Updated: 6/12/2020

Peripheral Nerve Injury & Repair

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Introduction
  • Overview
    • peripheral nerve injuries encompass a range of reversible and irreversible impairments determined by injury level, axonal disruption, axon support structure damage, and time to treatment
      • treatment can involve observation, repair, tendon transfers or nerve grafting depending on the acuity, degree of injury, and mechanism of injury.
  • Epidemiology
    • incidence
      • major peripheral nerve injury sustained in 2% of patients with extremity trauma 
      • nerve injuries account for approximately 3% of injuries affecting the upper extremity and hand
    • demographics
      • males = females
    • risk factors
      • penetrating injuries
      • displaced fractures
  • Pathophysiology
    • mechanism 
      • stretching injury
        • 8% elongation will diminish nerve's microcirculation
        • 15% elongation will disrupt axons
        • examples
          • "stingers" refer to neurapraxia from brachial plexus stretch injury
          • suprascapular nerve stretching injuries in volleyball players
          • correction of valgus in TKA leading to common peroneal nerve palsy
      • compression/crush
        • fibers are deformed
          • local ischemia
          • increased vascular permeability
        • endoneurial edema leads to poor axonal transport and nerve dysfunction
        • fibroblasts invade if compression persists
          • scar impairs fascicular gliding
        • chronic compression leads to Schwann cell proliferation and apoptosis 
        • 30mm Hg can cause paresthesias
          • increased latencies
        • 60 mm Hg can cause complete block of conduction
      • laceration
        • sharp transections have a better prognosis than crush injuries
        • continuity of nerve disrupted
          • ends retract
          • nerve stops producing neurotransmitters
          • nerve starts producing proteins for axonal regeneration
    • pathophysiology 
      • presynaptic terminal & depolarization
        • electrical impulse transmitted to other neurons or effector organs at presynaptic terminal
        • resting potential established from an unequal distribution of ions on either side of the neuron membrane (lipid bilayer)
        • action potential transmitted by depolarization of resting potential
        • caused by influx of Na across membrane through three types of Na channels
          • voltage gate channels
          • mechanically gated channels
          • chemical-transmitter gated channels
      • regeneration process after transection 
        • distal segment undergoes Wallerian degeneration (axoplasm and myelin are degraded by phagocytes)
        • existing Schwann cells proliferate and line endoneurial basement membrane
        • proximal budding (occurs after 1 month) leads to sprouting axons that migrate at 1mm/day to connect to the distal tube
      • variables affecting regeneration  
        • contact guidance with attraction to the basal lamina of the Schwann cell
        • neurotropism
        • neurotrophic factors (factors enhancing growth and preferential attraction to other nerves rather than other tissues)
      • functional recovery during regeneration (in order)
        • sympathetic activity
        • pain
        • temperature sensation
        • touch
        • proprioception
        • motor function
        • motor function is the first to be lost and the last to recover 
    • pathobiology
      • Schwann cells proliferate and trophic factors are upregulated to promote regeneration
    • pathoanatomy
      • involvement of the axon, myelin, and supporting connective tissues influence regeneration potential
        • myelin disruption typically occurs before axon disruption 
        • axonal disruption leads to distal degeneration, requiring regeneration or repair to regain function
          • neuronal connective tissue structure provides a framework for regeneration 
            • endoneurium
            • perineurium
            • epineurium
  • Associated conditions
    • predictable nerve injuries arise from certain fracture patterns and clinical scenarios 
      • axillary nerve
        • anterior shoulder dislocation 
      • radial nerve
        • distal 1/3 humeral shaft (Holstein-Lewis) fractures  
        • prolonged compression along the humerus while intoxicated (Saturday night palsy)
        • extension-type supracondylar humerus fracture 
      • ulnar nerve
        • distal humerus ORIF
        • improper positioning on OR table
        • flexion-type supracondylar humerus fracture
      • anterior interosseus nerve 
        • extension-type supracondylar humerus fracture 
      • sciatic nerve
        • posterior hip dislocation 
      • common peroneal nerve 
        • correction of valgus alignment during a total knee arthroplasty 
      • superficial peroneal nerve
        • percutaneous plating of tibial fractures (holes 11-13) 
  • Prognosis  
    • natural history of disease
      • pain is first modality to return
      • advancing Tinel sign is most reliable indication of recovery
      • nerve repair or reconstruction is unpredictable after 6 months
        • reinnervation by 18 months is the goal for muscle preservation
    • prognostic variables
      • favorable 
        • younger age 
          • most important factor influencing success of nerve recovery (children have more favorable prognosis)
        • distal level of injury 
          • second most important (the more distal the injury the better the chance of recovery)
          • peripheral nerve injuries include those affecting the Brachial Plexus 
        • sharp transections and stretch injuries
          • have better prognosis than crush or blast injuries
      • negative
        • older age
        • proximal level of injury
        • crush injuries
        • repair delay 
          • worse prognosis of recovery (time limit for repair is 18 months
    • prognosis with treatment 
      • variable on several factors including injury location, age of patient, and type of injury
        • neurapraxia resolves with conservative measures
        • axonotmesis and neurotmesis may improve with repair, tendon transfers, and/or nerve transfers
        • the endoneurium must be intact for full recovery of an injured peripheral nerve 
        • may lead to chronic neuropathic pain
Anatomy
  • Blood supply
    • extrinsic vessels
      • run in loose connective tissue surrounding nerve trunk
    • intrinsic vessels
      • plexus lies in epineurium, perineurium, and endoneurium 
  • Nerve structure   
    • epineural sheath
      • surrounds peripheral nerve 
    • epineurium
      • surrounds a group of fascicles to form peripheral nerve
      • functions to cushion fascicles against external pressure 
    • perineurium
      • connective tissue covering individual fascicles
      • primary source of tensile strength and elasticity of a peripheral nerve 
      • provides extension of the blood-brain barrier
      • provides a connective tissue sheath around each nerve fascicle
    • fascicles
      • a group of axons and surrounding endoneurium
    • endoneurium
      • loose fibrous tissue covering axons
      • participates in the formation of Schwann cell tube
    • myelin
      • made by Schwann cells
      • insulates axons to increase conduction velocity
        • conduction occurs at nodes of Ranvier
    • neuron cell
      • cell body - the metabolic center that makes up < 10% of cell mass
      • axon - primary conducting vehicle
      • dendrites - thin branching processes that receive input from surrounding nerve cells
    • Nerve fiber types
Fiber Type
Diameter (uM)
Myelination
Speed
Example
A
10-20
heavy
fast
touch
B
< 3
moderate
medium
ANS
C
< 1.3
none
slow
pain

