AAEM MINIMONOGRAPH 18 ABSTRACT: The clinical electrodiagnostic medicine (EDX) consultant asked to assess patients with suspected amyotrophic lateral sclerosis (ALS) has a number of responsibilities. Among the most important is to provide a clinical assessment in conjunction with the EDX study. The seriousness of the diagnoses and their enormous personal and economic impact require a high-quality EDX study based on a thorough knowledge of and experience with motor neuron diseases (MNDs) and related disorders. Clinical evalua- tion will help determine which of the EDX tools available to the EDX con- sultant should be applied in individual patients. Although electromyography (EMG) and nerve conduction study are the most valuable, each of the fol- lowing may be helpful in the assessment of selected patients based on their clinical findings: repetitive nerve stimulation, motor unit number estimate, single-fiber EMG, somatosensory evoked potential, autonomic function test, and polysomnography. The pertinent literature on these is reviewed in this monograph. The selection and application of these EDX tools depend on a thorough knowledge of the MNDs and related disorders. © 2000 American Association of Electrodiagnostic Medicine Muscle Nerve 23: 1488–1502, 2000 ELECTRODIAGNOSTIC STUDIES IN AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS JASPER R. DAUBE, MD Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905-0001, USA Following is an overview of motor neuron diseases defect has been identified in one form of hereditary (MNDs). This overview will introduce the MNDs, but ALS with an abnormal form of the enzyme superox- only an in-depth study of the disorders and pertinent ide dismutase.5 The locus of the abnormal gene has literature will enable an electrodiagnostic medicine been determined in childhood SMA and in (EDX) consultant to provide a full range of help. Kennedy’s syndrome (bulbospinal neuronopa- Most MNDs are diffuse system degenerations of un- thy).63,64,107 The World Federation of Neurology (El known etiology that selectively destroy upper and/or Escorial) criteria classify other MNDs into mimic, lower motor neurons.99,112 Although many are dif- coexisting, and variant disorders.36 “Motor neuron fuse, sporadic, and progressive, a small proportion is disease mimic disorders” are disorders in which the hereditary11,126 or focal.61 Amyotrophic lateral scle- motor neurons are secondarily involved, such as rosis (ALS) is the most common MND in adults; spondylotic myelopathy, spinal cord arteriovenous spinal muscular atrophy (SMA) is the most common malformation, exposure to exogenous toxins, lym- in children.57,69 The underlying molecular genetic phoma, other cancers, monoclonal and dysimmune gammopathies, vasculitis, motor polyradiculopathy, Abbreviations: EDX, electrodiagnostic medicine; AHC, anterior horn cell; multifocal motor neuropathy (MMN) with conduc- ALS, amyotrophic lateral sclerosis; CIDP, chronic inflammatory demyelin- tion block, chronic inflammatory demyelinating ating polyradiculoneuropathy; CMAP, compound muscle action potential; CV, conduction velocity; EMG, electromyography; MEP, motor evoked polyradiculoneuropathy (CIDP), hyperthyroid and potential; MMN, multifocal motor neuropathy; MND, motor neuron dis- hypothyroid states, Creuzfeldt–Jakob disease, and ease; MUNE, motor unit number estimate; MUP, motor unit potential; NCS, 3,8,56,73,82,110,119 nerve conduction study; SFEMG, single-fiber EMG; SMA, spinal muscular acute infections. Acute viral infec- atrophy; S-MUP, single motor unit potential tions that involve the motor neurons are polio, her- Key words: amyotrophic lateral sclerosis; EMG; motor neuron disease; 58,98 poliomyelitis; spinal muscular atrophy pes zoster, and some coxsackie viruses. Other Correspondence to: American Association of Electrodiagnostic Medi- hereditary degenerations, such as Friedreich’s ataxia cine, 421 First Avenue SW, Suite 300 East, Rochester, MN 55902; e-mail: [email protected] and multisystem atrophy (Shy–Drager syndrome) © 2000 American Association of Electrodiagnostic Medicine. Published can also have motor neuron involvement. Anterior by John Wiley & Sons, Inc. horn cells (AHCs) can be damaged in association 1488 AAEM MM#18: ALS and Other Motor Neuron Diseases MUSCLE & NERVE October 2000 with neoplasms, radiation, asthma, and hypoglyce- Involvement of upper motor neurons results in mia.24,81,121,139 “Motor neuron disease coexisting dis- weakness without atrophy. Reflexes are hyperactive, orders” occur in patients who have a pre-existing and pathologic reflexes are present. Spasticity is neurologic disease superimposed on ALS, such as common; with involvement at different levels, there diabetic neuropathy or ulnar neuropathy. “Motor may