Clinical–Electrophysiologic Correlations: Overview and Common Patterns

Axonal Loss Lesions

Understanding the pattern of changes that takes place over time (time-related changes) is essential in the interpretation of neuropathic lesions. With an axonal loss lesion, an orderly pattern of abnormalities develops over time on NCSs and EMG ( Table 16.1 ). Immediately after an axonal loss lesion (e.g., partial transection of a nerve), clinical weakness and numbness develop. However, wallerian degeneration of the nerve does not occur until days 3–5 for motor fibers and days 6–10 for sensory fibers ( Fig. 16.1 ). Before that time, distal NCSs remain normal. Thus, when the nerve is both stimulated and recorded distal to the lesion, it can still conduct well despite being effectively disconnected from its proximal segment. After wallerian degeneration occurs, NCSs become abnormal, showing changes consistent with axonal loss: amplitudes decrease, with relative preservation of conduction velocities (CVs) and distal latencies (DLs). Amplitudes for motor studies decline slightly earlier than for sensory nerves; this likely occurs due to failure first at the NMJs. If the largest and fastest axons have also been lost, there may be some slowing of CV and DL, but never into the demyelinating range (i.e., CV <75% of lower limit of normal; DL >130% of upper limit of normal).

On needle EMG, decreased recruitment of motor unit action potentials (MUAPs) occurs in weak muscles immediately with the onset of the lesion. Because some axons and their motor units have been lost, the only way to increase force is to fire the remaining available motor units faster, resulting in a pattern of decreased recruitment. No abnormal spontaneous activity or change in MUAP morphology is seen with the onset of the lesion; those changes take time to develop.

Within the next several weeks, abnormal spontaneous activity (i.e., denervating potentials – fibrillation potentials and positive sharp waves) develops. As discussed in Chapter 14 , it is well recognized that the time it takes for denervating potentials to develop depends on the length of nerve between the muscle being studied and the site of the lesion . In a lesion of the L5–S1 nerve roots (i.e., the longest distance between a lesion and the muscle), fibrillation potentials and positive sharp waves take 10–14 days to develop in the paraspinal muscles, 2–3 weeks in the proximal thigh, 3–4 weeks in the leg, and 5–6 weeks in the distal leg and foot. By extrapolating from these values, one can estimate the time it takes for denervating potentials to develop in other axonal loss lesions of nerves of different lengths.

Finally, in the chronic stages of axonal loss lesions, reinnervation follows denervation, which typically takes several months. Reinnervation results in changes in MUAP morphology. MUAPs become longer in duration, higher in amplitude, and polyphasic, reflecting increased numbers of muscle fibers per motor unit. If reinnervation is successful, months to years later spontaneous activity disappears, leaving only reinnervated MUAPs with decreased recruitment on needle EMG. In addition, sensory and especially motor amplitudes may improve on NCSs after successful reinnervation.

Thus, by looking at the combination of NCS findings (normal or abnormal), spontaneous activity (present or absent), MUAP morphology (normal or reinnervated), and recruitment (normal or decreased), one can estimate the time course of any neuropathic lesion associated with axonal loss.

Demyelinating Lesions

In pure demyelinating lesions ( Fig. 16.2 ), the pattern of abnormalities is different from that of axonal loss lesions and depends on the degree of demyelination. Myelin is essential to maintain the speed of nerve conduction. Accordingly, demyelination first results in marked slowing of CV, as well as prolongation of DLs and late responses. If demyelination is more severe, frank conduction block occurs, with its clinical correlates of sensory loss and weakness associated with blocking of sensory and motor fibers, respectively. Slowing alone, without conduction block, still allows the nerve action potential to reach its destination, albeit more slowly than normal. Pure slowing therefore does not result in any fixed weakness. On the sensory side, pure slowing may result in depressed or absent reflexes and a perception of altered sensation but not in fixed numbness.

The presence of conduction block has special importance in patients with demyelination. First, it implies that the clinical deficit (weakness, numbness) is secondary to demyelination and, accordingly, that recovery can occur with remyelination. Second, when present in entrapment neuropathies (e.g., radial neuropathy at the spiral groove, median neuropathy at the carpal tunnel), the finding of conduction block can be used to localize the lesion . Finally, in the evaluation of patients with demyelinating polyneuropathy, the presence of conduction block at non-entrapment sites has additional diagnostic significance because it differentiates acquired from inherited conditions. Conduction block characteristically occurs at non-entrapment sites in acquired demyelinating neuropathies, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP), but it is not seen in the various inherited demyelinating neuropathies (e.g., Charcot-Marie-Tooth type I) in which demyelination results only in uniform slowing.

