Chapter 19 Neurology and Electromyography Robert N. Kurtzke, MD

Transcription

1 Chapter 19 Neurology and Electromyography Robert N. Kurtzke, MD Neuromuscular Evaluation Most patients present to an orthopaedic surgeon reporting pain. The sensory examination is typically guided by the patient s specific complaint. Relevant to this discussion, nerve root injury or irritation causes pain and sensory disturbance that is more difficult to localize than focal nerve injury. C5 root involvement causes scapular pain with vague sensory change along the shoulder and upper arm. C6 and C7 root involvement also can cause retroscapular pain; C6 radiculopathy more reliably causes discomfort and numbness in the thumb and often the index finger, whereas C7 root involvement generally causes pain and numbness in the long and middle fingers. C8 and T1 radiculopathies are less common and produce pain and numbness in the medial forearm and ring and pinky fingers. In contrast to the vague sensory report of nerve root origin, focal peripheral nerve injury generally causes a more defined area of paresthesia, pain, and sensory loss. There is substantial sensory overlap of the various nerves and nerve roots, so that the area of greatest sensory involvement generally provides the most localizing information. The territory of pain and numbness described by the patient is often disassociated from the area of sensory loss demonstrated by the examiner. For example, a patient with carpal tunnel syndrome may report pain and numbness involving the entire hand radiating up the forearm, while the objective sensory loss is generally confined to the thumb, index, and middle fingers, and sometimes the ring finger. A simplified version of cervical and lumbosacral myotomes and the principal disorder to be differentiated is provided in Table 1. There is substantial overlap in the myotomes. The reflex examination provides additional clues to the level of dysfunction. The familiar reflexes are easily tested and in this context are most informative when asymmetry is present. Nerve Conduction Velocity Study and Electromyography Nerve conduction velocity studies and electromyography (EMG) are important aids in clarifying the clinical conditions of pain, numbness, and weakness. Nerve conduction is performed by stimulating a major nerve over accessible locations on the arm or leg and measuring a response using surface electrodes over the muscle or skin in the distribution of the nerve under Table 1 Cervical and Lumbosacral Myotomes and the Principal Differential Spinal Segment Myotome Principal Disorder to Be Differentiated C5 Supraspinatus, infraspinatus, deltoid Upper brachial plexopathy or isolated mononeuropathies (suprascapular, axillary nerves) C6 Biceps, brachioradialis, pronator teres Brachial plexopathy C7 Triceps, wrist, finger extensors and flexors Brachial plexopathy and isolated mononeuropathies (radial or median nerve) C8/T1 Finger extensors and flexors, intrinsic hand muscles Lower brachial plexopathy and focal neuropathy (radial, median, or ulnar) L2/L3 Hip flexion and thigh adduction Lumbar plexopathy L4 L5 Vastus lateralis, vastus medialis, rectus femoris, anterior tibialis, thigh adduction Anterior tibialis, peroneus longus, extensor hallucis longus, posterior tibialis, gluteus medius S1 Hamstrings, gastrocnemius Sciatic neuropathy Femoral neuropathy and lumbar plexopathy Sciatic neuropathy principally involving the peroneal fascicle or isolated peroneal neuropathy American Academy of Orthopaedic Surgeons Orthopaedic Knowledge Update 9 233

2 Section study (Figure 1). The most useful information includes the amplitude of the response and how quickly the response travels down the nerve measured by conduction velocity, distal motor latency, or, for the sensory nerves, distal latency. Motor nerve conduction velocity needs to be calculated because motor nerve impulses traverse the neuromuscular junction; this action requires additional time and does not reflect conduction along the nerve. Thus for motor nerves, the nerve is stimulated in a distal location (such as the median nerve over the wrist) and then at a proximal location (such as the me- Setup for median nerve motor study: recording electrode (wire on the right) over abductor pollicis brevis; reference electrode (wire on the left) over tendon; ground electrode on dorsum of the hand (wire not clearly visible). Stimulating electrode is over the median nerve at elbow. (Courtesy of American Association of Neuromuscular and Electrodiagnostic Medicine.) Figure 1 dian nerve at the elbow). The terminal or distal motor latency is subtracted from the proximal latency, providing the time it takes for