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Which statement most accurately describes the physiology of peripheral nerve regeneration following an axonotmesic lesion?
The proximal nerve segment undergoes Wallerian degeneration
Axon growth occurs from the distal segment to proximal segment
Neurotrophic factors direct phagocytic activity
Proximal axon budding allows for antegrade (or distal) axon migration
Axoplasm and myelin are degraded distally predominantly by Schwann cells for the first 12 months following injury
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Axonomesis is a disruption of the nerve axon following injury. Repair/regeneration of the nerve occurs via proximal budding, followed by antegrade (or distal) axon migration.
The peripheral nerve regeneration process begins with the distal segment undergoing Wallerian degeneration (axoplasm and myelin are degraded distally by phagocytes). Existing Schwann cells proliferate and line-up along the basement membrane. Proximal budding occurs after a one-month delay. This is followed by sprouting axons that migrate in an antegrade fashion to connect to the distal tube. Repair of the nerve can take months, and often have poor outcomes.
Lee et al. reviewed peripheral never injury and repair. They commented that Wallerian degeneration (i.e., breakdown of the axon distal to the site of injury) is initiated 48 to 96 hours after transection. The Schwann cells then align themselves longitudinally, creating columns of cells called Büngner bands. At the tip of the regenerating axon is the growth cone.
Illustration A shows a chart of peripheral nerve injury. The two main classification systems are Seddon and Sunderland. Video V is a lecture discussing peripheral nerve injury and management.
Answer 1: The distal nerve segment undergoes Wallerian degeneration.
Answer 2: Axon growth occurs from the proximal to distal segment.
Answer 3: Neurotrophic factors do not direct phagocytic activity.
Answer 5: Schwann cells do not degrade axoplasm and myelin.
Lee SK, Wolfe SW.
J Am Acad Orthop Surg. 2000 Jul-Aug;8(4):243-52. PMID: 10951113 (Link to Abstract)
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Average 4.0 of 16 Ratings
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?
Duration to time of repair
Length of repair
Postoperative physical rehabilitation
Type of autograft used
The clinical scenario describes an ulnar nerve laceration. Studies have shown that the ulnar nerve does not typically have good outcomes after nerve repair. (worse recovery than repairs of the tibial, radial, femoral, and musculocutaneous nerves)
Nerve injuries from gunshot injuries (GSWs) can cause both a direct injury to the nerve as well as surrounding structures (zone of injury). Many factors including age of patient, time to repair, repair level, and length of repair have been shown to be important determinants in nerve recovery following repair. The type of nerve graft (sural, saphenous, etc) used has not shown to be statistically significant in terms of functional recovery after nerve repair.
Secer et al.(J. Neurosurg) reviewed 2210 peripheral nerve lesions in 2106 patients which were injured by a GSW and who were treated surgically. Of the peripheral nerves repaired surgically, the tibial, median, and femoral nerve lesions showed the best recovery rate. The deep peroneal nerve, ulnar nerve, and brachial plexus lesions had the worst recovery.
Secer et al.(Surg. Neur.) found that of 455 patients with 462 ulnar nerve lesions only a good outcome was noted in 15.06% of patients who underwent high-level repair, 29.60% of patients who underwent intermediate-level repair, and 49.68% of patients after low-level repair. The authors also noted that a better functional recovery was noted in patients who were treated earlier.
Figure A shows a distal humerus fracture caused by a GSW.
Answer 1: Earlier nerve repairs typically have better functional results.
Answer 2: The lower level of nerve repair (more distal), the better functional results.
Answer 3: Shorter length of the nerve repair typically leads to better functional results.
Answer 4: Pre and post operative physical rehabilitation after nerve repairs has been shown to have better results.
Secer HI, Daneyemez M, Tehli O, Gonul E, Izci Y.
Surg Neurol. 2008 Feb;69(2):143-52; discussion 152. Epub 2007 Oct 29. PMID: 17967482 (Link to Abstract)
Secer HI, Daneyemez M, Gonul E, Izci Y
J. Neurosurg.. 2007 Oct;107(4):776-83. PMID: 17937222 (Link to Abstract)
Average 3.0 of 23 Ratings
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
Axonotmesis with ischemia origin
Axonotmesis with myelin disruption
Neurapraxia with ischemia origin
Neurapraxia with endoneurium disruption
The history and clinical presentation are consistent with ulnar entrapment neuropathy at the level of the cubital tunnel. This would be classified as a neuropraxia with ischemia origin.
Compression injuries to the peripheral nerves are often the result of micro-vascular dysfunction as the nerves traverse a high to low pressure gradient. Peripheral nerve injury can be classified as neuropraxia, axonotmesis and neurotmesis. Compressive neuropathies are typically neuropraxias, with local myelin damage but not compromise of the major components of the nerve. In axonotmesis, there is Wallerian degeneration and myelin loss distal to the site of injury. The most severe type is that of neurotmesis. Neurotmesis is composed of a spectrum of injury, in which all components are affected except for the perineurium or the endoneurium may be intact. The worst form of neurotmesis is that of nerve transection.