When a demyelinating lesion results in conduction block, clinical numbness and weakness develop acutely. Distal to the conduction block, the nerve continues to conduct normally, although it is effectively disconnected from its proximal segment. Accordingly, distal NCSs remain normal, as in acute axonal loss lesions. However, in contrast to axonal loss lesions, the underlying axon remains intact, and wallerian degeneration never occurs. NCSs remain normal distally. However, if the nerve is stimulated above the lesion, electrophysiologic evidence of focal demyelination (i.e., marked CV slowing, conduction block, or both) will be seen.

Conduction block nearly always means demyelination; however, in one unusual situation, conduction block may be seen in an axonal loss lesion. If, following a transection, NCSs are performed above and below the lesion during the first several days, before wallerian degeneration has occurred, a conduction block–like pattern will be seen ( Fig. 16.3 ). If the studies are repeated after 1 week, however, the distal nerve will have degenerated and the apparent block will no longer be present. Some refer to this as a pseudo–conduction block .

On needle EMG, recruitment decreases in a demyelinating lesion associated with conduction block because the number of available motor units has been reduced. Because the underlying axon remains intact, however, no wallerian degeneration occurs. Therefore, no denervation or subsequent reinnervation occurs. Reduced recruitment remains the only abnormality on needle EMG in a pure demyelinating lesion with conduction block . In cases in which demyelination results only in slowing, without conduction block, clinical muscle strength and its EMG correlate, recruitment, are normal. Thus, in cases where there is only slowing, without conduction block or any axonal loss, the entire needle EMG remains normal.

Pure demyelinating lesions are uncommon. Most demyelinating lesions have some secondary axonal loss, regardless of whether they are inherited or acquired, associated with conduction block or with slowing alone. Such cases will demonstrate a combination of axonal and demyelinating changes on nerve conduction and needle EMG studies. However, usually, it still is possible to determine if the primary underlying pathophysiology is demyelination or axonal loss.

Axonal Loss: Hyperacute

The pattern of hyperacute axonal loss occurs in axonal loss lesions less than 3 days old, prior to the beginning of wallerian degeneration. The result is an unusual combination of normal motor and sensory conductions distal to the lesion, despite clinical weakness and sensory loss. Late responses are also usually normal, unless the nerve has been completely transected proximally. If stimulation can be performed proximal to the lesion during this period, a marked drop in amplitude will be seen, mimicking conduction block, a finding usually associated with demyelination. On needle EMG, reduced MUAP recruitment in weak muscles is the only abnormality seen. Insufficient time has elapsed for either spontaneous activity or changes in MUAP morphology to have developed.

Hyperacute axonal loss is an unusual pattern, typically seen after trauma or nerve infarction. It can be difficult to differentiate this pattern from that seen with an acute demyelinating lesion associated with conduction block; the two are quite similar. Often, it is necessary to repeat the study after 1 weeks’ time. If the underlying pathology is axonal loss, wallerian degeneration will occur after about a week. Distal NCSs become abnormal, and the proximal “conduction block” disappears. Making this differentiation is important for determining the etiology of the lesion, as well as the prognosis (axonal loss has a much worse prognosis than demyelination).

Axonal Loss: Acute

The pattern of acute axonal loss occurs in lesions that are more than several days but less than several weeks old. Enough time has passed for wallerian degeneration to have occurred. Accordingly, NCSs are abnormal, showing evidence consistent with axonal loss. Amplitudes are decreased, with relatively normal CVs and DLs, unless some of the largest and fastest axons have been lost, in which case some slowing of CV and latency occurs. On needle EMG, decreased recruitment remains the only abnormality. Not enough time has elapsed for denervation potentials to develop (usually 2–6 weeks, depending on the length of the nerve between the lesion and the muscle tested). Again, acute axonal loss is an unusual pattern, typically seen after an event such as trauma or nerve infarction.

Axonal Loss: Subacute

The pattern of subacute axonal loss lesions occurs after several weeks, but not months. Compared with the hyperacute and acute patterns, enough time has elapsed to see spontaneous denervating potentials on needle EMG. Reinnervation has not yet occurred, however, and MUAP morphology remains normal. This pattern, similar to the acute and hyperacute axonal loss patterns, is unusual and is seen most often after trauma or nerve infarction.

Axonal Loss: Subacute–Chronic

The pattern associated with subacute-chronic axonal loss lesions occurs after a couple of months. Enough time has passed for wallerian degeneration (abnormal NCS results) and abnormal spontaneous activity (fibrillation potentials/positive sharp waves) to be demonstrated. In addition, reinnervation now is occurring, resulting in changes in MUAP morphology. MUAPs are long in duration, high in amplitude, and/or polyphasic, with decreased recruitment. In contrast to the patterns described earlier, this pattern is quite common; it is seen in most polyneuropathies.

