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Neurophysiology Simplified for Imagers Payam Mohassel, MD1
Vinay Chaudhry, MD2
1 Department of Neurogenetics, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 2 Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland
Address for correspondence Vinay Chaudhry, MD, Johns Hopkins Outpatients Center, 601 N. Caroline Street, JHOC 5072A, Baltimore, MD 21287 (e-mail: [email protected]).
Abstract Keywords
► electromyography ► nerve conduction study ► neuromuscular disease ► neuropathy ► myopathy
Electrodiagnostic studies are powerful diagnostic tools that complement the clinical evaluation of patients with neuromuscular disease. However, their proper interpretation requires a hypothesis-driven approach that depends on clinical information and physical examination findings. In principle, Bayesian methods of reasoning determine both the plan of examination and interpretation of results. Thus neuromuscular disease training with an understanding of peripheral nervous system anatomy, nerve and muscle physiology, pathophysiology, pathology, management, and prognosis are as important as technical training for performance of the test. In this article, geared toward imagers, we review the basic principles of electrodiagnostic studies, typical measurements, and their interpretation both in normal and common disease states.
Overview and Approach to Electrodiagnostic Studies Electrodiagnostic studies (EDS) of the peripheral nervous system are powerful clinical tools that aid in the diagnostic evaluation of patients with signs and symptoms attributable to the peripheral nervous system. Basic principles of electrophysiology were under development in the late 19th century. However, clinical use did not start until the mid-20th century. Since that time, electrodiagnostic characterization of many neuromuscular diseases has been meticulously accomplished and correlated with pathology. Together, they have improved the understanding of disease processes and have aided tremendously in the diagnosis of neuromuscular diseases. EDS are used as an extension of the neurologic examination. The primary goal of EDS is to help with localization of the lesion. Hence in a patient with weakness, EDS help with defining weakness as neurogenic (motor neuron, root, plexus, or peripheral nerve) or myopathic (neuromuscular junction or muscle) (►Fig. 1). Similarly, in a patient with paresthesia, localization to the dorsal root ganglia, root, plexus, or nerve can be achieved. The localization process also includes determining the distribution of the lesion (focal, multifocal, or generalized; one segment, multiple segments, or diffuse
Issue Theme Advanced Imaging of Peripheral Nerves; Guest Editor, Avneesh Chhabra, MD
within the nerve) and localizing to subcomponents of the peripheral nerve (axon or myelin sheath). The secondary goals of EDS include determining the approximate age of the injury (acute, subacute, chronic), determining the severity of the lesion (complete absence of a response may reflect complete loss of fibers or complete conduction block), helping define pathology/etiology of the lesion, helping plan/ monitor treatment, and serving as a guide to prognosis. Most routine EDS studies are composed of two different but related tests: nerve conduction studies (NCS) and electromyography (EMG). These are usually done in tandem and complement each other. Several physiologic and nonphysiologic factors including age, height, temperature of the tissue, volume conduction properties of active nerve fibers and muscle, and pathology influence EDS. Obtaining technically accurate and appropriate data, rational interpretation of the data, and clinical correlation form a dynamic continuum. Neuromuscular disease training with an understanding of peripheral nervous system anatomy, nerve and muscle physiology, neuromuscular disease processes and pathophysiology, pathology, management, and prognosis are as important as EDS training for performance of the test.1 We first briefly review the relevant neuromuscular anatomy and physiology as it relates to understanding basic EDS
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DOI http://dx.doi.org/ 10.1055/s-0035-1545075. ISSN 1089-7860.
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Semin Musculoskelet Radiol 2015;19:112–120.
Mohassel, Chaudhry
Fig. 1 Schematic representation of the motor unit (right) and some of the diseases of the motor unit (left). ALS, amyotrophic lateral sclerosis; AIDP, acute inflammatory demyelinating polyradicuoloneuropathy; AMAN, acute motor axonal neuropathy; GBS, Guillain-Barré syndrome; HMSN, hereditary motor and sensory neuropathy; MLD, metachromatic leukodystrophy; MMN, multifocal motor neuropathy; SMA, spinal muscular atrophy.
before discussing the technical issues of obtaining basic NCS and EMG measurements and their interpretation in the setting of pathologic change.
Functional Anatomy of the Peripheral Nervous System Relevant to Electrodiagnostic Studies The peripheral nervous system includes sensory neurons (dorsal root ganglia [DRGs]) and their axons. In addition, it includes motor neurons (anterior horn cells), their axons, neuromuscular junction, and muscle fibers (►Fig. 1). DRGs reside outside of the spinal cord and have two major axons: one enters the spinal cord through the dorsal sensory roots and the other exits the spinal foramen to project to the periphery and joins the motor ventral roots to form the “mixed” spinal roots. The centrally bound axon of the DRGs is not assessed in standard NCS, although their apparent preservation can have localizing value in case of lesions proximal to the DRG such as radiculopathies (see later).
However, any lesions distal to the DRG will result in loss of sensory responses in NCS that can be helpful in localization. The anterior horn cells, in contrast, send their projecting axons through the ventral roots. After exiting the spinal foramen, the mixed spinal roots usually give off posterior branches that innervate posterior trunk muscles and supply sensory innervation to trunk and proximal areas. They also give off anterior branches that innervate the extremities and anterior trunk. These anterior branches join complex connections in the cervical and lumbar areas and form the brachial and lumbosacral plexuses. Individual nerves are subsequently derived from the plexuses that innervate each individual skeletal muscle and supply innervation to the entire skin, muscle spindles, and Golgi tendon organs. The basic functional unit of the motor system, the motor unit, mirrors this anatomical organization to some extent: a motor neuron, its axons, the neuromuscular junction, and the muscle fibers that it innervates comprise a motor unit. Dysfunction along any of the components of the motor unit Seminars in Musculoskeletal Radiology
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may result in weakness. However, physiologic changes attributable to the dysfunction of each component can differ and be studied using EDS. For example, EMG with a needle electrode can provide information about different motor units within a given muscle. The sensory system is somewhat simpler in functional organization because it lacks a synapse in the peripheral nervous system, although the same principles of signal propagation apply. Signal propagation through the axons, sensory or motor, is achieved with action potentials, an all-or-none phenomenon. In unmyelinated axons, action potentials travel from the axon hillock toward the synapse rather continuously. In myelinated axons, salutatory conduction occurs from a node of Ranvier to the next. Nodes of Ranvier, enriched in voltage-gated sodium channels, are sandwiched in between two myelinated segments, each with its own Schwann cell. Neuropathies can be categorized based on their demyelinating, axonal, or mixed features. They can also be categorized based on the distribution and selective groups of the nerves they affect. Most neuropathies have a predilection for longer nerves, the so-called length-dependent neuropathies (e.g., diabetic neuropathy) and present as paresthesias in a stocking-glove distribution. Typically, axonal neuropathies present as length-dependent symmetrical neuropathy with the longest nerves of the body (i.e., those innervating the feet) being affected before shorter nerves (e.g., those innervating the thighs). Other neuropathies may affect the nerves in a non– length-dependent but symmetrical fashion, and proximal muscles may be equally or even more affected than distal ones. Typically, demyelinating neuropathies behave in this manner (e.g., chronic inflammatory demyelinating polyradiculopathy). In other neuropathies, the findings may be patchy, focal, multifocal, or asymmetric. Lesions affecting the cell body of the nerves (neuronopathies) or structural lesions of the nerve(s)/plexus may present in this manner.2 Standard NCS can only assess myelinated axon electrical conduction in aggregate form. They give little to no information about unmyelinated axons and their integrity and cannot assess individual axons. For example, patients with small fiber neuropathy that selectively affects small unmyelinated fibers, which usually transmit pain and temperature sensation, may have normal nerve conduction studies. NCS can help categorize these findings and aid in narrowing down the diagnostic possibilities, and the principles discussed here will become important in the interpretation of different measured components of EDS (see later).3
or mixed sensory motor symptoms, small fiber versus large fiber or length-dependent versus non–lengthdependent neuropathy versus neuronopathy may need to be in the differential diagnosis, respectively. For generalized motor symptoms, motor neuron disease, motor neuropathy, neuromuscular junction transmission defect, or myopathy may need to be considered. The choice of an electrodiagnostic procedure (i.e., NCS, EMG, and repetitive nerve stimulation [RNS] is guided by the appropriate differential diagnosis (►Fig. 2). 2. A routine study begins with NCS, which is an examination of conduction along peripheral motor and sensory nerves, and with testing for late responses. Next, EMG, which is a direct examination of skeletal muscle using needle electrodes, is performed to determine the pattern and degree of muscle abnormality to evaluate for myopathy or denervation changes. RNS at slow and fast rates is performed only if indicated to evaluate the neuromuscular junction. 3. Arriving at a diagnostic interpretation: This includes defining the possible anatomical site of the lesion (motor neuron, root, plexus, nerve, neuromuscular junction, or muscle), its extent (focal versus diffuse), and the possible pathologic process (axonal loss versus demyelination, inflammatory versus metabolic myopathy), giving clues as to the etiology and commenting on the prognosis, based on the clinical and electrodiagnostic examination.