Elhassan et al. review the pathophysiology of cubital tunnel syndrome. They report nerve dysfunction results from ischemic changes secondary to compression. Compressive effects on the nerves can last greater than 24 hours, even after the source of compression has been removed.
Rempel et al. review the pathophysiology of peripheral nerve compression syndromes. The authors indicate that deforming pressures to nerves are often the result of stenotic soft tissue canal boundaries. This leads to interference with local microvasculature of the nerve itself.
Answer 1, 2: Axonotmesis is considered a second degree nerve injury, characterized by Wallerian degeneration of axons distal to site of injury. Compression neuropathies are more often neuropraxias (1st degree nerve injury)
Answer 4: Compression neuropathies result from ischemic insult to the nerve
Answer 5: Neurotmesis may be characterized by complete disruption of all components of nerve (as in transection) or with disruption of all components except for the perineurium or the endoneurium. This is not characteristic of a compression neuropathy such as cubital tunnel syndrome.
Illustration A demonstrates the Wartenberg sign, where the patient has persistent small finger abduction/extension resulting from weakness of the 3rd palmar interosseous/small finger lumbrical.
Illustration B reveals clawing which results from over powering of the intrinsic muscles by the extensors; a tenodesis effect results in flexion of the PIP/DIP joints. This is more severe in ulnar nerve compression at Guyon’s canal.
Illustration C shows the Froment sign, where the FPL attempts to compensate for a deficient pinch, because of weakness of the adductor pollicis. Illustration D demonstrates atrophy of the 1st dorsal webspace from chronic compressive changes.
Illustration E demonstrates atrophy of the thenar compartment which is consistent with carpal tunnel syndrome.
Elhassan B, Steinmann SP.
J Am Acad Orthop Surg. 2007 Nov;15(11):672-81. PMID: 17989418 (Link to Abstract)
Rempel D, Dahlin L, Lundborg G.
J Bone Joint Surg Am. 1999 Nov;81(11):1600-10. PMID: 10565653 (Link to Abstract)
Average 3.0 of 19 Ratings
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?
Glycolide trimethylene carbonate conduit
Primary end-to-end repair
Polyglycolic acid conduit
Repair of segmental nerve loss in the hand using collagen conduits allows for nutrient exchange and accessibility of neurotrophic factors to the axonal growth zone during regeneration. While the other listed answers have been used, none has shown the efficacy of collagen conduits or autograft.
Li et al. describe the repair of peripheral nerves with a tubular collagen conduit and review supporting data from in vitro and in vivo primate studies to this regard.
Bertleff et al. describe the recovery of sensory nerve function after treatment of traumatic peripheral nerve lesions with a biodegradable poly(DL-lactide-epsilon-caprolactone) neurolac nerve guide, compared to their control of end-to-end repair, no autologous grafting. They show equal results between primary end-to-end repair and their synthetic graft.
Waitayawinyu et al. compared 2 synthetic polyglycolic acid conduits to autogenous nerve grafting using histopathologic and neurophysiologic analyses in a segmental defect rat model. They found that collagen conduits and autografts produced comparable results, which were significantly better than polyglycolic acid conduits.
Video V is a lecture discussing peripheral nerve injury and management.
Bertleff MJ, Meek MF, Nicolai JP
J Hand Surg Am. 2005 May;30(3):513-8. PMID: 15925161 (Link to Abstract)
Waitayawinyu T, Parisi DM, Miller B, Luria S, Morton HJ, Chin SH, Trumble TE.
J Hand Surg Am. 2007 Dec;32(10):1521-9. PMID: 18070638 (Link to Abstract)
Li ST, Archibald SJ, Krarup C, Madison RD.
Clin Mater. 1992;9(3-4):195-200. PMID: 10149970 (Link to Abstract)
Average 1.0 of 47 Ratings
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?
Of the choices listed, the radial nerve has the best opportunity for recovery.
Roganovic performed a prospective study of 393 graft repairs of the median, ulnar, radial, tibial, peroneal, femoral, and musculocutaneous nerves which showed that peripheral nerves differ significantly regarding the motor recovery potential, and the difference depends on the level of nerve repair. The following nerves had excellent recovery potential: the radial, musculocutaneous, and femoral nerves. The following nerves had moderate recovery potential: the median, ulnar, and tibial nerves. The following nerve had poor recovery potential: the peroneal nerve.
Mohler et al, recommends testing nerve action potentials at the time of nerve exploration to guide surgical treatment.
Roganovic Z, Pavlicevic G
Neurosurgery. 2006 Sep;59(3):621-33; discussion 621-33. PMID: 16955044 (Link to Abstract)
Mohler LR, Hanel DP.
