ALS is a disorder of the anterior horn cell that presents with progressive, painless weakness combined with upper motor neuron findings and the absence of sensory symptoms. It is an almost universally fatal disease, with an average life span from the time of diagnosis of 3 to 5 years.²⁸ Other disease processes that could potentially masquerade as ALS, such as polyradiculopathy, polyradiculoneuropathy, or MMNCB, must be entirely excluded because they can have treatment implications. EDX testing is helpful to confirm the diagnosis when it is clinically apparent, and to diagnose the condition when it is clinically suspected but too early to diagnose on clinical grounds alone (abnormal findings are usually present on needle examination long before they become clinically evident).

In this case, there is electrophysiologic evidence of rapid, severe denervation, with inadequate reinnervation (fibrillation potentials and polyphasic, varying, neurogenic MUPs on needle EMG), without any sensory involvement (normal SNAPs and low CMAPs on NCSs). Although the patient did not have any bulbar dysfunction, cranial-innervated muscles were also examined, with fasciculations and varying MUPs present. This indicated a very diffuse neurogenic process, which in the presence of hyperreflexia is most consistent with ALS.

If MMNCB is a strong clinical consideration, it is important to carefully evaluate for conduction block by stimulating at multiple segments of the nerve where possible; for example, the ulnar study can include wrist, below-elbow, above-elbow, upper arm, supraclavicular, and even nerve root stimulation. Conduction block is usually present at locations other than the typical sites of entrapment in MMNCB, and technical errors must be excluded when diagnosing conduction block, particularly with proximal sites of stimulation where spread of current to nearby nerves can lead to volume-conducted responses.

Another entity that can be mistaken for ALS at least on the basis of the EDX findings is inclusion body myositis. Although this is a myopathic disorder, patients will usually have mixed populations of both neurogenic-appearing (high amplitude, long duration, complex) MUPs and the more typical myopathic MUPs that one would expect to see. Particularly if the patient is allowed to excessively activate the muscle during MUP analysis, the myopathic MUPs will be drowned out by the larger ones, and the case can be misinterpreted as a primarily neurogenic process. Fibrillation and particularly fasciculation potentials are usually less evident in inclusion body myositis than in ALS, and a well-taken history and physical examination should also help to differentiate the two. Although the process is myopathic, due to a chronic, slowly progressive disease course, individual myofibers can lose their innervation because of fiber splitting and vacuolar change, with reinnervation then occurring. This is thought to be the most likely explanation for the neurogenic-appearing MUPs.

The NCSs in this case show a small but reproducible decrement on repetitive stimulation at baseline, without any facilitation after brief exercise. Neuromuscular junction disease was part of the differential diagnosis. Given the low CMAPs and the small decrement seen at rest, Lambert-Eaton myasthenic syndrome is a consideration, and it is important to exercise the muscle briefly (10 seconds) to look for facilitation. A decrement can be seen in ALS and some myopathic disorders because of immature and unstable neuromuscular junctions, and the clinical history and needle EMG findings are critical in differentiating such processes from neuromuscular junction disease.

In ALS, the needle examination typically shows profuse fibrillation and fasciculation potentials, and very complex (polyphasic), unstable MUPs. These findings must be present in at least three different spinal segments (e.g., an upper and lower limb, and thoracic paraspinal muscles), or two spinal segments in combination with bulbar muscles. Within those segments, two or more muscles with different segmental and peripheral nerve innervation must be affected before one can confidently conclude that a progressive motor neuron disease is present (this grading scale is based on the El Escorial criteria for possible or probable ALS).⁷

Case 6: Failure to Wean From the Ventilator

A 62-year-old man with a history of coronary artery disease status post bypass grafting, type 2 diabetes mellitus, and chronic renal insufficiency, was admitted with increasing shortness of breath and received a diagnosis of pneumonia. He subsequently developed acute respiratory failure requiring intubation and was transferred to the intensive care unit (ICU) where he was found to be in septic shock, and went on to develop multiorgan failure. He remained intubated and sedated for 10 days, after which he became more alert and responsive. Clinical examination at that time revealed severe weakness with almost no voluntary activation in both the upper and lower limbs, and attempts to wean from the ventilator repeatedly failed.

An EDX evaluation was performed 2 weeks after the initial episode of sepsis, at which time he had a flaccid quadriparesis, mild symmetric facial weakness, and symmetrically decreased muscle stretch reflexes. Sensory examination was unreliable, but he appeared to feel light touch throughout.

Differential Diagnosis

In the ICU setting, critical illness myopathy (CIM) and critical illness polyneuropathy are common causes of unexplained weakness.¹⁴ Other considerations should include neuromuscular junction disorders such as botulism or a myasthenic crisis, which can present with predominantly respiratory symptoms. Respiratory failure can be the initial presentation of ALS, as well as some myopathies such as acid maltase disease. Other myopathies that might present in the ICU should also be considered, including acute necrotizing myopathy and inflammatory myopathies (polymyositis, dermatomyositis), which can occasionally present fulminantly. A polyradiculoneuropathy should be considered, either acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) or in this case, diabetic polyradiculoneuropathy combined with severe deconditioning, given the history of 2 weeks of immobility in the ICU.

If the patient was presenting with isolated failure to wean from the ventilator without generalized weakness, one should also consider an isolated phrenic neuropathy. Phrenic nerve damage can occur unilaterally or bilaterally as a result of direct trauma or traction (most often during surgery), infiltrative lesions, or inflammatory processes such as neuralgic amyotrophy (Parsonage-Turner syndrome). Damage to the anterior horn cells within the spinal cord or the cervical roots supplying the phrenic nerves (C3–C5) can lead to respiratory failure, and can be seen with intrinsic cord problems such as infarction or as part of a more generalized process such as ALS.

EDX testing in the ICU is fraught with technical challenges related to patient positioning, inaccessibility of some nerves or muscles because of line placement, inability of the patient to cooperate with needle examination because of altered mental status or severe weakness, anticoagulant medications, and electrical interference from equipment, which can make sensory NCSs very difficult to obtain. Sometimes a study has to be limited because of these issues. The NCS and needle EMG findings for this case are presented in Table 11-7.

Table 11-7 Case 6: Nerve Conduction Studies and Electromyography

Discussion

NCSs in the limbs showed low-amplitude motor responses. The CMAPs had markedly prolonged durations, but the waveforms were very similar at both proximal and distal sites of stimulation without evidence of temporal dispersion or conduction block. Sensory NCSs were preserved with the exception of mild generalized slowing of both motor and sensory conduction velocities. Repetitive stimulation of the ulnar and peroneal nerves did not show a significant decrement at baseline. The patient was too weak to exercise and because of a low clinical suspicion for neuromuscular junction disease, it was elected not to proceed with high-frequency repetitive stimulation as a substitute for exercise (to evaluate for an incremental response in the CMAP as could be seen with Lambert-Eaton myasthenic syndrome).

