Differential Diagnosis

The patient presents with predominantly right hand and arm pain and paresthesias, and a nonfocal physical examination. The most likely cause for these symptoms would be a mononeuropathy (which could involve the median, ulnar, and/or radial nerves based on the distribution of symptoms) or cervical radiculopathy. A plexopathy should be considered, and with the gradual onset of symptoms, the most likely cause of such would be an infiltrative or compressive lesion. More generalized pathology such as polyradiculoneuropathy or length-dependent peripheral neuropathy would be unlikely to present in this manner, particularly given the positional nature of the symptoms. A musculoskeletal cause for the symptoms is certainly a consideration; patients with myofascial pain often have associated paresthesias (typically in a nondermatomal distribution), and such patients are frequently referred for EDX evaluation to exclude a neurogenic cause for their pain. Lastly, it is always prudent to consider a more central process such as a syrinx or a cortical lesion, but the intermittent nature and gradual onset of the symptoms make these less likely.

When evaluating for a mononeuropathy, it is helpful to consider the potential etiologies because this will determine which EDX studies should be performed. Although focal compression, such as carpal tunnel syndrome, is by far the most common etiology for a mononeuropathy, a more generalized process involving multiple nerves (e.g., mononeuritis multiplex, hereditary neuropathy with tendency to pressure palsies, multifocal motor neuropathy with conduction block) needs to be considered. Cervical radiculopathy is also high on the list of differential diagnoses, and as she reports paresthesias throughout the entire hand, this could reflect involvement of the C6, C7, and/or C8 nerve roots. The NCS and needle EMG findings for this case are shown in Table 11-2.

Table 11-2 Case 1: Nerve Conduction Studies and Electromyography

Discussion

Given the differential diagnosis outlined above, it is important to perform median and ulnar motor and sensory NCSs. A median F-wave was also performed because this may be prolonged where proximal slowing is present, such as in radiculopathy. When median neuropathy at the wrist (carpal tunnel syndrome) is a clinical consideration, we perform the median motor study first and then determine the most appropriate median sensory study based on the motor results. If the motor study is normal, as it was on the left, there are a number of different orthodromic or antidromic sensory studies that can be performed. We chose the orthodromic palmar sensory study on the left because it is one of the most sensitive techniques available and can be abnormal in cases of very mild median neuropathy.²⁹ Other options include radial-to-median distal latency comparison recording from the thumb, ulnar-to-median distal latency comparison recording from the fourth digit, or antidromic median sensory studies recorded from the most symptomatic digit.²⁹ If the motor distal latency is prolonged, a less sensitive but technically less challenging study such as a median antidromic sensory study would be appropriate, and that was the choice on the right. The ulnar sensory response must also be obtained to ensure there is not evidence for a more generalized process. In this case, the NCSs show evidence of a median neuropathy at the wrist, bilaterally, with focal slowing demonstrated by prolonged median motor and antidromic sensory latencies on the right, and relative prolongation of the orthodromic median palmar sensory distal latency on the left, compared with the ulnar response (with a difference greater than 0.3 ms considered abnormal).²⁹

Since the NCSs have confirmed the presence of a median neuropathy at the wrist, the purpose of the needle examination in this case is threefold: (1) to confirm the level of the median nerve lesion, (2) to provide additional information regarding severity, and (3) to exclude a superimposed process that could be contributing to the presenting symptoms, such as cervical radiculopathy. Examining a median-innervated thenar muscle provides the information on severity; in this case the finding of long-duration MUPs and some fibrillation potentials provides further evidence that this is a relatively severe lesion. Examining the pronator teres is helpful because this is a more proximal median-innervated muscle, and if normal, helps exclude a more proximal median neuropathy. Additionally, as the pronator teres is innervated by the C6 and C7 roots, a normal examination helps exclude a cervical radiculopathy at those levels. The deltoid also assesses for C5 and C6 root involvement, which can lead to similar symptoms. Examining the first dorsal interosseous helps exclude an ulnar neuropathy (unlikely given the normal ulnar NCS), but also excludes a C8 radiculopathy or lower trunk plexopathy as a cause for the abnormal findings in the abductor pollicis brevis muscle. Cervical paraspinal muscles were not examined in this case because all the findings on both NCSs and needle EMG pointed to carpal tunnel syndrome. However, if there is a strong clinical suspicion for recent-onset cervical radiculopathy, the paraspinals should be examined because they are often the first muscle to show changes on needle EMG.

Although the diagnosis in this case is bilateral median neuropathy at the wrist, consistent with carpal tunnel syndrome, the presentation highlights that many patients do not describe classic symptoms, and one must consider a broad differential diagnosis in such cases. In carpal tunnel syndrome, more than 50% of patients report sensory symptoms outside the median nerve distribution,³⁰ and this is a reason that EDX examination is critical in refining the clinical impression.

