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Radial nerve exploration and nerve grafting using autologous graft and AxoGen AVANCE nerve allograft

    Overview

    Learn the Radial nerve exploration and nerve grafting using autologous graft and AxoGen AVANCE nerve allograft surgical technique with step by step instructions on OrthOracle. Our e-learning platform contains high resolution images and a certified CME of the Radial nerve exploration and nerve grafting using autologous graft and AxoGen AVANCE nerve allograft surgical procedure.
    The radial nerve is vulnerable to injury as it courses around the humerus in the spiral groove. Most radial nerve injuries associated with low energy fractures are of a low-grade, typically a neurapraxia with some degree of demyelination affecting the large myelinated fibres (prolonged conduction block) or with some partial and minor axon disruption (mixed nerve injury). These injuries usually recover fully in 6-12 weeks without surgical intervention for the nerve injury. Delayed recovery may necessitate exploration and decompression at the lateral inter-muscular septum.
    One should be cautious when making such a diagnosis in the setting of a high energy injury, when there is neuropathic pain or when there is deterioration after intervention. In a case with intact function then loss after closed reduction and casting, one should anticipate that the nerve has been caught in the fracture and urgent exploration is warranted. At best the nerve will be swollen with haematoma compression at the lateral septum and decompression will improve the situation and the chance of recovery. When the onset of palsy follows surgical intervention with ORIF one should assume that there has been a direct nerve injury. The mechanism may be traction, entrapment under a plate, direct injury with a drill or screw. There is little merit in waiting and typically the pre-operative assessment is inadequate to confirm that intra-operative nerve trauma has occurred and unnecessary delay ensues whilst neurophysiology is requested.
    The case presented was referred to me at 8 months following fixation of a distal humeral fracture with a direct posterior approach and precontoured locking plates applied medially and posterolaterally to stabilise the fracture. Exploration confirmed injury to the radial nerve and the branch to brachioradialis from a drill bit with nerve rupture. A long gap of 7cm had resulted and the options for reconstruction are discussed.
    An AVANCE processed nerve allograft was selected for the main radial nerve trunk as a pain management and sensory recovery strategy with autologous sensory nerve graft from the posterior cutaneous nerve of the forearm to the branch to brachioradialis. The case was combined with a distal pronator teres tendon transfer to the extensor carpi radialis brevis and nerves transfers from the median nerve to the posterior interosseus nerve for digit extension. This strategy was selected due to the timing of presentation and the low chance of any meaningful recovery through a long segment autologous graft at this stage.

    Indications

    INDICATIONS
    Radial nerve dysfunction after high energy injury, following intervention (manipulation and cast or internal fixation), a painful nerve lesion, deterioration under observation or doubt about the status of the nerve. Dry skin is a sign of autonomic small fibre loss and implies a deeper lesion than the large fibre involvement alone typically seen with a demyelinating conduction block (neurapraxia).
    I define the indications for nerve exposure as the “D’s”:
    Diagnosis
    Decompression
    Displaced fracture fragments
    Delayed reduction of a Dislocation
    Delay in recovery
    Deepening lesion under observation
    Debilitating nerve pain
    Doubt regarding the provisional diagnosis
    Develops Dry skin
    SYMPTOMS & EXAMINATION
    The assessment should try and ascertain the status of the nerve immediately after injury. This is not always well documented and sometimes the patients are unable to recall whether there was active function in the wrist or finger extensors due to pain and cast immobilisation. Often they will be able to describe when they noted sensory disturbance and almost all recall the onset of neuropathic pain. I request all records pertaining to the injury including accident and emergency, initial trauma and orthopaedic examination, anaesthetic, operative, post-operative, clinic notes and neurophysiology. Copies of imaging are also important to look for sites of potential nerve injury.
    A thorough history should focus on timing of injury, loss of function, interventions and recovery to date. Any retained sensory of motor recovery is important in confirming physical continuity of the nerve. Neuropathic pain is the hallmark of a degenerative (Wallerian degeneration – axonopathy) lesion and it is essential to making a diagnosis. A Tinel’s sign should be looked for by tracing the nerve from distally to proximally and tapping gently. Pain in the distribution of the nerve is typical for an area of damage and neuroma formation. A distal Tinel’s sign suggests regeneration. The distance between the presumed site of injury (there may be a concomitant proximal Tinel’s from axon hold up in a neuroma in continuity) and the distal Tinel’s site can be used to define the rate of nerve regeneration. 2-3mm/day is favourable and implies a low grade axonopathy (Sunderland 2), 1-2 mm per day is indicative of a higher grade (Sunderland 3), less than 1mm per day is typical of a high grade (Sunderland 4 or) and no recovery a Sunderland 5 lesion.

