Electrodiagnostic Testing MAJ Min Ho Chang MD

Outline What is EDX? Anatomy & Physiology Nerve Injury Nerve Conduction Studies/Needle Exam Clinical Utility

EMG and Nerve Conduction Studies An extension of the Physical Examination Assess physiology of nerve and muscle Quantitates nerve and/or muscle injury Real time data Provides Useful Data Regarding Nerve Injury Diagnosis - Duration Prognosis - Site Treatment - Type Further Testing - Severity Terminology, EMG by itself does not include NCS

Anatomy & Physiology Motor Unit Anterior Horn Cell Axon Terminal Branches Neuromuscular Junction Muscle Fibers

Epineurium Perineurium Endoneurium Myelin Axons A nerve  is usually made up from a variety of fascicles . Each fascicle is encased by perineurium.  Inside the fascicle are a group of axons bathed in endoneurial fluid. The Endoneurium lines each individual axon and its myelin sheath Each axon has an insulating lining of myelin – a fatty material inside the Schwann cells. Between the fascicles is a fatty material called the interfascicular  epineurium.  The nerve is then wrapped in the main epineurium.  Even if the sensitive living axons are damaged, the conduit made up of epineurium and perineurium will often survive and provide a pathway for regrowing nerves.

Even few damages along nodes of ranvier can cause conduction block, saltatory conduction

Action Potential What makes it excitable is the possibility of depolarization or reversal of this potential. This occurs as the result of gated channels. Gated channels have gates which can open or close to allow particular ions to pass through the channel. They respond to a stimulus such as a voltage change, chemical,  mechanical, or other stimulus which causes them to open. On the cell membrane of a skeletal muscle cell ACh causes the gates of Na+ channels to open, allowing Na+ ions to enter the cell. Because it opposes the existing polarization of ions by letting positive ions into the cell, we say it depolarizes the membrane.  Many such channels opening at once can produce a significant membrane depolarization. Membrane depolarization in turn causes opening of voltage-gated channels (Slide 9) which are sensitive to reduced membrane potential. When a certain amount of depolarization occurs, called the threshold, it results in all of the voltage-gated channels opening and produces an action potential. CFL: Critical firing level

Nerve Fiber Classificaton Fiber Type Function Diameter Conduction Velocity Aα Proprioception, somatomotor, touch 10-20 50-120 Aβ Touch, pressure, extrafusal 4-12 25-70 Aγ Motor to muscle spindle 2-8 10-50 Aδ Pain (esp cold) 1-5 3-30 B Preganglionic autonomic 1-3 3-15 C Pain/temp/postganglionic autonomic/mechanoreceptor <1 <2

NMJ Anatomy Synaptic cleft Acetylcholine Motor end plate

Electrochemical Conduction Acetylcholine In presynaptic vesicles (Quanta=10000) Exocytosis via Ca++ mediated pathway

Muscle Fibers Each skeletal muscle fiber has many bundles of myofilaments. Each bundle is called a myofibril. The myofilaments of a myofibril are arranged in a regular fashion so that their ends are all lined up. This is what gives the muscle its striated appearance. The contractile units of the cells are called sarcomeres. The sarcoplasmic reticulum is a specialized endoplasmic reticulum that stores calcium ions needed for muscle contraction

MUSCLE CONTRACTION Troponin-Tropomyosin complex Calcium Binding Excitation-Contraction Coupling At rest actin and myosin are prevented from contacting each other by two other proteins: tropomyosin and the Ca++ binding protein troponin. Upon stimulation, Ca++ is released from internal stores and binds to troponin which induces a conformational change of tropomyosin and allows actin-myosin interaction. The myosin head can bind hydrolise ATP (loss of one phosphate)to ADP. This gives energy to the myosin head to bind to actin and to bend pushing the acting filaments along. ADP is then resubstituted with ATP and actin and myosin come apart. Hydrolisis of ATP will start another binding and sliding cycle.pushing the actin filament along and resulting in contraction of the cell The transverse tubular systems arise as invaginations of the plasmalemma and ramify as an intricate network within the sarcomere. They are conduits along which the action potential is transmitted to the depths of the sarcomere. The sarcoplasmic reticulum surrounds the myofibrils and ends as terminal cisterns which contain calcium. A pair of cisterns and a transverse tubule forms a triad. When an AP gets conducted down a TT, calicum is released from the terminal cistern which causes sliding of the filaments. This is called E-C coupling.