Phrenic CMAPs were also low amplitude bilaterally. Several techniques for phrenic NCSs have been described, but the CMAP can be technically difficult to obtain. The most frequent cause of unreliable findings is the misinterpretation of volume-conducted responses from nearby chest wall muscles.²⁵ It is important to stimulate the nerve in between inspiration and expiration because this results in the biggest response and minimizes movement artifact, although some patients are unable to comply with this instruction.

Based on the NCSs, the findings were most suggestive of CIM, with low-amplitude motor responses but relative preservation of sensory responses. The long-duration CMAPs were also very suggestive of CIM.¹ Needle EMG was limited by the inability of the patient to activate most muscles. Low-grade fibrillation potentials, however, were seen in most muscles examined, and when motor units could be briefly activated, they were noted to be of short duration, some were complex, and recruitment was markedly increased. The diaphragm was also studied, and the findings were consistent with the generalized myopathic process noted elsewhere. Needle examination of the diaphragm can be very helpful in determining the underlying pathophysiology of neuromuscular disorders, but does carry inherent risks because of the proximity of vital organs. Several techniques have been described, including an ultrasound-guided technique.⁶ One must weigh the potential risks against the importance of the additional diagnostic information the EMG examination can provide. Evaluation of MUPs can differentiate between neuropathic and myopathic processes, and evaluation for fibrillation potentials can provide information on the degree of axon loss or severity of the myopathic process. One must take care not to interpret low-amplitude, very complex, nascent MUPs as myopathic (nascent motor units are seen after severe nerve injury during early reinnervation), and the recruitment pattern is critical in differentiating the two.

The findings on needle EMG in this case, when taken in conjunction with the NCS findings, were consistent with a moderately severe myopathy, and in this clinical setting the most likely diagnosis is CIM. The generalized slowing of conduction velocities suggests a mild superimposed peripheral neuropathy, given the history of diabetes. The relative preservation of the sensory responses in this case argues against a diagnosis of critical illness polyneuropathy in a patient with severe, generalized weakness.

Case 7: Foot and Hand Numbness and Pain

A 46-year-old man had colon cancer diagnosed 4 months ago and underwent surgical resection followed by chemotherapy. He reports recent difficulty with balance and has been falling frequently, particularly if in the dark. He feels as if his sock is balled up in his shoe all the time, and he can no longer walk in bare feet because it feels as if he is walking on glass. There is also burning pain and uncomfortable tingling in both lower limbs that came on rather acutely about 2 months ago, followed shortly thereafter by similar symptoms in both hands. He is unable to feel the pen in his hand when writing and frequently drops things. He admits to regular alcohol intake before the diagnosis of cancer, drinking a six-pack of beer several times per week.

On examination, he appears unwell and is cachectic, with loss of hair evident on the shins. Hands and feet are cold to the touch. Sensory examination reveals loss of joint position sense at the toes and ankles, and glove-and-stocking distribution loss of sensation to pinprick and light touch to the mid forearm and knees, respectively. His gait is wide based and ataxic. Strength examination reveals mild weakness of the ankle groups, toe flexors and extensors, and hand intrinsic muscles, with normal strength proximally. Muscle stretch reflexes are absent at the knees and ankles. Plantar responses are downgoing.

Differential Diagnosis

The patient presents with symptoms suggestive of a rather rapid-onset, length-dependent peripheral neuropathy. There is a wide differential diagnosis to consider in cases of length-dependent peripheral neuropathy, although most are inherited, metabolic, toxic, or idiopathic.¹¹ In this case, the two most likely causative agents would be recent chemotherapy and the history of heavy alcohol intake. The relative subacute onset and the presence of positive sensory symptoms would argue for an acquired process. Although the presentation is characteristic of a length-dependent peripheral neuropathy, other possibilities should also be considered, including polyradiculoneuropathy, which can present with predominantly length-dependent symptoms (e.g., acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, diabetic polyradiculoneuropathy). Multiple mononeuropathies would not typically present in such a symmetric fashion. The prominent sensory symptoms make muscle, neuromuscular junction, and anterior horn cell disease unlikely. The NCS and needle EMG findings are presented in Table 11-8.

Table 11-8 Case 7: Nerve Conduction Studies and Electromyography

Discussion

EDX testing is critical in the evaluation of peripheral neuropathies. The information obtained, including the pattern of involvement, severity, and in many cases, the histopathology can have implications for treatment. Changes seen on NCSs depend on whether the neuropathic process is primarily demyelinating or axonal. In axonal peripheral neuropathy, CMAPs and SNAPs are low amplitude, with relatively normal conduction velocities and distal latencies. In demyelinating peripheral neuropathy, slowing of conduction velocity, prolongation of distal latencies, and absolute prolongation of F-waves are the predominant findings. If the process is patchy, temporal dispersion and conduction block can be seen. In inherited neuropathies such as hereditary motor sensory neuropathy (Charcot-Marie-Tooth disease) type I, III, or IV, where the demyelination is uniform and affects the entire length of the nerve, there is no dispersion or block, but conduction velocities are profoundly slowed, often out of proportion to clinical findings or symptoms.

The findings on NCSs in this case were most consistent with an axonal peripheral neuropathy, with mild generalized slowing of conduction velocities, borderline distal latencies, and significant loss of amplitude (with sensory fibers affected more than motor). The sural response was still within normal limits for age, and therefore the medial plantar study was performed, because it is a more sensitive test for sensory neuropathy in younger patients. The electrophysiologic confirmation of length-dependent peripheral neuropathy is based on the distribution of findings on needle examination. In this case, distal muscles were abnormal with large MUPs and fibrillation potentials, and more proximal muscles had normal findings. It is important to examine a proximal muscle with the same myotomal innervation to confirm that the process is length dependent (e.g., if the medial gastrocnemius is abnormal, the gluteus maximus should be examined because both distal and proximal muscles are predominantly S1 innervated). Paraspinal muscles should also be normal. Changes are typically more profound in the lower limbs, but it is often helpful to document the length-dependent pattern in the upper limbs by showing abnormalities in a hand intrinsic muscle and normal findings in a more proximal muscle such as the triceps or deltoid. Although alcohol is a very common cause of peripheral neuropathy, the abruptness of onset and severity of the symptoms and EDX findings argued against that as the primary etiology in this case. The likely etiology was thought to be vincristine toxicity, a component of his chemotherapy regimen. When the vincristine was discontinued, his symptoms gradually improved over the following months.

Case 8: Bilateral Hand Weakness and Numbness

A 63-year-old woman without significant medical history presents with a 2- to 3-year history of numbness and weakness of both hands. The symptoms are present constantly with no clear relationship to activity, and are not worse at night. She frequently drops objects and can no longer perform fine motor activities such as using buttons or zippers. She is right hand dominant and thinks the right hand might be slightly worse. She denies neck or upper limb pain. Review of systems is notable for progressive difficulties with balance and frequent falls, and she feels that her legs are generally weaker but does not describe focal weakness such as foot drop. There are no reported bowel or bladder changes; however, on further questioning, she reports nocturia times four.

