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Background: Traumatic peripheral nerve injury, with an annual incidence reported to be approximately 13-23 per 100,000 people, is a serious clinical condition that can often lead to significant functional impairment and permanent disability. Although nerve transfer has become increasingly popular in the treatment of brachial plexus injuries, satisfactory results cannot be obtained even with total nerve root transfer, especially after serious injuries. To overcome this problem, we hypothesize that the application of stem cells in conjunction with nerve transfer procedures may be a viable alternative to more aggressive treatments that do not result in adequate improvement. Similarly, some preliminary studies have shown that adipose stem cells combined with acellular nerve allograft provide promising results in the repair of brachial plexus injury. The purpose of this study was to assess the efficacy of combining adipose-derived stem cells with nerve transfer procedure in a rat brachial plexus injury model., Methods: Twenty female Wistar rats weighing 300-350 g and aged 8-10 weeks were randomly divided into two groups: a nerve transfer group (NT group) and a nerve transfer combined adipose stem cell group (NT and ASC group). The upper brachial plexus injury model was established by gently avulsing the C5-C6 roots from the spinal cord with microforceps. A nerve transfer from the ulnar nerve to the musculocutaneous nerve (Oberlin procedure) was performed with or without seeded allogeneic adipose tissue-derived stem cells. Adipose tissue-derived stem cells at a rate of 2 × 10 6  cells were injected locally to the surface of the nerve transfer area with a 23-gauge needle. Immunohistochemistry (S100 and PGP 9.5 antibodies) and electrophysiological data were used to evaluate the effect of nerve repair 12 weeks after surgery., Results: The mean latency was significantly longer in the NT group (2.0 ± 0.0 ms, 95% CI: 1.96-2.06) than in the NT and ASC group (1.7 ± 0.0 ms, 95% CI: 1.7-1.7) (p < .001). The mean peak value was higher in the NT group (1.7 ± 0.0 mV, 95% CI: 1.7-1.7) than in the NT and ASC group (1.7 ± 0.3 mV, 95% CI: 1.6-1.9) with no significant difference (p = .61). Although S100 and PGP 9.5 positive areas were observed in higher amounts in the NT and ASC group compared to the NT group, the differences were not statistically significant (p = .26 and .08, respectively)., Conclusions: This study conducted on rats provides preliminary evidence that adipose-derived stem cells may have a positive effect on nerve transfer for the treatment of brachial plexus injury. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings., (© 2024 Wiley Periodicals LLC.)

Background: The aim of the current study is to investigate the first and second lumbrical nerves as potential fibers donors to the deep motor branch of the ulnar nerve to avoid intrinsic atrophy in high ulnar nerve injuries., Methods: Sixteen fresh frozen cadaveric hands were dissected, the radial lumbrical nerves accessed, and a coaptation, either in reverse end-to-side or in double end-to-side through a bridge nerve graft, was created to the deep motor branch of ulnar nerve. Semithin sections were taken from samples of donor and recipient nerves for qualitative (nerve architecture) and quantitative studies (fiber count and donor/recipient ratio)., Results: The first lumbrical showed a robust trunk and a superior axon density (9,126.50 ± 2,923.41 axons/mm 2 ) to the ulnar motor branch (7,506.50 ± 1,137.50 axons/mm 2 distal to the opponens tunnel and 7,947.75 ± 1,741.24 axons/mm 2 before its terminal branching); the ulnar motor branch showed a higher axon number (2,633.51 ± 410.00 distal to the opponens tunnel and 2,345.75 ± 2,101.56 before its terminal branching) than the first lumbrical (1,410.56 ± 823.89); section areas occupied by axons were higher in proximal (0.20 ± 0.16) and distal (0.26 ± 0.20) ulnar samples than the first lumbrical (0.17 ± 0.16). Donor/recipient ratio first lumbrical/deep motor branch of the ulnar nerve were 1:1.86 (distal to the opponens tunnel) and 1:1.67 (at its terminal branching); data about the second lumbrical were ruled out because of bias., Conclusions: A transfer from the first lumbrical nerve to the deep motor branch of the ulnar nerve in palm is suitable to avoid intrinsic atrophy., (© 2018 Wiley Periodicals, Inc.)

