Introduction: End-to-side nerve repair is an experimental technique for repairing peripheral nerves when severe injury renders the proximal nerve stump not available for end-to-end repair or for conventional nerve grafting techniques. This study uses a large animal model to compare two variations of end-to-side neurorrhaphy techniques with conventional clinically established methods of nerve repair to assess the feasibility of end-to-side suture as a technique for possible future clinical use. Methods: 12 age and weight matched sheep underwent end-to-side neurorrhaphy of the distal stump of the transected median nerve to the lateral side of the adjacent intact ulnar nerve through an epineurial window. 12 sheep underwent the same procedure as above but with the proximal stump of the transected median nerve similarly attached 2cm proximal to the first neurorrhaphy site to create a double end-to-side model. 18 sheep underwent conventional methods of nerve repair. All the experiments were randomized and the author performed all the surgery. The nerve repairs were assessed electrophysiologically and histologically and the muscles supplied by the repaired nerves were assessed physiologically at one-year post repair. Normal median nerves and donor ulnar nerves were also tested in the same ways. Results: There were no significant differences in the outcomes of nerve repair between different conventional techniques. Half the end-to-side repairs failed but the double end-to-side repair consistently supported nerve regeneration. Both end-to-side methods were inferior to conventional techniques of nerve repair in all measures of outcome except twitch and tetanic muscle tensions. The function of the donor ulnar nerves in terms of conduction velocity was compromised in the double end-to-side repair but not the end-to-side repair. Discussion and Conclusions: End–to-side nerve repair did support nerve regeneration but it was all or nothing. It is likely that the double end-to-side neurorrhaphies regenerated more consistently than the single end-to-side neurorrhaphies due the conduit effect of the donor ulnar nerve bridge supporting axon growth. Donor ulnar nerve damage in the double end-to-side group suggests regeneration may have occurred from terminal sprouts rather than collateral sprouts. Although end-to-side neurorrhaphy did support nerve regeneration with sometimes good return of muscle function, the use of this technique as a clinical tool at this time cannot be recommended

Skeletal muscle grafts, when thawed after freezing, can be used to repair peripheral nerves. This method was used after transection of the median nerve in the upper arm in marmosets. Examination at 28 days showed total denervation of flexor carpi radialis; at 150 days electrophysiological evidence of recovery of nerve conduction across the graft and of muscle activation was seen. Sections at this time showed nerve fibres and new functional neuromuscular junctions in the muscle. It is concluded that effective reinnervation of target muscles is possible after peripheral nerve repair using skeletal muscle autografts

The outcomes of 261 nerve injuries in 100 patients were graded good in 173 cases (66%), fair in 70 (26.8%) and poor in 18 (6.9%) at the final review (median 28.4 months (1.3 to 64.2)). The initial grades for the 42 sutures and graft were 11 good, 14 fair and 17 poor. After subsequent revision repairs in seven, neurolyses in 11 and free vascularised fasciocutaneous flaps in 11, the final grades were 15 good, 18 fair and nine poor. Pain was relieved in 30 of 36 patients by nerve repair, revision of repair or neurolysis, and flaps when indicated. The difference in outcome between penetrating missile wounds and those caused by explosions was not statistically significant; in the latter group the onset of recovery from focal conduction block was delayed (mean 4.7 months (2.5 to 10.2) vs 3.8 months (0.6 to 6); p = 0.0001). A total of 42 patients (47 lower limbs) presented with an insensate foot. By final review (mean 27.4 months (20 to 36)) plantar sensation was good in 26 limbs (55%), fair in 16 (34%) and poor in five (11%). Nine patients returned to full military duties, 18 to restricted duties, 30 to sedentary work, and 43 were discharged from military service. Effective rehabilitation must be early, integrated and vigorous. The responsible surgeons must be firmly embedded in the process, at times exerting leadership

A total of 38 patients with leprosy and localised nerve damage (11 median at the wrist and 37 posterior tibial at the ankle) were treated by 48 freeze-thawed skeletal muscle autografts ranging between 2.5 cm and 14 cm in length. Sensory recovery was noted in 34 patients (89%) and was maintained during a mean period of follow-up of 12.6 years (4 to 14). After grafting the median nerve all patients remained free of ulcers and blisters, ten demonstrated perception of texture and eight recognised weighted pins. In the posterior tibial nerve group, 24 of 30 repairs (80%) resulted in improved healing of the ulcers and 26 (87%) demonstrated discrimination of texture. Quality of life and hand and foot questionnaires showed improvement; the activities of daily living scores improved in six of seven after operations on the hand, and in 14 of 22 after procedures on the foot. Another benefit was subjective improvement in the opposite limb, probably because of the protective effect of better function in the operated side. This study demonstrates that nerve/muscle interposition grafting in leprosy results in consistent sensory recovery and high levels of patient satisfaction. Ten of 11 patients with hand operations and 22 of 25 with procedures to the foot showed sensory recovery in at least one modality.

