Peripheral Nerve Suture Research Articles

Morphological Foundations of Restoration of Motor Innervation in Injuries of Peripheral Nerves

The problem of restoration of motor innervation is considered to be challenging due to a significant proportion of the peripheral nerve damage in the general structure of peacetime and wartime injuries, as well as a high risk of permanent function loss of the affected limb. Injuries of the peripheral nerves result in a complex of pathophysiological processes from both – the side of damaged nerve stems and the side of denervated target tissues. Moreover, the morphological picture of tissue changes is both degenerative and regenerative simultaneously. The process of secondary degeneration of the distal segments of crossed axons is similar to aseptic inflammation and is a prerequisite for the subsequent regeneration of nerve fibers. The process of reinnervation of the distal segment of the crossed nerve stem has a certain similarity with the development of peripheral nerves in the embryonic period, but the branches of regenerating axons move in the distal direction along the preserved neuriluminal tubes. A prolonged absence of motor innervation causes pronounced dystrophic changes in muscle fibers and intercellular spaces filling with the fibrous connective tissue; this, in turns, may result in a lack of functional limb restoration even if the terminal branches of the damaged nerve are adequately reinnervated. The restoration of contractile activity of reinnervated muscles is morphologically determined by the functional hypertrophy of the preserved muscle fibers, since the complete restoration of the innervation of all muscle fibers is practically not achievable due to the peculiarities of the peripheral nerve suture technique and the patterns of nerve fiber regeneration. Thus, an understanding of the patterns and morphological manifestations of degenerative-regenerative processes in tissues with injuries of peripheral nerves will allow substantiating the need for reconstructive plastic interventions on nerve stems from morphological points of view, based on the possibilities of achieving significant functional results.

Reduction of neural scarring after peripheral nerve suture: An experimental study about collagen membrane and autologous vein wrapping

The effects of a collagen membrane and a technique of autologous vein wrapping on scar formation after peripheral nerve suture are investigated. Forty-eight sciatic nerves from Wistar rats were transected and repaired, then allocated to a control group C (n=16) and two experimental groups: in group A (n=16) the repair line was covered by the collagen membrane, and in group B (n=16) the repair line was wrapped by an external jugular venous graft. Three months later, it was observed that adhesions in the surrounding tissues were significantly less in groups A and B compared to group C, and significantly less in group A than in the group B. Histological analysis revealed no significant reduction of extraneural or intraneural scar tissue in groups A or B compared to group C. However intraneural fibrosis was significantly less in the group A than in the group B. It was concluded that the collagen membrane was effective in reducing neural scar formation after peripheral nerve suture. Autologous vein wrapping also showed a favorable effect in this indication despite less successful histological outcomes.

Inhibition of nitric oxide synthase promotes facial axonal regeneration following neurorrhaphy

Reconnection of interrupted peripheral nerve by microsurgical suture is a common clinical practice. However, the extent to which peripheral neurorrhaphy improves nerve regeneration and functional recovery remains unsatisfactory. Here, we used anatomical and electrophysiological techniques to investigate the temporal correlation between the expressions of oxidative stress-related biomarkers such as neuronal nitric oxide synthase (nNOS) and the facial axonal regeneration after an immediate facial nerve repair in adult rats since peripheral nerve lesion is well known to induce a dramatic increase of NOS expression in the affected neuronal cell bodies. We found that compared to nerve cut without suture, facial nerve repair not only caused the facial axonal regeneration but also consistently prevented the fluctuations of expressions of oxidative stress-related biomarkers in 10 weeks postlesion. To further elucidate the role of nitric oxide (NO) in the axonal degeneration/regeneration, four different NOS inhibitors were applied to additional rats after facial nerve cut or repair. Both of facial nerve cut + NOS inhibition and facial nerve repair + NOS inhibition were seen to prevent the alterations of expressions of the biomarkers, no matter which NOS inhibitor was used. Moreover, we found that facial nerve repair + NOS inhibition promoted earlier and better axonal regeneration than facial nerve repair, demonstrated by labeling of neuromuscular junctions, retrograde tracing, and electromyography. These results provide direct evidence that peripheral nerve suture and/or treatment of NOS inhibitors can maintain the homeostasis of oxidative stress-related biomarkers, especially nNOS in neuronal cell bodies. These actions may thus facilitate the axonal regeneration.