MUSCLE FIBER TYPES Type 1 Type 2 “Slow Twitch” Small Cell Body Thinner axon Type 2 “Fast Twitch” Larger Cell Body Thicker Axon EMG tests type 1, which is recruited first. Therefore steroid myopathy predominately affecting type 2 fibers can’t be tested for. The central nervous system can increase the strength of muscle contraction by the following: Increasing the number of active motor units (ie, spatial recruitment) Increasing the firing rate at which individual motor units fire to optimize the summated tension generated (ie, temporal recruitment) Both mechanisms occur concurrently. The primary mechanism at lower levels of muscle contraction strength is the addition of more motor units, even though this increases the firing rate of the initially recruited motor units. The recruitment of different units takes precedence over increase in firing rate until nearly all motor units are recruited. At this level and beyond, motor units may be driven to fire in their secondary range to rates greater than 50 Hz.

MUSCLE FIBER TYPES

NERVE INJURY Seddon’s Classification Neurapraxia (Conduction Block) Axonotmesis Neurotmesis Sunderland’s Classification Type 1: Neurapraxia Types 2-4: Axonotmesis Type 5: Neurotmesis

Neurapraxia Demyelination Axon Intact No Wallerian Degeneration Action Potential slowed Prognosis Good This designates a mild degree of neural insult that results in conduction failure across the affected segment. (Conduction Block). It is reversible, and the conducting properties of the nerve above and below the lesion site are NORMAL. Wallerian degeneration does not occur since the axon is intact and there is continuity. It typically occurs from compression and systemic processes that cause local demyelination with AP slowing and failure across the compressed aspect. Large myelinated fibers are more susceptible than small unmyelinated. A mild clinical correlate is the leg falling asleep from crossing our legs. Fibs should not be observed.

Wallerian Degeneration If an axon is severed, the part of the axon distal to the site of injury will disintegrate. Also known as anterograde degeneration. It occurs at the distal stump of the site of injury and usually begins within 24 hours of a lesion. Prior to degeneration distal axon stumps tend to remain electrically excitable. After injury, the axonal skeleton disintegrates and the axonal membrane breaks apart

Axonotmesis Axon disrupted Connective Tissue (endoneurial/perineural) may or may not be intact. Wallerian Degeneration DOES occur Denervation Prognosis depends In Seddon, the endoneurium is intact (as are the peri and epi), but degeneration occurs so one can anticipate denervation of the corresponding musculature and absence of sensory modalities. All tissues become inexcitable distal to the site of injury and the length of recovery depends upon the distance from the lesion to the end organ. Prognosis good in Type 2, and gets poorer with Types 3 and 4.

Neurotmesis Axon and connective tissue disrupted Complete severance of nerve Surgical Repair Poor prognosis Poor prognosis even with surgery

Mechanisms of Recovery Remyelination Collateral Sprouting Regeneration Recovery from peripheral nerve trauma may occur by three mechanisms: remyelination, collateral sprouting of axons, and regeneration from the proximal site of injury. Remyelination is the fastest of these reparative processes, occurring over 2--12 weeks, depending on the extent of the injury. Following degeneration of injured distal axon fragments, collateral sprouts from intact neighboring axons may provide innervation to denervated muscle fibers. This process takes between 2 to 6 months. In cases of severe axonal injury, collateral sprouting is not sufficient to provide innervation to all muscle fibers. Further clinical recovery depends on regeneration from the proximal site of injury, which may require up to 18 months. The timing of recovery depends on the distance of the lesion from the denervated target muscle. Proximal regeneration occurs at a rate of 6--8 mm per day, whereas distal regeneration occurs at 1--2 mm per day [11]. The prerequisite for regeneration is an intact Schwann cell basal lamina tube to guide and support axonal growth to the appropriate target muscle. Schwann cell tubes remain viable for 18--24 months after injury