Coaxial autografts of skeletal muscle which had been frozen then thawed were used to repair injured digital nerves in eight patients. Assessment from three to 11 months after operation showed recovery to MRC sensory category S3+ in all but one patient, an excellent level of recovery. We conclude that bespoke muscle grafts treated and used in this way may offer significant advantages over conventional nerve grafts or cable grafts especially where large peripheral nerves are involved.

About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.

We describe 261 peripheral nerve injuries sustained in war by 100 consecutive service men and women injured in Iraq and Afghanistan. Their mean age was 26.5 years (18.1 to 42.6), the median interval between injury and first review was 4.2 months (mean 8.4 months (0.36 to 48.49)) and median follow-up was 28.4 months (mean 20.5 months (1.3 to 64.2)). The nerve lesions were predominantly focal prolonged conduction block/neurapraxia in 116 (45%), axonotmesis in 92 (35%) and neurotmesis in 53 (20%) and were evenly distributed between the upper and the lower limbs. Explosions accounted for 164 (63%): 213 (82%) nerve injuries were associated with open wounds. Two or more main nerves were injured in 70 patients. The ulnar, common peroneal and tibial nerves were most commonly injured. In 69 patients there was a vascular injury, fracture, or both at the level of the nerve lesion. Major tissue loss was present in 50 patients: amputation of at least one limb was needed in 18. A total of 36 patients continued in severe neuropathic pain.

This paper outlines the methods used in the assessment of these injuries and provides information about the depth and distribution of the nerve lesions, their associated injuries and neuropathic pain syndromes.

Nerve transfer is an emerging treatment to restore upper limb function in people with tetraplegia. The objective of this study is to examine if a flexible collage sheet (FCS) can act as epineurial-like substitute to promote nerve repair in nerve transfer. A preclinical study using FCS was conducted in a rat model of sciatic nerve transection. A prospective case series study of nerve transfer was conducted in patients with C5-C8 tetraplegia who received nerve transfer to restore upper limb function. Motor function in the upper limb was assessed pre-treatment, and at 6-,12-, and 24-months post-treatment. Macroscopic assessment in preclinical model showed nerve healing by FCS without encapsulation or adhesions. Microscopic examination revealed that a new, vascularised epineurium-like layer was observed at the FCS treatment sites, with no evidence of inflammatory reaction or nerve compression. Treatment with FCS resulted in well-organised nerve fibres with dense neurofilaments distal to the coaptation site. Axon counts performed proximal and distal to the coaptation site showed that 97% of proximal axon count of myelinated axons regenerated across the coaptation site after treatment with CND. In the proof of concept clinical study 17 nerve transfers were performed in five patients. Nerve transfers included procedures to restore triceps function (N=4), wrist/finger/thumb extension (N=6) and finger flexion (N=7). Functional motor recovery (MRC ≥3) was achieved in 76% and 88% of transfers at 12 and 24 months, respectively. The preclinical study showed that FCS mimics epineurium and enable to repair nerve resembled to normal nerve tissue. Clinical study showed that patients received nerve transfer with FCS experienced consistent and early return of motor function in target muscles. These results provide proof of concept evidence that CND functions as an epineurial substitute and is promising for use in nerve transfer surgery

Abstract. Nerve transfer has become a common and often effective reconstructive strategy for proximal and complex peripheral nerve injuries of the upper limb. This case-based discussion explores the principles and potential benefits of nerve transfer surgery and offers in-depth discussion of several established and valuable techniques including: motor transfer for elbow flexion after musculocutaneous nerve injury, deltoid reanimation for axillary nerve palsy, intrinsic re-innervation following proximal ulnar nerve repair, and critical sensory recovery despite non-reconstructable median nerve lesions