Nerve Conduction Studies Technique and Principles As the name implies, NCS measure electrical signal propagation along a given nerve. In principle, the operator stimulates the nerve at one site and measures the electrical response at another. Electrical stimulation of a nerve generates action potentials. Smaller nerve fibers usually reach the threshold at lower currents of stimulation. As the intensity of the stimulation is increased, additional larger axons become stimulated until a point when additional stimulation does not recruit additional
Components of a Complete Electrodiagnostic Evaluation 1. History taking and neuromuscular examination, which lead to the differential diagnostic possibilities and a plan of evaluation. For focal sensory and/or motor symptoms, the question is generally an entrapment neuropathy versus radiculopathy. For focal motor symptoms, motor neuronopathy, radiculopathy, plexopathy, or motor neuropathy may be the consideration. For generalized sensory Seminars in Musculoskeletal Radiology
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Fig. 2 Components of a complete electrodiagnostic study. EMG, electromyography; NCS, nerve conduction study; RNS, repetitive nerve stimulation.
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Motor Nerve Conduction Studies (►Fig. 3) In simple terms, motor NCS evaluate the electrical signal propagation in myelinated motor axons. The motor nerve is stimulated
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proximal to the muscle it innervates with the recording electrodes placed over the muscle. The measured response is the aggregate muscle fiber action potentials, that is, compound muscle action potential (CMAP). Different components of the CMAP can be obtained and measured, each one most reflective of a subgroup of motor axons and their integrity.
Distal Latency Distal latency refers to the time (in milliseconds) from stimulus onset to the first detection of CMAP deflection. It includes the time for motor nerve action potential (through the fastest conducting myelinated axons) to travel from the stimulation site to the neuromuscular junction, synaptic vesicle release, postsynaptic depolarization, and finally muscle action potential. Under most circumstances, variability in distal latency can be attributed to the change in motor nerve action potential conduction time. In essence, distal latency depends most on the integrity of the largest myelinated motor axons. In practice, a prolonged distal motor latency indicates demyelination or loss of the largest myelinated axons in the segment of the nerve between stimulating and recording electrodes.
Amplitude and Area Under the Curve CMAP amplitude is the voltage (in millivolts) change measured from the baseline to the negative peak of CMAP waveform. In other words, CMAP amplitude depends on
Fig. 3 Sensory and motor nerve conduction study (NCS) along with F waves and H reflex.
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axons. This is the so-called supramaximal stimulation. NCS can be reliably obtained only if each nerve is studied at supramaximal stimulation. Over- and understimulation can both result in unreliable and aberrant measurements. As a result, most reliably assessed nerve segments usually course close to the skin. Proximal and deeper nerves are more difficult to assess.4 Another important issue is the appropriate recording of electrode placement and knowledge of standard stimulation sites for each nerve. Misplaced electrodes can result in falsepositive results. Cold temperature can also exaggerate sensory nerve action potential amplitude and underestimate conduction velocity. Surface skin temperature can be measured and taken into account when interpreting a study. Three different types of NCS can be performed in principle: motor, sensory, or mixed NCS. Sensory and motor conduction studies are used most frequently. For each measurement, different variables can be obtained, each containing information about a component of the nerve and the population of myelinated axons it is made up of. Late responses, F wave and the H reflex, can help provide information for more proximal parts of the peripheral nervous system albeit with less specificity. These are discussed later.5
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the peak of an aggregate measurement (i.e., CMAP), and as a result, it depends on synchrony as much as each individual motor unit action potential amplitude. In simpler terms, CMAP amplitude is an aggregate of the most synchronous muscle fiber action potentials. In a normal nerve it usually estimates the number of intact motor units. The innervation ratio of motor axons is usually constant. So, in most typical cases, a low CMAP amplitude reflects motor axon loss. However, demyelinating lesions distal to the stimulation site or severe neuromuscular junction dysfunction or severe myopathies can result in low CMAP amplitude. In an acute injury (e.g., traumatic nerve injury), before collateral sprouting and reinnervation can occur, the degree of loss of CMAP amplitude can be used to estimate the severity of motor axon loss. This is usually compared with CMAP amplitude on the unaffected side. However, after reinnervation and collateral sprouting occur, CMAP amplitude will improve over time. In those circumstances, the degree of CMAP decrement will underestimate the extent of axonal loss. In other words, the innervation ratio of each intact motor axon increases and should be taken into account in estimating severity. In these cases, needle EMG can help in evaluation. Area under the curve (AUC) refers to the surface area under the negative portion of the CMAP waveform and in effect is a product of time and voltage. AUC more accurately estimates the total number of intact axons because it does not rely on synchrony. In a normal nerve, it is less useful. However, in cases of demyelinating disease, it is a better estimate of axon integrity than CMAP amplitude. For example, in pure demyelinating lesions of the motor nerves, in spite of complete preservation of motor axons, CMAP amplitude may be reduced (owing to dyssynchrony of muscle fiber action potentials), but the AUC would remain unchanged.
Conduction Velocity Conduction velocity refers to the velocity of signal propagation along a given nerve segment. As discussed earlier, motor distal latency includes the time required for motor nerve conduction to the neuromuscular junction (NMJ), but also the time needed for NMJ transmission and muscle action potential generation. To measure the motor nerve conduction velocity, two different sites of the motor nerve are stimulated, and distance between the two is measured. The difference in the motor distal latency between the proximal and distal site of stimulation cancels out all the components except the time for motor conduction in the segment between stimulation sites. Thus motor nerve conduction velocity can be reliably measured. Because it depends on distal latency, conduction velocity estimates the maximum velocity of the fastest (i.e., largest) conducting myelinated motor axons.
Duration CMAP duration is usually measured in the negative phase, the time between the first negative deflection until the Seminars in Musculoskeletal Radiology
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return to baseline. Duration depends on the lowest and highest (i.e., range) conduction velocities of motor axons and estimates synchrony. Under normal physiologic conditions, the more proximal the stimulus site, the longer the CMAP duration. However, this change is usually minimal albeit detectable. In focal segmental demyelinating disease, the dyssynchrony is exaggerated the most and prolongation of CMAP duration ensues. Diffuse and homogeneous demyelinating disease (e.g., Charcot-Marie-Tooth disease type 1) and nonselective motor axonal loss have more subtle effects on CMAP duration.
Sensory Nerve Conduction Studies As the name implies, sensory NCS evaluate the sensory nerves. A sensory nerve is stimulated at one site, and sensory nerve action potential (SNAP) is measured at the recording site (►Fig. 3). Sensory NCS can be performed orthodromically (i.e., the same direction as physiologic action potential conductance) or antidromically. Sensory nerve action potentials have much lower amplitudes (microvolts) compared with CMAP (millivolts) and are much more prone to artifact. So as a whole they are more technically challenging to perform. However, interpretation of sensory NCS can in some ways be easier.