Physical examination shows a spastic, scissoring gait, increased muscle stretch reflexes in the upper and lower limbs, upgoing plantar response on the right, normal sensation to pinprick and joint position sense in the lower extremities, and decreased sensation to pinprick in the ulnar aspect of both hands. Strength is normal in both lower limbs and in the proximal upper limb muscles. There is moderate weakness in the intrinsic hand muscles, with some atrophy, and in the extensor digitorum communis bilaterally. Cranial nerve examination is normal.

Differential Diagnosis

The clinical presentation is most notable for upper motor neuron findings with diffuse hyperreflexia and lower limb spasticity. There is some mild atrophy suggesting lower motor neuron involvement, but this is less clear and a clear indication for EMG. The upper motor neuron findings should alert one to the possibility of ALS, but could certainly be seen with a cervical myelopathy or a bilateral cortical process. ALS would be less likely in this case given the sensory symptoms, although a coexisting peripheral neuropathy or superimposed mononeuropathies would be possible. Bilateral median and/or ulnar neuropathies are a relatively common cause of bilateral hand weakness and numbness but would not explain the upper motor neuron signs. NCS and EMG findings are shown in Table 11-9.

Table 11-9 Case 8: Nerve Conduction Studies and Electromyography

Discussion

The primary purpose of the EDX studies in this setting is to determine whether there is lower motor neuron involvement, and if present, whether it is diffuse or limited to a specific localizing region. NCSs showed low-amplitude median and ulnar motor responses with preservation of the sensory responses. This implies that the lesion is either proximal to the dorsal root ganglion or at the level of the muscle itself (in this case the latter is unlikely given the prominent sensory symptoms). Lesions proximal to the dorsal root ganglion can involve the nerve root or the anterior horn cell. No motor dispersion and no conduction blocks were noted. A lower limb motor study was normal, arguing against a more diffuse process. Needle examination showed fibrillation potentials and neurogenic MUPs in bilateral C8–T1-innervated muscles, including the paraspinals, indicating pathology at the level of the nerve roots or anterior horn cell. Neurogenic MUP changes were also seen in C7-innervated muscles, without fibrillation potentials, suggesting mild, chronic C7 involvement. Given the presentation and potential concern for ALS, muscles in the lower limb as well as the thoracic paraspinal and genioglossus (tongue) muscles were examined, and the only finding of note was poor voluntary motor unit activation, which can be seen in spasticity or when the patient is giving poor effort. Also, no fasciculation potentials were identified, making ALS unlikely.

These findings are most consistent with multiple bilateral cervical radiculopathies or focal anterior horn cell disease, with uncompensated denervation evident at the C8–T1 levels bilaterally. Focal anterior horn cell disease can be seen with intrinsic spinal cord pathology or in focal motor neuron disease (diplegic amyotrophy).¹⁷ Such changes could also be seen in early ALS; however, subclinical involvement would typically be noted in the form of unstable, complex MUPs and fasciculations in a more widespread distribution. The most likely explanation for these findings in this case, given the spasticity in the lower limbs and the numbness in the hands despite normal sensory studies, would be cervical stenosis with associated cord compression. Because one cannot differentiate between nerve root and anterior horn cell disease on the basis of electrophysiologic findings, it is important to take into account the clinical presentation and any other available diagnostic testing such as imaging, when reporting the final impression. In this case, magnetic resonance imaging of the cervical cord showed severe stenosis with cord signal change at the C7–8 level.

Case 9: Leg Pain and Weakness

A 63-year-old man presents with a 3-week history of severe right thigh pain. The pain came on suddenly, waking him from sleep, and is the most severe pain he has ever experienced. He describes the pain as burning with occasional lancinating, shock-like sensations as well as numbness in the anterior right thigh, and reports progressive weakness such that he is now reliant on a wheelchair because he has fallen multiple times when his knee gives out. He denies any trauma. Associated with this has been a 20-lb unintentional weight loss that he attributes to loss of appetite secondary to the severe pain. The medical history is notable for peripheral arterial disease status post iliofemoral bypass on the right, aortic valve replacement for which he is receiving long-term treatment with warfarin, and recently diagnosed type 2 diabetes for which he has just started an oral hypoglycemic medication. Also noted is a longstanding history of low back pain without radicular features but without any recent exacerbations.

On examination he appears to be in pain even when resting on the examination couch. There is atrophy of the right thigh. Gait is antalgic, and he ambulates with his right knee held in extension. Muscle stretch reflexes are absent at the right quadriceps, right hip adductors, and bilateral Achilles tendon. Sensation to pinprick was reduced in a stocking distribution from the ankles distally, with absent vibration sense at the toes, and hyperesthesia to pinprick was noted in the right anterior medial thigh. Strength testing is notable for barely antigravity strength of the right hip flexors, quadriceps, and hip adductors, but he has significant pain associated with testing that might be preventing full effort. He has moderate weakness of the right ankle dorsiflexors and hip abductors, with no definite weakness of the toe flexors and ankle plantar flexors. Strength in the left lower limb is normal.

Differential Diagnosis

The diagnosis that should come to mind immediately with this history is diabetic lumbar radiculoplexus neuropathy (diabetic amyotrophy).¹³ The history of sudden onset of severe pain, prominent weakness, recently diagnosed diabetes, and significant weight loss are quite typical of this entity. Other causes of lumbar plexopathy, as well as an acute severe lumbar radiculopathy, would also be obvious considerations. The distribution of weakness suggests multilevel root involvement, L2–L4 predominantly. It would be important to know whether he had undergone any recent interventions related to the peripheral arterial disease, because a compressive hematoma in the region of the femoral nerve or lumbar plexus can present with thigh pain and weakness. An acute necrotizing myopathy could rarely present with focal pain and weakness such as this, although the sensory symptoms make that unlikely in this case.

The goals of EDX testing in this case are to identify as accurately as possible the level of pathology to help direct the diagnostic workup, and to evaluate the severity of axonal loss to provide prognostic information. The NCS and EMG findings are presented in Table 11-10.

Table 11-10 Case 9: Nerve Conduction Studies and Electromyography

Discussion

Peroneal and tibial motor studies were performed with F-waves, to evaluate for proximal conduction block or slowing. The lower limb CMAPs were reduced, but more severely reduced in the affected limb. The sural responses were also reduced or absent, and in conjunction with the borderline conduction velocities would suggest an underlying peripheral neuropathy. Although a femoral motor NCS could be performed given the marked weakness in femoral-innervated muscles, this is not performed routinely because it is technically more challenging and more uncomfortable for the patient. The sural sensory study was performed to provide baseline information regarding the presence of a coexisting peripheral neuropathy, although an absent response can be normal in patients older than 60 years. In this case a saphenous sensory study might have been helpful. Although less technically reliable than the sural study, if a greater than 50% drop in amplitude of the saphenous sensory is detected when compared with the noninvolved limb, this suggests pathology distal to the dorsal root ganglion at the level of the lumbar plexus or femoral nerve.