    This patient had pain at the lateral arm with a mild Tinel’s sign, no distal motor or sensory function and no distal Tinel’s sign. There was dry skin initially but this had resolved. The fracture of the distal humerus was consolidating with 2 of the medially inserted screws long at the lateral supracondylar ridge at the site of Tinel’s sign. There was normal function in the triceps but no motor function in brachioradialis or below in the radial nerve.
    IMAGING
    Radiographs of the humerus fracture and fixation are useful. Computed tomography is helpful in complex cases and to define screw penetration and proximity to nerves when plain imaging is inconclusive. It is also helpful in the setting of heterotopic bone and abundant fracture callus.
    Ultrasound imaging is useful to look at the course of a nerve and to define swellings that could be proximal to compression points or the site of a neuroma. Ultrasound is operator dependent and as such I prefer to explore nerves surgically because a pathophysiological grade of injury cannot be defined by ultrasound and requires direct visualisation and intra-operative nerve stimulation.
    ALTERNATIVE OPERATIVE TREATMENT
    A radial nerve discontinuity is optimally treated with autologous nerve graft reconstruction, typically 3-4 cables of reversed sural nerve for a defect of 5cm or more. In late presenting cases there is a role for tendon transfer reconstruction of the wrist, finger and thumb extensors using PT to ECRB, FCR to EDC and PL to EPL. The decision whether to explore the radial nerve and reconstruct in such cases is a challenging one. Exploration is helpful in the setting of pain and to define the cause and site of injury in medicolegal cases due to iatrogenous injury. It also allows assessment of any retained function which can be optimised by decompression and neurolysis. However in a complete lesion the tendon transfer reconstruction provides useful function restoration (motor) but the sensory loss is often well tolerated and therefore grafting for sensation (in the absence of pain) is worthy of discussion with the patient but the potential donor morbidity from autologous nerve harvest may not be acceptable to both surgeon and patient. In this setting the use of a processed nerve allograft avoids the donor site concerns, can help manage injury site pain and provides a route for regenerating sensory axons to bridge the gap to the distal stump. Whether useful additional motor function is achieved in such cases is still not proven, although there is emerging evidence from the RANGER study to support this, the evidence for sensory recovery is stringer based on greater utilisation in sensory nerves to date.

    Distal median to radial nerve transfers using FDS branches to ECRB and FPL/PL fascicles transferred to the PIN are gaining in popularity but there are no good clinical series to date. The advantage is that reconstruction can target the original muscles in their original bed rather than the alteration of vector of pull that follows tenotomy and tendon transfer with disruption of the sarcomere resting length. The recovery is relatively fast due to reinnervation distances of 3-4 inches. However useful function is not seen until 9-12 months following transfer. I consider this option when patients wish to maintain finger extension independence, full wrist flexion (typically reduced with FCR to EDC tendon transfer) and the presentation is too late to consider functional restoration through grafting due to the reinnervation distances involved (typically 10 inches or more).
    AVANCE processed nerve allograft was selected in this case due to the late presentation and the distal reconstruction strategy employed for motor recovery with a non-critical sensory loss. This is a human processed nerve allograft tissue that provides a high density of endoneurial tubes for axon regeneration. The graft is provided frozen and comes in a number of diameters (1/2mm; 2/3mm; 3/4mm; 4/5mm) and lengths (up to 70mm). Typically a number of sizes should be available in the hospital tissue bank to allow tension free reconstruction without excessive waste as it is an expensive product.
    NON-OPERATIVE MANAGEMENT
    There is no role for waiting for spontaneous recovery in this clinical setting. Often unnecessary delay follows poor assessment and over reliance on interval neurophysiological testing with nerve conduction studies and electromyography (EMG). If there is no evidence of polyphasia (reinnervation) by 3 months in the brachioradialis then this implies that the nerve lesion is complete with discontinuity (either anatomically or certainly functionally). A low grade axonal injury should have regenerated already (2-3mm per day) and as such this finding should prompt referral to a nerve specialist. In the setting of some early recovery on EMG a nerve specialist can follow up the patient and if there is a delay in further recovery, this can be picked up in just 4-6 weeks and prompt earlier intervention than would result from awaiting further interval EMGs. The nerve specialist will be able to detect early motor sequential innervation using knowledge of the radial nerve anatomy and the muscle squeeze test. Reinnervation results in muscle tenderness on squeeze prior to onset of muscle contraction.
    CONTRAINDICATIONS
    The main contraindications to use of allograft are active infection at the site of nerve injury and patient refusal to have allograft tissues implanted.

    Setup

    The patient was consented for exploration under general anaesthesia without a tourniquet initially for the radial nerve exposure. The limb was marked and the site of Tinel’s sign noted. The anaesthetic team were informed that antibiotic prophylaxis would be required due to the wound in proximity to metalwork and the potential for allograft implantation. The anaesthetic was also requested to be delivered in such a way that intra-operative nerve stimulation could be undertaken.
    Equipment required included a basic hand / nerve set with additional Travers and Norfolk and Norwich self-retaining retractors, malleable retractors, Mixter forceps, sloops, DeBakey forceps, neurotomes and blades, nerve stimulator, microinstruments, Tisseel fibrin glue and an operating microscope. AVANCE processed nerve allograft sizes 4/5 x 50mm and 4/5 x 70mm were available in the tissue bank freezer in the theatre suite. In addition an orthopaedic small fragment locking fixation tray and periosteal elevator was available in case of need to exchange or remove metalwork from the distal humerus.
    The patient was positioned supine on the operating table and the second stage of the WHO pre-surgery checklist completed.

    Operation – 1

    The patient has a complete wrist and digit drop from loss of radial nerve function.

    The patient is positioned supine on an operating table under general anaesthesia with the arm to be operated fully exposed from axilla to hand. The site of surgery is marked with a cross at the point of maximum Tinel’s sign.

    The limb is prepped and draped leaving the whole arm exposed. No tourniquet is applied for the radial nerve exposure but can be later applied for any tendon or nerve transfer surgery that may be required at the forearm level once the nerve is exposed and a definitive surgical plan is reached.

    The skin is opened along the course of the radial nerve using an anterolateral approach. The previous approach was posterior to internally fix the distal humerus. The posterior approach would not give sufficient exposure of the radial nerve in the distal 1/3 of the upper arm and so a new incision was planned.

    Bipolar diathermy is used to cauterise small perforating vessels that pass through this neurovascular plane. Careful haemostasis must be maintained throughout becaus ethis is a well vascularised area and heavy bleeding can follow damage to vessels accompanying the nerve, obscuring the view and risking iatrogenous nerve injury.

    Initially a Travers self-retaining retractor is placed in the wound edges and Jamieson scissors are used to dissect through the subcutaneous tissues to the fascia, identifying cutaneous nerve branches.