the stimulus to travel from the proximal to the distal location (in this example, from the elbow to the wrist). The distance is measured by a tape measure in centimeters or millimeters and divided by the time it takes for the impulse to travel from the elbow to the wrist, providing the conduction velocity for that segment. Because sensory nerves have no neuromuscular junctions, calculating conduction velocity is not necessary nor does it provide additional information over the distal latency. Sensory conduction velocities are still reported as another means of describing sensory nerve function (Figure 2). Conduction velocity, sensory latency, and distal motor latencies all reflect the speed with which the impulse travels down the nerve and this generally reflects the integrity of the insulating myelin sheath. Focal conduction slowing implies focal pathology and can help localize the lesion. The most common clinical scenario using focal conduction slowing is the prolongation of the sensory and motor latencies at the wrist in persons with carpal tunnel syndrome. The other important datum provided by nerve conduction velocity studies is the amplitude of the response, which reflects the integrity of the axons. Low-amplitude sensory or motor responses usually imply axon loss. In some situations, low-amplitude response can be seen with disturbance of the insulating myelin; this is typified by focal neuropathy, such as ulnar neuropathy at the elbow. In this situation, the motor response has a robust amplitude when the nerve is stimulated distally (for example, at the wrist); however, with stimulation above or proximal to the site of compression (for example, at the elbow), the amplitude of the response drops by more than 40%. This finding is called conduction block and implies sufficient damage to the nerve to cause focal de- Figure A, Normal responses recorded over abductor pollicis brevis. A1 (top trace) response, stimulating median nerve at the wrist; A2 (bottom trace) response, stimulating median nerve at the elbow. B, Normal sensory response for median nerve stimulating the nerve over the wrist, recording over D2 (index finger). (Courtesy of American Association of Neuromuscular and Electrodiagnostic Medicine.) Orthopaedic Knowledge Update 9 American Academy of Orthopaedic Surgeons

3 Chapter 19: Neurology and Electromyography Figure 3 Normal motor unit action potentials firing at normal rates and numbers for given level of effort. See text for details. (Courtesy of American Association of Neuromuscular and Electrodiagnostic Medicine.) myelination, but not necessarily axon loss. Conduction block is generally readily reversible, whereas axon loss typically requires axon regeneration, a slower and less complete process. EMG involves placing a small needle electrode in the belly of the muscle. Normal muscle is electrically quiet at rest; when activated, the muscle produces electrical activity that is picked up by the needle. Early investigators determined the nature of nerve supply to the muscle and constructed the concept of the motor unit. The motor unit is composed of the motor neuron/anterior horn cell, the exiting motor nerve axon, and the muscle fibers it supplies. Anatomic and physiologic studies reveal that there are different numbers of motor units in various muscles, but the number of motor units per muscle is of an order of magnitude in the hundreds. Additionally, the number of muscle fibers belonging to a specific motor unit varies from muscle to muscle. One axon might supply only a small number of muscle fibers in muscles requiring finely graded control (such as extraocular and laryngeal muscles) compared with one axon supplying hundreds of muscle fibers in larger muscles such as the vastus or gastrocnemius muscles. Muscle fibers of adjacent motor units intermingle, and individual motor unit territory is in the range of 5 to 10 mm. In healthy muscle, the motor unit action potential recorded by the needle electrode has typical shape, duration, and amplitude that can be quantitated. Duration is the most informative feature of the motor unit action potential, a concept proposed in the early 1950s and confirmed by computer-assisted studies. 