Structure
A peripheral nerve contains axons supported by connective-tissue layers:
- endoneurium surrounds individual axons
- perineurium surrounds fascicles
- epineurium surrounds the whole nerve
Schwann cells form myelin around many peripheral axons.
A peripheral nerve contains axons surrounded by Schwann cells. Individual fibres lie within endoneurium, fascicles are enclosed by perineurium and the whole nerve is invested by epineurium. The perineurium contributes importantly to the blood-nerve barrier and maintenance of the intrafascicular environment.
The nerve receives a longitudinal and segmental vascular supply. Excessive circumferential dissection can therefore compromise blood supply even when gross continuity is preserved.
Action potential
The resting membrane potential is maintained by selective membrane permeability and ion gradients. Depolarisation opens voltage-gated sodium channels; repolarisation is mainly driven by potassium efflux.
Myelin allows saltatory conduction between nodes of Ranvier and markedly increases conduction velocity.
Seddon classification
- neurapraxia: conduction block without axonal discontinuity
- axonotmesis: axon disrupted but supporting connective-tissue pathways are variably preserved
- neurotmesis: complete disruption of the nerve
Sunderland classification
- Grade I: neurapraxia
- Grade II: axon disrupted; endoneurium intact
- Grade III: axon and endoneurium disrupted; perineurium intact
- Grade IV: fascicular architecture disrupted; epineurium remains
- Grade V: complete nerve transection
- a mixed lesion may contain different grades within the same nerve
Wallerian degeneration
After significant axonal injury, the distal axon degenerates. Schwann cells and macrophages clear debris. Schwann cells proliferate and align within the distal nerve pathway, creating a favourable route for regenerating axons when the architecture is preserved.
After axonal interruption, the distal axon degenerates. Schwann cells and macrophages clear debris. Proximally, the neuron mounts a regenerative response. Schwann cells align within the distal pathways and provide trophic support for advancing axonal sprouts.
Axonal regeneration is often quoted at roughly a millimetre per day, but functional recovery is influenced by:
- injury level
- age
- gap length
- scarring
- quality of repair
- target distance
- motor end-plate survival
- misdirection of regenerating axons
Regeneration
Axonal sprouts arise from the proximal segment. A commonly used clinical estimate for regeneration is about 1 mm/day, but functional recovery also depends on:
- injury level
- age
- distance to target muscle
- scar and gap
- accuracy of axonal guidance
- duration of denervation
Nerve conduction studies
Nerve conduction studies assess:
- latency
- conduction velocity
- amplitude
Demyelinating lesions tend to slow conduction or prolong latency. Axonal loss more often reduces response amplitude.
Electromyography
EMG evaluates electrical activity in muscle. Denervation and reinnervation produce characteristic changes that develop over time, so the timing of the test matters.
Tinel sign
A progressing Tinel sign may indicate axonal regeneration along a nerve but is not a complete measure of recovery.
Clinical principles
- neurapraxia usually recovers without axonal regeneration
- higher Sunderland grades have progressively worse spontaneous recovery
- prolonged denervation reduces the potential for useful motor recovery
- examination and serial clinical progress remain essential; electrodiagnostic tests are adjuncts
Myelination and conduction
Myelinated axons conduct rapidly by saltatory conduction between nodes of Ranvier. Larger-diameter, heavily myelinated fibres generally conduct faster. Unmyelinated fibres conduct more slowly.
Schwann cells provide myelin in the peripheral nervous system and play a central role in regeneration after axonal injury.
Injury classification
Seddon described:
- neurapraxia: conduction block without axonal discontinuity
- axonotmesis: axonal disruption with variable preservation of connective-tissue pathways
- neurotmesis: complete structural disruption
Sunderland expanded the classification according to which supporting layers remain intact. This is clinically useful because preservation of endoneurial tubes greatly improves the precision of axonal regeneration.
Nerve repair
The aims of repair are to restore continuity with:
- accurate fascicular alignment where possible
- minimal tension
- atraumatic handling
- good vascularity
- limited foreign material
A direct repair is preferred when a tension-free coaptation is possible. A gap that cannot be closed without harmful tension usually requires grafting or another reconstructive strategy. Nerve transfers can shorten the distance to the target by connecting an expendable donor fascicle or nerve to a denervated recipient.
Compression neuropathy
Compression impairs intraneural blood flow and axonal transport before causing structural axonal damage. Symptoms can therefore be intermittent early and become persistent with more advanced disease.
Double-crush concepts are often discussed, but symptoms should still be localised clinically and electrophysiologically rather than assumed to arise from multiple lesions.
Clinical assessment
Document:
- sensory territory
- motor power using a consistent grading system
- autonomic/trophic change
- provocative signs
- two-point discrimination where relevant
- progression over time
Tinel's sign may advance distally during regeneration but is not a substitute for objective return of motor or sensory function.
Electrophysiology
Nerve-conduction studies assess conduction across segments of nerve. Electromyography assesses muscle denervation and reinnervation. Very early studies after acute axonal injury may not yet show the full extent of denervation because Wallerian degeneration takes time.
FRCS synthesis
The key relationship is structure preserved → better guidance for regeneration. Classification is not an academic list; it predicts the biological pathway available for recovery and therefore influences observation versus exploration and reconstruction.