be spastic dysarthria with pseudobulbar palsy, or neuron disease variant disorders” occur in patients spastic gait. Damage to upper motor neurons is with ALS in whom the autonomic, sensory, or an- manifest on needle electromyography (EMG) only other component of the nervous system is involved as abnormalities of motor unit discharge patterns. along with the motor system. Electrodiagnostic In contrast, lower motor neuron damage in ALS medicine testing is particularly important for identi- produces both clinical and electrophysiological ab- fying and distinguishing the coexisting diseases and normalities. Degeneration of AHCs and their pe- some of the mimic disorders (Table 1). ripheral axons results in loss of muscle innervation. With the identification of underlying mecha- Denervated muscle becomes weak, flaccid, and atro- nisms of the MND, options for therapy have become phic, the typical signs of lower MND. The nerve ter- available. Some have already been shown to have minals of remaining intact motor units retain their small benefits, but many others are being investi- capacity for collateral sprouting and will reinnervate gated. The ability of EDX studies to quantitate the the denervated muscle fibers. Weakness and atrophy lower motor neuron damage make these studies an do not occur as long as the reinnervation can keep integral part of clinical therapeutic trials. pace with the loss of AHCs. Up to one half of the A number of disorders may resemble a MND, motor neurons innervating a muscle may be lost in especially those with focal cord involvement such as ALS before clinical signs of weakness or atrophy are syringomyelia, tumors of the spinal cord, spinal cord found.27 As more motor neurons progressively die, arteriovenous malformations, infarction, or congen- compensation fails and weakness develops. After po- ital dysplasias of the spinal cord. The most common liomyelitis, as another example of the capability of cause of localized cord damage that can mimic MND collateral sprouting, a few motor neurons that sprout is bony spine disease, such as cervical and lumbar to reinnervate denervated muscles can maintain nor- spondylosis, which impinges on the spinal cord or mal strength when 90% of the neurons have been nerve roots. The EDX consultant must attempt to lost. The regenerating axons are irritable and often differentiate these problems from MND. This can be discharge spontaneously, resulting in fasciculations, quite difficult because both spondylotic myelopathy especially after exercise. and MND may be focal at onset and remain asym- metrical. AMYOTROPHIC LATERAL SCLEROSIS With the exception of “variant” disorders, MNDs Clinical. The major determinant of ALS is progres- do not show clinical involvement of the sensory or sive loss of motor neurons. The loss of motor neu- other components of the nervous system. Some rons usually begins in one area, is asymmetrical, and forms of MND selectively affect the upper motor later becomes evident in other areas. The first signs neurons as in primary lateral sclerosis; some selec- of ALS may be either upper or lower motor neuron tively affect the lower motor neurons, as in progres- loss. Recognition of upper motor neuron involve- sive SMA; others, such as Kennedy’s syndrome, have ment depends on clinical signs; the electrophysi- specific distributions. The most common disorder, ological changes that occur with upper motor neu- ALS, involves both upper and lower motor neurons. ron damage are neither specific nor sensitive enough to provide help. Table 1. Disorders sometimes mistaken for ALS that must be In contrast, EDX testing is of major help in iden- considered during electrodiagnostic evaluation. tifying lower motor neuron involvement; lower mo- Cervical spondylosis tor neuron abnormalities are typically evident on Motor polyradiculopathy electrodiagnostic testing before they are clinically Multifocal motor conduction block recognizable. Needle EMG and nerve conduction CIDP Peripheral neuropathy studies (NCSs) can assist in both identifying the pres- SMA ence of and documenting the progression of the loss Focal amyotrophy of lower motor neurons that occurs in ALS, thus Primary lateral sclerosis minimizing the common occurrence of early misdi- Multiple sclerosis agnosis.10,40 However, the variations in the findings Myositis MG among patients with ALS require better definition of the criteria for diagnosis.9 AAEM MM#18: ALS and Other Motor Neuron Diseases MUSCLE & NERVE October 2000 1489 The World Federation of Neurology has classi- fied ALS into definite (upper motor neuron and lower neuron signs at three levels); probable (upper motor neuron and lower motor neuron signs at two levels), possible (upper and lower motor neuron signs at one level or