Needle EMG is used to map out the involved myotomes, with severe denervation and poor activation as well as markedly reduced recruitment in all L2–L4 innervated muscles examined on the right. There is also moderate active denervation noted in the tibialis anterior muscle, which is supplied by the L4 and L5 nerve roots and lumbar plexus. Mild fibrillation potentials were also present in the lumbar paraspinals, but not to the same degree as in the right thigh muscles. Some longstanding neurogenic changes were noted in distal L5- and S1-innervated muscles (indicated by long-duration, high-amplitude MUPs, but no increase in turns or phases), without corresponding changes in the gluteus medius or gluteus maximus muscles. These findings confirm the length-dependent peripheral neuropathy evident on NCSs.

The EDX findings are most consistent with a severe, subacute right lumbar radiculoplexopathy superimposed on a more long-standing, mild, length-dependent peripheral neuropathy. The hallmark of plexopathy on EDX testing is denervation findings in multiple different nerve root and peripheral nerve territories, with normal paraspinal muscles, and loss of both SNAP and CMAP amplitudes on NCSs. The lesion is distal to the dorsal root ganglion, with low amplitude or absent sensory responses reflecting Wallerian degeneration of sensory axons.

In this case there is also mild denervation in the right lumbar paraspinal muscles, which is consistent with a radiculoplexus neuropathy as is typically seen with diabetic and nondiabetic inflammatory plexopathies.¹³ It is helpful to check one or two of the most severely affected muscles in the contralateral limb to evaluate for subclinical involvement, which is also very suggestive of an inflammatory etiology. Imaging of both the lumbar spine and plexus is recommended to rule out a compressive or infiltrative lesion, even in cases such as this with a history typical of diabetic radiculoplexus neuropathy (diabetic amyotrophy). This can be diagnostically challenging because the electrophysiologic findings could easily reflect multiple compressive radiculopathies, and in this age-group, imaging may show significant spondylosis and stenosis. The key to diagnosis involves carefully obtaining a clinical history. In this setting, the acute onset in conjunction with the prominent weight loss would lead one down the correct path to diagnosis.

Case 10: Weakness and Fatigue

A 45-year-old woman presents with weakness and fatigue. Although relatively nonspecific, she reports fatigue especially as the day progresses and worsening functional limitations (such as going up stairs). There is no complaint of pain or sensory symptoms. She denies dysphagia or weight loss, but does report intermittent diplopia. Physical examination shows normal strength in limb and trunk muscles, normal cranial nerve examination, normal muscle stretch reflexes, and normal sensory examination. With repetitive strength testing there did appear to be a slight degree of fatigue, but this was equivocal. There were no fasciculations noted.

Differential Diagnosis

The evaluation of weakness and fatigue is a relatively common referral for EDX testing. The differential diagnosis is quite broad and the accompanying signs and symptoms generally help narrow the diagnosis. In this case the symptoms are relatively nonspecific. In the absence of any sensory symptoms, a process affecting muscle, neuromuscular junction, motor axon, or anterior horn cell would seem most likely. The lack of significant weakness, normal reflexes, and lack of fasciculations would argue against motor neuron disease. A pure motor peripheral neuropathy would be unlikely. A mild myopathy is a consideration, and a serum creatine kinase level was ordered, which was normal. This does not entirely exclude myopathy but makes it less likely. The clinical course and report of intermittent diplopia and possible fatigable weakness suggest the possibility of a neuromuscular disorder, specifically myasthenia gravis.

The EDX evaluation in this case includes standard NCSs in addition to needle EMG. The NCSs include repetitive stimulation to distal and proximal muscles at rest and after exercise (Table 11-11). Needle examination was performed on proximal and distal muscles of the upper and lower limbs.

Table 11-11 Case 10: Nerve Conduction Studies and Electromyography

Discussion

Routine NCSs showed normal CMAP and SNAP amplitudes. In this case there was no significant decrement to 2-Hz repetitive stimulation when recorded over the abductor digiti minimi, but there was a consistent pattern of decrement with at least partial repair when recorded over the trapezius and a facial muscle (Figure 11-2). The EMG revealed no abnormal spontaneous activity and varying MUP morphology of the same MUP without other morphologic changes in primarily proximal muscles. The EDX testing was critical to confirm the diagnosis of a neuromuscular junction disorder. The degree of decrement was mild but reproducible, with the expected greater involvement of proximal muscles. This has been shown by Özdemir and Young,²² who found abnormalities in the abductor digiti minimi in 59% of patients, but in greater than 80% when proximal repetitive stimulation was performed. Typically this would be performed on the spinal accessory or facial nerves because these are technically less challenging. Recent reports also describe this technique recording over the masseter for those who present with dysphagia or jaw weakness.²⁶ Proximal lower limb repetitive stimulation can be performed on the femoral nerve with percutaneous near-needle stimulation if necessary, otherwise a decrement might be noted in the tibialis anterior. The typical amplitude decrement is a smooth pattern of decline, which becomes maximal at the fourth or fifth response but has the greatest relative reduction between the first and second responses (Figure 11-3). If stimulation were continued past the fifth response there would be stabilization, presumably associated with mobilization of acetylcholine stores. If the decrement is not smooth or the major decrement does not occur between the first and second responses, this should be attributed to technical factors until proven otherwise (Figure 11-4). Immediately after brief exercise, there should be at least a partial repair of the decrement, characterized by return of the CMAP to the baseline amplitude of the first response in the train. During the 2 to 4 minutes after exercise, there is postactivation exhaustion that will again show a smooth decrement that can exceed that at rest. A consistent decrement of greater than 10% in two nerves with typical repair and postexercise exhaustion is necessary to support the diagnosis.³¹ In myasthenia gravis, there can be a decrement at rest if more severe disease, or a decrement after exercise (generally 1 minute) in more mild disease.

FIGURE 11-2 Two-hertz repetitive stimulation performed at rest, after brief exercise and 3 minutes postexercise in a case of mild myasthenia gravis.

FIGURE 11-3 Two-hertz repetitive stimulation. A normal pattern to repetitive stimulation shows no decrement (A). The pattern of decrement in a disease state characterized by the greatest drop occurring between the first and second response (B).

FIGURE 11-4 Two-hertz repetitive stimulation with a nonphysiologic decrement created by movement of the subject.

A decrement to repetitive stimulation is not specific to a neuromuscular junction disorder, as it can be seen with relatively rapidly progressive neurogenic disorders such as progressive motor neuron disease. In this case, the needle examination showed normal MUP morphology and lack of abnormal spontaneous activity, which would argue against a process affecting motor neurons or their axons. Finally, the preservation of CMAPs and the lack of postexercise facilitation would argue for a postsynaptic defect typical of myasthenia gravis, rather than a presynaptic disorder such as Lambert-Eaton myasthenic syndrome. This was confirmed by acetylcholine receptor antibodies.

