Objective: To develop a standardized model of stretch–crush sciatic nerve injury in mice, and to compare outcomes of crush and novel stretch–crush injuries using standard manual gait and sensory assays, and compare them to both semi-automated as well as deep-learning gait analysis methods. Methods: Initial studies in C57/Bl6 mice were used to develop crush and stretch–crush injury models followed by histologic analysis. In total, 12 eight-week-old 129S6/SvEvTac mice were used in a six-week behavioural study. Behavioral assessments using the von Frey monofilament test and gait analysis recorded on a DigiGait platform and analyzed through both Visual Gait Lab (VGL) deep learning and standardized sciatic functional index (SFI) measurements were evaluated weekly. At the termination of the study, neurophysiological nerve conduction velocities were recorded, calf muscle weight ratios measured and histological analyses performed. Results: Histological evidence confirmed more severe histomorphological injury in the stretch–crush injured group compared to the crush-only injured group at one week post-injury. Von Frey monofilament paw withdrawal was significant for both groups at week one compared to baseline (p < 0.05), but not between groups with return to baseline at week five. SFI showed hindered gait at week one and two for both groups, compared to baseline (p < 0.0001), with return to baseline at week five. Hind stance width (HSW) showed similar trends as von Frey monofilament test as well as SFI measurements, yet hind paw angle (HPA) peaked at week two. Nerve conduction velocity (NCV), measured six weeks post-injury, at the termination of the study, did not show any significant difference between the two groups; yet, calf muscle weight measurements were significantly different between the two, with the stretch–crush group demonstrating a lower (poorer) weight ratio relative to uninjured contralateral legs (p < 0.05). Conclusion: Stretch–crush injury achieved a more reproducible and constant injury compared to crush-only injuries, with at least a Sunderland grade 3 injury (perineurial interruption) in histological samples one week post-injury in the former. However, serial behavioral outcomes were comparable between the two crush groups, with similar kinetics of recovery by von Frey testing, SFI and certain VGL parameters, the latter reported for the first time in rodent peripheral nerve injury. Semi-automated and deep learning-based approaches for gait analysis are promising, but require further validation for evaluation in murine hind-limb nerve injuries.
Reverse end-to-side (RETS) distal transfer is gaining popularity in cases of proximal nerve damage with the nerve in continuity, allowing the nerve to potentially retain its ability to regenerate and recover. While preserving the original axon pool, RETS could provide an additional pool of motor axons and/or possibly "babysit" the muscle endplates and distal denervated nerve Schwann cells until reinnervation from the original pool occurs. The authors present a video demonstrating anterior subcutaneous transposition of the ulnar nerve at the elbow coupled with a distal anterior interosseous nerve to ulnar nerve RETS in a case of severe posttraumatic ulnar neuropathy at the elbow. The video can be found here: https://stream.cadmore.media/r10.3171/2022.9.FOCVID2282
BACKGROUND: The depth of connective tissue window in the side of a recipient nerve in reverse end-to-side transfers (RETS) remains controversial. OBJECTIVE: To test whether the depth of connective tissue disruption influences the efficiency of donor axonal regeneration in the context of RETS. METHODS: Sprague-Dawley rats (n = 24) were assigned to 1 of the 3 groups for obturator nerve to motor femoral nerve RETS: group 1, without epineurium opening; group 2, with epineurium only opening; and group 3, with epineurium and perineurium opening. Triple retrograde labeling was used to assess the number of motor neurons that had regenerated into the recipient motor femoral branch. Thy1-GFP rats (n = 8) were also used to visualize the regeneration pathways in the nerve transfer networks at 2- and 8-week time point using light sheet fluorescence microscopy. RESULTS: The number of retrogradely labeled motor neurons that had regenerated distally toward the target muscle was significantly higher in group 3 than that in groups 1 and 2. Immunohistochemistry validated the degree of connective tissue disruption among the 3 groups, and optical tissue clearing methods demonstrated donor axons traveling outside the fascicles in groups 1 and 2 but mostly within the fascicles in group 3. CONCLUSION: Creating a perineurial window in the side of recipient nerves provides the best chances of robust donor axonal regeneration across the RETS repair site. This finding aids nerve surgeons by confirming that a deep window should be undertaken when doing a RETS procedure.
The disappointing outcomes of conventional nerve repair or grafting procedures for proximal ulnar nerve injuries have led the scientific community to search for better alternatives. The pronator quadratus branch of the anterior interosseous nerve has been transferred to the distal ulnar motor branch in a reverse end-to-side fashion with encouraging results. This transfer is now becoming commonly used as an adjunct to cubital tunnel decompression in patients with compressive ulnar neuropathy, underscoring the need for this knowledge transfer to the neurosurgical community. However, the mechanism of recovery after these transfers is not understood completely. We have reviewed the existing preclinical and clinical literature relevant to this transfer to summarize the current level of understanding of the underlying mechanisms, define the indications for performing this transfer in the clinic, and identify the complications and best practices with respect to the operative technique. We have also attempted to identify the major deficiencies in our current level of understanding of the recovery process to propose directions for future research.
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