Current Approaches to Common Neuromuscular Problems
Jasper R. Daube, MD Timothy R. Dillingham, MD, MD Mark B. Bromberg, MD, PhD Robert A. Werner, MD, MS
2008 COURSE A AANEM 55th Annual Meeting Providence, Rhode Island
Copyright © September 2008 American Association of Neuromuscular & Electrodiagnostic Medicine 2621 Superior Drive NW Rochester, MN 55901 Printed by Johnson Printing Company, Inc. ii Current Approaches to Common Neuromuscular Problems
Faculty
Mark B. Bromberg, MD, PhD Jasper R. Daube, MD Department of Neurology Professor of Neurology University of Utah Department of Neurology Salt Lake City, Utah Mayo Clinic Dr. Bromberg began his academic career in basic science research. He Rochester, Minnesota received his doctorate in neurophysiology from the Department of Dr. Daube attended medical school in Rochester, New York at the Physiology at the University of Vermont and conducted research in University of Rochester. His internship in internal medicine was com- the somatosensory and motor systems. He attended medical school at pleted at North Carolina Memorial Hospital in Chapel Hill, North the University of Michigan and completed his neurology training and Carolina and his residency in neurology was completed in Madison, neuromuscular-EMG fellowship there also. He was on the faculty of Wisconsin at the University of Wisconsin Hospital. He completed a the University of Michigan in 1994, when he joined the University of fellowship in clinical neurophysiology both electromyography (EMG) Utah. He is a professor in the Department of Neurology and Director and electoencephalography (EEG) from the Mayo Graduate School of of the Neuromuscular Program, the EMG laboratory, and the Muscular Medicine in Rochester, Minnesota. Dr. Daube is a long-time member Dystrophy Association clinics. His clinical interests focus on amyotrophic of the AANEM and was president of the association when the Executive lateral sclerosis, myasthenia gravis, and neuropathies. His research inter- Office was created in Rochester, Minnesota. His is board certified in by ests are in quantitative EMG, including motor unit estimation (MUNE) both the American Board of Electrodiagnostic Medicine and the American and algorithms for automated motor unit analysis. Board of Psychiatry and Neurology. His interests include EMG, amyo- trophic lateral sclerosis, and neuromuscular disease.
Authors had nothing to disclose.
Course Chair: Timothy R. Dillingham, MD, MS
The ideas and opinions expressed in this publication are solely those of the specific authors and do not necessarily represent those of the AANEM. iii
Timothy R. Dillingham, MD, MS Robert A. Werner, MD, MS Professor and Chair Professor and Chief Physical Medicine and Rehabilitation Department of Physical Medicine and Rehabilitation Medical College of Wisconsin Ann Arbor Veteran's Affairs Medical Center Milwaukee, Wisconsin Ann Arbor, Michigan Dr. Dillingham is professor and chairman of the Department of Physical Dr. Werner is a professor in the Department of Physical Medicine Medicine and Rehabilitation at the Medical College of Wisconsin, in and Rehabilitation (PMR) and Chief of the Physical Medicine and Milwaukee, Wisconsin. Dr. Dillingham graduated from the University of Rehabilitation service at the Ann Arbor Veteran's Adminstration (VA) Washington School of Medicine in Seattle, Washington in 1986. In 1990, Medical Center. He also has a faculty appointment in occupational he completed his residency training in physical medicine and rehabilita- medicine within the School of Public Health and in the Center for tion at the University of Washington. Dr. Dillingham’s electrodiagnostic Ergonomics within Industrial and Operations Engineering. He is a 1983 research assessed needle EMG in persons with suspected radiculopathy. graduate of the University of Connecticut's School of Medicine and com- Health services research and epidemiology are areas of research interest for pleted his PMR residency at the University of Michigan Medical Center. him as well. He recently used Market Scan claims data to determine who He completed a research fellowship sponsored through the National provides electrodiagnostic services in the United States and differences in Institute on Disability and Rehabilitation Research in 1991. Dr. Werner’s study outcomes by different providers in persons with diabetes. interests include electromyography, pain management, and industrial rehabilitation. Dr. Werner is Co director of the Ann Arbor VA Chronic Pain Clinic. He has over 70 publications in peer-reviewed journals and has been successful in receiving grant funding from several sources includ- ing the National Institute of Health, the Center for Disease Control, the National Institute for Occupational Safety and Health, Johns Hopkins University Center for Visual Display Terminals and Health Research, and the United States Postal Service. Dr. Werner has received awards for research writing from the Association of Academic Physiatrists, the American Academy of PMR, and the American College of Occupational and Environmental Medicine. Dr. Werner is on the editorial board for Archives of Physical Medicine and Rehabilitation, Muscle & Nerve, Journal of Occupational Rehabilitation, and Topics in Stroke Rehabilitation. iv
Please be aware that some of the medical devices or pharmaceuticals discussed in this handout may not be cleared by the FDA or cleared by the FDA for the specific use described by the authors and are “off-label” (i.e., a use not described on the product’s label). “Off-label” devices or pharmaceuticals may be used if, in the judgement of the treating physician, such use is medically indi- cated to treat a patient’s condition. Information regarding the FDA clearance status of a particular device or pharmaceutical may be obtained by reading the product’s package labeling, by contacting a sales representative or legal counsel of the manufacturer of the device or pharmaceutical, or by contacting the FDA at 1-800-638-2041. v Current Approaches to Common Neuromuscular Problems
Contents
Faculty ii
Objectives v
Course Committee vi
Electrophysiologic Testing in Generalized Weakness 1 Jasper Daube MD Evaluating the Patient With Suspected Radiculopathy 9 Timothy R. Dillingham, MD, MS An Approach to the Patient With Peripheral Neuropathy 23 Mark B. Bromberg, MD, PhD A Practical Approach to the Patient Presenting With Numbness 31 Robert A. Werner, MD
CME Activity and Faculty Evaluation 37
O b j e c t i v e s —After attending this session, participants will (1) obtain the conceptual framework for patient history and physical examination for common neuromuscular disorders, (2) understand the strengths and limitations of the needle EMG examination in the evaluation of these disorders, and (3) understand the anatomy and physiology of peripheral nerve and muscle and the pathophysiologic changes that occur with common neuromuscular disorders. P rerequisite —This course is designed as an educational opportunity for physicians. A c c r e d i t a t i o n St a t e m e n t —The AANEM is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. CME Cr e d i t —The AANEM is accredited by the ACCME to provide continuing medical education (CME) for physicians. The AANEM designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s) TM. Each physician should only claim credit commensurate with the extent of their participation in the activity. This event is an Accredited Group Learning Activity as defined by the Maintenance of Certification Program of The Royal College of Physicians and Surgeons of Canada. CME for this activity is available 9/08 - 9/11. vi
2007-2008 AANEM COURSE COMMITTEE Anthony E. Chiodo, MD, Chair Ann Arbor, Michigan
Shawn J. Bird, MD Erick A. Grana, MD Simon Zimnowodzki, MD Philadelphia, Pennsylvania Tampa, Florida Chicago, Illinois
Kevin B. Boylan, MD Thomas Y.C. Pang, MD Sasa Zivkovic, MD Jacksonville, Florida Chicago, Illinois Pittsburgh, Pennsylvania
Gary L. Branch, DO David Bryan Shuster, MD Owosso, Michigan Dayton, Ohio
2007-2008 AANEM PRESIDENT Peter D. Donofrio, MD Nashville, Tennessee 1
Electrophysiologic Testing in Generalized Weakness
Jasper Daube MD Department of Neurology Mayo College of Medicine Rochester, Minnesota
INTRODUCTION TABLE 1 Distribution of electromyography diagnoses during 1 year in an academic electromyography laboratory Patients with symptoms of weakness are commonly referred for a nerve conduction study (NCS) and electromyogram (EMG) to look for the one of many different peripheral neuromuscular dis- No abnormalities 3634 26% orders that may account for their symptoms. The identifiable eti- Focal nerve disorders 6098 43% ologies are distributed among myopathies, motor neuron diseases, Peripheral neuropathy 1934 14% polyradiculoneuropathies, and neuromuscular junction disorders Weakness 1480 11% Myopathy 590 4% Motor neuron disease 377 3% Since identifiable causes of weakness make up only 11% of patients Polyradiculoneuropathy 348 3% seen in an EMG laboratory, a well-defined approach should be Demyelinating neuropathy 101 1% available when they do appear. A clinical history to define the tem- Neuromuscular junction 64 <1% poral course, distribution of symptoms, previous testing, previous treatments, and treatment outcomes should be combined with a focused neurological examination. Testing cranial nerves, strength, unrecognized central disorders are referred for an EMG and NCS, gait, tone, reflexes, and sensation before starting the study allows a such as foot drop in a stroke or paraparesis with a spinal cord lesion. much more focused and efficient study. Among these weakness is The electrodiagnostic (EDX) physician should therefore do a limited particularly important for planning the testing. evaluation to assure that the process is not central in origin.
Generalized weakness in the outpatient or inpatient settings can EMG and NCS are a major part of the full evaluation of a patient have very different clinical pictures and approaches to the prob- with each of the peripheral causes of weakness: myopathy, neuro- lems. Fatigue, weakness, cramps, and myalgia are common com- muscular junction disorder, peripheral neuropathy, polyradiculopa- plaints in the outpatient setting, often without definitive findings thy, and motor neuron disease. EMG and NCS include a wide on clinical examination. Hospitalized patients usually have more range of different tests for these disorders that cannot all be per- prominent deficits; in the intensive care unit they may be close to formed on every patient. The EDX physician must select those tests quadriplegic. Thus careful assessment of the clinical weakness is that will most reliably and efficiently define the underlying disorder. needed to identify the clinical problems that must be considered. While a referring physician’s concern about specific clinical entities must be given high priority in determining the tests to select, the re- Patients with weakness are often referred by other physicians for ferring physician usually does not have the expertise and experience EMG and NCS to assess for a specific disorder of concern to them. of an EDX physician. The EDX physician should therefore perform Weakness can occur with both central and peripheral diseases that a clinical examination to determine the tests that will be performed are usually readily distinguished clinically. Occasional patients with focusing particularly on signs of objective weakness. 2 Electrophysiologic Testing in Generalized Weakness AANEM Course
CHARACTERIZATION OF OBJECTIVE CLINICAL With the exception of certain rare muscle disorders, focal pro- WEAKNESS FOR PLANNING EMG AND NCS TESTING cesses require specific approaches to EMG and NCS that will not be discussed in this manuscript. A neurologic examination is critical to planning the EMG and NCS that would most efficiently and accurately define the underlying dis- While there are exceptions, the time course of the disease often order in a patient with weakness. Basic strength testing can guide the provides clues to the specific nature of a peripheral neuromuscular testing by suggesting the likelihood of possible underlying diseases. disease. Acute processes suggest toxic neuropathies or myopathies; Reflex and sensory testing are helpful in selected situations. subacute onset over days to weeks is likely an inflammatory dis- order such as myositis and Guillain-Barre syndrome. Transient Within the group of myopathies, as well as in other neuromuscular disorders are often metabolic, while fluctuating weakness is typical diseases, there can be quite different clinical pictures. For example, of myasthenia gravis. Disorders evolving over years generally are a myopathy may be distal as well as proximal, or neuromuscular genetic or “degenerative” such as the dystrophies and MND. junction diseases may get weaker (myasthenia gravis) or stronger (Lambert-Eaton myasthenic syndrome) with exercise. And there Patient examples will be used to demonstrate approaches to may be mixtures: polyradiculopathy often occurs in association with weakness in different clinical settings. peripheral neuropathy, and is referred to as a polyradiculoneuropathy. The occurrence of such combinations will be identified as equal likeli- Case 1: 67-year-old woman with leg weakness hood of polyradiculopathy and peripheral neuropathy. None the less, there is sufficient similarity of the diseases within each of these catego- • 8-year history of slowly progressive, painless weakness ries to classify them separately in defining the appropriate testing. • 8 years ago - trouble arising from floor • 4 years ago - trouble arising from chair The distribution of the weakness assists in defining the likelihood • 2 years ago - falls, give way of left leg of each of the major types of peripheral neuromuscular disease. The • Denies atrophy, fasciculations, muscle pain, sensory symptoms, determination of likelihood is based on the usual clinical picture or any upper extremity or trunk symptoms of a category of disease and the frequency of its occurrence in the • Previous EMG and NCS normal population. Clinical Examination: Uses upper extremities to arise from seated Each of the diseases could present distribution of the weakness position. with any one of the distributions, but the likelihood varies with the specific type of disease. The major disease groups will be referred • -2 weakness quadriceps with mild, bilateral atrophy to with abbreviations: myopathy (Myop), neuromuscular junction • -1 to -2 weakness left>right finger flexors and wrist flexors (NMJ), peripheral neuropathy (PN), polyradiculopathy (PolyRad), • Remainder of neurologic examination is normal, including motor neuron disease (MND). Likelihood is defined by the greater reflexes and sensory examination than (“>”) signs. EMG/NCS and report- see insert Generalized distribution – clear evidence of weakness in many areas This patient demonstrates the importance of the clinical exami- nation and the information that EDX studies can provide. Each Diffuse = similar weakness in all limb and trunk muscles of these should be kept in mind in performing EDX studies. An Myop > PolyRad= PN > NMJ > MND EMG report will be enhanced for the referring physician by com- Proximal = predominantly in proximal, limb-girdle muscles menting on these. Myop >> PolyRad > NMJ > MND > PN Distal = predominantly in distal limb muscles • Confirm clinical impression PN = PolyRad > MND > Myop > NMJ • Disease type Cranial = predominantly in cranial muscles • Disease location MND > NMJ > Myop > PolyRad > PN • Define severity Asymmetrical = greater weakness on one side, but not focal • Identify subclinical disease (see below) • Define course MND > NMJ > Myop > PolyRad > PN • Identify other associated disease Focal = specific, usually unilateral area, not just asymmetrical Focal weakness is most commonly a mononeuropathy, limited to the distribution of individual nerves, such TOOLS FOR TESTING PERIPHERAL NEUROMUSCULAR as carpal tunnel syndrome or ulnar neuropathy. DISORDERS Radiculopathies and plexopathies are also typically focal in their distribution, a single root or a component of the A patient with objective weakness in one of the defined distribution brachial or lumbo-sacral plexus. listed above on clinical examination will help to determine the type Muscle – rarely, focalweakness may be due to a muscle disease and extent of testing that is needed. The following EDX tools should AANEM Course Current Approaches to Common Neuromuscular Problems 3 be considered for testing. Their specific applications are discussed muscles can define the underlying pathology in most patients. A separately below. normal study makes a neuromuscular disorder an unlikely cause of weakness. Short duration, low amplitude motor unit action- • NCS potentials are typical of a myopathy. Combined with fibrillation • Repetitive nerve stimulation potentials and an excess of polyphasic MUAPs, these findings • EMG suggest muscle fiber necroses and/or regeneration, which can occur • Single fiber EMG (SFEMG) in many myopathies, but especially inflammatory. Myopathies • Interference analysis typically show an increased turns/amplitude ratio with interference • Turns/amplitude pattern analysis.
Variation in the size and shape of a single MUAP with or without NCS short duration is a sign of NMJ disease, but can also occur in neurogenic disorders with denervation and ongoing reinnervation. Motor NCS - Patients with weakness may demonstrate a number Unstable individual MUAPs should be sought in each patient of abnormalities on motor NCS that assist in localizing the process with weakness. along the peripheral neuraxis. A low compound muscle action potential (CMAP) can occur in any of the neuromuscular diseases, More precise identification of the severity of a disorder is aided but are less common in myopathy and NMJ disorders. Slow by quantitation of the duration, amplitude, and phases of 30 or conduction, temporal dispersion, or conduction block are signs of more individual MUAPs. Quantitation of an interference pattern demyelination that suggest acute or chronic, acquired demyelinating with a mixture of superimposed MUAPs can be analyzed by polyradiculopathies (AIDP or CIDP) or a multifocal motor neurop- interference pattern analysis in which the amplitude and turns are athy. Repetitive stimulation with exercise often shows the decrement measured at a fixed force. and/or facilitation of a defect of neuromuscular transmission. Reduced MUAP recruitment with long duration, polyphasic Late responses - Prolonged F-wave latencies or R1 blink latencies MUAPs are evidence of a neurogenic disorder. The presence of are signs of the proximal slowing seen in patients with weakness fibrillation potentials and unstable MUAPs indicate a progressing due to polyradiculopathies, particularly early in the course when disorder, or less likely, ongoing reinnervation. Neurogenic disorders other abnormalities on NCS may not be evident. typically show decreased turns/amplitude ratio with interference pattern analysis. Sensory NCS - Low amplitude sensory responses and/or slow con- duction, especially in the sural or medial plantar nerves in patients SFEMG with weakness without sensory findings, suggest the possibility of a subclinical peripheral neuropathy as might occur in diabetes, Specialized needle EMG recordings with a 500 Hz filter and myopathies such as inclusion body myositis. However, some more rapid sweep settings allow the isolated recording of disorders, such as amyloidosis or sarcoidosis, may affect nerve and individual muscle fibers. Variation in the interval between two muscle (neuromyopathies). fibers in a single MUAP (jitter) can provide very sensitive evidence of a NMJ disorder. Increased jitter with normal or Repetitive Nerve Stimulation mildly short duration MUAPs is the most sensitive test for NMJ disorders, and may be seen in muscles without decrement in Repetitive nerve stimulation testing should be considered in all myasthenia gravis. Increased jitter with long duration, polyphasic patients who complain of generalized weakness, as they will oc- MUAPs is evidence of a progressing neurogenic disorder such casionally identify an unsuspected NMJ disorder. The extent of as MND. testing depends on the level of suspicion of a NMJ disorder; if the suspicion is high, distal and proximal nerve-muscle testing before and Case 2: 20-year-old college student 2 weeks progressive after exercise should be performed in the limbs with greatest weak- generalized weakness ness. A decrement is evidence of a disorder of the NMJ; repair 2–3 minutes after exercise suggests myastheniagravis. Marked facilitation Day 1 Myalgia, headache, sore throat, fever is typical of Lambert-Eaton myasthenic syndrome, especially if the Day 10 Student Health: penicillin for “strep throat”, CMAP amplitudes are low. Repetitive CMAP suggest congenital persistent emesis which requires more extensive complicated, testing that will not be Day 11 Emergency Room - Urinary retention, lethargy, unsteady reviewed here. Day 12 Diplopia, mild proximal weakness, brisk deep tendon reflex (DTR), bilateral Babinski Day 13 Reduced reflexes, progressive weakness, shortness of EMG breath (SOB), tachycardia Day 14 Hospitalized: Head computed tomography and Testing muscle with a needle recording electrode is the single most magnetic resonance imaging scans normal; Cerebrospinal useful study of patients with weakness. Examination of weak fluid (CSF) cells and protein increased 4 Electrophysiologic Testing in Generalized Weakness AANEM Course
EMG Diagnosis – Guillain–Barré with myelopathy, polyradiculoneu- ropathy, and autonomic neuropathy While EMG or NCS testing could be performed first, in a patient Treatment Plan: Start 5 days intravenous immunoglobulin (IVIg) with suspected MND it is often more efficient to begin with EMG/NCS #1 and report – see insert EMG testing, sampling weak muscles in the weakest limb in the EMG/NCS #2 and report – see insert distributions of different nerves and roots. If the abnormalities EMG/NCS #3 and report – see insert are outside the distribution of a single nerve or root, it is most efficient to then move to muscles in another limb, e.g., anterior Case 2 demonstrates the evolution of a clinical disorder in which tibial, medial gastrocnemius and vastus medialis in the leg, or first EMG provides valuable clinical guidance for both prognosis and dorsal interosseous, biceps, and triceps in the arm. If abnormality clinical guidance. All the EMG/NCS abnormalities found in is found in two limbs, thoracic paraspinal muscles at two levels can neuromuscular diseases evolve over time. These changes should be sampled with a goal of finding abnormalities at three levels of be kept in mind in interpreting findings. The typical evolution of the neuraxis. If changes are found at only two levels, or if there EMG findings in a patient with weakness from an acute axonal loss is bulbar weakness, cranial innervated muscles like the trapezius, is shown in Table 2. masseter, or tongue should be tested. Unstable, polyphasic MUAPs can provide evidence of denervation early in the course of the Table 2 Evolution of electromyography findings in an acute neurogenic disease when fibrillations may be minimal. If necessary, diaphragm disorder EMG should be considered.
1 week 2 weeks 6 weeks 6 months Fibrillation Potentials None Some Many None or tiny NCS
(severity dependent) If changes of MND are found on EMG, NCS can be limited to the Recruitment Reduced Reduced Reduced Reduced limb with greatest weakness to be sure there is not a superimposed Phases Normal Polyphasic Polyphasic Normal mononeuropathy or peripheral neuropathy. A critical finding in (polyphasic) distinguishing the changes of a mononeuropathy from MND is Duration Normal (Long) Long Long normal sensory potentials with low amplitude motor responses. Other None Unstable Unstable Complex Repetitive TESTS TO CONSIDER IN A PATIENT WITH SUSPECTED Discharge POLYRADICULOPATHY The remainder of this review will include a brief summary of the approach to weakness in each of the major groups of neuromus- PolyRad are often demyelinating disorders with significant slowing cular disease followed by a detailed review of the considerations in of conduction or conduction block. NCS testing provides the most assessing a patient for possible myopathy. definitive evidence of a PolyRad. NCSs are generally performed first with particular attention to motor NCSs. NCSs in a pure axonal PolyRad will be less informative, but necessary to demon- TESTS TO CONSIDER IN A PATIENT WITH SUSPECTED strate the extent of axonal loss. MND
Evaluation of MND is complicated by the variety of initial presenta- NCS tions both in distribution and clinical manifestations. Amyotrophic lateral sclerosis (ALS), the most common MND, typically presents Starting with the most involved limb, median, ulnar, peroneal, and with focal signs that may be one arm, one leg, bulbar, respiratory or tibial nerves are tested with particular attention to F-wave latencies and trunk in that order of frequency. Presentation may be with purely distal latencies. If conduction velocity is slowed at all distally, the F-wave lower motor neuron, purely upper motor neuron, or a mixture of latency should be compared with an estimated F-latency. PolyRad will signs in each area. Two reliable clues to ALS are: presence of motor typically show more slowing proximally with a longer F-wave latency with no sensory findings, EMG abnormalities outside the distribu- than F-wave latency estimate. If proximal slowing is not clearly shown tion of clinical findings. ALS should be considered in every patient by distal nerve testing, proximal conduction is most efficiently tested with focal deficit if there are no sensory findings, such patients 1) with blink R1 latency. Although technically more difficult, proximal with foot drop, but no pain or sensory loss, hand weakness, but no slowing can also be identified by percutaneous, needle stimulation pain or sensory loss, difficulty swallowing, but no pain or sensory of the nerve “root” (spinal nerve) with recording from the hypoth- loss, etc. Other signs can be helpful in suggesting specific MND. enar, biceps, abductor hallucis, or extensor digitorum brevis muscles. Facial fasciculations suggest Kennedy’s disease; very long standing, minimally progressive, symmetrical, predominantly proximal weak- EMG ness suggests a spinal muscular atrophy, Asymmetric distribution of widespread neurogenic MUAPs with a minimum of fibrillation can If clear evidence of PolyRad is found on NCS, the purpose of EMG be residuals of poliomyelitis. becomes to determine the extent and distribution of axonal loss AANEM Course Current Approaches to Common Neuromuscular Problems 5
(fibrillation potentials). Selected weak muscles in one arm and leg, • Examine multiple areas within a muscle since findings may be and paraspinal muscles are usually sufficient. scattered, giving particular attention to superficial layers where ab- normalities are often more prominent in inflammatory myopathies
TESTS TO CONSIDER IN A POSSIBLE PERIPHERAL • If abnormalities are not found in the limbs, test thoracic paraspi- NEUROPATHY nal muscles at two levels and test cranial muscles with significant weakness Despite the wide variety of forms of PN the approaches are similar with a focus on NCS. Both the axonal and demyelinating forms are • If abnormalities are found in one limb, compare at least one identified by similar testing. The criteria for distinguishing them muscle in the other ipsilateral limb to fully define the distribution should be familiar to the EDX physician, but will not be discussed in this manuscript. • Quantitate MUAPs in the weakest muscles if clear abnormalities are not found
NCS The following NCS protocol is recommended:
Since the disorder is typically distal and length dependent, testing Test the weakest limb with motor NCS and F-waves. If weakness the leg on the most involved side first (or the least involved if is particularly prominent in radial or musculocutaneous innervated there is severe atrophy) including peroneal/anterior tibial, if there muscles, test radial and/or musculocutaneous nerves for focal are no responses distally. F-wave testing is important to identify slowing or conduction block to exclude multifocal motor neuropa- combined PN and PolyRad. If both disorders are present the thy with conduction block F-wave latency and F-wave latency estimate will be similar; if there is no PolyRad, the F-wave latency will be shorter than the If there is a history of fatigable weakness, look for NMJ disorders by estimate. It is particularly important to compare proximal and testing repetitive stimulation before and after exercise in clinically distal amplitudes and configuration. Significantly lower ampli- weak muscles, (e.g., accessory/trapezius, musculocutaneous/biceps, tude with proximal stimulation can identify a focal conduction axillary/deltoid, femoral/rectus femoris). block (distinct from focal slowing); an irregular spreading of the CMAP shape identifies temporal dispersion, another sign of a Findings in Myopathy demyelinating process. The distribution of abnormality in many myopathies, especially inflammatory is proximal and paraspinal, but often with prominent EMG changes in the anterior tibial muscle. A few myopathies, especially fascio scapulo humeral (FSH) dystrophy and DM2 myotonic dys- The purpose of EMG is primarily to confirm the extent and trophy may have different findings in muscles near each other or be distribution of axonal loss (fibrillation potentials), and should asymmetrical. These require more sampling to identify. A limited test distal, proximal and paraspinal muscles if there are any number of myopathies have distal weakness, especially the relatively clinical or NCS signs of proximal involvement. EMG of distal common inclusion body myositis (Table 3). arm muscles often demonstrates axonal loss with not clinical signs, usually only long duration motor unit potentials. If no Table 3 Myopathies with predominantly distal weakness fibrillation potentials are found in standard muscles, intrinsic foot muscles (abductor hallucis and dorsal interossei) will often show abnormality. _o Inclusion body myositis - usually o Polymyositis - infrequently o Centronuclear myopathy (dynamin 2) TESTS TO CONSIDER IN A POSSIBLE MYOPATHY WITH A o Nebulin distal myopathy FOCUS ON INFLAMMATORY MYOPATHIES o Central core myopathy o Myotonic dystrophy o Distal dystrophies While either EMG or NCS testing could be performed first, in a pos- o Amyloid sible myography it is often more efficient to begin with EMG testing, sampling weak muscles in the weakest limb in the distributions of MUAPs in a myopathy become shorter in duration and lower different nerves and roots. in amplitude as muscle fibers are destroyed by the disease. The changes are typically proportional to the weakness. In severe disease The following needle EMG protocol is recommended: MAUPs may have only a tiny potential from one remaining fiber in the MUAP. Increased MUAP turns and phases results from dif- • Test two or three of the weakest muscles and a less involved ferential fiber conduction velocity with loss of synchrony because muscle searching for fibrillation potentials, unstable MUAPs and of fiber atrophy or small regenerating fibers. SFEMG also shows short duration and/or polyphasic potentials abnormalities with increased jitter due to reinnervation, and in- 6 Electrophysiologic Testing in Generalized Weakness AANEM Course creased fiber density due to fiber splitting and reinnervation. Early TABLE 6 Major Categories of Inflammatory Myopathies Listed by in the course of a myopathy, the findings may be patchy or subtle, Density of Fibrillation requiring widespread and thorough sampling of muscles. Keep in mind each of the neuromuscular disorders that may show short Polymyostis duration MUAPs (Table 4). Dermatomyositis Inclusion body myositis Disorders that can result in short duration MUAPs Table 4 Overlap syndromes Connective tissue diseases sometimes with neuropathy
Scleroderma o Myopathy with muscle fiber destruction o Neuromuscular junction disorders with severe block or end Sjogrens plate destruction Systemic lupus erythematosus o Periodic paralysis and other membrane disorders Rheumatoid o Neuropathy with primarily nerve terminal damage Penicillamine o Late stage, severe neurogenic disorder Amyloid o Early regeneration after a severe neurogenic process Bacterial myositis – Clostridia, tuberculosis, Lyme, syphilis, Whipple’s MUAPs = motor unit action potentials disease Viral myositis – human immune deficiency virus, Coxackie, influenza EMG is limited in its ability to distinguish between different eti- Parasitic myositis – trichinosis, toxoplasmosis, cystercycosis, ologies. Although the findings reflect the underlying muscle fiber echinococcus pathology and physiology, pathologic changes in different disorders Sarcoid myopathy may produce similar EMG changes such that the findings are not Eosinophilia-myalgia syndrome Focal myositis specific for individual diseases. The absence of abnormal MUAP Vasculitis changes in a clearly weak muscle can occur in some endocrine or metabolic myopathies, especially steroid myopathy. Other discharges have varying significance. Complex repetitive discharges indicate long duration of disease, but do not suggest a Fibrillation potentials occur by a number of mechanisms, including specific type. A limited number of myotonic discharges can be seen segmental necrosis of fibers, fiber splitting, and from regenerating in many myopathies and in long-standing neurogenic processes. If muscle fibers. Fibrillation potentials may be few in number and they are more prominent, specific diseases listed in Table 7 should scattered. They tend to fire slowly at less that 4 Hz. Positive wave- be considered. form fibrillation potentials are often seen. Muscle fiber atrophy results in very tiny MUAPs in long-standing disease. Myopathies Table 7 Myopathies with myotonic discharges with fibrillation potentials are listed in Table 5.