    A second Travers retractor is place in the proximal wound. A small cutaneous nerve is identified. These branches emanate from the main radial nerve trunk and can be used to trace proximally to identify the position of the main nerve trunk within a scarred bed. The branches should be protected throughout the procedure to avoid iatrogenic traction injury.

    The small cutaneous branch is a terminal branch of the posterior cutaneous nerve of the arm and is tagged with a white sloop using a 90 degree fine tipped Mixter forceps to retrieve the sloop deep to the nerve.

    The cutaneous branch is tagged. The small anterior branch may hamper exposure of the main radial nerve and may need to be sacrificed. The nerve can be used as a source of autologous graft later in the procedure.

    A more substantial sensory branch is identified passing through to the deep fascia of the upper arm and terminating in the posterior forearm. The nerve is stimulated to demonstrate no motor function. It is tagged with a yellow sloop.

    Sloops can be used to provide gentle traction on nerves, to assist exposure of other structures and to help with neurolysis of branches. Sloops minimise direct nerve handling and reduces the risk of iatrogenous injury.

    The plane between the brachioradialis and the brachialis is developed to identify the radial nerve.

    The radial nerve is swollen and firm and a clip is passed deep to it to facilitate passage of a sloop.

    The radial nerve is tagged with a blue sloop.

    There is dense scarring in the region of the lateral intermuscular septum and the area is carefully dissected to free the radial nerve proximally. Care should be taken because the nerve to brachioradialis lies adajcent to the nerve trunk with the posterior cutaneous nerve of the forearm also lying in this plane. It is a vascular plane with the profunda brachii and venae comitantes passing distally to anastomose with the lateral collateral vessels from the forearm. The branch to ECRL arises more distally from the posterolateral aspect of the radial nerve in this interval 3-4cm beyond the lateral intermuscular septum.

    The tissues and scar are released exposing a constricted and scarred epineurium of the radial nerve.

    The radial nerve is now exposed in the lower spiral groove and the lateral intermuscular septum has been release. There is a neuroma in the main nerve above the blue sloop. This area is thickened and firm. Distally the nerve peters into scar. This distal pathoanatomy needs defining further.

    N = Neuroma in radial nerve
    PCNF = Posterior cutaneous nerve of forearm
    C = Constriction of main nerve at site of lateral intermuscular septum
    S = Scar
    BR = Branch to brachioradialis

    A proximal second blue sloop is passed to allow decompression of the radial nerve at the intermuscular septum and a 360 degree external neurolysis. On the posterior aspect there is a tether around a branch point which is likely to be a cutaneous nerve but must be traced and identified. there is no motor stimulation on this branch.

    The take-off of a nerve is identified and tagged with a red sloop and then traced distally into scar.

    The distal end of the nerve branches superficial to the deep fascia. This confirms that it is a branch to the posterior cutaneous nerve of the forearm. A Mixter is passed deep to it in preparation for passing another sloop. It might be useful later as an autologous nerve branch.

    A second red sloop is placed around the distal part of the cutaneous nerve.

    The sloops can be used to retract the nerve branches and maintain some tension during neurolysis. This technique avoids excessive handling of the nerves which could cause an inadvertent iatrogenous injury.

    Performing the external neurolysis of the cutaneous nerve branch.

    The nerve is traced throughout its course. There is a zone of injury with epineural loss. There is no neuroma to feel but motor conduction across this nerve using intra-operative nerve stimulation is absent. It passes to skin and is identified as a cutaneous nerve which is distally damaged. The proximal part may be useful as an autologous nerve graft.

    Operation – 2

    The photography position is changed to follow the distal exploration of the main radial nerve trunk in the blue sloop as it passes in the interval between the lateral mobile wad muscles (BR,ECRL, ECRB) and the medially the biceps and the brachialis.

    The nerve peters into scar. The tip of the DeBakey forceps are on the lateral supracondylar ridge and a screw tip is palpable at this site from the medial plate fixation.

    The distal radial nerve stump is not readily palpable in continuity with the proximal radial nerve in the dense fibrotic scar.

    The Mixter is passed under the distal radial nerve stump.

    The wound is extended distally to expose the intermuscular interval and identify the distal stump of the radial nerve beyond the zone of injury. The Mixter is under the distal radial nerve stump.

    A blue sloop is introduced to the jaws of the Mixter.

    The distal radial nerve stump is tagged with a second blue sloop and the area of scar is exposed revealing a screw tip from the medial plate fixation
    S = screw tip

    Screw tip in the bed of the radial nerve.

    Using the blue sloop for retraction the distal stump can be freed from scar and traced proximally to the site of injury.

    The periosteal elevator is used to expose the screw tips in the radial nerve bed.
    BR = the brachioradialis motor branch is see arising from the scarred radial nerve and passing to the muscle
    PCNF = posterior cutaneous nerve of forearm (red sloops)
    It is not possible to achieve contraction with neurolysis and stimulation on the Br branch. There is proximal discontinuity in scar.

    A second screw tip is identified more proximal to the first. These are the screw highlighted as being too long on the radiograph of the humeral fixation. The zone of injury is around these screws but the extent of the radial nerve damage and discontinuity is suggestive of a high energy injury such as avulsion due to the nerve being caught on a drill bit.

    A rough estimate of the potential nerve gap to be reconstructed is taken. In this case the estimate was 60-70mm and a decision was made to send for a 70mm AVANCE processed nerve allograft and to use autograft from one of the cutaneous nerve branches (PCNF) to rebuild the damaged nerve to brachioradialis. A distal tendon and nerve transfer was planned due to the time since injury and this had possibility had been discussed with the patient pre-operatively as part of the consent process.