 

Classification
  • Seddon Classification
    • neurapraxia 
      • same as Sunderland 1st degree, "focal nerve compression"
      • nerve contusion or stretch leading to reversible conduction block without Wallerian degeneration
      • pathophysiology
        • usually caused by local ischemia
        • histopathology shows focal temporary demyelination of the axon (axon remains intact)
        • endoneurium remains intact
      • electrophysiologic studies
        • nerve conduction velocity slowing or a complete conduction block
        • no fibrillation potentials 
      • prognosis
        • recovery prognosis is excellent
    • axonotmesis 
      • same as Sunderland 2nd-4th degree
      • incomplete nerve injury more severe than neurapraxia
      • pathophysiology
        • axon and myelin sheath disruption leads to focal conduction block with Wallerian degeneration 
        • variable degree of connective tissue disruption
      • electrophysiologic studies
        • fibrillations and positive sharp waves on EMG
      • prognosis
        • unpredictable recovery
    • neurotmesis
      • encompasses Sunderland 5th degree
      • complete nerve division with disruption of endoneurium
      • pathophysiology
        • all connective tissues disrupted
        • focal conduction block with Wallerian degeneration
      • electrophysiologic studies
        • fibrillations and positive sharp waves on EMG
      • prognosis
        • no recovery unless surgical repair performed 
        • neuroma formation at proximal nerve end may lead to chronic pain
Seddon Type
Degree
Myelin Intact
Axon Intact
Endoneurim Intact
Wallerian Degen.
Reversible
Neurapraxia
1st
No
Yes
Yes
No
Reversible
Axonotmesis
2nd-4th
No
No
Variable
Yes
Variable
Neurotmesis
5th
No
No
No
Yes
Irreversible
  • Sunderland Classification
    • 1st degree
      • same as Seddon's neurapraxia
    • 2nd degree
      • included within Seddon's axonotmesis
      • intact endoneurium, perineurium and epineurium
    • 3rd degree 
      • included within Seddon's axonotmesis
      • endoneurium injured with endoneurial scarring
      • intact perineurium and epineurium
      • most variable degree of recovery
    • 4th degree
      • included within Seddon's axonotmesis
      • endoneurium and perineurium injured
      • intact epineurium
      • nerve in continuity but at the level of injury there is complete scarring across the nerve
      • unsatisfactory regeneration
      • may lead to neuroma-in-continuity
    • 5th degree
      • same as Seddon's neurotmesis
      • completely severed or transected nerve involving all layers
      • regeneration not possible without repair

