Review articleThe evolution of nerve transfers for spinal cord injury
Introduction
Clinical functional restoration following spinal cord injury (SCI) has relied on maximizing the function that can be achieved by the myotomes which remain under volitional control. This is seen in its simplest form through the use of orthotic devices that utilize purely mechanical means to enhance grasp and improve hand positioning to provide some degree of independence (Tubbs and Pound, 2019). However, these devices can be cumbersome and bulky and still rely upon a caregiver to don and doff. They certainly do not replace the priority of independent control of the hands.
The polio epidemic of the late 1800s was followed by huge numbers of upper extremity injuries provided by the World Wars (Brown et al., 2012b; Vanaclocha-Vanaclocha et al., 2017). These led to the development and refinement of tendon transfers (Sammer and Chung, 2009), which became the primary surgical intervention to provide functional recovery in the upper extremity. In a tendon transfer procedure, a muscle, that is still well controlled but not critical for function, is repositioned so that it can perform the function of the muscle that no longer works. For example, 3 muscles contribute to elbow flexion – the biceps, brachialis and brachioradialis. Therefore, loss of one of the three muscles is well tolerated. The distal end of the brachioradialis can be repositioned so that it flexes the thumb of a paralyzed hand [Fig. 1]. With this exchange, no appreciable elbow flexion is lost, but the patient is now able to perform a pinch – a critical function to be sure. While these tendon transfer procedures may provide some degree of functional improvement in as many as 70% of the patients with tetraplegia (Khalifeh et al., 2019a, Khalifeh et al., 2019b), they can be somewhat disfiguring, the movement can be unnatural - altering the biomechanics of the limb, and an extended period of immobilization is typically required post-operatively. Such immobilization makes a patient with limited independence become essentially totally dependent for a period of time, which is a primary reason many patients do not opt for these procedures (Brown, 2012).
Nerve transfers employ a similar concept to that of tendon transfers. Instead of moving muscles, a nerve that has retained volitional control is cut and sutured to a nerve that has lost control due to injury [Fig. 2]. The axons from the source nerve then grow and supply the formerly paralyzed muscle, restoring its control. In this case, the original muscle “awakens” to accomplish its original function, restoring essentially normal biomechanics. The “cue” to drive that movement has changed. That is, early on a patient must attempt to perform the action of the “donor nerve” to drive the recovered movement in the target muscle. With practice and plasticity, over time the function becomes relatively normally incorporated. For example, a common nerve transfer used in patients with tetraplegia to restore finger extension is to cut the radial nerve branches that innervate the supinator muscle and suture them to the posterior interosseous nerve which provides finger extension. When these supinator axons reach the finger extensor muscles, the patient will initially have to try to supinate the wrist (rotating the palm towards the ceiling) in order to achieve hand opening. Over time and with practice, central plasticity results in this “supination cue” no longer being required and the movement becomes more natural – that is, eventually the patient simply thinks “open hand” in order to achieve that function.
When the spinal cord is injured, three segments result: the region of the cord that is subjected to the injury – the injured metamere (IM); the normal region rostral to this – the supralesional segment (SLS); and the lesion inferior to this – the infralesional segment(ILS) (Brown, 2012) [Fig. 3]. The IM is the site of direct cord injury and typically includes destruction of the local grey matter, which invariably includes the soma of the spinal lower motor neurons (SMNs) and, consequently, their associated axons within the peripheral nerves that emanate from that segment. Loss of these peripheral axons results in denervation of the target muscle at that level. The consequences of this are underrecognized, but result in a lower motor neuron injury with associated atrophy, fatty degeneration and eventual loss of muscle integrity of those muscles that were the target of that spinal motor neuron (Jonsson et al., 2013; Mandeville et al., 2017). In contrast to this, the ILS has lost volitional control via disconnection from the upper motor neurons (UMNs), but the SMNs within this segment continue to innervate target muscle, thereby maintaining the muscle's integrity and potential for recovery even years later. In a motor complete SCI, the paralyzed muscles of the ILS typically have tone, retained reflexes, and may exhibit “spasms”, but they have no volitional control. It is these axons which, while not providing any volitional control, maintain the distal nerve and muscle integrity. This is what allows for nerve transfers to still be an option years later.
As discussed above, at the IM loss of the SMN soma and associated peripheral axons from the injury site results in a limited time window for recovery of those muscle targets, as degeneration and fibrosis of the distal associated peripheral nerve and muscle will ensue. After this transpires, sending new axons to these targets is typically unsuccessful and movement cannot be restored to these muscles. In the IM, the denervation begins at the time of initial injury, and nerve transfer should be performed within a year to salvage the distal targets, with earlier intervention providing more robust results. As a result, pre-operative planning in patients with tetraplegia requires delineation of the extent and severity of SMN injury contributing to the arm and hand paralysis. If it is extensive and severe, SLS nerves should be transferred to the axon-depleted nerves of the IM region during the window of opportunity in order to recover these targets. After that time has transpired, though, the opportunity to recover these muscles is lost. In contrast, because their targets have axons present (though non-functional), ILS muscles can be recovered with a nerve transfer even very late following the original injury – even decades. In this case, the ILS axons that are only providing tone and spasticity to the paralyzed muscles of the infralesional segment are essentially exchanged for functional and cortical-controlled axons from the SLS via nerve transfer [Fig. 4].
Section snippets
Restorative options for the upper extremity
Both tendon and nerve transfers utilize spared volitionally controlled yet redundant muscles that are of sufficient strength for reassignment to a new, more desired function. Nerve transfers, however, offer distinct advantages over tendon transfers [Table 1]. Some requirements for ideal tendon transfers are a functioning muscle which is immediately adjacent to the missing muscle which, when repositioned, can provide a straight line of pull to the target tendons. With tendon transfers, muscle
Nerve transfers for lower body
Unlike the environment provided by the upper extremity where nerve branches from different root levels are in close proximity, in the lower extremity there are many fewer branches and much longer distances to navigate, making devising good nerve transfers challenging. There are two primary goals to be considered in the patient regarding lower body control: ambulation and bowel/bladder control. While the former has received the most media attention, the latter is consistently rated as a higher
Preservation of distal nerve targets
Degeneration of the distal nerve and muscle due to denervation presents a major barrier for recovery of lower spine lesions of the conus or cauda equina. Even if we could find an adequate axon source to recover the lower extremities via nerve transfers, simply performing the transfer at the required proximal location near the lumbrosacral root origin would render the ultimate result less than optimal given the distance required for these axons to travel. This distance would be measured in feet,
Conclusion
Nerve transfers have evolved to become a powerful intervention for functional restoration following cervical cord injury (Brown et al., 2017). Key principles that result in an effective nerve transfer have been developed through successful implementation in peripheral nerve and brachial plexus repair and have now been demonstrated to also be effective when applied to persons with SCI. The key features of a successful nerve repair: the repair is in close proximity to the target muscle, a pure
Declaration of Competing Interest
There are no competing interests to disclose.
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