A comparative assessment of lengthening followed by end-to-end repair and isograft repair of chronically injured peripheral nerves.

In order to repair chronic nerve injuries (injuries repaired after a long delay), the damaged nerve segments are resected and stumps are bridged by grafts. Autografts remain the gold-standard, but outcomes are typically poor, even after long periods of recovery. In a recent study, we described the use of a nerve lengthening device to gradually elongate the proximal stump of a transected nerve towards the distal stump, enabling a tension-free end-to-end repair. This approach showed significantly improved outcomes in comparison to autografts in repairing acutely injured nerves. In this study, we compared the use of nerve lengthening/end-to-end repair (LETER) to isograft repair of chronically transected nerves in a rat model. Structural and functional regenerative outcomes following LETER were comparable to isograft-based repair, with no significant differences found in outcomes involving functional recovery or axon growth. These data demonstrate the feasibility of nerve lengthening as a viable graft-free strategy for repairing chronically injured nerves. Not unexpectedly, outcomes for chronic nerve injuries were less favorable in both groups compared to repair of acutely injured nerves. Nonetheless, the findings provide insight into barriers to restoring function after chronic nerve injury through novel comprehensive characterization of a diverse set of neuromuscular outcomes. This analysis revealed key parameters predicting functional recovery.

Nerve stretching: a history of tension.

Stretch injuries are among the most devastating forms of peripheral nerve injury; unfortunately, the scientific understanding of nerve biomechanics is widely and impressively conflicting. Experimental models are unique and disparate, victim to different testing conditions, and thus yield gulfs between conclusions. The details of the divergent reports on nerve biomechanics are essential for critical appraisal as we try to understand clinical stretch injuries in light of research evidence. These conflicts preclude broad conclusion, but they highlight a duality in thought on nerve stretch and, within the details, some agreement exists. To synthesize trends in nerve stretch understanding, the author describes the literature since its introduction in the 19th century. Research has paralleled clinical inquiry, so nerve research can be divided into epochs based largely on clinical or scientific technique. The first epoch revolves around therapeutic nerve stretching-a procedure known as neurectasy-in the late 19th century. The second epoch involves studies of nerves repaired under tension in the early 20th century, often the result of war. The third epoch occurs later in the 20th century and is notable for increasing scientific refinement and disagreement. A fourth epoch of research from the 21st century is just dawning. More than 150 years of research has demonstrated a stable and inherent duality: the terribly destructive impact of stretch injuries, as well as the therapeutic benefits from nerve stretching. Yet, despite significant study, the precise border between safe and damaging stretch remains an enigma.

[Stretch-induced axon growth: a universal, yet poorly explored process]. / La croissance axonale par étirement : un processus universel encore peu exploré.

The growth of axons is a key step in neuronal circuit assembly. The axon starts elongating with the migration of its growth cone in response to molecular signals present in the surrounding embryonic tissues. Following the formation of a synapse between the axon and the target cell, the distance which separates the cell body from the synapse continues to increase to accommodate the growth of the organism. This second phase of elongation, which is universal and crucial since it contributes to an important proportion of the final axon size, has been historically referred to as "stretch-induced axon growth". It is indeed likely to result from a mechanical tension generated by the growth of the body, but the underlying mechanisms remain poorly characterized. This article reviews the experimental studies of this process, mainly analysed on cultured neurons so far. The recent development of in vivo imaging techniques and tools to probe and perturb mechanical forces within embryos will shed new light on this universal mode of axonal growth. This knowledge may inspire the design of novel tissue engineering strategies dedicated to brain and spinal cord repair.

[New treatment for peripheral nerve defects: nerve elongation].

Peripheral nerve defects are still a major challenge in clinical practice, and the most commonly used method of treatment for peripheral nerve defects is nerve transplantation, which has certain limitations and shortcomings, so new repair methods and techniques are needed. The peripheral nerve is elongated in limb lengthening surgery without injury, from which we got inspirations and proposed a new method to repair peripheral nerve defects: peripheral nerve elongation. The peripheral nerve could beelongated by a certain percent, but the physiological change and the maximum elongation range were still unknown. This study discussed the endurance, the physiological and pathological change of peripheral nerve elongation in detail, and got a lot of useful data. First, we developed peripheral nerve extender which could match the slow and even extension of peripheral nerve. Then, our animal experiment result confirmed that the peripheral nerve had better endurance for chronic elongation than that of acute elongation and cleared the extensibility of peripheral nerve and the range of repair for peripheral nerve defects. Our result also revealed the histological basis and changed the rule for pathological physiology of peripheral nerve elongation: the most important structure foundation of peripheral nerve elongation was Fontana band, which was the coiling of nerve fibers under the epineurium, so peripheral nerve could be stretched for 8.5%-10.0% without injury because of the Fontana band. We confirmed that peripheral nerve extending technology could have the same repair effect as traditional nerve transplantation through animal experiments. Finally, we compared the clinical outcomes between nerve elongation and performance of the conventional method in the repair of short-distance transection injuries in human elbows, and the post-operative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group. On the whole, all of these experimental results revealed the physiological phenomenon of peripheral nerve elongation, and described the physiological change and stretch range in detail. The systematic research results have filled the blank in this field, which is very helpful for clinical limb lengthening surgery, the design of elongation surgery and the evaluation of the peripheral nerve stretch injury. Peripheral nerve elongation will become an innovative treatment technology in repairing peripheral nerve defects.

