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 to 5 for motor fibers and days 6 to 10 for sensory fibers (Figure 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).

Table 16–1 Time-Related Changes in Axonal Loss

FIGURE 16–1 Effect on compound muscle action potential and sensory nerve action potential amplitudes following wallerian degeneration.

Following an axonal loss lesion, the distal nerve degenerates over the next several days, with an accompanying decrease in motor and sensory amplitudes. If NCSs are performed immediately after an axonal loss injury, they will be normal, provided both the stimulation and recording sites are distal to the injury. Note in the figure that the amplitude declines earlier for motor than sensory nerves; this likely occurs due to failure first at the neuromuscular junctions.

(From Katirji, B., 1998. Electromyography in clinical practice: a case study approach. St. Louis, Mosby.)

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. 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. Consider these examples at both extremes of nerve length:

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, motor and sensory 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 (Figure 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.

FIGURE 16–2 Demyelination and nerve conduction studies.

Demyelination results in marked slowing of conduction velocity and, if severe enough, conduction block. The underlying axon remains intact, however, and wallerian degeneration does not occur. Nerve conduction parameters vary in demyelination, depending on the site(s) of demyelination. A: Demyelination affecting proximal, intermediate, and distal segments of nerve. This distribution results in conduction velocity slowing, prolonged distal latencies (DLs), prolonged late responses, reduced distal amplitudes, and conduction block between distal and proximal stimulation sites. B: Demyelination affecting only distal nerve segments. This distribution results in prolonged DLs and reduced distal amplitudes, when the nerve is stimulated at the wrist and elbow. Because late responses also travel through the distal segment, they are prolonged as well. Conduction velocities are normal, however, and no conduction block is seen between the usual distal and proximal stimulation sites. If a more distal site can be stimulated (e.g., the palm), then a conduction block pattern may be seen between the more distal stimulation site (palm) and the usual distal stimulation site (wrist). C: Demyelination affecting only proximal nerve segments. In this pattern, DLs, amplitudes, and conduction velocities are normal. The only abnormality on routine studies may be prolongation of late responses. If it is possible to stimulate a very proximal site, a conduction block pattern may be seen between the very proximal stimulation site and the usual proximal stimulation site (elbow).

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, nerve conduction studies 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 (Figure 16–3). If the studies are repeated after one 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.

FIGURE 16–3 Hyperacute axonal loss and “conduction block.”

After an axonal loss injury (e.g., transection), wallerian degeneration occurs in motor fibers 3 to 5 days later. Before that time, the nerve can still be stimulated and recorded distal to the injury, despite being disconnected from its proximal segment. If the nerve is stimulated proximal to the injury, however, a conduction block pattern will be present, a finding usually associated with demyelination. If the study is repeated after 1 week’s time, the nerve will have degenerated. All amplitudes will be reduced, and the previously noted “conduction block” will no longer be present. In the figure above, stimulating at the wrist and elbow immediately after a proximal axonal loss injury results in normal amplitudes, conduction velocity, and latencies. If the nerve is stimulated at the axilla, an apparent conduction block will be present.

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 week’s 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 motor and sensory 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

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