Mateusz Gładysz FESSH prep

FESSH prep Peripheral nerve injury Repair Schwann cell phenotype, decline of regenerative support with delay, chronic denervation of the distal pathway, effect of age, motoneuron survival after axotomy

Biology of peripheral nerve degeneration and regeneration

Last reviewed v1.0

FESSH-063Peripheral nerve injury●○○ basic

Regarding the biology of degeneration and regeneration after peripheral nerve transection:

  1. 1.Most motoneurons die after a peripheral nerve transection, and this is the main reason for poor motor recovery after repair.

  2. 2.After nerve injury, Schwann cells of the distal nerve convert to a repair phenotype that clears myelin, helps prevent neuronal death and supports axon growth and guidance.

  3. 3.The capacity of the denervated distal nerve to support regeneration persists indefinitely, so the delay between injury and repair has little effect on motor recovery.

  4. 4.In experimental delayed nerve repair, long-term denervated muscle can still accept reinnervation, each regenerated axon supplying more muscle fibres than normal.

  5. 5.After microsurgical repair of median and ulnar nerve transections, patients younger than 16 years have a better chance of satisfactory motor recovery than adults older than 40.

FESSH marking: +1 per correct statement, 0 for blank, −1 for incorrect. Click the same TRUE/FALSE button twice to clear it.

Question ID
FESSH-063
First published
Last reviewed
Version
v1.0
Answer key and explanations — open after answering

  1. 1. Most motoneurons die after a peripheral nerve transection, and this is the main reason for poor motor recovery after repair.

    False

    Motoneurons, and to a lesser extent sensory neurons, survive peripheral nerve injury; the limiting factors are slow axon outgrowth across the injury site and declining support for regeneration. In Fu and Gordon's experiments, prolonged axotomy reduced the capacity of motor axons to regenerate, contributing to poor recovery after delayed repair.

    • Gordon T. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers. Hand Clin. 2016;32(2):103-17. PMID 27094884
    • Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy. J Neurosci. 1995;15(5 Pt 2):3876-85. PMID 7751952

  2. 2. After nerve injury, Schwann cells of the distal nerve convert to a repair phenotype that clears myelin, helps prevent neuronal death and supports axon growth and guidance.

    True

    Jessen and Mirsky describe how myelin and Remak Schwann cells are reprogrammed into repair cells after injury. Together with the switch of injured neurons to a growth mode, this response gives peripheral nerves their regenerative potential.

    • Jessen KR, Mirsky R. The Success and Failure of the Schwann Cell Response to Nerve Injury. Front Cell Neurosci. 2019;13:33. PMID 30804758

  3. 3. The capacity of the denervated distal nerve to support regeneration persists indefinitely, so the delay between injury and repair has little effect on motor recovery.

    False

    The support that chronically denervated Schwann cells give to regenerating axons declines progressively with time and with the distance of the injury from its targets; in human nerves the repair-cell markers c-Jun and p75NTR fall during long-term denervation. Clinically, in Ruijs's individual-patient meta-analysis of median and ulnar nerve repairs, each month of delay reduced the odds of satisfactory motor recovery (odds ratio 0.94 per month).

    • Gordon T. Nerve Regeneration: Understanding Biology and Its Influence on Return of Function After Nerve Transfers. Hand Clin. 2016;32(2):103-17. PMID 27094884
    • Ruijs AC, Jaquet JB, Kalmijn S, Giele H, Hovius SE. Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair. Plast Reconstr Surg. 2005;116(2):484-94; discussion 495-6. PMID 16079678
    • Wilcox MB, Laranjeira SG, Eriksson TM, Jessen KR, Mirsky R, Quick TJ, et al.. Characterising cellular and molecular features of human peripheral nerve degeneration. Acta Neuropathol Commun. 2020;8(1):51. PMID 32303273

  4. 4. In experimental delayed nerve repair, long-term denervated muscle can still accept reinnervation, each regenerated axon supplying more muscle fibres than normal.

    True

    In Fu and Gordon's nerve cross-anastomosis model, each regenerated axon reinnervated three to five times more muscle fibres than normal, so the denervated muscle itself was not the limiting factor. Recovery was poor because far fewer axons regenerated through the deteriorating intramuscular nerve sheaths: beyond six months of denervation the mean motor unit number was 15, against 137 after immediate suture. Reinnervated fibres also failed to recover fully from denervation atrophy.

    • Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci. 1995;15(5 Pt 2):3886-95. PMID 7751953

  5. 5. After microsurgical repair of median and ulnar nerve transections, patients younger than 16 years have a better chance of satisfactory motor recovery than adults older than 40.

    True

    In Ruijs's meta-analysis of individual data on 623 median and ulnar nerve injuries, patients younger than 16 had over four times the odds of satisfactory motor recovery of those older than 40 (odds ratio 4.3, 95% CI 1.6–11.2). Age was also a significant predictor of sensory recovery.

    • Ruijs AC, Jaquet JB, Kalmijn S, Giele H, Hovius SE. Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair. Plast Reconstr Surg. 2005;116(2):484-94; discussion 495-6. PMID 16079678