    Nerve stimulation confirms no motor units within the radial nerve or the nerves to brachioradialis (blue sloops). There is discontinuity of the main nerve trunk in scar and so debridement is needed to identify a healthy fascicle structure proximally and distally with bleeding nerve ends.

    Further distal neurolysis is possible using the sloop as a retraction aid.

    The zone of injury is now fully cleared in preparation for excision of the proximal stump neuroma. The long screws can be removed or shortened through the posterior incision. In this case it is possible to route the nerve allograft away from the screws. It is too early to remove all the metalwork and the second parallel anterolateral incision renders the intervening skin bridge at risk of ischaemia at this stage.

    A neurotome is a device for holding a nerve and allowing clean sectioning of the distal debridement part without unnecessary handling of the nerve end. They come in a variety of sizes and a suitable size is chosen to grasp the nerve during sectioning.
    The BR branch will need reconstructing from the proximal radial nerve stump after debridement.

    A 6mm neurotome is selected here. The jaws open fully and it can be placed around the proximal nerve above the scar at the level of the neuroma.

    A neurotome blade is attached to a handle and passed through a guide slot in the neurotome. This allows a clean section of the nerve.

    The nerve is sectioned at the level of the neuroma.
    Note that the branch to the BR branch will need reconstruction from the proximal stump.
    In the distal blue sloop is the distal radial nerve trunk and the branch to ECRL.

    The proximal stump has a fibrotic appearance with no bleeding and no fascicle structure. This is still neuroma and scar and further debridement is necessary.
    The proximal blue sloop is now around the scar and the take off of the branch to BR which will need debriding and grafting separately from the main radial nerve trunk.
    Reversed autologous sensory nerve will be used to reconstruct this critical motor nerve for which there is no tendon transfer or motor nerve transfer option.

    Sequential debridements are performed at 1-2mm intervals moving proximally to identify normal nerve tissue.

    At this point after two debridements there is some punctate bleeding but the fascicle structure is still unclear. There is still extensive perineurial scar and grafting at this point will result in no functional recovery and further neuroma formation at the proximal allograft. Further debridement is essential.

    A third debridement is performed on the proximal stump.

    There is now a fascicle structure and interfascicular bleeding. This is a satisfactory proximal stump to graft from. There is still a little interfascicular scar and so a fourth debridement of a further 2mm is performed.
    When grafting a nerve subconsciously the operator is concerned about creating a long gap due to the perceived risk of worse regeneration and also the concern regarding insufficient autologous graft. AVANCE processed nerve allograft can be selected of a sufficient length after debridement for a bespoke reconstruction and avoids these risks. It is well established in the literature that longer nerve gaps (60mm or more) do worse than shorter gaps with autologous grafting. This is indicative of the higher energy transfer, delay to surgery, inadequate debridement and impaired neural regeneration over longer distances.

    Assessment of the proximal stump for grafting after final debridement.

    DRN and ECRL = distal radial nerve and extensor carpi radialis longus branch
    BR = branch to brachioradialis
    PRN = proximal radial nerve

    Operation – 3

    A healthy proximal stump.

    The same procedure is performed at the BR distal stump to remove scarred nerve and provide a health target for autologous nerve grafting.

    There is no bleeding and no fascicle structure. Further debridement is necessary of the BR branch. It has been injured in this zone in the same way as the main radial nerve trunk.

    A neurotome is used sequentially on the distal stump of the radial nerve.

    The distal stump diameter is between neurotome sizes and so the tissue to be debrided may be stabilised in the neurotome jaws with forceps.

    A fascicle structure and bleeding are apparent after two debridements. A further small section must be taken to go beyond a peripheral rim of interfascicular epineurium scar seen in the 7-11 o’clock position.

    The final gap between the proximal and distal radial nerve stumps is measured at 70mm and the allograft may now be defrosted.

    This photograph shows the sequential debridement specimens from the nerve. Note that there is no definite fascicle structure and homogenous appearance of scar. Towards the ends of the debridement there is the partial appearance of a fascicular structure.

    The gap to the BR branch is measured at 42mm. This will be reconstructed directly with a reversed sensory autograft.

    The PCNF is identified and harvested above its injury zone. This will be used to graft from the proximal stump to the BR branch.

    The PCNF has branch points and this is why sensory autograft is reversed to reduce axonal escape from the regeneration axons.
    The PCNF is sectioned proximally as it arises from the main radial nerve.

    Distally the PCNF is sectioned above its injury zone and it is then reversed and positioned in the gap between the proximal radial nerve and the brachioradialis branch.

    The distal end of the reversed sensory (PCNF) branch is sutured using 8’0 nylon, microinstruments and the operating microscope.

    Completion of the distal co-aptation with interrupted sutures x 3.

    The proximal end is debrided to fix the gap in preparation for suture.

    Microscope-assisted suture of the proximal autologous nerve graft from the radial nerve trunk to the brachioradialis branch.

    Trimming the sutures at the proximal co-aptation site.

    The AxoGen AVANCE processed nerve allograft is provided in a tray that can be opened and saline can be applied to the graft to defrost it. This is a 70mm 4/5mm diameter allograft and it is harvested between branch points and so there is no need for reversal. It may be placed either way around in the nerve gap depending on the best diameter match between donor and recipient nerves.

    Care should be taken when opening the allograft tray and there is a tab to hold the bottom of the tray securely. Here the saline is added to the tray to defrost the allograft.

    The allograft is sutured to the gap with 8’0 nylon using microinstruments and the operating microscope.

    The completed proximal co-aptation. There are both allograft and the autologous sensory graft to brachioradialis arising from the proximal stump. The BR fascicle was identified as anatomically discrete from the remainder of the proximal stump under the operating microscope.

    A close up view of the neurorraphy site.