Differential Diagnosis

This is a very common referral to the electromyographer with the primary differential diagnosis being a cervical radiculopathy, median neuropathy at the wrist or myofascial syndrome. A brachial plexopathy is possible but unlikely in the absence of trauma or a history of carcinoma. Although an idiopathic brachial plexopathy (Parsonage-Turner syndrome) could present spontaneously, the pattern of pain and weakness would be unusual. The sensory findings confirmed on clinical examination would argue against a myofascial process and narrow the diagnosis. The pattern of sensory loss could be seen with either a median neuropathy or cervical radiculopathy, but the mild triceps weakness and reflex changes would certainly argue for a radiculopathy, most likely in the C7 distribution. Given the triceps and finger extensor weakness, a radial neuropathy would also need to be excluded with the EDX evaluation. NCSs and needle EMG were performed (Table 11-3).

Table 11-3 Case 2: Nerve Conduction Studies and Electromyography

Discussion

The EDX findings are relatively straightforward, showing fibrillation potentials in radial- and some median-innervated muscles of the forearm as well as paraspinal muscles. Because these finding occur in two or more muscles innervated by the same root (C7) but different peripheral nerves, the diagnosis of a cervical radiculopathy is most likely. The presence of fibrillation potentials in cervical paraspinal muscles strengthens that conclusion. The patterns of findings do, however, raise some additional points. Because each muscle is innervated by two or more roots, there is significant variability in the pattern of findings, and this can make localization to a single root difficult. In this case, radial-innervated muscles seem more involved with relative preservation of the pronator teres. The flexor carpi radialis was clearly involved, however, suggesting that in this patient the pronator teres might have predominant C6 innervation. Although the radial sensory is not a routine study, it can be very helpful. If the findings are primarily in the radial distribution, a normal radial sensory study would be consistent with a preganglionic process and make radial neuropathy or brachial plexopathy much less likely. The sensory studies can be particularly helpful when there has been a previous cervical spine surgery, and paraspinal needle examination might be unreliable. The other inconsistency in this case is the large, stable MUPs noted, which would reflect longstanding reinnervation and would not be consistent with the relatively acute onset of symptoms. The history noted a previous episode several years ago, and these findings are more consistent with an underlying longstanding or old C7 radiculopathy with an acute exacerbation. The borderline median sensory distal latency raises the possibility of a superimposed median neuropathy at the wrist; further studies with either palmar orthodromic sensory responses or comparative sensory studies to the thumb or ring finger might be indicated.

Differential Diagnosis

The most likely etiology for these symptoms would be a brachial plexopathy or cervical radiculopathy. The distribution of weakness involves multiple peripheral nerves and at least two root levels (C6, C7, and possibly also C5). Sensory symptoms fall within the C6 dermatome, but could also be due to more peripheral involvement of the lateral antebrachial cutaneous nerve. Although anterior horn cell disease could present with this pattern of weakness, the pain and numbness make this unlikely. Mononeuritis multiplex could present with severe pain and multiple peripheral nerve involvement; however, the distribution in this case would be unusual.

Given the history, an infiltrative plexopathy caused by breast carcinoma would be of primary concern; however, the sudden onset of symptoms would argue for an inflammatory/idiopathic brachial plexopathy. In this case a radiation-induced injury should also be considered, but the acute and painful onset would also make this less likely. The finding of myokymia on needle examination is very helpful in such cases, because this is much more frequently found in radiation plexopathy than in cases of metastatic infiltration of the plexus.^15,19 The NCSs and needle EMG for this patient are listed in Table 11-4.

Table 11-4 Case 3: Nerve Conduction Studies and Electromyography

Discussion

NCSs are important in this case to determine which peripheral nerves are affected, whether both motor and sensory fibers are involved, and to assess the severity of axonal loss (which is helpful with regards to prognosis). If sensory nerve action potentials (SNAPs) are low amplitude, this reflects pathology distal to the nerve root at the level of the plexus or peripheral nerve. Needle examination is used to map out the distribution of involvement, using knowledge of anatomy, particularly the brachial plexus, to differentiate between peripheral nerve, plexus, and root involvement.