Table 5 Myopathies with fibrillation potentials Myotonic dystrophy, both DM1 and DM2 Paramyotonia congenita Myotonia congenita o All inflammatory myopathies Hyperkalemic periodic paralysis o Inclusion body myositis - often with a mixture of short and long Potassium sensitive myotonia duration motor unit action potentials Centronuclear myopathy o Critical illness myopathy Hypothyroid myopathy o Congenital myopathies - centronuclear, nemaline, congenital fiber- Statin-associated myopathy type disproportion Acid maltase deficiency o Muscular dystrophies - dystrophinopathies, fascio scapulo humeral, Amyloid myotonic dystrophy DM1 and DM2, some limb-girdle muscular dystrophy (LGMD), most distal dystrophies o Toxic: acute alcoholic myopathy, lipid lowering drugs The two forms of myotonic dystrophies, DM1 and DM2 differ o Metabolic: acid maltase, other glycogen storage diseases after clinically with myalgia and asymmetry in DM2. Differences in an attack, hyperkalemic periodic paralysis, paramyotonia, response to repetitive stimulation and the character of the myo- K-sensitive myotonia, tonic discharges allow them to be distinguished from each other o Rhabdomyolysis – may be quite prominent and more important from an inflammatory myopathy. o Muscle trauma – including previous surgery and injections A number of reports have shown that the distribution of myotonic The common occurrence of fibrillation potentials in an inflamma- discharges in DM2 is more prominent and may be limited to proxi- tory myopathy and the much greater incidence of inflammatory mal in the legs. It is therefore important to look there. In addition myopathy than other myopathies, make inflammatory myopathy while both DM1 and DM2 have myotonic discharges in DM2 they far more likely in a patient with weakness, short duration MUAPs generally wane rather than wax and wane. The end of slow-waning and fibrillation potentials. There are differences in density of fibril- discharges in DM2 has characteristics that are similar to fibrillation lation potentials among the myopathies as shown in Table 6. potentials. The limited distribution of DM2 and the difference in AANEM Course Current Approaches to Common Neuromuscular Problems 7 pattern can result in a patient having what appears to be fibrillation Table 9 Myopathies more likely to have low compound muscle achm potentials with short duration MUAPs, like an inflammatory myo- potentials amplitudes on nerve conduction studies pathy. A more extensive search for myotonic discharges is needed in some patients with myalgia and minimal weakness who might have DM2. Inflammatory o Inclusion body myositis The abnormalities in inflammatory myopathy evolve over time. o Severe polymyositis Early on the findings are patchy or subtle, requiring thorough- Dystrophies ness and widespread sampling for the short MUAPs and fi- o Distal muscular dystrophies brillation potentials. The MUAPs become more polyphasic o Distal myopathies with disease progression to where they have some features of o Myotonic dystrophy a chronic neurogenic process, including reduced recruitment o Facioscapulohumeral dystrophy o Emery-Dreifuss muscular dystrophy and long-duration MUAPs. In chronic stages, MUAPs become more polyphasic with satellite potentials with mixed short-and Enzyme deficiencies long-duration MUAPs. Mild NCS changes may appear. A long o Debrancher enzyme deficiency standing inflammatory myopathy cannot be readily distinguished o Acid maltase deficiency from inclusion body myositis, whose apparent incidence is in- Other myopathies creasing as specific biopsy staining for the disorder has become o Congenital myopathy more prominent. o Nemaline myopathy o Central core myopathy Before concluding that a patient’s clinical and EMG/ o Centronuclear myopathy NCS findings are due to an inflammatory myopathy, o Myofibrillary myopathy attempts should be made to assure that other mimicdisorders are excluded (Table 8). Table 10 Neuromyopathies
TABLE 8 Disorders to rule out In a suspected inflammatory myopathy Connective tissue disorders
Other Myopathies Systenic lupis Eoythematosus Enzyme deficiencies Rheumatoid arthritis Congenital myopathies Mixed connective tissue disease Necrotizing myopathies Sjogrens Toxins and drugs Polyarteritis nodosa Alcohol Congenital myopathies Ischemia Myofibrillary (desmin) Heat Mitochondrial disorders Injections Metabolic myopathies Hypokalemia Acid maltase deficiency Paraneoplastic Debrancher enzyme deficiency Other neuromuscular disease Mitochondrial disorders Neuromuscular junction disorders Polyradiculopathy Drugs Spinal muscular atrophy Cyclosporin Amyotrophic lateral sclerosis Vincristine Chloroquine Colchicine NCSs in myopathies are usually normal, or show only low am- Other plitude responses if the weakness is sufficiently severe, but others Sarcoidosis should be considered as well (Table 9). Amyloid Slow motor conduction or sensory NCS abnormalities suggest the additional presence of a neuropathy. While long-duration Among the most difficult muscle problems for the EDX physi- MUAPs can occur with chronic myopathies, neuromyopathies cian are patients with myalgia and fatigue who have no weakness are disorders that involve both nerve and muscle directly, and or other clinical deficits. They are often classified and treated as must be considered when these combinations are found. They fibromyalgia, but it must be recalled that some myopathies may occur most commonly in connective tissue diseases, but do have these as primary symptoms (Table 11). Some of them can be occur in other myopathies, particularly drugs or toxins as listed readily identified with EMG and muscle biopsy, but others will in Table 10. require more specific testing. 8 Electrophysiologic Testing in Generalized Weakness AANEM Course
Table 11 Muscle disorders underlying myalgia and fatigue in some Case 4: 29- year-old woman with muscle aches patients Healthy - 5 years muscle aches Mild elevations of creatine kinase (300 - 550) Endocrine Examination normal Hyperthyroid Mild weakness, limited to left triceps Hypothyroid Normal NCS EMG/NCS and report – see insert Metabolic Lipid storage Case 5: 45–year-old interior designer with 3 months Mitochondrial generalized weakness
Drug – cholesterol lowering agents Diplopia brain stem astrocytoma-stable 2 yrs after radiation therapy Inflammatory Temporal lobe herpes simplex virus (HSV) Polymyositis encephalitis-better 1 year after Acyclovir Trichinosis Bulbar dysfunction from tumor-dexameth asme Sarcoid and Temazolamide 2 mo progressive weakness with no other symptoms Dystrophy or signs Myotoric dystrophy DM2 CSF and EMG performed at home - axonal and Becker demyelinating neuropathy Caveolinopathy Hospital transfer - quadriparetic with deep vein Calpainopathy thrombosis Normal reflexes and sensation Clinical Examples of the Application of These Principles MRI 10 mm mass and residuals of HSV EMG/NCS and report – see insert
Case 6: 84-year-old woman with weakness Case 3: 65–year-old woman with fatigue 2 years of difficulty with household chores, “tired” Diabetes mellitus and hypothyroidism with 2 months of Difficulty squatting during exercise painless arm weakness EMG 1 year ago – normal NCS and EMG Examination: Proximal symmetric arm weakness, Limited improvement on Sertaline normal reflexes Examination - mild proximal weakness; normal NCS - normal reflexes, cranial nerves, sensation, gait EMG/NCS and report - see insert EMG/NCS and report – see insert 9 Evaluating the Patient With Suspected Radiculopathy
Timothy R. Dillingham, MD, MS Professor and Chair Department of Physical Medicine and Rehabilitation Medical College of Wisconsin Milwaukee, Wisconsin
INTRODUCTION In the lumbar spine, the attachment and shape of the poste- Cervical and lumbosacral radiculopathies are conditions involving rior longitudinal ligament predisposes the nucleus pulposis to a pathological process affecting the spinal nerve root. Commonly, herniation in a posterolateral direction where it is the weakest. The this is a herniated nucleus pulposis that anatomically compresses a dorsal root ganglion (DRG) lies in the intervertebral foramen and nerve root within the spinal canal. Another common etiology for this anatomical arrangement poses major implications for clinical radiculopathy is spinal stenosis resulting from a combination of EDX of radiculopathy. Intraspinal lesions can cause weakness due degenerative spondylosis, ligament hypertrophy, and spondylolis- to their effects on the motor axons which originate in the ante- thesis. Inflammatory radiculitis is another pathophysiological rior and lateral gray matter and pass through the lumbar spine as process that can cause radiculopathy. It is important to remember, spinal roots. These roots form the “cauda equina,” or horse’s tail, however, that other more ominous processes such as malignancy the name used to describe this anatomic structure. Intraspinal and infection can manifest the same symptoms and signs of radicu- lesions can also produce sensory loss by damaging the dorsal lopathy as the more common causes. roots, which are composed of central processes from the sensory nerve cell bodies in the DRG, as they project to the spinal cord. This manuscript deals with the clinical approach used in an Electrophysiologically, severe axonal damage intraspinally results in electrodiagnostic (EDX) laboratory to evaluate a person with neck spontaneous activity on needle electromyography (EMG) and possi- pain, lumbar spine pain, or limb symptoms which are suggestive of bly reduced compound muscle action potentials (CMAPs). However, radiculopathy. Given the large differential diagnosis for these symp- the sensory nerve action potentials (SNAPs) are preserved. This toms, it is important for EDX physicians to develop a conceptual anatomical relationship provides a mechanism for further confirm- framework for evaluating these referrals with a standard focused ing whether or not a lesion is radicular (intraspinal). A destructive history and physical examination and a tailored EDX approach. intramedullary (spinal cord) lesion at T11 can produce EMG find- Accurately identifying radiculopathy by EDX whenever possible ings in muscles innervated by any of the lumbosacral nerve roots and provides valuable information for treatment and minimizes other manifest the precise findings on needle EMG as those seen with a invasive and expensive diagnostic and therapeutic procedures. herniated nucleus pulposis at any of the lumbar disc levels. For this reason, the EDX physician cannot determine for certain the anatomic location of the lumbar intraspinal lesion producing distal muscle SPINE AND NERVE ROOT ANATOMY: DEVIATIONS FROM EMG findings in the lower limbs. EMG can only identify the root or THE EXPECTED roots that are physiologically involved, but not the precise anatomic site of pathology within the lumbar spinal canal. The anatomy of the bony spine, supporting ligamentous struc- tures, and neural elements provides a unique biomechanical In a prospective study of 100 patients with lumbosacral radiculopa- system that allows tremendous strength, yet flexibility. The thy who underwent lumbar laminectomy, EMG precisely identified interested reader can consult standard anatomy texts for further the involved root level 84% of the time.68 EMG failed to accurately discussions. The important structural issues that relate to radicu- identify the compressed root in 16% of patients. However, at least lopathy are addressed in this manuscript. half of the failures were attributable to anomalies of innervation. 10 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Another component to this study involved stimulating the nerve tion then the examiner should have a heightened suspicion for a roots intraoperatively with simultaneous recording of muscle activ- musculoskeletal disorder. However, whereas a musculoskeletal dis- ity in the lower limb using surface electrodes. These investigators order identified on examination makes a normal EDX study more demonstrated variations in root innervations, such as the L5 root likely, the presence of a musculoskeletal disorder does not exclude innervating the soleus and medial gastrocnemius in 16% of a an abnormal EDX study with reliability or specificity. Common sample of 50 patients. Most subjects demonstrated dual innerva- musculoskeletal disorders that produce symptoms similar to those tions for most muscles.68 produced by a cervical radiculopathy are shown in Table 1.
Regarding the cervical nerve roots and the brachial plexus, there Shoulder impingement, lateral epicondylitis, and de Quervain’s are many anatomic variations. Perneczky described an anatomic tenosynovitis are easily identifiable conditions that are extraordi- study of 40 cadavers where in all cases there were deviations narily common. Even with a positive EDX test showing an entrap- from accepted cervical root and brachial plexus anatomy.47 Levin, ment neuropathy or radiculopathy, treatment of a concomitant Maggiano, and Wilbourn examined the pattern of abnormalities musculoskeletal disorder can often improve overall symptoms. on EMG in 50 cases of surgically proven cervical root lesions.39 A range of needle EMG patterns was found with EMG demonstrat- Common entrapment neuropathies can present with symptoms ing less specificity for the C6 root level, but more specificity and similar to radiculopathy. Median neuropathy at the wrist and consistent patterns for C8, C7, and C5 radiculopathies. In subjects ulnar neuropathy at the elbow are common conditions for which with C6 radiculopathies, half the patients showed findings similar patients are referred for EDX, and complicate the EDX assessment to those with C5 radiculopathies and the other half demonstrated for radiculopathy. Plexopathies such as idiopathic brachial neuritis C7 patterns. can pose diagnostic dilemmas for the EDX consultant as pain, weakness, and sensory loss are all common symptoms in both plex- These findings underscore the limitations of precise localization for opathies and radiculopathies. root lesions by EMG. The EDX physician should maintain an un- derstanding of these anatomic variations to better convey the level of certainty with respect to diagnostic conclusions. COMMON MUSCULOSKELETAL DISORDERS MIMICKING LUMBOSACRAL RADICULOPATHY
COMMON MUSCULOSKELETAL DISORDERS MIMICKING Conditions that present with symptoms similar to those of lum- CERVICAL RADICULOPATHY bosacral radiculopathy are shown in Table 2. In this author’s opinion, one of the most readily treatable, yet under-recognized The symptoms of radiculopathy are nondescript and not specific conditions is trochanteric bursitis and illiotibial band syndrome. for radiculopathy. Many other neurologic and musculoskeletal The illiotibial band originates at the illiac crest and has tendinous conditions can produce pain, weakness, and sensory symptoms. In contributions from the gluteus maximus and tensor fascia latae. It addition to the standard peripheral neurologic examination, one runs the length of the thigh and crosses the knee joint inserting of the most helpful maneuvers is to ask the patient where it hurts, on the lateral condyle of the tibia. This band is part of the fascia then carefully palpate that area. If pain is reproduced by this palpa- lata, a layer of dense strong connective tissue enveloping the thigh
Table 1 Musculoskeletal conditions that commonly mimic cervical radiculopathy
Condition Clinical symptoms/signs Fibromyalgia syndrome Pain all over, female predominance, often sleep problems, tender to palpation in multiple areas Polymyalgia rheumatica >50 years old, pain and stiffness in neck shoulders and hips, high ESR Sternoclavicular joint arthropathy Pain in anterior chest, pain with shoulder movement (adduction), pain on direct palpation Acromioclavicular joint arthropathy Pain in anterior chest, pain with shoulder movement (adduction), pain on direct palpation Shoulder bursitis, impingement syndrome, Pain with palpation, positive impingement signs, pain in C5 distribution bicipital tendonitis Lateral epicondylitis “tennis elbow” Pain in lateral forearm, pain with palpation and resisted wrist extension De Quervain’s tenosynovitis Lateral wrist and forearm pain, tender at abductor pollicis longus or extensor pollicis brevis tendons, positive Finkelstein test Trigger finger, stenosing tenosynovitis Intermittent pain and locking of a digit in flexion of finger flexor tendons
ESR = erythrocyte sedimentation rate AANEM Course Current Approaches to Common Neuromuscular Problems 11 like a stocking. It is extremely strong laterally where it becomes the symptoms. Most radiculopathies present with symptoms in one illiotibial band. Where it crosses the hip, trochanteric bursitis can limb. Multiple radiculopathies such as are seen in cervical spinal occur. The lateral femoral condyle of the knee can also be a site of stenosis or lumbar stenosis, may cause symptoms in more than one tendinitis as well, particularly in runners. Trochanteric bursitis and limb. A focused neuromuscular examination that assesses strength, illiotibial band syndrome are two conditions which respond well reflexes, and sensation in the affected limb and the contralateral to corticosteroid injections and a rehabilitation program aimed at limb provides a framework for EDX assessment. stretching this musculotendinous band. They are commonly mis- taken for lumbosacral radiculopathy. An algorithmic approach to utilizing physical examination and symptom information to tailor the EDX evaluation is shown in Pain at the bottom of the foot with symptoms of burning and Figure 1. In this approach, the patient’s symptoms, and physical tingling is frequently plantar fasciitis. Dorsiflexing the foot and pal- examination signs of sensory loss and weakness create a conceptual pating the plantar fascia will identify taut painful tendinous bands framework for approaching these sometimes daunting problems. if plantar fasciitis is present. Admittedly, there are many exceptions to this approach with considerable overlap in conditions which might fall in multiple Neuralgic amyotrophy from diabetes is a condition that is often categories. Radiculopathies and entrapment neuropathies are ex- difficult to distinguish from lumbosacral radiculopathy. It often amples of such conditions with a variety of clinical presentations presents with thigh pain and on EMG appears more like proximal and physical examination findings, such that they are included lumbosacral plexus mononeuropathies with frequent involvement in both focal symptom categories with and without sensory loss. of the femoral nerve. Diabetic thoracic radiculopathy is a distinct In the case of a person with lumbosacral radiculopathy, a positive syndrome with abdominal wall or thoracic wall pain, and weight straight leg raise test may be noted in the absence of motor, reflex, loss, but has a good prognosis. In diabetic thoracic radiculopathy, or sensory changes. Conditions such as myopathies and polyneu- intra-abdominal and intra-thoracic conditions must first be ex- ropathies better fit this algorithmic approach given that symptoms cluded. The EMG findings of denervation in the abdominal or and physical examination signs are somewhat more specific. Figure thoracic wall musculature are consistent with this clinical entity. 1 also contains musculoskeletal disorders and denotes how they fall into this conceptual framework. The EDX physician must be willing to Mononeuropathies such as peroneal, tibial, and femoral, pose modify the EDX examination in response to nerve conduction and diagnostic challenges and the EDX consultant should sample EMG findings and adjust the focus of the examination in light of enough muscles with EMG in different peripheral nerve distri- new information. butions to confirm that findings are not localized to a particular peripheral nerve distribution. The implications of symptoms and signs on EDX findings were investigated by Lauder and colleagues for cohorts of patients with upper or lower limb symptoms as well suspected cervical and lum- PHYSICAL EXAMINATION bosacral radiculopathies.35,36 Even though physical examination findings were better at predicting who would have a radiculopathy, The EDX examination is an extension of the standard clinical many patients with normal examinations had abnormal EMG examination. The history and physical examination are vital initial studies, indicating that clinicians should not curtail EDX testing steps in determining what conditions may be causing the patient’s simply because the physical examination is normal. For lower limb
Table 2 Common musculoskeletal disorders mimicking lumbosacral radiculopathy
Condition Clinical symptoms/signs Fibromyalgia syndrome and polymyalgia rheumatica As in Table 1 Hip arthritis Pain in groin, anterior thigh, pain with weight bearing, positive Patrick’s test Trochanteric bursitis Lateral hip pain, pain with palpation on lateral and posterior hip Illiotibial band syndrome Pain along outer thigh, pain with palpation Knee arthritis Pain with weight bearing Patellofemoral pain Anterior knee pain, worsen with prolonged sitting Pes anserinus bursitis Medial proximal tibia pain, tender to palpation Hamstring tendinitis, chronic strain Posterior knee and thigh pain, can mimic positive straight leg raise, common in runners Baker’s cyst Posterior knee pain and swelling Plantar fasciitis Pain in sole of foot, worsened with weight bearing activities, tender to palpation Gastrocnemius-soleus tendinitis, Calf pain, worsened with sports activities, usually limited range of motion compared to asymptomatic limb, chronic strain 12 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Figure 1 Algorithmic approach to structuring the electrodiagnostic examination based upon physical examination signs and the location of the patient’s symptoms. Focal symptoms refer to single limb symptoms whereas generalized symptoms are present when the patient complains of symptoms affecting more than one limb. (Modified from Dillingham TR. Electrodiagnostic approach to patients with suspected radiculopathy. Phys Med Rehabil Clin N Am 2002;13:567-588, with permission.) symptoms, loss of a reflex or weakness dramatically increased the number of muscles is discussed in detail below. An EMG study is likelihood of having a radiculopathy by EMG. Losing the Achilles considered confirmatory for a radiculopathy if EMG abnormalities reflex for instance, resulted in an odds ratio of 8.4 (p<0.01)—eight are found in two or more muscles innervated by the same nerve times the likelihood of having a radiculopathy (S1 level) by EMG with root and different peripheral nerves, yet muscles innervated by ad- this physical examination finding.35 Weakness in any leg muscle jacent nerve roots are normal.66 This definition assumes that other group resulted in about 2.5 times greater chance of identifying a generalized conditions such as polyneuropathy are not present. lumbosacral radiculopathy on EMG.35 Bilateral limbs are often necessary to study, particularly if a single Similar findings were noted for upper limb symptoms. For in- limb shows EMG findings suggestive of radiculopathy and the stance, if a reflex was lost or weakness was noted, the likelihood of patient has symptoms in both the studied and the contralateral limb. having a cervical radiculopathy confirmed by EMG was about 4 If bilateral limbs are involved, the EDX physician should have a low times more likely.36 Combinations of findings, particularly weak- threshold for studying selected muscles in an upper limb (if the lower ness plus reflex changes, resulted in a 9-fold greater likelihood of limbs are abnormal on EMG) or a lower limb (if both upper limbs cervical radiculopathy.36 are abnormal), to exclude a generalized process such as polyneuropa- thy or motor neuron disease. Likewise, additional NCSs are appro- Guidelines for Radiculopathy Evaluation priate to exclude other suspected conditions and the EDX consultant should have a low threshold for expanding the study. The American Association of Neuromuscular & Electrodiagnostic Medicine’s (AANEM) guidelines recommend that for an optimal evaluation of a patient with suspected radiculopathy, a needle EMG H REFLEXES, F WAVES, AND NERVE CONDUCTION STUDIES screen of a sufficient number of muscles and at least one motor and one sensory nerve conduction study (NCS) should be performed Nerve conduction studies, H reflexes, and F waves are not very in the involved limb.1 The NCSs are necessary to exclude polyneu- useful for confirming radiculopathy. They are useful, however, to ropathy. The sufficiency of the EMG screen and a recommended exclude polyneuropathy or mononeuropathies. AANEM Course Current Approaches to Common Neuromuscular Problems 13
H Reflexes London and England41 reported two cases of persons with neuro- H reflexes have commonly been used to determine whether a ra- genic claudication from lumbosacral spinal stenosis. They dem- diculopathy demonstrates S1 involvement.65 It is a monosynaptic onstrated that the F-wave responses could be reversibly changed reflex that is an S1 mediated response and can differentiate to some after 15 minutes of ambulation which provoked symptoms. This extent L5 from S1 radiculopathy. Many researchers have evalu- suggested an ischemia-induced conduction block in proximal ated their sensitivity and specificity with respect to lumbosacral motor neurons. A larger scale study of this type might find a use radiculopathies and generally found a range of sensitivities from for F waves in the identification of lumbosacral spinal stenosis and 32-88%.31,38,40,43,51,66 However, many of these studies suffered delineate neurogenic from vascular claudication. from lack of a control group, imprecise inclusion criteria, or small sample sizes. Motor and Sensory Nerve Conduction Studies
Marin and colleagues43 prospectively examined the H reflex and the Standard motor and sensory NCS may not be helpful in identify- extensor digitorum brevis reflex in 53 normal subjects, 17 patients ing a cervical or lumbosacral radiculopathy, however they should with L5, and 18 patients with S1 radiculopathy. Patients included be performed to screen for polyneuropathy and exclude common in the study had all of the following: (1) radiating low back pain entrapment neuropathies if the patient’s symptoms could be ex- into the leg; (2) reduced sensation or weakness or positive straight plained by a focal entrapment. leg raise test; and (3) either EMG evidence of radiculopathy or structural causes of radiculopathy on magnetic resonance imaging Plexopathies often pose a diagnostic challenge, as they are similar (MRI) or computed tomography (CT) imaging. The H-reflex to radiculopathies in symptoms and signs. In order to distinguish maximal side-to-side latency difference was 1.8 ms as derived from plexopathy from radiculopathy, sensory responses which are ac- the normal group. They analyzed the sensitivity of the H reflex for cessible in a limb should be tested. In plexopathy, they are likely side-to-side differences greater than 1.8 ms or a unilaterally absent to be reduced in amplitude, whereas in radiculopathy they are H reflex on the affected side. The H reflex only demonstrated a generally normal. If substantial axonal loss has occurred at the 50% sensitivity for S1 radiculopathy and 6% for L5 radiculopathy, root level, the CMAP recorded in muscles innervated by that but had a 91% specificity. Amplitudes were not assessed in this root may be reduced in both plexopathies and radiculopathies. study. These results suggest that the H reflex has a low sensitivity This is usually when severe axonal loss has occurred such as with for S1 root level involvement. cauda equina lesions or penetrating trauma that severely injures a nerve root. The distal motor latencies and conduction ve- H reflexes may be useful to identify subtle S1 radiculopathy, yet locities are usually preserved as they reflect the fastest conducting there are a number of shortcomings related to these responses. They nerve fibers.66 can be normal with radiculopathies,43 and because they are medi- ated over such a long physiological pathway, they can be abnormal due to polyneuropathy, sciatic neuropathy, or plexopathy.66 They SOMATOSENSORY EVOKED POTENTIALS, DERMATOMAL are most useful in the assessment for polyneuropathy. SOMATOSENSORY EVOKED POTENTIALS, AND MAGNETIC EVOKED POTENTIALS In order to interpret a latency or amplitude value and render a judgement as to the probability that it is abnormal, precise The AANEM guidelines examined the literature and concluded population-based normative values encompassing a large age- that somatosensory evoked potentials (SEPs) may be useful for cer- range of normal subjects must be available for NCS comparisons. vical spondylosis with cord compression. Likewise, in lumbosacral Falco and colleagues18 demonstrated in a group of healthy elderly spinal stenosis, dermatomal somatosensory evoked potentials subjects (60-88 years old), that the tibial H reflex was present and (DSEPs) may be useful in defining levels of deficits.1 recorded bilaterally in 92%. Most elderly subjects are expected to have normal H-reflex studies and when abnormalities are found in Physiological evidence of multiple or single root involvement in these persons, the EDX consultant should critically evaluate these lumbosacral spinal stenosis can be documented with DESPs and findings and the clinical scenario before attributing H-reflex abnor- may be useful in the case where spinal canal narrowing is minimal malities to the aging process. and the patient has symptoms. This testing also complements standard needle EMG. Snowden and colleagues found that for F Waves single and multilevel lumbosacral spinal stenosis, DSEPs revealed 78% sensitivity relative to spinal imaging.55 In this well-designed F waves are late responses involving the motor axons and axonal prospective study, DSEP criteria as well as inclusion criteria pool at the spinal cord level. They can be assessed and classified were precisely defined. The predictive value for a positive test by using the minimal latency, mean latency, and chronodispersion was 93%. or scatter.66 As in the case of H reflexes, they demonstrate low sensitivities and are not specific for radiculopathy, rather they are a Yiannikas, Shahani, and Young demonstrated that SEPs may be better screen for polyneuropathy. Published sensitivities range from useful for cervical myelopathy.67 In this study, in 10 patients with 13-69%, however these studies suffer from many of the shortcom- clinical signs of myelopathy, all 10 had abnormal peroneal SEPs ings described for H-reflex studies.31,52,59 and 7 had abnormal median SEPs. 14 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Maertens de Noordhout and colleagues examined motor and SEPs investigators questioned the clinical utility of both segmental and in 55 persons with unequivocal signs and symptoms of cervical dermatomal SEPs in the evaluation of patients with suspected spinal myelopathy.42 In this group 87% showed gait disturbances, unilateral/unilevel L5 and S1 nerve root compromise, finding and 82% showed hyperreflexia. MRI was not the diagnostic stan- little utility for these tests in persons with single level lumbosacral dard as these authors felt that MRI was prone to overdiagnosis; radiculopathy. metrizamide myelography showed unequivocal signs of cervical cord compression for all patients. Magnetic stimulation of the cortex was performed and the responses measured with surface PURPOSE OF EDX TESTING electrodes. In these subjects 89% demonstrated abnormalities in motor evoked potentials (MEP) to the first dorsal interosseus EDX testing is expensive and uncomfortable for patients, therefore, muscle and 93% had one MEP abnormality. At least one SEP it is important to understand why it is performed and the expected abnormality was noted in 73%. This study demonstrated the po- outcomes. EDX testing serves several important purposes: tential usefulness of these techniques for identifying subtle cord compression. = It effectively excludes other conditions that mimic radicul- opathy such as polyneuropathy or entrapment neuropathy. Tavy and colleagues examined whether MEPs or SEPs assisted Haig and colleagues demonstrated that the referring diagnostic in identifying persons with radiological evidence of cervical cord impression is often altered with EDX testing.23 compression but who were without clinical markers for myelopa- thy.60 All patients had clinical symptoms of cervical radiculopa- = EDX testing can to some extent suggest severity, or extent of the thy, but not myelopathy. In this group MEPs were normal in 92% disorder beyond the clinical symptoms. Involvement of other and SEPs were normal in 96%. These investigators concluded that MEPs and SEPs are normal in most cases of persons with extremities can be delineated or the involvement of multiple asymptomatic cervical stenosis. This indicates that abnormal roots may be demonstrated, such as in the case of lumbosacral MEPs and SEPs are likely to be true positive findings and not spinal stenosis. false positives related to mild asymptomatic cord compression. It is important to remember that cervical spondylosis is a process = There is utility in solidifying a diagnosis. An unequivocal that causes a continuum of problems including both radiculopa- radiculopathy on EMG in an elderly patient with nonspecific thy and myelopathy. or mild lumbar spondylosis or stenosis on MRI reduces diag- nostic uncertainty and identifies avenues of management such The inherent variability and difficulty in determinations as to as lumbar corticosteroid injections or decompression surgery in what constitutes normal evoked potentials prompted investiga- certain situations. tion. Dumitru and colleagues examined the variations in latencies with SEPs.17 In 29 normal subjects, they examined the ipsilateral = Outcome prediction may be possible. If surgical intervention intertrial variations, arithmetic mean side-to-side differences and maximum potential side-to-side differences with stimulation of is planned for a lumbosacral radiculopathy, a positive EMG the superficial peroneal sensory nerve, sural nerve and L5 and preoperatively improves the likelihood of a successful outcome S1 dermatomes with respect to P1 and N1 latencies and peak- postoperatively. This is an area that deserves more research to-peak amplitudes. Considerable ipsilateral intertrial variation attention.57,58 was observed and side-to-side comparisons revealed a further increase in this inherent variation regarding the above measured parameters. They suggested an additional parameter with which EMG AND DIAGNOSTIC SENSITIVITIES to evaluate SEPs: the maximum side-to-side latency difference. The need for EMG, particularly in relationship to imaging Dumitru and colleagues, in a study involving persons with uni- of the spine, has been recently highlighted.49 Needle EMG lateral and unilevel L5 and S1 radiculopathies, evaluated derma- is particularly helpful in view of the fact that the false posi- tomal and segmental somatosensory evoked potentials.15 History, tive rates for MRI of the lumbar spine are high, with 27% physical examination, imaging studies, and EDX medicine evalu- of normal subjects having a disc protrusion.26 For the cervi- ations clearly defined patients with unilateral/unilevel L5 or S1 cal spine the false positive rate for MRI is much lower with nerve root compromise. Regression equation analysis for corti- 19% of subjects demonstrating an abnormality, but only 10% cal P1 latencies evaluating age and height based on comparable showing a herniated or bulging disc.3 Radiculopathies can patient and control reference populations revealed segmental and occur without structural findings on MRI, and likewise without dermatomal sensitivities for L5 radiculopathies to be 70% and EMG findings. The EMG only evaluates motor axonal loss or 50%, respectively, at 90% confidence intervals. Similar sensi- motor axon conduction block and for these reasons a radicul- tivities were obtained for 2 standard deviation mean cortical P1 opathy affecting the sensory root will not yield abnormalities latencies. Side-to-side cortical P1 latency difference data revealed by EMG. If the rate of denervation is balanced by reinnerva- segmental and dermatomal sensitivities for S1 radiculopathies to tion in the muscle, then spontaneous activity is less likely to be 50% and 10%, respectively, at two standard deviations. These be found. AANEM Course Current Approaches to Common Neuromuscular Problems 15
The sensitivity of EMG for cervical and lumbosacral radiculopa- to identify subtle radiculopathies or spinal stenosis with greater thies has been examined in a number of studies. The results of some precision. of these studies are tabulated in Table 3. Table 3 lists the “gold stan- dards” against which these EMG findings were compared. Studies using a clinical standard may reflect a less severe group, whereas IDENTIFICATION AS A SEPARATE CONCEPT FROM those using a surgical confirmation may indicate a more severely SENSITIVITY involved group. The sensitivity for EMG is unimpressive, ranging from 49-92% in these studies. EMG is not a sensitive test, yet it Because EDX is a composite assessment composed of various tests, likely has a higher specificity. The issue of specificity and its value a fundamental question is when the point of diminishing returns in EDX was underscored by Robinson.49 It is apparent that EMG is has been reached. Some radiculopathies cannot be confirmed by not a good screening test. In terms of screening tests, MRI is better needle EMG, even though the signs and symptoms along with for identifying subtle structural abnormalities, with EMG to assess imaging results suggest that radiculopathy is the correct diagnosis. their clinical relevance and exclude other disorders. A screening EMG study involves determining whether or not the radiculopathy can be confirmed by EMG. If the radiculopathy cannot be confirmed, then presumably no amount of muscles can PARASPINAL MUSCLE EXAMINATION identify the radiculopathy. If it can be confirmed, then the screen should identify this possibility with a high probability. The process Paraspinal muscles are important to study for a variety of reasons of identification can be conceptualized as a conditional probabil- but there are some important caveats regarding their examina- ity: Given that a radiculopathy can be confirmed by needle EMG, tion. In one study, Date and colleagues demonstrated that lumbar what is the minimum number of muscles which must be examined paraspinal muscles in asymptomatic subjects over 40 years old in order to confidently recognize or exclude this possibility? This showed denervation potentials approximately 30% of the time.7 is a fundamentally different concept from sensitivity. It involves Nardin and colleagues similarly noted up to 48% of normal sub- understanding and defining the limitations of a composite test jects having fibrillations or positive sharp waves in at least one site (group of muscles). with the prevalence higher for those over 40 years of age.44