Case 11: Progressive Lower Greater Than Upper Limb Weakness

A 69-year-old man presents with an 18-month history of progressive limb weakness that is greater in the lower than in the upper limbs. This is particularly notable when walking up stairs. He also reports numbness in the toes as well as a worsening grip strength, the latter characterized by dropping objects. He denies significant upper limb sensory symptoms. There has been no dysphagia, dysarthria, dyspnea, or bladder dysfunction. There has been approximately a 15-lb intentional weight loss, but the patient specifically notes atrophy of the quadriceps. The medical history is significant only for hypertension and hyperlipidemia. There is no family history of similar symptoms. The patient had been previously seen elsewhere with the diagnosis of polymyositis. Prednisone was initiated 4 months ago without improvement. The physical examination revealed a relatively thin gentleman with clear atrophy appreciated primarily in the quadriceps. Cranial nerve testing and mental status were normal. Strength testing showed bilateral quadriceps weakness of 3/5; hip abductor, 4/5; tibialis anterior, 4/5; shoulder girdles, 4/5; and finger flexors, 3/5. The weakness did not appear to be fatigable, and there was no improvement of motor strength with repetitive contraction. Muscle stretch reflexes were reduced but present at the knees and ankles, without facilitation after brief muscle contraction. Babinski reflexes were downgoing and Hoffmann’s reflex was absent. Sensory examination was intact to pinprick and proprioception. No fasciculation potentials were observed. Carpal tunnel provocative maneuvers were normal, and there did not appear to be significant thenar atrophy.

Differential Diagnosis

The primary symptoms and clinical findings are related to proximal limb weakness, which in this case appears to be most severe in the quadriceps where there is clear atrophy. There is also weakness in the finger flexors. Although the clinical history of hand weakness certainly raises the more common suspicion of median neuropathy at the wrist, the findings on this examination are more consistent with the long finger flexors. A unifying diagnosis for the motor-greater-than-sensory symptoms would be a polyradiculopathy or polyradiculoneuropathy. The mild sensory symptoms without significant clinical sensory findings can be relatively nonspecific. The proximal pattern of lower limb involvement would suggest a myopathy, and the specific pattern of quadriceps and finger flexor involvement would be relatively typical of inclusion body myositis (IBM). Other potential dystrophies such as proximal myotonic dystrophy (DM2) or inflammatory myopathies such as polymyositis or dermatomyositis are also possible. A motor neuron disease is possible but less likely in the absence of long tract signs. A disorder of neuromuscular transmission is possible and will need to be excluded with the EDX studies. NCSs and needle EMG were performed (Table 11-12).

Table 11-12 Case 11: Nerve Conduction Studies and Electromyography

Discussion

Motor NCSs were performed on distal motor nerves as well as the spinal accessory nerve. The primary purpose for spinal accessory stimulation was to perform repetitive stimulation, which in this case was negative. This would argue against but not entirely exclude a disorder of neuromuscular transmission. CMAP amplitudes were borderline or mildly reduced, with sparing of the conduction velocities and distal latencies. No motor dispersion or conduction blocks were noted. The sural response was absent suggesting some degree of sensory axon loss, whether part of a unifying diagnosis or as a separate peripheral neuropathy. The differential diagnosis has narrowed slightly, but EMG examination is critical for the diagnosis. The EMG provided many clues regarding the diagnosis, most notable of which were mixed MUPs in several muscles, primarily short duration and low amplitude, suggestive of a myopathy. Some large MUPs were also seen, which could indicate an underlying peripheral neuropathy or a chronic myopathy. Associated with this were fibrillation potentials, which in the setting of short MUPs would generally reflect some degree of myonecrosis, fiber splitting, or vacuolar changes. These findings would be consistent with an inflammatory myopathy, but the specific pattern again gives clues to differentiate polymyositis from IBM. The particular involvement of the quadriceps in the lower limbs is typical of IBM,²⁴ and greater involvement of the forearm finger flexors in the upper limb is relatively common. In polymyositis the findings can be relatively diffuse but tend to be more proximally predominant in the upper and lower limbs. The clinical history also provides some clues in that the patient had previously attempted treatment with prednisone. Corticosteroids are not generally effective in IBM, and there is generally no clear pharmacologic treatment to suppress the process. Neurogenic abnormalities characterized by some large MUPs are not uncommonly seen in IBM. These large MUPs could represent either collateral sprouting to split fibers that have lost nerve supply over a period of time (as in a chronic myopathy), or in this case a probable underlying mild peripheral neuropathy. The sensory response can be helpful to separate these possibilities. IBM can be misdiagnosed as a progressive motor neuron disease if one focuses on the large MUPs and does not recognize the underlying short-duration, low-amplitude MUPs that can be present at lower levels of activation. In this case a biopsy was performed of the vastus lateralis, which was conclusive for IBM. Prednisone was discontinued because it can be a factor in type II fiber atrophy and the potential for increased weakness.¹⁶

Case 12: Acute Right Foot Drop

A 52-year-old heavy equipment operator presents with an acute right foot drop. The symptom onset was sudden approximately 4 weeks ago and associated with mild back pain after a routine workday. The primary physician examined the patient at 1 week and thought this was most likely a peroneal neuropathy at the knee, and put the patient on work restriction and reevaluated the patient a week later. There had been no improvement in the symptoms, so he was referred for EMG. In the interim the patient had reported some increased pain in the right lateral calf that was present continuously at a level of 3/10. Comorbidities include a 40–pack-year smoking history, obesity, and diabetes. The patient reports an intentional 30-lb weight loss over the last 2 months and has been involved in a regular aerobic and weightlifting program. He has been unable to continue with this program recently because of increased pain and the foot weakness. Physical examination reveals a prominent right foot drop with ambulation and the inability to stand on the right heel.

Differential Diagnosis

A very limited physical examination is reported because the design of the EDX study will mirror the findings that should be present on the physical examination. The most obvious diagnostic possibilities would be a peroneal neuropathy versus an L5 radiculopathy. The most common site of a peroneal neuropathy would be compressive at the fibular head, possibly in association with the weight loss. A sciatic involvement or less likely, a plexopathy, needs to be considered. With the smoking history and weight loss, a mass lesion such as a metastatic lung carcinoma leading to a cauda equina lesion is possible, but in this case the findings were purely unilateral and without sphincter disturbance. NCSs and needle examination were performed (Table 11-13).

Table 11-13 Case 12: Nerve Conduction Studies and Electromyography

Discussion

Table 11-14 describes the typical electrophysiologic findings for various causes of foot drop. The abnormalities in this case confirm an L5 radiculopathy. The NCSs, particularly the normal superficial peroneal sensory response, and the paraspinal abnormalities also argue for a radiculopathy rather than a peripheral nerve injury. It is important to perform a sensory study of a nerve in the root distribution for the clinically weak muscle or a corresponding sensory study for the reduced CMAP, or both. In this case the peroneal CMAP was reduced, and the normal superficial sensory response, in comparison with the contralateral limb, gave a clue to a presynaptic process. If the tibial CMAP amplitude had been reduced, then the sural study would have been more appropriate (because they both arise primarily from the S1 root). The other critical feature for the diagnosis of a radiculopathy is the presence of neurogenic abnormalities, preferably fibrillation potentials, in two or more limb muscles innervated by the same root but by different peripheral nerves. In this case there was involvement of distal L5 peroneal- and tibial-innervated muscles as well as a proximal superior gluteal–innervated L5 muscle. A sciatic neuropathy is excluded by the gluteus medius findings, the abnormal paraspinal findings, and the normal sensory responses.