Sunderland Grade
Myelin Sheath
Axon
Endoneurim
Perineurium
Epineurium
I
Disrupted
Intact Intact
Intact
Intact
II
Disrupted
Disrupted
Intact
Intact
Intact
III
Disrupted
Disrupted
Disrupted
Intact
Intact
IV Disrupted
Disrupted Disrupted Disrupted Intact
V Disrupted Disrupted Disrupted Disrupted Disrupted
 
Studies
  • Nerve conduction studies 
    • Electromyography (EMG)
    • Nerve conduction velocity (NCV)
  • EMG
    • assesses function at the neuromuscular junction
    • often the only objective evidence of a compressive neuropathy (valuable in workers' compensation patients with secondary gain issues)
    • characteristic findings
      • denervation of muscle
        • fibrillations
        • positive sharp waves (PSW)
        • fasciculations
      • neurogenic lesions
        • fasciculations
        • myokymic potentials
      • myopathies
        • complex repetitive discharges
        • myotonic discharges
  • NCV 
    • assesses large myelinated fibers
    • focal compression and demyelination leads to
      • increase latencies (slowing) of NCV
        • distal sensory latency of > 3.2 ms are abnormal for CTS
        • motor latencies > 4.3 ms are abnormal for CTS
      • decreased conduction velocities less specific that latencies
        • velocity of < 52 m/sec is abnormal
      • motor action potential (MAP) decreases in amplitude 
      • sensory nerve action potential (SNAP) decreases in amplitude
Treatment
  • Nonoperative
    • observation with sequential EMG
      • indications
        • neuropraxia (1st degree)
        • axonotmesis (2nd degree)
        • gunshot wounds affecting brachial plexus
          • assess extent of recovery over 3 months
      • outcomes 
        • variable recovery depending on degree of injury
        • most nerve deficits that present after a closed fracture or dislocation will resolve with observation alone
  • Operative 
    • direct muscular neurotization
      • indications
        • transected unrepairable nerve ending at risk of forming neuroma
        • plan for integrated prosthesis
      • outcomes 
        • degree of functional recovery varies
        • decreases neuroma formation
        • promising results with targeted muscle reinnervation (TMR) for amputees
    • surgical repair
      • indications
        • neurotmesis (3rd-5th degree)
        • early surgical exploration: penetrating trauma, iatrogenic injury, vascular injury, progressive deficits
          • exception: gunshot wounds affecting brachial plexus may be observed
        • 1-3 weeks after gunshot injury with confirmed neurotmesis 
          • allows time for zone of injury to be declared
      • outcomes
        • variable and dependent on multiple factors (i.e., patient age, level of injury, type of injury, time to repair, etc.) 
          • fascicular repair outcomes are similar to epineurial repair
          • best recovery when performed within 7-14 days of injury
        • reinnervation and sensory re-education may take several years
    • nerve grafting
      • indications
        • gaps that prevent tension-free direct repair
      • outcomes 
        • variable and dependent on multiple factors (i.e., patient age, level of injury, type of injury, time to repair, etc.)
        • quality of nerve recovery drops with gaps >5mm
    • nerve transfer
      • indications
        • proximal nerve injury
          • goal to deliver new axons and stimulus before degeneration of motor endplates and irreversible muscle damage
          • priority is to restore shoulder abduction/external rotation, elbow flexion, and finger function
        • loss of shoulder abduction and external rotation
          • spinal accessory nerve (CN XI) to suprascapular nerve
        • loss of shoulder abduction and flexion
          • Leechavengvong procedure: triceps motor branch of radial nerve to axillary nerve
        • loss of elbow flexion
          • Oberlin transfer: FCU motor branch to upper trunk/musculocutaneous nerve
      • outcomes
        • potentially similar outcomes as tendon transfer for irreparable proximal nerve injuries
    • tendon transfer   
      • indications
        • return of function through nerve regeneration is not expected 
      • outcomes 
        • better with age <30 and more distal locations due 
        • improved in children due to neuroplasticity
        • one grade of motor strength loss is expected following transfer
Techniques
  • Observation with sequential EMG
    • technique
      • 'active surveillance' daily or weekly by the same surgeon
        • exploration indicated if no functional recover after 3 months
      • functional splinting
