Efficacy evaluation of personalized coaptation in neurotization for motor deficit after peripheral nerve injury: A systematic review and meta-analysis

Abstract

Introduction: Peripheral neurotization, recently as a promising approach, has taken effect in recovering motor function after damage to a peripheral nerve root. Neural anastomosis comprised of nerve conduit and neurorrhaphy participates in the nerve reconstruction. Current literature lacks evidence supporting an individualized coaptation for rescue of locomotor loss in rat subjects with paraplegia secondary to peripheral nerve injury (PNI).

Methods: This meta-analysis intends to qualify the specificity of gap-specific coaptation in treating a paralyzed limb following PNI. We used a highly sensitive search strategy to identify all published studies in multiple databases up to 1 May 2019. All identified trials were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.

Results: Twelve studies, including 349 rat subjects, met eligibility criteria. For a medium nerve defect (0.5-3.0 cm), nerve conduit was more likely than neurorrhaphy to precipitate axon regeneration and improve motor outcome of the hemiplegic limb (OR = 3.61, 95% CI = 1.80, 7.26, p < .0003) at 3-month follow-up, whereas neurorrhaphy might take its place in promoting limb motor function in a small nerve gap (<0.5 cm) (OR = 0.48, 95% CI = 0.22, 1.07, p < .007). For a small nerve defect, nerve conduit still demonstrated visible effectiveness in recovery of limb motion albeit poorer than neurorrhaphy (OR = 1.50, 95% CI = 0.92, 2.47, p < .05).

Conclusion: Selective neurotization facilitates motor regeneration after nerve transection, and advisable choice of neural coaptation can maximize functional outcome on an individual basis.

Keywords: functional recovery; neurotization; neurotube; peripheral nerve injury; personalized coaptation.

Figure 1

Flowchart of the literature search

Figure 2

Risk of bias assessment for randomized controlled trials. “+”, low risk of bias; “−”, high risk of bias; and “?”, indicates unclear risk of bias

Figure 3

Forest plot with OR estimating with the corresponding 95% CI for favorable outcome (defined as BBB ≥ 9) associated with nerve conduit versus neurorrhaphy for individual trials and the pooled population at 1‐month, 2‐month, and 3‐month follow‐ups (subjects in all gaps). CI, confidence interval; BBB, Basso, Beattie, and Bresnahan for locomotor functional recovery; OR, odds ratio

Figure 4

Forest plot with OR estimating with the corresponding 95% CI for (a) favorable outcome (defined as BBB ≥ 9 and SFI ≥ 40) associated with nerve conduit versus neurorrhaphy individual trials and the subgroup population stratified by size of defect for 2‐month follow‐up (b). CI, confidence interval; BBB, Basso, Beattie, and Bresnahan for locomotor functional recovery; OR, odds ratio

Figure 5

Forest plot with OR estimating with the corresponding 95% CI for the proportion of rats with poor outcome in motor function (defined as BBB < 9 or SFI < 40) associated with nerve conduit versus neurorrhaphy for individual trials and the pooled population at 1‐month, 2‐month, and 3‐month follow‐ups (rats in all defects). CI, confidence interval; BBB, Basso, Beattie, and Bresnahan for locomotor functional recovery; OR, odds ratio; SFI, sciatic functional index

Figure 6

Funnel plot to detect publication bias. No significant funnel asymmetry was observed which could indicate publication bias (p‐value for Egger test was .27). logOR, Natural logarithm of the OR; SE of logOR, standard error of the logOR