1,2 Amplitude is another important feature, but is more dependent on how close the needle electrode is to the muscle fibers in the motor unit generating the potential. Some motor unit action potentials appear serrated or polyphasic in disease state in both myopathies and neuropathies; when polyphasic potentials appear in excessive numbers, that finding is considered abnormal. The other major electromyographic finding of interest is how the motor units are brought to work, or recruited. Recruitment tends to be a more subjective assessment of the numbers of motor unit action potentials active for a given level of muscular effort provided by the patient (Figure 3). On the EMG screen, with increasing levels of effort, more motor unit action potentials are seen and heard and at a high level of effort produce an interference pattern, where so many units are firing that the individual units cannot be distinguished analogous to a forest of trees. In neurogenic illness, there is a dropout of motor units and by necessity, the ones remaining will fire more rapidly to compensate for the reduced numbers available for work. Consequently, fewer motor unit action potentials are heard and seen during EMG, producing a reduced recruitment pattern or incomplete interference pattern of fast-firing motor unit action potentials. In severe neurogenic illness, the interference pattern can be so diminished as to produce what is termed a discrete interference pattern, in which individual motor unit action potentials can be discerned. In nerve disease and some muscle diseases, EMG abnormalities include muscle membrane instability that manifests as spontaneous muscle fiber discharges called insertional positive waves and fibrillation potentials. Because they are produced by single muscle fibers, fibrillation potentials have short durations, 1 to 5 ms, and a crisp high-pitched sound with regular discharge rate. Positive sharp waves also originate from individual muscle fibers and generally have the same significance as fibrillation potentials. Positive sharp waves have a downward or positive deflection that looks like shark teeth on the EMG screen; the appearance is believed to be the result of depolarization of the electrode-damaged segment of the muscle fiber. Fibrillation potentials and insertional positive waves typically appear several weeks after an injury (Figure 4). As previously stated, with nerve disease or focal nerve injury, dropout of anterior horn cells or nerve fibers may occur and EMG will record reduced numbers of active motor unit action potentials or reduced recruitment. The remaining motor unit action potentials change over time, becoming longer in duration and larger in amplitude as reinnervation occurs (Figure 5). In muscle disease, membrane instability may also manifest as fibrillation potentials and insertional positive waves, but the recruitment and motor unit action potential changes are different. Whereas in nerve disease there is dropout of motor units, in muscle disease there is random dropout of individual muscle fibers, which produce motor unit action potentials of shorter duration and typically smaller amplitude. Because individual motor unit action potentials represent fewer muscle fibers, which generate less force, individual units need to be recruited earlier at lower levels of effort and a full interference pattern may be seen even with mild to moderate levels of effort. American Academy of Orthopaedic Surgeons Orthopaedic Knowledge Update 9 235

4 Section Figure 4 Fibrillation potentials: spontaneous discharges of individual muscle fibers (left panel). Positive sharp waves: discharges from individual muscle fibers generally have the same significances as fibrillation potentials (right panel). See text for details. (Courtesy of American Association of Neuromuscular and Electrodiagnostic Medicine.) Figure 5 A long duration (920 ms) motor unit action potential, with reinnervation, is shown. See text for details. (Courtesy of American Association of Neuromuscular and Electrodiagnostic Medicine.) EMG can readily distinguish between nerve and muscle disease and can typically determine whether the pattern of abnormal muscles belongs to an individual nerve or nerve root or whether the representative abnormalities suggest plexus involvement or a generalized neuropathy. Nerve conduction velocity studies can help determine whether there is focal or generalized neuropathy, and a combination of nerve conduction velocity studies and EMG can distinguish focal neuropathy from radiculopathy. Disorders Associated With Neuropathy Neuropathy refers to nerve disease but implies a generalized dysfunction, usually in length-dependent fashion so that the longest nerves are affected first and have the greatest degree of dysfunction. The nerve bundles are composed of hundreds of individual nerve fibers, varying in size from small unmyelinated or thinly myelinated fibers to large, thickly myelinated fibers. Neuropathy can be clinically and electrically segregated into axonal neuropathy or demyelinating neuropathy. Demyelinating polyneuropathy is characterized electrically by slow conduction