Background: Distal nerve transfer has proven efficacy. The purpose of this study was to investigate if an injured nerve can be used as a donor nerve for transfer, and to determine the threshold of injury., Materials and Methods: Rat's left ulnar-nerves in the axilla with different degrees of injury were selected as the donor nerves for transfer, and the musculocutaneous-nerves the target nerves for being re-innervated. Six rats each served as positive and negative controls: Group A, intact ulnar-nerve transfer; and Group E, the ulnar-nerve was cut but no transfer. Ten rats each were assigned to Group B to Group D with 25%, 50%, and 75% transected ulnar-nerve, respectively and all were transferred to the musculocutaneous-nerve. After a 12-week recovery period, outcomes were evaluated., Results: Biceps muscle weight measurements showed all experimental groups-D 0.28 ± 0.02 g/72%, C 0.28 ± 0.03 g/73%, B 0.29 ± 0.04 g/74%, and A 0.29 ± 0.04 g/80%-were lighter than group H 0.36 ± 0.04 g, which were all statistically significant (P < 0.001). Muscle tetanus contraction force measurements were the lowest in group D35 ± 8.6 g/69%. Groups C and B measured 41 ± 8.5 g/75% and 40 ± 2.2 g/77% and group A 41 ± 9.4 g/95%, respectively. Group H showed muscle contraction force of 52 ± 7.2 g, which was statistically significant when compared to experimental groups (P < 0.05-0.001). EMG measurements of the biceps muscles showed: group D was 3.6 ± 0.7 mV/69%, group C was 3.6 ± 0.6 mV/75%, and group B was 4.2 mV ± 0.7/81%. Group H was5.1 ± 0.7 mV and statistically significant different when compared with experimental groups (P < 0.05-0.001).Axon counts of healthy ulnar-nerve (Group H) were 1849 ± 362. Axon counts of the injured ulnar-nerve were in group B 1447 ± 579/78%, group C 1051 ± 367/57% and group D 567 ± 230/31%., Conclusion: The donor nerve should be healthy in order to provide optimal result. A big nerve (e.g., ulnar nerve) but injured with at least 75% axon spared is still potentially effective for transfer. In contrast, a small nerve (e.g., intercostal nerve) once injured with 75%axon spared would be considered a suboptimal donor nerve., (© 2017 Wiley Periodicals, Inc.)

Background: With complete plexus injuries or late presentation, free functional muscle transfer (FFMT) becomes the primary option of functional restoration. Our purpose is to review cases over a 10-year period of free functioning gracilis muscle transfer after brachial plexus injury to evaluate the effect of different donor nerves used to reinnervate the FFMT on functional outcome., Methods: A retrospective study from April 2001 to January 2011 of a single surgeon's practice was undertaken. During this time period 22 patients underwent FFMT at Washington University in St Louis, Missouri for elbow flexion., Results: Thirteen patients for whom FFMT was performed for elbow flexion met all of the requirements for inclusion in this study. Average time from injury to first operation was 12.8 months (range 4-60), and average time from injury to FFMT was 29 months (range 8-68). Average follow-up was 31.8 months (range 11-84). The nerve donors utilized included the distal accessory nerve, intercostal with or without rectus abdominis nerves, medial pectoral nerves, thoracodorsal nerve, and flexor carpi ulnaris fascicle of ulnar nerve. Functional recovery of elbow flexion was measured using the MRC grading system which showed 1 M5/5, 5 M4, 4 M3, and 3 M2 outcomes., Conclusion: Intraplexal donor motor nerves if available will provide better transferred muscle function because they are higher quality donors closer to the muscle and can be done in one stage without a nerve graft. Otherwise, intercostal, rectus abdominis, or the distal accessory nerve should be used in a staged fashion. © 2016 Wiley Periodicals, Inc. Microsurgery 37:377-382, 2017., (© 2016 Wiley Periodicals, Inc.)

