Nerve Repair and Grafting in the Upper Extremity

S. Houston Payne, Jr., MD

J South Orthop Assoc. 2001;10(2) 

In This Article

Natural History

Classification of Nerve Injury

In 1943, Seddon[22] published a classification of nerve injury based on the function of the injured nerve and continuity of nerve tissue ( Table 1 ).[23] Neurapraxia describes a conduction block, though the continuity of all structures is preserved. The conduction block results from a focal demyelinating injury after compression. Common examples are nerve injury after tourniquet pressure and ulnar nerve palsy after prolonged compression from poor positioning during surgery. The conduction block is restored once the myelin regeneration is complete, a process which may take weeks or months.

Axonotmesis indicates a loss of axon continuity, though the endoneural tube is preserved. This structural injury results in wallerian degeneration. Severe crush or traction injuries can produce this lesion. With the loss of continuity, axon regeneration is required, and thus the time to recovery is significantly longer than seen in neurapraxia and in some cases may not occur at all. However, since the endoneural tubes remain intact, the specificity of recovery is excellent.

Neurotmesis indicates a complete loss of continuity and destruction of the interior anatomy of the nerve. In this case spontaneous regeneration does not occur. Sunderland[24] subdivided axonotmesis into three categories to indicate the continuity of the various components of internal nerve anatomy. In the first of these groups, a Sunderland II injury, the endoneural tube is preserved but axon degeneration occurs. In a Sunderland III injury, the axon and endoneural tubes are disrupted, but the perineurium remains intact. In the next group, Sunderland IV, perineural continuity is also lost, but the epineurium remains intact.

Wallerian degeneration is the predictable sequence of events that occurs in both the axonal process and cell body after axon division. It occurs distal to the point of severance.[23] This process clears the Schwann cell tubes in preparation for regenerating axons. Calcium-dependent proteolytic enzymes begin the process by breakdown of axoplasm components into granular material.[25] The ability of the distal axon to transmit action potentials diminishes as the process continues. Motor conduction is absent after approximately 9 days and sensory conduction after 11 days.[26] Macrophages from the Schwann cell and the peripheral circulation phagocytize myelin. The macrophages contain peripheral markers, which are a powerful stimulus to NGF production by the Schwann cell. After myelin is cleared, the individual Schwann cells proliferate within the original myelinated tube, forming a continuous line of cells called Büngner's bands. The Schwann cells also have surface markers that are favorable to axon growth.

The cell body reacts to axotomy by altering its metabolic activity in preparation for new axonal regeneration. The sudden cessation of trophic support by NGF from the periphery is a prime stimulus to the cell body changes.

After axon division, degeneration occurs also in the proximal nerve stump. This extends proximally for several internodal segments. Regeneration begins at the level of the most distal, intact node of Ranvier. Multiple sprouts originate from each regenerating axon. Collateral sprouts extend from the internodal area and advance inside the basal lamina. Terminal sprouts arise from the tip of the divided axon.[27] The most distal part of the regenerating sprout is a highly specialized structure known as the growth cone. It is capable of continuously sampling the surrounding environment and supporting growth along desirable pathways. Projections at the growth cone tip, called filopodia, can extend and retract in a matter of minutes.[28] Schwann cell proliferation is necessary for axon growth. The Schwann cell basement membrane has multiple molecules that stimulate and guide axon growth, in which NGF has been most carefully studied. Nerve growth factor molecules and receptors increase after injury and profoundly stimulate and direct axon growth.

Once the axon contacts Schwann cells, the myelination process begins. However, this occurs only if the axon was originally myelinated, regardless of the previous status of the distal nerve tube. The signal for myelination is located in the parent neuron and is not changed by the local environment of the regenerating axon.[29] Axons that reach a target organ mature and increase in diameter.[30]

The rate of axon growth in humans is 1 to 2 mm/day.[31] This rate may be increased by "conditioning." Several nerve insults can result in this conditioning response; crush is a common example.[32] Conditioning has not been found useful in enhancing regeneration in the clinical setting.

The accuracy with which regenerating axons can reinnervate appropriate target organs in the correct location dramatically affects function after nerve injury. Localization to the correct area is called topographic specificity. Cortical mapping after sensory reinnervation reveals significant disorganization and confirms that topographic specificity is poor, at best.[33] Similarly, precise topographic specificity in regenerating motor axons would result in reinnervation of the correct muscle and fiber type. This level of specificity is not achieved clinically.

There is, however, clear evidence that motor nerves do preferentially reinnervate motor pathways.[34] This preference is supported by the degenerated axon tube, regardless of whether the end organ is present. Experimental evidence indicates that markers, which support the regenerating axon, exist along the motor pathway. Motor axons that initially enter sensory pathways are selectively "pruned," presumably because of a lack of support by the tube itself.

In summary, a motor nerve will selectively innervate the correct type of pathway. However, topographic specificity is still primarily dependent on appropriate orientation at a macroscopic level at the time of the nerve repair.


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