    RN = proximal radial nerve trunk
    A = AVANCE allograft
    Au = autograft to brachioradialis

    The distal neurorraphy is completed in the same way. The allograft is sutured just proximal to the division of the distal stump into the radial nerve (ECRB,PIN,SRN component) and the ECRL branch.

    The completed distal neurorraphy.

    Operation – 4

    Tisseel fibrin glue is used to support the co-aptation sites and reduce the need for too many sutures.

    Proximal neurorraphy Tisseel application.

    Distal autograft to BR branch Tisseel application.

    Application of Tisseel to the distal co-aptation site.

    The completed proximal reconstruction: PCNF autologous graft to nerve to brachioradialis and AVANCE processed nerve allograft to the radial nerve.
    The microsurgical background is still in place to provide contrast.

    The completed proximal reconstruction with suture and Tisseel glue to support the autologous graft to the nerve to brachioradialis and the allograft reconstruction of the radial nerve gap. The sloops can now be carefully removed.

    The AxoGen AVANCE processed nerve allograft in situ prior to would closure.

    The length and position of the nerve grafts and both proximal and distal co-aptation sites should be documented in relation to a bone prominence. This is useful for outpatient post-operative surveilance and measuring rates of recovery. It is also a key component of the RANGER registry study on the use of Avance processed nerve allograft in reconstruction of nerve gaps. The wound is irrigated and haemostasis achieved prior to closure.

    The subcutaneous tissues are opposed with interrupted vicryl 3’0 sutures.

    The wound edges are closed with staples and a bulky dressing is applied. The allograft is inserted tension free and as such simply maintaining the arm in a sling for 2 weeks is sufficient immobilisation for this nerve graft.
    The wound is ready for dressing application.
    In this case a distal PT to ECRB tendon transfer and FCR/PL fascicle (median) to PIN (radial) nerve transfer was performed due to the length of the gap, the severity of the injury and the delay from injury. These addendum procedures will be covered separately in OrthOracle because they can be performed in isolation as a reconstructive strategy for a high grade, non-recovering radial nerve palsy.

    Post Operative

    The procedure was combined with a distal tendon transfer (PT to ECRB) and median to nerve transfers in the forearm (FCR/PL to PIN). These procedures are covered separately.

    Recommended Reading

    There are many factors that affect the outcome from a peripheral nerve reconstruction including severity of the injury, delay to reconstruction, adequacy of debridement, method of reconstruction, tension in the reconstruction, distance of the denervated targets from the injury site and patient factors including age and co-morbidities.
    The gold standard for reconstruction of a critical nerve gap is reversed autologous sensory nerve graft. The sural nerve is typically harvested for a main nerve trunk with a gap of 5cm or more due to the need for 3-5 cables (a total of 25cm of nerve). The sural nerve has little donor site morbidity but necessitates general anaesthesia. There are sall risks of painful neuroma at the proximal donor harvest site plus risks or DVT, PE and donor site infection. The balance of risk and benefit should be weighed for each patient.
    There is an abundance of data on AVANCE allograft utilisation and safety from medical publications and from the RANGER registry study in the USA. The efficacy data is strong for digital nerves and the numbers of sensory nerves and mixed motor-sensory nerves are smaller currently. Comparative data from autologous versus allograft reconstruction is limited. As such my practice is to use allograft in cases of pure sensory nerve reconstruction in otherwise sensitised individuals (neuroma reconstruction) where there is a significant risk of donor site sensitisation; in cases where there is another viable motor reconstruction (distal motor nerve transfer) and reconstruction is for pain, sensory recovery and no-critical motor recovery; in cases where there is insufficient autologous nerve available; in cases where recovery is unlikely but the prime objective is pain management; contraindications to general anaesthesia or lower limb surgery; failed primary autologous graft reconstruction and in cases where patients choose this technique.
    NICE, the national institute for health and care excellence in the UK have issued guidance on the use of processed nerve allograft in nerve repair: NICE Interventional Procedure Guidance: 597 (www.nice.org.uk/guidance/ipg597).Enhanced governance arrangements and audit of outcomes is recommended for use outside sensory digital nerve in the hand. A summary of the guidance and the published literature is provided below.
    AVANCE processed nerve allograft is provided frozen in a number of sizes and the appropriate graft can be selected after debridement and defining the nerve gap.

    References for median to radial nerve transfers:
    Mackinnon SE1, Roque B, Tung TH. Median to radial nerve transfer for treatment of radial nerve palsy. Case report. 2007 Sep;107(3):666-71
    Wilson Z. Ray, Susan E. Mackinnon. Clinical Outcomes following median to radial nerve transfers. J Hand Surg Am. 2011;36(2):201-208