      • rehabilitation focusing on sensory reeducation and prevention of joint contracture
  • Direct muscular neurotization
    • technique
      • insert proximal nerve stump into nearby muscle belly
  • Surgical repair
    • Epineurial repair 
      • approach
        • primary repair of the epineurium 
        • requires resection of proximal neuroma and distal glioma to healthy fascicles
        • alignment aided by epineurial blood vessels
      • technique
        • resect zone of injury until "mushrooming" of the fascicles is observed
        • repair should be tension free in well-vascularized wound bed
          • tensioned closures compromise perfusion; inhibit Schwann cell activation and regeneration; and cause scar formation
        • length can be gained with nerve transposition and neurolysis
    • Fascicular repair
      • approach
        • similar to epineural repair, but also repair the perineural sheaths (individual fascicles are approximated under a microscope)
          • theoretically provides more accurate alignment of axons over epineurial repair
      • technique
        • fascicular matching
          • topographical sketches can be used for visual alignment
          • electrical stimulation 
            • proximal end: identifies sensory fascicles in awake patients 
            • distal end: identifies motor fascicles in acute injuries, before significant Wallerian degeneration
          • histologic staining
      • complications
        • potentially increased scarring and damage to blood supply 
  • Nerve grafting post
    • approach
      • create tension-free repair by using a graft that is at least 10% longer than gap 
      • ensure scar from nerve ends is completely resected
    • technique
      • autologous graft
        • gold standard for segmental defects > 5cm   
        • nerve autographs harvested should result in the least morbidity possible
          • medial and lateral antebrachial cutaneous 
          • posterior interosseus nerve terminal branches
          • sural
        • "cabling" used to create longer graft by connecting nerves in series
      • acellular allograft
        • traditionally used for gaps <5cm
        • not as effective as autograft, but have shown promise for large defects unable to be bridged by autograft alone
      • conduits
        • defects up to 20 mm
          • allow coaptation ends without tension, typically small sensory nerves
          • synthetic polyglycolic acid, polycaprolactone, and collagen-based
          • collagen conduits allow nutrient exchange and accessibility to neurotrophic factors to the axonal growth zone during regeneration
    • complications
      • donor nerve neuroma formation
      • immune response and rejection of allograft
  • Nerve transfer 
    • approach
      • redundant or non-essential nerve transferred to a nerve affected by a proximal injury 
      • select donor motor nerves close to target muscles 
    • technique
      • coaptation techniques
        • end-to-end
        • end-to-side
          • donor nerve attached to the recipient nerve through perineurial window
          • goal to "supercharge" damaged nerve by preservation of motor endplates until new axons can regenerate from more proximal injury
  • Tendon transfer
    • approach
      • maintain or restore passive joint mobility before tendon transfer
      • redundant or non-essential muscle-tendon unit transferred to restore a lost function 
      • optimal to have one straight line of pull and transfer of muscle synergistic to lost function
      • one tendon transfer should perform one function
    • technique
      • select donor and recipient with similar power 
        • power determined by cross-sectional area
      • select synergistic donor and recipient 
        • i.e. wrist extensors and finger flexors
      • set appropriate excursion
        • can be adjusted with pulley or tenodesis effect
        • Smith 3-5-7 rule
          • 3 cm excursion - wrist flexors, wrist extensors
          • 5 cm excursion - EDC, FPL, EPL
          • 7 cm excursion - FDS, FDP
    • complications
      • adhesions, poor tendon gliding
Complications
  • Neuroma formation
    • incidence
      • true incidence unknown due to most being asymptomatic
      • up to 30% in amputees has been reported
    • treatment
      • non-operative
        • pharmacolgical (i.e., gabapentin, anticonvulsants, antidepressants, etc.)
        • local nerve distruction (i.e., injection of phenol or botulinum toxin, cautery, etc.)
        • rehabilitation 
        • work modification
      • operative
        • resection
        • targeted muscle reinnervation (TMR)
 