Latency SNAP latency can be measured from the negative deflection peak or at the onset. Some laboratories use the peak latency because it is more reliably pinpointed for measurement, but sensory nerve conduction velocity cannot be deduced from it. Other laboratories use onset latency and report nerve conduction velocity measurements. Unlike distal motor latency, sensory onset latency measurement does not depend on synaptic transmission and is solely reflective of the fastest conducting sensory axons. As a result, sensory nerve conduction velocity can be used instead of the latency measurement.
Amplitude SNAP amplitude is routinely measured from the negative peak to the positive peak of the waveform (in microvolts). Similar to CMAP amplitude, SNAP amplitude is the aggregate measure of all individual sensory fibers. However, SNAP amplitude is more prone to normal physiologic measurement confounders such as dispersion or phase cancellation. As a result, most SNAP amplitudes are measured at fixed and standard distances from the recording electrodes.
Conduction Velocity Sensory nerve conduction velocity (NCV) can be measured by using a single stimulation site, as previously described. The distance between the recording and the stimulating electrodes is measured on the skin surface, and the onset latency is used as time. Similar to motor conduction velocity, sensory NCV is the conduction velocity of the fastest conduction (i.e., largest) myelinated sensory axons.
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Late Responses
Electromyography (Needle EMG)
The motor and sensory nerve conduction study techniques just described mostly assess distal nerve segments. Although proximal nerve segment stimulation can be achieved, the results tend to require higher stimulation intensities and may be associated with unreliable results due to technical issues such as stimulation of adjacent nerves, difficult-to-reach supramaximal stimulation, and patient discomfort among others. In addition, the most proximal portions of the nerve trunks, plexuses, and roots still cannot be assessed. Late responses, the F response and the H reflex, are used routinely to assess the most proximal portions of the nerve. They are much more limited compared with distal nerve segment studies but can add valuable information, especially when the abnormalities are limited to the most proximal portions of the nerves.
Needle EMG is an important part of EDS and complements the NCS. Information obtained from EMG can help confirm suspected pathologic processes and assess the distribution of abnormalities effectively. Given the discomfort associated with EMG and the large number of muscles that could be potentially studied, the operator should have a detailed knowledge of anatomy and most importantly a hypothesis-driven approach to avoid subjecting the patient to uncomfortable and unnecessary studies. The EMG needle in essence is an electrode that is inserted into the muscle and samples the electrical activity of muscle fibers of a single motor unit in the area immediately around it. Two major components of needle EMG include evaluation of spontaneous activity at rest and assessment of the voluntary motor units upon activation.
F Responses The F response, or F wave, is a late motor response. Similar to motor NCS, it is measured over the muscle. When a distal nerve segment is stimulated, the electrical signal travels in both directions, distally and proximally. CMAP is measured first (M response), which is the result of the distally traveling electrical signal, in other words from the stimulation site toward the muscle. The proximally traveling signal reaches the anterior horn cells in the spinal cord. A few of these motor neurons may backfire action potentials, which will again reach the muscle, although much later than the original M response. The F response can be obtained from nearly all motor nerves. In addition to its longer latency, the F response also has a much lower amplitude, representing the smaller number of motor units that are activated at the level of the spinal cord. Different components of the F response can be measured, such as its persistence, latency, chronodispersion, and amplitude. However, the most reliable and useful measure is probably the F-wave motor latency, an indirect assessment of the entire motor nerve including its proximal portions. An abnormal distal segment study is sufficient to cause an abnormal F-wave latency. Therefore, an abnormally prolonged F-wave response is most helpful when distal segment studies are normal because it localizes the lesion to the proximal portions of the motor nerve.
H Reflex Unlike the F response, the H reflex is a true reflex with a sensory afferent and a motor efferent portion. Due to technical issues, it is most reliably measured in the lower extremities from the tibial nerve. The afferent sensory signal travels the Ia sensory fibers to the spinal cord. After synaptic transmission onto α motor neurons, a motor response is elicited and measured over the muscle. Similar to the F response, the latency is most commonly used in interpretation. A prolonged or absent H reflex is in general nonspecific and can be seen in polyneuropathy, proximal neuropathy, plexopathy, or radiculopathy.
Spontaneous Activity Normal muscle fibers at rest do not usually show any spontaneous electrical activity. Two major exceptions include endplate noise (near the neuromuscular junction) and endplate spikes. Both have a characteristic appearance that differentiates them from abnormal spontaneous activity. Endplate noise is the result of miniature endplate potentials, the subthreshold depolarization potentials that occur as a result of normal quantal releases of acetylcholine at the NMJ. Endplate spikes are muscle fiber action potentials that are also found near the NMJ, and they have a characteristic initial negative (upgoing) deflection. They most commonly result from irritation of an axonal twig near the NMJ by the needle. Abnormal spontaneous activity can be broadly classified into those originating in abnormal muscle fibers or abnormal nerve fibers. They each have a particular appearance morphologically as well as acoustically and can be differentiated readily by the experienced EMG physician. Explanation of each abnormal pattern is beyond the scope of this article. ►Table 1 summarizes the major characteristics of the most commonly encountered spontaneous activity on needle EMG testing.
Voluntary Motor Unit Action Potentials Voluntary motor unit action potentials (MUAPs) are assessed when the patient voluntarily contracts a muscle after the needle electrode is placed. Morphology, duration, and characteristic appearance of MUAPs may differ from muscle to muscle. In addition, older patients may have MUAPs that are longer in duration. In general, increased duration and amplitude of MUAPs suggest denervation with subsequent reinnervation via collateral sprouting. Short duration and small amplitude MUAPs are most indicative of a myopathic process. With experience, one can recognize abnormalities of MUAP morphology readily, especially based on the company they keep in NCS and the recruitment pattern. Recruitment is another important physiologic measure of motor unit physiology that can help differentiate neurogenic
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Table 1 Spontaneous activity in needle electromyography Spontaneous activity
Source
Characteristics
Most common causes
Endplate noise
MEPPs
Irregular, usually negative, 20–40 Hz
Normal, found near the NMJ with endplate spikes
Endplate spikes
Terminal axon/twig
Irregular, initial negative deflection
Normal, found near the NMJ
Fibrillation potentials
Muscle fiber
Mostly regular, biphasic or triphasic, 10–100 µV
Active denervation, inflammatory myopathies and dystrophies
Positive sharp waves
Muscle fiber
Mostly regular, initial positive and a prolonged negative phase, 10–100 µV
Similar to fibrillation potentials
Complex repetitive discharges
Muscle
Groups of complex spikes that repeat at high frequency (20–150 Hz)
Chronic neuropathy or myopathy
Myotonia
Muscle fiber
Brief spikes that fire 20–150 Hz with a waxing and waning pattern
Myotonic disorders, acid maltase deficiency, myotubular myopathies, rarely denervation
Fasciculations
A single motor unit
Low frequency (1–2 Hz), irregular
Normal variant, motor nerve pathology (i.e., motor neuron disease, radiculopathy, etc.)
Myokymia
Motor unit
Rhythmic, grouped, repetitive discharges, 5–60 Hz
Radiation induced neuropathy
Cramps
Motor units
Painful, involuntary muscle contraction, high frequency, irregular firing of MUAPs
Benign, neuropathy, metabolic myopathies or endocrine disease
Neuromyotonia
Motor units
High frequency (150–300 Hz), decrementing, discharges
Autoimmune channelopathies (e.g., Isaac syndrome), other rare conditions
Abbreviations: MEPP, miniature endplate potential; MUAP, motor unit action potential; NMJ, neuromuscular junction.