Secondary nerve lengthening to obtain full knee extension in popliteal pterygium syndrome.

Microsurgical nerve lengthening was performed in two siblings presenting a popliteal pterigium syndrome with a knee flexion contracture of 80 degrees. After the first attempt for nerve lengthening and knee extension elsewhere, a repeated lengthening was required due to continuing tip-toe walking and recurrent knee contracture at the age of 3 years. An extensive external and internal interfascicular microsurgical neurolysis resulted in a lengthening of the nerves. A full length of leg procedure had to be performed, inclusive of Achilles tendon lengthening to obtain a complete extension of the knee and a 90-degree ankle flexion. Maintaining the leg in a fully extended position was obtained with a dynamic splinting in the first month after the operation. When timing the operation we have to consider the importance of adequate precision of the microsurgical neurolysis, down to the identification of the Fontana bands, and the adequate postoperative splinting.

Neuroma-in-continuity of the median nerve managed by nerve expansion and direct suture with vein conduit.

Autologous nerve grafting is the current standard for bridging large gaps in major sensory and motor nerves. It allows both function and pain improvement with predictable results. Clinical observations of nerve elongation caused by tumours have prompted experimental animal studies of induced gradual elongation of the nerve stump proximal to the gap. This technique allows direct suturing of the two nerve ends to bridge the gap. Here, we describe a case of neuroma-in-continuity of the median nerve managed by resection and direct suture after nerve elongation with a tissue expander. We are not aware of similar reported cases. Secondary repair 3 years after the initial injury improved the pain and hypersensitivity and restored a modest degree of protective sensory function (grade S1).

Simultaneous gradual lengthening of proximal and distal nerve stumps for repair of chronic peripheral nerve defect in rats.

We investigated nerve regeneration of rat sciatic nerves after chronic injury of 15 mm-defect by the gradual lengthening of proximal and distal nerve stumps. Thirty days after the primal injury, both stumps were grasped and lengthened at a rate of 1 mm per day using external nerve-lengthening devices for 15 days. Then end-to-end neurorrhaphy was performed. After the lengthening, both stumps were evaluated by immunohistochemical analysis. Nerve regeneration was evaluated by electrophysiological and histological studies at 12 weeks after the repair. In the lengthened proximal stump, Schwann cells and axons existed along the whole nerve stump. In the lengthened distal stump, Schwann cells exist along the overall length. The whole nerve trunk was lengthened. The nerve regeneration was comparable with the delayed end-to-end suture without nerve defect. We showed the feasibility of direct gradual lengthening of proximal and distal nerve stumps for the treatment of chronic segmental nerve defect.

New treatment for peripheral nerve defects: reconstruction of a 2 cm, monkey median nerve gap by direct lengthening of both nerve stumps.

We have developed a new treatment for peripheral nerve defects: nerve-lengthening method, and confirmed the efficacy and safety of our method using cynomolgus monkeys. A 20-mm defect in the median nerve of monkey's forearms was repaired through the simultaneous lengthening of both nerve stumps with original nerve-lengthening device. To evaluate nerve regeneration after neurorrhaphy, electrophysiological, histological, and functional recovery were examined and compared to the standard autografting. Nerve conduction velocity, axon maturation, and the result of functional test were superior in the nerve-lengthening method than in the autografting. And there were no adverse events associated with our method. We concluded that this method is practical for clinical application.

The current role of tissue engineering in head and neck reconstruction.

Tissue engineering is an emerging field that has the potential to revolutionize the field of reconstructive surgery by providing off-the-shelf replacement products. The literature has become replete with tissue engineering studies, and the aim of this article is to review the contemporary application of tissue-engineered products. The use of tissue-engineered cartilage, bone and nerve in head and neck reconstruction is discussed.