NERVE INJURY Collateral Sprouting Recovery from peripheral nerve trauma may occur by three mechanisms: remyelination, collateral sprouting of axons, and regeneration from the proximal site of injury. Remyelination is the fastest of these reparative processes, occurring over 2--12 weeks, depending on the extent of the injury. Following degeneration of injured distal axon fragments, collateral sprouts from intact neighboring axons may provide innervation to denervated muscle fibers. This process takes between 2 to 6 months. In cases of severe axonal injury, collateral sprouting is not sufficient to provide innervation to all muscle fibers. Further clinical recovery depends on regeneration from the proximal site of injury, which may require up to 18 months. The timing of recovery depends on the distance of the lesion from the denervated target muscle. Proximal regeneration occurs at a rate of 6--8 mm per day, whereas distal regeneration occurs at 1--2 mm per day [11]. The prerequisite for regeneration is an intact Schwann cell basal lamina tube to guide and support axonal growth to the appropriate target muscle. Schwann cell tubes remain viable for 18--24 months after injury

REINNERVATION (FIBER TYPE GROUPING) In chronic denervating processes such as chronic neuropathy and motor neuron disease, remaining healthy axons sprout and synapse with denervated fibers (collateral reinnervation). As a result of the combined denervation and reinnervation, motor units enlarge, and their fibers, instead of being scattered, come to lie adjacent to one another. In histochemical stains, such motor units appear as groups of myofibers of the same histochemical type (fiber type grouping). When ultimately these motor units lose their innervation and there are no healthy axons left to connect with them, all their fibers shrink together (group atrophy).

For Practical Purposes “Demyelinating Injury” Neurapraxia (Conduction Block) Diffuse Demyelination Good prognosis “Axonal Injury” Axonotmesis Neurotmesis Prognosis depends on length/severity Conduction block refers to the inability of an AP to propagate beyond a specific region of nerve.

NCS/EMG NCS EMG

INSTRUMENTATION Electrodes Active (Recording) Reference Ground GROUND “G1”, “E1” Action Potential Electrical “Noise” Reference “G2”, “E2” No Action Potential Ground Excess Charge GROUND G2 G1

NERVE CONDUCTION STUDIES The recorded AP is composed of multiple subcomponent action potentials arising from the individual fibers of the nerve, each with their own slightly different conduction velocities. The fastest fibers will arrive first

3 Main AP measured Compound Motor Action Potential (CMAP) Sensory Nerve Action Potential (SNAP) Compound Nerve Action Potential (CNAP) The concept of 4cm separation does not apply for a CMAP and applies only for sensory studies. Will not go into detail on finer differences among these studies Summation of action potentials Amplitude – sum of axons polarized Latency – fastest fiber

NCS Parameters Latency Amplitude Conduction velocity determined by conduction velocity of the nerve, neuromuscular junction & muscle Amplitude determined by number of muscle fibers activated Conduction velocity determined by conduction velocity of the fastest fibers

Important Patterns Axonal Loss Demyelination Conduction Block Decreased amplitude Maintain latency Demyelination Prolonged latency Conduction Block 50% drop in amplitude (variable) In order to asses for reduced amplitude, comparison to a previous baseline value, control/reference value, or opposite side is needed. Although axon loss leads to decreased amplitude, the reverse is not always true. (Conduction Block). Mild slowing of CV and prolongation of latency can occur if largest and fastest fibers are lost. At one extreme, all fibers except the fastest ones can be lost. At the other extreme, all fibers except the slowest fibers can be lost…in which case overall velocity cannot be lower than that of the slowest fibers. The slowest fibers tend to be 75% of the lower limit of normal, thus if overall CV is less then 75% lower limit of normal, this suggests something other than axon loss. For latency, if overall latency is greater than 130% the upper limit of normal, the same applies.

Important Patterns Proximal Lesions (Radiculopathy) Sensory Nerve Root Proximal to DRG Peripheral Axon Intact Motor Nerve Root Distal to Anterior Horn Cell Axonal Degeneration Occurs

NERVE CONDUCTION STUDIES: Important Patterns

NEEDLE EMG Summation of MUAP

Needle EMG Parameter Spontaneous Muscle Membrane Electrical Activity Motor Unit Configuration Motor Unit Recruitment

Spontaneous Activity: Electrical Waveforms not under voluntary control Healthy muscle is normally electrically silent at rest Spontaneous Activity is electrical waveforms that are not under voluntary control. Placing a needle in healthy muscle tissue at rest normally results in complete electrical silence

Abnormal Spontaneous Activity Positive Sharp Wave (“PSW”) Same significance as Fib Fibrillation Potential (“Fib”) Membrane Instability Denervation Myopathy Trauma In the presence of instability, the muscle’s resting membrane potential becomes less negative (so increases from -80 to -60 mV), and it will oscillate. Thus it is easier for the fiber to reach threshold and depolarize. Can be triphasic or biphasic. Its regularity typically distinguishes it from an endplate spike PSWs are typically biphasic with an initial positive phase followed by a slow, small negative return to baseline Both are regular with a firing frequency from 0.5 to 10 Hz, sometimes up to 30 Hz.