Suture of Transected Nerve Suppresses Expression of BH3-Only Protein Noxa in Nerve-Transected Motor Neurons of C57BL/6J Mouse

Disrupted peripheral nerves are typically sutured as spontaneous recovery does not always occur. However, the molecular mechanisms involved in nerve regeneration following end-to-end nerve suture are obscure. Here, we investigated effects of end-to-end nerve suture after peripheral nerve transection on motor neurons, using the C57BL/6J mouse hypoglossal nerve injury model. In this animal model, 60-80% of injured motor neurons gradually progress to neuronal death, while the remaining injured neurons survive and regenerate. Mice were divided into the Cut and Suture groups. In the Cut group, the right hypoglossal nerve was transected. In the Suture group, the right hypoglossal nerve was transected and then was repaired using end-to-end nerve suture. We assessed differences between the Cut and Suture groups by analyzing the neuronal survival rate by thionine staining and the nerve terminal regeneration rate by vesicular acetylcholine transporter (VAChT) immunohistochemistry, which is a marker for cholinergic presynaptic terminal. We found that 82.9% of motor neurons survived in the Suture group, whereas only 39.2% of motor neurons did in the Cut group 56 days after surgery. At that time point, 86% of presynaptic terminals compared to controls were regenerated in the Suture group, and 21% were regenerated in the Cut group. These results demonstrate that peripheral nerve suture prevented death of nerve-transected motor neurons and promoted nerve regeneration. We also examined expression profiles of major survival and death signal-associated genes in hypoglossal nuclei using in situ hybridization and real-time polymerase chain reaction (PCR). Although most of the survival- and death-associated genes were regulated in a similar manner in both groups, expression of BH3-only protein Noxa mRNA was significantly lower in the Suture than in the Cut group. A significant suppression of Noxa expression by the Suture may be a major reason why nerve suture induces survival and regeneration of nerve-injured motor neurons.

Assessment of Sensibility after Nerve Injury and Repair: A Systematic Review of Evidence for Validity, Reliability and Responsiveness of Tests

Recovery of sensibility after peripheral nerve injury and repair needs to be assessed using psychometrically robust measures. In this study the literature was reviewed to identify what tests are available to quantify sensibility and to assess their validity, reliability and responsiveness. The databases Medline, CINAHL, Embase and AMED were searched for studies reporting the psychometric properties of sensibility tests. While there is a plethora of tests and studies reporting the outcomes after peripheral nerve suture only a few of the tests have evidence of validity, reliability and responsiveness. Currently the touch threshold test using monofilaments such as the Weinstein Enhanced Sensory Test (WEST) or Semmes-Weinstein Monofilament Test (SWMT) and the shape-texture identification (STI) test for tactile gnosis are the only tests which meet criteria for a standardized test and have had their psychometric properties evaluated and quantified.

Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron.

Motoneurons reinnervate the distal stump at variable rates after peripheral nerve transection and suture. In the rat femoral nerve model, reinnervation is already substantial 3 weeks after repair, but is not completed for an additional 7 weeks. However, this "staggered regeneration" can be temporally compressed by application of 20 Hz electrical stimulation to the nerve for 1 hr. The present experiments explore two possible mechanisms for this stimulation effect: (1) synchronization of distal stump reinnervation and (2) enhancement of regeneration speed. The first possibility was investigated by labeling all motoneurons that have crossed the repair at intervals from 4 d to 4 weeks after rat femoral nerve transection and suture. Although many axons did not cross until 3-4 weeks after routine repair, stimulation significantly increased the number crossing at 4 and 7 d, with only a few crossing after 2 weeks. Regeneration speed was studied by radioisotope labeling of transported proteins and by anterograde labeling of regenerating axons, and was not altered by stimulation. Attempts to condition the neuron by stimulating the femoral nerve 1 week before injury were also without effect. Electrical stimulation thus promotes the onset of motor axon regeneration without increasing its speed. This finding suggests a combined approach to improving the outcome of nerve repair, beginning with stimulation to recruit all motoneurons across the repair, followed by other treatments to speed and prolong axonal elongation.

