Nerve Reconstructive Procedures Research Articles

Heterologous fibrin biopolymer as an emerging approach to peripheral nerve repair: a scoping review.

Nerve injuries present a substantial challenge within the medical domain due to their prevalent occurrence and significant impact. In nerve injuries, a range of physiopathological and metabolic responses come into play to stabilize and repair the resulting damage. A critical concern arises from the disruption of connections at neuromuscular junctions, leading to profound degeneration and substantial loss of muscle function, thereby hampering motor tasks. While end-to-end neurorrhaphy serves as the established technique for treating peripheral nerve injuries, achieving comprehensive morphofunctional recovery remains a formidable challenge. In pursuit of enhancing the repair process, alternative and supportive methods are being explored. A promising candidate is the utilization of heterologous fibrin biopolymer, a sealant devoid of human blood components. Notably, this biopolymer has showcased its prowess in establishing a stable and protective microenvironment at the site of use in multiple scenarios of regenerative medicine. Hence, this scoping review is directed towards assessing the effects of associating heterologous fibrin biopolymer with neurorrhaphy to treat nerve injuries, drawing upon findings from prior studies disseminated through PubMed/MEDLINE, Scopus, and Web of Science databases. Further discourse delves into the intricacies of the biology of neuromuscular junctions, nerve injury pathophysiology, and the broader utilization of fibrin sealants in conjunction with sutures for nerve reconstruction procedures. The association of the heterologous fibrin biopolymer with neurorrhaphy emerges as a potential avenue for surmounting the limitations associated with traditional sealants while also mitigating degeneration in nerves, muscles, and NMJs post-injury, thereby fostering a more conducive environment for subsequent regeneration. Indeed, queries arise regarding the long-term regenerative potential of this approach and its applicability in reconstructive surgeries for human nerve injuries.

Systematic Review With Meta-Analysis: Are Muscle Transfers a Satisfactory Treatment Option to Restore Shoulder Abduction in Delayed Adult Brachial Plexus Injuries?

Brachial plexus injuries usually result in significant upper limb disabilities and shoulder joint instability. Primary nerve reconstruction procedures are more effective if performed within six months from the injury. Secondary procedures, including muscle transfers, are usually indicated for delayed presentation (>6 months) or when the outcomes of primary procedures are unsatisfactory.A comprehensive systematic search of the MEDLINE, EMBASE, AMED, PubMed, and Cochrane databases was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including demographic information, time to surgery, the extent of brachial plexus injury, surgical techniques, follow-up duration, and functional outcomes were collected and tabulated. Meta-analysis was conducted using Review Manager (RevMan) 5.4 software ([Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Seven studies were eligible to be included in this review, with a total of 218 patients. The average patient age was 28.39 ± 3 years, with a mean time to surgery of 29.87 ± 18 months. Forty-six (46) patients (21.10%) were treated as delayed presentation and 172 patients (78.89%) had muscle transfer performed as a secondary procedure. The mean time at follow-up was 18.86 ± 13.5 months. Upper trapezius muscle transfer was the most common transferred muscle (100%) either in isolation (n=159, 72.93%) or in combination with lower trapezius transfer (n=59, 27.06%). The mean preoperative and postoperative shoulder abduction were 12.22 ± 10.09 degrees and 58.36 ± 32.33 degrees, respectively (p < 0.05). Meta-analysis shows a statistically significant difference (CI at 95%, p<0.05) favoring postoperative shoulder abduction.Muscle transfers especially upper trapezius transfer could be a satisfactory secondary procedure to restore shoulder abduction and enhance shoulder joint stability.