Table 11-14 Representative Findings for Various Neurogenic Etiologies for Foot Drop^∗

Case 13: Hand Weakness, Worsening Gait, and Progressive Foot Drop

A 28-year-old man presents with a history of hand weakness, worsening gait over the past 3 to 4 years, and progressive foot drop with subjective reports of “cramping.” He denies any other pain or sensory symptoms. Occasionally he chokes on liquids but has no diplopia or dysarthria. The symptoms are relatively constant, although he does tend to trip more when fatigued. The medical history is significant for borderline diabetes. Family history is notable for some family members with “muscular dystrophy,” but the patient offers little detail. The symptoms have progressed to the point where he is falling weekly and is having difficulty with fine motor control of the hands, with “cramping” when grasping objects. This is especially severe during cold weather. The physical examination shows a well-nourished gentleman with some premature frontal balding. There is mild atrophy of the anterior compartment of the lower leg. Gait evaluation reveals moderate foot drop bilaterally, slightly worse on the right, with compensation by circumduction. He is unable to walk on heels and has difficulty walking on toes. Strength testing shows distally predominant weakness, particularly in the tibialis anterior. Grip strength is mildly reduced, but more notable is difficulty releasing the grasp consistent with grip myotonia. Percussion myotonia is noted in the thenar muscles. There are no sensory deficits, and muscle stretch reflexes are normal.

Differential Diagnosis

The primary feature of the clinical history and examination is that of distally predominant weakness without sensory deficits. Although a peripheral neuropathy or multiple compressive neuropathies are possible, the lack of sensory symptoms would make these less likely. Multifocal processes such as a hereditary neuropathy with liability to pressure palsies can present with multiple mononeuropathies and minimal sensory symptoms, but the history of gradual progression in this case would make this less likely. Multifocal motor neuropathy with conduction block is also possible. A motor neuron disease is within the differential, but a relatively rapidly progressive process such as ALS would be unlikely given the prolonged history. The history of difficulty with grasp relaxation is characteristic of a myotonic disorder, and the presence of clinical weakness would suggest, in this case, a disorder with both myotonia and a myopathy. NCSs and needle EMG were performed (Table 11-15).

Table 11-15 Case 13: Nerve Conduction Studies and Electromyography

Discussion

The primary finding on this study is the myotonia, which appears to be more predominant distally. In association with this are myopathic MUPs, again in a distal pattern. The potential etiology of myotonia is relatively broad, but with other clinical features such as weakness, and more importantly the pattern of weakness, the differential diagnosis can be narrowed (Boxes 11-2 and 11-3).

In this case, there is clear weakness in addition to the myotonia, which reinforces the suspicion of a distally predominant myopathy, most likely myotonic dystrophy (see Table 11-15). EDX testing is important to better define the degree and pattern of myotonia, as well as to define whether there is an associated myopathy. Specialized techniques such as repetitive stimulation, response to cooling, or response to exercise will generally confirm the diagnosis. Table 11-16 outlines the typical responses to these techniques with various myotonic disorders. Of particular note is the response to repetitive stimulation that occurs in many myotonic disorders. This is characterized by a decremental response at rest, which is very similar to that seen in neuromuscular junction disorders. It differs physiologically, however, in that it is likely caused by membrane inactivation.^2,¹⁸ There is also a repair after brief exercise, but distinguishing it from neuromuscular junction disorders is a clear reduction of the CMAP amplitude immediately after exercise. This phenomenon is seen in most myotonic disorders, except in proximal myotonic myopathy. The absence of neuromuscular junction abnormalities and the proximal pattern of weakness are helpful characteristics that can be used to distinguish this disorder.²⁷ This case is relatively typical of myotonic dystrophy, and this was confirmed with genetic testing.

Table 11-16 Clinical and Electrophysiologic Features of the Common Myotonic Disorders

Case 14: Progressive Lower Limb Weakness and Numbness

A 52-year-old woman presents with a 2-year history of progressive numbness and weakness involving the distal upper and lower limbs bilaterally. The symptoms initially started with numbness in the left side of her face, but then progressed to involve her feet and then her hands. She denies any pain but is finding it increasingly difficult to perform her activities of daily living; she trips and falls quite often when ambulating, and now uses a cane. She has also noted difficulty walking up stairs or getting up from a low chair. She is unable to perform fine motor activities with her hands, such as using buttons or holding her utensils. More recently she has developed dizziness if she gets up too quickly. She denies any family history of neurologic symptoms. She reports that the symptoms had been gradually progressive for several months but then seemed to progress quite suddenly (prompting her to seek medical evaluation). Her medical history is significant for hypertension and mild type 2 diabetes, which has been managed with dietary modification with good blood sugar control.

On examination, cranial nerves are intact with no sensory deficit in the face. She ambulates with a steppage gait bilaterally because of a flaccid foot drop. There is prominent weakness distally (toe flexors and extensors, ankle groups, finger and wrist extensors and flexors, hand intrinsic muscles), with mild weakness proximally. Sensation to pinprick is absent to the mid calf and to the wrist, with absent joint position sense in the feet. Reflexes are hypoactive but symmetric throughout with the exception of the ankle jerks, which are absent bilaterally.

Differential Diagnosis

With unequivocal sensory symptoms and signs, anterior horn cell, muscle, and neuromuscular junction disease are all essentially excluded unless part of a coexisting process. Plexopathy is also unlikely because of the involvement of all four limbs. The clinical presentation is most suggestive of a peripheral neuropathy that could be length dependent. Given the examination findings of proximal weakness, however, a polyradiculoneuropathy or a multifocal neuropathy should also be considered. With a 2-year history of progressive symptoms, an inherited neuropathy and various causes of acquired neuropathy (including toxic, metabolic, infectious, paraneoplastic, immune mediated, or inflammatory) are all potential etiologies. The history of stepwise progression and the possible dysautonomia make chronic inflammatory demyelinating neuropathy (CIDP) a strong consideration. The NCS and EMG findings are shown in Table 11-17.

Table 11-17 Case 14: Nerve Conduction Studies and Electromyography

Discussion

Because of involvement of both upper and lower limbs without significant asymmetry of symptoms, NCSs were performed on one side only with the assumption that findings should be similar on the contralateral side. F-waves were performed to evaluate for proximal slowing, and nerves were stimulated at multiple sites to look for conduction block outside the usual sites of entrapment. On needle examination, both distal and proximal muscles were studied in multiple different nerve root and peripheral nerve territories, to determine whether the process was diffuse or restricted to specific peripheral nerves. The paraspinal muscles were examined to help differentiate polyradiculoneuropathy from length-dependent neuropathy.