Table 2 Repetitive nerve stimulation Condition
RNS 2–3/s
RNS 10–25/s
Normal
Decrement up to 10%
Increment < 50%
Myasthenia gravis
Decrement > 10% in weak muscles
Lambert-Eaton myasthenic syndrome
May decrement > 10%
Often increment > 50%
Abbreviation: RNS, repetitive nerve stimulation.
or myogenic disease. However, interpretation of recruitment abnormalities especially in mild cases can be difficult. Reduced recruitment refers to a decrease in the number of MUAPs available for voluntary activation. It is most commonly found in neurogenic disease, either demyelinating or axonal. Early recruitment refers to the activation of multiple motor units for the degree of contraction elicited. It probably represents the reduction in motor unit contraction force due to loss of muscle fibers as occurs in myopathies. As a result, to maintain the same force, many more MUAPs need to be activated, leading to “early” recruitment.6
muscular transmission.7 The test procedure is exactly the same as for motor conduction studies. RNS can also be performed on abductor digit minimi, biceps, deltoid, trapezius, and facial muscles. Proximal muscles give a higher percentage of positive results for myasthenia gravis, and distal muscles can be used for presynaptic disorders of neuromuscular junction. Low rates (2–3 Hz) are used for testing for postsynaptic disorders; high rates (20–50 Hz) are used for presynaptic disorders. ►Table 2 summarizes the RNS findings in pre- or postsynaptic disorders of neuromuscular transmission
Repetitive Nerve Stimulation
Summary
RNS tests for myasthenia gravis, Lambert-Eaton myasthenic syndrome, botulism, or other suspected disorders of neuro-
EDS can be invaluable in diagnostic evaluation of patients with peripheral nervous system disease. However, their
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Electrodiagnostic measure
Myopathies
Neuropathies Axonal
Demyelinating
Distal latency
Normal
Normal or mildly prolonged
Prolonged
Amplitude
Normal; may be reduced
Reduced
Normal; reduced if demyelination distal to stimulation site
Conduction velocity
Normal
Normal or mildly reduced
Reduced
Late response latency
Normal
Normal or mildly prolonged
Prolonged
Spontaneous activity
PSW, Fibs, myotonia, CRD
PSW, Fibs, myokymia, fasciculations, CRD, etc.
Usually none
Recruitment
Early
Reduced
Reduced
MUAP amplitude
Reduced
Increased
Unchanged
MUAP duration
Reduced
Increased
Unchanged
Abbreviations: CRD, complex repetitive discharges; Fibs, fibrillation potentials; PSW, positive sharp waves.
Table 4 Findings in different diseases Sensory NCS
Motor NCS
Needle EMG
RNS
Distribution
Motor neuron disease: ALS, polio, SMA
Nl
As in motor axonal neuropathies
Spontaneous activity and MUAPs as in axonal neuropathies but diffusely
–
Cranial, cervical, thoracic, LS
Radiculopathy: disk/tumor
Nl
Axonal loss in root distribution
Focal denervation as in axonal neuropathies
–
C5–C7 or L4–S1 myotome
Plexopathy: immune/malignant
Sensory axon loss
Motor Axonal loss in plexus distribution
Denervation in plexus distribution
–
Brachial or LS plexus distributions
Axonal neuropathy: metabolic, toxic, inherited, inflammatory
Sensory axonal loss
Motor axonal loss
Denervation in length-dependent distribution
Length-dependent distribution
Demyelinating neuropathy: GBS, CIDP, MMN, CMT1a
Sensory demyelination
Motor-demyelinating features
Reduced recruitment
Focal- entrapments Multifocal MMN Generalized: GBS, CIDP Generalized uniform CMT
Botulism/LEMS
Nl
Reduced CMAP
Nl or may show instability of the MUAP
High-rate RNS shows an increment response
Diffuse
Myasthenia gravis
Nl
Nl
Nl or may show instability of the MUAP
Low-rate RNS shows a decrement response
Ocular, bulbar, proximal more than distal
Myopathy
Nl
Nl
Myopathic MUAPs with or without abnormal spontaneous activity
Proximal more than distal
Abbreviations: ALS, amyotrophic lateral sclerosis; CIDP, chronic inflammatory demyelinating polyradiculopathy; CMAP, compound muscle action potential; CMT1, Charcot-Marie-Tooth neuropathy type 1; EMG, electromyography; GBS, Guillain-Barré syndrome; LEMS, Lambert-Eaton myasthenic syndrome; LS, lumbosacral; MMN, multifocal motor neuropathy; MUAP, motor unit action potential; NCS, nerve conduction study; Nl, normal; RNS, repetitive nerve stimulation; SMA, spinal muscular atrophy. a Inflammatory demyelinating neuropathies are multifocal diseases with signs of demyelination that vary between nerves as well as along the length of the nerve. Seminars in Musculoskeletal Radiology
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Table 3 Basic abnormal findings
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interpretation requires a hypothesis-driven approach that depends on clinical information and physical examination findings. In principle, Bayesian methods of reasoning drive the choice of nerves and muscles studied both in NCS and needle EMG. In electrodiagnosis, the plan of the examination is as important as the interpretation of the results. An electrodiagnostic plan is not static and may need to be modified as the examination proceeds, for the results initially obtained may suggest additional diagnostic possibilities not previously considered. An incomplete study whose results are “properly” interpreted is as misleading as a complete study that is poorly interpreted. In the following section, we provide a few tables to overview common abnormalities in electrodiagnostic tests that suggest pathologic processes in muscle or nerve that suggest demyelinating disease, axonal pathology, or mixed processes. As described in this article, these are oversimplified but can be used as a reference for basic interpretation of abnormalities (►Tables 3 and 4).
receive intravenous immunoglobulin, or steroids that are clearly beyond the forte of the test alone. 3. A very frequent error is overcalling a neuropathy “demyelinating” due to a reduced CV. The most common reasons for this are cold limbs, loss of the fastest conducting fibers with reduced amplitudes, and overly strict adherence to normal values such that any CV less than normal is called “demyelinating” even if only 1 to 3 ms below normal. Most demyelinating neuropathies have multiple abnormal findings, not just one or two. 4. For some conditions, normal tests results do not rule out a disease. This may be true in symptomatic radiculopathy, myasthenia gravis, small fiber neuropathies, large fiber sensory dysfunction, UMN dysfunction, timing of NCS (GBS changes may evolve over a period of time and it may take 2–3 weeks for Wallerian degeneration changes to take place after a nerve injury), and proximal nerve dysfunction.8 Similarly, abnormal results may not always be clinically relevant such as carpal tunnel syndrome, subclinical neuropathies, or radiculopathies.
Limitations and Errors in EDS 1. Like the neurologic examination, most conclusions should be supported by more than a single abnormal value especially in generalized diseases. A single abnormal test result rarely indicates a larger problem. A common problem is when the study conclusion is not supported by the data but rather is a clinical conclusion. For example, a study with all normal data inappropriately concluded, “This study is diagnostic of a small fiber neuropathy.” Sometimes a study is reported as “the study is consistent with carpal tunnel syndrome, thoracic outlet syndrome, or radial tunnel syndrome, etc.” with minimal data to support these statements. The study conclusions derive from the study data, whereas a separate clinical correlation conclusion derives from the entire picture. 2. Although study data may allow an educated guess about the etiology, pathogenesis, and treatment, unless supporting data are available, one should be careful of such comments. For example, a study may show mononeuropathy multiplex, but mononeuritis multiplex assumes inflammation that the study could not have shown. Often comments are made that the patient should have surgery,
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Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Boston, MA: Butterworth-Heinemann; 2005:1–23 Kimura J, Machida M, Ishida T, et al. Relation between size of compound sensory or muscle action potentials, and length of nerve segment. Neurology 1986;36(5):647–652 Dorfman LJ. The distribution of conduction velocities (DCV) in peripheral nerves: a review. Muscle Nerve 1984;7(1):2–11 Chaudhry V, Cornblath DR, Mellits ED, et al. Inter- and intraexaminer reliability of nerve conduction measurements in normal subjects. Ann Neurol 1991;30(6):841–843 Barry DT. AAEM minimonograph #36: basic concepts of electricity and electronics in clinical electromyography. Muscle Nerve 1991; 14(10):937–946 Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Boston, MA: Butterworth-Heinemann; 2005:199–213 Cornblath DR. Disorders of neuromuscular transmission in infants and children. Muscle Nerve 1986;9(7):606–611 Chaudhry V, Cornblath DR. Wallerian degeneration in human nerves: serial electrophysiological studies. Muscle Nerve 1992; 15(6):687–693
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Copyright of Seminars in Musculoskeletal Radiology is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Neurophysiology Simplified for Imagers Payam Mohassel, MD1
Vinay Chaudhry, MD2
1 Department of Neurogenetics, National Institute of Neurological
Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 2 Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland
Address for correspondence Vinay Chaudhry, MD, Johns Hopkins Outpatients Center, 601 N. Caroline Street, JHOC 5072A, Baltimore, MD 21287 (e-mail: [email protected]).