A morphologic and histologic study of the radial nerve and its branches at potential compression sites

ObjectivesThis study examined variations in the termination level of the radial nerve (RN) and the morphometry of the RN and its branches at potential compression sites. Additionally, we digitally analysed histological sections of the RN, the superficial branch of the radial nerve (SBRN), and the posterior interosseous nerve (PIN). MethodsWe conducted this study on 14 formalin fixed adult cadavers. The lengths of the RN, SBRN, and PIN were measured up to potential compression sites, using appropriate surface skeletal landmarks as reference points. We histologically evaluated the fascicular and non-fascicular areas and the number of axons in each nerve. All parameters were statistically analysed using a paired t-test. ResultsWe found variations in the bifurcation of the RN with respect to the biepicondylar line (BEL). However, the course of RN terminal branches was constant in the forearm. There was a significant histological difference between the fascicular and non-fascicular areas of the PIN. There was no significant difference in the total number of axons in the SBRN and PIN. Finally, we observed that the intramuscular length of the PIN within the supinator muscle was variable and that the SBRN had more fascicles compared to the RN and PIN. ConclusionsIn our study, the RN and PIN had more variable morphometry compared to that of the SBRN. The histologic evaluation and quantification of these nerves at their potential compression sites could serve as a guide for surgeons planning nerve reconstruction procedures.

Preclinical Validation of SilkBridgeTM for Peripheral Nerve Regeneration.

Silk fibroin (Bombyx mori) was used to manufacture a nerve conduit (SilkBridgeTM) characterized by a novel 3D architecture. The wall of the conduit consists of two electrospun layers (inner and outer) and one textile layer (middle), perfectly integrated at the structural and functional level. The manufacturing technology conferred high compression strength on the device, thus meeting clinical requirements for physiological and pathological compressive stresses. As demonstrated in a previous work, the silk material has proven to be able to provide a valid substrate for cells to grow on, differentiate and start the fundamental cellular regenerative activities in vitro and, in vivo, at the short time point of 2 weeks, to allow the starting of regenerative processes in terms of good integration with the surrounding tissues and colonization of the wall layers and of the lumen with several cell types. In the present study, a 10 mm long gap in the median nerve was repaired with 12 mm SilkBridgeTM conduit and evaluated at middle (4 weeks) and at longer time points (12 and 24 weeks). The SilkBridgeTM conduit led to a very good functional and morphological recovery of the median nerve, similar to that observed with the reference autograft nerve reconstruction procedure. Taken together, all these results demonstrated that SilkBridgeTM has an optimized balance of biomechanical and biological properties, which allowed proceeding with a first-in-human clinical study aimed at evaluating safety and effectiveness of using the device for the reconstruction of digital nerve defects in humans.

The Inverted Free Functioning Gracilis Muscle Transfer For Restoration of Elbow Flexion Following Delayed Presentation or Failed Primary Nerve Reconstruction of Upper Trunk Injuries.

Free functional gracilis transfer is a well-established technique for restoring active elbow flexion in brachial plexus injuries following delayed presentation or failed nerve reconstruction procedures. In cases of delayed presentation or failed nerve reconstruction following upper trunk injuries, the lower trunk intraplexal median and ulnar nerves are spared, thereby making them available to reinnervate the transferred gracilis. Therefore, we have inverted the conventional free functional gracilis orientation so as to orient the flap's recipient nerve in closer proximity to donor median or ulnar nerve fascicles to enable a short, tension-free coaptation in the middle to distal arm. Herein is our descriptive surgical technique for performing an inverted free functional gracilis muscle transfer in order to restore elbow flexion in the setting of an upper trunk injury.

The Effectiveness of Nerve Reconstruction Procedure with Flap Coverage for Iatrogenic Nerve Injury around the Wrist Joint

The Effectiveness of Nerve Reconstruction Procedure with Flap Coverage for Iatrogenic Nerve Injury around the Wrist Joint

Nerve injuries of the upper extremity and hand.

A nerve injury has a profound impact on the patient’s daily life due to the impaired sensory and motor function, impaired dexterity, sensitivity to cold as well as eventual pain problems.To perform an appropriate treatment of nerve injuries, a correct diagnosis must be made, where the injury is properly classified, leading to an optimal surgical approach and technique, where timing of surgery is also important for the outcome.Knowledge about the nerve regeneration process, where delicate processes occur in neurons, non-neuronal cells (i.e. Schwann cells) and other cells in the peripheral as well as the central nervous systems, is crucial for the treating surgeon.The surgical decision to perform nerve repair and/or reconstruction depends on the type of injury, the condition of the wound as well as the vascularity of the wound.To reconnect injured nerve ends, various techniques can be used, which include both epineurial and fascicular nerve repair, and if a nerve defect is caused by the injury, a nerve reconstruction procedure has to be performed, including bridging the defect using nerve-grafts or nerve transfer techniques.The patients must be evaluated properly and regularly after the surgical procedure and appropriate rehabilitation programmes are useful to improve the final outcome.Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160071. Originally published online at www.efortopenreviews.org

Decellularized Nerves for Upper Limb Nerve Reconstruction: A Systematic Review of Functional Outcomes.