NCSs in this case show low-amplitude median antidromic and absent lateral antebrachial cutaneous sensory responses, which implies that the lesion is distal to the dorsal root ganglion at the level of the plexus or peripheral nerve. The normal median motor response (C8, T1, lower trunk) in the presence of a low-amplitude median sensory response (C6, C7, middle trunk) suggests the lesion is proximal to the median nerve and at the level of the plexus. The median sensory response on the left is mildly low amplitude with a prolonged distal latency, most likely representing a preexisting median neuropathy at the wrist of the type seen in carpal tunnel syndrome. The musculocutaneous compound muscle action potential (CMAP) is absent on the right but easily elicited on the left. This study was performed because the more easily obtained median and ulnar motor studies are both derived from C8–T1 axons and therefore are spared in this case.

Needle examination supports recent severe denervation involving most of the C5- and C6-innervated muscles examined, placing the lesion at the level of the upper trunk of the brachial plexus (involvement of the supraspinatus and the supinator localizes the lesion proximal to the lateral cord), with more mild involvement of some middle trunk muscles. The findings in the serratus anterior suggest the lesion is very proximal, because the long thoracic nerve forms directly off the C5, C6, and C7 ventral rami. Cervical paraspinal muscles showed a few fibrillation potentials, indicating some degree of nerve root involvement, but these were much less prominent than in some of the affected limb muscles.

The needle EMG findings, when taken in combination with the NCS results, are most consistent with a severe right upper, and to a lesser extent, middle trunk brachial plexopathy, with evidence to suggest mild cervical root involvement also. Given the somewhat patchy nature of the needle EMG findings, the absence of trauma, and the classic history of severe pain at onset followed by weakness that persists, the cause is almost certainly inflammatory and is typical of neuralgic amyotrophy or Parsonage-Turner syndrome.³² Often a particular peripheral nerve will be severely involved. For example, patients can present with sudden onset of severe dyspnea that is worse when recumbent, because of involvement of the phrenic nerve. They can also present with a classic anterior interosseous neuropathy with weakness only involving the flexor pollicis longus, flexor digitorum profundus to the second and third digits, and the pronator quadratus. Such cases are frequently misdiagnosed as entrapment neuropathy. Therefore it is critical when evaluating such cases to perform a careful needle examination, looking for patchy involvement outside the muscles that are clearly involved clinically. This includes a search for subclinical contralateral limb involvement, to avoid unnecessary surgery in such cases. A careful history should quickly alert the electromyographer to the likely diagnosis in such cases. Imaging of the cervical spine in this setting can be helpful in excluding a compressive process, but care should be taken to not assign clinical significance to mild spondylotic changes. Imaging of the brachial plexus can also reveal signal abnormalities, and in this case it would also be indicated to exclude an infiltrative process.

Differential Diagnosis

The patient presents with numbness and tingling in a right ulnar nerve distribution and weakness of intrinsic hand muscles. Given the history of compression, the most likely cause for these symptoms would be mononeuropathy involving the ulnar nerve at the wrist or elbow. Such symptoms could also represent a more generalized process such as a hereditary neuropathy with a tendency to pressure palsies, or mononeuritis multiplex (typically the latter would be painful). Other considerations should include lower trunk or medial cord brachial plexopathy and C8/T1 radiculopathy. Anterior horn cell disease involving the lower cervical cord is unlikely given the sensory symptoms. Rarely a spinal cord lesion such as a syrinx or a cortical infarct might present in this way. NCS and needle EMG findings for this case are shown in Table 11-5.

Table 11-5 Case 4: Nerve Conduction Studies and Electromyography

Discussion

NCSs showed a low-amplitude ulnar motor response on the right, with slowed conduction velocity and borderline distal latency. There was a significant reduction in the CMAP amplitude between the elbow and wrist stimulation sites suggesting a conduction block. This was confirmed with stimulation at the below-elbow site, followed by short-segment stimulation (inching) between the elbow and below-elbow sites (Figure 11-1). There was also significant slowing localized to the elbow segment (evident as a conduction velocity in the above-elbow to wrist segment that was more than 10 ms slower than the conduction velocity of the below-elbow to wrist segment). The left ulnar motor response was normal but the ulnar sensory response was low amplitude with a slowed conduction velocity. With normal median motor and sensory studies on the right, these findings are most suggestive of bilateral ulnar neuropathy at the elbow, more pronounced on the right.

FIGURE 11-1 Conduction block of the ulnar nerve. The nerve is stimulated at five sites (A through E), 2 cm apart. A drop in amplitude is looked for to indicate conduction block. The five separate traces are superimposed underneath the individual tracings to show the conduction block more clearly.