Abstract Keywords
► electromyography ► nerve conduction study ► neuromuscular disease ► neuropathy ► myopathy
Electrodiagnostic studies are powerful diagnostic tools that complement the clinical evaluation of patients with neuromuscular disease. However, their proper interpretation requires a hypothesis-driven approach that depends on clinical information and physical examination findings. In principle, Bayesian methods of reasoning determine both the plan of examination and interpretation of results. Thus neuromuscular disease training with an understanding of peripheral nervous system anatomy, nerve and muscle physiology, pathophysiology, pathology, management, and prognosis are as important as technical training for performance of the test. In this article, geared toward imagers, we review the basic principles of electrodiagnostic studies, typical measurements, and their interpretation both in normal and common disease states.
Overview and Approach to Electrodiagnostic Studies Electrodiagnostic studies (EDS) of the peripheral nervous system are powerful clinical tools that aid in the diagnostic evaluation of patients with signs and symptoms attributable to the peripheral nervous system. Basic principles of electrophysiology were under development in the late 19th century. However, clinical use did not start until the mid-20th century. Since that time, electrodiagnostic characterization of many neuromuscular diseases has been meticulously accomplished and correlated with pathology. Together, they have improved the understanding of disease processes and have aided tremendously in the diagnosis of neuromuscular diseases. EDS are used as an extension of the neurologic examination. The primary goal of EDS is to help with localization of the lesion. Hence in a patient with weakness, EDS help with defining weakness as neurogenic (motor neuron, root, plexus, or peripheral nerve) or myopathic (neuromuscular junction or muscle) (►Fig. 1). Similarly, in a patient with paresthesia, localization to the dorsal root ganglia, root, plexus, or nerve can be achieved. The localization process also includes determining the distribution of the lesion (focal, multifocal, or generalized; one segment, multiple segments, or diffuse
Issue Theme Advanced Imaging of Peripheral Nerves; Guest Editor, Avneesh Chhabra, MD
within the nerve) and localizing to subcomponents of the peripheral nerve (axon or myelin sheath). The secondary goals of EDS include determining the approximate age of the injury (acute, subacute, chronic), determining the severity of the lesion (complete absence of a response may reflect complete loss of fibers or complete conduction block), helping define pathology/etiology of the lesion, helping plan/ monitor treatment, and serving as a guide to prognosis. Most routine EDS studies are composed of two different but related tests: nerve conduction studies (NCS) and electromyography (EMG). These are usually done in tandem and complement each other. Several physiologic and nonphysiologic factors including age, height, temperature of the tissue, volume conduction properties of active nerve fibers and muscle, and pathology influence EDS. Obtaining technically accurate and appropriate data, rational interpretation of the data, and clinical correlation form a dynamic continuum. Neuromuscular disease training with an understanding of peripheral nervous system anatomy, nerve and muscle physiology, neuromuscular disease processes and pathophysiology, pathology, management, and prognosis are as important as EDS training for performance of the test.1 We first briefly review the relevant neuromuscular anatomy and physiology as it relates to understanding basic EDS
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DOI http://dx.doi.org/ 10.1055/s-0035-1545075. ISSN 1089-7860.
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Semin Musculoskelet Radiol 2015;19:112–120.
Mohassel, Chaudhry
Fig. 1 Schematic representation of the motor unit (right) and some of the diseases of the motor unit (left). ALS, amyotrophic lateral sclerosis; AIDP, acute inflammatory demyelinating polyradicuoloneuropathy; AMAN, acute motor axonal neuropathy; GBS, Guillain-Barré syndrome; HMSN, hereditary motor and sensory neuropathy; MLD, metachromatic leukodystrophy; MMN, multifocal motor neuropathy; SMA, spinal muscular atrophy.
before discussing the technical issues of obtaining basic NCS and EMG measurements and their interpretation in the setting of pathologic change.
Functional Anatomy of the Peripheral Nervous System Relevant to Electrodiagnostic Studies The peripheral nervous system includes sensory neurons (dorsal root ganglia [DRGs]) and their axons. In addition, it includes motor neurons (anterior horn cells), their axons, neuromuscular junction, and muscle fibers (►Fig. 1). DRGs reside outside of the spinal cord and have two major axons: one enters the spinal cord through the dorsal sensory roots and the other exits the spinal foramen to project to the periphery and joins the motor ventral roots to form the “mixed” spinal roots. The centrally bound axon of the DRGs is not assessed in standard NCS, although their apparent preservation can have localizing value in case of lesions proximal to the DRG such as radiculopathies (see later).
However, any lesions distal to the DRG will result in loss of sensory responses in NCS that can be helpful in localization. The anterior horn cells, in contrast, send their projecting axons through the ventral roots. After exiting the spinal foramen, the mixed spinal roots usually give off posterior branches that innervate posterior trunk muscles and supply sensory innervation to trunk and proximal areas. They also give off anterior branches that innervate the extremities and anterior trunk. These anterior branches join complex connections in the cervical and lumbar areas and form the brachial and lumbosacral plexuses. Individual nerves are subsequently derived from the plexuses that innervate each individual skeletal muscle and supply innervation to the entire skin, muscle spindles, and Golgi tendon organs. The basic functional unit of the motor system, the motor unit, mirrors this anatomical organization to some extent: a motor neuron, its axons, the neuromuscular junction, and the muscle fibers that it innervates comprise a motor unit. Dysfunction along any of the components of the motor unit Seminars in Musculoskeletal Radiology
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may result in weakness. However, physiologic changes attributable to the dysfunction of each component can differ and be studied using EDS. For example, EMG with a needle electrode can provide information about different motor units within a given muscle. The sensory system is somewhat simpler in functional organization because it lacks a synapse in the peripheral nervous system, although the same principles of signal propagation apply. Signal propagation through the axons, sensory or motor, is achieved with action potentials, an all-or-none phenomenon. In unmyelinated axons, action potentials travel from the axon hillock toward the synapse rather continuously. In myelinated axons, salutatory conduction occurs from a node of Ranvier to the next. Nodes of Ranvier, enriched in voltage-gated sodium channels, are sandwiched in between two myelinated segments, each with its own Schwann cell. Neuropathies can be categorized based on their demyelinating, axonal, or mixed features. They can also be categorized based on the distribution and selective groups of the nerves they affect. Most neuropathies have a predilection for longer nerves, the so-called length-dependent neuropathies (e.g., diabetic neuropathy) and present as paresthesias in a stocking-glove distribution. Typically, axonal neuropathies present as length-dependent symmetrical neuropathy with the longest nerves of the body (i.e., those innervating the feet) being affected before shorter nerves (e.g., those innervating the thighs). Other neuropathies may affect the nerves in a non– length-dependent but symmetrical fashion, and proximal muscles may be equally or even more affected than distal ones. Typically, demyelinating neuropathies behave in this manner (e.g., chronic inflammatory demyelinating polyradiculopathy). In other neuropathies, the findings may be patchy, focal, multifocal, or asymmetric. Lesions affecting the cell body of the nerves (neuronopathies) or structural lesions of the nerve(s)/plexus may present in this manner.2 Standard NCS can only assess myelinated axon electrical conduction in aggregate form. They give little to no information about unmyelinated axons and their integrity and cannot assess individual axons. For example, patients with small fiber neuropathy that selectively affects small unmyelinated fibers, which usually transmit pain and temperature sensation, may have normal nerve conduction studies. NCS can help categorize these findings and aid in narrowing down the diagnostic possibilities, and the principles discussed here will become important in the interpretation of different measured components of EDS (see later).3
or mixed sensory motor symptoms, small fiber versus large fiber or length-dependent versus non–lengthdependent neuropathy versus neuronopathy may need to be in the differential diagnosis, respectively. For generalized motor symptoms, motor neuron disease, motor neuropathy, neuromuscular junction transmission defect, or myopathy may need to be considered. The choice of an electrodiagnostic procedure (i.e., NCS, EMG, and repetitive nerve stimulation [RNS] is guided by the appropriate differential diagnosis (►Fig. 2). 2. A routine study begins with NCS, which is an examination of conduction along peripheral motor and sensory nerves, and with testing for late responses. Next, EMG, which is a direct examination of skeletal muscle using needle electrodes, is performed to determine the pattern and degree of muscle abnormality to evaluate for myopathy or denervation changes. RNS at slow and fast rates is performed only if indicated to evaluate the neuromuscular junction. 3. Arriving at a diagnostic interpretation: This includes defining the possible anatomical site of the lesion (motor neuron, root, plexus, nerve, neuromuscular junction, or muscle), its extent (focal versus diffuse), and the possible pathologic process (axonal loss versus demyelination, inflammatory versus metabolic myopathy), giving clues as to the etiology and commenting on the prognosis, based on the clinical and electrodiagnostic examination.