velocity, prolonged sensory and motor latencies, and generally preserved amplitudes. EMG may reveal reduced recruitment and a paucity of spontaneous activity unless there is concomitant axonal damage. In contrast, axonal neuropathy typically is characterized by reduced sensory and motor amplitudes on nerve conduction velocity studies, with normal latencies and velocities. EMG in axonal neuropathy reveals fibrillation potentials and positive waves, generally in distal muscles, with reduced recruitment and features of reinnervation large-amplitude, long-duration motor unit action potentials. Reinnervation typically means that the neuropathy has been present for some time, at least 6 to 12 months. Axonal neuropathy is often idiopathic, but may be caused by a metabolic disturbance such as the neuropathy of diabetes or a toxic disturbance that can occur with alcoholism or cisplatin-induced neuropathy. Demyelinating neuropathy is grouped into inherited and acquired forms. The most common inherited demyelinating neuropathy is Charcot-Marie-Tooth disease type 1A. In most inherited demyelinating polyneuropathies, conduction velocities are uniformly slow; for example, if the velocity in the median nerve is 25 m/s, it is similarly slow in the ulnar and peroneal nerves in contrast to acquired demyelinating neuropathy, in which conduction velocities may vary from nerve to nerve. 3 Another feature of acquired neuropathy, which generally distinguishes it from inherited neuropathies, is conduction block, in which compound muscle action 236 Orthopaedic Knowledge Update 9 American Academy of Orthopaedic Surgeons

5 Chapter 19: Neurology and Electromyography potential amplitude drops by more than 40% on proximal stimulation in comparison with distal stimulation. Conduction block is highly suggestive of acquired demyelinating neuropathy. The most common acquired demyelinating neuropathy is Guillain-Barré syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy (CIDP). The patient s history provides the first clues in formulating the differential diagnosis of neuropathy; the symptoms are numbness, tingling, and pain or weakness alone or in combination. The tempo of progression of the symptoms provides additional information. Acute neuropathy is usually either toxin or immunemediated, whereas an indolent progressive neuropathy can be inherited, toxic, or diabetic. Physical examination may disclose muscular wasting and weakness, loss of reflexes, and sensory loss in a stocking-glove distribution. Reduced vibratory sensation and joint position sensation suggest demyelinating neuropathy, as does reflex loss with weakness disproportionate to muscular atrophy. Delayed or reduced cold sensation over the feet, preserved reflexes, and preserved proximal strength in a patient with burning feet are features typical of small fiber axonal neuropathy. History and physical examination can generally differentiate peripheral neuropathy from lumbosacral polyradiculopathy or cervical myelopathy, but nerve conduction velocity studies and EMG are more sensitive and also better distinguish between a generalized sensorimotor neuropathy and less common disorders such as mononeuritis multiplex or multifocal demyelinating neuropathy. Diabetic Neuropathy Diabetes is considered to be the most common cause of peripheral neuropathy in the United States and other developed countries. Because of a trend of increased body fat observed in recent years that has often been associated with dyslipidemia and insulin resistance, type 2 diabetes may become an increasingly frequent cause of neuropathy in the United States. Neuropathy in patients with diabetes is often a relatively symmetric, nerve length-dependent process causing stocking-glove sensory disturbance, pain, and numbness with distal weakness. Because nerve cells are the longest cells in the body, it is not surprising that these metabolically active cells should suffer accelerated breakdown and an impaired repair process in the diabetic state. It is somewhat surprising that impaired glucose tolerance, to a level not generally considered to cause diabetes, is also associated with peripheral neuropathy. Idiopathic neuropathy should now be evaluated not only with fasting blood glucose but also a 2-hour glucose tolerance test. 4 In addition to the generalized neuropathy that affects many patients with diabetes, there is also an increased incidence of focal neuropathy, including carpal tunnel syndrome and ulnar neuropathy at the elbow or wrist. Focal and regional neuropathy can occur in patients with diabetes on a compressive, ischemic, or inflammatory basis alone or in combination. Diabetic radiculopathy, plexopathy, or proximal neuropathy may occur on an inflammatory or ischemic basis, causing proximal pain and weakness that can mimic compressive radiculopathy. 