NCSs in this case were diffusely abnormal, with prolonged distal latencies, markedly slowed conduction velocities, and low CMAP and SNAP amplitudes. The median motor study showed evidence of conduction block in the forearm, and the ulnar motor study showed conduction block between the below-elbow and wrist sites of stimulation. When evaluating for conduction block, it is important to rule out technical explanations for the drop in amplitude, such as understimulation at the proximal site or overstimulation at the distal site resulting in spread of current to other nerves and a volume-conducted response. F-waves were markedly prolonged, also suggesting proximal conduction block or slowing. Sensory responses were notable for preservation of the sural response with low median and ulnar sensory responses. This pattern of sural sparing is relatively typical for CIDP but not specific.¹² Blink responses were also performed to evaluate for very proximal slowing, and were abnormal, with prolongation of both the R1 and R2 responses.

EMG examination showed markedly reduced recruitment in both proximal and distal muscles, consistent with conduction block. MUPs were complex, reflecting denervation and ongoing reinnervation in proximal muscles. The fibrillation potentials and long-duration MUPs in distal muscles reflect more significant axonal loss. This constellation of findings is most consistent with CIDP. The patient underwent cerebrospinal fluid examination, which showed an increased protein level with a normal white blood cell count, and sural nerve biopsy, which showed changes consistent with inflammation, confirming the diagnosis.

The classic electrophysiologic picture in CIDP is that of demyelination, evident on both motor and sensory NCSs. Focal demyelination is seen as conduction block or focal slowing, and often distal latencies are markedly prolonged and conduction velocities severely slowed with relative preservation of amplitude. Proximal responses are dispersed in comparison with responses obtained with distal stimulation (temporal dispersion), and this is the hallmark of demyelination (Figure 11-5). Prolonged F-waves may be one of the earliest signs of more proximal slowing, which can alert the clinician that this is in fact a polyradiculoneuropathy, as opposed to a length-dependent process. Often there is associated axonal loss (and in rare cases this is the predominant picture). This is evident as loss of amplitude on NCSs, and fibrillation potentials and polyphasic large MUPs on EMG examination. Usually changes are more severe distally, although paraspinal muscles are also affected, indicating nerve root involvement.

FIGURE 11-5 Dispersion of the tibial compound muscle action potential. Trace A is the response recorded with proximal stimulation, which is significantly longer in duration, with altered morphology, in comparison with trace B, which is the response recorded after stimulation at the ankle.

One of the most important diagnoses to exclude when evaluating a patient with possible CIDP is inherited demyelinating sensorimotor neuropathy (Charcot-Marie-Tooth [CMT] disease type I, III, or IV), because this has important treatment implications. Many patients with mild forms of CMT disease are relatively asymptomatic and can go undiagnosed, making the family history less obvious. The history is slowly progressive, often dating back to childhood when a patient might recall being somewhat clumsy or unable to keep up with other children. This is different from CIDP, in which the onset is relatively abrupt, and has a progressive, stepwise or recurrent course with a positive response to immunotherapy. As in this case, autonomic dysfunction can be seen with CIDP. Conduction block, significant temporal dispersion, and evidence of proximal slowing (prolonged F-waves or prolonged blink reflexes) are key findings on electrophysiologic testing that help differentiate acquired forms of demyelinating neuropathies from CMT disease. Similarly, on needle examination, markedly reduced recruitment in the absence of significant axonal loss (indicative of conduction block) is more suggestive of an acquired process. The clinical and EDX criteria for CIDP are outlined in Box 11-4.

BOX 11-4 Clinical Diagnostic and Electrodiagnostic Criteria for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Clinical Diagnostic Criteria

Inclusion Criteria

• Typical CIDP

• Chronically progressive, stepwise, or recurrent symmetric proximal and distal weakness and sensory dysfunction of all limbs, developing over at least 2 months; cranial nerves may be affected, and

• Absent or reduced muscle stretch reflexes in all limbs

• Atypical CIDP—one of the following, but otherwise as in “Typical CIDP” (muscle stretch reflexes may be normal in unaffected limbs):

• Predominantly distal weakness (distal acquired demyelinating sensory)

• Pure motor or sensory presentations, including chronic sensory immune polyradiculoneuropathy affecting the central process of the primary sensory neuron

• Asymmetric presentations (multifocal acquired demyelinating sensory and motor Lewis-Sumner syndrome)

• Focal presentations (e.g., involvement of the brachial plexus or of one or more peripheral nerves in one upper limb)

• Central nervous system involvement (may occur with otherwise typical or other forms of atypical CIDP)

Exclusion Criteria

• Diphtheria, drug or toxin exposure likely to have caused the neuropathy

• Hereditary demyelinating neuropathy—known or likely because of family history, foot deformity, mutilation of hands or feet, retinitis pigmentosa, ichthyosis, liability to pressure palsy

• Presence of sphincter disturbance

• Multifocal motor neuropathy

• Antibodies to myelin-associated glycoprotein

Electrodiagnostic Criteria

• Definite—at least one of the following:

• At least 50% prolongation of motor distal latency above the upper limit of normal values in two nerves, or

• At least 30% reduction of motor conduction velocity below the lower limit of normal values in two nerves, or

• At least 20% prolongation of F-wave latency above the upper limit of normal values in two nerves (>50% if amplitude of distal negative peak CMAP <80% of lower limit of normal values), or

• Absence of F-waves in two nerves if these nerves have amplitudes of distal negative peak CMAPs at least 20% of lower limit of normal values plus at least one other demyelinating parameter in at least one other nerve, or

• Partial motor conduction block—at least 50% amplitude reduction of the proximal negative peak CMAP relative to distal, if distal negative peak CMAP at least 20% of lower limit of normal values, in two nerves, or in one nerve plus at least one other demyelinating parameter in at least one other nerve, or

• Abnormal temporal dispersion (>30% duration increase between the proximal and distal negative peak CMAP) in at least two nerves, or

• Distal CMAP duration (interval between onset of the first negative peak and return to baseline of the last negative peak) of at least 9 ms in at least one nerve plus at least one other demyelinating parameter in at least one other nerve

• Probable

• At least 30% amplitude reduction of the proximal negative peak CMAP relative to distal, excluding the posterior tibial nerve, if distal negative peak CMAP at least 20% of lower limit of normal values, in two nerves, or in one nerve plus at least one other demyelinating parameter in at least one other nerve

• Possible

• As in electrodiagnostic criteria for “Definite” but in only one nerve

CIDP, Chronic inflammatory demyelinating polyradiculoneuropathy; CMAP, compound muscle action potential.

Case 15: Progressive Weakness

A 65-year-old man presents with a 6-month history of progressive weakness characterized by difficulty rising from a chair and ascending stairs. He denies pain but does report mild “numbness” of the toes. There are no visual or bulbar symptoms. Bladder and bowel function are normal. The medical history is significant for well-controlled diabetes mellitus and chronic obstructive pulmonary disease. He has a 40–pack-year smoking history. The patient also reports a 25-lb weight loss during this period. Physical examination reveals mild proximal weakness in hip flexion, knee extension, and hip abduction (Medical Research Council 4/5) with difficulty rising from a squat position. There is also mild weakness in shoulder internal and external rotation bilaterally. Cranial nerve examination is normal. Sensory examination is grossly intact to light touch, pinprick, and proprioception. Muscle stretch reflexes are absent throughout.