This is a systematic review for evaluating the evidence for functional outcomes after decellularized nerve use in clinical setting. Decellularized nerves are allografts whose antigenic components have been removed, leaving only a scaffold that promotes the full regeneration of axons. Literature research was performed using the PubMed/MEDLINE database for English language studies with the keywords "decellularized nerve" and "processed nerve allograft." Inclusion criteria were prospective and retrospective case reviews in clinical settings. Exclusion criteria were case reports and case series. We retrieved six level VIII studies and one level VI study (classified according to the Jovell and Navarro-Rubio scale) with a total of 131 reconstructions. The basic data ranges of the studies were as follows: patient age, 18 to 86 years; duration between initial injury and nerve reconstruction procedure, 8 hours to 4 years; and follow-up period, 40 days to 2 years. The maximum lengths of the nerve gap for chemically washed decellularized nerves and cryopreserved decellularized nerves were 50 and 100 mm, respectively. Quantitatively, the functional outcome ranges were as follows: static two-point discrimination, 3 to 5 mm; and moving two-point discrimination, 2 to 15 mm. For motor assessment, all patients had a > M3 Medical Research Council score. It is also important to notice that a large variability occurs in almost every factor in the reviewed studies. Our study is the first to summarize the clinical results of decellularized nerves. Decellularized nerves have been used to bridge nerve gaps ranging from 5 to 100 mm with associated satisfactory outcomes in static and moving two-point discriminations.

Results of nerve reconstructions in treatment of obstetrical brachial plexus injuries.

The aim of this study was to evaluate the results achieved using various surgical techniques in patients with partial and total obstetrical brachial plexus palsy. From 2000 to 2013, 33 patients with obstetrical brachial plexus injury underwent surgery. Twenty had follow-up periods greater than 24 months and met the criteria for inclusion in the study. All patients were evaluated using the Active Movement Scale. The outcomes of different nerve reconstructive procedures including nerve transfers, nerve grafting after neuroma resection and end-to-side neurorrhaphy are presented. The overall success rate in upper plexus birth injury was 80 % in shoulder abduction, 50 % in external rotation and 81.8 % in elbow flexion with median follow-ups of 36 months. Success rate in complete paralysis was 87 % in finger and thumb flexion, 87 % in shoulder abduction and 75 % in elbow flexion; the median follow-up was 46 months. Useful reanimation of the hand was obtained in both patients who underwent end-to-side neurotization. Improved function can be obtained in infants with obstetrical brachial plexus injury with early surgical reconstruction.

Free functional gracilis muscle transfer in children with severe sequelae from obstetric brachial plexus palsy

We present 4 children between 6 and 13 years suffering from severe sequelae after a total obstetric brachial plexus lesion resulting in a hand without functional active long finger flexion. They had successfully reanimated long finger flexion using a free functional gracilis muscle transfer. These children initially presented a total obstetric brachial plexus palsy without neurotisation of the lower trunk in an early microsurgical nerve reconstruction procedure.We describe our indications for this complex microsurgical procedure, the surgical technique and the outcome.

Nerve injuries and posttraumatic therapy

Peripheral nerve injuries are a common clinical problem and can represent a major challenge, especially after trauma. In order to achieve optimal therapy, an early and adequate diagnosis with subsequent therapy is critical for functional preservation and restoration. Especially after complete severance of a peripheral nerve, the surgical techniques for nerve coaptation are an important prerequisite for peripheral nerve regeneration. The importance and necessity of adequate nerve coaptation and nerve transplantation are presented in detail. In addition, the types of primary and secondary nerve reconstruction procedures are described as well as the optimal time point of nerve repair. This article provides a comprehensive overview of the possibilities for diagnosis and intervention after nerve injury, additionally including an algorithm for surgical intervention. Furthermore, possible pitfalls and factors for improving the functional outcome are presented to optimize results with trauma-related nerve injury.