Purpose: Prolonged denervation resulting from deferred nerve repair or long distance between the muscle and the repaired nerve, leads to major alterations concerning muscle fibre degeneration and their replacement by fibrous or fatty tissue. These structural modifications of the muscle are unfavourable for reinnervation and consequently affect the final functional outcome after peripheral nerve repair with its corollary of reduced muscle force. The purpose of this work was to assess the potential for regeneration of denervated-reinnervated muscles and their improvement with adjuvant cell therapy using in situ transfer of cultured autologus satellite cells. Material and methods: This work was conducted with the tibialis anterior muscle in different groups of New Zealand rabbits. The experimental model was a sectioned common fibular nerve and immediate or deferred (two months) microsurgical nerve suture. In vivo functional measurements and histomorphological analyses were performed four months after nerve repair. Results: Reinervation led to loss of mucle weight and maximal force (Fmax) which were greater with longer deferral of repair. Transfer of satellite cells performed immediately after reinervation did not improve muscle properties. Conversely, transfer of satellite cells two months after nerve suture increased Fmax 25% (p < 0.01) and muscle weight 28% (p = 0.005) in comparison with control muscles undergoing reinervation without cell transfer. Furthermore, the morphology of the muscle was improved as demonstrated by anti-myosine labelling studies. Discussion: Adjuvant cell therapy allows, in certain conditions, an improvement in functional recovery after peripheral nerve injury. Its clinical application still raises a certain number of ethical issues but taking into consideration data currently available, it would be reasonable to propose this therapeutic approach in humans to reduce involution of the denervated muscle and improve its receptivity for regenerating axons after peripheral nerve repair. Better post-operative results could be expected

The October 2015 Research Roundup360 looks at: Wasted implants; Biofilms revisited; Peri-operative anticoagulation not required in atrial fibrillation; Determinants in outcome following orthopaedic surgery; Patient ‘activation’ and outcomes; Neuroplasticity and nerve repair; KOOS Score in predicting injury?

Evaluations of 32 adults with 50 complete digital nerve injuries were made more than 1 year after surgery. Twenty patients were men and 12 were women. The mean age of the patients at operation was 30 years. The mean follow-up time was 2 years. Patients were excluded if they had a skin graft, had a second surgery after digital nerve repair or graft, were diagnosed with diabetes, had additional proximal nerve injuries, had postoperative infections, had a complete digital amputation or had a dorsal digital nerve injury. According to the initial injury mechanism, patients were classified into three grades : grade I was defined as a sharp, clean-cut injury, grade II was mild crush and grade III was a severe crush injury. Overall, there were 30 primary digital nerve repairs, 12 secondary repairs and 8 secondary nerve grafts. Moving and static two-point discrimination was determined on both lateral aspects of the injured and contralateral uninjured digits. Digits with primary repairs in mild or severe crush injuries had significantly worse two-point discrimination compared with digits that had a primary repair of a simple laceration. Futhermore, in mild crush injuries, digits with secondary nerve grafting had significantly better results than those with primary repair. Patients under 30 years age had better results than those over 30 years. These results support the hypothesis that better recovery is obtained if tension is avoided at the nerve repair site in mild crush injuries

The April 2013 Wrist & Hand Roundup. 360 . looks at: whether botox is just for Hollywood; supercharging nerve repairs; YouTube research; options for Keinbock’s disease; volar plates; driving and plasters; symptomatic radial malunion; and MRI and acute scaphoid fractures

We investigated the effect of delay before nerve repair on neuropathic pain after injury to the brachial plexus. We studied 148 patients, 85 prospectively and 63 retrospectively. The mean number of avulsed spinal nerves was 3.2 (1 to 5). Pain was measured by a linear visual analogue scale and by the peripheral nerve injury scale. Early repair was more effective than delayed repair in the relief from pain and there was a strong correlation between functional recovery and relief from pain

A previously fit and well 58 year old male suffered from a bilateral psoas haematoma (PH) following 52 days of veno-venous extracorporeal membranous oxygenation (VV-ECMO) for severe Coronavirus disease (COVID-19), refractory to all non-invasive and medical therapies. He developed multiple complications, including inability to walk or weight-bear, due to lumbar plexopathy triggered by bilateral PH compression, compounded by COVID-19-related mononeuritis multiplex. The patient was referred to our institution with a known diagnosis of bilateral PH and after spinal multidisciplinary team (MDT) input, was deemed not for surgical or interventional radiology treatments. The patient received extensive neurorehabilitation, coordinated by multiple MDTs. Although PH has been correlated to COVID-19, to the best of our knowledge this is the first reported case of such a complex presentation resulting in a dramatic bilateral PH. Health records from 3 large UK teaching hospitals were collected regarding treatment and follow up appointments, following patient's written informed consent. Patient's comorbidities, duration in hospital units, MDT inputs, health assessments, mobilisation progress and neurologic assessments, were all recorded. Data was collected retrospectively then prospectively due to lengthy in-patient stay. The literature review was conducted via PubMed and open access sources, selecting all the relevant studies and the ECMO guidelines. Patient received treatment from 3 different units in 3 hospitals over 212 days including 103 days in neurorehabilitation. Involvement of physiotherapy, dietitians, speech and language teams, neurologist, neurophysiotherapists, occupational therapists was required. The patient progressed from a bed-bound coma and inability to walk, to standing with lower limb backslab at discharge. Additionally, he was referred for elective exploratory surgery of the psoas region for scar debridement and potential nerve graft repair of the lumbosacral plexus. The surgery outcome is cautiously optimistic, with some improvement in nerve conduction studies, however is currently unknown regarding recovery progress and return to premorbid functional baseline. The novelty of this presentation yields significant learning points regarding early recognition of PH, requirements for vast MDT input and specialist use of VV-ECMO in severe COVID-19 patients. It also highlights the broad pathophysiology of SARS-CoV-2 causing neuropathy and coagulopathy; understanding this will optimise robust anticoagulation guidelines, required in VV-ECMO

