biology of nerve injury and repair
TRANSCRIPT
![Page 1: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/1.jpg)
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
![Page 2: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/2.jpg)
Nerve Structure and Function
Nerves are living “electrical cables” connecting the limbs to the brain
![Page 3: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/3.jpg)
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
![Page 4: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/4.jpg)
Axons are arranged in FASCICLES
ENDONEURIUM
PERINEURIUM
EPINEURIUM- BLOOD VESSELS- NERVI NERVORUMsensation to nerve trunk
GLIDING PLANEbetween nerve trunk and surrounding tissues
Nerve Trunk
![Page 5: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/5.jpg)
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
![Page 6: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/6.jpg)
Nerve Injuries
![Page 7: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/7.jpg)
Crush injury
Sharp laceration
Traction injury
MECHANISM OF INJURY
![Page 8: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/8.jpg)
Avulsion injury – CANNOT REPAIR, CANNOT REGENERATE!
![Page 9: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/9.jpg)
Bonney/Birch Non-degenerative Degenerative
![Page 10: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/10.jpg)
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
![Page 11: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/11.jpg)
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
![Page 12: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/12.jpg)
Neurotropism
Nerve
Nerve
Tendon
Neurotropic factors from cut end
Lundborg
Axons prefer to regenerate towards distal cut end of nerve
![Page 13: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/13.jpg)
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
![Page 14: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/14.jpg)
“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
![Page 15: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/15.jpg)
3 months post-lacerationConstant Tinel’s median nerve distributionVery tender
![Page 16: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/16.jpg)
Cortical reorganisation
Apoptosis of cell bodies in spinal cord
Degeneration of end-organs
Effects of Peripheral Nerve Injury
![Page 17: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/17.jpg)
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
![Page 18: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/18.jpg)
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
![Page 19: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/19.jpg)
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!
![Page 20: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/20.jpg)
Loss of sweating dry and scaling Skin atrophy ulceration
Degeneration of denervated skin
CPN repair 9 months
CPN repair 12 months
![Page 21: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/21.jpg)
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.
![Page 22: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/22.jpg)
• 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
![Page 23: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/23.jpg)
Types of nerve repair
![Page 24: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/24.jpg)
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
![Page 25: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/25.jpg)
Overcoming Tension
Narrow the Gap◦ Mobilise nerve◦ Transpose nerve◦ Position joints
Bridge the Gap◦ Nerve graft◦ Nerve conduit
Bypass the Gap – distal nerve transfer
![Page 26: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/26.jpg)
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
![Page 27: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/27.jpg)
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
![Page 28: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/28.jpg)
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
![Page 29: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/29.jpg)
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)
![Page 30: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/30.jpg)
Regeneration across different conduits
![Page 31: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/31.jpg)
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
![Page 32: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/32.jpg)
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
![Page 33: Biology of nerve injury and repair](https://reader035.vdocuments.mx/reader035/viewer/2022062903/58ed21721a28abea708b457d/html5/thumbnails/33.jpg)
Thank You
Recommended reading:Birch R. Surgical Disorders of the Peripheral Nerves, 2nd Edition. 2011Lundborg G. Nerve Injury and Repair, 2nd Edition. 2004