Subjective outcome related to donor site morbidity after sural nerve graft harvesting: a survey in 41 patients

BackgroundThe sural nerve is the most commonly used nerve for grafting severe nerve defects. Our aim was to evaluate subjective outcome in the lower leg after harvesting the sural nerve for grafting nerve defects.MethodsForty-six patients were asked to fill in a questionnaire to describe symptoms from leg or foot, where the sural nerve has been harvested to reconstruct an injured major nerve trunk. The questionnaire, previously used in patients going through a nerve biopsy, consists of questions about loss of sensation, pain, cold intolerance, allodynia and present problems from the foot. The survey also contained questions (visual analogue scales; VAS) about disability from the reconstructed nerve trunk.ResultsForty-one out of 46 patients replied [35 males/6 females; age at reconstruction 23.0 years (10–72); median (min-max), reconstruction done 12 (1.2-39) years ago]. In most patients [37/41 cases (90%)], the sural nerve graft was used to reconstruct an injured nerve trunk in the upper extremity, mainly the median nerve [19/41 (46%)].In 38/41 patients, loss of sensation, to a variable extent, in the skin area innervated by the sural nerve was noted. These problems persisted at follow up, but 19/41 noted that this area of sensory deficit had decreased over time. Few patients had pain and less than 1/3 had cold intolerance. Allodynia was present in half of the patients, but the majority of them considered that they had no or only slight problems from their foot. None of the patients in the study required painkillers. Eighty eight per cent would accept an additional sural nerve graft procedure if another nerve reconstruction procedure is necessary in the future.ConclusionsHarvesting of the sural nerve for reconstruction nerve injuries results in mild residual symptoms similar to those seen after a nerve biopsy; although nerve biopsy patients are less prone to undergo an additional biopsy.

Axillary nerve injury in young adults—An overlooked diagnosis? Early results of nerve reconstruction and nerve transfers

An injury to the axillary nerve from a shoulder trauma can easily be overlooked. Spontaneous functional recovery may occur, but occasionally reconstructive surgery is required. The time frame for nerve reconstruction procedures is from a neurobiological view crucial for a good functional outcome. This study presents a group of operatively and non-operatively treated young adults with axillary nerve injuries caused by motorcycle accidents, where the diagnosis was set late. Ten young men (median age at trauma 13 years, range 9–24) with an axillary nerve injury were diagnosed by examination of shoulder function and electromyography (EMG). The patients had either a nerve reconstruction procedure or were treated conservatively and their recovery was monitored. The axillary nerve was explored and reconstructed at a median of 8 months (range 1–22 months) after trauma in 8/10 patients. Two patients were treated non-operatively. In 4/8 cases, a reconstruction with sural nerve graft was performed and in 1/8 case only exploration of the nerve was made (minor neuroma). In 3/8 cases a radial nerve branch transfer to the axillary nerve was chosen as the procedure. The shoulder was mobilised after 3 weeks with physiotherapy and the patients were monitored regularly. Functional recovery was observed in 9/10 cases (median follow up 11 months, range 7–64) with EMG signs of reinnervation in seven patients. Axillary nerve function should not be overlooked in young patients with a minor shoulder trauma. Nerve reconstruction can successfully recreate function.

Facial Nerve Repair With Gore-Tex Tube and Adipose-Derived Stem Cells: An Animal Study in Dogs