Previously, we showed that undifferentiated bone marrow stromal cell (uBMSC) implantation and vessel insertion into a nerve conduit facilitated peripheral nerve regeneration in a rodent model. In this study, we investigated the efficacy of the uBMSC-laden vessel-containing conduit in repair of segmental nerve defects, using a canine model. Eight beagle dogs were used in this study. Thirty-millimeter ulnar nerve defects were repaired with the conduits (right forelimbs, n = 8) or autografts (left forelimbs, n = 7). In the conduit group, the ulnar artery was inserted into the l-lactide/ε-caprolactone tube, which was filled with autologous uBMSCs obtained from the ilium. In the autograft group, the reversed nerve segments were sutured in situ. At 8 weeks, one dog with only nerve repair with the conduit was sacrificed and the regenerated nerve in the conduit underwent immunohistochemistry for investigation of the differentiation capability of the implanted uBMSCs. In the remaining seven dogs, the repaired nerves underwent electrophysiological examination at 12 and 24 weeks and morphometric measurements at 24 weeks. The wet weight of hypothenar muscles was measured at 24 weeks. At 8 weeks, almost 35% of the implanted uBMSCs expressed glial markers. At 12 weeks, amplitude (0.4 ± 0.4mV) and conduction velocity (18.9 ± 14.3m/s) were significantly lower in the conduit group than in the autograft group (3.2 ± 2.5 mV, 34.9 ± 12.1 m/s, P < 0.05). Although the nerve regeneration in the conduit group was inferior when compared with the autograft group at 24 weeks, there were no significant differences between both groups, regarding amplitude (10.9 ± 7.3 vs. 25.3 ± 20.1 mV; P = 0.11), conduction velocity (23.5 ± 8.7 vs 31.6 ± 20.0m/s; P = 0.35), myelinated axon number (7032 ± 4188 vs 7165 ± 1814; P = 0.94), diameter (1.73 ± 0.31 vs 2.09 ± 0.39μm; P = 0.09), or muscle weight (1.02 ± 0.40 vs 1.19 ± 0.26g; P = 0.36). In conclusion, this study showed that vessel-containing tubes with uBMSC implantation may be an option for treatment of peripheral nerve injuries. However, further investigations are needed. © 2015 Wiley Periodicals, Inc. Microsurgery 36:316-324, 2016., (© 2015 Wiley Periodicals, Inc.)

The purpose of this study was to observe whether the results of the median nerve fascicle transfer to the biceps are equivalent to the classical ulnar nerve fascicle transfer, in terms of elbow flexion strength and donor nerve morbidity. Twenty-five consecutive patients were operated between March 2007 and July 2013. The patients were divided into two groups. In Group 1 (n = 8), the patients received an ulnar nerve fascicle transfer to the biceps motor branch. In Group 2 (n = 15), the patients received a median nerve fascicle transfer to the biceps motor branch. Two patients with follow-up less than six months were excluded. Both groups were similar regarding age (P = 0.070), interval of injury (P = 0.185), and follow-up period (P = 0.477). Elbow flexion against gravity was achieved in 7 of 8 (87.5%) patients in Group 1, versus 14 of 15 (93.3%) patients in Group 2 (P = 1.000). The level of injury (C5-C6 or C5-C7) did not affect anti-gravity elbow flexion recovery in both the groups (P = 1.000). It was concluded that the median nerve fascicle transfer to the biceps is as good as the ulnar nerve fascicle transfer, even in C5-C7 injuries., (© 2014 Wiley Periodicals, Inc.)

The upper brachial plexus injury leads to paralysis of muscles innervated by C5 and C6 nerve roots. In this report, we present our experience on the use of the combined nerve transfers for reconstruction of the upper brachial plexus injury. Nine male patients with the upper brachial plexus injury were treated with combined nerve transfers. The time interval between injury and surgery ranged from 3 to 11 months (average, 7 months). The combined nerve transfers include fascicles of the ulnar nerve and/or the median nerve transfer to the biceps and/or the brachialis motor branch, and the spinal accessory nerve (SAN) to the suprascapular nerve (SSN) and triceps branches to the axillary nerve through a posterior approach. At an average of 33 months of follow-up, all patients recovered the full range of the elbow flexion. Six out of nine patients were able to perform the normal range of shoulder abduction with the strength degraded to M3 or M4. These results showed that the technique of the combined nerve transfers, specifically the SAN to the SSN and triceps branches to the axillary nerve through a posterior approach, may be a valuable alternative in the repair of the upper brachial plexus injury. Further evaluations of this technique are necessary., (Copyright © 2011 Wiley-Liss, Inc.)

