OVERVIEW AND DESCRIPTION
Fundamentals
Nerve Conduction Studies (NCSs) are a method to perform an extracellular recording of the intracellular process of neuron or muscle depolarization and action potential propagation along the axon or muscle fiber1. This is performed by recording action potentials (APs) for all the axons that compromise a peripheral nerve. The recording of nerve signal transmission occurs at the surface of the skin using specialized electrodes. A ground electrode is used to help minimize electrical interference from the equipment, ambient surroundings and the patient. Contrary to popular teaching, the ground electrode does not direct stray charges away from the body and serves only to minimize interferences with the recording electrodes.22 The course of the specific peripheral nerve being studied is identified using anatomical landmarks and knowledge of neuroanatomy. A stimulator electrode consisting of a cathode and anode is used to deliver an electrical stimulus of variable intensity and duration. A stimulus with sufficient strength to cause all of the axons to depolarize and propagate an AP is termed supramaximal stimulation. It is commonly used for NCS1 and is necessary to ensure that all axons have been evaluated in the study. The depolarization and subsequent AP propagation is detected by a recording electrode, referred to as G1 or “pick up” electrode, and the reference electrode, referred to as G21.
Several pieces of information are collected from the resulting action potential. Typically, a preset distance, the length in centimeters between the cathode of the stimulating electrode and the G1 electrode, is recorded. The time (in milliseconds) that elapses between stimulus and depolarization is called the signal response latency. The nerve conduction velocity (meters/second) is calculated from the measured distance and signal response latency. The signal amplitude (measured in micro- or millivolts) represents the maximal AP depolarization and voltage gradient of all depolarized fibers of a peripheral nerve as measured at the G1 electrode, representing the number of axons present.
Motor NCS can be recorded by stimulating a mixed sensorimotor or pure motor nerve and recording on a muscle this nerve innervates. Sensory NCS can be recorded by stimulating a sensorimotor or pure sensory nerve and recording at a separate location on the same nerve. Normal values for each NCS are determined based on recordings and calculations in asymptomatic subjects. Historically, these values have been provider- or lab-specific. However, in 2016, the Normative Data Task Force (NDTF), formed via an initiative from the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM), released a study on a set of rigorous consensus-based methodological criteria, which could be used to help standardize Nerve Conduction Values across all providers.7 As a result of these stringent criteria, a literature search was preformed from 1990-2012 of published peer‐reviewed articles for 11 commonly assessed sensory and motor NCS.8 Using only those few studies that met the consensus criteria, the NDTF published what they considered to be a suitable resource for providers in an attempt to standardized NCS.
The summation of the motor neuron APs, transmission through the neuromuscular junction, and subsequent muscle fiber AP is termed the Compound Motor Action Potential (CMAP). The CMAP includes information about the number of afferent motor axons the nerve contains, the diameter and amount of myelin of those axons, the function of the neuromuscular junction (NMJ), and the number of excitable muscle fibers. The signal amplitude reflects the total number of motor neurons and muscle fibers that depolarize. The G1 electrode is placed over the muscle belly at the motor point, while the G2 electrode is placed over an electrically silent area, such as a tendon or bone, and the stimulation given over the nerve, proximal to the G1 electrode. The time from the stimulus to the initial deflection (onset latency) is recorded for CMAPs only and reflects the myelin quality of the largest, fastest axons contained in the nerve.1 In order to calculate a conduction velocity of the CMAP, two stimulation sites (one proximal and one distal) need to be recorded. Because the G1 electrode is placed on the muscle belly, the response latencies include the time it takes for transmission across the unmyelinated, terminal axon and NMJ, as well as AP propagation through the muscle. The CMAP conduction velocity can be calculated along any proximal region of nerve using this calculation:
Ddistal – dproximal
vconduction = _________________________
Ldistal – lproximal
where d is distance in cm, and l is response latency in time (seconds). 1
The terminal axon and NMJ transmission time and muscle AP will be constant between the two sites and subtracted out, allowing calculation of the conduction velocity of the segment of motor nerve between the two stimulation sites.
The summation of the sensory neuron APs of a peripheral nerve is termed the Sensory Nerve Action Potential (SNAP). In antidromic recording, the stimulus is delivered in the opposite of the physiologic direction. An antidromic response in sensory NCS is proximal to distal. Orthodromic recording measures AP propagation in the normal physiological direction. An orthodromic response in sensory NCS is distal to proximal. The more common method of recording SNAPs is antidromic due to larger signal amplitudes and ease of recording.2 The G1 electrode is placed over the skin along the course of the nerve and the G2 electrode is placed 3-4 cm distal to G1 along the same course. In antidromic stimulation, the stimulating electrode is then placed proximal to G1 along the nerve with the cathode closer than the anode to G1.