Electrical Stimulation Promotes Motoneuron Regeneration without Increasing Its Speed or Conditioning the Neuron

Motoneurons reinnervate the distal stump at variable rates after peripheral nerve transection and suture. In the rat femoral nerve model, reinnervation is already substantial 3 weeks after repair, but is not completed for an additional 7 weeks. However, this "staggered regeneration" can be temporally compressed by application of 20 Hz electrical stimulation to the nerve for 1 hr. The present experiments explore two possible mechanisms for this stimulation effect: (1) synchronization of distal stump reinnervation and (2) enhancement of regeneration speed. The first possibility was investigated by labeling all motoneurons that have crossed the repair at intervals from 4 d to 4 weeks after rat femoral nerve transection and suture. Although many axons did not cross until 3-4 weeks after routine repair, stimulation significantly increased the number crossing at 4 and 7 d, with only a few crossing after 2 weeks. Regeneration speed was studied by radioisotope labeling of transported proteins and by anterograde labeling of regenerating axons, and was not altered by stimulation. Attempts to condition the neuron by stimulating the femoral nerve 1 week before injury were also without effect. Electrical stimulation thus promotes the onset of motor axon regeneration without increasing its speed. This finding suggests a combined approach to improving the outcome of nerve repair, beginning with stimulation to recruit all motoneurons across the repair, followed by other treatments to speed and prolong axonal elongation.

Peripheral nerve suture

Peripheral nerve suture (neurorrhaphy) is a method of nerve repair that has been employed for many years, although the development and spread of microsurgery has helped to improve the techniques used. Now, by using microscopes and microsurgical techniques, peripheral nerve suturing can be performed more precisely and atraumatically than in the past. The technique is now indicated for a wider range of cases, including suturing of the brachial plexus and its branched axillary nerve, and for digital nerves. In addition to conventional epineurial sutures, a funicular suture has been introduced, and results using these two methods are now being compared. Advances have also been made in the field of rehabilitation, including the introduction of electromyogram (EMG) biofeedback therapy and re-education of sensation. Included in the issues that need to be further addressed are the treatment of nerve injuries caused by severe crushing and traction, and misdirection of regenerated nerves. It is hoped that more studies will be carried out to encompass a broad range of topics, from basic research to promote nerve regeneration to rehabilitation. In this paper, the author reviews the past 20years, experience of peripheral nerve suturing, discusses the problems encountered, and outlines future prospects.

Measuring outcome in median nerve injuries

Assessing the functional outcome of peripheral nerve suture in the hand requires a battery of tests which are valid, reliable and comprehensively evaluate cutaneous sensibility. This study explores the relationship between a battery of sensory tests and the patient's capacity to perform everyday functional activities. An analysis of the interrelationship between all outcome variables reveals that the tests of sensibility do not predict the patients' ability to use their hands in everyday activities, thus indicating that patients are able to compensate for sensory deficit through the use of vision and bilateral use of the hands. An assessment of outcome should therefore include an additional measure of performance on daily living tasks.

The Validation of Measures of Outcome Following Suture of Divided Peripheral Nerves Supplying the Hand

Erik Moberg pioneered the idea of validating measures of sensory function following peripheral nerve suture by correlating their results with those of functional tests. However it is important that powerful prior variables (age at suture, time elapsed since suture and delay between injury and suture) be controlled. Failure to do this may result in spurious correlations, as illustrated by analysis of two sets of data, one collected by the author and the other given in the classic paper of Onne (1962).

The validation of measures of outcome following suture of divided peripheral nerves supplying the hand

Erik Moberg pioneered the idea of validating measures of sensory function following peripheral nerve suture by correlating their results with those of functional tests. However it is important that powerful prior variables (age at suture, time elapsed since suture and delay between injury and suture) be controlled. Failure to do this may result in spurious correlations, as illustrated by analysis of two sets of data, one collected by the author and the other given in the classic paper of Önne (1962).

Does the use of the operating microscope improve the results, of peripheral nerve suture?

Does the use of the operating microscope improve the results, of peripheral nerve suture?

Preferential reinnervation of motor nerves by regenerating motor axons

Regeneration of axons into inappropriate distal nerve branches may adversely affect functional recovery after peripheral nerve suture. The degree to which motor axons reinnervate sensory nerves, and vice versa, has not been determined. In these experiments, HRP is used to quantify the sensory and motor neurons that reinnervate sensory and motor branches of the rat femoral nerve after proximal severance and repair. Motoneurons preferentially reinnervate the motor branch in juveniles and adults, even if the repair is intentionally misaligned or a gap is imposed between proximal and distal stumps. A specific interaction thus occurs between regenerating motor axons and the Schwann cell tubes that lead to the motor branch. This interaction is independent of mechanical axon alignment.

Epineurial Suture versus Epi-perineurial Suture: A Comparative Clinical Study

There are many types of peripheral nerve suture today. The deluge of information on nerve suture contributes to the confusion about which type of suture should be selected. The purpose of our study was to compare results of epineurial suture vs. epi-perineurial suture in twenty-one patients who have median nerve injury at the wrist. These patients satisfied eleven factors that influenced nerve repair. Ten nerves were repaired by epineurial suture with 7-0 or 8-0 nylon. Eleven patients were repaired by epi-perineurial suture with 8-0, 9-0 or 10-0 nylon. All sutures were done under magnification with use of microsurgical technique. No significant differences were detected between the results of epineurial suture and epi-perineurial suture. The epineurial suture technically is less cumbersome to perform. Our results suggest that epineurial suture is more satisfactory for most of the peripheral nerve repairs.

