A 47-year-old man presented several years after sustaining a traumatic transfemoral amputation of the left lower extremity and subsequent above-knee revision amputation. He reports intense neuropathic pain that emanates from a consistent location along the posterior aspect of his left residual thigh. Direct pressure over this specific point exacerbates his symptoms and as a result the patient has considerable difficulty wearing his prosthesis to ambulate. Upon exploration, a large-end neuroma involving the distal sciatic nerve was discovered (▶Fig. 26.1).
After a peripheral nerve is severed (neurotmesis), Wallerian degeneration occurs distal to the site of injury, followed by axonal sprouting and elongation that is guided by a multitude of local neurotrophic factors. When the distal end of the severed peripheral nerve is available, the optimal intervention is to perform end-to-end neurorrhaphy in order to allow the regenerating axons to reestablish contact with the distal nerve segment. However, in the setting of amputation, the distal nerve segment is absent and consequently the regenerating axons are prone to form an end neuroma consisting of a disorganized mass of axonal spouts, Schwann cells, fibroblasts, and capillaries. Symptomatic neuroma occurs in up to a third of patients with major limb amputation. In patients who experience traumatic amputation injury, the incidence of residual limb pain can be as high as 70%.
Although the experience of neuroma pain itself can be quite debilitating, a serious functional consequence of persistent pain in the residual limb is the inability to wear a prosthetic device. This leads to considerable limitations in a patient’s capacity to perform activities of daily living and a significantly decreased quality of life. As a result of neuroma pain, patients with a major upper extremity amputation frequently forego the functional advantages of an artificial limb and may not even tolerate a passive, cosmetic prosthesis. Those with a lower extremity amputation may suffer even more significant morbidity due to the loss of ambulation. Therefore, all patients with limb loss should be carefully evaluated for symptomatic neuromas. If present, the neuromas should be surgically addressed to allow the patient to comfortably wear a prosthesis.
Various nonsurgical therapies for neuroma pain have been described, including desensitization therapy, injection of the neuroma with chemicals that attempt to inhibit axonal regeneration, and numerous medications such as antidepressants, anticonvulsants, and narcotics. However, definitive treatment involves surgical exploration, excision of the neuroma bulb, and an effort to either to reduce the pain of a recurrent neuroma or to prevent the reformation of a recurrent neuroma. The most commonly performed option to address recurrent neuroma pain is to bury the end of the nerve into normal muscle tissue after neuroma excision. With this method, the end neuroma is expected to reform, but the muscle serves as a biological cushion that mitigates the incitement of painful neuroma symptoms.
More recently, investigation into novel strategies to control neuroprosthetic limbs has led to techniques that inhibit neuroma formation. These approaches prevent the development of a disorganized and hyperexcitable neuroma bulb by promoting guided axonal regeneration and subsequent reinnervation of denervated muscle. For example, targeted muscle reinnervation (TMR) is a method whereby a nerve transfer is performed to provide sprouting axons a distal target for reinnervation in order to prevent reformation of an end neuroma. After the neuroma bulb is excised from the symptomatic nerve, a specific recipient motor branch is selected and divided, which results in selective denervation of the target muscle. Coaptation is then performed between the proximal nerve (which formerly had the neuroma) and the distal recipient motor branch, allowing the axons to regenerate toward and subsequently reinnervate the denervated muscle.
The regenerative peripheral nerve interface (RPNI) is a novel strategy to prevent neuroma formation in transected peripheral nerves. The RPNI consists of a residual peripheral nerve that is implanted into a free skeletal muscle graft either at the time of limb amputation or after excision of a neuroma bulb (▶Fig. 26.2). Because the muscle fibers within the free graft are both nonvascularized and denervated, they will undergo a process of degeneration followed by regeneration and are subsequently reinnervated by the sprouting axons of the implanted nerve. In this manner, the RPNI encourages the formation of new neuromuscular junctions within the free muscle graft, thereby greatly reducing the number of aimless axons at the end of the nerve and reducing the chance of neuroma recurrence. Multiple RPNIs can be performed at the site of limb amputation using a piece of free muscle graft for each available peripheral nerve end.