Similar to a CMAP, the signal amplitude reflects the total number of neurons that depolarize. However, SNAP amplitudes are several orders of magnitude smaller and are measured in microvolts rather than millivolts. Both the onset response latency and peak response latency are useful for SNAPs.2 The peak response latency is helpful because it is a more reliable and reproducible, particularly given the overall small amplitudes of a SNAP and reflects a variety of diameters of sensory nerve axons.1 The onset response latency reflects the AP propagation time for the largest, fastest sensory axons and is used to calculate the SNAP conduction velocity. Because the sensory nerve is myelinated and lacks a NMJ, the distance between cathode and G1 electrode is used for the numerator and the onset response latency is used as the denominator.
Proximal responses that are commonly evaluated are F-responses and H-reflex, and are often termed late responses. The H-reflex is a mono-synaptic reflex arc, resulting from a submaximal stimulation of the sensory fibers of the tibial nerve behind the knee at low intensity and high duration. The H-reflex study is orthodromic – starting with sensory fibers that travel proximally, synapsing in the spinal cord, reflexively triggering an AP in motor neurons that travel distally, where the recording electrode obtains the waveform. The H-reflex is typically used to test proximal S1 segments, but also has utility in the assessment of C6 or C7 radiculopathy by evaluating the C7 spinal reflex arc at the flexor carpi radialis.
In contrast, the F-response is generated from a supramaximal antidromic stimulation of motor neurons. After synapsing with interneurons, an orthodromic motor nerve AP returns resulting in stimulation of the muscle from which the signal is obtained. F-responses are commonly obtained from ulnar, median, fibular (peroneal), and tibial nerves, but can be obtained from any peripheral nerve in the body.
Common Errors Affecting Accuracy
Above all else, technical errors, such as incorrect electrode placement, measurement errors, poor instrument maintenance, or the incorrect use of filters on the recording equipment, can impact the accuracy of NCS findings. Operator error should be an electrodiagnostician’s first thought when unusual findings are recorded.
Decreased temperature leads to delayed Na+ channel inactivation and prolonged depolarization, which results in a larger voltage change and an increase in CMAP and SNAP signal amplitudes. The delay in Na+ channel inactivation will delay AP propagation and saltatory conduction, thus delaying onset response latencies and conduction velocities.1 These effects tend to be more prominent in SNAPs than in CMAPs.
A lack of supramaximal stimulation can lead to artificially low signal amplitudes.2 Too intense of a stimulus can lead to co-stimulation of adjacent nerves through volume conduction of the electrical signal in tissues, which may lead to artificially high signal amplitude or faster conduction velocities. A common indicator of volume conduction is a sudden change in waveform morphology from its traditional pattern after the stimulus intensity has been increased. One typically sees this change after reaching maximum amplitude and increasing the intensity beyond supramaximal stimulation. However, in smaller or leaner patients, volume conduction can also occur at low stimulus intensities. In addition, too intense of a stimulus will enlarge the area of depolarization, leading to nerve activation further distal to the cathode at the time of stimulation, resulting in a decreased distal latency.2
Another common error is improper electrode placement. If the G1 is not placed over the motor point, the amplitude will be artificially lowered, which could be misconstrued as an axonal problem. One may also see an initial positive deflection or variation from the typical waveform, as evidences of an improperly placed G1 electrode. Additionally, in sensory studies, if G1 and G2 are too close or too far away, the resulting waveform can be affected.
Stimulating with the cathode distal to the anode can also produce error. This mistake, termed polarity reversal or anodal block, can artificially prolong latency and decrease conduction velocity measurements.
Failure to account for patient height, weight, age and gender can also produce error. Longer nerves, in general, have slower conduction velocities due to the smaller diameter of the nerve as it tapers distally. Taller individuals may have slowed conduction velocities due to more tapering of the nerve and the tendency of recording NCS distally in the limbs. Additionally, longer limbs tend to be cooler than shorter ones due to the physical limitations of euthermia resulting from arterial and venous flow.1 NCSs are more difficult to obtain in obese individuals, due to signal attenuation. Conduction velocities tend to slow with age. If using reference values for younger individuals, these velocities could be artificially construed as prolonged. The NDTF data takes into account all these factors.8
Anomalous innervations can also contribute to errors. Without prompt recognition, the presence of an accessory peroneal nerve, Martin-Gruber anastomosis (a median to ulnar anastomosis in the forearm) or other anatomic variation can lead to the false interpretation of normal findings as pathologic.1,2
Neuropathology – NCS Correlation
Nerve conduction studies are commonly used to evaluate for specific nerve injury or entrapment, but can also help with the diagnosis of polyneuropathies, myopathy or NMJ disorders. Lesions of the motor or sensory axon typically result in loss of CMAP and SNAP amplitudes. Decreased distal latency and conduction velocity is only seen when there is severe large fiber loss. While postsynaptic NMJ disorders tend to have normal latencies, amplitudes and conduction velocities, presynaptic NMJ disorders have variable CMAP amplitudes.