Nerve Conduction Studies Technique and Principles As the name implies, NCS measure electrical signal propagation along a given nerve. In principle, the operator stimulates the nerve at one site and measures the electrical response at another. Electrical stimulation of a nerve generates action potentials. Smaller nerve fibers usually reach the threshold at lower currents of stimulation. As the intensity of the stimulation is increased, additional larger axons become stimulated until a point when additional stimulation does not recruit additional
Components of a Complete Electrodiagnostic Evaluation 1. History taking and neuromuscular examination, which lead to the differential diagnostic possibilities and a plan of evaluation. For focal sensory and/or motor symptoms, the question is generally an entrapment neuropathy versus radiculopathy. For focal motor symptoms, motor neuronopathy, radiculopathy, plexopathy, or motor neuropathy may be the consideration. For generalized sensory Seminars in Musculoskeletal Radiology
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Fig. 2 Components of a complete electrodiagnostic study. EMG, electromyography; NCS, nerve conduction study; RNS, repetitive nerve stimulation.
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Motor Nerve Conduction Studies (►Fig. 3) In simple terms, motor NCS evaluate the electrical signal propagation in myelinated motor axons. The motor nerve is stimulated
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proximal to the muscle it innervates with the recording electrodes placed over the muscle. The measured response is the aggregate muscle fiber action potentials, that is, compound muscle action potential (CMAP). Different components of the CMAP can be obtained and measured, each one most reflective of a subgroup of motor axons and their integrity.
Distal Latency Distal latency refers to the time (in milliseconds) from stimulus onset to the first detection of CMAP deflection. It includes the time for motor nerve action potential (through the fastest conducting myelinated axons) to travel from the stimulation site to the neuromuscular junction, synaptic vesicle release, postsynaptic depolarization, and finally muscle action potential. Under most circumstances, variability in distal latency can be attributed to the change in motor nerve action potential conduction time. In essence, distal latency depends most on the integrity of the largest myelinated motor axons. In practice, a prolonged distal motor latency indicates demyelination or loss of the largest myelinated axons in the segment of the nerve between stimulating and recording electrodes.
Amplitude and Area Under the Curve CMAP amplitude is the voltage (in millivolts) change measured from the baseline to the negative peak of CMAP waveform. In other words, CMAP amplitude depends on
Fig. 3 Sensory and motor nerve conduction study (NCS) along with F waves and H reflex.
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axons. This is the so-called supramaximal stimulation. NCS can be reliably obtained only if each nerve is studied at supramaximal stimulation. Over- and understimulation can both result in unreliable and aberrant measurements. As a result, most reliably assessed nerve segments usually course close to the skin. Proximal and deeper nerves are more difficult to assess.4 Another important issue is the appropriate recording of electrode placement and knowledge of standard stimulation sites for each nerve. Misplaced electrodes can result in falsepositive results. Cold temperature can also exaggerate sensory nerve action potential amplitude and underestimate conduction velocity. Surface skin temperature can be measured and taken into account when interpreting a study. Three different types of NCS can be performed in principle: motor, sensory, or mixed NCS. Sensory and motor conduction studies are used most frequently. For each measurement, different variables can be obtained, each containing information about a component of the nerve and the population of myelinated axons it is made up of. Late responses, F wave and the H reflex, can help provide information for more proximal parts of the peripheral nervous system albeit with less specificity. These are discussed later.5
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the peak of an aggregate measurement (i.e., CMAP), and as a result, it depends on synchrony as much as each individual motor unit action potential amplitude. In simpler terms, CMAP amplitude is an aggregate of the most synchronous muscle fiber action potentials. In a normal nerve it usually estimates the number of intact motor units. The innervation ratio of motor axons is usually constant. So, in most typical cases, a low CMAP amplitude reflects motor axon loss. However, demyelinating lesions distal to the stimulation site or severe neuromuscular junction dysfunction or severe myopathies can result in low CMAP amplitude. In an acute injury (e.g., traumatic nerve injury), before collateral sprouting and reinnervation can occur, the degree of loss of CMAP amplitude can be used to estimate the severity of motor axon loss. This is usually compared with CMAP amplitude on the unaffected side. However, after reinnervation and collateral sprouting occur, CMAP amplitude will improve over time. In those circumstances, the degree of CMAP decrement will underestimate the extent of axonal loss. In other words, the innervation ratio of each intact motor axon increases and should be taken into account in estimating severity. In these cases, needle EMG can help in evaluation. Area under the curve (AUC) refers to the surface area under the negative portion of the CMAP waveform and in effect is a product of time and voltage. AUC more accurately estimates the total number of intact axons because it does not rely on synchrony. In a normal nerve, it is less useful. However, in cases of demyelinating disease, it is a better estimate of axon integrity than CMAP amplitude. For example, in pure demyelinating lesions of the motor nerves, in spite of complete preservation of motor axons, CMAP amplitude may be reduced (owing to dyssynchrony of muscle fiber action potentials), but the AUC would remain unchanged.
Conduction Velocity Conduction velocity refers to the velocity of signal propagation along a given nerve segment. As discussed earlier, motor distal latency includes the time required for motor nerve conduction to the neuromuscular junction (NMJ), but also the time needed for NMJ transmission and muscle action potential generation. To measure the motor nerve conduction velocity, two different sites of the motor nerve are stimulated, and distance between the two is measured. The difference in the motor distal latency between the proximal and distal site of stimulation cancels out all the components except the time for motor conduction in the segment between stimulation sites. Thus motor nerve conduction velocity can be reliably measured. Because it depends on distal latency, conduction velocity estimates the maximum velocity of the fastest (i.e., largest) conducting myelinated motor axons.
Duration CMAP duration is usually measured in the negative phase, the time between the first negative deflection until the Seminars in Musculoskeletal Radiology
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return to baseline. Duration depends on the lowest and highest (i.e., range) conduction velocities of motor axons and estimates synchrony. Under normal physiologic conditions, the more proximal the stimulus site, the longer the CMAP duration. However, this change is usually minimal albeit detectable. In focal segmental demyelinating disease, the dyssynchrony is exaggerated the most and prolongation of CMAP duration ensues. Diffuse and homogeneous demyelinating disease (e.g., Charcot-Marie-Tooth disease type 1) and nonselective motor axonal loss have more subtle effects on CMAP duration.
Sensory Nerve Conduction Studies As the name implies, sensory NCS evaluate the sensory nerves. A sensory nerve is stimulated at one site, and sensory nerve action potential (SNAP) is measured at the recording site (►Fig. 3). Sensory NCS can be performed orthodromically (i.e., the same direction as physiologic action potential conductance) or antidromically. Sensory nerve action potentials have much lower amplitudes (microvolts) compared with CMAP (millivolts) and are much more prone to artifact. So as a whole they are more technically challenging to perform. However, interpretation of sensory NCS can in some ways be easier.