In sharp contrast to these findings, Dumitru, Diaz, and King HOW MANY AND WHICH MUSCLES TO STUDY examined the lumbosacral paraspinal muscles and intrinsic foot muscles with monopolar EMG.15 These investigators recorded po- The concept of a screening EMG encompasses identifying the pos- tentials and found that there were irregularly firing potentials with sibility of an EDX-confirmable radiculopathy. If one of the muscles similar waveform characteristics as fibrillations and positive sharp in the screen is abnormal, the screen must be expanded to exclude waves (PSW). By excluding irregularly firing potentials (atypical other diagnoses, and to fully delineate the radiculopathy level. endplate spikes) they found much lower false positive paraspinal Because of the screening nature of the EMG exam, EDX physicians findings than the investigators above, with only 4% of their normal with experience should look for more subtle signs of denervation, subjects showing regularly firing fibrillations or PSW potentials. and if present in the screening muscles, then expand the study to They felt that the higher prevalences of spontaneous activity previ- determine if these findings are limited to a single myotome or pe- ously reported were due to not fully appreciating the similarity ripheral nerve distribution. If they are limited to a single muscle, between innervated and denervated spontaneous single muscle the clinical significance is uncertain. fiber discharges. This quantitative study underscores the need to assess both firing rate and rhythm as well as discharge morphology The Cervical Radiculopathy Screen when evaluating for fibrillations and positive waves in the lumbar paraspinal muscles. Electrodiagnostic physicians should take care Dillingham and colleagues conducted a prospective multi-center not to over-diagnose paraspinal muscle EMG findings by mistaking study evaluating patients referred to participating EDX laboratories irregularly firing endplate spikes for fibrillations. with suspected cervical radiculopathy.10 A standard set of muscles were examined by needle EMG for all patients. Those with elec- Paraspinal muscles (PM) may be abnormal in patients with spinal trodiagnostically confirmed cervical radiculopathies, based upon cancers,4,32,33 or amyotrophic lateral sclerosis,30 and following EMG findings, were selected for analysis. The EMG findings in spinal surgery54 or lumbar puncture.7 this prospective study also encompassed other neuropathic findings: (1) positive sharp waves, (2) fibrillation potentials, (3) complex Investigations over the last decade have provided insights into repetitive discharges, (4) high-amplitude, long-duration motor better quantification and examination of lumbosacral paraspinal unit action potentials, (5) increased polyphasic motor unit action muscles. The lumbar paraspinal muscle examination has been potentials, or (6) reduced recruitment. There were 101 patients refined through investigations that used a grading scale for the with EDX confirmed cervical radiculopathies representing all cer- findings.19,20,21,22 The “mini PM” score provides a quantitative vical root levels. When paraspinal muscles were one of the screen- means of deriving the degree of paraspinal muscle denervation.19 It ing muscles and neuropathic findings were assessed, five muscle distinguishes normal findings from EMG findings in persons with screens identified 90-98% of radiculopathies, 6 muscle screens radiculopathy. This novel and quantitative technique may prove identified 94-99% and seven muscle screens identified 96-100% 16 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Table 3 Selected studies evaluating the sensitivity of EMG ginal increases in identification. Individual screens useful to the EDX relative to various “gold standards.” Unless otherwise stated the physician are listed in Tables 4 and 5. In some instances a particular EMG parameters used in sensitivity calculations were fibrillation muscle cannot be studied due to wounds, skin grafts, dressings, or potentials. infections. In such cases the EDX physician can use an alternative screen with equally high identification. These findings were consis- tent with those derived from a large retrospective study.33 STUDY SAMPLE GOLD EMG SIZE STANDARD SENSITIVITY The Lumbosacral Radiculopathy Screen LUMBOSACRAL (RADICULOPATHY) A prospective multicenter study was conducted at five institutions 10 Weber and Albert64 42 Clinical + Imaging 60% by Dillingham and colleagues. Patients referred to participating HNP EDX laboratories with suspected lumbosacral radiculopathy were recruited and a standard set of muscles examined by needle EMG. Nardin and colleagues45 47 Clinical 55% Patients with EDX-confirmed lumbosacral radiculopathies were 31 Kuruoglu and colleagues 100 Clinical 86% selected for analysis. As described above for the prospective cervical Khatri and colleagues28 95 Clinical 64% study, neuropathic findings were analyzed along with spontaneous Tonzola and colleagues62 57 Clinical 49% activity. There were 102 patients with EDX confirmed lumbosacral radiculopathies representing all lumbosacral root levels. When Schoedinger53 100 Surgically proven 56% paraspinal muscles were one of the screening muscles, 4 muscle 27 Knutsson 206 Surgically proven 79% screens identified 88-97%, 5 muscle screens identified 94-98%, Young and colleagues68 100 Clinical and imaging 84% * and 6 muscle screens 98-100% (Tables 6, 7, and 8). When paraspi- Linden and Berlit40 19 Myelography and CT 78% nal muscles were not part of the screen, identification rates were lower for all screens and eight distal muscles were necessary to LUMBOSACRAL identify 90%. As with cervical radiculopathy screens, assessing (SPINAL STENOSIS) for neuropathic findings increases identification rates. If only four Hall and colleagues24 68 Clinical + myelogram 92% muscles can be tested due to limited patient tolerance, as seen in Johnson and colleagues27 64 Clinical + myelogram 88% † Table 6, and if one of these muscles are the paraspinals, few EDX- confirmable radiculopathies will be missed. A large retrospective CERVICAL study noted similar findings, concluding that five muscles identi- (RADICULOPATHY) fied most electrodiagnostically confirmable radiculopathies.37 Berger and colleagues2 18 Clinical 61% 9 Partanen and colleagues46 77 Intraoperative 67% Dillingham and Dasher re-analyzed data from a study published by Knutsson almost forty years earlier.29 In this detailed study, 206 Leblhuber and colleagues38 24 Clinical + myelogram 67% patients with sciatica, underwent lumbar surgical exploration. All 56 So and colleagues 14 Clinical 71% subjects underwent a standardized 14 muscle EMG evaluation by Yiannikas and 20 Clinical and/ 50% the author (Knutsson) using concentric needles. The examiner was colleagues67 or radiographic blinded to other test results and physical examination findings. In Tackman and Radu59 20 Clinical 95% addition to the EMG and surgical information, myelogram and Hong, Lee, and Lum25 108 Clinical 51% physical examination data were derived. In this re-analysis, screens of four muscles with one being the lumbosacral paraspinal muscle * Both fibrillations or large motor units >8 mV were considered yielded (1) an identification rate of 100%, (2) a 92% sensitivity positive. with respect to the intraoperative anatomical nerve root compres- † This study assessed EMG parameters and used quantitative sions, and (3) an 89% sensitivity with respect to the clinical inclu- 9 EMG with a unique grading scale not used in clinical sion criteria. This study, using data from 4 decades ago, confirmed practice. Fibrillations were infrequent. This limits the that a 4 muscle screen provides high identification. These findings generalizability of this otherwise strong study. are consistent with contemporary work showing that screens with relatively few muscles (five or six) are sufficient. CT = computerized tomography; EMG = electromyography; HNP = herniated nucleus pulposis As described above, recent research efforts were undertaken to refine and streamline the EMG examination. The strongest studies, (Tables 4 and 5). When paraspinal muscles were not part of the contemporary prospective multicenter investigations, provide the screen, eight distal limb muscles recognized 92-95% of radicul- best estimates of a sufficient number of muscles.10,11 In summary, opathies. Without paraspinal muscles, the identification rates were for both cervical and lumbosacral radiculopathy screens the optimal consistently lower. If one only considers fibrillations and positive number of muscles appears to be six muscles which include the sharp waves in the EMG assessment, identification rates are lower. paraspinal muscles and represent all root level innervations. When Six muscle screens including paraspinal muscles yielded consistently paraspinal muscles are not reliable, then eight nonparaspinal high identification rates and studying additional muscles lead to mar- muscles must be examined. AANEM Course Current Approaches to Common Neuromuscular Problems 17
Table 4 Five muscle screen identifications of patients with Table 5 Six muscle screen identifications of the patients with cervical radiculopathies cervical radiculopathies (muscle identification criteria described in Table 2) MUSCLE SCREEN NEUROPATHIC SPONTANEOUS ACTIVITY MUSCLE SCREEN NEUROPATHIC SPONTANEOUS Without Paraspinals ACTIVITY deltoid, APB, FCU, 92% 65% Without Paraspinals triceps, PT deltoid, APB, FCU, 93% 66% biceps, triceps, 85% 54% triceps, PT, FCR EDC, FCR, FDI deltoid, triceps, 84% 58% biceps, triceps, FCU, 87% 55% EDC, FDI, FCR EDC, FCR, FDI biceps, triceps, 91% 60% deltoid, triceps, 89% 64% PT, APB, FCU EDC, FDI, FCR, PT With Paraspinals biceps, triceps, EDC, 94% 64% deltoid, triceps, PT, 98% 80% APB, PSM PT, APB, FCU biceps, triceps, EDC, 95% 73% With Paraspinals FDI, PSM deltoid, EDC, FDI, 90% 73% deltoid, triceps, PT, 99% 83% PSM, FCU APB, EDC, PSM biceps, FCR, APB 95% 77% biceps, triceps, EDC, 96% 75% PT, PSM FDI, FCU, PSM The screen detected the patient with cervical radiculopathy if any muscle deltoid, EDC, FDI, 94% 77% in the screen was one of the muscles which were abnormal for that patient. PSM, FCU, triceps Neuropathic findings for non-paraspinal muscles included positive waves, fibril- lations, increased polyphasic potentials, neuropathic recruitment, increased biceps, FCR, APB, 98% 79% insertional activity, CRDs, or large amplitude long duration motor unit action PT, PSM, triceps potentials. For paraspinal muscles the neuropathic category included fibrillations, increased insertional activity, positive waves, or CRDs. Spontaneous activity APB = abductor pollicis brevis; CRD = complex repetitive discharge; EDC = referred only to fibrillations or positive sharp waves. extensor digitorum communis; FCR = flexor carpi radialis; FCU = flexor carpi ulnaris; FDI = first dorsal interosseous; PSM = lumbosacral paraspinal muscles; APB = abductor pollicis brevis; CRD = complex repetitive discharge; EDC = PT = pronator teres. extensor digitorum communis; FCR = flexor carpi radialis; FCU = flexor carpi ulnaris; FDI = first dorsal interosseous; PSM = cervical paraspinal muscles; PT = pronator teres. (Adapted with permission, Dillingham and colleagues. Identification of cervical radiculopathies: optimizing the electromyographic screen. Am J LUMBAR SPINAL STENOSIS Phys Med Rehabil 2001;80:84-91.) 10 There are fewer studies examining spinal stenosis and EMG. Another way to think of this: For lumbosacral spinal stenosis, Hall and colleagues showed To minimize harm, six in the leg and six in the arm. that 92% of persons with imaging confirmed stenosis had a positive EMG.24 They also underscored the fact that 46% If one of the six muscles studied in the screen is positive with a neu- of persons with a positive EMG study did not demonstrate ropathic finding, there exists the possibility of confirming EDX that paraspinal muscle abnormalities, only distal muscle find- a radiculopathy is present. In this case, the examiner must study ad- ings. For 76% of patients, the EMG showed bilateral myo- ditional muscles. Nerve conductions should be undertaken as well to tomal involvement.24 determine if this muscle finding is due to a mononeuropathy. If more extensive EMG testing reveals that the findings are limited to a single muscle, and NCSs exclude mononeuropathy, then the single muscle LIMITATIONS OF THE Needle EMG SCREEN finding remains inconclusive and of uncertain clinical relevance. These cervical and lumbosacral muscle screens should If none of the six muscles are abnormal, the examiner can be con- not substitute for a clinical evaluation and differential diagnosis fident in not missing the opportunity to confirm by EDX that a formulation by the EDX physician. Rather, the information radiculopathy is present, and can curtail additional painful EMG from investigations described earlier in the article allows studies. The patient may still have a radiculopathy, but other tests the EDX consultant to streamline the EMG evaluation and such as MRI will be necessary to confirm this clinical suspicion. This make more informed clinical decisions regarding the probability logic is illustrated in Figure 2. of missing an EDX-confirmable radiculopathy when a given 18 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Table 6 Four muscle screen identifications of patients with Table 7 Five muscle screen identifications of patients with lumbosacral radiculopathies. lumbosacral radiculopathies
muscle Screen Neuropathic Spontaneous Screen Neuropathic Spontaneous Activity Activity Four Muscles Five Muscles Without Paraspinals Without Paraspinals ATIB, PTIB, MGAS, RFEM, SHBF 88% 77% ATIB, PTIB, MGAS, RFEM 85% 75% VMED, TFL, LGAS, PTIB, ADD 76% 59% VMED, TFL, LGAS, PTIB 75% 58% VLAT, SHBF, LGAS, ADD, TFL 68% 50% VLAT, SHBF, LGAS, ADD 52% 35% ADD, TFL, MGAS, PTIB, ATIB 86% 78% ADD, TFL, MGAS, PTIB 80% 67% Five Muscles With Paraspinals Four Muscles ATIB, PTIB, MGAS, PSM, VMED 98% 91% With Paraspinals VMED, LGAS, PTIB, PSM, SHBF 97% 84% ATIB, PTIB, MGAS, PSM 97% 90% VLAT, TFL, LGAS, PSM, ATIB 97% 86% VMED, LGAS, PTIB, PSM 91% 81% ADD, MGAS, PTIB, PSM, VLAT 94% 86% VLAT, TFL, LGAS, PSM 88% 77% ADD, MGAS, PTIB, PSM 94% 86% ADD = adductor longus; ATIB = anterior tibialis; CRD = complex repetitive dis- charge; LGAS = lateral gastrocnemius; MGAS = medial gastrocnemius; PSM = lumbosacral paraspinal muscles; PTIB = posterior tibialis; RFEM = rectus The screen identified the patient if any muscle in the screen was abnormal for femoris; SHBF = short head biceps femoris; TFL = tensor fascia lata; VLAT = that patient. The muscle either demonstrated neuropathic findings or spontane- vastus lateralis; VMED = vastus medialis. ous activity. Neuropathic findings for non-paraspinal muscles included positive waves, fibrillations, increased polyphasic potentials, neuropathic recruitment, increased insertional activity, CRDs, or large amplitude long duration motor unit SPECIFICITY OF THE EMG SCREEN action potentials. Spontaneous activity referred only to fibrillations or positive sharp waves. For paraspinal muscles the neuropathic category included fibrilla- Tong and colleagues,61 examined the specificity in persons age 55 and tions, increased insertional activity, positive waves, or CRDs. older who were asymptomatic. A standardized EDX study was con- ducted by a blinded EDX physician using a monopolar needle to assess ADD = adductor longus; ATIB = anterior tibialis; CRD = complex repetitive five leg muscles and the paraspinal muscles. discharge; LGAS = lateral gastrocnemius; MGAS = medial gastrocnemius; PSM = lumbosacral paraspinal muscles; PTIB = posterior tibialis; RFEM = There were 30 subjects with a mean age of 65.4 yrs (SD 8.0). When rectus femoris; SHBF = short head biceps femoris; TFL = tensor fascia lata; only positive sharp waves or fibrillations were counted as abnormal, VLAT = vastus lateralis; VMED = vastus medialis. (Adapted with permission (two limb muscles plus associated lumbar paraspinal muscle abnor- from Dillingham and colleagues. Identification of cervical radiculopathies: opti- mal, two limb muscles abnormal, or one limb muscle plus associated mizing the electromyographic screen. Am J Phys Med Rehabil 2001;80: lumbar paraspinal muscle abnormal) a 100% specificity was noted 84-91) 10 in most of the diagnostic criteria. When at least 30% polyphasia in the limb muscles was considered as abnormal, the respective speci- set of muscles are studied. Performing a focused history and physical ficities were 97%, 90%, and 87%. The specificity for plexopathy was examination is essential, and these screens should not supplant such 100% when only positive sharp waves or fibrillations were used, clinical assessments or a more detailed EDX study when circum- and it remained 100% when increased polyphasia was added. This stances dictate. study demonstrated that needle EMG has excellent specificity for lumbosacral radiculopathy and plexopathy when the appropriate diag- It is important to remember that the EMG screens for cervi- nostic criteria are used. 61 cal and lumbosacral radiculopathies were validated in a group of patients with limb symptoms suggestive of radiculopathies. These screens will not provide sufficient screening power if a SYMPTOM DURATION AND THE PROBABILITY OF brachial plexopathy is present or if a focal mononeuropathy FIBRILLATIONS such as a suprascapular neuropathy is the cause of the patient’s symptoms. The EDX physician should always perform EMG on Previously, a well-defined temporal course of events was thought to weak muscles to increase the diagnostic yield. The six muscle occur with radiculopathies despite the absence of studies that support EMG tests do not sufficiently screen for myopathies or motor such a relationship between symptom duration and the probability neuron disease. It is incumbent upon the EDX physician to for- of spontaneous activity in a muscle. It was a common belief that in mulate a differential diagnosis and methodically evaluate for the acute lumbosacral radiculopathies, the paraspinal muscles denervated diagnostic possibilities, further refining the examination as data first, followed by distal muscles, and that later reinnervation began are acquired. with paraspinal muscles and then with distal muscles. This paradigm AANEM Course Current Approaches to Common Neuromuscular Problems 19 was recently challenged by a series of investigations.12,13,14,48 For both There are few studies that examine outcomes and the usefulness EDX confirmed lumbosacral and cervical radiculopathies, symptom of EDX in predicting treatment success, the exception being sur- duration had no significant relationship to the probability of finding gical outcomes for lumbar discectomy. Tullberg and colleagues spontaneous activity in paraspinal or limb muscles. evaluated 20 patients with lumbosacral radicular syndromes who underwent unilevel surgery for disc herniations.63 They evaluated The findings from these investigations underscored the fact that the these patients before surgery and 1 year later with lower limb pathophysiological processes involved with cervical and lumbosacral EMG, NCS, F waves, and SEPs. They showed that the EDX find- radiculopathies are complex.12,13,14,48 Diagnostic EMG findings, mani- ings did not correlate with the level defined by computerized to- fested as a result of these processes, cannot be predicted by this overly mography for 15 patients. However, those patients in whom EDX simplistic, symptom-duration explanation. Symptom duration should testing preoperatively was normal were significantly more likely not be invoked to explain the presence or absence of paraspinal or to have a poor surgical outcome (p<0.01). In spite of the fact that limb muscle spontaneous activity in persons suspected of having a the sample size in this study was small, the significant correlation radiculopathy. of a normal EDX study with poor outcome suggests that this may be a true relationship.
IMPLICATIONS OF AN ELECTRODIAGNOSTICALLY Spengler and Freeman described an objective approach to CONFIRMED RADICULOPATHY the assessment of patients preoperatively for laminectomy and discectomy for lumbosacral radiculopathy.57 Spengler and col- It is important that the EDX physician not forget that EMG does leagues confirmed and underscored these previous findings regard- not indicate the exact cause of the symptoms, only that axonal loss ing objective methods to assess the probability of surgical success is taking place. A spine tumor, herniated disc, bony spinal stenosis, preoperatively.58 In this preoperative screening evaluation, the inflammatory radiculitis, or severe spondylolisthesis can all yield the EMG findings were combined with imaging, clinical, and psycho- same EMG findings. This underscores the need to image the spine logical assessments. The EMG findings figured prominently (one with MRI to assess for significant structural causes of electrodiagnosti- quarter of the scale) — those patients with positive EMGs were cally confirmed radiculopathy. A negative EMG test should not curtail more likely to have better surgical outcomes. This was particularly obtaining an MRI if clinical suspicion for radiculopathy is high. Given true when the EMG findings correlated with the spinal imaging the low sensitivities of needle EMG, it is not an optimal screening test, findings in a person without psychological or dysfunctional but rather a confirmatory and complementary test to spinal imaging. personality issues.
Figure 2 Implications of a positive or negative electromyography (EMG) screening evaluation. Note that a positive result will usually warrant further EMG testing to fully define the pathology, and a negative test could lead to nerve conduction or other testing to consider other diagnoses. PSM = paraspinal muscles; MRI = magnetic resonance imaging; SNRB = selective nerve root block. (Modified from Dillingham TR. Electrodiagnostic approach to patients with suspected radiculopathy. Phys Med Rehabil Clin N Am 2002;13:567-588, with permission.) 20 Evaluating the Patient With Suspected Radiculopathy AANEM Course
Table 8 Six muscle screen identifications of patients with The outcomes for cervical radiculopathy are generally good in the lumbosacral radiculopathies absence of myelopathy.50
Screen Neuropathic Spontaneous Saal, Saal, and Yurth demonstrated that persons with cervical disc Activity herniations have a similar favorable clinical course as persons with 50 Six Muscles Without Paraspinals lumbosacral radiculopathy. These patients were managed with pain management strategies incorporating medications, rehabilitation ATIB, PTIB, MGAS, RFEM, 89% 78% with cervical traction and exercises, and epidural or selective nerve SHBF, LGAS root injections if medications failed to control pain. In this series, the VMED, TFL, LGAS, PTIB, 83% 70% majority of patients (24 of 26) achieved successful outcomes. ADD, MGAS VLAT, SHBF, LGAS, 79% 62% ADD, TFL, PTIB SUMMARY ADD, TFL, MGAS, PTIB, 88% 79% ATIB, LGAS One cannot minimize the importance of the clinical evaluation and Six Muscles With Paraspinals differential diagnosis formulation by the EDX physician to guide testing. The needle EMG examination is the most useful EDX test ATIB, PTIB, MGAS, PSM, 99% 93% but is limited in sensitivity. EMG screening examinations using VMED, TFL six muscles are possible that optimize identification yet minimize VMED, LGAS, PTIB, PSM, 99% 87% patient discomfort. EMG findings must be interpreted relative to SHBF, MGAS the patient’s clinical presentation, and the consultant should tailor VLAT, TFL, LGAS, PSM, 98% 87% the EDX study to the clinical situation. Electromyography comple- ATIB, SHBF ments spinal imaging and often raises other diagnostic possibilities ADD, MGAS, PTIB, PSM, 99% 89% in addition to confirming clinical suspicians. VLAT, SHBF VMED, ATIB, PTIB, PSM, 100% 92% SHBF, MGAS REFERENCES VMED, TFL, LGAS, PSM, 99% 91% ATIB, PTIB 1. AAEM Guidelines in electrodiagnostic medicine. Muscle Nerve 1999;22:S1-S300. ADD, MGAS, PTIB, PSM, 100% 93% 2. Berger AR, Busis NA, Logigian EL, Wierzbicka M, Shahani ATIB, SHBF BT. Cervical root stimulation in the diagnosis of radiculopathy. Neurology 1987;37:329-332. ADD = adductor longus; ATIB = anterior tibialis; CRD = complex repetitive dis- 3. Boden SD, McCowin PR, Davis DO, Dina TS, Mark AS, Wiesel charge; LGAS = lateral gastrocnemius; MGAS = medial gastrocnemius; PSM S. Abnormal magnetic-resonance scans of the cervical spine in as- = lumbosacral paraspinal muscles; PTIB = posterior tibialis; RFEM = rectus ymptomatic subjects. A prospective investigation. J Bone Joint Surg femoris; TFL = tensor fascia lata; SHBF = short head biceps femoris; VLAT = 1990;72A:1178-1184. vastus lateralis; VMED = vastus medialis. 4. Boruta PM, LaBan MM. Electromyographic findings in patients with low back pain due to unsuspected primary and metastatic spinal or paraspinal muscle disease. Clin Orthop 1981;161:235-241. 5. Bush K, Cowan N, Katz DE, Gishen P. The natural history of sci- It has become apparent over the last 2 decades that the natural atica associated with disc pathology: A prospective study with clinical history of both lumbosacral radiculopathy and cervical radiculopa- and independent radiological follow-up. Spine 1992;17:1205-1212. thy, with or without structural findings on MRI, is very favorable. 6. Cinotti G, Postacchini F, Weinstein JN. Lumbar spinal stenosis and A classic investigation by Henrik Weber64 showed that surgery for diabetes. Outcome of surgical decompression. J Bone Joint Surg a herniated nucleus pulposis causing sciatica was more effective at 1994;76B:215-219. pain control at 1 year, but beyond that conservative treatment had 7. Danner R. Occurrence of transient positive sharp wave like activity in the paraspinal muscles following lumbar puncture. Electromyogr equal results compared to the surgically managed group. Of partic- Clin Neurophysiol 1982;22:149-154. ular note was the fact that weakness did not correlate with outcome 8. Date ES, Mar EY, Bugola MR, Teraoka JK. The prevalence of and even for persons with motor weakness, a good outcome with lumbar paraspinal spontaneous activity in asymptomatic subjects. conservative treatment was the norm, and surgery did not improve Muscle Nerve 1996;19:350-354. (wrong reference in paper Date motor return. Other investigators in cohort outcome studies dem- study labeled 7) onstrated that the majority of persons suffering lumbosacral radicu- 9. Dillingham TR, Dasher KJ. The lumbosacral electromyographic screen: lopathy can resolve their symptoms.5,27,40,61 In fact, on follow-up revisiting a classic paper. Clin Neurophysiol 2000;111:2219-2222. MRI studies, lumbosacral disc herniations and disc fragments 10. Dillingham and colleagues TR, Lauder TD, Andary M, Kumar S, resolve in 76% of patients.5 Pezzin LE, Stephens RT, Shannon S. Identification of cervical ra- AANEM Course Current Approaches To Common Neuromuscular Problems 21
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Neurology 1988;38:1879-1881. 19. Haig AJ. Clinical experience with paraspinal mapping. II: A simplified 39. Levin KH, Maggiano HJ, Wilbourn AJ. Cervical radiculopathies: technique that eliminates three-fourths of needle insertions. Arch comparison of surgical and EMG localization of single-root lesions. Phys Med Rehabil 1997;78:1185-1190. Neurology 1996;46:1022-1025. 20. Haig AJ, LeBreck DB, Powley SG. Paraspinal mapping. Quantified 40. Linden D, Berlit P. Comparison of late responses, EMG studies, and needle electromyography of the paraspinal muscles in persons motor evoked potentials (MEPs) in acute lumbosacral radiculopa- without low back pain. Spine 1995;20:715-721. thies. Muscle Nerve 1995;18:1205-1207. 21. Haig AJ, Moffroid M, Henry S, Haugh L, Pope M. A technique for 41. London SF, England JD. Dynamic F waves in neurogenic claudica- needle localization in paraspinal muscles with cadaveric confirmation. tion. Muscle Nerve 1991;14:457-461. Muscle Nerve 1991;14:521-526. 42. Maertens de Noordhout A, Remacle JM, Pepin JL, Born JD, 22. Haig AJ, Talley C, Grobler LJ, LeBreck DB. Paraspinal mapping: Delwaide PJ. Magnetic stimulation of the motor cortex in cervical quantified needle electromyography in lumbar radiculopathy. Muscle spondylosis. Neurology 1991;41:75-80. Nerve 1993;16:477-484. 43. Marin R, Dillingham TR, Chang A, Belandres PV. Extensor digi- 23. Haig AJ, Tzeng HM, LeBreck DB. The value of electrodiagnostic torum brevis reflex in normals and patients with radiculopathies. consultation for patients with upper extremity nerve complaints: a Muscle Nerve 1995;18:52-59. prospective comparison with the history and physical examination. 44. Nardin R, Raynor EM, Rutkove SB. Electromyography of lum- Arch Phys Med Rehabil 1999;80:1273-1281. brosacral paraspinal muscles in normal subjects. Neurology 24. Hall S, Bartleson JD, Onofrio BM, Baker HL Jr, Okazaki H, O’Duffy 1997;48:A147. JD. Lumbar spinal stenosis. Clinical features, diagnostic procedures, 45. Nardin RA, Patel MR, Gudas TF, Rutkove SB, Raynor EM. and results of surgical treatment in 68 patients. Ann Intern Med Electromyography and magnetic resonance imaging in the evaluation 1985;103:271-275. of radiculopathy. Muscle Nerve 1999;22:151-155. 25. Hong CZ, Lee S, Lum P. Cervical radiculopathy. Clinical, radio- 46. Partanen J, Partanen K, Oikarinen H, Niemitukia L, Hernesniemi J. graphic and EMG findings. Orthop Rev 1986;15:433-439. Preoperative electroneuromyography and myelography in cervical 26. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, root compression. Electromyogr Clin Neurophysiol 1991;31:21-26. Malkasian D, Ross JS. Magnetic resonance imaging of the lumbar 47. Perneczky A, Sunder-Plassmann M. Intradural variant of cervical spine in people without back pain. N Engl J Med 1994;331:69-73. nerve root fibres. Potential cause of misinterpreting the segmental 27. Johnsson KE, Rosen I, Uden A. Neurophysiologic investigation of location of cervical disc prolpases from clinical evidence. Acta patients with spinal stenosis. Spine 1987;12:483-487. Neurochir (Wien) 1980;52:79-83. 28. Khatri BO, Baruah J, McQuillen MP. Correlation of electromyogra- 48. Pezzin LE, Dillingham TR, Lauder TD, Andary M, Kumar S, phy with computed tomography in evaluation of lower back pain. Stephens RT, Shannon S. Cervical radiculopathies: relationship Arch Neurol 1984;41:594-597. between symptom duration and spontaneous EMG activity. Muscle 29. Knutsson B. Comparative value of electromyographic, myelographic, Nerve 1999;22:1412-1418. and clinical-neurological examinations in diagnosis of lumbar root compression syndrome. Acta Orthop Scand 1961;49:1-123. 49. Robinson LR. Electromyography, magnetic resonance imaging, 30. Kuncl RW, Cornblath DR, Griffin JW. Assessment of tho- and radiculopathy: it’s time to focus on specificity. Muscle Nerve racic paraspinal muscles in the diagnosis of ALS. Muscle Nerve 1999;22:149-150. 1988;11:484-492. 22 Evaluating the Patient With Suspected Radiculopathy AANEM Course
50. Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated 60. Tavy DL, Franssen H, Keunen RW, Wattendorff AR, Hekster RE, cervical intervertebral disc with radiculopathy. Spine 1996;21:1877- Van Huffelen AC. Motor and somatosensory evoked potentials 1883. in asymptomatic spondylotic cord compression. Muscle Nerve 51. Sabbahi MA, Khalil M. Segmental H-reflex studies in upper and 1999;22:628-634. lower limbs of patients with radiculopathy. Arch Phys Med Rehabil 61. Tong HC, Haig AJ, Yamakawa KS, Miner JA. Am J Phys Med 1990;71:223-227. Rehabil. 2006 Nov;85(11):908-12 - New reference added old 52. Scelsa SN, Herskovitz S, Berger AR. The diagnostic utility of F number in yellow. waves in L5/S1 radiculopathy. Muscle Nerve 1995;18:1496-1497. 62. Tonzola RF, Ackil AA, Shahani BT, Young RR. Usefulness of elec- 53. Schoedinger GR. Correlation of standard diagnostic studies with trophysiological studies in the diagnosis of lumbrosacral root disease. surgically proven lumbar disk rupture. South Med J 1987;80:44-46. Ann Neurol 1981;9:305-308. 54. See DH, Kraft GH. Electromyography in paraspinal muscles fol- 63. Tullberg T, Svanborg E, Isaccsson J, Grane P. A preoperative and lowing surgery for root compression. Arch Phys Med Rehabil postoperative study of the accuracy and value of electrodiagnosis in 1975;56:80-83. patients with lumbosacral disc herniation. Spine 1993;18:837-842. 55. Snowden ML, Haselkorn JK, Kraft GH, Bronstein AD, Bigos SJ, 64. Weber F, Albert U. Electrodiagnostic examination of lumbosacral Slimp JC, Stolov WC. Dermatomal somatosensory evoked potentials radiculopathies. Electromyogr Clin Neurophysiol 2000;40:231-236. in the diagnosis of lumbosacral spinal stenosis: comparison with 65. Weber H. Lumbar disc herniation: a controlled prospective study imaging studies. Muscle Nerve 1992;15:1036-1044. with ten years of observation. Spine 1983;8:131-140. 56. So YT, Olney RK, Aminoff MJ. A comparison of thermography 66. Wilbourn AJ, Aminoff MJ. AAEM Minimonograph #32: The elec- and electromyography in the diagnosis of cervical radiculopathy. trodiagnostic examination in patients with radiculopathies. Muscle Muscle Nerve 1990;13:1032-1036. Nerve 1998;21:1612-1631. 57. Spengler DM, Freeman CW. Patient selection for lumbar discectomy: 67. Yiannikas C, Shahani BT, Young RR. Short-latency somatosensory- An objective approach. Spine 1979;4:129-134. evoked potentials from radial, median, ulnar, and peroneal nerve 58. Spengler DM, Ouellette EA, Battie M, Zeh J. Elective discectomy for stimulation in the assessment of cervical spondylosis. Arch Neurol herniation of a lumbar disc: additional experience with an objective 1986;43:1264-1271. method. J Bone Joint Surg 1990;72A:230-237. 68. Young A, Getty J, Jackson A, Kirwan E, Sullivan M, Parry CW. 59. Tackmann W, Radu EW. Observations of the application of elec- Variations in the pattern of muscle innervation by the L5 and S1 trophysiological methods in the diagnosis of cervical root compres- nerve roots. Spine 1983;8:616-624. sions. Eur Neurol 1983;22:397-404. 23
An Approach to the Patient With Peripheral Neuropathy
Mark B. Bromberg, MD, PhD Department of Neurology University of Utah Salt Lake City, Utah
INTRODUCTION cal disease. However, it is equally inappropriate to carry forward a tentative neurologic diagnosis that is not tenable. One approach Symptoms of numbness and tingling are common neurologic com- is to determine whether the symptoms make sense anatomically plaints. The evaluation of a peripheral neuropathy (PN) can seem (based on the organization of the peripheral or central nervous daunting given the long list of potential causes and the number systems) or pathophysiologically (based on types of peripheral of available diagnostic tests, including antibody and genetic test nerve and central nervous system pathology). EDX studies can panels. However, the evaluation is manageable using a structured determine the presence of PNS involvement. If there is no evidence approach. This manuscript presents elements of such an approach for a neurologic basis for the symptoms, a gentle but frank discus- based on a systematic evaluation of symptoms and signs and elec- sion into issues in a patient’s life is appropriate. trodiagnostic (EDX) findings (Table 1). Clinical characterization is achieved by asking direct historical questions and conducting This manuscript will focus on peripheral neuropathies. Disorders thoughtful clinical tests. The role of EDX testing is stressed because primarily affecting other portions of the PNS, such as radiculopa- it provides unique information on the pathologic features of the thies and plexopathies, will not be considered. neuropathy not otherwise available from symptoms and clinical signs. The process is divided into 7 steps. With a full characteriza- tion, the list of potential causes becomes shorter and the appropri- PERTINENT PERIPHERAL NERVOUS SYSTEM ANATOMY ate selection of informative tests more manageable. This approach, in various forms, has been described elsewhere.11,12,14 A simple working view of PNS anatomy is useful when evaluating for a peripheral neuropathy. The PNS can be divided into auto- As clinical features are elicited, it is important to appreciate that not nomic and somatic components. Autonomic nerve fibers markedly all symptoms of numbness, sensory loss, and weakness are due to outnumber somatic fibers, but symptoms and signs of autonomic peripheral nerve disease. The exercise of neurologic localization is nerve dysfunction are rare compared to those associated with an essential element to assure peripheral nervous system (PNS) pa- somatic nerve dysfunction. When present, prominent autonomic thology. The most common errors in localization are failure to di- signs provide an important clue to specific causes of a neuropathy, agnose central nervous system pathology and somatization. Clinical but most diagnostic efforts focus on somatic nerves. features suggestive of a myelopathy include numbness that does not follow a stocking-glove or dermatomal distribution (numbness Step 1 involving both legs to the waist or above), numbness affecting one limb or side of the body, and pathologic tendon reflexes. In these The first step when evaluating a patient with suspected PN is de- circumstances, other diagnostic tests can help confirm central termining if there is involvement of sensory nerves, motor nerves, nervous system involvement. or both. The distribution of nerve involvement may not be obvious from symptoms, but can be determined accurately by EDX studies. Sensory symptoms attributable to somatization are common but This can be explained by the fact that damage to sensory nerves challenging because the clinician does not want to miss a neurologi- results in more frequent symptoms than damage to motor nerves. 24 An Approach to the Patient With Peripheral Neuropathy AANEM Course