5 The most common example of this is diabetic amyotrophy, characterized by severe pain in the hip girdle and thigh, usually associated with pronounced wasting and weakness of the thigh muscles, loss of the knee jerk, and often with pronounced weight loss, sometimes of 20 to 40 pounds (diabetic cachexia). This syndrome often affects older adults with type 2 diabetes that is often well controlled, without the typical complications of advanced diabetes. It is believed that ischemia from microvasculitis is the principal cause of this proximal radicular plexopathy. 6 The course of diabetic amyotrophy is progression of severe pain, asymmetric thigh-wasting, and weakness for several weeks, but pain and weakness may last for many months and recovery may take several years. Intractable pain often requires narcotic analgesia. Neurologic evaluation, lumbar and pelvic imaging, nerve conduction velocity studies, and EMG often distinguish this condition from malignancy, compressive radiculopathy, or canal stenosis. Guillain-Barré Syndrome Guillain-Barré syndrome is caused by an immunemediated attack on the peripheral nerve causing segmental demyelination, which causes conduction slowing on nerve conduction velocity studies and conduction block, where the compound muscle action potential amplitude drops more than 40% when the nerve is stimulated proximal to the site of demyelination. The clinical characteristics include loss of tendon reflexes, vague numbness and tingling, and progressive weakness disproportionate to sensory complaints. A good number of patients report aching muscular back pain; these patients may present to the orthopaedic surgeon for their first medical encounter. The diagnosis is complicated by the fact that loss of tendon reflexes takes time and so the patient may have preserved reflexes when first examined. Many patients experience upper respiratory or gastrointestinal infection in the weeks preceding examination by the physician. A diarrheal illness from Campylobacter infection can be associated with severe Guillain-Barré syndrome. Weakness may progress over hours or days and typically hits its nadir after several weeks, sometimes leading to complete paralysis. These patients should be hospitalized and their vital capacity monitored, as many of them require ventilatory support. The diagnosis remains clinical, but is supported by elevated spinal fluid protein without pleocytosis. Nerve conduction velocity studies and EMG can provide early diagnostic information by demonstrating evidence of acquired acute demyelinating polyneuropathy before spinal fluid abnormalities are evident and reflexes are lost. As noted earlier, the features of an acute acquired demyelinating polyneuropathy include prolonged sensory and distal motor latencies, conduction slowing in nerves to variable degrees, and conduction block. Another feature typical of Guillain-Barré American Academy of Orthopaedic Surgeons Orthopaedic Knowledge Update 9 237

6 Section syndrome is the preservation of sural nerve responses, when median and ulnar sensory nerve action potentials are abnormal either in latency or amplitude; this finding is called sural sparing. Nerve conduction velocity studies also provide early prognostic information. Preserved compound muscle action potential amplitudes are a favorable feature and bode well for ultimate motor function and ambulation. Plasmapheresis and intravenous immunoglobulin therapy shorten the duration of the illness, the time of hospitalization, ventilator dependence, and time to ambulation. 7 Despite the autoimmune basis, steroid therapy does not benefit patients with Guillain-Barré syndrome. 8 A small group of patients initially suspected to have Guillain-Barré syndrome will ultimately exhibit symptoms of CIDP, a chronic disorder with progressive weakness or a relapsing course. In other patients with CIDP a subacute or insidiously progressive neuropathy develops; nerve conduction velocity studies disclose demyelinating features. Spinal fluid protein is generally elevated. CIDP is also amenable to intravenous immunoglobulin therapy or plasmapheresis, and these patients generally benefit from steroid therapy, in contrast to patients with Guillain-Barré syndrome. Hereditary Sensorimotor Neuropathy/ Charcot-Marie-Tooth Disease This group of neuropathies was originally classified according to clinical characteristics and inheritance patterns but will be increasingly refined and sometimes redefined by genetic testing. Charcot-Marie-Tooth disease is a clinical disorder