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