Funicular orientation by electrical stimulation and internal neurolysis in peripheral nerve suture

Funicular orientation by electrical stimulation and internal neurolysis in peripheral nerve suture

Epineurial Nerve Suture

The final chapter on the results of peripheral nerve suture has not been written. Continued interest of investigators in this area will probably lead to improve results in the future. The biology of repair remains a determining factor once meticulous technique has been exercised by the surgeon. Epineurial neurorrhaphy is the standard technique today for peripheral nerve suture.

Funicular orientation by electrical stimulation and internal neurolysis in peripheral nerve suture

Eleven peripheral nerve lacerations around the wrists of ten patients were treated with funicular suture or nerve graft. In three freshly lacerated nerves funicular orientation could be made only by electrical stimulation to both cut ends. The electrophysiological method was also utilised to obtain funicular orientation of a proximal stump in eight old nerve lacerations. However, funicular orientation of the distal stump of old lacerations, which was not responsive to electrical stimulation, was performed anatomically by internal neurolysis from a terminal branching area up to a distal stump. By six months after the operation, motor and sensory functions of the patients with funicular suture had recovered to an excellent degree with rapid reinnervation.

Experimental regeneration in peripheral nerves and the spinal cord in laboratory animals exposed to a pulsed electromagnetic field

Peripheral nerve section and suture was performed in 132 rats. Postoperatively half the animals were exposed to a pulsed electromagnetic field each day and half were kept as controls. Nerve conduction studies, histology and nerve fibre counts all indicated an increased rate of regeneration in the treated animals. A similar controlled study of spinal cord regeneration following hemicordotomy in cats has been started, and preliminary results indicate that when the animals are sacrificed three months after the hemicordotomy, the pulsed electromagnetic therapy has induced nerve fibre regeneration across the region of the scar.

A contribution to peripheral nerve suture technique.

A contribution to peripheral nerve suture technique.

THE SURGERY OF THE PERIPHERAL NERVES.

In contrast to the CNS, peripheral nerves have the ability to regenerate. This ability has been utilized for a long time in the therapy of injuries of peripheral nerves. The aim of the present research was to assess the achievements in reconstructive surgery including nerve grafting and peripheral nerve suture repair in our clinic.During the 16-year period from 1986 to 2001 we surgically treated 116 patients with peripheral nerve lesions. The cases of lesions of the brachial plexus, partial peripheral nerve lesions and postoperative revision, as well as the attempts of reconstruction of cervical nerves and neurolysis are not included in this work. We analysed the results of surgery in our patients who where subjected to treatment of peripheral nerves in the arms (95 patients) and legs (21 patients). In 53 patients reconstructive surgery was performed by suture repair of peripheral nerve, which included treatment of 65 nerves, 10 patients were treated by suture repair of 2 nerves and repair of 3 nerves in one patient. In 42 patients we reconstructed 45 peripheral nerves of the hand by autograft. The total number of 42 patients compromised 37 males and five females. The average age was 36 years. Double nerve reconstruction (ulnar and median) was accomplished in three patients. In the remaining 21 patients (14 males and seven females) we performed 21 reconstruction operations of 24 injured nerves in the lower extremities, of which 8 operations of 9 nerves involved suture repair of peripheral nerves and 13 operations of 15 nerves were performed using a nerve graft. Their average age was 39.7 years. The average period between primary treatment and operation was 6.7 months. In five cases the interval exceeded 12 months. Operations were performed by microtechnique. All patients were subject to several postoperational tests aimed at the estimation of the degree of recovery in sensory and motor adaptation. The evaluation was performed according the Seddon classification (1975). Motor recovery was evaluated according to a five-point scale and the degree of sensory recovery according to a four-point scale. Recovery of grade M4 and S3 (or higher) was considered an excellent or very good result and grades M3 and S2 were considered a good result. Results corresponding to grades M0-M2 and S0-S1 were considered to be insufficient.The results of reconstruction operations of peripheral nerves injuries were dependent on the patient's age, the period between the injury and operation, the length of the autograft, the location of the injury, the type of injured nerve and the character of the injury (Fig. 2, Tab. 7, Ref: 15).