of progressive wasting and weakness in the distal leg, especially peronealinnervated muscles associated with high arched feet and hammer toes, that was first described in the late 1880s. Clinical heterogeneity and variable inheritance patterns led to classifications that will likely be supplanted by molecular genetic identification of the culpable gene and abnormal protein. Nerve conduction velocity studies and EMG facilitated classification into primarily demyelinating versus axonal neuropathies, and this classification still holds value. Genetic confirmation of suspected inherited neuropathies is now available for more than a dozen conditions, and that number will grow as genetic testing sophistication increases. Patients with Charcot-Marie-Tooth disease are often evaluated for foot deformity or foot pain; the orthopaedic surgeon recognizes the potential neuropathic process and often discovers a family history of similar foot deformity or neuropathy. Nerve conduction velocity studies show significant nerve conduction slowing, often in the range of 20 m/s, and EMG may show evidence of reinnervation in distal muscles. The nerve conduction abnormalities are generally uniform in Charcot-Marie-Tooth disease type 1A, but in a related disorder, hereditary neuropathy with predisposition to pressure palsy (HNPP), some nerves may be more affected than others. Both conditions are caused by abnormalities of the peripheral myelin protein 22 (PMP- 22) coded on chromosome 17. In Charcot-Marie-Tooth disease type 1A, there is duplication of the PMP-22 gene, whereas in HNPP, the PMP-22 gene is deleted. 9 In either situation, the duplication or the deletion leads to dysfunction in the compact myelin sheath laid down by the Schwann cell and the myelin disruption accounts for the conduction slowing evident on nerve conduction velocity studies. The clinical disability is not caused by the slow conduction, but rather subsequent axonal degeneration secondary to interruption in Schwann cell/axon interaction. Patients with HNPP may have symptoms suggesting carpal tunnel syndrome, ulnar neuropathy, or foot drop suspected to be caused by peroneal neuropathy. A thorough patient history may disclose previous episodes of similar symptoms but these patients may not show the typical features of inherited neuropathy, such as the high arched feet. Nerve conduction velocity studies reveal abnormalities of demyelinating polyneuropathy, more prominent at sites of common compression, such as the ulnar nerve at the elbow, the peroneal nerve at the fibular head, or the median nerve in the carpal tunnel. Multiple Sclerosis Multiple sclerosis (MS) is a disease of the central nervous system with an autoimmune component clinically expressed by relapses and remission of inflammation and demyelination of the brain and spinal cord. The cause is unknown but it may be an environmental trigger that produces the disease in those who are genetically susceptible. Epidemiologic studies suggest a specific trigger, perhaps a virus. 10 The myelin of the central nervous system is laid down by the oligodendroglia and is distinct from peripheral nerve myelin, which is laid down by Schwann cells. In MS attacks, symptoms depend on the specific site in the brain or spinal cord involved in the inflammatory response. Common symptoms include numbness and tingling, band-like sensations, urinary frequency and urgency, double vision, visual loss, and ataxia. When the lesion of MS involves the spinal cord, it can cause the syndrome of acute transverse myelitis with progressive numbness and weakness below the site of the lesion, often with a sensory level. Although the diagnosis is still clinical, it has been greatly facilitated by MRI, which shows high signal lesions in a characteristic periventricular distribution in the brain or in the spinal cord. Spinal fluid analysis reveals scant white blood cells, mild elevation in protein, and an increase in immunoglobulin synthesis with oligoclonal banding. Clinically, there are not many conditions that mimic MS; although uncommonly, lupus can involve the nervous system as can sarcoidosis. Patients with suspected MS and cervical spondylosis can present a diagnostic and therapeutic conundrum. When the cardinal symptoms and signs are those of progressive spastic paraparesis and MRI discloses spondylosis with severe canal stenosis in patients with prior neurologic symptoms suggesting MS, these patients may benefit from neurologic consultation, cerebral MRI, and visual-evoked potentials to investigate otherwise subclinical involvement of the optic nerves 238 Orthopaedic Knowledge Update 9 American Academy of Orthopaedic Surgeons