Lesions affecting myelin lead to conduction slowing and are demonstrated by prolonged distal latencies for distal entrapments. For proximal entrapments, loss of conduction velocity across that specific segment, termed conduction block across that segment can be demonstrated.
Another feature of diseases or injuries to myelin include conduction block, which is defined as a drop in the amplitude during stimulation proximal to the lesion, but a normal amplitude on distal stimulation. This finding indicates that some of the individual axon’s impulses fail to traverse the area of injury, although that nerve is still alive, viable and able to be stimulated distal to the site of entrapment.
Temporal dispersion may also occur with demyelinating lesions. When some axons have slowed APs through a region and others conduct normally, the resultant waveform is a curve that is wider due to a larger difference between the fastest and slowest fibers. Moreover, the spreading of AP velocities results in a lower amplitude, as there are not as many APs coming in at the exact peak time.1,2
RELEVANCE TO CLINICAL PRACTICE
With the many ways that nerve conduction studies are used, the choice of tests to do on any one patient needs to be individualized. A history and physical examination prior to study will lead to a differential diagnosis. The differential diagnosis will then dictate what sensory and motor nerve conduction studies and proximal responses to evaluate. Doing a routine nerve conduction “screen” is inappropriate.5,19 Electrodiagnosticians should never lose sight that the NCS, and EMG, is an extension of their physical exams. NCS are not diagnostic in isolation and should be accompanied by needle EMG.19 Using NCS to make a diagnosis requires a detailed understanding of the history, physical exam, and interpretation of NCS and EMG findings.11
Nerve conduction studies are useful in evaluating for generalized neuropathies. In axonal neuropathies, the primary abnormality will be the loss of SNAP and CMAP amplitudes with proximal or distal testing. Prolongation of distal latency or decrease in conduction velocity will only occur after extensive large fiber loss and is only a secondary feature. In acquired demyelinating neuropathies, salient nerve conduction findings include the loss or prolongation of F-wave latencies and H-reflexes, prolonged distal latencies, decreased conduction velocities, and the presence of conduction block with proximal stimulation, as well as temporal dispersion. In congenital demyelinating neuropathies, similar findings are seen but without the features of conduction block or temporal dispersion.
The most common generalized neuropathy is diabetic peripheral neuropathy. While the entirety of the disease is beyond the scope of this review, there have been advances in the literature as it relates to NCS usage. First, an A1C >9% and the presence of neuropathic pain show a strong correlation with NCS pathology.9 Second, the development of pathology in NCS of diabetic neuropathy appear to follow a specific pattern of initially reduced sensory amplitudes and slowed motor velocities, followed by reduced motor and sensory amplitudes and prolonged motor latencies with disease progression.9 Moreover, studies have demonstrated that radial nerve SNAP abnormalities on NCS may be the most strongly correlated with peripheral neuropathy severity. This knowledge could serve as useful with regards to monitoring disease progression treatment response.14 Finally, with regards to improvement in diabetic control and NCS, for every 1% improvement in A1c conduction velocity will improve by roughly 1.3 m/s.10
The Blink Reflex, first described by Kimura, is a way to use NCS to assess the facial nerve.13 Primarily, the tool has been used in assessment of Bell’s palsy. In essence, it’s the “analogue to the physiologic corneal reflex.”12 One can use the blink reflex NCS to make quantitative assessments regarding the severity of an injury and the prognosis.12
CUTTING EDGE CONCEPTS / EMERGING ISSUES
Motor unit number estimation is a nerve conduction technique that is used in research settings to allow the estimation of the number of nerve axons in a motor nerve. Although primarily used in ALS research, its application could extend to other motor axonal disorders such as post-polio syndrome and radiculopathy. It might also be useful in evaluating nerve recovery after surgical repair. There are multiple methods of this technique which are time consuming and challenging to complete. Further techniques might be more useful in the clinical setting to be able to follow patients over time.4
There are ongoing studies investigating the total number of limbs required to diagnosed a distal symmetric polyneuropathy. Current practice is to include both lower limbs, but newer evidence suggests that this practice may lead to unnecessary studies, increased cost to the health care system, while providing limited diagnostic utility.18
While it is understood that NCS is the best method for quantitative information regarding the presence, severity, and prognosis of peripheral neuropathy,15 there is some emerging evidence that alternative tools for assessing median neuropathies at the wrist or ulnar neuropathies at the elbow, namely ultrasound, may be similar or even superior.16,17 Furthermore, there is some suggestion that ultrasound may unveil median neuropathies at the wrist, which NCS may miss.17
Current research includes focus on developing normative values for more proximal nerve studies, including the axillary nerve,20 accessory nerve20 and medial femoral sensory nerve.21 The goal of these studies is to follow the NDTF guidelines7,8 to develop standardized reference values for these lesser-studied proximal nerves.
