Summary Peripheral nerve injuries encompass a range of reversible and irreversible impairments determined by injury level, axonal disruption, and time to treatment. Diagnosis can be made based on clinical examination and confirmed with EMG/NCS. 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 Etiology Pathophysiology mechanism of injury 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) 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 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 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 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 < 3cm 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 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) 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