Elucidating The Effects Of Delayed Nerve Repair On Motor Vs. Sensory Functional Recovery: A Systematic Review And Meta-analysis
Karim A. Sarhane, MD, MSc1, Heather Shappell, PhD1, Benjamin Slavin, BS1, Nicholas von Guinneau, MD1, Philip Hanwright, MD1, Gregory H. Borschel, MD2, Sami H. Tuffaha, MD1.
1Johns Hopkins University, Baltimore, MD, USA, 2University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada.
PURPOSE:Meaningful recovery of motor function following peripheral nerve injury requires timely reinnervation of muscle before atrophy occurs. In contrast, sensory recovery is thought to be less time-sensitive because sensory receptors are relatively spared from atrophy. Conventional wisdom holds that meaningful sensory recovery can be achieved regardless of the duration of delay. However, this thinking has been challenged by recent insights from animal research demonstrating that Schwann cells within the distal stump lacking axonal interaction senesce and lose their capacity to support axonal regeneration. The clinical implications of these experimental findings remain unclear. In this study, we systematically examined the literature for cases of secondary nerve repair to determine the relative impact of delay on sensory vs. motor recovery.
METHODS:We reviewed all articles describing outcomes following repair of median, ulnar, and radial nerves from 1970-2018. We performed a meta-analysis of patient outcomes to determine the differential effect of delay on motor and sensory recovery. We fit a linear mixed effects model with change in BMRC recovery score as the outcome. We included duration of delay, motor vs. sensory classification, interaction between outcome and delay, and pre-operative functional score as fixed effects. We included a random subject effect to account for multiple observations on the same subject. We then performed backwards step-wise regression utilizing additional covariates (type of nerve, location and type of injury, and adjacent injuries). Our final model allowed us to predict motor and sensory recovery based on the duration of delay, type of nerve, location of injury, and pre-operative M/S functional score.
RESULTS:Out of 1621 screened articles, 21 articles with a total of 448 patients met inclusion criteria. After adjusting for preoperative score, we found that the negative effects of delay are more than twice as large for motor recovery than sensory recovery (p<0.01). Backwards step-wise regression yielded a final model that included pre-operative score, motor vs. sensory classification, delay, location of injury, type of nerve, an interaction between delay and motor vs. sensory, and an interaction between type of nerve and motor vs. sensory as significant predictors of recovery (p<0.05). The effect of delay on recovery remained significantly different for motor vs. sensory groups after adjustment (Fig.1, p<0.01). Moreover, our model allowed us to predict recovery based on type of nerve, injury location, and delay (Fig.2).
CONCLUSION:This study demonstrates that delayed nerve repair has a greater deleterious effect on motor than sensory functional recovery. This finding supports the hypothesis that chronic denervation of the distal regenerative pathway has a modest effect on motor and sensory recovery in comparison to the more pronounced effects of muscle atrophy on motor recovery. Importantly, this study provides the first model that can predict motor and sensory recovery following nerve repair based on the duration of delay.
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