J Am Acad Orthop Surg. 2006 Jan;14(1):32-7. PMID: 16394165 (Link to Abstract)
Average 2.0 of 31 Ratings
Axon regeneration almost always occurs following a Sunderland second-degree nerve injury because which anatomic structure is not injured?
Following a Sunderland second-degree injury, axon regeneration is possible because the endoneurium is intact.
There are two classification schemes for peripheral nerve injuries, which include the Seddon and the Sunderland systems. Under the Sunderland classification, a second-degree injury is considered a part of the axonotmesis spectrum. The endoneurium, perineurium and epineurium are still intact. This enables complete functional recovery.
Lee et al. review the pathophysiology and evaluation of peripheral nerve injuries. They note that in Sunderland type two injuries, there is physiologic disruption of the axons. Because the endoneurium is still intact, axons are able to regenerate. This process takes months.
Illustration A is a schematic of the various stages of peripheral nerve injury.
Answers 1, 3: Although the epineurium and perineurium are intact in a Sunderland type 2 injury, axon regeneration is possible because of an intact endoneurium.
Answers 4, 5: The myelin sheath and Schwann cells are disrupted in axonotmesis.
Average 2.0 of 34 Ratings
Vitamin B12 deficiency is a known cause of which the following?
Inability to whistle
Peripheral sensory neuropathy
Increased deep tendon reflexes
Vitamin B12 deficiency is a known cause of peripheral sensory neuropathy and B12 levels should be evaluated in patients presenting with peripheral sensory neuropathy. It is associated with decreased deep tendon reflexes, pathologic reflexes like Babinski's sign, and fatigue/depression. The inability to whistle is associated with fascioscapular dystrophy. Hydrophobia is associated with rabies infection.
Smith and Singleton evaluated 138 patients referred with predominantly sensory symptoms to identify a standardized approach to diagnosis. They recommend that patients be tested for glucose tolerance and vitamin B(12) concentration in all cases, but that other tests should be performed only when the clinical scenario is suggestive.
Steiner et al. describe a case report of a patient with vitamin B12 sensory peripheral neuropathy and associated EMG evidence of nerve demyelination as the potential cause for the observed clinical symptoms.
Smith AG, Singleton JR.
Arch Intern Med. 2004 May 10;164(9):1021-5. PMID: 15136313 (Link to Abstract)
Steiner I, Kidron D, Soffer D, Wirguin I, Abramsky O.
J Neurol. 1988 Jan;235(3):163-4. PMID: 2835439 (Link to Abstract)
Average 3.0 of 14 Ratings
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?
Free nerve endings
Merkel's skin receptors are slowly adapting skin receptors that detect pressure, texture, and low frequency vibration and can be appropriately evaluated by static two-point discrimination. Merkel's disk receptors adapt slowly and sense sustained pressure, texture, and low-frequency vibrations.
Szabo et al state in their review that static and moving two point discrimination are best to initially evaluate innervation density for both quickly and slowly adapting fibers. Vibratory moving 2 point discrimination is best for evaluation of quickly adapting fibers.
Meissner corpuscle, a rapidly adapting sensory receptor, is very sensitive to touch. Pacinian corpuscles are ovoid in shape, measuring approximately 1 mm in length. They respond to high-frequency vibration and rapid indentations of the skin. Ruffini corpuscles are slowly adapting receptors that detect stretching of the skin.
Illustration A demonstrates Meissner's corpuscles (A), Pacinian corpuscles (B), Merkel's receptor (C), free nerve ending (D), and Ruffini corpuscles (E). Illustration B displays the function and location of the receptors.
Szabo RM, Madison M.
Orthop Clin North Am. 1992 Jan;23(1):103-9. PMID: 1729659 (Link to Abstract)
Average 2.0 of 37 Ratings
Which of the following peripheral nerve structures functions to cushion the nerve against external pressure?
The epineurium is a supportive sheath surrounding peripheral nerves that cushions fascicles against external pressure. It is comprised of a loose meshwork of collagen and elastin fibers that are aligned parallel with the nerve fibers.
Illustration A & B depicts the contents of a nerve including epineurium, perineurium, and endoneurium.
Answer 1: Endoneurium is a fibrous tissue that covers the axon, Schwann cell, and myelin of each nerve fiber.
Answer 2: Fibronectin and laminin are extracellular matrix glycoproteins that facilitate directional nerve fiber branching.
Answer 3: N-cadherin is an adhesive membrane glycoproteins on neural ectoderm and facilitate growing axons.
Answer 4: Perineurium is a dense connective tissue which surrounds nerve fascicles. It provides high tensile strength. The perineurium also limits diffusion within the intraneural environment and subsequently prevents injury from edema.
Average 3.0 of 26 Ratings
HPI - 29 year old male with laceration to volar distal forearm from breaking glass with arm.
When examining the nerve ends after a traumatic laceration, how do you determine if there is healthy nerve tissue on each end of the nerve?
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