    NICE: Processed nerve allografts to repair peripheral nerve discontinuities IPG 597
    1 Recommendations:
    1.1 Current evidence on the safety and efficacy of processed nerve allografts to repair peripheral nerve discontinuities is adequate to support the use of this procedure for digital nerves provided that standard arrangements are in place for clinical governance, consent and audit.
    1.2 The evidence on the safety of processed nerve allografts to repair peripheral nerve discontinuities in other sites raises no major safety concerns. However, current evidence on its efficacy in these sites is limited in quantity. Therefore, for indications other than digital nerve repair, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
    1.3 Clinicians wishing to do processed nerve allografts to repair peripheral nerve discontinuities in sites other than the digital nerves should:
    Inform the clinical governance leads in their NHS trusts.
    Ensure that patients understand the uncertainty about the procedure’s efficacy on mixed nerve repair and provide them with clear written information. In addition, the use of NICE’s information for the public is recommended.
    Audit and review clinical outcomes of all patients having processed nerve allografts to repair peripheral nerve discontinuities
    1.4 This procedure should only be done by surgeons with training and experience in peripheral nerve repair.
    1.5 Patient selection should take into consideration the site, type of nerve (motor, sensory, mixed) and the size of the defect.
    1.6 NICE encourages further research into processed nerve allografts to repair peripheral nerve discontinuities. This should include information on the type of nerve repaired, the anatomical site, the size of the defect, patient reported outcome measures, functional outcomes, time to recovery and long-term outcomes (12 months to 18 months).
    2 Indications and current treatments
    2.1 Peripheral nerve damage can be caused by trauma or surgery, and can lead to reduced sensation and mobility of the affected limb or region. If direct repair is not possible because the section of nerve discontinuity is too long, grafts or artificial nerve conduits can be used.
    2.2 Autologous nerve grafting (using another nerve from the same patient) is used most frequently (usually using the sural nerve from the leg). However, this can be associated with donor site morbidity. Untreated allografts (using a nerve from a donor) have also been used. However, postoperative immunosuppressive treatment is needed with untreated allografts.
    3 The procedure
    3.1 Acellular processed nerve allografts are nerves from deceased human donors that have had their immunogenic components removed using tissue processing techniques. They are stored frozen until implantation and are available in different sizes. Immunosuppressive treatment is not needed.
    3.2 The procedure is done under general anaesthesia. The injured nerve is exposed, and the nerve ends are cleared of necrotic tissues and resected to allow for tension-free alignment with the graft. The graft is sutured to the exposed nerve ends. After grafting, limb splinting may be needed for several weeks to allow optimal nerve regeneration. The typical length of an allograft implant is 1 cm to 3 cm.
    3.3 The aim of the procedure is to bridge the peripheral nerve discontinuity to allow axonal regeneration and growth through the allograft towards the distal nerve.
    4 Effiicacy
    This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
    4.1 In a randomised controlled trial (RCT) of 23 patients needing digital nerve repair comparing processed nerve allograft (PNA) with treated bovine graft at 12-month follow-up, static 2-point discrimination assessment (s2PD, which tests the ability to discern the difference between 1 and 2 static pressure points) was statistically significantly better in the PNA group (n=5) than the bovine graft group (n=7; 5±1 mm versus 8±5 mm, p<0.05). In the same study, moving 2-point discrimination assessment (m2PD) was not statistically significantly different between the PNA group and the bovine graft group (5±1 mm versus 7±5 mm, p>0.05) at 12-month follow-up.
    In a non-randomised comparative study of 153 patients needing digital nerve repair comparing PNA repair (n=72) with tension-free suture nerve repair (n=81), s2PD scores (excellent plus good, defined as the ability to distinguish between 2 static pressure points at a maximum distance of 15 mm) were not statistically significantly different between the PNA group (67% [48/72]) and the tension- free suture group (64% [52/81]) at 6-month follow-up (p=0.749). In a case series of 17 patients with digital nerve injuries treated by PNA grafting, s2PD was excellent or good in 78% (14/18) of digits repaired, at a mean follow-up of 15 months. In the RCT of 23 patients, Semmes–Weinstein monofilament test (testing of pressure threshold using a monofilament; range: 2.833=normal sensation to 6.650=residual sensation) was statistically significantly better in the PNA group than the treated bovine graft group (3.6±0.7 versus 4.4±1.4, p<0.05) at 12-month follow-up. In the same study, thermal sensation was totally improved from baseline at 12-month follow-up and not statistically significantly different between the treatment (PNA group: from 7% [1/14] to 100% [6/6] and bovine graft group: from 33% [3/9] to 100% [7/7]).
    In a case series of 64 patients needing nerve repair in the upper extremity and treated by grafting using PNA, there was meaningful recovery in 75% (48/64) of all patients. Univariate analysis showed that distal sites of injuries have a statistically significantly higher likelihood of recovery than proximal upper limb sites (odds ratio [OR] 5.606, 95% confidence interval [CI] 1.663 to 18.903; p<0.05). In the same study, discontinuities smaller than 30 mm had a statistically significantly greater likelihood of meaningful repair than those greater than 50 mm (OR 14.333, 95% CI 2.143 to 95.848; p<0.05).
    In a case series of 26 patients with lingual nerve and inferior alveolar nerve discontinuities treated by PNA grafting, meaningful sensory recovery was assessed using a neurosensory test improvement tool (ranging from normal=best, through mild, moderate and severe to complete=worse). At 12-month follow-up, neurosensory test improvement scores were normal in 52% (12/23), mild in 9% (2/23), moderate in 26% (6/23) and severe in 13% (3/23) of patients. In the same study, neurosensory improvement was reported in 86% (12/14) of patients with discontinuities 8–20 mm in length and 89% (8/9) of patients with discontinuities 30–70 mm in length.
    In the RCT of 23 patients, disability of the arm, shoulder and hand score (DASH: 0=no disability, 100=most severe disability) was not statistically significantly different between the PNA group (5±6.5) and the bovine graft group (8±6.3) at 12-month follow-up (p=0.318).