Differential Diagnosis

The primary finding on clinical examination is proximal muscle weakness, with the leading diagnostic possibilities being myopathy, neuromuscular junction disorder, motor neuron disease, polyradiculoneuropathy, or debility. The relatively symmetric proximal findings with loss of reflexes make motor neuron disease less likely. The mild sensory symptoms and loss of muscle stretch reflexes raise the possibility of a polyradiculoneuropathy, which can be seen with diabetes in association with prominent weight loss versus coexisting peripheral neuropathy and myopathy. An inflammatory myopathy such as inclusion body myositis or polymyositis remains in the differential. Given the prominent weight loss, the possibility of a paraneoplastic process involving any of these muscles or nerves or a presynaptic neuromuscular junction disorder must be considered. Motor and sensory NCSs, repetitive stimulation studies, and needle EMG were performed (Table 11-18).

Table 11-18 Case 15: Nerve Conduction Studies and Electromyography

Discussion

NCSs showed markedly reduced CMAP amplitudes as well as borderline sensory amplitudes. The conduction velocities were relatively spared, and there was no evidence for motor conduction blocks or dispersion. Needle examination showed varying MUPs throughout without abnormal spontaneous activity. MUP morphology revealed an increased proportion of short-duration, low-amplitude MUPs in some proximal muscles. If the electromyographer were to quit at this point without performing repetitive stimulation, the conclusion could be that the patient has a proximally predominant myopathy in addition to a mild underlying peripheral neuropathy. This conclusion would be incorrect, and some inconsistencies in this regard need to be recognized. The degree of weakness was relatively mild, but the CMAPs were markedly reduced, clearly out of proportion to the clinical examination. In addition, there was prominent MUP variation that would not be expected to this degree in a myopathy. The examiner performed repetitive stimulation on distal upper and lower limb muscles as well as the weak quadriceps. As noted in Figure 11-6, there was a marked increase of the CMAP amplitude immediately after brief exercise, with greater than doubling of the baseline response (greater than 200% facilitation). This was associated with partial repair of the subsequent responses of the train and further decrement out to 3 minutes after exercise. This pattern of low-amplitude baseline CMAPs, decrement to repetitive stimulation, and greater than 200% facilitation after brief exercise is consistent with a presynaptic neuromuscular junction disorder, specifically Lambert-Eaton myasthenic syndrome (LEMS).⁸ A mild underlying peripheral neuropathy is also probable. Further questioning of the patient revealed prominent small-fiber symptoms such as dry mouth, dry eyes, and erectile dysfunction, which may be seen either from the LEMS or a small-fiber peripheral neuropathy. On reexamination, the muscle stretch reflexes were relatively normal after brief muscle contraction, again consistent with a presynaptic neuromuscular junction disorder. P/Q voltage-gated calcium channel antibodies were positive in this patient. They are found in approximately 90% of patients with LEMS.²⁰ The patient was found to have small cell lung carcinoma.

FIGURE 11-6 Two-hertz repetitive stimulation to the ulnar and facial nerves in a presynaptic neuromuscular junction disorder.

Case 16: “Drooping” of the Right Face

A 54-year-old otherwise healthy man awoke and was noted by his wife to have “drooping” of the right face. He noted the inability to close the right eye completely and was drooling out of the right side of the mouth while attempting to brush his teeth. He was brought to the emergency department, where a comprehensive neurologic examination showed right facial weakness involving all peripheral facial branches including the frontalis. There was trace movement of the orbicularis oculi and oris. The remainder of the cranial nerve examination including ocular movements, jaw strength, facial sensory, and palatal and tongue movements was normal. Mild hyperacusis was reported. The patient did report a moderate headache, and a computed tomography scan was performed that was normal. The patient received a diagnosis of right facial neuropathy and was told to contact his primary physician for follow-up the next day. The patient was referred to the EMG laboratory 13 days after onset to determine the prognosis for recovery and exclude other potential causes.

Differential Diagnosis

The clinical history and physical examination are consistent with a lower motor neuron process involving the right facial nerve. The most likely cause would be idiopathic facial neuropathy (Bell’s palsy). Other potential causes for acute-onset facial weakness include an infectious process such as herpes zoster or Lyme disease, granulomatous disorders such as sarcoid, or other inflammatory- or immune-mediated processes such as acute inflammatory demyelinating polyneuropathy or mononeuritis multiplex. Subacute or chronic facial paralysis could be seen with a tumor of the cerebellar pontine angle or structural process around the ear or parotid gland (cholesteatoma, salivary tumor). An upper motor neuron process is unlikely because the frontalis would typically be relatively spared in such cases. NCSs were performed as in Table 11-19. Blink reflex results are noted in Table 11-20.

Table 11-19 Case 16: Nerve Conduction Studies and Electromyography

Table 11-20 Normal Values for Blink Reflexes

Discussion

Bilateral facial NCSs were performed, showing markedly reduced right facial CMAP amplitude. This alone would support a lower motor neuron process and exclude central causes. The left facial response was normal, and limited upper limb studies were performed to exclude a more diffuse polyradiculoneuropathy. Blink reflexes (Figure 11-7) revealed marked prolongation of the right R1 and ipsilateral R2 components (with normal contralateral R2 latency) when stimulating the right supraorbital nerve. When stimulating the left supraorbital nerve, there was prolongation of the contralateral R2 response. These findings are consistent with left efferent pathway involvement, specifically of the facial nerve. The needle examination revealed sparse fibrillation potentials with markedly reduced recruitment in right facial–innervated muscles. The masseter was examined to exclude more diffuse cranial neuropathies, and was normal.

FIGURE 11-7 Normal values for blink reflexes.

Recovery of facial function can be reasonably well predicted by physical examination and EDX abnormalities. In a study of the natural history of Bell’s palsy, Peitersen ²³ found complete recovery in 71% of patients overall, and in those with incomplete paresis at presentation, 94% recovered fully (as opposed to only 61% with complete paresis at presentation). Two thirds of patients recovered function within 3 months, but after 6 months no additional patients regained normal mimical function. EDX findings, particularly the CMAP amplitude, can also assist with prediction of recovery. An amplitude of 10% or less after 7 days in comparison with the contralateral response would generally predict poor recovery, whereas an amplitude of greater than 30% predicted full recovery within 3 months.²¹ Those with amplitudes of 10% to 30% had incomplete recovery over 6 to 8 months with some residual weakness or additional symptoms such as synkinesis or “crocodile tears.” Some have reported the utilization of stimulus thresholds within the first 72 hours.¹⁰ In this study, those with a stimulation threshold of greater than 10 mA did more poorly. In this case, the patient had some sparing of motor function as well as a facial CMAP amplitude of greater than 30%, arguing for complete recovery.

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