- Deroide N, Bousson V, Mambre L, Vicaut E, Laredo JD, Kubis N. Muscle MRI STIR signal intensity and atrophy are correlated to focal lower limb neuropathy severity. Eur Radiol. Mar 2015;25(3):644-51. doi:10.1007/s00330-014-3436-y
- Kamath S, Venkatanarasimha N, Walsh MA, Hughes PM. MRI appearance of muscle denervation. Skeletal Radiol. May 2008;37(5):397-404. doi:10.1007/s00256-007-0409-0
- Schelke MW, Barcavage S, Lampshire E, Brannagan TH. Post-COVID-19 vaccine small-fiber neuropathy and tinnitus treated with plasma exchange. Muscle Nerve. Oct 2022;66(4):E21-E23. doi:10.1002/mus.27696
- Waheed W, Carey ME, Tandan SR, Tandan R. Post COVID-19 vaccine small fiber neuropathy. Muscle Nerve. Jul 2021;64(1):E1-E2. doi:10.1002/mus.27251
- Mahajan S, Zhang F, Mahajan A, Zimnowodzki S. Parsonage Turner syndrome after COVID-19 vaccination. Muscle Nerve. Jul 2021;64(1):E3-E4. doi:10.1002/mus.27255
- Gemignani F. Small Fiber Neuropathy and SARS-CoV-2 Infection. Another piece in the long COVID puzzle? Muscle Nerve. Apr 2022;65(4):369-370. doi:10.1002/mus.27495
- Abrams RMC, Simpson DM, Navis A, Jette N, Zhou L, Shin SC. Small fiber neuropathy associated with SARS-CoV-2 infection. Muscle Nerve. Apr 2022;65(4):440-443. doi:10.1002/mus.27458
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Original Version of the Topic
Subhadra L. Nori, MD. Physiological principles underlying electrodiagnosis and neurophysiologic testing. 9/20/2014.
Previous Revision(s) of the Topic
Jason Kiene, MD, Benjamin Westerhaus, MD, David Sherwood, DO. Physiological principles underlying electrodiagnosis and neurophysiologic testing. 4/19/2020
Jason Kiene, MD
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Andrew Hiett, MD
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