    In a case series of 108 patients needing nerve repair, there was no sensory recovery because of graft failure in 5% (4/76) of patients at last follow-up and surgical revision was needed.
    In the RCT of 23 patients, at 12-month follow-up, pain measured using a visual analogue scale (VAS, 0=no pain, 10=extreme pain) had improved from baseline in both groups (PNA group: from 4.7±3.4 to 0.5±0.6; treated bovine graft: from 4.4±2.1 to 0.9±1.0) but there was no statistically significant difference between the groups (p=0.432). In another case series of 26 patients needing PNA after resection of neuromas of the foot and ankle, mean ordinal pain score (0=no pain to 10=worse pain) statistically significantly reduced from 7.5 points at baseline to 4.9 points at a mean 66-week follow-up (difference 2.6, range +2.0 to −8.0; p=0.016). In the same study, patient reported outcome measurement information system scores were used to assess the impact of pain on patients’ behaviour and daily function (reported as T-scores with a population mean of 50 and a standard deviation of 10). Pain behaviour T-score decreased by 7.3 (range+2.0 to −22.0) from 63.0 at baseline (percentile decrease of 24%, p<0.003). Pain interference T-score decreased by 11.3 (range +2.0 to −27.0) from 68.0 at baseline (mean percentile change of 31%, p<0.003).
    In a case series of 17 patients with digital nerve injury treated by grafting with PNA, pain (measured using a VAS: 0=no pain, 10=extreme pain) worsened in 1 patient (VAS score increased from 5 at baseline to 8 at 15-month follow)
    In the non-randomised comparative study of 153 patients, difference in satisfaction rate was not statistically significantly different between the PNA group and the tension-free suture group (2.02%, 95% CI −6.07 to 10.87) at 6-month follow-up.
    The specialist advisers listed key efficacy outcomes as re-innervation of target organs, nerve regeneration rate, clinical sensory and motor outcome scales, and patient reported outcomes.
    5 Safety
    This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
    5.1 Tenolysis was needed in 3% (2/78) of patients at 6-month follow-up in a non- randomised comparative study of 153 patients needing digital nerve repair comparing processed nerve allograft (PNA) repair (n=72) with tension-free suture nerve repair (n=81).
    5.2 Neuroma was reported after 1 nerve repair of 132 nerves in a case series of 108 patients needing nerve repair.
    5.3 Local infection that improved after treatment (not specified) was reported in 1 patient in a case series of 15 patients treated by PNA grafting.
    5.4 In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse events: immunological reaction or rejection, and inflammatory reaction to preservatives. They considered that the following were theoretical adverse events: immunological reaction or rejection, inflammatory reaction to preservatives and sub-optimal results because of preference in using the allograft when patients could be treated by more established interventions.
    6 Committee comments
    6.1 The grafts used in this procedure are regulated by the Human Tissue Authority.
    6.2 The grafts can be used in a variety of anatomical sites but most published evidence reviewed by the committee came from the repair of digital nerves.
    6.3 The type of nerve being repaired (motor, sensory, mixed) and the size of the defect potentially affect the outcome.
    6.4 The use of this type of graft avoids the need to harvest a donor nerve from the same patient, and avoids the use of non-human-derived tissue and immunosuppression.
    1.1 Current evidence on the safety and efficacy of processed nerve allografts to repair peripheral nerve discontinuities is adequate to support the use of this procedure for digital nerves provided that standard arrangements are in place for clinical governance, consent and audit.
    1.2 The evidence on the safety of processed nerve allografts to repair peripheral nerve discontinuities in other sites raises no major safety concerns. However, current evidence on its efficacy in these sites is limited in quantity. Therefore, for indications other than digital nerve repair, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
    1.3 Clinicians wishing to do processed nerve allografts to repair peripheral nerve discontinuities in sites other than the digital nerves should:
    Inform the clinical governance leads in their NHS trusts.
    Ensure that patients understand the uncertainty about the procedure’s efficacy on mixed nerve repair and provide them with clear written information. In addition, the use of NICE’s information for the public is recommended.
    Audit and review clinical outcomes of all patients having processed nerve allografts to repair peripheral nerve discontinuities
    1.4 This procedure should only be done by surgeons with training and experience in peripheral nerve repair.
    1.5 Patient selection should take into consideration the site, type of nerve (motor, sensory, mixed) and the size of the defect.
    1.6 NICE encourages further research into processed nerve allografts to repair peripheral nerve discontinuities. This should include information on the type of nerve repaired, the anatomical site, the size of the defect, patient reported outcome measures, functional outcomes, time to recovery and long-term outcomes (12 months to 18 months).
    2 Indications and current treatments
    2.1 Peripheral nerve damage can be caused by trauma or surgery, and can lead to reduced sensation and mobility of the affected limb or region. If direct repair is not possible because the section of nerve discontinuity is too long, grafts or artificial nerve conduits can be used.
    2.2 Autologous nerve grafting (using another nerve from the same patient) is used most frequently (usually using the sural nerve from the leg). However, this can be associated with donor site morbidity. Untreated allografts (using a nerve from a donor) have also been used. However, postoperative immunosuppressive treatment is needed with untreated allografts.
    3 The procedure
    3.1 Acellular processed nerve allografts are nerves from deceased human donors that have had their immunogenic components removed using tissue processing techniques. They are stored frozen until implantation and are available in different sizes. Immunosuppressive treatment is not needed.
    3.2 The procedure is done under general anaesthesia. The injured nerve is exposed, and the nerve ends are cleared of necrotic tissues and resected to allow for tension-free alignment with the graft. The graft is sutured to the exposed nerve ends. After grafting, limb splinting may be needed for several weeks to allow optimal nerve regeneration. The typical length of an allograft implant is 1 cm to 3 cm.
    3.3 The aim of the procedure is to bridge the peripheral nerve discontinuity to allow axonal regeneration and growth through the allograft towards the distal nerve.
    4 Effiicacy
    This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