Step 2 Table 1 Questions to address in a structured approach to evaluating peripheral neuropathies The second step is determining the distribution of involvement (Table 2). Peripheral neuropathies most commonly follow one of several general patterns. Polyneuropathies are roughly symmetric Step 1: in distribution and tend to affect nerves in a length dependent Which parts of the peripheral Somatic, autonomic, both manner, with longest nerves first (stocking-glove distribution).21 nervous system? Motor, sensory, both Polyradiculoneuropathies include nerve roots as well as peripheral Step 2: nerves, leading to diffuse symptoms in both proximal and distal What is the distribution? Distal predominant distributions. Mononeuropathies involve the distribution of a Distal and proximal single nerve with motor and sensory disturbance in a nerve distri- Dermatomal Radicular bution. Mononeuritis multiplex may become confluent and rela- Plexopathy tively symmetric, but a step-wise progression can usually be elicited from the history. Neuropathies that do not follow these patterns Step 3: What is the time course? are important to recognize, and the pathology may be identifiable Rate of progression (acute, based on their unusual pattern. chronic, insidious) Step 4: What are the clinic findings? Symptoms TIME COURSE Signs Physical features (high arches, Step 3 hammer toes Medical conditions (contributing diseases, drugs Every disease has a momentum or time course. The third step is Family history determining the time course to help focus the differential diagnosis (Table 3). Acute neuropathies progress over days to several weeks, Step 5: What is the underlying pathology? Primary axonal, primary while chronic neuropathies progress over many months to years, demyelinating (conduction and may have an insidious onset. block) Step 6: Table 2 Patterns of peripheral nerve involvement and examples Are there underlying medical Diseases (diabetes, renal of neuropathies. conditions? failure, collegan vascular) Surgeries (barosurgery) Step 7: Symmetric, length dependent Diabetes Is there a family history of a History of foot deformities or distribution Drugs polyneuropathy? gait difficulties Toxins Examination of suspected Metabolic family members Symmetric, proximal and distal Acute inflammatory Damage to sensory nerves disrupts connections between receptors distribution demyelinating and nerve endings leading to altered function and sensory symp- polyradiculoneuropathy toms. The same degree of damage to motor nerves may not affect Chronic inflammatory strength because collateral reinnervation of denervated muscle fibers demyelinating preserves motor function and obscures symptoms. Furthermore, polyradiculoneuropathy most neuropathies affect distal lower extremity muscles first, and weakness of toe flexion will not be readily apparent to the patient. Asymmetric, nerve or plexus Diabetic amyotrophy An additional factor is that sensory nerves have both peripheral and distribution Idiopathic plexopathy central branches, and damage to distal portions of sensory fibers Mononeuritis multiplex represents a double disconnection. Asymmetric, unusual Porphyria Many neuropathies are described by their symptoms, at times em- Leprosy phatically so (“a pure sensory or pure motor neuropathy”), when Tangier disease in fact there may be evidence for both motor and sensory nerve Multifocal motor conduction involvement. It is important for the physician to gather all the data block neuropathy and assess and classify neuropathies based on their pathological involvement and not solely on symptoms.8 Autonomic, unusual Amyloidosis AANEM Course Current Approaches to Common Neuromuscular Problems 25
Table 3 Examples of acute and chronic neuropathies discharges. Positive sensory symptoms are easily recognized and are frequently volunteered by the patient as chief complaints. Positive motor symptoms may not be recognized by the patient, and should Acute (days to weeks) Acute inflammatory demyelinating be actively sought because they may be the only clinical manifesta- polyradiculoneuropathy tion of motor nerve involvement. The discrepancy between patient Porphyria perception of sensory and motor symptoms is due to two factors. Acute toxic exposure (arsenic) First, collateral reinnervation occurs with loss of motor fibers, which Mononeuritis multiplex Proximal diabetic neuropathy tends to preserve muscle strength, whereas the same degree of sensory Idiopathic plexopathy fiber loss is essentially permanent and symptomatic. Second, mild Paraneoplastic sensory weakness of distal muscles (intrinsic foot muscles) does not usually neuronopathy affect motor function to a noticeable degree. Chronic (months to years) Diabetic polyneuropathy Chronic inflammatory demyelinating Table 4 Examples of positive and negative sensory and motor polyradiculoneuropathy symptoms Charcot-Marie-Tooth hereditary neuropathy Idiopathic SENSORY MOTOR SYMPTOMS SYMPTOMS Positive Paresthesias Fasciculations Pain (burning, squeezing, Cramps SUMMARY OF DIAGNOSTIC STEPS 1-3 electric-like, hyper sensitivity)
The site of initial involvement, the distribution of involvement, Negative Numbness Weakness and the pattern of progression can be combined. For example, Reduced or lack of sensation Atrophy Postural instability a pattern suggesting acute inflammatory demyelinating polyra- diculoneuropathy (AIDP), also known as Guillain-Barré syndrome, includes symptoms involving both distal and proximal limbs with Sensory Signs progression over 2 to 4 weeks.20 A similar distribution of distal and proximal symptoms and signs, but progressing over several months, Clinical testing of sensory function is a subjective endeavor. Although suggests chronic inflammatory demyelinating polyradiculoneurop- attempts are made to assess a number of individual sensory modali- athy (CIDP). Acute onset of asymmetric painful proximal neuropa- ties and nerve fiber types, distinctions between modalities and fiber thy in the setting of symmetric distal sensory loss suggests diabetic types may be more apparent than real. While there are examples of proximal amyotrophy with a polyneuropathy.3 Mononeuritis large fiber neuropathies (Friedreich's ataxia) and small fiber neu- multiplex is suggested by a stepwise progression involving single ropathies (Tangier's disease), most sensory modalities (light touch nerve distributions. The majority of neuropathies will be chronic. through pain) can be conveyed by both large and small diameter A symmetric motor and sensory neuropathy with an ill-defined fibers. Further, clinical testing (light touch, stroking, sharp instru- insidious onset raises the question of a familial neuropathy, and ments) usually activates a variety of receptor types. An important it is important to seek evidence for involvement in childhood and clinical variable is patient attention. It is advisable to develop an other family members. individual set of tests that are informative. It is important to not become bogged down in incongruities during the examination with a large battery of tests. CLINICAL FEATURES Step 4 The following information is offered as a guide to selecting a set of clinical sensory tests. Findings from formal psychophysical labora- tory testing of sensory perception should be combined with a set of The fourth step in the evaluation is determining the clinical informative clinical tests of sensory function.10 A variety of cutaneous features, including symptoms and signs, physical aspects, identi- receptor types subserve low-threshold mechanoreception, and mech- fication of potential underlying medical conditions, drug use, and anoreceptors are most sensitive to moving stimuli. In formal testing, family history. controlled stimuli are applied to restricted areas of skin. In contrast, clinical testing of mechanoreception may include touch or stroking, Symptoms and likely activates a variety of receptor types. Psychophysical testing for vibration perception confirms equal sensitivity for frequencies Elicitation of a full spectrum of symptoms is helpful in narrow- from 64 Hz to 512 Hz. Nociceptive stimulation is perhaps the most ing diagnostic possibilities and guiding symptomatic treatment. challenging. It is difficult to separate stimulus properties of nocicep- Neuropathic symptoms may be positive or negative in nature (Table tion from pressure and it is possible for a subject to distinguish a 4).24,27 Positive symptoms imply spontaneous discharges in nerve sharp from a dull stimulus without feeling pain. Nociceptive stimuli fibers, while negative symptoms imply loss of normally conducted are felt to be conveyed by “small fibers,” but some nociceptive 26 An Approach to the Patient With Peripheral Neuropathy AANEM Course receptors are innervated by myelinated fibers. Formal testing of reflex arc with sensory and motor nerve components, but the arc noxious stimuli has been by hot and cold stimuli using special equip- is much more vulnerable to sensory nerve damage. As an example, ment, and it is not clear how well temperature detection can be as- ankle plantar flexion strength is relatively preserved in all but sessed with clinical testing using the cold end of a tuning fork. the most severe neuropathies, yet ankle reflexes are lost early on. Accordingly, an absent Achilles tendon reflex is an objective indica- Reliable and informative results can be obtained from the clinical tion of a significant degree of sensory nerve damage. It is important tests listed below. to be assured that the reflex is truly absent by performing a number of reinforcing maneuvers while testing. Touch threshold. Patient detection of the lightest touch or strok- ing on the dorsum of the hand and foot represents a measure of Motor Signs low threshold sensory perception. Use of a 10 g filament is another method to distinguish light touch thresholds. Motor signs include muscle atrophy and weakness. Mild distal atrophy can be appreciated by assessing the prominence of exten- Vibration threshold. Patient perception of when a tuning fork sor tendons in the feet and finding a thin foot. Prominent tendons applied to a finger or toe dies out is a measure of vibration threshold. and thin feet suggest loss of intrinsic foot muscle bulk. A certain Vibration perception is felt to represent large fiber function. A 128 amount of denervation and atrophy occur with age, which must be Hz tuning fork dies out more slowly than a 256 Hz fork and is easier considered. Weakness can be appreciated by testing muscles that to use. The patient must understand the need to indicate complete can be just overcome in normal individuals. Accordingly, flexion disappearance. The time interval (in seconds) from when the vibra- and extension of the lesser toes and extension of the great toe are tion extinguishes in the patient compared to the observer is a measure informative when weakness is subtle. Ankle dorsiflexion weakness of impairment. will occur with greater severity of the neuropathy, but it is rare for plantar flexion to be weak until very late in a neuropathy. The angle Sharp stimulus threshold. A patient’s ability to distinguish between between the shin and the foot is a clue to distal weakness: in normal the lightly applied “pokey” feeling from the sharp end of a safety pin individuals it is about 130 degrees, but with weakness of anterior compared to the similarly lightly applied dull end likely represents muscles, the angle increases and can be 180 degrees in the setting discrimination of more noxious stimuli from light touch. of a neuropathy. Fallen arches also suggest intrinsic foot weakness. In the hands, atrophy of the first dorsal interosseous muscle and Position threshold. Patient perception of changes in joint position weakness of finger abduction are informative. is usually exquisite. Any errors in direction, or false perception of movement, are abnormal. Orthopedic Signs
The tests of light touch, the distinguishing the sharp end of the safety Inspection of the foot for high arches and hammertoes is informa- pin, and position sense should be performed with the patient blinded tive because it suggests a long-standing neuropathy. The shape of to the exercise. the foot is determined by the interplay of muscular forces acting on the various bones in the foot. Weakness of extensor muscles leads to The sensory examination can be focused to answer several useful clini- a foreshortened foot (high arches) and hammertoes.22 cal questions. Most information about the neuropathy should come from the patient’s history, and the sensory examination should be con- Autonomic Signs firmatory. Two questions to consider for a symmetric polyneuropathy are the presence of a distal-to-proximal gradient, and the severity of As discussed earlier, autonomic nerve fibers make up the major- nerve damage. Patients can contribute to determining sensory gradi- ity of fibers in a nerve but account for a minority of symptoms. ent and severity. It is surprising how readily a patient can mark a point Evidence for autonomic nerve dysfunction comes from symptoms on their limb below which sensation is abnormal and above which it of orthostatic dizziness and impotence in men. Clinical signs of is normal. The gradient can be confirmed clinically by asking if light autonomic dysfunction are an orthostatic blood pressure change. touch is perceived less strongly at a distal point compared to a proxi- Dry and scaly skin on the feet is a clue to autonomic dysfunction. mal point. Severity of light touch loss can be addressed by asking the Dry eyes and mouth (sicca syndrome) represent reduced tear and patient to estimate the relative percent value of light touch sensation salivary gland activity, and raise the question of Sjögren's syndrome at the involved site compared to the face. Severity of vibration loss can that can be associated with sensory neuropathies. be estimated by the time difference between vibration extinguishing for the patient compared to the examiner. PN NERVE PATHOLOGY Questions to consider for an asymmetric neuropathy are whether the sensory loss follows a nerve distribution, a radicular distribution, or Step 5 a complex pattern best explained by a plexopathy. Underlying pathologic processes are poorly understood for most Tendon reflexes. An objective measure of sensory nerve function is neuropathies. However, the consequences of the processes can the deep tendon reflex. The deep tendon reflex is a monosynaptic be viewed clinically as causing three patterns of peripheral nerve AANEM Course Current Approaches to Common Neuromuscular Problems 27 damage: primary axonal, primary demyelinating, and a combina- Nerve Conduction Studies tion of the two. The fifth step is determining the predominant pathologic process. Primary axonal damage usually follows a distal Primary axonal loss and demyelination. The question of underlying predominant pattern because longer nerves tend to be affected pathology is the most challenging question to answer. Distinctions first.21 This results in symptoms and signs in a distal-to-proximal are based primarily on motor nerve conduction velocity values. gradient that can be demonstrated clinically by a stocking-glove Nerve conduction measures of distal latency, conduction velocity distribution, with more pronounced abnormalities distally than and F-wave latency focus on the fastest conducting fibers. Experience proximally within a limb, and more in legs than in arms. Primary indicates that severe axonal loss has relatively little effect on nerve demyelination can occur at multiple foci along nerves, leading conduction. Changes in conduction can be expressed as percentages to both distal and proximal involvement at onset or early in of the laboratory limits of normal: lower limits of normal (LLN) for the course, that can be demonstrated clinically by finding both conduction velocity, and upper limits of normal (ULN) for distal distal and proximal weakness and sensory disturbance.21 In ad- latency and F-wave latency. Thus in amyotrophic lateral sclerosis, dition, demyelinating polyradiculoneuropathies involve roots of as an example of a pure and severe axonal motor neuropathy, distal nerves innervating both proximal and distal muscles and skin. latencies are rarely longer than 125% of the ULN, conduction veloci- Demyelinating neuropathies usually include a variable degree ties rarely slower than 70% of the LLN, and F-wave latencies rarely of axonal damage, and the distinction between primary de- longer than 125% of the ULN.7 myelination and a combination of demyelination and axonal damage can be challenging. EDX studies are helpful in making The distinction between demyelinating and axonal pathology is this distinction. based on showing a degree of slowed conduction greater than ex- pected for axonal loss alone. Just how slow is slower than expected Mononeuropathies generally have axonal pathology. An excep- has been the subject of controversy. Several sets of nerve conduction tion is asymmetric neuropathies characterized by focal conduc- limits for primary demyelination have been proposed and tested.6 tion block. The distinction between axonal and conduction block The problem of sensitivity and specificity looms large because some mononeuropathies can be made with EDX testing. demyelinating neuropathies are mild, and nerve conduction values will over lap with normal values and abnormal values encountered Collateral reinnervation represents an important compensatory in axonal neuropathies. Table 5 lists nerve conduction guidelines for mechanism in peripheral neuropathies. Loss of motor nerve axons considering primary demyelination. initiates sprouting of terminal branches from intact axons to rein- nervate denervated muscle fibers. This compensates and preserves Table 5 Nerve conduction value guidelines to help distinguish muscle strength until 50% or more motor axons degenerate, at primary axonal from primary demyelinating neuropathies which time reinnervation can not keep up and the muscle becomes clinically weak. This means that muscle strength is not a sensitive measure of whether motor nerves are involved in a peripheral neu- Limits of Axonal Limits of Demyelinating ropathy. Needle electromyography (EMG), however, is sensitive to Pathology Pathology the process of reinnervation. Distal latency <120% ULN >130% ULN Conduction velocity >70% ULN <70% ULN EDX Features Proximal: distal <50% >50% amplitude Perhaps the most important element in the diagnostic evalua- tion is EDX testing because nerve conduction and needle EMG Abnormal temporal Smooth waveform Irregular waveform studies provide objective information on the peripheral nervous dispersion system not available from the history and clinical examination. F-wave latency <130% ULN >130% ULN Characterization by EDX features can thus narrow the differ- 8 ential diagnostic list. EDX test results are considered from two ULN = upper limit of laboratory normal values; LLN = lower limit of laboratory directions: by the EDX physician conducting the study, and by normal values the consultant reviewing an existing study. The performance and interpretation of EDX studies can be optimized for both the performer and reviewer by following several principles. The Demyelination and conduction block. Although distal latency, EDX test should be used as a direct extension of the neurologic conduction velocity, and F-wave latency measure the speed of the examination to answer specific questions: (1) Confirm which por- fastest conducting fibers, it is possible to assess the conduction tions of the peripheral nervous system are involved; sensory only, speed of the remainder of the fibers in the response by looking for motor only, or both. In this regard, step 5 complements step 1; abnormal temporal dispersion. Quantitatively, temporal dispersion (2) Confirm the distribution of involvement: symmetric poly- can be assessed by the duration of the negative compound muscle neuropathy, single nerves, or another pattern; (3) Determine the action potential (CMAP) waveform. Temporal dispersion represents pathologic mechanism: primary axonal, primary demyelination, the spectrum of arrival times of nerve impulses from the range of or a mixture; (4) Determine the severity and time course: mild or nerve fiber conduction velocities. Abnormal temporal dispersion is severe, recent or chronic. caused by a greater degree of slowing of individual nerve fibers due to 28 An Approach to the Patient With Peripheral Neuropathy AANEM Course demyelination. Abnormal temporal dispersion leads to a greater degree of phase cancellation in the waveform leading to a reduction of the amplitude of the CMAP to more proximal stimulation compared to the amplitude following more distal stimulation. If individual nerve fibers slow to a halt, i.e., conduction block, there will also be a reduction of the CMAP amplitude to more proximal stimulation, and thus a drop in amplitude of the proximal response by greater than 50% indicates increased temporal dispersion and greater phase cancellation, or conduction block, or both. There are guidelines to help distinguish between abnormal temporal dispersion and conduc- tion block (Table 6).17,28 In abnormal temporal dispersion there will be an amplitude reduction of the proximal response but little change in the areas of the response. In addition, there will be a prolonga- tion of the negative peak duration. In conduction block there will be a reduction of both amplitude and area with little change in the negative peak duration. However, many clinical examples include Figure 1 Differences between normal and abnormal temporal dis- a combination of abnormal temporal dispersion and conduction persion stimulating at the wrist, elbow, and axilla. block. What is most important is that abnormal temporal dispersion Left set of waveforms: Normal changes in motor responses with and conduction block suggests a demyelinating pathology. greater conduction distances due to normal temporal dispersion. Right set of waveforms: Marked changes in motor responses with greater Table 6 Nerve conduction value guidelines to help distinguish conduction distances due to abnormal temporal dispersion. Note initial between abnormal temporal dispersion, conduction block, or a low response amplitude with further loss with greater conduction dis- combination of the two tances, and irregularities of the waveform. Oscilloscope settings: 5 ms/ div and 5 mV/div.
CMAP CMAP Negative CMAP Negative Amplitude Peak Area Peak Duration Conduction block <50% <50% ≤30% Conduction block/ <50% <50% >30% Abnormal temporal dispersion Temporal <50% >50% >30% dispersion
CMAP = compound muscle action potential. Lange D, Trojaborg W, Latov N, Hays A, Younger D, Uncini A, Blake D, Hirano M, Burns S, Lovelace R, Rowland L. Multifocal motor neuropathy with conduction block: Is it a distinct clinical entity? Neurology 1992;42:497-505.17
Abnormal temporal dispersion can be assessed qualitatively because it will also affect the smooth shape of the CMAP wave- form, and wave form irregularities should be sought by inspection (Figure 1). Assessing for abnormal temporal dispersion is impor- tant because a group of hereditary neuropathies, Charcot-Marie- Tooth type 1, are characterized by slow conduction velocity but no abnormal temporal dispersion (Figure 2).18
Needle EMG Figure 2 Motor nerve conduction study stimulating at the wrist The needle EMG examination is important because it is the most and elbow showing slow conduction velocity with normal tempo- sensitive measure of motor nerve involvement. CMAP amplitude ral dispersion in Charcot-Marie-Tooth hereditary neuropathy type 1A. is a measure of axonal loss, but collateral reinnervation will com- pensate early for mild degrees of loss, and CMAP amplitude will Top set of waveforms: Slow velocity (18 m/s) from subject with Charcot- not be a sensitive measure of early loss. The presence of abnormal Marie-Tooth hereditary neuropathy type 1A with normal changes in wave- temporal dispersion (fibrillation potentials and positive waves) is forms reflecting normal temporal dispersion. Bottom set of waveforms: sensitive signs of denervation. Reduced motor unit recruitment Normal velocity (52 m/s) with normal changes in waveforms reflecting normal indicates a neuropathic cause of denervation. The chronicity of temporal dispersion. Oscilloscope settings: 5 ms/div and 5 mV/div. AANEM Course Current Approaches to Common Neuromuscular Problems 29 motor nerve loss can be assessed by the degree of complexity of the are rarely a factor.1 Gastric resection or stapling procedures 1,15 motor unit action potentials; highly complex or polyphonic poten- may predispose to vitamin B12 deficiency. Other vitamin tials support an ongoing enervating process, while high amplitude deficiencies are rare in North America. On the other hand, but simple potentials support a very longstanding enervating vitamin B6 toxicity can occur at doses readily available to process. In the latter situation, a longstanding and slowly progres- health and nutrition enthusiasts.5 Ethanol as a neurotoxin in a sive denervation lends support for a hereditary neuropathy. well-nourished individual is controversial, and is probably uncom- mon in all but chronic heavy users.13,16 Thyroid dysfunction is also controversial. Hypothyroidism is common, but there are few well- SUMMARY OF DIAGNOSTIC STEPS 1-5 documented examples of polyneuropathy attributed to mild thyroid dysfunction.26 Rheumatologic disorders can be associated with At the conclusion of the clinical and EDX evaluation (steps 1-5), vasculitic neuropathies. a full characterization of the peripheral neuropathy should emerge (Table 7). The differential diagnostic list is relatively short under Medication use, both current and past, should be sought for a each type of neuropathy.8 At this point, a review of the medical number of compounds. Cancer chemotherapeutic drugs such and family histories can be incorporated to give a complete as cisplatin, vincristine, and the taxols are neurotoxic. There is a characterization and a meaningful series of laboratory tests can question whether previous exposure to neurotoxic chemothera- be ordered. peutic drugs can be a predisposing factor for neuropathies from another cause, and has been shown to occur for vincristine in Table 7 Clinical and electrodiagnostic characteristics of the setting of Charcot-Marie-Tooth type 1A hereditary neuropa- peripheral neuropathies thies.14 Among commonly used drugs, nitrofurantoin and amio- darone can be neurotoxic. Infrequently used neurotoxic drugs include disulfiram, gold, and isoniazid. Recreational inhaled Clinical characteristics Acute compounds, including n-hexane in glue sniffing should also Chronic be considered.25 Familial Symmetric Asymmetric FAMILY HISTORY
Electrodiagnostic Uniform demyelinating, mixed Step 7 characteristics sensorimotor polyneuropathy Segmental demyelinating, motor > sensory polyneuropathy It is likely that hereditary neuropathies account for a larger than Axon loss, motor > sensory appreciated percentage of mild and very chronic idiopathic neu- polyneuropathy ropathies. Step 7 assesses this possibility.9 Interestingly, among Axon loss, sensory neuropathy or large families with known hereditary neuropathies, only 20% of neuronopathy affected family members seek medical attention because of symp- Axon loss, mixed sensorimotor toms. Accordingly, a full family history with detailed queries to polyneuropathy the patient and relatives (if necessary over the telephone) about Axon loss, motor neuropathy or symptoms and signs that may suggest a hereditary neuropathy can neuronopathy be fruitful (Table 8). Mixed axon and demyelinating sensorimotor polyneuropathy Table 8 Questions pertinent to a long-standing (familial) neuropathy MEDICAL HISTORY Step 6 Difficulty with running, sports, or military activities There are long lists of medical conditions and drugs that cause High arched feet or predispose to peripheral neuropathy, but careful review reveals Hammer or curled-up toes that some associations are rare and may reflect chance occur- Surgery for hammer toes rences. Step 6 is to assess possible factors. In practical terms, a limited number of systemic diseases relate to peripheral neu- Claw hands ropathies. Diabetes is the most common underlying disease, Wasting of muscles not only for frank diabetes, but also for undocumented diabetes Foot troubles, foot ulcers (impaired glucose tolerance).23 Renal failure is also a cause of Use of braces neuropathy, but not until the creatinine level is over 5 mg/dl.2 Diseases of the gastrointestinal tract are uncommonly associated Arthritis or poliomyelitis (incorrect diagnosis) with peripheral neuropathies, and inflammatory bowel diseases Difficulty walking on heels and toes 30 An Approach to the Patient With Peripheral Neuropathy AANEM Course
OTHER DIAGNOSTIC TESTS 9. Dyck P, Oviart K, Lambert E. Intensive evaluation of referral unclassified neuropathies yields improved diagnosis. Ann Neurol 1981;10:222-226. A number of ancillary diagnostic tests are available for special cir- 10. Dyck P, Karnes J, O'Brien P, Zimmerman I. Detection thresholds cumstances. These tests should be used when there is evidence from of cutaneous sensation in humans. In: Dyck P, Thomas P, Lambert the history and examination findings that they will be informa- E, Bunge R, editors. Peripheral neuropathy, 2nd edition, volume 1. tive. Lumbar puncture for cerebral spinal fluid can be informative Philadelphia: WB Saunders; 1984. p 1103-1136. for evidence of breakdown of the blood-nerve barrier by elevated 11. Dyck P, Dyck J, Chalk C. The 10 P's: A mnemonic helpful in char- protein when root involvement is suspected, as in AIDP and CIDP. acterization and differential diagnosis of peripheral neuropathy. Abnormal cells can suggest other processes, such as an infectious Neurology 1992;42:14-18. 12. Dyck P, Dyck J, Grant I, Feasley R. Ten steps in characterizing and di- process. Peripheral nerve biopsy can provide evidence for vasculitis, agnosing patients with peripheral neuropathy. Neurology 1996;47:10- amyloidosis, and infiltrative conditions. Skin biopsies can confirm 17. 19 damage to intraepidermal nerve endings. Recently, tests for anti- 13. Erdem S, Kissel J, Mendell J. Toxic neuropathies: Drugs, metals, bodies against various gangliosides and for paraneoplastic conditions and alcohol. In: Mendell J, Kissel J, Cornblath D, editors. Diagnosis have become widely available. Antibody tests should be ordered with and management of peripheral nerve disorders. Oxford: Oxford caution because the diagnostic yield of these tests is low.29 University Press; 2001. p 297-343. 14. Graf W, Chance P, Lensch M, Eng L, Lipe H, Bird T. Severe vin- cristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer SUMMARY 1996;77:1356-1362. 15. Juhasz-Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic At the conclusion of the evaluation that includes a full charac- complications of gastric bypass surgery for morbid obesity. Neurology 2007;68:1843-1850. terization and a rational set of diagnostic tests a diagnosis should 16. Koike H, Misu K, Hattiori N, Ito H, Hirayama M, Sobue G. Painful be forthcoming. However, it should be kept in mind that despite alcoholic polyneuropathy with predominant small-fiber loss and best efforts, it is important to appreciate that a good percentage of normal thiamine status. Neurology 2001;56:1727-1732. neuropathies, perhaps 20%, will remain undiagnosed despite an 17. Lange D, Trojaborg W, Latov N, Hays A, Younger D, Uncini A, exhaustive evaluation.9 Ordering more laboratory tests is seldom Blake D, Hirano M, Burns S, Lovelace R, Rowland L. Multifocal informative, and may lead to false positive findings. A periodic motor neuropathy with conduction block: Is it a distinct clinical review of a patient’s history and inquiry for new symptoms may entity? Neurology 1992;42:497-505. be helpful. 18. Lewis R, Sumner A. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology 1982;32:592-596. 19. McArthur J, EA S, Hauer P, Cornblath D, Griffin J. Epidermal nerve REFERENCES fiber density. Normative reference range and diagnostic efficiency. Arch Neurol 1998;1998:1513-1520. 1. Albers J, Nostrant T, RIggs J. Neurologic manifestations of gastroin- 20. Ropper A, Wijdicks E, Truax B. Guillain-Barré syndrome. testinal disease. Neurologic Clinics 1989;7:525-548. Philadelphia: FA Davis; 1991. 2. Amato A, Kissel J, Mendell J. Neuropathies associated with organ 21. Sabin T. Classification of peripheral neuropathy: The long and the system failure, organ transplantation, metabolic disorders, and cancer. short of it. Muscle Nerve 1986;9:711-719. In: Mendell J, Kissel J, Cornblath D, editors. Diagnosis and manage- 22. Sabir M, Lyttle D. Pathogenesis of pes cavus in Charcot-Marie- ment of peripheral nerve disorders. Oxford: Oxford Univerity Press; Tooth disease. Clin Orthop 1983;175:173-178. 2001. p 565-591. 23. Singleton J, Smith A, Bromberg M. Increased prevalence of im- 3. Barohn R, Sahenk Z, Warmolts J, Mendell J. The Burns-Garland syn- paired glucose tolerance i patients with painful sensory neuropathy. drome (diabetic amyotrophy). Revisited 100 years later. Arch Neurol Diabetes Care 2001;24:1448-1453. 1991;48:1130-1135. 24. Sivak M, Ochoa J, Fernández J. Positive manifestations of nerve fiber 4. Barohn R. Approach to peripheral neuropathy and neuronopathy. dysfunction: Clinical, electrophysologic, and pathologic correlations. Semin Neurology 1998;18:7-18. In: Brown W, Boulton C, editors. Clinical electromyography, 2nd 5. Berger A, Schaumburg H, Schroeder C, Apfel S, Reynolds R. Dose edition. Boston: Butterworth-Heinemann; 1993. p 117-147. response, coasting, and differential fiber vulnerability in human 25. Smith A, Albers J. N-hexane neuropathy due to rubber cement sniff- toxic neuropathy: A prospective study of pyridoxine neurotoxicity. ing. Muscle Nerve 1997;20:1445-1450. Neurology 1992;42:1367-1370. 26. Swanson J, Kelly J, McConahey W. Neurologic aspects of thyroid 6. Bromberg M. Comparison of electrodiagnostic criteria for primary dysfunction. Mayo Clin Proc 1981;56:504-512. demyelination in chronic polyneuropathy. Muscle Nerve 1991;14:968- 27. Trials AHPoEfDN. Positive neuropathic sensory symptoms as end- 976. points in diabetic neuropathy trials. J Neurol Sci 2001;189:3-5. 7. Cornblath D, Kuncl R, Mellits E, Quaskey S, Clawson L, Pestronk 28. Van den Bergh PY, Pieret F. Electrodiagnostic criteria for acute and A, Drachman D. Nerve conduction studies in amyotrophic lateral chronic inflammatory demyelinating polyradiculoneuropathy. Muscle sclerosis. Muscle Nerve 1992;15:1111-1115. Nerve 2004;29:565-574. 8. Donofrio P, Albers J. AAEM minimonograph #34: Polyneuropathy: 29. Wolfe G, El-Feky W, Katz J, Bryan W, Wians F, Barohn R. Antibody Classification by nerve conduction studies and electromyography. panels in idiopathic polyneuropathy and motor neuron disease. Muscle Nerve 1990;13:889-903. Muscle Nerve 1997;20:1275-1283. 31
A Practical Approach to the Patient Presenting With Numbness
Robert A. Werner, MD Professor and Chief Department of Physical Medicine and Rehabilitation Ann Arbor VA Health System Ann Arbor, Michigan
LOCALIZATION OF THE PROBLEM USING HISTORY AND EXAMINATION
Numbness can be the result of a disease process located in the central nervous system (CNS) or the peripheral nervous system (PNS). It can often be localized by the patient’s history alone. It is important to recognize both the timing and onset of the patient’s symptoms and the distribution of the patient’s signs and symptoms. Localizing a patient’s deficits to a specific area of the nervous system frequently can be accomplished with attention to the distribution of symptoms (e.g., right versus left, arm versus leg, proximal versus distal, sym- metric versus asymmetric, and the presence of facial involvement). Determining the characterstics of symptoms (sensory and motor or sensory) and the temporal features (acute or chronic, or static or progressive) is also helpful.
Obtaining a clear history is important. The patient’s complaints of “numbness” can include a range of sensory disturbances. The patient can describe “tingling,” “burning,” or a true loss of sensa- tion simply as “numbness.” It is important to be specific when Figure 1 Human figure. The patient can mark location of each of questioning the patient to clearly define the range of symptoms. these symptoms: pain (xxx), numbness (///) and tingling (\\\) on the This will help in identifying the etiology of the disease process. The figures. simultaneous evaluation of the distribution of these complaints can significantly refine the differential diagnosis. Recognition of the common symptoms may have a major impact on appropriate treatment and may allow early management which can minimize populations of neurons are vulnerable in specific disease processes. long-term residual deficits for the patient. The use of a question- The vulnerability may arise from the effect of a disease on a spe- naire with a human figure is helpful in defining the symptoms and cific vascular territory (e.g., stroke, vasculitis, aneurysm), a space their distribution (Figure 1). occupying lesion (e.g., tumor, herniated disk) or an autoimmune, inflammatory attack on the nervous system. Taking the patient's The extent and characteristics of the patient’s symptoms are related history can frequently help the physician determine the localization to the specific portion of the nervous system injured. Different (Tables 1 and 2). 32 A Practical Approach to the Patient Presenting With Numbness AANEM Course
imaging (MRI) scan may confirm the presence of a lacunar Table 1 Patient’s description of sensory loss likelihood of the infarct or a hemorrhagic infarction. Relative to other brain localization regions, the thalamus is more vulnerable to hemorrhage resulting from hypertension in the brain. Tingling PNS > CNS Burning PNS > CNS Parietal lobe lesions cause contralateral numbness associated with loss of discriminatory sensation. The patient may feel Total loss of feeling CNS* > PNS** touch but may not localize it well. Patients may experience Poor coordination*** CNS = PNS weakness as well as numbness but sensory complaints are more prominent. CNS = central nervous system; PNS = peripheral nervous system
* Localization to the central nervous system would most commonly involve uni- SPINAL CORD lateral signs and symptoms except with spinal cord lesions where symptoms are usually bilateral. Lesions in the spinal cord resulting only in numbness ** Peripheral nervous system lesions can be either multifocal or, commonly, bilat- are not common. Most cause both numbness and weak- eral and symmetric. Early signs in a neuropathy may involve only one extremity ness. This is due to the close proximity of motor and sensory (usually the feet) but peripheral involvement would be much less likely with all neurons and their pathways in the spinal cord and exist- unilateral complaints. ing nerve roots. Inflammatory lesions can selectively affect sensory pathways. This can result in profound sensory *** Poor coordination can result from either central (cerebellar, brainstem) or pe- ripheral (impaired proprioception, nerve, dorsal root ganglion) pathology. disturbances that are typically bilateral. Disorders such as acute myelitis and multiple sclerosis can present as primarily sensory disturbances.
The distribution of lesions affecting the CNS are usually distinct from those affecting the PNS (Table 3). NERVE ROOT/DORSAL ROOT GANGLION
This manuscript explores the possible disorders that can cause Sensory and motor nerve roots are separate as they exit the numbness along the neuroaxis, starting at the brain and moving spinal cord but combine at the level of the dorsal root gan- out to the spinal cord and then peripheral nerves. glion. The most common cause of nerve root injury is due to a herniated vertebral disk. This typically results in radi- ating pain frequently with both motor and sensory fibers BRAIN involved. The involvement in the dermatome of multiple nerve roots suggests a problem other than a structural lesion. Numbness may be secondary to a lesion of the parietal lobe Consideration must be given to an inflammatory, neoplastic, or or thalamus (ventral posteromedial nucleus). Thalamic lesions infectious process. produce contralateral sensory loss and numbness, but these may be painful. An abrupt onset suggests a cerebral vascular event Selective involvement of the dorsal root ganglion cells causes a and may be seen with lacunar infarcts secondary to hypertension. profound sensory loss. The differential diagnosis of a dorsal root The patient would typically have sudden onset of contralateral ganglionopathy is a short list which includes heavy metals and sensory loss without other weakness. A magnetic resonance paraneoplastic syndromes.
