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Updated: Dec 11 2024

Peripheral Nerve Injury & Repair

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  • Summary
    • Peripheral nerve injury is a relatively common condition that encompasses a range of reversible and irreversible impairments determined by injury level, axonal disruption, and time to treatment.
    • Diagnosis is typically clinical with a combination of known injury with a nerve deficit. Advanced imaging such as ultrasound or MRI may be used to characterize nerve morphology after injury; however, EMG/NCS is a mainstay of evaluating both nerve injury and nerve recovery. Surgical exploration is confirmatory for traumatic nerve injuries. 
    • Treatment may involve observation, primary repair, nerve reconstruction with grafting, tendon transfers, nerve transfers, or a combination thereof depending on acuity, degree of injury, nerve quality, and mechanism of injury.
  • Epidemiology
    • Incidence
      • 16.9 per 100,000 per year 
      • peripheral nerve injury sustained in 2.6% of upper extremity trauma and 1.2% of lower extremity trauma 
      • nerve injuries account for approximately 3% of injuries affecting the upper extremity and hand
    • Demographics
      • males (80%) >> females 
      • younger in age, average age of 32-39 
    • Risk factors
      • penetrating and/or high energy trauma
      • crush injuries
      • significantly displaced fractures
  • Etiology
    • Pathophysiology
      • mechanism of injury
        • stretching injury
          • 8% elongation will diminish nerve's microcirculation by 50% in rat sciatic nerve model 
            • 15% elongation will disrupt bloodflow by 80% in the same model
          • 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
          • prominent pins through anterior ulnar cortex in tension band construct for olecranon fixation
        • 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)
  • 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
        • autonomic nervous system (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 Classification
        • Seddon Type
        • Myelin intact
        • Endoneurium intact
        • Wallerian Degeneration
        • Reversible
        • Neuropraxia
        • No
        • Yes
        • No
        • Reversible
        • Axonotmesis
        • No
        • Variable
        • Yes
        • Variable
        • Neurotmesis
        • No
        • No
        • Yes
        • Irreversible
    • Sunderland Classification
      • 1st degree
        • same as Seddon's neurapraxia (loss of myelin sheath)
      • 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 Classification
          • Grade
          • Axon
          • Endoneurium 
          • Perineurium
          • Epineurium
          • I
          • Intact
          • Intact
          • Intact
          • Intact
          • II
          • Disrupted
          • Intact
          • Intact
          • Intact
          • III
          • Disrupted
          • Disrupted
          • Intact
          • Intact
          • IV
          • Disrupted
          • Disrupted
          • Disrupted
          • Intact
          • V
          • Disrupted
          • Disrupted
          • Disrupted
          • Disrupted
  • Imaging
    • Ultrasound (High-resolution ultrasound) 
      • Indication: neuropathy from entrapment/compression or trauma may help localize entrapment, nerve ends in lacerations, neuromas
      • Findings: may help localize entrapment, nerve ends in lacerations, neuromas
        • real time dynamic evaluation
        • better assessment of superficial nerves 
      • Compliments electrodiagnostic studies
    • MRI/MRN (Magnetic resonance neurography) 
      • Indication: traumatic nerve injury, particularly brachial plexus injuries
      • Findings: similar to ultrasound
        • better detection of muscle denervation
        • better as assessment of deeper structures
        • better static resolution than ultrasound
  • Studies
    • Electrodiagnostic 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)  and regenerative peripheral nerve interfaces (RPNI) 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
            • proximal injuries to the ulnar nerve may benefit from end-to-side transfer of the AIN to deep motor branch of ulnar nerve to improve early hand intrinsic function
          • Key motor nerve transfers
            • shoulder abduction and external rotation
              • spinal accessory nerve (CN XI) to suprascapular nerve
            • shoulder abduction and flexion
              • Leechavengvong procedure: medial triceps motor branch of radial nerve to axillary nerve
            • elbow flexion
              • Oberlin transfer: FCU motor branch of ulnar nerve to biceps brachii branch of musculocutaneous nerve
              • Double Oberlin transfer: Oberlin + redundant median nerve fascicle from FCR or FDS to brachialis branch of musculocutaneous nerve 
            • ulnar intrinsic function
              • AIN to ulnar motor "supercharge
          • Sensory transfers have also been described
        • outcomes
          • can vary widely based on patient demographics, mechanism of injury, time from injury, and status of motor endplates
          • success is defined as M3 motor or greater, with many patients achieving M4
          • advantage over tendon transfer is easier rehabilitation; no need for cortical reorganization  
      • tendon transfer
        • indications
          • return of function through nerve regeneration is not expected
        • Key tendon transfers
          • shoulder external rotation
            • lower trapezius to infraspinatus
          • elbow flexion
            • proximal advancement of flexor-pronator mass
            • pec major, latissimus dorsi, triceps, or trapezius muscle to biceps 
          • radial neuropathy
            • wrist extension: PT to ECRB
            • thumb extension/abduction: PL or FDS IV (ring) to EPL
              • when using FDS IV, you can split so one slip is in EPL and the other is in EIP for index finger extension
            • finger MCPJ extension: 
              • Jones: FCU to EDC
              • Brand: FCR to EDC
              • Boyes: FDS to EDC
          • median neuropathy 
            • thumb opposition: EIP to APB opponensplasty
            • thumb flexion: BR to FPL
            • index finger flexion: side-to-side FDP transfer
          • ulnar neuropathy
            • MPJ stabilization (determined by Bouvier test):
              • simple claw (positive Bouvier): zancolli lasso FDS around A1 pulleys
              • complex claw (negative Bouvier): extrinsic extensors unable to extend IPJ when MPJ flexed
                • FDS into lateral bands
                • FCR into lateral bands with intercalary grafting
            • ulnar sided finger flexion
              • side to side FDP transfer of ring and small fingers into FDP of median innervated FDP tendons
        • 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' weekly by the same surgeon
          • baseline EMG/NCS typically done at 3-4 weeks 
          • 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
      • 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
          • nerve autografts harvested should result in the least morbidity possible
            • medial and lateral antebrachial cutaneous
            • posterior interosseus nerve terminal branches
            • sural
          • cabling can be used for donor-recipient size mismatch
        • acellular/decellular allograft
          • provides a scaffold for the host Schwann cells to build upon 
          • shown to be effective for gaps up to 7cm
          • not as effective as autograft, but have shown promise for large defects unable to be bridged by autograft alone
        • conduits
          • made up of type 1 collagen
          • indications
            • defects up to 20 mm
              • rely on the formation of a fibrin clot formation to serve as a scaffold for host cell Schwann cells to build upon
              • 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
          • traditional end-to-side or reverse end-to-side
            • traditional: recipient, injured nerve distal stump is attached to donor nerve through perineurial window
            • reverse: donor nerve attached to the recipient, damaged 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
          • targeted muscle reinnervation (TMR)
          • regenerative peripheral nerve interface (RPNI)
  • 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
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What type of graft is typically used for defects <5cm?
    • acellular/decellular allograft
      • provides a scaffold for the host Schwann cells to build upon 
      • shown to be effective for gaps up to 7cm
      • not as effective as autograft, but have shown promise for large defects unable to be bridged by autograft alone

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