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Questions (15)
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(OBQ13.9) Figure A shows a traumatic laceration of the distal forearm with a 5cm segmental median nerve defect. Which of the following repair or reconstruction techniques would allow for the best recovery of motor function? Review Topic | Tested Concept

QID: 4644
FIGURES:
1

Autogenous venous nerve conduit

4%

(141/3931)

2

Collegen synthetic nerve conduit

9%

(359/3931)

3

Biodegradable polyglycolic acid

1%

(25/3931)

4

Processed nerve allograft

3%

(99/3931)

5

Nerve autograft

84%

(3285/3931)

L 2 B

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(OBQ13.24) Which statement most accurately describes the physiology of peripheral nerve regeneration following an axonotmesic lesion? Review Topic | Tested Concept

QID: 4659
1

The proximal nerve segment undergoes Wallerian degeneration

15%

(736/5075)

2

Axon growth occurs from the distal segment to proximal segment

3%

(168/5075)

3

Neurotrophic factors direct phagocytic activity

7%

(330/5075)

4

Proximal axon budding allows for antegrade (or distal) axon migration

70%

(3549/5075)

5

Axoplasm and myelin are degraded distally predominantly by Schwann cells for the first 12 months following injury

5%

(261/5075)

L 3 B

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(OBQ12.210) A 55-year-old male laborer comes in with a chief complaint of clumsiness with his right hand for the past 3 months including difficulty using a hammer while at work. He has had no injury to the right upper extremity. On physical examination, he has persistent small finger abduction/extension with finger extension and active adduction. An EMG is performed and demonstrates ulnar nerve conduction velocities of 31 m/sec (normal >52m/sec). The patient symptoms are most accurately described as: Review Topic | Tested Concept

QID: 4570
1

Axonotmesis with ischemia origin

11%

(507/4499)

2

Axonotmesis with myelin disruption

18%

(800/4499)

3

Neurapraxia with ischemia origin

57%

(2565/4499)

4

Neurapraxia with endoneurium disruption

11%

(502/4499)

5

Neurotmesis

2%

(83/4499)

L 4 B

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(OBQ12.46) The patient sustains the injury seen in Figure A from a gunshot injury. The physical exam is notable for lack of sensation in his fourth and fifth digits as well as a positive Froment's sign. Which of the following factors has not been shown to be a significant prognostic indicator of functional recovery following nerve repair? Review Topic | Tested Concept

QID: 4406
FIGURES:
1

Duration to time of repair

11%

(601/5253)

2

Repair level

7%

(377/5253)

3

Length of repair

9%

(480/5253)

4

Postoperative physical rehabilitation

25%

(1303/5253)

5

Type of autograft used

47%

(2461/5253)

L 4 C

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(OBQ09.268) You are seeing a 24-year-old male in the emergency room after he was involved in a knife fight. He has severed the common digital nerve to the index finger on his dominant hand, with an 8mm gap between nerve ends. In counseling him about repair, which of the following options is as good as autologous nerve grafting? Review Topic | Tested Concept

QID: 3081
1

Glycolide trimethylene carbonate conduit

5%

(130/2706)

2

Collagen conduit

61%

(1652/2706)

3

Silicone sleeve

6%

(174/2706)

4

Primary end-to-end repair

16%

(423/2706)

5

Polyglycolic acid conduit

12%

(319/2706)

L 3 C

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(OBQ08.30) Which of the following nerves has the most favorable regenerative potential in restoring motor function after a graft repair within half a year after being injured? Review Topic | Tested Concept

QID: 416
1

Median

23%

(654/2872)

2

Ulnar

10%

(277/2872)

3

Radial

60%

(1717/2872)

4

Tibial

4%

(103/2872)

5

Peroneal

4%

(107/2872)

L 3 C

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(OBQ05.66) Axon regeneration almost always occurs following a Sunderland second-degree nerve injury because which anatomic structure is not injured? Review Topic | Tested Concept

QID: 952
1

Epineurium

23%

(365/1574)

2

Endoneurium

52%

(818/1574)

3

Perineurium

10%

(156/1574)

4

Myelin sheath

10%

(163/1574)

5

Schwann cell

3%

(54/1574)

L 4 D

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(OBQ05.218) Vitamin B12 deficiency is a known cause of which the following? Review Topic | Tested Concept

QID: 1104
1

Inability to whistle

0%

(10/3247)

2

Peripheral sensory neuropathy

96%

(3123/3247)

3

Increased deep tendon reflexes

3%

(91/3247)

4

Urinary retention

0%

(4/3247)

5

Hydrophobia

0%

(5/3247)

L 1 D

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(OBQ04.257) Which of the following peripheral nerve structures functions to cushion the nerve against external pressure? Review Topic | Tested Concept

QID: 1362
1

Endoneurium

6%

(83/1277)

2

Fibronectin

2%

(22/1277)

3

N-cadherin

1%

(7/1277)

4

Epineurium

68%

(872/1277)

5

Perineurium

23%

(290/1277)

L 3 D

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(OBQ04.248) Which of the following structures are slowly adapting skin receptors that detect pressure, texture, and low frequency vibration and are best evaluated by static two-point discrimination? Review Topic | Tested Concept

QID: 1353
1

Meissner's corpuscles

18%

(208/1183)

2

Pacinian corpuscles

48%

(572/1183)

3

Merkel's receptor

27%

(318/1183)

4

Free nerve endings

2%

(20/1183)

5

Ruffini corpuscles

5%

(54/1183)

L 5 C

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