Table 2 Distribution and characteristics of patient complaints along the neuraxis
Distribution Facial Involvement Characteristic Pain Brain Unilateral often sensory + motor no
Spinal Cord Bilateral no sensory + motor poss.
Nerve Root Unilateral no sensory + motor yes
Nerve Unilateral or possible sensory, motor, Bilateral autonomic or combo yes
Neuromuscular Junction often bilateral yes, but not always motor no
Muscle Bilateral rare motor rare AANEM Course Current Approaches to Common Neuromuscular Problems 33
as a symptom in the most distal aspects of the affected nerve. A Table 3 Etiologic classifications affecting the central versus. slow progression from distal to proximal would strongly suggest peripheral nervous system a peripheral neuropathy in the differential diagnosis. Sensory complaints due to nerve root compression or irritation can also Peripheral Nervous progress slowly. However, these lesions are commonly characterized Etiology Central Nervous System System by pain in the affected root distribution. The sensory complaints from a nerve root injury or generalized neuropathy can be episodic, Vascular stroke, arterial-venous peripheral vascular particularly earlier in their course. Sensory disturbances from brain malformation claudication disease or spinal cord injury (typically vascular events) usually evolve more Structural tumor, disk tumor, disk acutely. Numbness or paresthesias due to multiple sclerosis typically Inflammatory infection, vasculitis neuropathy, vasculitis, happens over days and may be episodic. infection, myositis An acute or subacute onset with rapid progression of sensory Genetic myopathy, motor neuron disease neuropathy complaints, accompanied usually by weakness, is consistent with Immune- localization to the brain, spinal cord, nerve root, or nerve. Typically, ischemic injury is associated with sudden onset of sensory symp- Mediated Multiple sclerosis, myelopathy neuropathy, toms. Inflammatory disorders can develop quickly and progress neuromuscular over several days and can affect any part of the neuraxis. In the junction disease brain, acute onset of sensory symptoms is typically accompanied by weakness and/or encephalopathy. The differential diagnoses would PERIPHERAL NERVE include stroke, multiple sclerosis, cancer (lymphoma, metastasis), and infection. In the nerve root, acute sensory symptoms are likely Peripheral nerve injury is the most common reason for sensory dis- due to compression from a disk or trauma. In the peripheral nerve, turbances, especially numbness. However, peripheral nerve injury the possible etiologies are more extensive but some require timely frequently presents with both motor and sensory symptoms. The and appropriate management. Acute inflammatory demyelinating causes for a predominantly sensory neuropathy can be better under- polyneuropathy often requires prompt management to maintain stood if upon presentation the salient features of the patient’s sensory the airway and initiate treatment. Arsenic, thallium, tick paralysis, complaints are recognized. The goal is to distinguish between small and porphyria are other problems that start with numbness but fiber sensation (e.g., light touch, pain, and temperature) and large may result in a rapidly progressive disability for the patient and fiber sensation (e.g., position sensation and partial vibratory sensation). require urgent treatment (Table 4). The list of possible etiologies that result in sensory neuropathy is long. It is also important to recognize some distinguishing features of the Table 4 Considerations of differential diagnosis for neuropathy patient’s sensory disturbance, such as past history and family history. in patients with sensory complaints using the onset and Diabetes, alcohol abuse, chronic use of medication or vitamins, and progression as criteria history of similar sensory problems in the family are significant clues to identifying a proper etiology. In the United States and many European countries, diabetes is the most common cause of neuropathy. However, ACUTE (Days) CHRONIC (Weeks - Months) leprosy remains the most common cause of neuropathy worldwide. The Immune Guillain-Barré & variants, Chronic demyelinating etiologies can be categorized as toxic, immune, metabolic, inherited, Vasculitis neuropathy or mechanical. Toxins Botulism, Buckthorn, Heavy Metals Diphtheria;Tick; Arsenic; Environmental Chemicals HISTORY OF THE PRESENT ILLNESS Organophosphates; Thallium; Vacor
Knowing the timing of the onset of the symptoms as well as the Drugs Captopril (few case reports); family history and any occupational exposures can be helpful in Chemotherapeutic Agents understanding the disease process and fine-tuning the evaluation. Gangliosides; Gold; Nitrofurantoin; Suramin; Onset Zimeldine Metabolic Porphyria Porphyria, Diabetes A slow, progressive numbness or sensory disturbance is frequently described as distal numbness or tingling in the toes. This may Nutritional Vitamin toxicity or deficiency progress proximally into the feet and then up the legs and involve the hands as well (i.e., a stocking/glove distribution). The most Hereditary Hereditary motor and sensory distal segments of the nerve are most dependent upon axonal neuropathy hereditary transport for delivery of vital proteins and neurotransmitters. Any sensory neuropathy) process that interrupts axonal flow will be recognized by the patient 34 A Practical Approach to the Patient Presenting With Numbness AANEM Course
Family History Pathology in the CNS is characterized by pathologically brisk re- flexes and extensor plantar reflexes. Additionally there can be in- Family history can be helpful in identifying the etiology of neuropathy, creased tone and spasticity. Pathology in the PNS would result in particularly if a family member has had symptoms similar to the pa- diminished or absent reflexes along with atrophy and/or reduced tient's problems. The genetics of inherited neuropathy has significantly muscle tone. Asymmetric or absent reflexes suggest a focal neu- improved over the last decade and has increased the understanding of ropathy or radiculopathy. In a predominantly sensory neuropathy, the normal biology of nerve tissue. The hereditary motor and sensory the type of sensory loss can help indicate the nerve fibers involved neuropathies (i.e., Charcot-Marie-Tooth neuropathies) are now better (i.e., small fiber versus large fiber, or a mixed picture). The mo- understood and represent a group of disorders with overlapping dalities of sensory loss which should be tested include those listed clinical characteristics but distinct pathology. Some can be identified in Table 6. by currently available commercial laboratory tests. Inherited disorders affecting only sensation (e.g., hereditary sensory neuropathy) are quite Table 6 Sensory modalities which should be included on a rare. They may involve either small fiber sensory loss (pain and tem- thorough examination and their anatomic correlates perature) or loss of larger sensory fibers (proprioception, vibration). Identifying the type of sensory loss on examination can help refine the Modality Fiber type (Periphery) Tract (Central) differential diagnosis. Light touch small fiber Spinothalamic Occupational Exposure Temperature small fiber Spinothalamic Pinprick small fiber Spinothalamic Incidental exposure to agents that are toxic to nerve may be 2-point discrimination small fiber Spinothalamic easily missed on a routine history and review of systems. Contact with solvents, glues, fertilizer, oils, and lubricants can result in (parietal) a neuropathy that cannot be distinguished from other causes of Proprioception large fiber Dorsal columns idiopathic or hereditary etiology. Vibration both small and large fiber Medications The most useful information from the sensory examination results Injury to nerve caused by medications or vitamins is sometimes from the distribution of the deficit (symmetric versus asymmetric) overlooked. Over-the-counter oral preparations can result in a and the quality of the sensory loss. predominantly sensory neuropathy (even at therapeutic doses). Patients with a neuropathy from some other cause may have Sensory loss and neuropathy frequently can be associated with an exacerbation of their symptoms when taking some over-the- systemic diseases such as diabetes and several connective tissue dis- counter medications (Table 5). orders. Clinical signs on the general examination can be helpful if there is evidence of multiple organ systems disorders. Autoimmune, Table 5 Selected medications associated with a sensory or inflammatory, metabolic, and neoplastic disease are some of the a sensory predominant neuropathy which should be avoided in types of systemic illness which can present with peripheral nerve patients with a pre-existing peripheral neuropathy involvement resulting in numbness, paresthesia, and/or weakness. Careful attention to key clinical signs on general examination chloramphenicol metronidazole phenytoin nitrofurantoin can result in the underlying disease as well as the etiology for the neuropathy. cisplatin nitrous oxide pyridoxine taxol ethambutol nucleosides thalidomide Evaluation: Work-Up glutethemide didianoside dapsone hydralazine dideoxycytosine disulfram One of the primary goals in patient work-up is to identify a treat- able underlying process. Evaluation should include serologic and isoniazid stavudine radiographic evaluation where appropriate to clarify the differential diagnosis and treatment plan (Table 7). EXAMINATION CNS In addition to the body diagram, the physical examination can be helpful in localizing the site of injury. Evaluation of deep tendon Sensory loss or numbness localized to the CNS is most typically reflexes examines both an afferent component to carry input from associated with stroke or inflammatory disease. Evaluation of a the muscle tendon to the spinal cord and an efferent component patient with a suspected stroke, primarily involving sensation, to produce a muscle twitch during a reflex. The reflex is affected should include screening risk factors such as hypertension, diabetes, by descending cortical-spinal inputs that mitigate or enhance the cholesterol, tobacco use, and arrhythmia. An MRI of the brain is reflex arc. The arc reflects a specific root level and can be helpful usually indicated. Ischemic or inflammatory disease thought to in the localization of the process. be localized to the spinal cord should be evaluated by an MRI AANEM Course Current Approaches to Common Neuromuscular Problems 35
Table 7 Initial screening evaluation for suspected lesions based work-up. These tests can help localize nerve/muscle pathology upon the localization of sensory loss and suggest an etiology. NCSs especially are helpful in identifying treatable causes of neuropathy by demonstrating primary demyeli- nating processes. Impairment of conduction velocity or evidence Localization Laboratory tests Radiology Other of conduction block in a focal region or in multiple regions can Brain Hb-A1c , lipid MRI with contrast EKG, ECHO help define a demyelinating neuropathy. On the other hand, a profile, ESR, ANA, Transcranial Doppler possible reduced amplitude of the evoked response is more characteristic of CBC, electrolytes, Carotid doppler Holter an axonal neuropathy. It is important to note that axonal loss can RPR be the result of a primary pathologic process attacking the axon or Spinal cord Routine laboratory screen MRI with contrast LP with may be secondary to demyelination. Evaluating pressure, protein opening underlying illness, chemistry and cytology The EMG examination assesses the rate, amplitude, and frequency B12 of electrical impulses being transmitted by the muscle. While NCSs Nerve Root Not usually CT or MRI of the NCS and can differentiate demyelinating versus axonal, the EMG is able to Indicated suspected area EMG distinguish between the presence of denervation versus a primary Nerve Hb-A1c , ESR, Not usually indicated NCS and muscle disease (myopathic process). The role of EMG in assessing ANA, CBC, Possible nerve & EMG a patient with only numbness is limited since it is only testing the electrolytes, RPR, muscle biopsy motor nerves. However, a patient complaining of sensory loss in SPEP, a radicular pattern may not be aware of any motor weakness (and
immunofixation, B12 the physical examination may be normal), but the EMG may As indicated: demonstrate some motor axon involvement as the EMG can detect ANCA, cryoglobulins abnormalities with much greater sensitivity than the physical exam- ination. It would take a 50% loss motor fibers to detect weakness ANA = antinuclear antibody; ANCA = anti-neutrophil cytoplasmic autoantibodies; on physical examination while a loss of only 5% can be detected by CBC = complete blood count; CT = computed tomography; ECHO = echocardio- EMG. The added sensitivity in detecting abnormalities of motor gram; EKG = electrocardiogram; EMG = electromyography; ESR = erythrocyte units can implicate a combined motor-sensory etiology. sedimentation rate; LP = lumbar puncture; MRI = magnetic resonance imaging; NCS = nerve conduction study; RPR = rapid plasma reagin; SPEP = serum protein electrophoresis BIBLIOGRAPHY 1. Donofrio P. Evaluating the patient with peripheral neuropathy. In: and a lumbar puncture. The presence of elevated protein and an AANEM 2006 Course A: Numbness, tingling, pain and weakness: a increased number of white blood cells in the cerebrospinal fluid basis course in electrodiagnostic medicine. Rochester, MN: AANEM. suggests inflammation (myelitis). It is more difficult to define p 23-33. the specific etiology. Viral pathogens such as varicella, human T 2. Kimura J. Electrodiagnosis in diseases of nerve and muscle: prin- cell lymphotropic virus type 1, and human immunodeficiency ciples and practice. Philadelphia: FA Davis; 1983. virus have been demonstrated by high viral titers. Multiple scle- 3. Rosenfeld J, Martin RA, Bauer D. Numbness: a practical guide rosis is a clinical diagnosis requiring multiple signs and symp- for family physicians. http://www.aan.com/familypractice/pdf/ FINAL%20NUMBNESS%203.pdf toms at more than one point in time and MRI frequently can 4. Sunderland S. Nerves and nerve injuries, 2nd edition. New York, demonstrate plaques. Churchill Livingstone; 1978. p 483-490. Electrodiagnosis
The evaluation of the functional health of peripheral nerves by nerve conduction studies (NCSs) and of affected muscles by needle electromyography (EMG) is often an essential component of the 36 AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine
Francis O. Walker, MD E. Peter Bosch, MD Morris A. Fisher, MD Michael H. Rivner, MD John C. Kincaid, MD Ernest W. Johnson, MD
2008 COURSE B AANEM 55th Annual Meeting Providence, Rhode Island
Copyright © September 2008 American Association of Neuromuscular & Electrodiagnostic Medicine 2621 Superior Drive NW Rochester, MN 55901 Printed by Johnson Printing Company, Inc. ii CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine
Faculty Francis O. Walker, MD Morris A. Fisher, MD Professor of Neurology Professor Director of the EMG Laboratory Department of Neurology Wake Forest University Loyola University Stritch School of Medicine Winston-Salem, North Caroline Maywood, Illinois Dr. Walker is currently Professor of Neurology and Director of the EMG Dr. Fisher is a graduate of Harvard Medical School. He received his neu- Laboratory at Wake Forest University. He is a long time member of the rology training as well as a Fellowship in Clinical Neurophysiology at the American Association of Neuromuscular & Electrodiagnostic Medicine Massachusetts General Hospital in Boston, Massachusetts. For the past (AANEM) and has served on over 8 different committees task forces. He 16 years, he has been Professor of Neurology at Loyola University Stritch has also been the chair of the Workshop Committee. He has presented School of Medicine in Maywood, Illinois and an attending neurologist at numerous hands-on workshops, conducted courses, and organized sympo- the Hines Veterans Administration Hospital in Hines, Illinois. His current sia for the AANEM. He has trained 35 EMG fellows, received the Class of positions include Acting Chief of Neurology and Director of the Clinical 1997 Teaching Award at Wake Forest University School of Medicine, and Neurophysiology Laboratories at the Hines VA Hospital. Dr. Fisher has has authored or co-authored over 100 papers in peer reviewed journals. served on the Board of Directors of what is now the American Association Currently he is on the Examination Committee of the American Board of of Neuromuscular and Electrodiagnostic Medicine. He has also been on Neuromuscular Medicine and serves on the steering committees of three the Board of Directors and served as President of the American Academy major multicenter clinical trials. His interest in neuromuscular ultrasound of Clinical Neurophysiology. He is an author of over 90 articles in peer dates back to the mid 1980s when he began exploring the technique for its reviewed journals and book chapters. Dr. Fisher has an ongoing interest use in characterizing myopathies and evaluating fasciculations. in F waves and has funded research in the investigation of diabetic neu- ropathies. E. Peter Bosch, MD Michael H. Rivner, MD Department of Neurology Mayo Clinic Professor of Neurology Scottsdate, Arizona Medical College of Georgia Dr. Bosch attended medical school in Innsbruck, Austria, at the University Augusta, Georgia of Innsbruck. His residency in neurology was completed at the University Dr. Michael Rivner is a Charbonnier Professor of Neurology at the of Iowa in Iowa City, Iowa. He also did a Neuromuscular Fellowship at Medical College of Georgia (MCG) in Augusta, Georgia. He is the direc- Tufts-New England Medical Center in Boston, MA. He has been listed in tor of the EMG laboratory and clinical neurophysiology training program. Who’s Who for Physicians and Top Doctors in America numerous times. Dr. Rivner received his medical degree from Emory University in 1978. He is certified by the American Board of Psychiatry and Neurology and He performed his neurology training at the Medical College of Georgia holds several other specialty certifications. He is Professor of Neurology from 1978-1982 and a neuromuscular fellowship at the Medical College at the Mayo Clinic College of Medicine and currently practices in the of Georgia from 1982-1983. He has been on the faculty at MCG since Department of Neurology at Mayo Clinic Scottsdale. His interests include 1983. neuromuscular disorders, motor neuron disease, myopathies, myasthenia gravis, nerve and muscle pathology, amyotrophic lateral sclerosis, and clini- cal therapeutic studies of neuromuscular disorders
Dr. Morris A. Fisher disclosed he has done consulting work for NeuroMetrix. Any conflict has been resolved according to ACCME guidelines. Course Chair: Anthony E. Chiodo, MD
The ideas and opinions expressed in this publication are solely those of the specific authors and do not necessarily represent those of the AANEM. iii
John C. Kincaid, MD Ernest W. Johnson, MD Faculty Emeritus Professor Department of Neurology Department of Physical Medicine and Rehabilitation Indiana University School of Medicine The Ohio State University Indianapolis, Indiana Columbus, Ohio Dr. John Kincaid is a long-time member of the American Association of Dr. Johnson received his medical degree from The Ohio State University Neuromuscular & Electrodiagnostic Medicine (AANEM) and is certified in Columbus, Ohio, interned at Philadelphia General Hospital, and com- by the American Board of Electrodiagnostic Medicine. Dr. Kincaid has pleted his residency in physical medicine and rehabilitation at Ohio State served on 24 AANEM committees and is the AANEM’s delegate to the University under the sponsorship of the National Foundation of Infantile American Medical Association’s House of Delegates. In addition, he is a Paralysis. He has edited the textbook Practical EMG, and authored over Carrier Advisory Committee member for the Indiana Medicare carrier and 143 peer-reviewed articles. He established the Super EMG continuing has been a consultant to several health insurance companies for reviewing medical education course in 1978, and is still involved in planning and coverage policies, new technologies, and fraudulent billing practices. Dr. teaching the course. Currently, Dr. Johnson is an emeritus professor at Kincaid has been full-time faculty in the neurology department at Indiana Ohio State University. He has conducted research on electrodiagnostic University’s School of Medicine for 27 years, and holds a joint appoint- medicine in recurrent carpal tunnel syndrome and the use of H waves in ment in the department of Physical Medicine and Rehabilitation. upper limb radiculopathies. Dr. Johnson is past-president of the AANEM, AAPM&R, AAP, former chair of the American Board of Electrodiagnostic Medicine, and has been editor of the American Journal of Physical Medicine and Rehabilitation. iv Numbness, Tingling, Pain, and Weakness AANEM Course
Please be aware that some of the medical devices or pharmaceuticals discussed in this handout may not be cleared by the FDA or cleared by the FDA for the specific use described by the authors and are “off-label” (i.e., a use not described on the product’s label). “Off-label” devices or pharmaceuticals may be used if, in the judgement of the treating physician, such use is medically indi- cated to treat a patient’s condition. Information regarding the FDA clearance status of a particular device or pharmaceutical may be obtained by reading the product’s package labeling, by contacting a sales representative or legal counsel of the manufacturer of the device or pharmaceutical, or by contacting the FDA at 1-800-638-2041. v CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine
Contents
Faculty ii
Objectives v
Course Committee vi
Why Neuromuscular Ultrasound is Ready for Prime Time 1 Francis O. Walker MD
Neuromuscular Ultrasound is Not Ready for Prime-Time Use 5 E. Peter Bosch, MD F Waves – Physiology and Clinical Uses 11 Morris A. Fisher, MD
F-Wave Studies are of Limited Clinical Value 17 Michael H. Rivner, MD
Needle EMG Should be a Routine Component of the Electrodiagnostic Evaluation of Carpal Tunnel Syndrome 21 John C. Kincaid, MD
Appropriate Testing for Carpal Tunnel Syndrome 23 Ernest W. Johnson, MD
CME Self-Assessment Test 27
O b j e c t i v e s —After attending this session, participants will develop an understanding of, and be able to incorporate into their practice, arguments in favor of and against the following: (1) the use of F waves in disorders of the peripheral nervous system and nerve roots as well as the central nervous system; (2) the circumstances in which performing a needle EMG adds useful information in the evaluation of suspected carpal tunnel syndrome; and (3) the role of diagnostic ultrasound in the evaluation of neuromuscular disorders. P rerequisite —This course is designed as an educational opportunity for physicians. A c c r e d i t a t i o n St a t e m e n t —The AANEM is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. CME Cr e d i t —The AANEM is accredited by the ACCME to provide continuing medical education (CME) for physicians. The AANEM designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s) TM. Each physician should only claim credit commensurate with the extent of their participation in the activity. This event is an Accredited Group Learning Activity as defined by the Maintenance of Certification Program of The Royal College of Physicians and Surgeons of Canada. CME for this activity is available 9/08 - 9/11. vi
2007-2008 AANEM COURSE COMMITTEE Anthony E. Chiodo, MD, Chair Ann Arbor, Michigan
Shawn J. Bird, MD Erick A. Grana, MD Simon Zimnowodzki, MD Philadelphia, Pennsylvania Tampa, Florida Chicago, Illinois
Kevin B. Boylan, MD Thomas Y.C. Pang, MD Sasa Zivkovic, MD Jacksonville, Florida Chicago, Illinois Pittsburgh, Pennsylvania
Gary L. Branch, DO David Bryan Shuster, MD Owosso, Michigan Dayton, Ohio
2007-2008 AANEM PRESIDENT Peter D. Donofrio, MD Nashville, Tennessee 1
Why Neuromuscular Ultrasound is Ready for Prime Time
Francis O. Walker MD Professor of Neurology Director of the EMG Laboratory Wake Forest University Winston-Salem, North Caroline
INTRODUCTION In ulnar neuropathy at the elbow,4,7,26 similar findings prevail, Whether a physician should seriously consider learning neuromus- although there is a significantly fewer number of studies. Again, cular (NM) ultrasound (US) and use it as part of the routine evalu- studies show that US is a robust technique for identifying ulnar ation of patients seen in an electrodiagnostic (EDX) laboratory is neuropathy at the elbow, but none of these studies are adequate in debatable. An argument affirming the use of US is based on an terms of head-to-head comparisons of US with nerve conduction analysis of the scientific evidence and an evaluation of the future studies (NCSs). of US. The evidence shows that US offers valuable contributions in regards to several common disorders in which EDX testing is Experience with radial nerve palsy at the spiral groove and peroneal currently used for diagnostic confirmation, and that there is con- neuropathy at the fibular head have yielded similar findings, 16,23 siderable promise for other unique applications in NM disorders. but the studies are fewer than those for ulnar neuropathy at the The evolution of US imaging also strengthens the argument for elbow with a smaller number of patients studied. Interestingly, using US. peroneal nerve palsies, particularly if not associated with weight loss or known leg crossing, have a fairly high incidence of association with sonographically evident cysts.23 COMMON ENTRAPMENT NEUROPATHIES IN WHICH US IS USEFUL CHALLENGES OF COMPARATIVE STUDIES There are perhaps 50 citations in PubMed that focus on the sen- sitivity of US in carpal tunnel syndrome (CTS). The data can Will it be possible to establish US or NCSs as superior in terms of be summarized fairly simply; US is robustly specific and sensitive specificity and sensitivity in diagnosing entrapment neuropathies? in the diagnosis of CTS.1,2,3,8,10,12,14,15,17,18,20,22,24,28 The relative There are at least four plausible reasons to assume that this will quality of these studies is not uniform, but there is considerable not occur. weight in the multiplicity of studies performed. Depending on the study, the quality is of greater, lesser, or equivalent specificity First, currently there is no single golden standard for the diagno- and sensitivity to EDX testing, depending on how CTS is defined, sis of entrapment neuropathies, so it is futile to expect certainty and which types of US and EDX parameters for diagnosis are used. with any comparative study of diagnostic tests for these problems. Since EDX techniques have been perfected for diagnosing CTS As such, there will always be an error factor for any computed for the last five decades, it probably maintains a slight edge in this specificity and sensitivity for any technique.2 Second, at this time, regard, but the data is not conclusive. There are clear instances there is no uniform consensus as to which of the many available where EDX tests can confirm CTS when US is normal, and clear EDX tests generates the best specificity and sensitivity for CTS, instances where US can diagnose the disorder where EDX studies the most common entrapment neuropathy. It could be mixed are normal. palmars, multiple sensory nerve comparisons, inching, near nerve 2 Why Neuromuscular Ultrasound is Ready for Prime Time AANEM Course studies, or a combination of these and electromyography (EMG). tumor. In entrapment neuropathies, because treatment is often Since experts cannot agree on the ideal EDX tests for CTS, it elective and intervention typically carries low morbidity, slight is problematic to compare EDX testing to another technique improvements in diagnostic specificity or sensitivity are unlikely (or if a comparison is performed, some experts will be dissatis- to significantly improve outcomes from current standard practices, fied with the choice of EDX protocol). There is similar debate which already incorporate a healthy appreciation of imperfect regarding the precise EDX techniques needed to diagnose other diagnostic certainty. entrapment neuropathies. In selecting a diagnostic test to help confirm a suspected case of Third, in like manner, it is difficult to determine which US entrapment neuropathy, multiple factors influence the test choice. technique is optimal for diagnosing an entrapment neuropathy. Key elements of such a decision are time (e.g., does the patient Measuring nerve enlargement, although conceptually simple, need to make a separate visit to have the test conducted), expense, involves a number of choices. The physician must decide if it and discomfort. At this time, US, which is painless, has a clear should be measured by using the cross sectional area of the nerve, advantage in terms of comfort over EDX testing. Patients and its thickness (diameter) 4 or flattening ratio.10,17 The measure- referring physicians are particularly sensitive to the perceived pain ment site must also be determined. This could be a pre-ordained of an EDX procedure. US is the first technology to offer a pain- anatomic site, but there is debate as to which site should be used. less alternative to electrodiagnosis for evaluating common entrap- For example, for the median nerve at the wrist, should it be placed ment neuropathies. Additionally, US can be performed at a lower at the distal wrist crease or the level of the hook of the hamate?20 cost and is more time efficient. Generally, for the patient and Is it preferable to evaluate the nerve over several centimeters and referring physician, US need not establish diagnostic superiority, record the area of maximal swelling? Is it better to use a ratio12 it simply needs to approximate that of EDX assessment for there to measure the thickness of the nerve at the involved site and to be a compelling case for its routine, or in select cases, perhaps compare it to the contralateral side or an uninvolved site that is exclusive use. more proximal?6,12 Should a trace method or some other method be used for calculating cross sectional area?3 Should hypoechoic For example, some clinicians treat mild or mild to moderate CTS changes in the nerve be graded subjectively or measured precisely with splinting and steroid injections into the carpal tunnel, reserv- with some sort of quantitative program?25 How important is in- ing surgery for those who fail these conservative measures. If the cluding an assessment of nerve mobility in terms of sagittal sliding, EDX consultant routinely performs needle EMG of the abductor diving among the tendons with wrist flexion, or subluxation at pollicis brevis in cases of suspected CTS, they may quite reason- the elbow?25 Should US values be corrected for factors such as ably decide that such cases should be initially referred for US age and body size which may correlate with nerve cross sectional evaluation. If the result is clearly abnormal, and an evaluation of area?6,7,8 Until there is a consensus about which EDX and US patients in the author’s laboratory has shown that 100% of patients protocols are optimal for identifying entrapment neuropathies, it with cross sectional areas of the median nerve exceeding 0.2 cm2 will be difficult to design a comparative study that provides truly have abnormal NCS findings indicative of CTS,8 then it might be conclusive results. reasonable to forgo further EDX testing and inject steroids into the carpal tunnel (perhaps using US guidance). If the patient failed Fourth, it is not known what level of variation exists across EDX therapy, at that point, further EDX tests might be warranted. In laboratories in terms of qualifications of the technicians and this case, it is logical that the steroid injection, although associated physicians involved, and standardization in the techniques em- with a very low likelihood of other complications, would likely ployed. For example, there are still a number of laboratories that be associated with less discomfort than the needle EMG and do not routinely check the temperature of the extremities before multiple shocks. performing NCSs. Unfortunately, it is not known how much variation exists in conducting US techniques. However, clearly It is important to determine what information EDX testing and there is variation and it is likely to be significantly greater for US can provide that is not captured by a specificity and sensitiv- US and EDX testing than for other specific types of procedures ity analysis in the evaluation of entrapment neuropathies. One with test results that are based on hard copy images or blocks of of the challenges with statistical assessment of diagnostic pro- tissue amenable to peer review by other experts at subsequent cedures such as EDX studies or NM US that generate complex intervals. Therefore, a comparison of techniques in an optimal information is that the information generated cannot be reduced single laboratory setting would not predict the amount of vari- to a single number. For example, in CTS, EDX tests provide ance in technical accuracy of a procedure being performed in information about the severity, may identify an entrapment multiple laboratories. neuropathy, determine the extent to which axons or myelin are involved, and reveal the relative health of nearby nerves. In selecting a diagnostic test, it is important to consider the Furthermore, in cases of complete median neuropathy from CTS, advantages one may have over another in regards to sensitiv- EDX testing may provide sufficient evidence to help a surgeon ity, specificity, as well as other such factors. Greater certainty in decide not to operate because it would be unlikely that the diagnosis is needed most in disorders in which therapeutic options disorder would improve enough to warrant surgical morbidity. carry considerable risks. The discomfort of a biopsy is appropri- Baseline studies are helpful for post-operative evaluations of failed ate for the evaluation of a potentially malignant nerve or muscle surgical intervention. AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 3
US cannot be as specific as EDX tests with respect to axonal versus Another use of US is in the prevention of surgical complications. myelin damage or completeness of nerve injury, but it can provide An interesting study recently showed that preoperative mapping of some evidence as to muscle atrophy in the appropriate nerve dis- the sural nerve could be used to identify it before surgery, a process tribution.21 It can precisely identify the location and extent of that could reduce the likelihood of its compromise in Achilles focal nerve swelling or identify nerve transaction.5 Additionally, tendon repair.11 Another recent report showed that by identifying it can provide information on the ability of the nerve to slide in vascular anomalies commonly associated with an atypical anatomic the sagittal and axial planes (an observation that is key in certain course of the recurrent laryngeal nerve, the incidence of inadvertent rehabilitation protocols for CTS and its surgical repair),6 patho- injury to the nerve was reduced.13 Although it was never studied, it logic vascularity (using power Doppler),17 the extent to which the seems likely that mapping the course of the spinal accessory nerve lumbricals or flexor digitorum muscles penetrate into the carpal before surgery in the area might prevent inadvertent injuries of this tunnel during wrist flexion and extension (factors which may nerve, which is an not uncommon occurrence.19 contribute to CTS and which may be amenable to surgical resec- tion of small portions of problematic hypertrophic muscle),6,8 the Developments in US Technology echogenicity of the nerve (which may reflect increased fluid content and be associated with swelling or venous retention)6, the integ- One of the most compelling reasons for physicians to adopt US rity of the transverse carpal ligament (of interest in patients with in their practice is related to the pace of technological advance- failed recent carpal tunnel release), anomalous nerve branching or ment in sonographic imaging. Over the last decade, there has splitting, the presence of cysts or tumors, and the relationship of been a steady evolution in the quality and availability of high- the nerve to vascular structures, such as persistent median arter- resolution probes in clinical US. A reduction in the size of the equip- ies.6 Obviously, it is unlikely that a standard statistical analysis of ment and cost of instrument operation, enhanced digital features specificity and sensitivity will be able to incorporate the diversity of that facilitate storing, sharing, and post-processing analyses, sim- qualitative and quantitative information relevant to CTS obtained plification of application, and newer techniques for image display, in EDX or US studies, nor is it sensible to make clinical deci- measurement of elastance,27 and innovations in contrast material sions in regards to testing based on an incomplete analysis of the are notable improvements. During the coming decade, further ad- data available. vances in US technology are likely to continue. EDX technology is fairly static and could still be performed on instruments available Both US and NCSs have fairly high specificity and sensitivity for 40 years ago, and barring unexpected discoveries, it is unlikely to CTS and for ulnar neuropathy at the elbow. Due to the absence of significantly change over the course of the next decade. a gold standard for diagnosis, debate over optimal techniques, the difficulty in reducing complex information into single variables, The Role of Electrodiagnosis and US and variations in practice patterns and quality across different laboratories, it would be difficult to confer convincing superiority In the last 30 years, imaging has revolutionized the evaluation of dis- to either technique in a way that is applicable to the diversity of orders of the central nervous system (CNS). Much of the ability to laboratory settings. understand newer imaging modalities (magnetic resonance imaging [MRI], positron emission tomography, and functional MRI) has come from correlation studies with pre-existing imaging techniques THE FUTURE OF NEUROMUSCULAR US of angiography, plain radiographs, myelography, and computed Other Potential Uses of US in NM Medicine tomography (CT). In the field of NM disorders, however, there is no solid corpus of experience with imaging. As such, the key techniques that currently provide the most helpful correlative inter- US, as previously alluded to, can be used therapeutically to guide pretation of US images are the clinical evaluation and EDX testing. injections of steroids as well as guide therapeutic injections of botu- Fortunately, US technology is readily accessible to practitioners of linum toxin, particularly for electrically silent tissues such as the electrodiagnosis, individuals who are skilled in the clinical evalua- salivary glands.9 Another potential indication for US is in screen- tion of NM patients and skilled in the interpretation of EDX and ing large populations of at-risk individuals for early signs of CTS, other laboratory findings such as genetic tests, serology, and histo- or to screen selected family members for hypertrophic hereditary pathology. It would be unthinkable to try to manage severe mul- neuropathy. The portability and non-invasiveness of the technique tiple sclerosis or recurrent cerebrovascular disease without imaging makes it more palatable to participants for such studies as com- today, and given the continued advances in imaging technologies, pared to EDX testing. US may be able to accurately identify mus- this may be true of NM disorders in the future. The large com- culoskeletal disorders, which often mimic symptoms of entrapment munity of involved physicians who are members of the American neuropathies. Thus, if a patient has a negative EDX work-up for Association of Neuromuscular & Electrodiagnostic Medicine is a suspected neurogenic process, US may be able to identify other uniquely positioned to elucidate the best strategies for applying treatable conditions such as tendonitis or bursitis. Currently, there imaging to best enhance the diagnosis and care of patients with is not a sufficient number of published studies on the use of US in NM disorders. By becoming involved now at this critical juncture this fashion. However, it seems likely it will become an informative of advancing and receding technologies, clinicians will be able to direction of inquiry because US is a routinely accepted technique establish themselves as the experts in the emerging area of imaging for diagnosing a variety of musculoskeletal ailments. inNM disease. 4 Why Neuromuscular Ultrasound is Ready for Prime Time AANEM Course