    4.1 In a randomised controlled trial (RCT) of 23 patients needing digital nerve repair comparing processed nerve allograft (PNA) with treated bovine graft at 12-month follow-up, static 2-point discrimination assessment (s2PD, which tests the ability to discern the difference between 1 and 2 static pressure points) was statistically significantly better in the PNA group (n=5) than the bovine graft group (n=7; 5±1 mm versus 8±5 mm, p<0.05). In the same study, moving 2-point discrimination assessment (m2PD) was not statistically significantly different between the PNA group and the bovine graft group (5±1 mm versus 7±5 mm, p>0.05) at 12-month follow-up.
    In a non-randomised comparative study of 153 patients needing digital nerve repair comparing PNA repair (n=72) with tension-free suture nerve repair (n=81), s2PD scores (excellent plus good, defined as the ability to distinguish between 2 static pressure points at a maximum distance of 15 mm) were not statistically significantly different between the PNA group (67% [48/72]) and the tension- free suture group (64% [52/81]) at 6-month follow-up (p=0.749). In a case series of 17 patients with digital nerve injuries treated by PNA grafting, s2PD was excellent or good in 78% (14/18) of digits repaired, at a mean follow-up of 15 months. In the RCT of 23 patients, Semmes–Weinstein monofilament test (testing of pressure threshold using a monofilament; range: 2.833=normal sensation to 6.650=residual sensation) was statistically significantly better in the PNA group than the treated bovine graft group (3.6±0.7 versus 4.4±1.4, p<0.05) at 12-month follow-up. In the same study, thermal sensation was totally improved from baseline at 12-month follow-up and not statistically significantly different between the treatment (PNA group: from 7% [1/14] to 100% [6/6] and bovine graft group: from 33% [3/9] to 100% [7/7]).
    In a case series of 64 patients needing nerve repair in the upper extremity and treated by grafting using PNA, there was meaningful recovery in 75% (48/64) of all patients. Univariate analysis showed that distal sites of injuries have a statistically significantly higher likelihood of recovery than proximal upper limb sites (odds ratio [OR] 5.606, 95% confidence interval [CI] 1.663 to 18.903; p<0.05). In the same study, discontinuities smaller than 30 mm had a statistically significantly greater likelihood of meaningful repair than those greater than 50 mm (OR 14.333, 95% CI 2.143 to 95.848; p<0.05).
    In a case series of 26 patients with lingual nerve and inferior alveolar nerve discontinuities treated by PNA grafting, meaningful sensory recovery was assessed using a neurosensory test improvement tool (ranging from normal=best, through mild, moderate and severe to complete=worse). At 12-month follow-up, neurosensory test improvement scores were normal in 52% (12/23), mild in 9% (2/23), moderate in 26% (6/23) and severe in 13% (3/23) of patients. In the same study, neurosensory improvement was reported in 86% (12/14) of patients with discontinuities 8–20 mm in length and 89% (8/9) of patients with discontinuities 30–70 mm in length.
    In the RCT of 23 patients, disability of the arm, shoulder and hand score (DASH: 0=no disability, 100=most severe disability) was not statistically significantly different between the PNA group (5±6.5) and the bovine graft group (8±6.3) at 12-month follow-up (p=0.318).
    In a case series of 108 patients needing nerve repair, there was no sensory recovery because of graft failure in 5% (4/76) of patients at last follow-up and surgical revision was needed.
    In the RCT of 23 patients, at 12-month follow-up, pain measured using a visual analogue scale (VAS, 0=no pain, 10=extreme pain) had improved from baseline in both groups (PNA group: from 4.7±3.4 to 0.5±0.6; treated bovine graft: from 4.4±2.1 to 0.9±1.0) but there was no statistically significant difference between the groups (p=0.432). In another case series of 26 patients needing PNA after resection of neuromas of the foot and ankle, mean ordinal pain score (0=no pain to 10=worse pain) statistically significantly reduced from 7.5 points at baseline to 4.9 points at a mean 66-week follow-up (difference 2.6, range +2.0 to −8.0; p=0.016). In the same study, patient reported outcome measurement information system scores were used to assess the impact of pain on patients’ behaviour and daily function (reported as T-scores with a population mean of 50 and a standard deviation of 10). Pain behaviour T-score decreased by 7.3 (range+2.0 to −22.0) from 63.0 at baseline (percentile decrease of 24%, p<0.003). Pain interference T-score decreased by 11.3 (range +2.0 to −27.0) from 68.0 at baseline (mean percentile change of 31%, p<0.003).
    In a case series of 17 patients with digital nerve injury treated by grafting with PNA, pain (measured using a VAS: 0=no pain, 10=extreme pain) worsened in 1 patient (VAS score increased from 5 at baseline to 8 at 15-month follow)
    In the non-randomised comparative study of 153 patients, difference in satisfaction rate was not statistically significantly different between the PNA group and the tension-free suture group (2.02%, 95% CI −6.07 to 10.87) at 6-month follow-up.
    The specialist advisers listed key efficacy outcomes as re-innervation of target organs, nerve regeneration rate, clinical sensory and motor outcome scales, and patient reported outcomes.
    5 Safety
    This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
    5.1 Tenolysis was needed in 3% (2/78) of patients at 6-month follow-up in a non- randomised comparative study of 153 patients needing digital nerve repair comparing processed nerve allograft (PNA) repair (n=72) with tension-free suture nerve repair (n=81).
    5.2 Neuroma was reported after 1 nerve repair of 132 nerves in a case series of 108 patients needing nerve repair.
    5.3 Local infection that improved after treatment (not specified) was reported in 1 patient in a case series of 15 patients treated by PNA grafting.
    5.4 In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse events: immunological reaction or rejection, and inflammatory reaction to preservatives. They considered that the following were theoretical adverse events: immunological reaction or rejection, inflammatory reaction to preservatives and sub-optimal results because of preference in using the allograft when patients could be treated by more established interventions.
    6 Committee comments
    6.1 The grafts used in this procedure are regulated by the Human Tissue Authority.
    6.2 The grafts can be used in a variety of anatomical sites but most published evidence reviewed by the committee came from the repair of digital nerves.
    6.3 The type of nerve being repaired (motor, sensory, mixed) and the size of the defect potentially affect the outcome.
    6.4 The use of this type of graft avoids the need to harvest a donor nerve from the same patient, and avoids the use of non-human-derived tissue and immunosuppression.

    Reference

    • orthoracle.com

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