NEEDLE EMG: Spontaneous Activity Pattern recognition

Motor Unit Analysis Morphology Stability Recruitment Duration Amplitude Phases Stability Recruitment Henaman’s size principle Duration (measured in ms) is the time from initial deflection from baseline to final return to baseline. It reflects and depends on the number of muscle fibers within the motor unit and the dispersion of their polarizations over time, thus the total depolarization of all the single muscle fibers forming one motor unit. Since all the fibers do not depolarize at the same time, the duration will reflect how dispersed the depolarizations are. Duration correlates with pitch, so short duration sound crisp and static-like while long duration sound thuddy. Duration is increased by reinnervation (increased fibers per motor unit) or temporal dispersion. It is decreased by loss of fibers/atrophy.

Common Patterns Axonal Loss Demyelinating Lesion Myopathy PSWs and Fibs present Decreased Recruitment MUAP changes Increased Duration Polyphasia Increased Amplitude Demyelinating Lesion NO PSW’s and Fibs No MUAP changes Myopathy

Common Patterns EMG and NCS changes evolve over time….. Wallerian Degeneration 3-5 days for motor fibers 6-10 days for sensory fibers Reinnervation

Evolution of NCS/EMG Changes Axonal Loss <3 days old No Wallerian Degeneration DISTAL NCS normal!! No PSWs/Fibs Normal MUAPs Decreased Recruitment Distal studies will be normal even though the patient may have clinical weakness and sensory loss

Evolution of NCS/EMG Changes Axonal Loss: 1-6 weeks old NCS: Decreased Amplitude Normal CV* Normal Latency* EMG: Fibs/PSWs present Decreased Recruitment Normal MUAP Can have decreased CV and increased latency if fastest fibers are lost Rule of thumb, hence earliest time for study about 3 weeks

Evolution of NCS/EMG Changes Axonal Loss: Months-Years Later NCS: Decreased Amplitude Normal CV* Normal Latency* EMG: No Fibs/PSWs Decreased Recruitment MUAP Long Duration High Amplitude Polyphasic Amplitude will eventually normalize after years due to regeneration and sprouting. Fibs/PSWs resolve

Evolution of NCS/EMG Changes Demyelination NCS Decreased Conduction Velocity Prolonged Latency Variable changes in Amplitude Normal EMG!! Conduction Block NCS Decreased Amplitude Prolonged Latency EMG Decreased Recruitment Normal MUAPs No PSWs/Fibs Both are not affected by time. Conduction Block abnormalities are found only if NCS is performed across the block and if EMG muscle is tested distal to the block.

Clinical Use Common Entrapment Syndrome Median at the Wrist (CTS) Ulnar at the Elbow Peroneal Palsy at the Fibular Head

Carpal Tunnel EDX Grading Simple Grading Scheme for median neuropathies at the wrist - Mild --> sensory latencies prolonged - Moderate --> motor latencies prolonged - Severe --> motor amplitude reduced and/or evidence of EMG abnormalities on EMG.

CTS Clinical Pearl By 6 months post-surgery, the maximum improvement in latencies will have occurred 1/2 of patients post surgery do not return to normal latencies Must compare to post-operative latencies to pre-op latenciec to determine an unsuccessful surgery If no preoperative latencies, wait another 3-6 months and assess the interval change

Tarsal Tunnel EMG: Footwear and trauma cause low level of spontaneous activity in foot muscles Controversial

Radiculopathy Can confirm the presence of a radiculopathy with or without findings on imaging studies EMG is not needed in all radic patients Most useful w/ multi-level pathology on MRI but inconclusive PE Can help determine location of radiculopathy Multi-level radics present in 12-30% Excludes other possible diagnoses Can determine time course or severity of radiculopathy 1% of lbp, but common request