Prefabricated nerve conduits advance histomorphological and functional outcomes in nerve regeneration of the sciatic nerve of the rat.

Bridging a nerve defect is sometimes necessary to achieve nerve regeneration after injury. Different methods and conduit designs have been considered, but only isograft transplants or prefabricated conduits are available. This study presents a comparison of prefabricated conduits and isograft transplants in rats, with the aim of making suggestions for clinical settings. In rats of inbred strains LEW and DA, a 1.5cm defect of the sciatic nerve was reconstructed by isograft (n=10) or conduit (n=10). Untreated rats (n=10), sham-operated rats (n=10) and nerves of the non-operated contralateral limb served as controls. Regeneration was evaluated by histomorphological examination and with walking track analysis of the ankle stance angle (ASA) and the sciatic functional index (SFI). After 16 weeks, myelinization and ASA in the conduit group were significantly superior to that in the isograft group. There was no significant difference in SFI between the groups. Reconstruction in the isograft group showed a negative impact on the non-operated side. Conduits and isografts did not reach the morphological or functional levels of untreated or sham-operated animals. The results suggest preferential conduits should be used for nerve reconstruction.

Repair of the sciatic nerve defect with a direct gradual lengthening of proximal and distal nerve stumps in rabbits.

BACKGROUND: The current clinical repair method used for the segmental peripheral nerve defect is autogenous nerve grafting. However, this method has several inherent disadvantages. Therefore, the authors have invented an alternative method for repairing the segmental peripheral nerve defect with a direct gradual lengthening of nerve stumps. In this study, for the clinical application, the authors developed a new external nerve-lengthening device for lengthening peripheral nerve stumps daily without anesthesia. METHODS: In this study, a nerve segment 20 mm in length was resected from the rabbit sciatic nerve. In the nerve-lengthening group, direct nerve lengthening was performed in the proximal and distal nerve stumps at a rate of 1 mm/day without anesthesia. After being lengthened for 22 days, both proximal and distal nerve stumps were evaluated by immunohistochemical analysis. When confirming that both nerve stumps were successfully lengthened, a direct end-to-end neurorrhaphy was performed. As a control, 20-mm-long autografting was performed immediately after nerve resection. Nerve regeneration was evaluated by electrophysiologic and histologic examination at 16 weeks after the first operation in both the nerve-lengthening and the control groups. RESULTS: The results of both electrophysiologic evaluation and histologic examination showed that the nerve-lengthening group performed significantly better than the autografting group. CONCLUSION: The gradual nerve-lengthening procedure can be used as an alternative therapeutic method for repairing segmental peripheral nerve defects, which proved to be advantageous over widely adopted autogenous nerve grafting.

Repair of peripheral nerve defect by direct gradual lengthening of the distal nerve stump in rats: cellular reaction.

We investigated the effects of direct gradual lengthening of the distal stump of a peripheral nerve and subsequent nerve regeneration in rats. A segment 10 mm long was resected from rat sciatic nerve. The distal nerve stump was fixed to a ring and pulled directly at a rate of 1 mm/day using an original external nerve distraction device. After distraction for 10, 15, and 20 days, the lengthened nerves were evaluated macroscopically and immunocytochemically. At day 20, the mean (SD) distances from the ring to the 3 mm and 6 mm distal part, which were marked with sutures on the epineurium, were 7 (0.5) mm and 12.1 (0.5) mm, respectively, and the number of Schwann cells in the lengthening group had increased to twice that of control group. The distal stump of a peripheral nerve including the epineurium, endoneurium, and proliferation of Schwann cells can be lengthened directly. This method also made it possible to lengthen the nerve stump longitudinally and to control both the rate and distance. We think that this method may be used in the treatment of peripheral nerve injury.

Repair of peripheral nerve defect by direct gradual lengthening of the distal nerve stump in rats: effect on nerve regeneration.

We investigated the use of direct lengthening of the distal stump of a peripheral nerve to compare the results of nerve regeneration using the direct lengthening method with simple end-to-end suture and autografting in rats. A segment 10 mm long was resected from the rat sciatic nerve (n=18 in each group). The distal nerve stump was fixed to a ring and pulled at a rate of 1 mm/day for 20 days using an original external nerve distraction device. The results showed that the degree of nerve regeneration in the lengthened group was superior to that of the grafted group electrophysiologically and histologically, but there were no significant differences between the lengthened and end-to-end suture groups. We conclude that direct lengthening of the distal stump of a peripheral nerve can promote nerve regeneration similar to that observed in a Wallerian degenerated nerve. We think that this technique may be used for the treatment of peripheral nerve injuries.