CONCLUSION 10. El-Karabaty H, Hetzel A, Galla TJ, Horch RE, Lücking CH, Glocker FX.The effect of carpal tunnel release on median nerve flattening and nerve conduction. Electromyogr Clin In conclusion, regarding the value of US, the following points Neurophysiol. 2005;45(4):223-227. should be able to obtain a broad consensus: 11. Flavin R, Gibney RG, O'Rourke SK. A clinical test to avoid sural nerve injuries in percutaneous Achilles tendon repairs.Injury. 1) US and EDX testing are complementary diagnostic tests that 2007;38(7):845-847. can contribute to patient care. 12. Hobson-Webb LD, Massey JM, Juel VC, Sanders DB. The ultrasonographic wrist-to-forearm median nerve area ratio in 2) MRI or CT alone, on current relatively low-resolution scanners carpal tunnel syndrome. Clin Neurophysiol. 2008;119(6):1353-1357. without clinical or EDX correlation, are less likely to be informative 13. Iacobone M, Viel G, Zanella S, Bottussi M, Frego M, Favia G. than high-resolution US imaging with such correlation. The usefulness of preoperative ultrasonographic identification of nonrecurrent inferior laryngeal nerve in neck surgery. Langenbecks 3) The discomfort of EDX testing may have had a negative impact Arch Surg. 2008. [Epub ahead of print] 14. Kele H, Verheggen R, Bittermann HJ, Reimers CD. The potential on referrals to NM experts. The addition of a painless, informative, value of ultrasonography in the evaluation of carpal tunnel syn- diagnostic technique may enhance referrals, particularly for those drome.Neurology. 2003;61(3):389-391. unusually sensitive to discomfort (e.g., children) and those in need 15. Koyuncuoglu HR, Kutluhan S, Yesildag A, Oyar O, Guler K, Ozden of serial studies of complex NM problems. A.The value of ultrasonographic measurement in carpal tunnel syn- drome in patients with negative electrodiagnostic tests. Eur J Radiol. 4) Innovation in imaging technology is currently outpacing 2005;56(3):365-9. innovation in EDX technology. 16. Lo YL, Fook-Chong S, Leoh TH, Dan YF, Tan YE, Lee MP, Gan HY, Chan LL. Rapid ultrasonographic diagnosis of radial entrapment 5) In time, it seems likely that NM US will likely find unique neuropathy at the spiral groove. J Neurol Sci. 2008;271(1-2):75-79. diagnostic, preventative, and therapeutic indications beyond its use 17. Mallouhi A, Pülzl P, Trieb T, Piza H, Bodner G. Predictors of carpal in the evaluation of common entrapment neuropathies. tunnel syndrome: accuracy of gray-scale and color Doppler sonography. AJR Am J Roentgenol. 2006 May;186(5):1240-1245. 18. Mondelli M, Filippou G, Gallo A, Frediani B. Diagnostic utility of ul- For these reasons, US should be embraced by NM and trasonography versus nerve conduction studies in mild carpal tunnel EDX physicians. syndrome. Arthritis Rheum. 2008;59(3):357-366. 19. Morris LG, Ziff DJ, Delacure MD. Malpractice litigation after surgi- cal injury of the spinal accessory nerve: an evidence-based analysis. REFERENCES Arch Otolaryngol Head Neck Surg. 2008;134(1):102-107. 20. Nakamichi K, Tachibana S. Ultrasonographic measurement of 1. Altinok MT, Baysal O, Karakas HM, Firat AK. Sonographic evalu- median nerve cross-sectional area in idiopathic carpal tunnel syn- ation of the carpal tunnel after provocative exercises. J Ultrasound drome: Diagnostic accuracy. Muscle Nerve. 2002;26(6):798-803. Med. 2004;23(10):1301-1306. 21. Severinsen K, Andersen H. Evaluation of atrophy of foot muscles 2. Bachmann LM, Jüni P, Reichenbach S, Ziswiler HR, Kessels AG, in diabetic neuropathy -- a comparative study of nerve conduction Vögelin E. Consequences of different diagnostic "gold standards" in studies and ultrasonography. Clin Neurophysiol. 2007;118(10):2172- test accuracy research: Carpal Tunnel Syndrome as an example. Int J 2175. Epidemiol. 2005;34(4):953-955. 22. Swen WA, Jacobs JW, Bussemaker FE, de Waard JW, Bijlsma JW. 3. Bayrak IK, Bayrak AO, Tilki HE, Nural MS, Sunter T. Ultrasonography Carpal tunnel sonography by the rheumatologist versus nerve con- in carpal tunnel syndrome: comparison with electrophysiological stage duction study by the neurologist. J Rheumatol. 2001;28(1):62-69. and motor unit number estimate. Muscle Nerve. 2007;35(3):344-348. 23. Visser LH. High-resolution sonography of the common peroneal 4. Beekman R, Wokke JH, Schoemaker MC, Lee ML, Visser LH. Ulnar nerve: detection of intraneural ganglia. Neurology. 2006;67(8):1473- neuropathy at the elbow: follow-up and prognostic factors determin- 1475. ing outcome. Neurology. 2004;63(9):1675-1680. 24. Visser LH, Smidt MH, Lee ML. High-resolution sonography 5. Cartwright MS, Chloros GD, Walker FO, Wiesler ER, Campbell WW. versus EMG in the diagnosis of carpal tunnel syndrome. J Neurol Diagnostic ultrasound for nerve transection. Muscle Nerve. 2007 Neurosurg Psychiatry. 2008 Jan;79(1):63-67. ;35(6):796-799. 25. Walker FO. Neuromuscular ultrasound. Neurol Clin. 2004 22(3):563- 6. Cartwright MS, Passmore LV, Yoon JS, Brown ME, Caress JB, Walker 590, FO. Cross-sectional area reference values for nerve ultrasonography. 26. Wiesler ER, Chloros GD, Cartwright MS, Shin HW, Walker FO. Muscle Nerve. 2008;37(5):566-571. Ultrasound in the diagnosis of ulnar neuropathy at the cubital 7. Cartwright MS, Shin HW, Passmore LV, Walker FO. Ultrasonographic tunnel.J Hand Surg [Am]. 2006;31(7):1088-1093. findings of the normal ulnar nerve in adults. Arch Phys Med Rehabil. 27. Zheng YP, Li ZM, Choi AP, Lu MH, Chen X, Huang QH. 2007;88(3):394-396. Ultrasound palpation sensor for tissue thickness and elasticity 8. Cartwright MS, Shin HW, Passmore LV, Walker FO. Ultrasonographic measurement--assessment of transverse carpal ligament. Ultrasonics. Reference Values for Assessing the Normal Median Nerve in Adults. 2006;44 Suppl 1:e313-317. J Neuroimaging. 2008 28. Ziswiler HR, Reichenbach S, Vögelin E, Bachmann LM, Villiger 9. Dogu O, Apaydin D, Sevim S, Talas DU, Aral M. Ultrasound-guided PM, Jüni P. Diagnostic value of sonography in patients with sus- versus 'blind' intraparotid injections of botulinum toxin-A forthe pected carpal tunnel syndrome: a prospective study. Arthritis Rheum. treatment of sialorrhoea in patients with Parkinson's disease.Clin 2005;52(1):304-311. Neurol Neurosurg. 2004;106(2):93-96. 5
Neuromuscular Ultrasound is Not Ready for Prime-Time Use
E. Peter Bosch, MD Department of Neurology Mayo Clinic Scottsdale, Arizona
INTRODUCTION (Phalen’s sign). However, the clinical usefulness of these tests is High-resolution ultrasound (US) has made it possible to image limited due to the wide range of sensitivities (38% to 85%) and peripheral nerves and muscle. The application of this tech- specificities (54% to 98%).9 The conditions associated with CTS nique to neuromuscular (NM) disorders has sparked considerable are numerous, but most cases seen in routine practice are idiopathic. interest among NM clinicians. It provides clinicians with an Underlying conditions frequently associated with CTS include dia- imaging tool to evaluate anatomical detail at sites where disordered betes, hypothyroidism, pregnancy, and rheumatoid arthritis. functions have been identified. US is noninvasive, painless, and less expensive than electrodiagnostic (EDX) studies, conventional EDX studies are used to confirm the clinical diagnosis of CTS, computed tomography, or magnetic resonance imaging (MRI). to define the severity of nerve damage, exclude other conditions However, the question remains as to whether NM US is ready for producing similar symptoms such as proximal median nerve prime time as defined by its use in routine clinical practice outside lesions, brachial plexopathy, and cervical radiculopathies (espe- academic centers. Though the use of US in musculoskeletal trauma cially, C6 and C7), and uncover a co-existing polyneuropathy. A or in interventions guiding peripheral nerve blocks or botulinum critical review of the literature of EDX studies3 in CTS provides toxin injections will not be reviewed, the diagnostic value of US in scientific evidence that median motor and sensory nerve conduc- common NM disorders will be addressed. tion studies are valid and reproducible studies that can confirm the clinical diagnosis of CTS with a high degree of sensitivity (>85%) VALUE OF US IN THE DIAGNOSIS OF CARPAL TUNNEL and specificity (95%). Despite using more sensitive comparative SYNDROME median-ulnar studies, a small group of patients (10% to 15%) with clinical symptoms compatible with CTS will have normal Carpal tunnel syndrom (CTS) results from an entrapment of the EDX studies. median nerve at the wrist and is the most frequent reason patients are referred for EDX studies. According to population studies, it COULD IMAGING STUDIES USING US BE OF is the most common entrapment neuropathy with a prevalence of ADDITIONAL DIAGNOSTIC VALUE? 6% in women and 0.6% in men.21 The clinical diagnosis rests on typical core symptoms of wrist, arm pain, and hand paresthesia that In 1993, the Quality Standards Subcommittee of the American is provoked by sleep or sustained hand grip and relieved by changes Academy of Neurology 2 stated that the benefits of diagnostic in hand posture or shaking of the hands. Additional core symp- imaging techniques such as US had yet to be fully established. toms include sensory symptoms in digits 1, 2, 3, and part of the Since then, more than 200 citations of sonography or US and CTS 4th digit, as well as thenar atrophy and weakness in more advanced have appeared in PubMed. Among NM physicians in the United cases.1 Provocative tests are based on eliciting paresthesia by tapping States, US is not a universally accepted or widely applied test. High on the nerve at the wrist (Tinel’s sign) or by flexion of the wrist resolution US provides morphologic information of the content 6 Neuromuscular Ultrasound is Not Ready for Prime-Time Use AANEM Course
(i.e., the median nerve, deep and superficial finger flexor tendons, agreement beyond chance, for EDX studies using the median- possible ganglion cysts, tumors, anomalous muscles, median artery) ulnar distal sensory latency difference versus clinical evaluation was and surrounding tissues (flexor retinaculum and carpal bones) of 0.64; that for US kappa was 0.69, indicating substantial agreement the carpal tunnel. Four characteristic features have been described between both tests.18 Combining US and EDX studies did not by US in patients with well-defined CTS: (1) increase of the cross significantly improve sensitivity and specificity. sectional area (CSA) of median nerve at the entry of the carpal tunnel at the level of the pisiform bone; (2) increase in the CSA at Should EDX Studies be Abandoned in Favor of US in the level of the pisiform bone compared to the CSA at the level of the Diagnosis Of CTS? the distal radius; (3) increase in the flattening ratio determined as the ratio of the nerve’s major to minor axis at the level of the hook Each investigation yields different information. High resolution US of the hamate; and (4) significant displacement or bowing of the offers the advantage of yielding structural information of the carpal flexor retinaculum.7 tunnel and its content. In addition, it is less expensive, painless, and therefore, preferred by patients. On the other hand, sonography is Case-controlled studies comparing US findings in patients with an operator dependent test that requires special training. It takes confirmed CTS to normal control subjects report on the pathologi- about 6 months to train a rheumatologist to become an expert cal swelling of the median nerve by assessing the CSA at variable sonographer.17 Whether NM clinicians can achieve competency in levels using different landmarks along the carpal tunnel.16,19 The a shorter training period is not known. cut off values of the CSA considered abnormal in these studies have ranged from 9.8 to 11 mm2, which overlap in part with EDX studies are readily available in the United States and can normal control values (7.8 to 10.2 mm2). When selecting cases be performed in community and academic centers according with confirmed CTS and control subjects, patients with borderline to established guidelines. EDX studies not only confirm the or mild disease are frequently omitted, resulting in unusual high presence of CTS, but are also able to determine its severity and define diagnostic accuracy that cannot be expected in clinical reality. demyelination versus axonal loss; differentiate CTS from other mimicking lesions such as C6 - C7 cervical radiculopathies, proxi- Evaluating a new diagnostic test requires an independent blind mal median nerve and brachial plexus lesions; and detect an under- comparison of the gold standard in consecutive patients with lying polyneuropathy. Despite the higher cost and slight discomfort, suspected CTS to reliably determine its accuracy and clinical valid- EDX studies should not be abandoned in patients with suspected ity. Among the more than 200 citations on sonography and CTS CTS. US should be considered a complementary study whenever in PubMed, only four are prospective studies (Table 1). Three structural abnormalities of the carpal tunnel are suspected, or when studies18,22,23 used clinical criteria supported by EDX studies, while less invasive endoscopic surgical techniques are planned. Swen and colleagues17 used the beneficial response after operative treatment as the diagnostic gold standard. The four studies con- US IN THE DIAGNOSIS OF ULNAR NEUROPATHY AT cluded that US is comparable to EDX studies in the diagnosis of THE ELBOW CTS. US has an excellent power to rule in CTS for median nerve CSA greater than 12 mm2 with a post-test probability of greater Ulnar neuropathy at the elbow (UNE) is second only to CTS as than 90%.23 The kappa co-efficient, or ratio of actual to potential the most common entrapment neuropathy affecting the upper
Table 1 Prospective studies of diagnostic value of ultrasound for carpel tunnel syndrome
Author Patients/wrists Gold Standard CSA mm2 Sensitivity % Specificity % +LR Swen17 63 >90% ≥ 10 70 63 1.9 improvement at entry after surgery Wong22 120/193 Clin +EDX; ≥ 9 93 56 2.1 DML > 4ms; at inlet M-U SLD >0.4 ms ≥ 10 86 74 3.3 Zisweiler23 71/101 Clin +EDX Largest DML >4.2 ms ≥ 12 44 100 19.9 SCV <41m/s ≥ 10 82 87 6.3 Visser18 168/ Clin +EDX >10 78 91 8.7 DML >3.8 ms at inlet M-U SLD >0.4 ms
CSA = cross sectional area of median nerve; DML = distal motor nerve latency; EDX = electrodiagnostic; + LR = positive likelihood ratio; M-U SLD = median ulnar sensory latency digit 4 difference; SCV = antidromic median sensory conduction velocity. AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 7 extremity (UE). The ulnar nerve at the elbow may potentially be lesions (3.3 mm2) compared to electrophysiologically defined compressed at four sites that include (from proximal to distal): demyelinating lesions (2.5 mm2). At the cut-off value of ≥ 2.5 the medial intermuscular septum, the epicondylar groove, the mm for the largest ulnar nerve diameter (measured at the medial humero-ulnar arcade (i.e., the arcuate ligament that joins the two epicondyle, and 2 cm proximally & distally), the investigators heads of the flexor carpi ulnaris), and the exit of the nerve from reported a sensitivity of 80%, specificity of 91% , and positive the flexor carpi ulnaris muscle. The clinical spectrum of UNE likelihood ratio of 9. In the subgroup of patients who had nonlo- ranges from paresthesias in the fourth and fifth digits to sensory calizing abnormalities on EDX studies, US confirmed ulnar nerve impairment in the territory of the ulnar nerve with or without swelling at the elbow in 85% of subjects. (Table 2). If confirmed atrophy and weakness of ulnar innervated muscles. In contrast by additional studies, diagnostic US may replace MRI in the local- to CTS, localizing the ulnar nerve lesion at the elbow is more ization of ulnar nerve lesions in patients with nonlocalizing EDX difficult and technically challenging with EDX studies. Unless abnormalities. Diagnostic US is a promising adjunct technique partial motor conduction block or focal slowing of motor conduc- to EDX studies in the diagnosis of UNE. However, standardiza- tion velocity across the elbow can be documented, EDX studies tion of the techniques and additional well-designed prospective may reveal nonlocalizing abnormalities in cases of pure axonal studies are needed before this test can be recommended for routine injury at the elbow. Needle electromyography (EMG) of ulnar clinical practice. innervated forearm muscles, such as flexor carpi ulnaris and flexor digitorum, may frequently be normal even in such proximal lesions US IN THE EVALUATION OF HYPERTROPHIC because of fascicular sparing. In 1999, the American Association NEUROPATHIES of Neuromuscular & Electrodiagnostic Medicine (AANEM)2 published guidelines to optimize EDX studies for UNE. The EDX High resolution US is capable of identifying peripheral nerves and studies have reported sensitivities ranging from 37% to 86%, and the brachial plexus in the UEs. Deeply situated nerves in the lower specificities of 95% or greater. Ulnar neuropathy at the wrist, C8 extremity are more difficult to depict.8 Problems that emerge while radiculopathy, lower trunk/medial cord brachial plexopathy, or imaging nerves with US include difficulty in the identification of even motor neuron disease can mimic UNE. deeper situated nerves, nerves that are surrounded by fat or beneath bony structures, the imaging provides a relatively small field of CAN DIAGNOSTIC US IMPROVE THE LOCALIZATION view, and the quality of the image being operator dependent. US OF UNE ? has the potential to identify focal, multifocal, and diffuse enlarge- ment of peripheral nerves. The reference values of the CSA of A limited number of studies using diagnostic US have documented peripheral nerves have recently been published. Diffusely enlarged segmental ulnar nerve swelling along its course at the elbow.11 nerves may be seen in hypertrophic neuropathies which include The focal nerve swelling has been measured using the maximal hereditary neuropathies (i.e., Charcot Marie Tooth disease types 1 diameter of the ulnar nerve,5 its maximal CSA along the elbow,10,20 and 3, Refsum's disease, and neurofibromatosis), and acquired neu- or a ratio of the nerve diameter between medial epicondyle and ropathies such as chronic inflammatory demyelinating neuropathy, elbow joint level.11 Two case control studies of 14 and 33 UNE leprosy, and rarely multifocal motor neuropathy. Confirming en- patients confirmed significantly increased ulnar nerve CSA as larged peripheral nerves are of limited diagnostic value in patients compared to healthy volunteers.10,20 One study reported a sensi- with CMT1A or chronic inflammatory demyelinating polyneu- tivity of 93% and specificity of 95%, while the other reported a ropathy. Imaging studies are of much greater diagnostic importance sensitivity of less than 50%. Applying the test in healthy control in hypertrophic mononeuropathies, which are single nerves with subjects to determine its specificity artificially increases the results focally enlarged segments. Perineurioma, chronic inflammatory de- because healthy volunteers are not part of the clinical spectrum of myelinaying mononeuropathy, leprosy, lymphoma, and peripheral patients. Prospective studies of patients with suspected UNE are nerve sheath tumors are the pathologic conditions producing focal needed to evaluate the validity of US as a diagnostic test. A single hypertrophic mononeuropathy. MRI is used to identify the extent prospective study5 of 123 patients with suspected UNE compared of the enlarged nerve and its signal characteristics. A targeted fascic- to 56 healthy control subjects confirmed an enlarged diameter of ular biopsy of the involved nerve by a skilled surgeon is often neces- the ulnar nerve at the medial epicondyle. Additionally, the ulnar sary to achieve a pathological diagnosis. To recommend a fascicular nerve diameter was significantly larger in patients with axonal biopsy of a mixed nerve based on abnormal US images alone at this
Table 2 Prospective study of diagnostic ultrasound in ulnar neuropathy at the elbow
Author Patients/Control subjects Standard UNE diameter mm Sensitivity % Specificity % + LR Beekman5 123/56 control subjects Clin + EDX Cut off ≥ 2.5 80 91 9.0 (95% CI 74-87) (95% CI 86-96)
CI = confidence intervals; Clin = clinical criteria; CI = condifence intervalEDX = electrodiagnostic criteria similar to American Association of Electrodiagnostic Medicine (AAEM) recommendations; + LR = positive likelihood ratio. UNE = ulnar neuropathy at elbow; US = ultrasound. Highest diagnostic yield in ulnar nerve with nonlocalizable EDX studies = 86%. 8 AANEM Course time would be inappropriate. US offers the advantage of being a guidelines and special certification of the US operators must be quick, less expensive screening examination. MRI provides a much established; (2) standardization of techniques is necessary, and (3) wider field of view, is better in detecting tumors or inflammatory more prospective studies according to Standards for Reporting of lesions by its signal characteristics, and most importantly, it is not Diagnostic Accuracy criteria are required to establish its true diag- operator dependent. nostic value in NM disorders.
High resolution US will not replace EDX studies in the evaluation of disorders of peripheral nerves, but may be used as an additional REFERENCES tool to improve diagnostic localization in entrapment neuropathies and provide information on structural abnormalities. 1. American Academy of Neurology. Practice parameter for carpal tunnel syndrome (summary statement). Report of the Quality MUSCLE US IN NM DISORDERS Standards Subcommittee of the American Academy of Neurology. Neurology 1993;43:2406-2409. NM disorders lead to changes in muscle morphology which can 2. American Association of Electrodiagnostic Medicine, AAEM be detected with US. Both atrophy and hypertrophy, abnormal Practice Topics in Electrodiagnostic Medicine. Practice Parameter for echo-intensity of muscles, and the presence of fasciculations can electrodiagnostic studies in ulnar neuropathy at the elbow: summary statement. Muscle Nerve 1999;22:408-411. be readily assessed.13 Muscle infiltration with fat and connective 3. American Association of Electrodiagnostic Medicine, American tissue causes increased echo-intensity, which are either visually Academy of Neurology, American Academy of Physical Medicine evaluated or quantified with computer assisted gray scale analysis. and Rehabilitation. Practice parameter for electrodiagnostic studies Myopathies can be distinguished from neurogenic muscle atrophy in carpal tunnel syndrome: summary statement. Muscle Nerve by different patterns of echo-texture. Myopathies cause a homog- 2002;25:918-922. enous increase in echo-intensity, whereas neurogenic disorders 4. Arts, IMP, van Rooij FG, Overeem S, et al. Quantitative muscle ul- have a more inhomogenous, moth eaten pattern that corresponds trasonography in amyotrophic lateral sclerosis. Ultrasound in Med & to groups of atrophic fibers. US is a valuable initial screening test Biol 2008; 34: 354-361. of NM disorders in children who poorly tolerate the needle EMG 5. Beekman R, Schoemaker MC, Van der Plas JP, et al. Diagnostic value examination. Prospective studies of children using quantitative of high-resolution sonography in ulnar neuropathy at the elbow. muscle echo-intensity have detected a NM disorder with a sensi- Neurology 2004;62:767-773. 6. Beekman R, Van der Plas JP, Uitdehaag BM, et al. Clinical, electrodi- tivity of 71% and specificity of 91%.12 The sensitivity is lower in agnostic, and sonographic studies in ulnar neuropathy at the elbow. children less than 3 years of age and in metabolic and mitochon- Muscle Nerve 2004;30:202-208. drial myopathies. 7. Beekman R, Visser LH. Sonography in the diagnosis of carpal tunnel syndrome: a critical review of the literature. Muscle Nerve The value of muscle US is limited in the diagnostic evaluation 2003;27:26-33. of adult NM disorders. Muscle echo-intensity is increased in in- 8. Beekman R, Visser, LH. High-resolution sonography of the periph- flammatory disorders. Inclusion body myositis has more atrophic eral nervous system – a review of the literature. Eur J Neurol 2004; muscles compared to other inflammatory myopathies. The sensi- 11:305-314. tivity of US detecting biopsy proven disease was not significantly 9. D’Arcy CA, McGee S. Does this patient have carpal tunnel syn- different from needle EMG and creatine kinase activity in a series drome? JAMA 2000;283:3110-3117. of patients with inflammatory myopathies.14 Muscle US may de- 10. Mondelli M, Filippou G, Frediani B, et al. Ultrasonography in ulnar neuropathy at the elbow: relationships to clinical and electrophysi- scribe the pattern of muscle involvement as accurately as a carefully ological findings. Clinical Neurophysiology 2008;38:217-226. performed NM examination can. Muscle US is rarely necessary to 11. Park G-Y, Kim J-M, Lee S-M. The ultrasonographic and electrodi- select a muscle for open biopsy. agnostic findings of ulnar neuropathy at the elbow. Arch Phys Med Rehabil 2004;85:1000-1005. In patients with amyotrophic lateral sclerosis (ALS), US demon- 12. Pillen S, Verrips A, van Alfen N et al. Quantitative skeletal muscle strates a combination of muscle atrophy, increased echo-intensity, ultrasound : Diagnostic value in childhood neuromuscular disease. and wide spread fasciculations. Increased echo-intensity has been Neuromuscul disord 2007; 17:509-516. found in muscles of three body regions (cranial, cervical and lum- 13. Pillen S, Arts IM, Zwarts MJ. Muscle ultrasound in neuromuscular bosacral) in the early stages of ALS in a small series of patients.4 disorders. Muscle Nerve 2008;37:679-693. US appears to be more sensitive in detecting fasciculations in lower 14. Reimers CD, Fleckenstein JL, Witt TN et al. Muscular ultrasound motor neuron disorders than visual inspection or needle EMG.15 in idiopathic inflammatory myopathy in adults. J neurol Sci1993; 166:82-92. Future studies using a prospective and blinded design are needed to 15. Reimers CD, Zieman U, Scheel A, et al. Fasciculations: Clinical, establish the role of US in ALS. electromyographic, and ultrasonographic assessment. J Neurol 1996;243:1432-1459. Diagnostic US seems to be a valuable tool in the evaluation of NM 16. Seror P. Sonography and electrodiagnosis in carpal tunnel syndrome disorders but warrants further study. Both EDX and US studies diagnosis, an analysis of the literature. Eur J Radiol 2008;67:146- should be considered complementary, one dealing with functional 152. aspects and the other with structural assessment. US is not yet ready for prime time use for the following reasons: (1) training AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 9
17. Swen WA, Jacobs JW, Bussemaker FE, et al. Carpal tunnel sonog- 21. Wilder-Smith EP, Seet RC, Lim EC. Diagnosing carpal tunnel syn- raphy by the rheumatologist versus nerve conduction study by the drome – clinical criteria and ancillary tests. Nature Clinical Practice neurologist. J Rheumatol 2001;28:62-69. Neurology 2006;2:366-374. 18. Visser LH, Smidt MH, Lee ML. High-resolution sonography 22. Wong SM, Griffith JF, Hui AC, et al. Carpal Tunnel Syndrome: versus EMG in the diagnosis of carpal tunnel syndrome. J Neurol Diagnostic usefulness of sonography. Radiology 2004;232:93-99. Neurosurg Psychiatry 2008:79:63-67. 23. Ziswiler HR, Reichenbach S, Vögelin E, et al. Diagnostic value of 19. Wiesler ER, Chloros GD, Cartwright MS, et al. The use of diagnostic sonography in patients with suspected carpal tunnel syndrome. ultrasound in carpal tunnel syndrome. J Hand Surg 2006;31A:726- Arthritis & Rheumatism 2005;52:304-311. 732. 20. Wiesler ER, Chloros GD, Cartwright MS, et al. Ultrasound in the diagnosis of ulnar neuropathy at the cubital tunnel. J Hand Surg 2006;31A:1088-1093. 10 Numbness, Tingling, Pain, and Weakness AANEM Course 11
F Waves – Physiology and Clinical Uses
Morris A. Fisher, MD Professor Department of Neurology Loyola University Stritch School of Medicine Maywood, Illinois
INTRODUCTION cally change the excitability of neighboring MNs. Renshaw cells are distributed widely throughout a MN pool, respond to increas- The F wave is an interesting electrophysiological artifact produced ingly intense stimulation by increasing their discharge frequency, by antidromic activation (“backfiring”) of motor neurons (MNs) and preferentially inhibit smaller MNs. Other possible physi- following distal electrical stimulation of motor nerve fibers.3 ological influences of antidromic volleys include the induction of Because they traverse the entire length of a peripheral nerve a large enough field potential within the ventral horn to change between the spinal cord and muscle, F waves provide a means the excitability of the MNs, as well as inhibition by direct recur- of examining transmission between stimulation sites in the arm, rent collaterals from one MN to another. leg, and in the related MNs in the cervical and lumbosacral cord. An adequate recording and interpretation of F waves requires an To have any influence on an F-wave discharge in a particular MN, understanding of their physiology. an antidromic volley in motor nerve fibers or orthodromic activ- ity in sensory fibers would have to reach that MN prior to its own Physiology of the F Wave antidromic activation. A time allowance must be made for the MUAPs to spread into the axonal collaterals within the ventral F waves are the result of antidromic activation (“backfiring”) of horn for synaptic activation of an interneuron, and then for the MNs. The probability that any one motor unit (MU) in a par- synaptic activation of the MN. Theoretically, this should be pos- ticular MN pool will generate an F wave is small.13 Some stimuli sible due to rise times for spinal cord MN excitatory postsynaptic in a train may not be followed by an F wave. Where F waves do potentials of at least 3 ms. This should also allow ample time for follow the direct response, their shape and size usually changes segmental inhibitory and excitatory influences. from stimulus to stimulus (Figure) because the MUs and the as- sociated motor unit action potentials (MUAPs) which generate The precise manner by which an antidromic action potential the F wave, change with each successive stimulus. triggers a second orthodromic action potential in the same MN has been examined only indirectly. Nevertheless, it is reasonable Physiological Factors Influencing the F wave to think that once the antidromic action potential reaches the so- madendritic (SD) membrane, the transmembrane currents asso- Electrical stimulation of peripheral nerves is associated with anti- ciated with the antidromic action potential might be sufficiently dromic activity in motor nerve fibers and orthodromic activity in strong enough to electrotonically reactivate the initial segment sensory fibers. They might influence the excitability of MNs and (IS). This requires that sufficient time has elapsed for the IS to thereby increase the chance of an F wave. For example, antidro- recover from a refractory state from the preceding antidromic mic activity caused by the invasion of collateral branches of the action potential. Once regenerated in the IS, the MUAP then motor nerve fibers in the ventral horn will activate the inhibitory returns to the periphery to activate the corresponding MU, thereby interneuronal Renshaw cells. The Renshaw cells will transynapti- generating an F wave. 12 FNumbness, Waves – PhysiologyTingling, Pain, and and Clinical Weakness Uses AANEM Course
portant. Since MN size directly correlates with axonal size and therefore, conduction velocity, selection could affect the size, and conductions in a series of F waves. However, all studies support- ing the absence of bias in the selection of MUs in F waves have been performed at submaximal stimulation. The relevance of such studies to situations where supramaximal stimuli are used, as in the usual clinical setting, is unclear. Empirically, there are strong argu- ments for thinking there is selective activation of the larger, faster conducting MUs in F waves. The potential range of conductions in F waves should be large, and yet this range is usually relatively small (about 15%). This is true despite the small number of F waves usually recorded. Conduction velocities using F-wave latencies have produced data similar to that for standard motor nerve conduction studies (NCSs) accordant with a consistent and selective activa- tion of the fastest conducting, and therefore, the largest MUs, in a series of F waves. In the author’s opinion, the evidence favors some bias toward preferential activation of larger MUs in F waves. Fortunately, whatever the theoretical issues, the observed variability in F- wave latencies is not as random or remarkable as to preclude their clinical use.
Methodology
F waves are ubiquitous in distribution. When recorded from distal muscles in the limbs, F waves are almost always separated from the direct M potential. With more proximal stimulation, F waves may be obscured by the preceding direct M response due to the shorter latency of the F waves. Collision techniques may be employed to cancel the effect of the direct M potential on the F waves and make it possible to measure the latencies of the F waves with proximal recordings.
F waves are usually recorded using surface electrodes in a belly- tendon fashion with the active electrode positioned over the in- nervation zone of the target muscle. When recording from calf muscles, both electrodes should be positioned over the muscle belly to reduce any pick up of late responses from more distant Figure F waves (right) with the associated M waves (left). The vari- muscles. As when recording H reflexes from the calf muscles, ability of F waves is emphasized with the responses superimposed the recording electrode can be positioned on the soleus, one-half as shown above. Chronodispersion is the difference between the the distance between the stimulation site in the popliteal fossa shortest and longest latencies. The persistence is 90% (i.e., one of and the superior aspect of the medial malleolus. The stimulat- the 10 responses is absent). The two largest F waves are repeater ing cathode should be proximal to the anodal electrode to avoid waves. Calibration per division: 5 mV for M waves, 500μV for F waves; anodal block. Because F waves may be affected by a previous 5 ms. (Reproduced with permission, Fisher MA, Hoffen B, Hultman, conditioning stimulus and F wave, the rate of stimulation should C. Normative F-wave values and the number of recorded F-waves. be less than 0.5 Hz. Muscle Nerve 1994;17:1185-1189.) F waves may be present following submaximal sitmulation, but This hypothesis for the generation of an F wave suggests that any they prove to be more prominent with supramaximal stimulations factors tending to speed up the recovery of the IS or which delay (i.e., 25% above that required for the maximum M wave) since and/or increase the magnitude of any antidromically induced de- the amplitudes of the F waves, as well as the frequency of occur- polarization of the SD membrane, might increase the chance of an rence (persistence) increases as the stimulus intensity increases. F wave. In contrast, any factors which do the reverse might reduce Supramaximal stimulation also provides a physiologically definable the chance of an F wave. and uniform environment in which F waves will occur.
