ABSTRACT
The slow axonal regeneration and consecutive delayed muscle reinnervation cause persistent functional deficits following peripheral nerve injury, even following sufficient surgical nerve reconstruction. Preclinically, adjunct ultrasound therapy has shown to significantly accelerate nerve regeneration and thereby improve muscle function compared to nerve reconstruction alone. However, although FDA-approved and clinically well-tested ultrasound devices for other conditions such as delayed-healing fractures are available, they have not been investigated for peripheral nerve injury yet. Aiming to provide a fast clinical translation, we evaluated EXOGEN (Bioventus LLC, Durham, USA), a clinical device for low-intensity ultrasound therapy in various treatment intervals following peripheral nerve surgery. Sixty rats, randomized to five groups of twelve animals each, underwent median nerve transection and primary epineural nerve reconstruction. Post-surgically the ultrasound therapy (duration: 2 min, frequency: 1.5 MHz, pulsed SATA-intensity: 30 mW/cm2, repetition-rate: 1.0 kHz, duty-cycle: 20%) was applied either weekly, 3 times a week or daily. A daily sham-therapy and a control-group served as references. Functional muscle testing, electrodiagnostics and histological analyses were used to evaluate nerve regeneration. The post-surgically absent grip strength recovered in all groups and increased from week four on without any significant differences among groups. The weekly treated animals showed significantly reduced target muscle atrophy compared to sham-treated animals (p = 0.042), however, with no significant differences to three-times-a-week-, daily treated and control animals. The number of myelinated axons distal to the lesion site increased significantly in all groups (p < 0.001) without significant difference among groups (p > 0.05). A full recovery of distal latency was achieved in all groups and muscle function and CMAP recurred with insignificant differences among groups. In conclusion, the clinically available FDA-approved ultrasound device did not promote the axonal regeneration following nerve injury in comparison to control and sham groups. This is in contrast to a conclusive preclinical evidence base and likely due to the insufficient ultrasound-intensity of 30 mW/cm2. We recommend the clinical investigation of 200-300 mW/cm2.
ABSTRACT
Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal reinnervation. As a consequence of slow nerve regeneration, target muscle function is often insufficient and leads to a lifelong burden. Recently, the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant developments. However, the problem of slow nerve regeneration has not been solved. In a recent meta-analysis, we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional outcomes. Here we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration, the current state of investigations and its possible future clinical applications.
ABSTRACT
Traumatic soft tissue and bone defects are demanding challenges for the reconstructive microsurgeons. Common and safe workhorses for these reconstructions are free microvascular flaps based on the subscapular system. In this article, we want to demonstrate the versatility of the serratus anterior muscle combined with other components of the subscapular system for reconstruction of complex lower extremity defects. Three patients with traumatic soft tissue and bone defects of the lower extremity were planned for reconstruction. The defects varied in size and could be covered by 1 or 2 slips of the serratus muscle or split muscle combined with latissimus dorsi muscle flap. In 1 case, the thoracodorsal lymph node package was included for addressing severe posttraumatic lymphedema after burn injury. In another case, the serratus slips served as coverage for a free scapula bone transplant. The chimeric flaps healed without complications; no further operations were needed for reconstruction. By the use of only 1 or 2 slips of the serratus muscle, we could prevent functional impairments for the patients and reduced further scarring compared with classic latissimus dorsi-(para-) scapular combinations.
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.