There is also research investigating the role of limb position and its affects conduction velocity across different limbs,23 as well as how anodal stimulation affects the waveforms and amplitudes of nerve conductions studies.25
GAPS IN KNOWLEDGE/EVIDENCE BASED
While the NDTF has published consensus guidelines on NCS standardization, there remain few studies that qualify via their selection criteria, and most of the normative data came from a single lab.8 The limited literature should be confirmed via larger multicenter trials. Moreover, the consensus guidelines will serve as an excellent roadmap for future research efforts on NCS standardization. Although the NDTF has put together preliminary collection of standardized reference values, most of these values came from a single lab and might not represent a diversified population. Additionally, the accepted margin for error was 97th percentile, which increases the possibility of type 2 errors. Eliminating variance in how nerve conduction studies are conducted and reported will allow for reproducibility and longitudinal evaluation that will allow NCS to be better compared to alternative testing methods.
Regarding electrical safety in patients with central lines, most of the studies researching this question have low power, and more research is needed to confirm electrical safety in patients with central catheters. Additionally, there is little data for electrical safety in patients with Swan-Ganz catheters.22
While newer research is investigating the use of ultrasound as a supplement concurrence with electrodiagnostic testing and NCSs, this practice is limited to larger, tertiary centers and may not be practical or cost-effective for an individual practitioner. Additionally, ultrasound studies tend to have low number of participants. More multi-center, high powered studies are needed to determine use of ultrasound in obese individuals and to confirm previous studies performed on non-obese study participants.25
There remains concern about fraud, waste and the quality of nerve conduction studies.19,26 The concern over the quality of nerve conduction studies heightened with the proliferation of handheld devices and mobile labs where large numbers of nerves are tested with lack of adherence to practices to avoid common errors in nerve conduction studies.5 AANEM has published articles defining and standardizing appropriate electrodiagnostic studies, including providing guidance and reasoning the NCSs should rarely be performed without subsequent needle EMG.19
REFERENCES
- Preston, D.C., Shapiro, B.E. Electromyography and Neuromuscular Disorders. Philadelphia, PA: Elsevier: 2005.
- Dumitru, D., Amato, A., Zwarts, M. Electrodiagnostic Medicine. Philadelphia, PA: Elsevier: 2001.
- Olney, R.K. (1999). Chapter 10. Consensus Criteria for the Diagnosis of Partial Conduction Block. Muscle Nerve 1999; 22: Supplement 8: S225-S229.
- Gooch Cl, et. Al. Motor unit number estimation: A technology and literature review. Muscle and Nerve. 2014;50(6):884-893. doi: 10.1002/mus.24442.
- AANEM Position Statement. Proper Performance and Interpretation of Electrodiagnostic Studies. 2014, available at https://www.aanem.org/getmedia/bd1642ce-ec01-4271-8097-81e6e5752042/Position-Statement_Proper-Performance-of-EDX_-2014.pdf . (date accessed 6/17/15).
- Sandin KJ, et. al. Clinical quality measures for electrodiagnosis in suspected carpal tunnel syndrome. Muscle and Nerve 2010;41(4):444-452. doi: 10.1002/mus.21617
- Dillingham, Timothy, et al. “Establishing High-Quality Reference Values for Nerve Conduction Studies: A Report from the Normative Data Task Force of the American Association Of Neuromuscular & Electrodiagnostic Medicine.” Muscle & Nerve. 2016;54(3):366-370. doi:10.1002/mus.25204.
- Chen, Shan, et al. “Electrodiagnostic Reference Values for Upper and Lower Limb Nerve Conduction Studies in Adult Populations.” Muscle & Nerve. 2016;54(3):371–377. doi:10.1002/mus.25203.