Selectivity of MUs in the F wave Analysis of F waves
Since there is a wide range in the physiological properties of MUs, F-wave latencies reflect the conduction times between the site of the question of selection bias in the generation of F waves is im- stimulation and the spinal cord. They also measure the time for AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 13
MN reactivation and the time for the centrifugally conducted Table 1 Suggested normative F-wave values (see text) action potential to activate the MU. Individual F-waves are gen- erated by the recurrent discharges from one to at the most a few MUs whose associated MUAPs and F-wave latencies differ from Latencies one another. Therefore, F waves are small, relative to the size Minimal Mean of the direct M potential (generally < 5%), and inherently vary APB (median) (-3.5)+0.063a+0.37d 0.04+0.056a+0.35d +2ms in size, latency, and shape from stimulus to stimulus (Figure). ADM (ulnar) (-1.5)+0.056a+0.36d (-0.40)+0.063a+0.35d +2ms There is uncertainty about the “turnaround” time for individual MUs. This time is said to be approximately 1 ms, but latency Soleus (tibial) 15.6+0.051a+0.31d 10.5+0.092a+0.43d +3ms variations of up to 3 ms for individual F waves have been noted EDB (peroneal) 46.3+3.2(ht 147-160) (-26.4)+0.112a+0.39ht* +5ms in humans. 49.3+3.8(ht 163-175) 52.8+4.2(ht 178 =193) The inherent variability of F waves dictates that a number of them should be recorded to insure that accurate, reproducible data AH (tibial) 47.3+3.6(ht 147-160) (-28.5)+0.131a+0.414ht* +5ms are obtained. In addition, because of the inherent variability of F 50.6+3.7(ht 163-175) waves, they are adequately evaluated only by analyzing a number 55.4+4.2(ht 178-193) of variables. The upper limit of normal values for mean F wave latency differences between sides are 2 ms for the hand, 3 ms for the soleus, and 4 ms for the foot. The most common F-wave variable reported is minimal latency. Given the frequent difficulty of accurately determining individual *Mean latency = M latency F-wave latencies and issues such as overlapping A waves, obvious •APB=abductor pollicis brevis; ADM=abductor digiti minimi; EDB=extensor problems occur. During the past 25 years, there has been at least digitorum one paper every 2 to 3 years that addresses this question. It has been concluded that other measures of F-wave latency such as brevis; AH=abductor hallucis mean latency measurements, should be used rather than minimal •a=age in years; d= distance in cm (for APB and ADM, C7 to superior aspect values.11 In addition, whatever latency measurement is used, radial styloid; for soleus, mid popliteal fossa to superior aspect of the medial it is critical for normative values to include the effect of limb malleolus); ht= height in cm length or height and to a lessor degree, age. Chronodispersion •latencies and regression equations shown with standard deviations refers to the difference between the minimal and maximal la- •regression equations for APB, ADM, and soleus from [26]; for EDB and AH tencies and thereby reflects the range of latencies in a series from [62] AQ – There are no references 26 and 62 – please insert citations of F waves. here but do not add to references.
F waves are readily discernible if they are greater than Chronodispersion* 40µV in peak-to-peak amplitude, and persistence refers to the APB 6.2 ms percentage of such responses following a series of stimuli. Depending ADM 5.5 ms on the physiological organization of the muscle, persistences will vary. In comparison, they are greater in antigravity muscles Soleus 7 ms such as the soleus (normally about 80% or greater) than the EDB 9.5 ms antigravity antagonists such as the tibialis anterior (normally about AH 9.3 ms 40%). Due to the variability of F waves, the amplitudes of F waves are best measured as mean values and related to the amplitude *upper limit of normal of the maximum M potential (i.e., the mean F/M ratio). Total durations from onset to the return to baseline have been Amplitudes (mean F/maximum M [mF/M] ratios)* measured. Identical responses in a series of F waves APB 22+10** are called repeater waves. Normal values for F-wave parameters used in the author’s laboratory are shown Soleus 25+12 in Table 1. *mean F amplitude in µV, maximum M in mV Due to the inherent variability of F waves, sufficient F waves **mean+SD must be collected to provide representative data. Twenty or more stimuli that provide 16 to 20 F waves may be needed for repeater waves. As few as two F waves may be adequate accurate measurements of latency and persistence.5 Having an for establishing an abnormal chronodispersion if the separation adequate number of stimuli as well as an appropriate mode in latency between these two responses is greater than normal. of F-wave analysis is important when comparing relatively Accurate measurement of chronodispersion requires more than 20 small latencydifferences between sides, as necessary in radicu- stimuli, with the possible need for 50 to 60. As many as 100 lopathies. A series of 20 F waves is adequate for mea- stimuli may be required to determine the number of individual suring mean F/M amplitude ratios and the percentage of repeater waves. 14 F Waves – Physiology and Clinical Uses AANEM Course
CLINICAL APPLICATIONS OF THE F WAVE Table 2 Polyneuropathies – Characteristic Findings Peripheral Neuropathies Axonal The evaluation of polyneuropathies is one of the most important • Mildly prolonged F-wave latencies functions for electrodiagnosis. The latencies of F waves are charac- • Increased mF/M values teristically prolonged in neuropathies and may be abnormal even • Increased repeater waves 8 when peripheral motor NCSs are normal. This may be due to Demyelinating the long length of nerve that is monitored by F waves. They may also be more sensitive than conventional motor NCSs in axonal • Prominently prolonged F-wave latencies (i.e., >150% of the expected value) neuropathies.6 F-wave latencies are the most stable and reliable 9 • Decreased persistence measurement for sequential NCSs in the same subjects and are • Absent F waves with relatively preserved M waves the most sensitive nerve conduction parameter in patients with diabetic neuropathies.2 Prolonged F-wave latencies that exceed mF/M = mean F/maximum M ratios 150% of the upper limit of normal have been considered highly suggestive of demyelinating neuropathies, as has the absence F waves in Radiculopathies of F waves in the presence of relatively preserved maximum M potentials.6 Experimentally, root injury is due to compression and inflammation. Demyelination would be produced and slowing of With the exception of latency, F-wave parameters can provide nerve conduction could be demonstrated. For this reason, one additional valuable electrophysiological information. For example, may expect that F waves might be of value in the electrophysiologi- the percentage of repeater waves is increased in neurogenic disorders, cal evaluation of radiculopathies. In fact, the use of F waves in the especially those associated with atrophy. Although a large number of radiculopathies has been controversial. F waves are required, increases in repeater waves have been reported to be a sensitive indicator of carpal tunnel syndrome. Increases in the Criticism durations of F waves may also be an early sign in diabetic neuropa- thies. Mean F/M amplitude ratios may be increased in neuropathies. The use of F waves in radiculopathies has been criticized because This is most characteristic of axonal injuries and is consistent with the injury may not involve all of the motor axons in that par- the increased amplitudes of the F waves and reduced amplitudes of ticular root. F waves are uniquely qualified to analyze radicular the maximum M potentials, which is so often a feature of injury where there may be axons that are injured, while others these neuropathies. may remain intact. F-wave parameters that can measure this range of normal versus abnormal conductions include mean, F-wave abnormalities have been reported in more than 90% of median, and maximum latencies, as well as chronodispersion. nerves studied in patients with acute and chronic acquired demy- The same debate applies to arguments that F waves cannot elinating neuropathies.6,8 This is consistent with the demyelinat- be used because the recording muscles may have multiple ing and focal proximal injury present in these patients. In these root innervation. 90% of nerves, abnormal latencies were present in less than half of these nerves. Other meaningful F-wave findings have included Another theoretical criticism of the use of F waves in absent responses as well as abnormal chronodispersion or persistent radiculopathies is based on the concept of “dilution”; namely, F-wave abnormalities in acquired demyelinaing neuropathies that the relatively small latency delay that is associated with have been at least as frequent as motor NCS abnormalities.6 F-wave compressed nerve root that would be obscured by the much abnormalities are so frequent in these patients that one should be longer F-wave latency. Modeling F-wave latency changes in hesitant in making such a diagnosis electrodiagnostically without radiculopathies using signal detection theory indicates that such findings. absolute F-wave latency does not influence the accuracy of detecting focal lesions. In fact, the important variable is Characteristic F-wave findings in axonal and demyelinating variance which makes the “dilution” argument irrelevant.7 This neuropathies are summarized in Table 2. What may be of greater argument in regards to “dilution” also ignores the ability to importantance is that F waves are usually critical in defining use appropriately analyzed F-wave latencies (i.e., mean laten- different patterns of electrodiagnostic abnormalities that can be cies) to reliably compare latency differences between sides and helpful in better establishing the etiology of a neuropathy.15 examine the information that may be obtained by analyzing other F-wave variables. F waves in Proximal Nerve Lesions Finally, the use of F waves in radiculopathies has been criticized F-wave latency prolongation has long been described in patients because the data essentially overlaps with that obtained with needle with focal proximal nerve lesions. This is consistent with observa- electromyography (EMG). This belief is not necessarily supported tions that F-wave abnormalities have a high sensitivity in acquired by available reports, based on the pathophysiology of root injury. neuropathies in which focal proximal demyelination may be the Needle EMG requires axonal injury, while F-wave abnormalities main pathological feature. can occur with demyelination. AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 15
The article most commonly cited in the criticism of F-wave use in less frequently with activation by muscle contraction, whereas MNs radiculopathies1 cannot be defended methodologically by current that discharge infrequently will increase their firing rate. Therefore, standards. For example, the analysis was based on only a few F at times, an increased central excitability results in a decreased dis- waves recorded from the antigravity antagonist extensor digitorum charge of larger MNs in an F wave, owing to blockage at the still brevis, and at least 75% of the patients had S1 radiculopathies in refractory initial segment of the MN. Despite this complexity, anal- muscles with unexpected abnormalities. yses of F waves are a valuable technique for monitoring central MN excitability. For example, F waves are decreased early after central Defense motor system injury that is associated with decreased reflexes and tone, while increased F-wave persistence and amplitudes have been Up to 90% of radiculopathies occur at the lumbosacral level, and noted with well established upper MN syndromes. up to 80% involve the L5 and/or S1 roots. These roots innervate muscles that are commonly used for F- wave recordings, namely the calf or small foot muscles. In contrast, nearly 90% of cervical CONCLUSION radiculopathies involve muscles innervated by roots (C5, C6, or C7) that are not commonly used for F-wave recordings. As a result, If used appropriately, F waves can be an important tool for meaningful information regarding the use of F waves in cervical evaluating the normal and abnormal physiology of the peripheral radiculopathies is not available. nervous system and the CNS. Currently, although F waves are underutilized, they maintain a well-established role in the Based on prolonged latencies or abnormal side to side differences, evaluation of peripheral nerve dysfunction with evidence to support sensitivities of 50% to 80% were reported about 30 years ago for their role in lumbosacral radiculopathies. With more sophisticated F waves used in the evaluation of lumbosacral radiculopathies. technology and the greater potential use of a multiparameter More recent studies using F-wave variables, in addition to minimal type of analyses, the importance of F waves in clinical EDX will F-wave latencies, have reported a sensitivity in L5/S1 radicul- likely increase. opathies comparable to that for needle EMG. In addition to mean latencies and latency comparison between sides, F wave variables of importance have included chronodispersion and persistence. REFERENCES Blinded studies using multiparameter analyses including F wave and compound muscle action potentials 4 have revealed a diag- 1. Aminoff MJ, Goodin DS, Parry GJ, Barbaro NM, Weinstein PR, Rosenblum M.. Electrophysiologic evaluation of lumbosacral rad nostic specificity of 84.3% and a sensitivity of 83.3% in patients icaulopthies:electromyography, late responses, and somatosensory with lumbosacral radiculopathies. In such patients, similar multipa- evoked potentials. Neurology1985;35:1514-1518. rameter analyses when compared to traditional EMG studies have 2. Andersen H, Stälberg E, Falck B. F-wave latency sensitive nerve con- revealed comparable positive and negative likelihood ratios with duction parameter in patients with diabetes mellitus. Muscle Nerve blinded neuroradiological evaluations. A multiparameter approach 1997;20:1296-130. has been recommended in other areas of EDX. 12 Several reports 3. Fisher MA: F Waves. In: Brown WF, Bolton CF, Aminoff have noted meaningful increases in F-wave chronodispersion– up M.J,editors. Neuromuscular Function and Disease. Philadelphia, WB. to 8 ms – in patients with lumbar spinal stenosis with standing, and Saunders; 2003. Vol 1, p 473-481. a recent study reports a meaningful decrease in F-wave persistence 4. Fisher, MA, Bajwa, R., Somashekar, K.N. Routine electrodiagnosis following a program of exercise.14 Such observations support the and a multiparameter technique in lumbosacral radiculopathies. Acta idea that F waves can monitor physiological changes at the level Neurol. Scand. In press. 5. Fisher MA, Hoffen B, Hultman, C. Normative F-wave values and the of the roots. number of recorded F-waves. Muscle Nerve 1994;17:1185-1189. 6. Fraser JL, Olney RK. The relative diagnostic sensitivity of differ- Conclusion ent F-wave parameters in various polyneuropathies. Muscle Nerve 1992;15:912-918. There are no convincing theoretical arguments or convincing 7. Gozani SN, Kong X, Fisher MA. Factors influencing F-wave latency studies indicating that F waves cannot be helpful in lumbosacral detection of lumbosacral root lesions using a detection a detection radiculopathies. The current evidence would support the usefulness theory based model. Clin Neurophysiol. 2006;117:1449-1457. of F waves in the EDX evaluation of radiculopathies where such 8. Kiers L, Clouston P, Zunigz G, Cros D. (1994) Quantitative studies of F-waves in Guillain-Barré syndrome and chronic inflammatory evidence of injury to the anterior rami could be helpful. demyelinating polyneuropathy. Electroenceph Clin Neurophysiol Central Nervous System Disorders and F waves 1994;93:255-264. 9. Kohara N, Kimura J, Kaji R, Goto Y, Ishii J. Multicenter analysis on intertribal variability of nerve NCSs: healthy subjects and patients F waves provide a physiological window into a segmental MN pool 10 with diabetic neuropathies. In: Kimura J, Shibishaski H, editors. excitability, even if not necessarily for short-term changes. In Recent Advances in Clinical Neurophysiology. Amsterdam: Elsevier; patients with upper MN syndromes due to central nervous system 1996. p 809-815. (CNS) lesions, antidromically activated MNs fire more frequently 10. Lin, J.Z. and Floeter, M.K. (2004). Do F-wave measurements detect than those in normal individuals.13 At the same time, this is com- changes in motor neuron excitability. Muscle Nerve 2004;30:289- plicated by the fact that frequently backfired MNs will discharge 294. 16 F Waves – Physiology and Clinical Uses AANEM Course
11. Nobrega JAM, Pinheiro DS, Manzano G.M., Kimura, J. Various 14. Wallbom AD, Geisser ME, Hiag AJ, Koch J, Guido C. Alterations aspects of F-wave values in a healthy population. Clin Neurophysiol of F wave parameters after exercise in symptomatic lumbar spinal 2004;115:2336-2342. stenosis. Am J Phys Med Rehabil 2008: 87:270-274. 12. Robinson LR, Micklesen PJ, Wang L. Strategies for analyzing nerve 15. Wilson J., Chawla, J., Fisher M. Sensitivity and specificity of electrodi- conduction data: superioriy of a summary index over single tests. agnostic criteria for CIDP using ROC curves: comparison to patients Muscle Nerve 1998;21:1166-117. with diabetes and MGUS neuropathies. J Neurol Sci. 2005;231: 13. Schiller HH and Stålberg E. (1978) F-waves studied with single fibre 19-28. EMG in normal subjects and spastic patients. J Neurol Neurosurg Psychiatry 1978;41,45-53. 17 F-Wave Studies are of Limited Clinical Value
Michael H. Rivner, MD Professor of Neurology Medical College of Georgia Augusta, Georgia
INTRODUCTION problem with the F wave relates to the fact that the response is generated by a single motor unit (MU). Sampling problems often The role of F-wave testing in the practice of clinical neurophysiology prevent small lesions from being detected clinically because the ma- is one of heated debate. Some believe this test has been jority of the neurons in the nerve are normal. There are five major employed to a point of overutilizization. While many clinical problems that limit the F-wave’s value as a clinical test (Table 1). neurophysiologists believe the test has wide applicability and can First, it is difficult to detect axonal damage with F waves since usually be used in most clinical situations, others feel it is of limited value. the latency of the fastest F wave will not be affected by axonal damage. The rationale for F-wave testing, the pitfalls in performing F-wave Second, due to sampling problems, small demyelinating lesions will testing, and the role of F-wave testing in specific clinical situations not affect the minimum F-wave latency. Third, an F wave will only will be examined. assess the normality of the nerve or nerve root stimulated and will not be useful for detecting abnormalities of other nerves and roots. This The F wave has been advocated as a method to determine the health point may seem obvious, but often F waves are used inappropriately of a population of motor nerves throughout their entire course.4 The in radiculopathy screens. The fourth problem is that adding several axons of motor nerves are stimulated antidromically, resulting in F waves to routine clinical studies will increase the likelihood of test depolarization of their cell bodies. Following the absolute refractory errors. Finally, normal values for F-wave latencies may not be inter- period, a limited number (often a single cell body) will be depolarized preted correctly. above threshold and produce a small late motor response known as an F wave. Since the F-wave response is usually the evoked response Table 1 Causes of F wave limitations of a single motor neuron, its size is small and its latency is variable since different motor neurons are usually activated with each stimu- 1) Wrong measurement obtained lus. Many different measurements are used by neurophysiologists to assess F-wave normality. The most commonly used measurement is 2) Sampling problems the minimum F-wave latency which is simply the shortest latency of 3) F waves are poorly applied clinically 5 to 10 different F-wave responses.5 Since this value only represents 4) Statistical errors the latency of a single nerve, many advocate using the mean F-wave 5) Interpretation errors due to poor normal values latency to better reflect the nerve’s function.5,12 Another method, called chronodispersion, measures the range between the shortest and longest F-wave latency. F-wave persistence, which is the number of definable F waves seen, then divided by the number of stimuli; and F WAVES IN AXONAL DAMAGE OR CONDUCTION BLOCK non-repeater F waves, which is the number of unique F waves seen in a series, are measurements that are less commonly used. While many neuropathies are due to focal demyelination that produce slowing, others cause axonal damage that result in Wallerian In theory, the F wave should be a valuable tool in the armamentaria degeneration. While a conduction delay will prolong the F wave, of the clinical neurophysiologist. Unfortunately, this test in actual conduction blocks and axonal degeneration will interfere with practice is of limited value and is clinically overutilized. The major F-wave conduction and result in no F-wave response. If the lesion 18 F-Wave Studies are of Limited Clinical Value AANEM Course is incomplete, the F-wave latency may be normal. As a result, it is number of tests without a clear plan will lead to error. Performing F still possible to have a significant axonal lesion and have a normal waves will also increase the number of tests performed. Therefore, F-wave latency. While F-wave persistence and repeater F-wave de- this could lead to a situation in which the probability of error by terminations may show abnormalities in these situations, these tests chance could become unacceptably high. For this reason, a single are difficult and time consuming to perform. As a result, they are abnormal F wave should be interpreted cautiously. rarely performed. NORMAL VALUES AND F WAVES SAMPLING PROBLEMS AND F WAVES Whenever numeric values are used in a clinical test, it is In an incomplete lesion typically seen in a radiculopathy, only a important to understand how the normal values were determined. small proportion of a root’s neurons are involved. The involved Unfortunately, the establishment of proper normal values is neurons may show conduction block, but the other uninvolved usually not given enough attention. Many laboratories use a neurons will be normal. The minimum F-wave latency will static value for the upper limit of normal. This method is flawed measure the latency of a normal neuron, which in many lesions will because F-wave latency is related to height and age.13,14 These make up the majority of the nerve. As a result, the F-wave latency values must be considered when establishing normal values for F will be normal. A mean F wave would better reflect these abnor- waves. If they are not considered, an F-wave latency in a very tall malities but these are usually also normal in incomplete lesions person may be considered prolonged when it is actually normal. such as a radiculopathy.1 F-wave chronodispersion might allow the Another variable to consider is nerve conduction velocity (NCV). involved neurons to be tested, but this technique is not uniformly It would be expected that if the conduction velocity of a nerve performed in most clinical laboratories. Therefore, because of is slowed, its F wave would be prolonged. Often the question is sampling problems, the F wave will be normal in most patients whether or not a more proximal lesion exists. In these cases, it is with small, incomplete lesions. important to factor out known NCV slowing to see if the F wave is longer than expected. In the case of a radiculopathy, it must be determined whether or not a proximal lesion exists at the root TESTING THE WRONG NERVES level that is the cause of the patient’s symptoms. If the NCV of a nerve is slowed, without factoring out its effects, it would not be F waves are often applied in situations where there is no possibility known if the prolonged F-wave latency is due to distal slowing or that they will be helpful. It may seem obvious that an F-wave a more proximal lesion. It was recently shown that correcting for abnormality in the medium nerve recording from the abductor NCV did not improve the F-wave sensitivity for radiculopathy.17 pollicis brevis (APB) muscle will not give information about the C6 The problem is that all of the patients studied had normal NCVs. nerve root, but reports have been seen in which multiple F waves Only in patients with abnormal NCVs would correction of the have been performed to rule out a C6 radiculopathy. Unfortunately, normal values for NCV improve the ability of an F wave to detect none of the nerves studied were innervated by the C6 root. While a proximal nerve lesion. In the case of neuropathy, if the NCV an F wave may be performed on any motor nerve, they are usually is slowed, a prolonged F wave without correcting for NCV can performed in only a few selected nerves. Generally, nerves that provide no additional information. If corrected for NCV, a pro- innervate distal muscles are chosen because they are relatively long longed F wave will indicate that another more proximal lesion is and have ample separation between the M response and the F present. While it is expected that with correction, the F wave will wave. Unfortunately, these nerves will only provide information more often be normal, since the slowing that had been accounted for a small number of nerve roots. Often nerve roots of interest for by the already known slowed NCV will be factored out, will innervate proximal muscles. These nerves may be studied, this method will allow previously undetected proximal lesions but because the F wave may overlap the M response, there is need to be discovered. for use of special, technically difficult, collision techniques. As a result, these nerves are rarely tested. There is little value in studying F waves in nerves where pathology is not suspected. THE USE OF F WAVES IN SPECIFIC CLINICAL Therefore, F waves should be applied judiciously and used only in SITUATIONS situations where they can be of value. F Waves in Radiculopathy
STATISTICAL ERRORS AND F WAVES The F wave is used most often in the evaluation of suspected radiculopathies. They are often tested in nerve areas innervated by As more clinical testing is performed, the likelihood of a result nerve roots other than those which are clinically relevant. Under being abnormal by chance alone becomes greater.15 As a result, one these situations, the test has limited value. The sensitivity of the must either limit themselves to highly specific and sensitive tests or F wave in cervical radiculopathy ranges from 10% to 20 %.16 In require more than a single abnormality before making a diagnosis. most series, either the needle examination is abnormal for the Therefore, it is important to know which tests are most sensi- patient to be included or the needle electromyography (EMG) tive when checking for specific diagnoses. To conduct an endless examination is abnormal more often than the F wave. Since the AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 19
F wave is rarely abnormal when the needle examination is normal, Table 2 F waves in cervical radiculopathy, Medical College of an F wave has limited clinical utility. In one study of patients with Georgia 1986-1996 (20,623 patients) magnetic resonance imaging confirmed cervical radiculopathy,10 F waves were abnormal in 55% of patients compared to 75% with # in population Abnormal F wave abnormal needle EMG. While 13% more patients were confirmed to have cervical radiculopathy if both the F waves and EMG Clinical symptoms of cervical 3324 16.0 % NA NA were utilized, there are several problems with this study. The first radiculopathy problem revolves around the fact that subjects with C5 radiculopa- Clinical symptoms and F-wave 2093 10.0 % 201 9.6 % thy had been excluded, thereby a population of patients had been data selected that were more prone to having F-wave abnormalities. Clinical symptoms and normal 1200 5.8 % 80 6.7% Secondly, multiple F-wave determinations were performed. These EMG authors studied minimum F wave, F-wave persistence, F-wave Clinical symptoms and 893 4.3 % 121 13.5% chronodispersion as well as their side-to-side comparisons, or a abnormal EMG total of six F-wave measurements. It is difficult to be certain what Clinical symptoms and EMG 154 0.7 % 29 18.3% the significance of a single F-wave abnormality is with this number C8 radiculopathy of measurements. Normal clinical examination 1005 4.9 % 31 3.1% with F-wave data Table 2 shows the results of 2093 patients studied at the Medical College of Georgia who had clinical symptoms of cervical radicu- Table reprinted from Rivner, M. H. The contemporary role of F-wave studies. 16 lopathy and F-wave data. In this group of patients, 10% had F-wave studies: limitations. Muscle & Nerve 1998;21:1101-1104 16 abnormal F waves. In patients with no evidence of radiculopathy, EMG = electromyography, NA = not available the F wave was abnormal 3% of the time. In patients with good clinical symptoms and a normal EMG, 7% had abnormal F waves. subclinical neuropathies, other studies are more sensitive. In the Therefore, the F wave is abnormal twice as often in patients with case of demylenating neuropathies, F waves are often abnormal. clinical symptoms consistent with a radiculopathy. With an abnor- In inflammatory neuropathies, F waves are usually prolonged.8 mal EMG, the likelihood of finding an abnormal F wave becomes Often F-wave abnormalities may be seen before other NCSs greater and approaches 20% of patients with needle EMG exami- become abnormal. In most cases, F-wave abnormalities are nation abnormalities consistent with a C8 radiculopathy. While all not seen in isolation but are associated with other abnormali- these values are statistically significant, on a clinical basis they are ties. Abnormalities in several nerves are needed to make a firm not very helpful. The F wave contributes additional information diagnosis of neuropathy. The association of F-wave abnormali- in only a few patients. In a patient with good clinical symptoms ties with those of standard NCSs is supportive of a neuropathy. and an otherwise normal EMG/nerve conduction study (NCS), In the case of generalized neuropathy, F waves are of value. it is unlikely that an isolated abnormal F wave would change the However, more than an isolated F-wave abnormality is needed management of the patient. As discussed, only a few patients with to make the diagnosis of a peripheral neuropathy. normal needle EMG examinations will have abnormal F waves.6 The significance of this isolated finding is limited, especially The use of F-wave values in a generalized neuropathy is of considering the number of tests performed on these patients. considerable interest. F waves would more likely be abnormal Similar findings were seen in lumbar-sacral radiculopathies.1,17,19 if their normal values were not corrected for NCV. With this It is the author’s opinion that F waves add little to the evaluation of correction, F waves would be abnormal less often, but testing cervical and lumbosacral radiculopathy. would indicate abnormalities that are not explained by the already slowed NCV recorded over the nerve. For example, in a patient F Waves in Peripheral Neuropathy with a peroneal NCV of 32 m/s, the F-wave latency would be longer than if the patient had a NCV of 45 m/s. The prolonged F waves have been shown to be helpful in the evaluation of F-wave latency in the patient with the slowed NCV is expected peripheral neuropathy. F waves are often abnormal in axonal and it is not known whether there are additional proximal lesions neuropathies, being only slightly less sensitive than sensory nerve unless a normal value that takes this slowed NCV into consider- amplitude.7 While F-wave persistence and chronodispersion ation is used. If the F-wave latency was slower than expected, this are needed to increase the test’s sensitivity, the test is still fairly would indicate that an additional conduction delay is to be found sensitive when only the minimal F-wave latency is used. F proximally. If the F-wave latency was corrected for the nerve’s waves have also been shown to be of value in assessing diabetic measured NCV, then it would be less likely to be abnormal. In neuropathies.2,9 In cases of mild diabetes, F waves are often ab- the case where it was not corrected, it would provide no more normal, much like other nerve measurements. In one study of information than can be obtained by standard NCSs. For patients with assymptomatic newly diagnosed diabetes,18 F waves this reason, an argument could be made that F waves should were abnormal in 12% of the patients. In this same study, H only be performed on nerves with normal NCV, or that one reflexes were abnormal in 22%, compound muscle action poten- should take the NCV into consideration if it is expected tial amplitude (CMAP) in 26%, motor potential area 32%, and that the F wave would provide additional information in a motor NCS 20% of the time. So while F waves are abnormal in generalized neuropathy. 20 F-Wave Studies are of Limited Clinical Value AANEM Course
F Wave in Focal Neuropathies REFERENCES
F wave advocates support its use in the detection of focal neu- 1. Aiello, I., Patraskakis, S., Sau, G. F., Zirattu, G., Bissakou, M., Patta, G., ropathies. Because the F-wave minimal latency measurement and Traccis, S. Diagnostic value of extensor digitorum brevis F-wave in will be normal unless significant demyelination is present that L5 root compression. Electromyography & Clinical Neurophysiology involves most of the axons in the nerve, a small area of focal de- 1990;30:73-76. 2. Andersen, H., Stalberg, E., and Falck, B. F-wave latency, the most myelination will usually not be detected by F-wave measurements. sensitive nerve conduction parameter in patients with diabetes mellitus. Therefore, if it is possible to directly stimulate across the suspected Muscle & Nerve 1997;20:1296-1302. lesion, it is better to use this direct approach. There have been 3. Argyriou, A., Polychronopoulos, P., Talelli, P., Chroni, E. F wave studies that show the utility of F waves in the diagnosis of carpal study in amyotrophic lateral sclerosis: Assessment of balance between tunnel syndrome (CTS), but in all cases, the patients were already upper and lower motor neuron involvement. Clin Neurophysiol diagnosed by having abnormalities in other NCSs.11 In addition, 2006;117:1260–1265. an abnormal F wave would not localize the lesion to the carpal 4. Fisher, M. A. AAEM Minimonograph :13: H reflexes and F waves: tunnel. It is rare that a prolonged median F wave would change physiology and clinical indications. Muscle & Nerve 1992;15:1223- a clinical decision about whether or not a patient has CTS. In 1233. very proximal lesions where there is no way to stimulate across 5. Fisher, M. A., Hoffen, B., and Hultman, C. Normative F wave values the lesion, F waves may be of limited value. Unfortunately, and the number of recorded F waves. Muscle & Nerve 1994;17:1185- 1189. as previously addressed, F-wave latency is a relatively insensitive 6. Fisher, M. A., Shivde, A. J., Teixera, C., and Grainer, L. S. Clinical test for an incomplete lesion. Other techniques such as chrono- and electrophysiological appraisal of the significance of radicular dispersion, F-wave persistence, or repeater F waves may be more injury in back pain. Journal of Neurology, Neurosurgery & Psychiatry sensitive but more experience is needed before these tests become a 1978;41:303-306. routine part of an electrodiagnostic (EDX) evaluation. These tests 7. Fraser, J. L. and Olney, R. K. The relative diagnostic sensitivity of dif- are too difficult and time consuming to perform on a routine basis. ferent F-wave parameters in various polyneuropathies. Muscle & Nerve 1992;15:912-918. F waves in Generalized Conditions 8. Kiers, L., Clouston, P., Zuniga, G., and Cros, D. Quantitative studies of F responses in Guillain-Barre syndrome and chronic inflammatory F-waves have been shown to be abnormal in generalized neuro- demyelinating polyneuropathy. Electroencephalography & Clinical pathic conditions such as amyotrophic lateral sclerosis (ALS).3 It is Neurophysiology 1994;93:255-264. 9. Kohara, N., Kimura, J., Kaji, R., Goto, Y., Ishii, J., Takiguchi, M., and important to check F waves in ALS so that a diagnosis of multifocal Nakai, M. F-wave latency serves as the most reproducible measure motor neuropathy is not missed. While F-wave latencies may be in nerve conduction studies of diabetic polyneuropathy: multicentre slightly long in ALS, other F-wave measurements are often more analysis in healthy subjects and patients with diabetic polyneuropathy. likely to be abnormal. F-wave amplitude is increased because the Diabetologia 2000;43:915-921. MUs are larger in ALS. In addition, the number of nonrepeater F 10. Lo, Y.L., Chan, L.L., Leoh, Th., Lim, W., Tan, S.B., Tan, C.T., Fook- waves and F-wave persistence are reduced in ALS. At this point, Chong, S. Diagnostic utility of F waves in cervical radiculopathy: the findings are supplemental to other EDX findings seen in this Electrophysiological and magnetic resonance imaging correlation. Clin condition. While these findings are of interest, the main value of F Neuro and Neurosurg 2008;110:58-61. waves, as well as other NCSs in ALS, is to exclude other diseases. 11. Menkes, D. L., Hood, D. C., and Bush, A. C. Inversion of the f-waves in median neuropathy at the wrist (carpal tunnel syndrome): an adjunctive electrodiagnostic method. J Contemp Neurol 1997;1:1-10. CONCLUSION 12. Nobrega, J. A., Manzano, G. M., and Monteagudo, P. T. A comparison between different parameters in F-wave studies. Clin Neurophysiol. 2001;112:866-868. In conclusion, F-wave testing is currently overutilized in routine 13. Nobrega, J., Pinheiro, D., Manzano, G., Kimura, J. Various aspects of clinical practice. Their value in radiculopathies is limited at best. f-wave values in a healthy population. Clin Neurophysiol. 2004;115: However, in most cases of generalized neuropathy, they are of value. 2336-42. In the case of focal demyelinating lesions, their use is limited to 14. Puksa, L., Stalberg, E., Falck, B. Reference values of f wave parameters situations in which it is not possible to record across the suspected in healthy subjects. Clin Neurophysiol. 2003;114: 1079-1090. lesion. In these instances, the test is relatively insensitive. It is 15. Rivner, M. H. Statistical errors and their effect on electrodiagnostic possible that other nonroutine methods of F-wave testing may medicine. Muscle & Nerve 1994;17:811-814. increase the value of these tests. Currently, these methods are too 16. Rivner, M. H. The contemporary role of F-wave studies. F-wave time consuming and difficult to use on a routine basis. However, studies: limitations. Muscle & Nerve 1998;21:1101-1104. 17. Toyokura, M. and Ishida, A. Diagnostic sensitivity of predicted F-wave in the proper clinical situation, they may be of value. latency by age, height, and MCV. Acta Neurol Scand. 2000;102:106- 113. 18. Trujillo-Hernandez, B., Huerta, M., Trujillo, X., Vasquez, C., Perez- Vargas, D., Millan-Guerrero, R. F-wave and H-reflex alterations in recently diagnosed diabetic patients. Jour Clin Neurosci 2005;12:763– 766. 19. Weber, F. and Albert, U. Electrodiagnostic examination of lumbosacral radiculopathies. Electromyogr.Clin Neurophysiol. 2000;40:231-236. 21
Needle EMG Should be a Routine Component of the Electrodiagnostic Evaluation of Carpal Tunnel Syndrome
John C. Kincaid, MD Department of Neurology Indiana University School of Medicine Clarian Health Partners
INTRODUCTION the presence of CTS is electrodiagnostically established by dem- onstrating slowing of median nerve conduction across the wrist Carpal tunnel syndrome (CTS) is caused by entrapment of the This is most commonly accomplished by finding prolongation median nerve as it passes from the distal forearm into the hand. of the median nerve distal latency, or slowing of the transcarpal The pathogenesis includes local demyelination and axon loss if the conduction velocity in laboratories that perform that calculation. compression is more advanced. Performing needle EMG without NCSs is insensitive in the identi- fication of CTS. Needle EMG abnormalities are present in about Demyelination declares its presence by slowing conduction speed 40% of currently reported patient series and up to half of those through the entrapped region. In CTS, this produces prolonga- will have fibrillation potentials. Needle EMG of thenar and other tion of the latency across the wrist. Conduction velocity is usually hand muscles can be uncomfortable and decrease patient satisfac- normal in the nerve proximal to the lesion, although in severe cases, tion with the testing. Performing the needle EMG also increases the forearm segment can also be slowed due to retrograde atrophy the cost of the study due to additional supplies required and pro- of the compressed axons. fessional component expenses. In a hospital-based laboratory, the base Medicare reimbursement for a single limb needle EMG The presence of axon loss is generally considered to be indicative of examination is approximately $38 for the technical fee while the a lesion which is more severe than one resulting from demyelina- professional component costs an additional $77. tion alone. Detection of axon loss in CTS might dictate a more aggressive approach to treatment such as promptly proceeding to The “pro” side of the argument is that performing NCSs without surgical decompression. Although axon loss can be inferred from needle EMG does not provide a direct assessment of the median reduction of the amplitude of the sensory and motor responses nerve axons. Equally important is that conditions with poten- in nerve conduction studies (NCSs) conduction block due to tially similar presentations like cervical radiculopathy, plexopathy, local demyelination could also produce low amplitude responses. or proximal median neuropathies will not be detected by NCSs Abnormalities found during the needle electromyography (EMG) alone. Modern needle electrodes are available in diameters as examination are generally considered to be more robust indicators small as 0.3 mm (30 gauge) and their use can significantly reduce of axon loss. In the needle EMG, the presence of abnormal resting patient discomfort. activity like fibrillation potentials and positive waves as well as ab- normal voluntary activity like enlarged motor unit action potentials Several published studies have examined the issue of what infor- are indicators of axon loss. mation needle EMG can contribute to the assessment of CTS. 1-4 Werner and colleagues showed that the presence of needle EMG abnormalities correlated with reduction of the amplitudes of the TO NEEDLE OR NOT TO NEEDLE, THAT IS compound muscle action potential (CMAP) and sensory nerve THE QUESTION action potentials (SNAPs).6 However, abnormal needle EMG find- ings could be found in patients whose CMAP or SNAP values were The “con” side of the argument that performing needle EMG still within a normal range, although below the normal mean. In should be a standard component of the evaluation of CTS is that the series of 480 patients, nearly half with CTS had needle EMG 22 Needle EMG Should be a Routine Component of the EDX Evaluation of CTS AANEM Course abnormalities and about half of those had fibrillation potentials. REFERENCES Needle EMG abnormalities correlated better with the degree of distal latency prolongation than response amplitude reduction. A 1. AANEM. Practice Parameter For Electrodiagnostic Studies In Carpal report by Vennix and colleagues also showed that needle EMG Tunnel Syndrome: Summary Statement. Muscle & Nerve 1993; abnormalities could be present in patients with CMAP amplitudes 16:1390-1391 of 7 mv, a value which many laboratories would consider to be 2. Balbierz J, Cottrell A, Cottrell W. Is Needle Examination Always Necessary in Evaluation of Carpal Tunnel Syndrome? Arch Phys within the range of normal values.5 The study also showed that the Med Rehabil 1998; 79: 514-516 presence of fibrillation potentials greatly increases when the distal 3. Gnatz S, Conway R. Issues & Opinions The Role of Needle EMG CMAP amplitude drops below 4 mv. About 7% of patients in the in the Evaluation of Patients with Carpal Tunnel Syndrome. Muscle latter series had needle EMG findings which identified additional & Nerve 1999; 22; 282-286 peripheral nerve lesions like cervical radiculopathy or proximal 4. Stevens J. AAEM Minimonograph #26: The Electrodiagnosis of median neuropathies. Carpal Tunnel Syndrome. Muscle & Nerve 1997; 20: 1477-1486 5. Vennix M, Hirsh D, Chiou-Tan F, Rossi D. Predicting Acute Some physicians choose to perform the needle EMG in any patient Denervation in Carpal Tunnel Syndrome. Arch Phys Med Rehabil referred for evaluation of CTS in whom NCS results showed 1998; 78:306-312. abnormalities greater than just relative prolongation of latency 6. Werner R, Albers J. Relation Between Needle Electromyography in trans-carpal sensory conduction studies like “palmar” type and Nerve Conduction Studies in Patients With Carpal Tunnel Syndrome. Arch Phys Med Rehabil 1995; 76:246-249. testing. The test may be performed to “rule out” carpal tunnel and cervical radiculopathy. 23
Appropriate Testing for Carpal Tunnel Syndrome
Needle EMG is NOT NEEDED
Ernest W. Johnson, MD Emeritus Professor Department of Physical Medicine and Rehabilitation The Ohio State University Columbus, Ohio
INTRODUCTION both median and ulnar, were compared across the carpal tunnel and proved to be an accurate and reliable measure of CTS.6,22 Carpal tunnel syndrome (CTS) is defined as a complex set of symp- toms resulting from compression of the median nerve in the carpal As the understanding of the median nerve anatomy improved, tunnel. Some of these symptoms include pain, burning or tingling, more branches were studied across the carpal ligament. More tech- paresthesias in the fingers and hands, and pain that sometimes niques were developed and compared for sensitivity and specificity. extends to the elbows. Current electrodiagnostic (EDX) instru- The comparison of radial and median sensory nerve action poten- mentation will identify this peripheral nerve dysfunction. There tial (SNAP) to digit 1 has been studied extensively and has proven can be NO EDX-negative CTS Today! to be of great value as both sensitive and specific in CTS.3,4,9,15,20
As recently as 1946, Gilliatt, one of the forefathers of EDX medi- cine, suggested that EDX and sweat tests were too “time consum- BEST PROCEDURE FOR CARPAL TUNNEL SYNDROME ing” to be used in a busy clinic for identifying CTS. In 1952, DIAGNOSIS Marinacci used only needle electromyography (EMG) to diagnose CTS. Since more sophisticated technology has been developed, Clearly, with the current technology, if there is compromise of the needle EMG has become less useful in the diagnosis and manage- median nerve within the carpal tunnel, there must be an abnormal- ment of CTS. ity found using EDX testing.