Synthetic conduits have been considered a viable option in nerve reconstructive procedures. They address the goal of entubulization and eliminate the disadvantages of autografts. However, despite all successful reports, none has contained regeneration characteristics, such as growth factors or essential cells, for nerve repair. The authors evaluated the capability of adipose-derived stem cells in Gore-Tex tubes to enhance facial nerve repair. Undifferentiated mesenchymal stem cells were extracted from the autogenous adipose tissues of 7 mongrel dogs. The frontal branch of the facial nerve was transected. A gap size of 7 mm was repaired with an expanded polytetrafluoroethylene tube filled with undifferentiated adipose-derived stem cells encapsulated in alginate hydrogel. The control sides were repaired with the tube and alginate alone. The healing phase was 12 weeks. Except in 2 control sides, an organized neural tissue was formed within the tubes. Compared with the normal nerve diameter, there was a decreased ratio of 29% and 39% in the experimental and control groups, respectively. Neurofilament-positive axon counts were 67% of normal values in the 2 groups. There was no significant difference between groups in histomorphometric parameters. Nerve conduction velocity in the experimental group (28.5 ± 3.5 m/s) was significantly greater than in the control group (16.2 ± 7 m/s). The experimental group also exhibited a greater maximal amplitude of action potential (1.86 ± 0.24 mV) than the control group (1.45 ± 0.49 mV). Addition of stem cells in the Gore-Tex tube enhanced the neural repair from a functional standpoint. However, for better functional and histologic results, differentiated Schwann cells and other mediators may be warranted.

Facial nerve reconstruction using a muscle flap following resection of parotid gland tumours with thorough recipient bed preparation

Recent innovations in facial nerve reconstruction procedures or 'restoration of facial expression', extremely important in patients' social activities, have provided some interesting findings. However, there has been little discussion of immediate facial nerve reconstruction following resection of a parotid carcinoma. In this article, details of our techniques and the concepts are presented. Ten patients underwent immediate facial nerve reconstruction following resection of a parotid carcinoma, with thorough 'recipient bed preparation', between October 2003 and October 2009. Postoperative radiotherapy was administered to seven cases, with an average radiation dosage of 55 Gy. Nerve reconstruction was performed using a sural nerve graft and either method 1, using a sternocleidomastoid and platysma muscle flap or method 2, using a pectoralis major muscle flap. Method 1 was used in six cases, and method 2 in four. Postoperative function was House Brackmann (HB) grade II in two cases, grade III in seven, grade IV in one and unassessable in one. Average Sunnybrook facial grading score was 50. No complications, such as contour deformity or Frey syndrome, were detected. We performed immediate facial nerve reconstruction following resection of parotid tumours with the emphasis on recipient bed preparation using a muscle flap, achieving the following objectives: (1) stable facial nerve reconstruction; (2) avoidance of contour deformity; and (3) prevention of Frey syndrome. We believe this is an extremely useful method, technically easy to perform and provides stable results.

Chirurgische Korrektur des paralytischen Lagophthalmus

Impairment of the peripheral or central part of the facial nerve causes an ipsilateral peripheral facial nerve paresis. It is quite a common syndrome and affects 20-35 persons per 100,000 per year in Western Europe and the United States. A possible complication of facial palsy is paralytic lagophthalmos with aesthetic and functional impairment for the patient. Beside primary nerve reconstructive procedures plastic-reconstructive procedures play a major role in correcting paralytic lagophthalmos. The eyebrow, upper and lower lids, medial and lateral lid angle as well as the lacrimal system need to be seen as functional units and can be corrected with local surgical procedures. Restoration of eye closure is the most important goal in treating the affected eye. Due to the significant aesthetic limitations and resultant psychological stress for the patient cosmetic aspects must be included in the surgical concept.

The epineural sleeve technique for nerve graft reconstruction enhances nerve recovery

The purpose of the study was evaluation of nerve recovery following epineural sleeve technique for graft reconstruction in rat sciatic nerve. This technique provides the epineural sleeve to cover and separate the site of coaptation. Animals were divided into three groups: CNG-conventional nerve grafting, ESN-epineural sleeve from recipient nerve stumps, ESG-epineural sleeve from graft. Nerve regeneration was evaluated by pin-prick, toe-spread test, walking track analysis and somatosensory-evoked potentials (SEP), gastrocnemius index (GI), and histomorphometric evaluation. Most parameters (SFI, SEPs, and GI) showed significantly better nerve recovery for ESN group when compared to conventional CNG group. Also ESG group revealed better result for SFI. Better functional results for ESN and ESG groups were further confirmed by histomorphometric analysis: higher axon density and diameters as well as thicker myelin sheath. Epineural sleeve graft technique may be promising method with potential application for nerve reconstructive procedures. Better functional nerve recovery can be anticipated.