Latency SNAP latency can be measured from the negative deflection peak or at the onset. Some laboratories use the peak latency because it is more reliably pinpointed for measurement, but sensory nerve conduction velocity cannot be deduced from it. Other laboratories use onset latency and report nerve conduction velocity measurements. Unlike distal motor latency, sensory onset latency measurement does not depend on synaptic transmission and is solely reflective of the fastest conducting sensory axons. As a result, sensory nerve conduction velocity can be used instead of the latency measurement.
Amplitude SNAP amplitude is routinely measured from the negative peak to the positive peak of the waveform (in microvolts). Similar to CMAP amplitude, SNAP amplitude is the aggregate measure of all individual sensory fibers. However, SNAP amplitude is more prone to normal physiologic measurement confounders such as dispersion or phase cancellation. As a result, most SNAP amplitudes are measured at fixed and standard distances from the recording electrodes.
Conduction Velocity Sensory nerve conduction velocity (NCV) can be measured by using a single stimulation site, as previously described. The distance between the recording and the stimulating electrodes is measured on the skin surface, and the onset latency is used as time. Similar to motor conduction velocity, sensory NCV is the conduction velocity of the fastest conduction (i.e., largest) myelinated sensory axons.
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Late Responses
Electromyography (Needle EMG)
The motor and sensory nerve conduction study techniques just described mostly assess distal nerve segments. Although proximal nerve segment stimulation can be achieved, the results tend to require higher stimulation intensities and may be associated with unreliable results due to technical issues such as stimulation of adjacent nerves, difficult-to-reach supramaximal stimulation, and patient discomfort among others. In addition, the most proximal portions of the nerve trunks, plexuses, and roots still cannot be assessed. Late responses, the F response and the H reflex, are used routinely to assess the most proximal portions of the nerve. They are much more limited compared with distal nerve segment studies but can add valuable information, especially when the abnormalities are limited to the most proximal portions of the nerves.
Needle EMG is an important part of EDS and complements the NCS. Information obtained from EMG can help confirm suspected pathologic processes and assess the distribution of abnormalities effectively. Given the discomfort associated with EMG and the large number of muscles that could be potentially studied, the operator should have a detailed knowledge of anatomy and most importantly a hypothesis-driven approach to avoid subjecting the patient to uncomfortable and unnecessary studies. The EMG needle in essence is an electrode that is inserted into the muscle and samples the electrical activity of muscle fibers of a single motor unit in the area immediately around it. Two major components of needle EMG include evaluation of spontaneous activity at rest and assessment of the voluntary motor units upon activation.
F Responses The F response, or F wave, is a late motor response. Similar to motor NCS, it is measured over the muscle. When a distal nerve segment is stimulated, the electrical signal travels in both directions, distally and proximally. CMAP is measured first (M response), which is the result of the distally traveling electrical signal, in other words from the stimulation site toward the muscle. The proximally traveling signal reaches the anterior horn cells in the spinal cord. A few of these motor neurons may backfire action potentials, which will again reach the muscle, although much later than the original M response. The F response can be obtained from nearly all motor nerves. In addition to its longer latency, the F response also has a much lower amplitude, representing the smaller number of motor units that are activated at the level of the spinal cord. Different components of the F response can be measured, such as its persistence, latency, chronodispersion, and amplitude. However, the most reliable and useful measure is probably the F-wave motor latency, an indirect assessment of the entire motor nerve including its proximal portions. An abnormal distal segment study is sufficient to cause an abnormal F-wave latency. Therefore, an abnormally prolonged F-wave response is most helpful when distal segment studies are normal because it localizes the lesion to the proximal portions of the motor nerve.
H Reflex Unlike the F response, the H reflex is a true reflex with a sensory afferent and a motor efferent portion. Due to technical issues, it is most reliably measured in the lower extremities from the tibial nerve. The afferent sensory signal travels the Ia sensory fibers to the spinal cord. After synaptic transmission onto α motor neurons, a motor response is elicited and measured over the muscle. Similar to the F response, the latency is most commonly used in interpretation. A prolonged or absent H reflex is in general nonspecific and can be seen in polyneuropathy, proximal neuropathy, plexopathy, or radiculopathy.
Spontaneous Activity Normal muscle fibers at rest do not usually show any spontaneous electrical activity. Two major exceptions include endplate noise (near the neuromuscular junction) and endplate spikes. Both have a characteristic appearance that differentiates them from abnormal spontaneous activity. Endplate noise is the result of miniature endplate potentials, the subthreshold depolarization potentials that occur as a result of normal quantal releases of acetylcholine at the NMJ. Endplate spikes are muscle fiber action potentials that are also found near the NMJ, and they have a characteristic initial negative (upgoing) deflection. They most commonly result from irritation of an axonal twig near the NMJ by the needle. Abnormal spontaneous activity can be broadly classified into those originating in abnormal muscle fibers or abnormal nerve fibers. They each have a particular appearance morphologically as well as acoustically and can be differentiated readily by the experienced EMG physician. Explanation of each abnormal pattern is beyond the scope of this article. ►Table 1 summarizes the major characteristics of the most commonly encountered spontaneous activity on needle EMG testing.
Voluntary Motor Unit Action Potentials Voluntary motor unit action potentials (MUAPs) are assessed when the patient voluntarily contracts a muscle after the needle electrode is placed. Morphology, duration, and characteristic appearance of MUAPs may differ from muscle to muscle. In addition, older patients may have MUAPs that are longer in duration. In general, increased duration and amplitude of MUAPs suggest denervation with subsequent reinnervation via collateral sprouting. Short duration and small amplitude MUAPs are most indicative of a myopathic process. With experience, one can recognize abnormalities of MUAP morphology readily, especially based on the company they keep in NCS and the recruitment pattern. Recruitment is another important physiologic measure of motor unit physiology that can help differentiate neurogenic
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Table 1 Spontaneous activity in needle electromyography Spontaneous activity
Source
Characteristics
Most common causes
Endplate noise
MEPPs
Irregular, usually negative, 20–40 Hz
Normal, found near the NMJ with endplate spikes
Endplate spikes
Terminal axon/twig
Irregular, initial negative deflection
Normal, found near the NMJ
Fibrillation potentials
Muscle fiber
Mostly regular, biphasic or triphasic, 10–100 µV
Active denervation, inflammatory myopathies and dystrophies
Positive sharp waves
Muscle fiber
Mostly regular, initial positive and a prolonged negative phase, 10–100 µV
Similar to fibrillation potentials
Complex repetitive discharges
Muscle
Groups of complex spikes that repeat at high frequency (20–150 Hz)
Chronic neuropathy or myopathy
Myotonia
Muscle fiber
Brief spikes that fire 20–150 Hz with a waxing and waning pattern
Myotonic disorders, acid maltase deficiency, myotubular myopathies, rarely denervation
Fasciculations
A single motor unit
Low frequency (1–2 Hz), irregular
Normal variant, motor nerve pathology (i.e., motor neuron disease, radiculopathy, etc.)
Myokymia
Motor unit
Rhythmic, grouped, repetitive discharges, 5–60 Hz
Radiation induced neuropathy
Cramps
Motor units
Painful, involuntary muscle contraction, high frequency, irregular firing of MUAPs
Benign, neuropathy, metabolic myopathies or endocrine disease
Neuromyotonia
Motor units
High frequency (150–300 Hz), decrementing, discharges
Autoimmune channelopathies (e.g., Isaac syndrome), other rare conditions
Abbreviations: MEPP, miniature endplate potential; MUAP, motor unit action potential; NMJ, neuromuscular junction.