Axonal Loss: Chronic

The chronic axonal loss pattern is seen months to years after the occurrence of a lesion that is no longer active. Reinnervation is complete, and denervating potentials have disappeared. Successful reinnervation often results in improved or even normal sensory and especially motor amplitudes on NCSs. MUAP abnormalities often persist indefinitely on needle EMG as a marker of the remote injury that is no longer active (e.g., old radiculopathy).

Demyelination (Slowing and Conduction Block): Single Proximal Lesion

An isolated proximal demyelinating lesion with focal slowing and conduction block produces an important pattern that, if not recognized, often creates confusion. Because the underlying axon remains intact, wallerian degeneration never occurs. Thus, despite clinical findings of weakness or numbness, distal motor and sensory conductions remain normal. Late responses (i.e., F and H waves) may be abnormal, signifying proximal block and slowing. Motor studies, if performed proximally across the lesion, demonstrate conduction block and focal slowing, the electrophysiologic signs of demyelination. Although they typically are not performed proximally, sensory studies would show similar findings. On needle EMG, the only abnormality is decreased recruitment in weak muscles, reflecting that blocked motor units are no longer available to help generate force. Without axonal loss, denervation and reinnervation never occur. This type of lesion often occurs as the result of an episode of prolonged compression or trauma (e.g., radial neuropathy at the spiral groove). Note that if this pattern is seen and the clinical history indicates that the lesion is less than 4 days old, distinguishing this pattern from a hyperacute axonal loss lesion may be difficult. Both will show “conduction block” at the site of the lesion. A repeat study in 1 week may be necessary to make the differentiation. In a purely demyelinating lesion, no drop in distal amplitude should be seen after 1 week, whereas in an axonal loss lesion, distal and proximal amplitudes will both be low after 1 week.

Demyelination (Slowing Alone): Single Proximal Lesion

When a single proximal demyelinating lesion results only in slowing and not in conduction block, the pattern of abnormalities is not as marked. Distal NCSs remain normal. Only late responses and studies performed across the lesion will be abnormal. In such a case, stimulation across the lesion site results only in slowing of CV. With no conduction block and no loss of motor units, however, the entire needle EMG pattern remains normal. This pattern, because of its few abnormalities, can be very difficult to recognize. It is occasionally seen, for example, in ulnar neuropathy at the elbow.

Demyelination (Slowing and Conduction Block): Single Distal Lesion

If conduction block and slowing occur between the distal stimulation site and the recording electrodes (e.g., median nerve at the wrist), a different pattern from those previously described emerges. Both motor and sensory amplitudes are decreased, associated with marked slowing of DLs. Sensory CV, typically calculated in the distal segment, is markedly slowed. However, motor CV, which is calculated in the proximal segment since it can be calculated only between two stimulation sites, one distal and one proximal, remains normal because the prolonged DL is subtracted out in the calculation. Late responses, which must also travel through the distal segment, are also prolonged. If stimulation distal to the lesion is possible (e.g., in the palm), a conduction block pattern will be seen for both motor and sensory fibers. On needle EMG, reduced recruitment in weak muscles is the only abnormality present. This pattern of distal demyelination is quite common and occurs frequently with distal entrapment neuropathies, especially carpal tunnel syndrome.

Demyelination (Slowing Alone): Single Distal Lesion

The pattern of distal demyelination with slowing alone differs from the one with coexistent conduction block. DLs are prolonged, and late responses are still abnormal. However, motor amplitude usually remains normal. In contrast, sensory amplitudes often decrease, not from conduction block but from the process of temporal dispersion and phase cancellation. The effects of temporal dispersion from demyelination and subsequent phase cancellation are always much more marked for sensory than for motor fibers. Sensory CV is markedly slowed. Without conduction block, the needle EMG is completely normal, including recruitment of MUAPs. This pattern also is quite common and is seen in many distal entrapment neuropathies.

Early Reinnervation After Severe Denervation

After severe or complete denervation, in which there are no nearby surviving axons, the only mechanism of reinnervation is regrowth of the axon from the site of injury. As the axon regrows, there comes a time when it reinnervates some but not all of the original muscle fibers. At that point, NCSs show a pattern consistent with marked axonal loss: very low amplitudes, with normal or mildly slowed velocities and latencies. MUAP morphology reveals short-duration, low-amplitude, polyphasic MUAPs, reflecting the reduced number of muscle fibers per motor unit. The morphology of these MUAPs is similar to those of acute myopathic MUAPs, and they are known as nascent units (see Chapter 15 ). The key factor that differentiates between nascent units and myopathic units is the recruitment pattern . Because nascent units follow severe denervation, recruitment is markedly reduced; in contrast, myopathic MUAPs are seen in the context of normal or “early” recruitment. Nascent units are uncommon but serve to reemphasize that not all small, short, polyphasic MUAPs are myopathic.