7 Chapter 19: Neurology and Electromyography and sometimes spinal fluid analysis. In some patients with both MS and spondylosis, surgical decompression can be offered after due consideration in an effort to minimize cord injury from progressive canal stenosis. Disease-modifying treatment is now available for MS, chiefly beta-interferons and glatiramer acetate. These agents reduce the severity of attacks and their frequency by one third; the number of MRI lesions and degree of long-term disability are also reduced. 11 These agents are currently injectable. Alternative immunotherapy has been attempted with more potent immunosuppressants such as cyclophosphamide and more recently mitoxantrone. These agents have significant potential toxicity and are currently not viewed as firstline therapy for patients with relapsing remitting disease, but are considered in patients with recalcitrant, severe relapsing, or progressive disease. In recent years, the natalizumab Tysabri (Biogen Idec, Cambridge, MA) was approved by the Food and Drug Administration for use in clinical practice. Tysabri is a monoclonal antibody that binds α-4-integrin on the surface of white blood cells and selectively inhibits adhesion and prevents lymphocytes from crossing the blood brain barrier into the inflamed brain and spinal cord. 12 Shortly after Food and Drug Administration approval, two patients being treated for MS developed progressive multifocal leukoencephalopathy, generally a fatal disorder, and a third patient who took the medication for Crohn s disease also developed progressive multifocal leukoencephalopathy. All three patients were recently or concomitantly receiving immunomodulating therapy. The medication is currently available under a supervised program developed in consultation with the Food and Drug Administration, and long-term results are not yet known. 13 Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig s disease, is a disorder causing relentlessly progressive muscular wasting and weakness and ultimately paralysis of limb, oropharyngeal, and respiratory muscles leading to death from respiratory failure in just a few years. The etiology of the disease is unknown and the disease is generally sporadic; although about 5% of patients with ALS have a familial form, with some of these patients mapping to the gene for superoxide dismutase on chromosome The diagnosis is based on clinical findings with signs of disease of the upper motor neuron (whose cell body lives in the motor cortex and whose fiber track runs through the white matter of the brain to the lateral column of the spinal cord), and the lower motor neuron (whose cell body lives in the anterior horn of the spinal column and whose process runs through the peripheral nerve to the muscle). Upper motor neuron dysfunction leads to spasticity, exaggerated reflexes, Hoffman and Babinski signs, and spastic dysarthria. Lower motor neuron dysfunction produces muscular atrophy, weakness, and clinical fasciculations. The diagnosis is generally secure when lower motor and upper motor neuron signs are present in the same limb and cranial nerve findings are present (dysarthria with wasting and twitching of the tongue). Nerve conduction velocity studies are generally normal in the early stages of the disease but as muscular atrophy progresses, the compound muscle action potential amplitude declines. Sensory nerve conduction velocity studies are normal. EMG discloses fasciculation potentials, fibrillation potentials, and positive waves with reduced recruitment of motor unit action potentials. Generally, there are signs of reinnervation with largeamplitude long-duration motor unit action potentials. Fasciculation potentials are spontaneous discharges of single motor units. Fasciculation potentials may be generated at a variety of sites from the anterior horn cell through axonal branches. When associated with other features of denervation (fibrillations, positive waves) and reinnervation, these fasciculation potentials are suggestive of ALS. Fasciculation potentials can be seen in other conditions with chronic denervation and in the syndrome of benign fasciculations and muscular cramps. In isolation, fasciculations can be a benign finding and they do not in and of themselves imply the presence of ALS. This is particularly important because some patients and physicians observe occasional fasciculations without other symptoms and can needlessly suspect ALS. EMG can bolster the clinical suspicion of ALS by revealing fibrillation potentials, positive waves, and long-duration large-amplitude motor unit action potentials with reduced recruitment in cranial and limb muscles of a patient presenting with spasticity and weakness. Currently, there is no satisfactory treatment for ALS. Riluzole is prescribed, but provides only modest benefits with studies suggesting prolongation of life or time to ventilator by a few months. 