Nerve allotransplantation has been used successfully in human subjects to restore function after traumatic nerve injury and avoid subsequent limb amputation. However, due to the morbidity associated with nonspecific immunosuppression, this reconstructive approach has been limited to patients with particularly severe nerve injuries. It would be desirable to broaden the indications for such procedures through development of less toxic antirejection therapies. A miniature swine model of nerve transplantation was used to investigate the effects of preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous infusion and injection of cultured major histocompatibility complex (MHC)-matched Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration through allografts injected with Schwann cells. Serial mixed lymphocyte assays demonstrated suppression of the recipient immune response to the donor antigen after pretreatment, but no additional neuroregenerative effect of donor alloantigen pretreatment.

We present 7 children with obstetric brachial plexus palsy treated by transferring two motor fascicles out of the ulnar nerve to the biceps nerve. Three were male, and 4 were female. The left-side brachial plexus was affected in 4 patients, and the right side in 3 patients. All children had vaginal delivery; two of them presented with shoulder dystocia. The average birth weight was 4300 g (range, 3620-5500 g). Average age at time of operation was 16 months (range, 11-24 months). The indication for the operation was absent active elbow flexion with active shoulder abduction against gravity in 4 cases, and no biceps function and bad shoulder function in 3 cases. Oberlin's ulnar nerve transfer was done in 4 cases without brachial plexus exploration in those children with good shoulder function, and exploration of the brachial plexus was performed in the other 3 cases with bad shoulder function. The average follow-up was 19 months (range, 13-30 months). Five children had biceps muscle >or=M(3) with active elbow flexion against gravity, and 2 children had biceps muscle

There is no known way to make paraplegics walk when their spinal cord is completely transected. Many researchers worldwide have been developing different methods to solve this problem. We believe that transferring a sound nerve from the upper limb to the main muscles of the hip could help paraplegics to walk, although light orthotic devices would still be needed. We chose to transfer the ulnar nerve because it is the longest in the upper limb and can reach the glutei without grafts. In addition, palsy of the ulnar nerve can be repaired by classical reconstructive surgery. After many years of research in animals and after obtaining permission from the Ethical Committee of the National Health Surgery, we operated on three human beings bilaterally. The first patient is walking. Two are still recovering., (Copyright 1999 Wiley-Liss, Inc.)

We investigated regeneration across a long nerve defect in the swine model to study extensive neural loss and long nerve gap. Most experiments have been conducted in the rodent model that, while an appropriate immunological model, only allows short nerve gaps to be studied. Twelve outbred swine received either an 8-cm ulnar nerve autograft or an allograft without immunosuppression. At 6 and 10 months, histomorphometry of the autografts demonstrated excellent nerve regeneration, while very poor regeneration was noted across the allografts. This confirmed that 8 cm are an adequate challenge independent of the spontaneous regeneration potential of axons seen in rodents. The swine ulnar nerve graft model causes minimal morbidity and will now be used with immunological manipulation of inbred animals.

Despite the introduction of microsurgical techniques into clinical practice, the results of surgical procedures involving the brachial plexus and peripheral nerves are still far from spectacular. We therefore studied the rat brachial plexus and its terminal branches in 203 rats. Detailed anatomic and morphologic analyses of the biceps brachii and musculocutaneous nerve, finger flexors, flexor carpi radialis, and the median nerve were performed. Various sources of conventional and vascularized nerve grafts were explored. After musculocutaneous nerve section or median nerve section, there were no articular contractures or automutilations, which constitutes an advantage for these experimental models over the sciatic nerve model. The brachial plexus and its terminal branches provide a good experimental model which can be used to assess the development and normal control of muscle function, examine the mechanisms underlying functional recovery, and test the effects of treatments to enhance recovery.

Our concept for the reconstruction of brachial plexus injuries includes an intercostal nerve transfer to the vascularized ulnar nerve graft. A free neurovascular latissimus dorsi is then transferred in a second stage operation. For optimization of the regeneration result, the operative planning of the second step includes nerve biopsies and enzymhistochemical evaluation for the distribution of motor axons. The staining method according to Scabolcz et al. is described and clinical cases are presented.