NCS usually WNL in radics; abnormalities are found on needle EMG SNAP is normal in lesions prox to DRG, and nearly all radics damage nv root proximal to DRG The NCS is done to r/o other conditions, specifically entrapment neuropathy and plexopathy

False positive rates on MRI are 10% (cervical) Radics can be seen without structural abnormalities on MRI Sensitivity ranges from 55-84% Slightly lower compared to MRI Sensitivity increases w/ neurologic abnormalities Specificity ranges upto 90-95% Slightly higher than MRI

EMG Caveats Time Course in Radiculopathy Acute phase: decreased MUAP recruitment but NML morphology Day 10-14: + waves/fibs in paraspinals Day 14-21: + waves/fibs in prox peripheral muscles Day 21-28: + waves/fibs in distal peripheral muscles (up to 5-6 wks total time) MUAP morphology is the same as denervation occurs, but polyphasia (also paraspinalproxdistal muscles) heralds reinnervation (over the course of months, i.e. chronic radic)

Caveats Limitations of Needle EMG May have NML EMG in acute phase If only demyelination is present, EMG can be NML (only sig CB w/ weakness will give decreased MUAP recruitment (rare in radic)) If sensory root is predominantly affected, EMG will be NML Different fascicles may be more or less involved (i.e. some muscles of a particular myotome may be involved while others spared)

Caveats The “double crush” Cervical radic (C6-C7) plus median neuropathy at the wrist C8-T1 radic plus ulnar neuropathy at the elbow Does not infer that radic predisposes to median neuropathy at the wrist

Peripheral Neuropathy

Plexopathy Compression (CABG) Inflammatory (Parsonage-Turner Syndrome) Radiation Injury (Radiotherapy) Traumatic Injury (Traction, laceration, missile) Ischemia (Diabetic amyotrophy)

Neurogenic Thoracic Outlet Syndrome Incidence 1:1,000,000 A partial lower trunk plexopathy or C8/T1 root injury Secondary to prominent C7 transverse process or prominent cervical rib Normal study focused on brachial plexus trunk essentially rules out

Other Pearls Electrodiagnostic studies are a supplement to, and not a replacement, for the history and physical examination Electrodiagnostic results are often time-dependent Electrodiagnostic studies are not “standardized” investigations and may be modified by the practitioner to answer the diagnostic question

EDX Testing

When to order EDX testing Neck/arm pain, back/leg pain, suspected CTS, peripheral neuropathy, weakness, wasting, cramps. Sort out these problems, establish etiology, assess severity, provide objective/prognostic information. Accurate diagnosis leads to effective treatment.

Typical diagnosis for consideration on EDX consultation Mononeuropathy Mononeuropathy Multiplex Radiculopathy Plexopathy (Brachial or Lumbosacral) Anterior Horn Cell Disorders Diffuse neuropathies Cranial neuropathies Neuromuscular Junction Disorders Myopathy Traumatic nerve injury Intervention vs wait Assess improvement 18 month time frame Or to help rule out, not fishing Need to have some clinical suspicion

When Not to order EDX Central Nervous System Disorders (Stroke, TIA, Encephalopathy, spinal cord injury) Multiple Sclerosis Total body fatigue, fibromyalgia Joint pain EDX consult is not a substitute for PM&R/Neurology/Orthopedic etc…

Counseling Patients Inform the patient about the test and the reasons behind it. Give them heads up about what to expect. Small gauge solid needle test portion Electrical stimulation portion Duration of test depends on findings but typically about 60minutes. Not the most comfortable but tolerable for just about anyone. Risks very small. Verbal consent only.

Reading EMG Reports Tailored to referring provider Specific questions from ie Hand surgeon, spine surgeon Fuzzier question, ie generalized weakness Two broad styles Tabular or narrative Most read final impression only Clinical Management usually deferred to referring provider Clinical vs Electro diagnostic impression An outline of the localization, severity, and acuity of the process Notation of other diagnoses that are detected/excluded Explanation of any technical problems

Summary: Utility of EMG/NCS Highly sensitive indicator of early nerve injury Detects dynamic and functional injury missed by MRI Provides information regarding chronicity of nerve injury Provides prognostic data Highly localizing Clarifies clinical scenarios when one disorder mimics another Identifies combined multi-site injury, avoiding missed diagnoses Identifies more global neuromuscular injury with focal onset Provides longitudinal data for charting course, response to therapy

QUESTIONS ?