Table 2 Repetitive nerve stimulation Condition
RNS 2–3/s
RNS 10–25/s
Normal
Decrement up to 10%
Increment < 50%
Myasthenia gravis
Decrement > 10% in weak muscles
Lambert-Eaton myasthenic syndrome
May decrement > 10%
Often increment > 50%
Abbreviation: RNS, repetitive nerve stimulation.
or myogenic disease. However, interpretation of recruitment abnormalities especially in mild cases can be difficult. Reduced recruitment refers to a decrease in the number of MUAPs available for voluntary activation. It is most commonly found in neurogenic disease, either demyelinating or axonal. Early recruitment refers to the activation of multiple motor units for the degree of contraction elicited. It probably represents the reduction in motor unit contraction force due to loss of muscle fibers as occurs in myopathies. As a result, to maintain the same force, many more MUAPs need to be activated, leading to “early” recruitment.6
muscular transmission.7 The test procedure is exactly the same as for motor conduction studies. RNS can also be performed on abductor digit minimi, biceps, deltoid, trapezius, and facial muscles. Proximal muscles give a higher percentage of positive results for myasthenia gravis, and distal muscles can be used for presynaptic disorders of neuromuscular junction. Low rates (2–3 Hz) are used for testing for postsynaptic disorders; high rates (20–50 Hz) are used for presynaptic disorders. ►Table 2 summarizes the RNS findings in pre- or postsynaptic disorders of neuromuscular transmission
Repetitive Nerve Stimulation
Summary
RNS tests for myasthenia gravis, Lambert-Eaton myasthenic syndrome, botulism, or other suspected disorders of neuro-
EDS can be invaluable in diagnostic evaluation of patients with peripheral nervous system disease. However, their
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Electrodiagnostic measure
Myopathies
Neuropathies Axonal
Demyelinating
Distal latency
Normal
Normal or mildly prolonged
Prolonged
Amplitude
Normal; may be reduced
Reduced
Normal; reduced if demyelination distal to stimulation site
Conduction velocity
Normal
Normal or mildly reduced
Reduced
Late response latency
Normal
Normal or mildly prolonged
Prolonged
Spontaneous activity
PSW, Fibs, myotonia, CRD
PSW, Fibs, myokymia, fasciculations, CRD, etc.
Usually none
Recruitment
Early
Reduced
Reduced
MUAP amplitude
Reduced
Increased
Unchanged
MUAP duration
Reduced
Increased
Unchanged
Abbreviations: CRD, complex repetitive discharges; Fibs, fibrillation potentials; PSW, positive sharp waves.
Table 4 Findings in different diseases Sensory NCS
Motor NCS
Needle EMG
RNS
Distribution
Motor neuron disease: ALS, polio, SMA
Nl
As in motor axonal neuropathies
Spontaneous activity and MUAPs as in axonal neuropathies but diffusely
–
Cranial, cervical, thoracic, LS
Radiculopathy: disk/tumor
Nl
Axonal loss in root distribution
Focal denervation as in axonal neuropathies
–
C5–C7 or L4–S1 myotome
Plexopathy: immune/malignant
Sensory axon loss
Motor Axonal loss in plexus distribution
Denervation in plexus distribution
–
Brachial or LS plexus distributions
Axonal neuropathy: metabolic, toxic, inherited, inflammatory
Sensory axonal loss
Motor axonal loss
Denervation in length-dependent distribution
Length-dependent distribution
Demyelinating neuropathy: GBS, CIDP, MMN, CMT1a
Sensory demyelination
Motor-demyelinating features
Reduced recruitment
Focal- entrapments Multifocal MMN Generalized: GBS, CIDP Generalized uniform CMT
Botulism/LEMS
Nl
Reduced CMAP
Nl or may show instability of the MUAP
High-rate RNS shows an increment response
Diffuse
Myasthenia gravis
Nl
Nl
Nl or may show instability of the MUAP
Low-rate RNS shows a decrement response
Ocular, bulbar, proximal more than distal
Myopathy
Nl
Nl
Myopathic MUAPs with or without abnormal spontaneous activity
Proximal more than distal
Abbreviations: ALS, amyotrophic lateral sclerosis; CIDP, chronic inflammatory demyelinating polyradiculopathy; CMAP, compound muscle action potential; CMT1, Charcot-Marie-Tooth neuropathy type 1; EMG, electromyography; GBS, Guillain-Barré syndrome; LEMS, Lambert-Eaton myasthenic syndrome; LS, lumbosacral; MMN, multifocal motor neuropathy; MUAP, motor unit action potential; NCS, nerve conduction study; Nl, normal; RNS, repetitive nerve stimulation; SMA, spinal muscular atrophy. a Inflammatory demyelinating neuropathies are multifocal diseases with signs of demyelination that vary between nerves as well as along the length of the nerve. Seminars in Musculoskeletal Radiology
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Table 3 Basic abnormal findings
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interpretation requires a hypothesis-driven approach that depends on clinical information and physical examination findings. In principle, Bayesian methods of reasoning drive the choice of nerves and muscles studied both in NCS and needle EMG. In electrodiagnosis, the plan of the examination is as important as the interpretation of the results. An electrodiagnostic plan is not static and may need to be modified as the examination proceeds, for the results initially obtained may suggest additional diagnostic possibilities not previously considered. An incomplete study whose results are “properly” interpreted is as misleading as a complete study that is poorly interpreted. In the following section, we provide a few tables to overview common abnormalities in electrodiagnostic tests that suggest pathologic processes in muscle or nerve that suggest demyelinating disease, axonal pathology, or mixed processes. As described in this article, these are oversimplified but can be used as a reference for basic interpretation of abnormalities (►Tables 3 and 4).
receive intravenous immunoglobulin, or steroids that are clearly beyond the forte of the test alone. 3. A very frequent error is overcalling a neuropathy “demyelinating” due to a reduced CV. The most common reasons for this are cold limbs, loss of the fastest conducting fibers with reduced amplitudes, and overly strict adherence to normal values such that any CV less than normal is called “demyelinating” even if only 1 to 3 ms below normal. Most demyelinating neuropathies have multiple abnormal findings, not just one or two. 4. For some conditions, normal tests results do not rule out a disease. This may be true in symptomatic radiculopathy, myasthenia gravis, small fiber neuropathies, large fiber sensory dysfunction, UMN dysfunction, timing of NCS (GBS changes may evolve over a period of time and it may take 2–3 weeks for Wallerian degeneration changes to take place after a nerve injury), and proximal nerve dysfunction.8 Similarly, abnormal results may not always be clinically relevant such as carpal tunnel syndrome, subclinical neuropathies, or radiculopathies.
Limitations and Errors in EDS 1. Like the neurologic examination, most conclusions should be supported by more than a single abnormal value especially in generalized diseases. A single abnormal test result rarely indicates a larger problem. A common problem is when the study conclusion is not supported by the data but rather is a clinical conclusion. For example, a study with all normal data inappropriately concluded, “This study is diagnostic of a small fiber neuropathy.” Sometimes a study is reported as “the study is consistent with carpal tunnel syndrome, thoracic outlet syndrome, or radial tunnel syndrome, etc.” with minimal data to support these statements. The study conclusions derive from the study data, whereas a separate clinical correlation conclusion derives from the entire picture. 2. Although study data may allow an educated guess about the etiology, pathogenesis, and treatment, unless supporting data are available, one should be careful of such comments. For example, a study may show mononeuropathy multiplex, but mononeuritis multiplex assumes inflammation that the study could not have shown. Often comments are made that the patient should have surgery,
Seminars in Musculoskeletal Radiology
Vol. 19
No. 2/2015
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Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Boston, MA: Butterworth-Heinemann; 2005:1–23 Kimura J, Machida M, Ishida T, et al. Relation between size of compound sensory or muscle action potentials, and length of nerve segment. Neurology 1986;36(5):647–652 Dorfman LJ. The distribution of conduction velocities (DCV) in peripheral nerves: a review. Muscle Nerve 1984;7(1):2–11 Chaudhry V, Cornblath DR, Mellits ED, et al. Inter- and intraexaminer reliability of nerve conduction measurements in normal subjects. Ann Neurol 1991;30(6):841–843 Barry DT. AAEM minimonograph #36: basic concepts of electricity and electronics in clinical electromyography. Muscle Nerve 1991; 14(10):937–946 Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders: Clinical-Electrophysiologic Correlations. 2nd ed. Boston, MA: Butterworth-Heinemann; 2005:199–213 Cornblath DR. Disorders of neuromuscular transmission in infants and children. Muscle Nerve 1986;9(7):606–611 Chaudhry V, Cornblath DR. Wallerian degeneration in human nerves: serial electrophysiological studies. Muscle Nerve 1992; 15(6):687–693
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