Peripheral nerve injury: Seddon, Sunderland, Wallerian degeneration and repair

Structure of a peripheral nerve

• Axons. Myelinated axons are wrapped by Schwann cells, one cell to each internode, with conduction jumping between the nodes of Ranvier (saltatory conduction). Unmyelinated C fibres travel in groups within a single Schwann cell.
• Endoneurium surrounds each axon and its Schwann cells.
• Perineurium surrounds each fascicle. It gives the nerve its tensile strength and forms the blood–nerve barrier.
• Epineurium surrounds the whole nerve and lies between fascicles (internal epineurium). It is the layer sutured in an epineurial repair.

Fibre size determines vulnerability. Compression and ischaemia affect large myelinated fibres first, so motor power, vibration and light touch go before pain and temperature. Local anaesthetics block small fibres first, so pain and autonomic function are lost before motor function.

Seddon and Sunderland

What happens after an axon is divided

• Distal to the injury: Wallerian degeneration. Within days the axon and its myelin break down. Macrophages clear the debris over the following weeks, and Schwann cells proliferate and line up as bands of Büngner, which guide regenerating axons.
• Proximal stump. Degeneration extends back to the next node of Ranvier. The cell body undergoes chromatolysis: it swells, its Nissl substance disperses and the nucleus moves to the periphery, as it switches to producing the proteins needed for regrowth.
• Regeneration. Sprouts with growth cones cross the gap, guided by Schwann cells and neurotrophic factors, and then advance at roughly 1 mm a day.
• The target organ. Denervated muscle atrophies and its motor end plates degenerate. After about 12–18 months, reinnervation no longer restores useful function. Sensory receptors tolerate a longer delay.
• Imperfect recovery. Axons may reach the wrong target, causing synkinesis, poor localisation and reduced two-point discrimination. Axons that escape the repair form a painful neuroma.

Assessment and investigations

• Clinical examination. Motor power on the MRC scale, sensation including two-point discrimination, and sweating: sympathetic fibres travel with the nerve, so denervated skin is dry. Repeated examination shows whether recovery is progressing.
• Tinel sign. Tapping over regenerating axons produces paraesthesia in the territory of the nerve. A sign that advances distally over successive weeks shows regeneration; one that stays at the level of injury suggests a neuroma.
• Nerve conduction studies. In neurapraxia, stimulation below the lesion still gives a normal response, and only conduction across the lesion is blocked. After an axonal injury the distal segment goes on conducting until Wallerian degeneration is complete, at about 10 days, so studies are usually delayed until then.
• Electromyography. Fibrillation potentials and positive sharp waves in denervated muscle appear at about two to three weeks. Small, polyphasic reinnervation potentials appear before any clinical recovery.
• Imaging. Ultrasound and MRI can show whether a nerve is in continuity.

Principles of management

• Closed injuries with a likely neurapraxia or axonotmesis are observed, with splintage and physiotherapy to keep joints supple, and repeated clinical and neurophysiological assessment. Failure of expected recovery prompts exploration.
• Clean, sharp division. Primary repair within days: a tension-free epineurial or group fascicular repair under magnification, aligning the fascicles using the surface vessels as a guide.
• Crush, blast or avulsion. Delayed repair at about three weeks, once the extent of the damaged segment is clear, with the nerve ends tagged at the first operation.
• A gap. An autologous nerve graft, most often the sural nerve, or a conduit for a short sensory gap. A repair under tension does badly.
• Late presentation or a proximal injury. Nerve transfers bring a nearby expendable motor nerve close to the target muscle; tendon transfers restore function once the muscle can no longer recover.
• Prognosis is better in children, with distal injuries, sharp mechanisms, short delays and pure motor or sensory nerves.

Classic injuries