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Meta-Analysis
. 2018 Feb 16;8(1):3168.
doi: 10.1038/s41598-018-21540-5.

Ultrasound and Shock-Wave Stimulation to Promote Axonal Regeneration Following Nerve Surgery: A Systematic Review and Meta-Analysis of Preclinical Studies

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Free PMC article
Meta-Analysis

Ultrasound and Shock-Wave Stimulation to Promote Axonal Regeneration Following Nerve Surgery: A Systematic Review and Meta-Analysis of Preclinical Studies

Simeon C Daeschler et al. Sci Rep. .
Free PMC article

Abstract

Limited regeneration after nerve injury often leads to delayed or incomplete reinnervation and consequently insufficient muscle function. Following nerve surgery, application of low-intensity ultrasound or extracorporeal shock waves may promote nerve regeneration and improve functional outcomes. Because currently clinical data is unavailable, we performed a meta-analysis following the PRISMA-guidelines to investigate the therapeutic effect of ultrasound and shock wave therapies on motor nerve regeneration. Ten ultrasound-studies (N = 445 rats) and three shock-wave studies (N = 110 rats) were identified from multiple databases. We calculated the difference in means or standardized mean difference with 95% confidence intervals for motor function, nerve conduction velocity and histomorphological parameters of treated versus sham or non-treated animals. Ultrasound treatment showed significantly faster nerve conduction, increased axonal regeneration with thicker myelin and improved motor function on sciatic functional index scale (week two: DM[95%CI]: 19,03[13,2 to 25,6], 71 animals; week four: 7,4[5,4 to 9,5], 47 animals). Shock wave induced recovery improvements were temporarily significant. In conclusion, there is significant evidence for low-intensity ultrasound but not for extracorporeal shock wave treatment to improve nerve regeneration. Prospective clinical trials should therefore investigate available FDA-approved ultrasound devices as adjunct postoperative treatment following nerve surgery.

Conflict of interest statement

The authors declare no competing interests

Figures

Figure 1
Figure 1
Flow diagram. Visualization of the literature search and the study selection process according to the PRISMA guidelines.
Figure 2
Figure 2
Meta-analysis. To compare the different scales used to measure identical outcome parameters in the included studies, we calculated the standardized mean difference (SMD) and calculated the DM afterwards in accordance with the Cochrane Handbook for Systematic Reviews. Shown are the standardized mean differences of walking track performance of animals treated with an ultrasound intensity of 200–300 mW/cm2 compared to sham or untreated animals four weeks following axonotmetic nerve injury and four weeks following implantation of biodegradable synthetic nerve conduit or reverse autograft.
Figure 3
Figure 3
Meta-analysis. Standardized mean differences of walking track performance of 200–500 mW/cm2 US treated compared to sham or untreated animals at specific time points following crush injury.
Figure 4
Figure 4
Risk of bias assessment of all included studies. The PRISMA guidelines require an analysis of potential biases, which would lead to under- or overestimation of the true intervention effect. Referring to the PRISMA guidelines, the authors judged the risk of bias (low-, unclear-, high risk of bias) for the following items for each included study: Selection bias, blinding of the surgeon, detection bias, attrition bias, reporting bias and other bias. Shown are the authors’ judgments about each risk of bias item for each study (upper part) and as percentages across all included studies (lower part).
Figure 5
Figure 5
Meta-analysis. Differences in means of multiple histomorphometrical parameters of 400–500 mW/cm2 US-treated animals compared to sham or untreated animals on various time points following nerve reconstruction via nerve conduit.
Figure 6
Figure 6
Meta-analysis. Difference in means of walking track performance of ESW-treated animals compared to untreated animals two weeks following crush injury with a considerable heterogeneity of I2 = 87% (n = 50).

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