Types of Nerve Injury (Seddon's Classification)

1. Neuropraxia (Mildest form)

   • Endoneurium intact
   • Axon intact
   • Mild demyelination
   • Causes mild conduction block leading to temporary weakness and sensory loss
   • Complete, spontaneous recovery expected
   • Examples: Crutch palsy, Saturday night palsy, stingers (sports injuries)

2. Axonotmesis (Moderate injury)

   • Endoneurium intact
   • Axon damaged/severed
   • Moderate demyelination
   • Moderate conduction block with more significant motor and sensory loss
   • Good recovery possible without surgery
   • Examples: Closed fractures, shoulder dislocations

3. Neurotmesis (Severe injury)

   • Endoneurium damaged (possibly perineurium and epineurium too)
   • Axon severed
   • Severe demyelination
   • Severe conduction block
   • Poor recovery prognosis, typically requires surgical intervention
   • Examples: Open fractures, deep lacerations, gunshot wounds

Nerve regeneration in axonotmesis

First degeneration, then regeneration!

Wallerian Degeneration Process

1. Proximal Segment Changes:
   • Chromatolysis: Nucleus shifts to periphery, Nissl bodies disperse, cell body swells
   • Protein synthesis increases to support regeneration
   • Breakdown of myelin and Schwann cells from injury site to adjacent upstream node of Ranvier
2. Distal Segment Changes:
   • Breakdown of axonal membrane, myelin sheaths, and some Schwann cells, from injury site to the nerve ending.
   • Endoneurium releases chemicals (serotonin, histamine) attracting macrophages
   • Macrophages clear axonal and myelin debris
   • Schwann cells remain in the distal segment

Nerve Regeneration Process

1. Axonal sprouts form from proximal stump (within 24 hours)
2. Sprouts grow toward distal stump at approximately 1.5mm per day
3. Schwann cells cling to axonal sprouts and begin remyelination
4. Proximal and distal stumps eventually reconnect
5. Nucleus returns to center position in cell body
6. Nissl bodies return to normal distribution

Leads to central chromatolysis

• Definition: the reaction of a neuronal cell body in response to an axonal injury
• Function: increase in protein synthesis to help restore the integrity of the damaged axon
• Characteristics
  • Swelling of the neuronal body
  • Dispersion of the Nissl bodies (which gives the name chromatolysis (chroma: color; lysis: disintegration))
    • The rough endoplasmatic reticulum of neurons.
  • Displacement of the nucleus to the periphery

Results in Wallerian degeneration

• Definition: an active neuronal degeneration process in response to axonal injury
• Function
  • To clear axonal debris and prevent scarring
  • Facilitate targeted reinnervation and functional recovery of tissues previously innervated by that axon before injury
• Characteristics
  • Initially retained electrical excitability of axonal membrane distal to the injury, lasting up to 36 hours
  • Progressive degeneration of distal segment cytoskeleton with dissolution of axonal membrane
  • Degradation of residual myelin sheath by macrophages and Schwann cells
    • In the central nervous system, phagocytic macrophages/microglia are recruited more slowly because of the blood-brain barrier. This slows removal of the myelin debris, which can persist for years in the degenerating tracts and suppress axonal growth via myelin-associated inhibitory factors.
  • The proximal stump either stays in place or retracts slightly
  • Ultimately, the cell body will sprout regenerative nerve fibers that, ideally, reinnervate the distal tissues.
  • Regeneration is significantly more efficient in the peripheral nervous system than in the central nervous system.
  • Good chance of at least partial recovery