At the end of the lecture the participant will be able to: 1. Understand the intracellular and extracellular processes that occur after a nerve injury, including Wallerian degeneration 2. Describe the classification of peripheral nerve injuries in relation to management and prognosis 3. Understand the physiology of nerve regeneration and its implication in modern nerve surgery including allografts and nerve conduits. 4. Describe the effects of peripheral nerve injury on distal structures (Motor and sensory end organs)

1. Dr Andrew Yam
MBBS, MRCS, MMED(Surg), FAMS(Hand Surg)
Hand and Peripheral Nerve Surgeon,
Hand Surgery Associates
Hand Surgery Associates
w w w . h a n d s u r g e r y s i n g a p o r e . c o m

2. Nerves are living “electrical cables”
connecting the limbs to the brain

3. NEURON
MOTOR NEURON SENSORY NEURON
CELL BODY
In 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
AXON
In the nerve trunks
Electrical signals to/from
the end-organs

4. Axons are arranged in
FASCICLES
ENDONEURIUM
PERINEURIUM
EPINEURIUM
- BLOOD VESSELS
- NERVI NERVORUM
sensation to nerve
trunk
GLIDING PLANE
between nerve trunk
and surrounding
tissues

5.  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

7. Crush injury
Sharp laceration
Traction injury
MECHANISM OF INJURY

8. Avulsion injury – CANNOT REPAIR, CANNOT REGENERATE!

9. Bonney/Birch Non-degenerative Degenerative

10. 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

11.  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
Neurotropism
Neurotrophism

12. Nerve
Neurotropic factors from cut end
Lundborg
Axons prefer to
regenerate towards
distal cut end of
nerve

13. Motor 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

14. “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
- J Tinel, 1915
Location of strongest Tinel’s sign and
maximum tenderness
=
Location of nerve injury

15. 3 months post-laceration
Constant Tinel’s median
nerve distribution
Very tender

16.  Cortical reorganisation
 Apoptosis of cell bodies in spinal cord
 Degeneration of end-organs

17.  Loss of sensory input
results in cortical
changes
 Delay to reinnervation
 shrinking cortical
representation
 Reinnervation
 disorganised
cortical representation
 almost always worse
than original
function
Lundborg, 2003

18. Wiberg et al
Delay to repair
Cell body death
Worse outcome
Less regeneration
Increased apoptosis in younger patients and
more proximal injury

19. 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
CONSISTENTLY SUCCESSFUL REINNERVATION ONLY WITHIN 12-18 MONTHS OF
DENERVATION!

20.  Loss of sweating  dry and scaling
 Skin atrophy  ulceration
CPN repair 9 months
CPN repair 12 months

21. The goals of nerve repair :
Decrease and enclose the gap between nerve
ends
Allow primary healing with minimal scarring
Create a favourable environment for the
regenerating nerve axon.

22. • 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

24. Axoguard brochure (Axogen, Inc)
TENSION IS BAD!!!
Devascularisation and scarring at repair
site
Neuropathic pain (possibly CRPS) post-
repair
Poorer outcome

25.  Narrow the Gap
◦ Mobilise nerve
◦ Transpose nerve
◦ Position joints
 Bridge the Gap
◦ Nerve graft
◦ Nerve conduit
Bypass the Gap – distal nerve transfer

26. Free nerve ends from all
tethering connective
tissues
Create most direct line
between stumps
Immobilise joints with
minimal nerve tension
until healed

27.  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

28. 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), 2011
DOI: 10.1098/rsif.2011.0438

29. Vein
Hollow non-biological synthetic tubes
(eg Neuragen, Chitosan, silicon tube)
Biological hollow synthetic tube
(eg Axoguard)
Processed human nerve allograft
(eg Avance)

31. Intraluminal guidance mechanisms
Factors supporting/enhancing
regeneration
Interface (Journal of the Royal Society), 2011
DOI: 10.1098/rsif.2011.0438

32.  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
AINUln motor branch

33. Recommended reading:
Birch R. Surgical Disorders of the Peripheral Nerves, 2nd Edition. 2011
Lundborg G. Nerve Injury and Repair, 2nd Edition. 2004