The purpose of the needle examination in this case, where the diagnosis appears evident from the NCSs, is to provide further information on severity, temporal profile, and as always, to exclude coexistent problems such as plexopathy, radiculopathy, or more generalized peripheral neuropathy. Both ulnar- and non–ulnar-innervated C8 and T1 muscles must be examined. Proximal ulnar muscles such as the flexor carpi ulnaris and/or flexor digitorum profundus to digits 4 and 5 should be examined to confirm a lesion at the elbow. The examiner must keep in mind, however, that a fascicular process can spare these fibers even if the lesion is proximal. Intrinsic hand muscles such as the first dorsal interosseous and abductor digiti minimi can be examined to evaluate the severity of the lesion, and non–C8-innervated muscles such as the flexor pollicis longus and extensor indicis proprius can rule out plexopathy or radiculopathy.

Findings of fibrillation potentials and reduced recruitment in proximal and distal ulnar-innervated muscles suggest moderately severe axonal loss in this case, with the lesion at the level of the elbow (because of the finding of conduction block on ulnar motor NCSs and involvement of the flexor carpi ulnaris on needle EMG). The presence of long-duration MUPs indicates the process has been present to some degree for more than a few weeks, predating the 2-week history that the patient reports.

Ulnar neuropathies are relatively common, generally presenting with varying degrees of sensory symptoms in the fourth and fifth digits as well as weakness of ulnar-innervated hand and sometimes forearm muscles. Sensory fibers are usually the most vulnerable and can show abnormalities in very mild neuropathies. Motor responses can be recorded from both the abductor digiti minimi and first dorsal interosseous muscles to improve sensitivity, as a normal response can be obtained from one of the muscles or the other because of the fascicular nature of nerve topography. The diagnosis of a focal ulnar neuropathy at the elbow is suspected with slowing across the elbow segment of greater than 10 m/s compared with the below-elbow segment, of if there is an amplitude drop of 20% over a 10-cm segment. If a question remains, sequential 2-cm stimulation across the elbow can confirm an ulnar neuropathy if there is a 10% drop over a 2-cm segment or a latency difference of greater than 0.7 ms.^4,5 An incidental median-to-ulnar crossover in the forearm can simulate an ulnar neuropathy and should always be excluded, particularly if there appears to be a conduction block in the forearm.

An ulnar neuropathy at the wrist (Guyon’s canal) will show prolonged motor and sensory distal latencies without evidence of conduction block at the elbow (and conduction velocities can be normal). The dorsal ulnar cutaneous sensory study can be useful in localizing more distal ulnar neuropathies; if the antidromic sensory response is low or absent but the dorsal ulnar cutaneous response is preserved, this implies the lesion is distal to the take-off of the dorsal ulnar cutaneous nerve, 5 to 8 cm proximal to the wrist. Side-to-side comparison of the dorsal ulnar sensory response is necessary, with a greater than 50% decrease in amplitude considered abnormal. Compression of the deep ulnar nerve can occur in the hand, and in such cases the motor response might be low amplitude with a prolonged distal latency, but the sensory responses will be spared. Needle EMG in that setting shows changes in ulnar-innervated intrinsic hand muscles only.

Differential Diagnosis

When a patient presents with progressive, painless weakness, one must always consider the possibility of amyotrophic lateral sclerosis (ALS), particularly when muscle stretch reflexes are normal or hyperreflexic in the presence of lower motor neuron weakness. Other causes for painless weakness include multifocal motor neuropathy with conduction block (MMNCB), which initially presents with weakness in a single peripheral nerve distribution, but progresses to involve multiple nerves. In early MMNCB, muscle bulk is typically preserved in the face of significant weakness, but with time patients develop axon loss with associated muscle atrophy and loss of reflexes. Reflexes would generally be reduced in the affected distribution as well. A lumbar plexopathy could explain the left lower limb weakness particularly given the history of mild sensory symptoms. In some cases of infiltrative or inflammatory etiology, bilateral involvement of the plexus can be seen. Although unusual in the absence of pain, multiple lumbosacral radiculopathies should be considered, particularly in the setting of diabetes, or as in this case with a background history of low back pain. When hyperreflexia is present, cervical or thoracic stenosis or intramedullary lesions are a possible explanation for brisk reflexes in an otherwise lower motor neuron problem at the level of the lumbar spine. Some myopathies can present with predominantly lower limb weakness; side-to-side asymmetry is common in inclusion body myositis, in which there is typically early involvement of the quadriceps and ankle dorsiflexors. His young age would generally argue against this. Inherited myopathies such as limb girdle dystrophy could also present with lower limb weakness and some asymmetry. Neuromuscular junction disease such as Lambert-Eaton myasthenic syndrome should be considered, but there is typically prominent proximal weakness with a fatigable component, depressed muscle stretch reflexes, and autonomic symptoms such as dry mouth. The NCS and EMG findings are presented in Table 11-6.

Table 11-6 Case 5: Nerve Conduction Studies and Electromyography

Discussion

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