- Souza, Rainha J. De, et al. “Nerve Conduction Studies in Diabetics Presymptomatic and Symptomatic for Diabetic Polyneuropathy.” Journal of Diabetes and Its Complications, vol. 29, no. 6, 2015, pp. 811–817., doi:10.1016/j.jdiacomp.2015.05.009.
- Bansal, V., Kalita, J., & Misra, U. K. (2006). Diabetic neuropathy. Postgraduate Medical Journal, 82, 95–100.
- Bland, Jeremy D. P. “Nerve Conduction Studies for Carpal Tunnel Syndrome: Gold Standard or Unnecessary Evil?” Orthopedics, vol. 40, no. 4, 2017, pp. 198–199., doi:10.3928/01477447-20170627-01.
- Hartmann, J. E. (2013). Blink Reflex. Encyclopedia of Otolaryngology, Head and Neck Surgery, 337–341. doi:10.1007/978-3-642-23499-6_904
- Kimura, Jun. “Assessment of Individual Nerves.” Electrodiagnosis in Diseases of Nerve and Muscle, 2013, pp. 99–146., doi:10.1093/med/9780199738687.003.0006.
- Zis, Panagiotis, et al. “Electrophysiological Determinants of the Clinical Severity of Axonal Peripheral Neuropathy.” Muscle & Nerve. 2019;59(4):491–493. doi:10.1002/mus.26425.
- Shabeeb, Dheyauldeen, et al. “Electrophysiological Measurements of Diabetic Peripheral Neuropathy: A Systematic Review.” Diabetes & Metabolic Syndrome: Clinical Research & Reviews, vol. 12, no. 4, 2018, pp. 591–600., doi:10.1016/j.dsx.2018.03.026.
- Omejec, Gregor, et al. “Diagnostic Accuracy of Ultrasonographic and Nerve Conduction Studies in Ulnar Neuropathy at the Elbow.” Clinical Neurophysiology, vol. 126, no. 9, 2015, pp. 1797–1804., doi:10.1016/j.clinph.2014.12.001.
- Borire, Adeniyi A., et al. “Sonographic Differences in Carpal Tunnel Syndrome with Normal and Abnormal Nerve Conduction Studies.” Journal of Clinical Neuroscience, vol. 34, 2016, pp. 77–80., doi:10.1016/j.jocn.2016.05.024.
- Dupuis, Janae E., et al. “Bilateral Nerve Conduction Studies in the Evaluation of Distal Symmetric Polyneuropathy.” Muscle & Nerve. 2019;60(3):305–307. doi:10.1002/mus.26616.
- American Association of Neuromuscular & Electrodiagnostic Medicine. “Proper Performance and Interpretation of Electrodiagnostic Studies.” [epub online ahead of print]. Muscle & Nerve. 2020;1-3. doi:10.1002/mus.26835.
- Day, Timothy J. “Optimal Reference Electrode Placement for Accessory and Axillary Nerve Conduction Studies.” [epub ahead of print]. Muscle & Nerve. 2020; doi:10.1002/mus.26847.
- Geney‐Castro, David Ernesto, et al. “Medial Femoral Cutaneous Nerve Conduction Study with Distal Recording: A Novel Technique.” Muscle & Nerve. 2020;61(3):383–386. doi:10.1002/mus.26788.
- London, Zachary N., et al. “Nerve Conduction Studies Are Safe in Patients with Central Venous Catheters.” Muscle & Nerve. 2017;56(2):321–323. doi:10.1002/mus.25497.
- Simon, Neil G., and Susan Walker. “The Role of Limb Position in the Interpretation of Nerve Conduction Studies.” Muscle & Nerve. 2017;56(3):353–354. doi:10.1002/mus.25657.
- Kanbayashi, Takamichi, et al. “Interaction of Cathodal and Anodal Stimulations in Nerve Conduction Studies.” Muscle & Nerve. 2019;59(6): 713–716. doi:10.1002/mus.26467.
- Cartwright, Michael S., et al. “Ultrasound Guidance for Sural Nerve Conduction Studies.” Muscle & Nerve.2019;59(6):705–707. doi:10.1002/mus.26465.
- AANEM Professional Practice Committee Establishing standards for acceptable waveforms in nerve conduction studies. Muscle & Nerve. 2020;61:280–287. https://doi.org/10.1002/mus.26751.
Original Version of the Topic
Anthony Chiodo, MD, Michael Wheaton, MD. Nerve conduction velocities. Originally published:09/09/2015
Author Disclosure
Jason Kiene, MD
Nothing to Disclose
David Sherwood, DO
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Benjamin Westerhaus, MD
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