Most injuries to the femoral nerve are iatrogenic in origin and occur during resection of large retroperitoneal tumours. When the defect is considerable a nerve graft is mandatory to avoid tension across the suture line. We describe two cases of iatrogenic femoral nerve injury which recovered well after reconstruction with long sural nerve grafts. The probable reasons for success were that we performed the grafting soon after the injury, the patients were not too old, the nerve repairs were reinforced with fibrin glue and electrical stimulation of the quadriceps was administered to prevent muscle atrophy. Good functional results may be obtained if these conditions are satisfied even if the length of a nerve graft is more than 10 cm

Purpose: Recovery of muscle function after nerve repair remains incomplete despite progress in microsurgical techniques. Potential for muscle recovery could be greatly improved. The purpose of our study was to demonstrate the functional impact of exogenous satellite cells in degenerated muscles. Material and methods: We used the anterior tibialis muscle (Ta) in rabbits (n=24) as our experimental model. Muscle degeneration was created by bilateral injections of cardio-toxin into the Ta. Five days later, the left Ta was injected with autologous satellite cells (SC) at multiple points. The same volume of culture medium was injected into the right Ta. Two months later, maximal isometric muscle force and stress resistance of the Ta was measured. Histoimmuno-chemical labellings were made. Results: The volume of cardiotoxin injected created two categories of muscles: recovery of former function was not possible with low dose cardiotoxin injections. Maximal isometric muscle force was less than 35% of the control. Transfer of SC restored nearly normal muscle force. Resistance to stress followed the same pattern. Recovery of maximal muscle force was possible with high-dose cardiotoxin injections. Resistance to stress was greater than the control (+ 35%). Transfer of SC did not modify results. The weight of the Ta increased for both cardiotoxin doses. There was an increase in the size of the fibres with or without SC transfer. Discussion: Injection of cardiotoxin induced muscle degeneration. With greater muscle degeneration, regeneration of muscle capacity was greater. Transfer of SC improved the functional result when muscle degeneration was incomplete. Improved resistance to stress after injection of high-dose cardiotoxin could result from changes in muscle myosin and fibrillary structure. Conclusion: Further studies are needed before clinical application to better understand the underlying mechanisms operating with satellite cell injections. Many applications could be proposed, particularly for surgical nerve repair, ischaemic heart failure, and myopathy

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

After big loos of substances of peripheral nerves, in order to connect proximal with distal stump, it is possible to use, in alternative to autologous grafting, different kind of conduits. The chitosan conduit and the muscle in vein technique showed very good results in pre clinical and clinical settings. We compared in this study the efficacy of empty chitosan conduit versus chitosan conduit enriched with fresh muscle fibbers (MIT) to improve peripheral nerve regeneration. The median nerve of rat was repaired by means of empty chitosan conduit or MIT (nerve gam 6mm, conduit length 10 mm). As control group we used auto grafting technique. We performed analysis at short term (7,14,28 days) and at long term (12 weeks) in order to register bimolecular modification (quantitative real time PCRand western blot), morphological modification (optic and electronic microscope) and functional changing (grasping test). Bimolecular analysis showed that muscle fibbers produced and released Neuregulin1, needed for regeneration and activity of Schwann cells. Otherwise also the autograft product Neuregulin1, instead no production was observed in empty conduit. So muscle fibbers compensate this fact. Morphological analysis showed that the first myelinc fibbers appear in MIT after 14 days, but not in empty tube. The results of our work are very interesting because can merge the easiness of the implantation of chitosan tube and the efficacy of fresh muscle fibbers, as previously demonstrated by muscle in vein technique. From a clinical point of view this procedure could be an alternative to auto grafting that is nowadays the gold standard for nerve repair, but present soma disadvantages