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Biology of Nerve Injury and Repair
Dr Andrew YamMBBS, MRCS, MMED(Surg), FAMS(Hand Surg)
Hand and Peripheral Nerve Surgeon, Hand Surgery Associates
Hand Surgery Associates www.handsurgerysingapore.com
Nerve Structure and Function
Nerves are living “electrical cables” connecting the limbs to the brain
NEURON
MOTOR NEURON SENSORY NEURON
CELL BODYIn spinal cord (motor neuron) or dorsal root ganglion (sensory neuron)
Communicates with neurons from the brain centres and spinal cord
Produces proteins for nerve function and regeneration
AXONIn the nerve trunks
Electrical signals to/from the end-organs
Axons are arranged in FASCICLES
ENDONEURIUM
PERINEURIUM
EPINEURIUM- BLOOD VESSELS- NERVI NERVORUMsensation to nerve trunk
GLIDING PLANEbetween nerve trunk and surrounding tissues
Nerve Trunk
Sensory◦ Eg, Digital nerves, superficial radial nerve
Motor◦ Eg, suprascapular nerve, posterior interosseous
nerve
Mixed sensory and motor◦ Eg, brachial plexus, ulnar nerve, median nerve,
high radial nerve
Types of Peripheral Nerve Trunks
Nerve Injuries
Crush injury
Sharp laceration
Traction injury
MECHANISM OF INJURY
Avulsion injury – CANNOT REPAIR, CANNOT REGENERATE!
Bonney/Birch Non-degenerative Degenerative
Wallerian Degeneration and Regeneration
Distal to injury – degeneration(up to 2 weeks to complete)
Cell body and axon proximal to injury- Regeneration 1-2 mm/day after degeneration complete
Growth cone from proximal stump attempts to find way to the end organ◦ 1-2 mm/day
Axonotmesis no gap most
axons reach target
Neurotmesis Gap misdirection, blockage by scar failure to reach target
Axonal Regeneration
Neurotropism
Neurotrophism
Neurotropism
Nerve
Nerve
Tendon
Neurotropic factors from cut end
Lundborg
Axons prefer to regenerate towards distal cut end of nerve
Neurotrophism
Motor Nerve
Motor Nerve
Sensory
Nerve
Motor axons growing toward a cut end of a motor fascicle will continue to grow and mature
Motor axons growing toward a cut end of a sensory fascicle will die back and disappear (pruning)
Different neurotrophic factors supporting growth of sensory and motor axons
Lundborg
“Pressure on an injured nerve trunk quite often produces a tingling sensation, felt by the patient at the periphery of the nerve and localized to a very precise area of the skin”
• Completely severed (neurotmesis) = constant location over time
• Regenerating axons (axonotmesis) = progressively moves towards the periphery along the nerve
• No regeneration (neurapraxia) = no tingling
Tinel’s SignAn important diagnostic and prognostic sign!
- J Tinel, 1915
Location of strongest Tinel’s sign and maximum tenderness
=Location of nerve injury
3 months post-lacerationConstant Tinel’s median nerve distributionVery tender
Cortical reorganisation
Apoptosis of cell bodies in spinal cord
Degeneration of end-organs
Effects of Peripheral Nerve Injury
Loss of sensory input results in cortical changes
Delay to reinnervation shrinking cortical representation
Reinnervation disorganised cortical representation almost always worse than original function
Cortical reorganisation
Lundborg, 2003
Apoptosis of cell bodies
Wiberg et al
Delay to repair
Cell body death
Worse outcome
Less regeneration
Increased apoptosis in younger patients and more proximal injury
Progressive muscle atrophy and degeneration over time- Replaced by fatty and fibrous tissues
- joint contractures- Permanent loss of muscle fibers over time
- poor function after reinnervation- Degeneration of motor end plates
- unable to reinnervate
Degeneration of denervated muscle
CONSISTENTLY SUCCESSFUL REINNERVATION ONLY WITHIN 12-18 MONTHS OF DENERVATION!
Loss of sweating dry and scaling Skin atrophy ulceration
Degeneration of denervated skin
CPN repair 9 months
CPN repair 12 months
Nerve RepairThe goals of nerve repair :Decrease and enclose the gap between nerve endsAllow primary healing with minimal scarringCreate a favourable environment for the regenerating nerve axon.
• Nerve healing across a gap = • Axonal regeneration (repair of the nerve cell)
• Axonal sprouting and growth cones• Branching and competition for targets• Guidance and misdirection
+
• Local wound healing (reconstitution of the nerve fiber)• “Intrinsic”
• Proliferation of endothelial cells, fibroblasts, Schwann cells from the stump epineurium reconstitute axonal tubes
• “Extrinsic”• Inflammation and migration of fibroblasts scar
Types of nerve repair
Effects of Tension on nerve repair
Axoguard brochure (Axogen, Inc)
TENSION IS BAD!!!Devascularisation and scarring at repair siteNeuropathic pain (possibly CRPS) post-repairPoorer outcome
Overcoming Tension
Narrow the Gap◦ Mobilise nerve◦ Transpose nerve◦ Position joints
Bridge the Gap◦ Nerve graft◦ Nerve conduit
Bypass the Gap – distal nerve transfer
Mobilisation, Transposition, Joint positioning
Free nerve ends from all tethering connective tissues
Create most direct line between stumps
Immobilise joints with minimal nerve tension until healed
Nerve graft Autograft
◦ “conventional”- <5-7cm- Well-vascularised bed- Many sources
◦ Vascularised- >7cm gap, poor bed
Allograft◦ Needs
immunosuppression
GRAFT/CONDUIT BETTER THAN DIRECT SUTURE UNDER TENSION
Conduit repair
Tube to enclose nerve ends without tension
For short gaps <20mm
Rely on native neurotropism and neurotrophism to align regenerating axons across a small gap
Interface (Journal of the Royal Society), 2011DOI: 10.1098/rsif.2011.0438
Types of conduit currently available
Vein
Hollow non-biological synthetic tubes(eg Neuragen, Chitosan, silicon tube)
Biological hollow synthetic tube(eg Axoguard)
Processed human nerve allograft (eg Avance)
Regeneration across different conduits
Ideal conduit properties (possible future conduits)
Intraluminal guidance mechanisms Factors supporting/enhancing regeneration
Interface (Journal of the Royal Society), 2011DOI: 10.1098/rsif.2011.0438
When distance for regeneration is too far to allow reinnervation before the target organ degenerates irreversibly
Transfer a healthy but expendable nerve to the distal stump of the injured nerve close to the target
Only 1/3 of the original number of motor axons are required for functional reinnervation
Nerve Transfer / Neurotisation -Bypassing very long gaps
AINUln motor branch
Thank You
Recommended reading:Birch R. Surgical Disorders of the Peripheral Nerves, 2nd Edition. 2011Lundborg G. Nerve Injury and Repair, 2nd Edition. 2004