The Lesions of the Facial Nerve and a Surgical Reconstruction Algorithm

Paralysis of the facial nerve (FNP) has a widely varied etiology. Pathological lesions of the skull base causing facial nerve paralysis may be divided into three groups: lesions of the brainstem, the posterior fossa, and the temporal bone. In our experience, FNP is seldom caused by removal of posterior fossa lesions such as acoustic neurinomas, especially when the continuity of the nerve was preserved. However, lesions compressing the facial nucleus at the brainstem and infectious infiltration of the FN in the temporal bone are more frequent causes. The surgical reconstruction strategy of the injured FN depends on several factors: unimpaired brainstem facial nucleus, the availability of the proximal FN in the posterior fossa, and functional integrity of the target muscles. It has been shown that primary reconstruction of the facial nerve has its supremacy over secondary reconstructive procedures. Nerve reconstruction procedures include direct sutures and grafting, cross face grafting, XII-VII transfer, and others. Ancillary reconstruction options may be subdivided into two major categories: static and dynamic. Static reconstructions constitute face lifting, netting, and suspension. Dynamic procedures include local muscle transfers and free vascularized and innervated muscle transfer. The free vascularized and innervated muscle transfer may be performed as a two-stage procedure or a one-stage procedure. We use the one-stage procedure in our clinic. Based on our experience with 16 patients with FN reconstructions, 8 patients with secondary static corrections, and 15 patients with secondary dynamic free vascularized and innervated nerve transfers, we conclude the following: (1) XII-VII is best suited for old candidates, where a facial nuclear involvement is present; (2) if ipsilateral XII-N is affected, a VII-VII cross face transfer is the next option; (3) in long-standing FNP a local dynamic procedure is valuable in old candidates and a free vascularized and innervated muscle transfer in the young.

Agmatine treatment and vein graft reconstruction enhance recovery after experimental facial nerve injury

The rate of nerve regeneration is a critical determinant of the degree of functional recovery after injury. Here, we sought to determine whether treatment with the neuroprotective compound, agmatine, with or without nerve reconstruction utilizing a regional autogenous vein graft would accelerate the rate of facial nerve regeneration. Experiments compared the following seven groups of adult male rats: (A) Intact untreated controls. (B) Sham operation with interruption of the nerve blood supply (controls). (C) Transection of the mandibular branch of the facial nerve (generating a gap of 3 mm) followed by saline treatment. (D) Nerve transection with unsutured autogenous vein (external jugular) graft reconstruction plus saline treatment. (E) Nerve transection with sutured vein graft approximation (coaptation of the proximal and distal nerve stumps) plus saline. (F) Nerve transection with sutured vein graft followed by agmatine treatment (four daily intraperitoneal injections of 100 mg/kg agmatine sulfate). (G) Nerve transection with unsutured vein graft followed by agmatine treatment. Functional recovery, as assessed by grading vibrissae movements and by recording nerve conduction velocity and numbers of regenerated axons, indicated that either vein reconstruction or agmatine treatment resulted in accelerated and more complete recovery as compared with controls. But best results were observed in animals that underwent combined treatment, i.e., vein reconstruction plus agmatine injection. We conclude that agmatine treatment can accelerate facial nerve regeneration and that agmatine treatment together with autogenous vein graft offers an advantageous alternative to other facial nerve reconstruction procedures.

59 Nerve action potential recording provides a valuable criterion selecting a qualified proximal coaptation site in nerve reconstruction

Since 5 years we routinely use nerve action potential recording as described by Kline and his co-workers for the exposed nerve not only to test for spontaneous nerve regeneration across a lesion, but also as an additional criterion to assess the quality of a proximal coaptation site for grafts or direct suture. Histology was used to control for the validity of this test. The correlation between neurography and histlogy is convincing whereas assessment of the nerve cross section with the operating microscope is not reliable with regard to the number and quality of nerve fibres present at the resection site. Therefore we recommend, to apply nerve action potential recording routinely in nerve reconstruction procedures to assess the quality of the proximal coaptation site especially in chronic lesions and when distension of the nerve, inflammation, heat, chemical injury or ischaemia play a role in the pathomechanism.