The intramuscular course of the inferior gluteal nerve in the gluteus maximus muscle and augmentation gluteoplasty.

The aim of this study was to elucidate the intramuscular course of the inferior gluteal nerve in the gluteus maximus muscle and its association with augmentation gluteoplasty. Twenty buttocks of 10 Korean adult cadavers (age range: 47-87, 7 men and 5 women) were used for the study. The inferior gluteal nerve (IGN) was traced from the infrapiriform foramen at the deep surface of gluteus maximus (GM) until the nerve thickness became 0.3 mm. The depth of the IGN was measured and the relative depth of the nerve was calculated according to the thickness of the GM at 15 points. The muscle thickness varied according to its location. The medial part (17.1-18.1 mm) was thicker than the lateral (14.5-15.7 mm) or inferior parts (14.5-14.7 mm). The IGN runs deep through the GM (59%-82% of muscle thickness). Except for below the Coccyx-Greater trochanter line, where the IGN was located (59%-62% depth), the IGN was traced to 63-82% of the depth in the GM. The IGN ran relatively superficial (below 70%) in the medial part of the GM, and was a little deeper (above 70%) in the lateral part. There results of this study showed that intramuscular augmentation gluteoplasty could be performed safely unless intramuscular dissection is performed too deeply.

Simultaneous gradual lengthening of both proximal and distal nerve stumps for repair of peripheral nerve defect in rats.

We investigated nerve regeneration following the repair of a segmental nerve defect induced by direct end-to-end neurorrhaphy after simultaneous gradual lengthening of both proximal and distal nerve stumps in rats. A 15-mm-long nerve segment was resected from the sciatic nerve of each rat. The proximal and distal nerve stumps, respectively, were directly lengthened at a rate of 1 mm/day using a custom-made external nerve-lengthening device. After being lengthened for 14 days, both nerve stumps were refreshed, and direct end-to-end neurorrhaphy was performed. For a control, 15-mm nerve grafting was performed immediately after nerve resection. Nerve regeneration was evaluated by motor nerve conduction velocity, muscle contraction force, and histological studies at 6, 8, and 14 weeks after initial nerve resection in both groups. As a result, at 8 and 14 weeks, the motor nerve conduction velocity was significantly higher in the nerve-lengthening group than in the autografting group. In addition, at 14 weeks, the tetanic force and wet weight of the gastrocnemius muscle were significantly higher in the nerve-lengthening group than in the autografting group. Histologically, the mean axonal diameter of myelinated nerve fibers and the total number of myelinated nerve fibers were also significantly higher in the nerve-lengthening group than in the autografting group for each evaluation period. It appears that the simultaneous gradual lengthening of both proximal and distal nerve stumps might have potential application in the repair of peripheral nerve defects.

[Primary clinical study on using end-to-end neurorrhaphy following rapid nerve expansion to repair facial nerve defect].

OBJECTIVE: To evaluate the clinical effect of end-to-end neurorrhaphy following rapid expansion of the nerve in repairing facial nerve defect. METHODS: From August 2000 to February 2005, 9 patients suffering from facial nerve defect were treated by the surgical method. The defect was caused by traffic injury(4 cases) , by cutting injury (2 cases) and falling wound (1 case). Seven cases showed prominent facial paralysis. The other 2 cases were invaded by parotid carcinoma, without remarkable paralysis. One case had unibranch defect, and the other 8 cases had multibranch defect. The nerve gap ranged from 1.5 cm to 3.0 cm. After both the proximal and the distal segment had been dissected, the nerve was elongated by the expander designed and manufactured. The expansion was done at a speed of 2.0 cm/30 min, and it lasted until the end-to-end neurorrhaphy can be done easily. The treatment result was evaluated according to Baker's classification and House-Brackmann's grading system. RESULTS: Nine patients were followed up 6-18 months. In 5 cases achieving good result, both dynamic look and static look of face were symmetric, the EMG peak value of mimetic muscle was 82%-95% of normal side. In 3 cases achieving fair result, the dynamic look and static look of face were basically symmetric, and the EMG peak value of mimetic muscle was 60%-90% of normal side. In 1 case achieving poor result, the function of mimetic muscle was improved slightly, and the EMG peak value of mimetic muscle was 55% of normal side. CONCLUSION: The satisfactory result can be obtained by end-to-end neurorrhaphy following rapid expansion of the nerve in condition that nerve defect is less than 3.0 cm.