15,16 The major thrust of treatment is supportive medical and emotional care. Severe cervical spondylosis can sometimes mimic ALS by causing cord compression from canal stenosis and multilevel radiculopathy from foraminal stenosis. In these patients, there may be wasting and weakness in arm muscles from nerve root compression and spasticity of the legs from spinal cord compression. Sensory symptoms may be minimal and urinary frequency or incontinence can be late features. Again, EMG is quite useful when it reveals evidence of lower motor neuron involvement in the spastic legs, or when it reveals abnormalities in the face or tongue, cranial innervated muscles that would be normal in cervical spondylosis. If clinical fasciculations are present in the legs of a person with suspected cervical spondylosis, ALS should be considered. Summary Nerve conduction velocity studies and EMG help clarify neuromuscular conditions for orthopaedic surgeons and neurologists, confirm suspected diagnoses, offer alternative diagnoses, and assist in formulating prognoses. The American Association of Neuromuscular and Electrodiagnostic Medicine provides educational material to physicians involved in the care of patients American Academy of Orthopaedic Surgeons Orthopaedic Knowledge Update 9 239

8 Section with neuromuscular and musculoskeletal conditions, and their Website offers links to other relevant Websites as well as educational materials in the form of monographs, slides, and articles. 17 Annotated References 1. Buchthal F, Pinelli P, Rosenfalck P: Action potential parameters in normal human muscle and their physiological determinants. Acta Physiol Scand 1954;32: Dorfman L, McGill K: AAEE minimonograph 29: Automatic quantitative electromyography. Muscle Nerve 1988;11: Lewis RA, Sumner AJ, Shy ME: Electrophysiological features of inherited demyelinating neuropathies: A reappraisal in the era of molecular diagnosis. Muscle Nerve 2000;23: Hoffman-Snyder C, Smith BE, Ross MA, Hernandez J, Bosch EP: Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy. Arch Neurol 2006;63: This report highlights the importance of the oral glucose tolerance test in patients with idiopathic neuropathy. It is recognized that many of those affected by small fiber axonal neuropathy have impaired glucose tolerance. 9. Chance PF, Alderson MK, Leppig KA, et al: DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell 1993;72: Kurtzke JF, Heltberg A: Multiple sclerosis in the Faroe Islands: An epitome. J Clin Epidemiol 2001;54: Goodin DS, Frohman EM, Garmany GP Jr, et al: Disease-modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002;58: Polman CH, O Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354: Natalizumab is a potentially powerful treatment for multiple sclerosis, but is complicated by the development of progressive multifocal leukoencephalopathy in two of the patients studied. 13. Kappos L, Bates D, Hartung HP, et al: Natalizumab treatment for multiple sclerosis: Recommendations for patient selection and monitoring. Lancet Neurol 2007; 6; This article provides a summary of the current position on recommendations for patient selection and monitoring of Tysabri and progressive multifocal leukoencephalopathy. 5. Dyck PJ, Kratz KM, Karness JL, et al: The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a populationbased cohort: The Rochester Diabetic Neuropathy Study. Neurology 1993;43: Dyck PJ, Windebank AJ: Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: New insights into the pathophysiology and treatment. Muscle Nerve 2002;25: Plasma Exchange/Sandoglobulin Guillain-Barré Trial Group: Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Lancet 1997;349: Hughes RA, van der Meche FG: Corticosteroids for treating Guillain-Barré syndrome. Cochrane Database Syst Rev 2000;3:CD Siddique T, Nijhawan D, Hentati A, et al: Molecular genetic basis of familial ALS. Neurology 1996;47(suppl 2): S27-S Bensimon G, Lacomblez L, Meininger V, et al: A controlled trial of riluzole in amyotrophic lateral sclerosis: ALS/Riluzole Study Group. N Engl J Med 1994;330: Lascomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V: Dose-ranging study of riluzole in amyotrophic lateral sclerosis: Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996;347: American Association of Neuromuscular and Electrodiagnostic Medicine Website. Available at: Accessed July 2, TABLE Orthopaedic Knowledge Update 9 American Academy of Orthopaedic Surgeons