In 1956, Dr. George Phalen, an orthopedist at the Cleveland When compromise of the median nerve occurs in the carpal canal, Clinic, noted that it was not necessary to use EDX testing for diag- only four things are possible: (1) axons are unaffected; (2) axons nosing CTS.18 He believed that physical findings were used almost are dead and inexcitable; (3) myelin is mildly affected and slowing exclusively for CTS diagnosis. Others have reported the sensitivity occurs; or (4) myelin is more severely compromised and conduc- and specificity of several tests used in the physical examination.12 tion is blocked. Most valuable was the weakness of the thenar muscle. The other test that was seen as valuable was the interesting finding of the wrist It is axiomatic that to best evaluate an entrapment of a peripheral ratio as both a sensitive and a specific test for CTS.7 nerve, one must stimulate the nerve both proximal and distal to the compromise. Furthermore, it becomes necessary to evaluate both Motor latency of the median nerve became popular in the 1960s. sensory and motor axons on both sides of the entrapment. Median sensory latencies became more widely employed as definitive techniques in the 1970s.10,16,22 Prior to the early 1960s, Thus for CTS, the sensory axons of the median nerve can be stimu- a motor latency greater than 5 ms was the objective test for CTS.10 lated at the wrist and midpalm with recording at digit 3 (long finger). Instruments became more sophisticated and eventually all signals Reference values are 3.1 ± .03 ms for latencies and 50 ± 6 µV at wrist were digitalized for greater accuracy. Antidromic sensory latencies stimulation (14 cm); 1.6 ± .02 ms and 60 ± 6 µV at midpalm (7 were quicker and easier than orthodromic techniques and they cm).27 Digit 3 is more sensitive than digit 2, which is more often the gradually assumed primacy in the diagnosis of CTS.23 This provided finger tested.16 More recently, studies have been performed to show a quick and precise method to compare the latency of the median the advantages of stimulating the motor axons of the median nerve nerve with those of radial and ulnar nerves. Latencies of mixed nerves, both proximal and distal to the carpal tunnel.5,13,17,26 24 Appropriate Testing for Carpal Tunnel Syndrome AANEM Course
Motor latency of the median nerve at wrist stimulation is 3.7 ± .03 ms Next, stimulate the median nerve (CMAP) at the wrist (8 cm) and and the amplitude is 5 mV to 20 mV (reference values from standard midpalm. Though the latency is irrelevant at midpalm (next to texts). At midpalm stimulation, the latency is irrelevant (over motor motor point), the amplitude is critically important as it represents point) but the increase in amplitude normally is less than 10%.17 the still-conducting axons and thus, the prognosis. In normal sub- With blocking of motor axons in the carpal tunnel, the compound jects, the CMAP amplitude increase is less than 10%. muscle action potential (CMAP) will be small when stimulating the median nerve at the wrist but will be increased at distal stimulation. In the past, latency and CMAP of the hypothenar was com- Furthermore, the CMAP at distal stimulation will represent only pared with the thenar (1 ms difference).10 Currently, it is not the living and still conducting axons, a semi-quantitative measure often utilized due to the variability in measurement at the wrist. of the severity of CTS.13,17,27 To identify how many axons are com- However, the amplitude can be a useful estimate of the expected promised, it is necessary to stimulate both proximal and distal to the CMAP (abductor pollicis brevis) if CTS is bilateral. The hypoth- carpal tunnel and to record motor and sensory fibers separately.21,22 enar amplitudes in normal subjects are within 1 mV of thenar amplitudes. More recently, latencies and CMAPs of interosseus and lumbrical muscles have been employed in the diagnosis MIXED NERVE STIMULATION of CTS.2,19
The mixed median nerve contains both sensory and motor axons, If there is still uncertainty in the diagnosis, the next recommenda- so that depending on the proportion of dysfunctional axons, SNAP tion is to stimulate the median and ulnar nerves at wrist (14 cm) and CMAP are avoked when the median nerve is stimulated both (SNAP digit 4). The latencies should be equal to or less than .03 proximal and distal to carpal ligament. Although some investigators ms; amplitudes – median 30 µV, ulnar 25 µV.8,14,24,25 have thought this to be the most sensitive technique, it is unable to separate sensory from motor compromise. For example, if the In the late 1980s, the transcarpal mixed nerve latencies were pro- motor axons are unaffected and the latency is normal while the posed as sensitive diagnostic studies for CTS.6,22 The following sensory latency is prolonged, a mixed nerve latency can be normal. were the amplitudes and latencies for the transcarpal, median, and ulnar nerves: (8 cm)– median 1.8 ± .2 ms, 60 to 150 µV, ulnar 1.8 ± .2 ms, 20-40 µV same latency (difference ≤ .03 ms). ACUTE CARPAL TUNNEL SYNDROME Needle EMG is generally not necessary for diagnosis unless Acute CTS occurs when a severe insult is suddenly presented to the there is any question about concomitant or other conditions. It median nerve in the carpal tunnel. Examples include a worker op- is important to note that the term “double crush syndrome" is erating a paint sprayer continuously over several hours, an amateur misleading.28 Cervical radiculopathy is not a direct or indirect playing hockey morning and afternoon every day for a week, or a cause of CTS. It is a consequence of multiple entrapments with worker continuously using a jackhammer for 4 to 5 hours. underlying vulnerable nerves (e.g., diabetic peripheral neuropathy). A detailed history and a meticulous physical examination should In acute CTS the major EDX abnormality is an increase in SNAP be sufficient to determine if the cause of the patients symptoms is or CMAP at stimulation, distal to the carpal ligament. This can be something other than CTS, or to identify a condition coexisting more than 100% even with normal values or with only a minimal with CTS. increase in the latency.5,17 NEEDLE EMG SHOULD NOT BE A SUBSTITUTE FOR A THIS AUTHOR’S PROCEDURE HISTORY AND PHYSICAL Screen for CTS If concomitant conditions are excluded and the diagnosis of CTS is established, then needle EMG is unnecessary. Screen the median and radial nerve SNAPs at the wrist (10 cm) to digit 1 (thumb). Bactrian sign will occur if the median and It is important to remember that reduced recruitment does radial nerves are stimulated simultaneously and the patient does not distinguish between conduction blocking and axonal have CTS. For example, the median SNAP will be prolonged and death. Positive waves and fibrillation potentials are only an the radial SNAP will be normal (making a double hump); normal indication of some axons’ death; they have little quantitative latency difference is greater than or equal to .3 ms. value due to sampling variability. Severity and prognosis are best determined by the most distal stimulation as it would When stimulating the median nerve (SNAP) at the wrist (14 cm, be a reflection of the remaining functioning axons. If an digit 3) and midpalm (7 cm), the distal latency should be slightly underlying peripheral neuropathy is suspected (e.g., diabetic), more than half of the total latency because the distal segment of the the ulnar, radial, and distal median segment will provide median nerve has a narrower diameter and conducts slower. Note clues to extend the EDX (i.e., sural, F waves, etc.).If these that the amplitude at midpalmar stimulation will be larger (phase is a confirmed diagnosis of CTS, there is no reason to do a cancellation), but always less than 30% larger in a normal subject. needle EMG. AANEM Course CROSSFIRES: Controversies in Neuromuscular and Electrodiagnostic Medicine 25
DISCUSSION • CMAP of an ulnar-innervated interosseus muscle com- Stimulation both proximally and distally to evaluate a peripheral pared to a median-innervated lumbrical I or II can be helpful in nerve compromise is clearly indicated during the EDX evaluation distinguishing CTS from an underlying neuropathy.2,19 of CTS.22 Certainly, both sensory and motor axons should be as- sessed separately for precise diagnosis. Because of the chronology of peripheral nerve injuries and the variability of nerve fiber damage, SUMMARY latencies do not provide sufficient information for complete evalu- ation. Amplitudes (CMAP, SNAP, and compound nerve action po- In diagnosing CTS, one should first screen for CTS with median tential) both proximal and distal to the carpal ligment are the most and radial SNAP to digit 1. The latency difference should be less important values in determining CTS severity and prognosis. than .03 ms. Next, stimulate the median nerve at the wrist (14 cm) and midpalm (7 cm), recording from digit 3. Allow for a SNAP While there are ample studies comparing different techniques, amplitude increase of less than 30%. Then, stimulate the median there are only a few that compare the amplitudes of the SNAPs. nerve at the wrist and distal to carpal ligament recording from the This is probable because the SNAP is larger at distal stimulation abductor pollicis brevis. Allow for a CMAP increase of less than (phase cancellation) and is affected more by temperature (i.e., 1 mV. it increases when cool).1 The temperature at distal palm can be measured easily with currently available instruments. Whether If CTS diagnosis is still not confirmed, perform a transcarpal study or not to warm the hand is controversial; in hands with over- (mixed nerve latency) and stimulate the median and ulnar nerve active sympathetic fibers, continued stimulations will change in midpalm and record over wrist (8 cm). Although Stevens22 the environment in spite of warming the hand. It is necessary suggests a difference of less than .2 ms, this author prefers .3ms. to be aware of SNAP changes secondary to cooling during the Note that the amplitude of median CNAP is 80 to 150 µV while EDX examination as a negative spike of SNAP will increase that of ulnar is only 20 to 40 µV. This is due to the superficial in duration and amplitude as well as cause the peak latency location of the median nerve at the wrist, while the ulnar nerve to increase). lies deep to the tendon of the flexor carpi ulnaris. Next, stimu- late the median and ulnar nerves at the wrist (14 cm), recording The distal stimulation of median motor fibers is complicated by from digit 4. The median SNAP is slightly larger (30 µV) and the proximity of the ulnar nerve and the ulnar innervation of the the latency difference is less than .3 ms. There is often a motor deep head of the flexor pollicis brevis in the thenar muscle group. artifact when stimulating the ulnar nerve. Stimulation of the median nerve with a needle (e.g., monopolar needle electrode) will facilitate the procedure. The shape of the Finally, stimulate the median and ulnar nerves at the wrist CMAP must be the same at both wrist and midpalmar stimula- (12 cm), recording over lumbrical I or II. Latencies differ tion points to ensure that the ulnar nerve is NOT stimulated. less than .5 ms. Note that the CMAP of lumbrical I or II is only 1 to 2 mV, while that of ulnar interosseus muscle is 4 to It is challenging to compare the median nerve values with 6 mV. those of the radial and ulnar nerves. Many studies have been performed and while some show varying results, it is fair In a previously conducted study, 20 2/3 SNAPs were combined to conclude: with different digits. This was found to increase the sensitivity of CTS diagnosis. • Digit 1 is the best and most sensitive digit to use when comparing radial to median SNAP. Besides its value in CTS The principal objective of the EDX examination in CTS diagnosis, there is additional value in identifying cervical radicul- is to confirm the diagnosis and to establish the stimulation opathy (second to foraminal stenosis where the sensory axons will severity. This can only be determined by recording SNAP be compromised at or distal to the dorsal ganglion and would and CMAP of the median nerve both proximal and distal to reduce the SNAP amplitude). One study suggested that the radial the entrapment. sensory branch was the least affected in diabetic neuropathy. Therefore, the comparison of median to radial nerves at digit 1 Needle EMG is unnecessary and causes additional discom- would be helpful to determine if CTS is occurring with underly- fort for the patient. It should not be routinely included in ing diabetic peripheral neuropathy.4 CTS EDX.
• Digit 3 is the best finger to study the median nerve SNAP both proximal and distal to carpal tunnel. This is probably REFERENCES because it is the longest portion of the median nerve. 1. Ashworth, NL, Marshall SC, Satkunam LE. The effect of tem- • Digit 4 SNAP with stimulation of median and ulnar perature on nerve conduction parameters in carpal tunnel syndrome. nerves is a useful technique to determine underlying neuropathy Muscle Nerve 1998;21:1089-1091. effects on CTS. Its advantage is that both nerves are being sub- jected to the same temperature variations. 26 Appropriate Testing for Carpal Tunnel Syndrome AANEM Course
2. Boonyapisit K, Katirji B, Shapiro BE, Preston DC. Lumbrical and 15. MacDonell RA, Schwartz MS, Swash M. Carpal tunnel syndrome: interossei recording in severe carpal tunnel syndrome. Muscle Nerve which finger should be tested? An analysis of sensory conduction in 2002;25:102-105. digital branches of median nerve. Muscle Nerve 1990;13:501-506. 3. Cassvan A, Ralescu S, Shapiro E, Moshkovski FG, Weiss J. Median 16. Monga T, Laidlow D. Carpal tunnel syndrome: measurement of and radial sensory latencies to digit 1 as compared with other sensory potentials using ring and index fingers. Am J Phys Med screening tests in carpal tunnel syndrome. Am J Phys Med Rehabil 1982;61:123-129. 1988;67:221-224. 17. Pease W, Cunningham ML, Walsh WE, Johnson EW. Determining 4. Cifu DX, Saleem S. Median-radial latency difference: its use in neurapraxia in carpal tunnel syndrome. Am J Phys Med Rehabil screening for carpal tunnel syndrome in 20 patients with demyelinat- 1988;67:117-119. ing peripheral neuropathy. Am J Phys Med Rehabil 1993;74:44-47 18. Phalen GS. Spontaneous compression of median nerve at the wrist. 5. Gordon C, Bowyer BL, Johnson EW. Electrodiagnostic charac- JAMA 1951;148:1128-1133. teristics of acute carpal tunnel syndrome. Arch Phys Med Rehabil 19. Preston D, Logigian E. Lumbrical and interossei recording in carpal 1987;68:545-548. tunnel syndrome. Muscle Nerve 1992;15:1253-1257. 6. Harmon R, Naylor A. Sensory and mixed nerve action potential dis- 20. Robinson L, Micklesen PJ, Wang L. Strategies for analyzing conduc- persion in median neuropathy at the wrist. Am J Phys Med Rehabil tion data: superiority of a summary index over single tests. Muscle 1998;78:213-215. Nerve 1998;21:1166-1171. 7. Johnson E, Gatens T, Poindexter D, Bowers D. Wrist dimensions: 21. Ross M, Kimura J. AAEM Case Report #2: The carpal tunnel syn- correlation with median sensory latencies. Arch Phys Med Rehabil drome. Muscle Nerve 1995;18:567-573. 1983;64:556-557. 22. Stevens J. AAEM Minimonograph #26. The electrodiagnosis of 8. Johnson E, Kukla RD, Wongsam PE, Piedmont A. Sensory laten- carpal tunnel syndrome. Muscle Nerve 1987;10:99-113 cies to the ring finger: normal values and relation to carpal tunnel 23. Tackman W, Kaeser HE, Magun HG. Comparison of orthodromic syndrome. Arch Phys Med Rehabil 1981;62:206-208. and antidromic sensory nerve conduction velocity in carpal tunnel 9. Johnson E, Sipski M, Lammertse T. Median and radial sensory syndrome. J Neurol 1981;224:257-266. latencies to digit 1: normal values and usefulness in carpal tunnel 24. Terzis S, Paschalis C, Metallinos IC, Papapetropoulos T. Early diag- syndrome. Arch Phys Med Rehabil 1987;68:140-141. nosis of carpal tunnel syndrome: comparison of sensory conduction 10. Johnson, E, Wells, R & Duran R:. Diagnosis of carpal tunnel syn- studies of four fingers. Muscle Nerve 1998;21:1543-1545. drome. 1962. Arch Phys Med & Rehabil 43:414. 25. Uncini A, Di Muzio A, Awad J, Manente G, Tafuro M, Gambi D. 11. Kothari M, Rutkove SB, Caress JB, Hinchey J, Logigian EL, Preston Sensitivity of three median-to-ulnar comparative tests in diagnosis of DC. Comparison of digital sensory studies in patients with carpal mild carpal tunnel syndrome. Muscle Nerve 1993;16:1366-1373. tunnel syndrome. Muscle Nerve 1995;18:1272-1276. 26. Vennix M, Hirsh DD, Chiou-Tan FY, Rossi CD. Predicting acute 12. Kuhlman K, Hennessey W. Sensitivity and specificity of carpal tunnel denervation in carpal tunnel syndrome. Arch Phys Med Rehabil syndrome signs. Am J Phys Med Rehabil 1997;76:451-457. 1998;79:306-312. 13. Lesser E, Venkatesh S, Preston DC, Logigian EL. Stimulation distal 27. Wongsam, P Johnson, E, & Weinerman, J: Carpal tunnel syndrome: to the lesion in patients with carpal tunnel syndrome. Muscle Nerve use of palmar stimulation of sensory fibers. Arch Phys Med & 1995;18:503-507. Rehab. 1983.64:1 14. Loong S, Seah C. Comparison of median and ulnar sensory nerve 28. Upton,A, McComas, A: The double crush in nerve entrapment action potentials in the diagnosis of carpal tunnel syndrome. J syndromes. Lancet.1973 August 18. (published as an hypothesis) Neurol Neurosurg Psychiatry 1971;34:750-754. Electrophysiologic Testing in Generalized Weakness Insert
Jasper Daube MD Department of Neurology Mayo College of Medicine Rochester, Minnesota
GENERALIZED WEAKENSS CLINICAL CASE FINDINGS COMMENT
Scattered, mytonic discharges in mulitple muscles Case 1 – 67-year-old woman with leg weakness REPORT 8-year history of slowly progressive, painless weakness Summary - NCSs are normal. Needle EMG shows fibrillation po- • 8 years ago - trouble arising from floor tentials and myotonic discharges with a mixture of short and long • 4 years ago - trouble arising from chair duration, polyphasic, rapidly recruited motor unit action potentials • 2 years ago - falls, give way of left leg (MUAPs) in proximal and distal muscles.
• Denies atrophy, fasciculations, muscle pain, sensory Interpretation – The findings are those of a chronic, severe, diffuse symptoms, or any upper extremity or trunk symptoms myopathy. Fibrillation potentials in myopathic disorders may indicate the presence of necrosis, splitting, or vacuolization of muscle fibers. • Previous needle electromyography (EMG) and nerve Mixed MUAPs can be seen in disorders that affect both nerve and conduction studies (NCSs) normal muscle or in very chronic myopathies such as inclusion body myositis (IBM), chronic polymyositis or some muscular dystrophies. IBM is Clinical Examination: Uses upper extremities to arise from seated most likely with this combination of EMG and clinical findings.
• -2 weakness quadriceps with mild, bilateral atrophy MUSCLE BIOPSY – IBM • -1 to -2 weakness left>right finger flexors and wrist flexors • Remainder of neurologic examination is normal, COMMENT including reflexes and sensory examination The distribution of weakness is an important clue to IBM. Mixed MUAP NCS – normal peroneal, tibial, and sural changes are also typical, but can be seen in very chronic myositis. EMG Fibrillation Recruit Duration Amplitude Phases Biceps brachii 0 reduced + long +short +low 25% FDI 0 +long +short +low 15% FCR ++ reduced +long +short +low 25% Medial gastroc. + reduced +long +short +high +low 25% TA + reduced +long +high 15% Vastus medialis + rapid +short +low 50% TFL + +long Paraspinal + +long +short +low 25%
EMG = electromyogrphy; FCR = flexor carpi radials; FDI = first dorsal interosseous; TA = tendon achilles; TFL = tensor fasciae latae Case 2: 20-year-old college student 2 weeks pro- REPORT gressive generalized weakness There has been marked progression of the disorder. There is now Day much clearer evidence of a widespread, demyelinating neuropathy 1. Myalgia, headache, sore throat, fever with distal involvement that could account for the paralysis. 10. Student Health: penicillin for “strep throat”, persistent emesis 11. Emergency Room - Urinary retention, lethargy, unsteady Day 23 IVIg 5 days - slow improvement; antibiotics continued 12. Diplopia, mild proximal weakness, brisk deep tendon reflex (DTR), bilateral Babinski Day 60 13. Reduced reflexes, progressive weakness, shortness of breath (SOB), tachycardia NCS 14. Hospitalized: Head CT and MRI normal; Cerebrospinal fluid (CSF) cells & protein increased NCSs reveal markedly reduced or absent compound muscle action potentials throughout with markedly slowed conduction velocities Diagnosis – Guillain–Barré with myelopathy, polyradiculoneu- and prolonged distal latencies. There is an ulnar conduction block ropathy, and autonomic neuropathy in the forearm on the left. The blink reflex was present, but mark- edly prolonged. Treatment Plan: Start 5 days intravenous immunoglobulin (IVIg) EMG Day 14 There are fibrillation potentials throughout, but with clear MUAP ac- NCS tivation of normal or mildly long duration in the proximal upper limb.
All motor amplitudes were low with no dispersion REPORT Median motor and peroneal responses absent No F waves The findings are now those of a severe polyradiculopathy with Conduction velocities and blink reflexes normal prominent demyelination, as well as moderate axon loss. There has Repetitive stimulation normal been improvement since the previous study. Fibrillation potentials are more prominent, but this reflects the Wallerian degeneration EMG that has occurred, and does not indicate a worsening.
Poor or no activation 3 months – Reflexes return; trachiostomy and PEG out Two muscles with reduced recruitment 6 months – Return to school with good limb strength No fibrillation potentials
REPORT COMMENT
Acute, severe, diffuse, axonal polyradiculopathy. A severe motor neu- The distinction between an axonal motor neuropahty (AMAN) ropathy with distal conduction block cannot be excluded, but is less and an acute demyelinating neuropathy is not always easy. Every likely. Repeat study in 7 - 10 days for more definitive information. attempt should be made to define the diagnosis and stop specific therapy too soon. Day 21 Total paralysis. Pulse dose methylprednisolone; tracheo- stomy; percutaneous endoscopic gastrostomy (PEG); C. dificile colitis; GM1 < 250; viral t/c (-) Case 3: 65 –year-old woman with fatigue NCS • 2 years of difficulty with household chores, “tired” Motor and sensory responses all showed marked reduction from • Difficulty squatting at “Curves”s the study of 9 days ago, despite high-intensity stimulation. The • EMG 1 year ago – normal NCS and EMG remaining, very low-amplitude responses had markedly long • Limited improvement on sertraline hydrochloride distal latencies and reduction in amplitude with proximal stimu- • Examination - mild proximal weakness including difficulty lation. No blink reflexes couldbe recorded. swallowing. Normal reflexes, cranial nerves, sensation, and gait EMG NCS No voluntary MUAPs could be activated in any muscle tested. Minimal fibrillation potentials were recorded only in hand and Motor and sensory NCSs are normal in the arm and leg, including cervical paraspinal muscles. F-wave latencies. Slow repetitive stimulation of ulnar/hypothenar, COMMENT accessory/trapezius and peroneal/anterior tibial muscles before and after exercise is normal. Myotonic discharges in DM2 are more prominent proximal, pre- dominantly wane, and may be few and far between. EMG Case 5: 45 –year-old interior designer with 3 months Needle EMG showed short duration MUAPs in several proximal generalized weakness muscles, including the genioglossus. A few fibrillation potentials were seen in the thoracic paraspinals. • Brain stem astrocytoma-stable 2 yrs after REPORT radiation therapy • Temporal lobe herpes simplex virus (HSV) encephalitis- The findings are those of a very proximal myopathy. The better year after acyclovir absence of many fibrillation potentials argues against, but does • Bulbar dysfunction from tumor-dexamethasone not exclude, an active inflammatory myopathy. and temazolamide • 2 mo progressive weakness with no other symptoms or signs BIOPSY • CSF and EMG performed at home - axonal and demyelinating neuropathy Sarcoidosis • Hospital transfer – flaccid quadriparesis with mild facial weakness and dyspnea COMMENT • Other cranial nerves, reflexes and sensation normal • MRI 10 mm mass and residuals of HSV; with deep While the clinical and EMG picture make an inflammatory vein thrombosis (DVT) myopathy most likely, a muscle biopsy should always be con- sidered to obtain a more definitive diagnosis. Sarcoidosis may EMG present initially with muscle involvement Short duration, polyphasic, stable MUAPs with rapid recruitment Case 4: 29-year-old woman with muscle aching in all muscles. Scattered fibrillation potentials
• Healthy - 5 years muscle aching NCS • Mild elevations of creatine kinase (CK) (300 - 550) • Examination normal CMAPs are low amplitude and markedly long duration without • Mild weakness, limited to left triceps dispersion. F-wave latencies are normal, but F waves are small. Normal sensory NCSs. Normal repetitive stimulation. NCS ADDITIONAL STUDIES Motor and sensory NCSs normal in arm and leg. Normal repetitive stimulation. Low amplitude MUAP with direct muscle stimulation. Normal motor unit number estimates. EMG REPORT Short duration MUAPs with mild, scattered fibrillation potentials in proximal muscles. The findings are those of a severe, generalized myopathy of the type seen with critical illness. This pattern can occur with high dose REPORT steroid medication.
The findings are mild, but consistent with a proximal myopathy, No evidence of an additional, neurogenic process or defect of possibly inflammatory. neuromuscular transmission was found.
BIOPSY FOLLOW-UP
Scattered, small, atrophic fibers with rare necrotic fibers. Consider Full return of strength after 4 months myotonic dystrophy, Type 2. COMMENT GENE TEST Critical illness myopathy can be difficult to distinguish from neu- Myotonic dystrophy type 2 (DM2) showed CCTG repeat expan- ropathy. Prolonged CMAP without dispersion and small MUAPs sions (>12,100 bp). Confirmed in relatives. are important distinguishing features. Case 6: 84- year-old woman with weakness
• Diabetes mellitus and hypothyroidism with 2 months of painless arm weakness • Examination: Proximal, symmetric arm weakness; normal sensation and reflexes
NCS
Normal
EMG
Proximal and distal muscles of the arm and leg show rapid recruit- ment of short duration MUAPs primarily in the proximal, muscles, a bit more in the arm than leg. A few scattered myotonic discharges were seen, but no fibrillation potentials were found.
REPORT
The findings are those of a proximal myopathy. The findings do not clearly suggest an inflammatory or other specific muscle disor- der. This pattern could be seen with a hypothyroid myopathy.
COMMENT
Severe hypothyroid myopathy often shows brief runs of myotonic like activity. Biopsy is nonspecific.