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Targeted Muscle Reinnervation (TMR) for neuroma treatment following above knee amputation

    Overview

    Learn the Targeted Muscle Reinnervation (TMR) for neuroma treatment following above knee amputation surgical technique with step by step instructions on OrthOracle. Our e-learning platform contains high resolution images and a certified CME of the Targeted Muscle Reinnervation (TMR) for neuroma treatment following above knee amputation surgical procedure.
    There are various potential sources of chronic nerve pain following amputation but approximately one quarter of lower limb amputees will develop chronic nerve pain specifically due to a symptomatic neuroma within the stump. Chronic nerve pain is a major source of disability in some patients following limb amputation, reducing engagement with rehabilitation programmes and tolerance of prosthetic use. There is an accompanying burden of psychosocial morbidity.
    Treatment of symptomatic neuromas is a challenge for the whole pain team as well as the peripheral nerve surgeon.
    Various surgical techniques are described, and varying degrees of success reported for each.
    During lower limb amputation surgery peripheral nerves are often divided under traction, allowing them to retract away from the stump into healthier tissue. This method however can lead to neuroma formation with spontaneous and evoked pain as well as allodynia, hyperalgesia and dysaesthesia, hallmarks of central sensitisation.
    Surgical treatment for an end neuroma may involve use of a capping device, burial of the stump within muscle or within a cortical bone window or anastomosis to another nerve or a a long nerve ‘graft to nowhere’. Results of these techniques are inconsistent, and treatment of these patients remains difficult.
    Targeted muscle reinnervation (TMR) involves a nerve transfer of the residual nerve end to a motor nerve that is no longer useful. This is performed as close as possible to its entry point into the muscle.
    TMR has shown success in the upper limb where it has been used to generate physiologically appropriate electromyography signals within muscles of the residual limb for prosthetic control. Significant reductions in neuroma pain have also been noted in these patients.
    Early results of TMR in the lower limb have shown promise in preventing or treating neuroma pain. It may be offered at the time of amputation as a preventative measure, or in the treatment of established, symptomatic neuroma in an amputation stump.
    Coapting sectioned nerve stumps onto recipient motor nerve branches encourages nerve regeneration into the target muscle, preventing the formation or recurrence of neuroma.
    In this section the workup and surgical technique in a patient with an established end neuroma following an above knee amputation stump is described.
    Readers will also find the following OrthOracle surgical techniques of interest:
    Targeted Muscle Reinnervation (TMR) of Superficial Radial Nerve using Axogen Avance processed nerve allograft
    Excision of a sural nerve end neuroma and application of a Polyganics NeuroCapTM
    Below knee amputation

    Indications

    INDICATIONS
    In a lower limb amputation stump, targeted muscle reinnervation (TMR) is indicated whenever there is a symptomatic end neuroma that can be identified.
    The technique of TMR is proven in prevention of neuromas and phantom pain in primary amputation as well as in secondary intervention for neuroma pain after amputation. In the lower limb, TMR has been used primarily to redirect axons from a mixed motor-sensory nerve stump after transection to a motor branch in the vicinity of the amputation to goo effect. When there are no motor branches available, or the risk of muscle wasting and therefore prosthetic fitting or padding is a concern, then development of a reconstructive peripheral nerve interface (RPNI) may be preferred. Osteointegration may be used to improve prosthetic interface with the skeleton in cases with poor muscle bulk, in short stomps and in cases where there is neuroma pain from a traditional socket interface.
    The indications for TMR are an established symptomatic neuroma after previous surgery, or a nerve transection injury that does not have a suitable distal nerve stump available for active reconstruction with a nerve graft.
    SYMPTOMS & EXAMINATION
    A quarter of lower limb amputees report localised neuroma pain within the stump. This can be difficult to differentiate from phantom limb sensations that are referred to the amputated part.
    Pain from an end neuroma within the stump manifests as a combination of pain that is evoked by local touch or pressure that stimulates local nerve endings within the neuroma. There is, in addition, the presence of spontaneous pain that the patient may describe as coming on at rest without any obvious trigger. The pain may be described as an electric shock, shooting burning, or tingling sensation. The effected area may also exhibit features of central sensitisation such as:
    Allodynia : Pain elicited by normally innocuous stimulation
    Hyperalgesia : Exaggerated and prolonged response to pain
    Secondary hyperalgesia : Pain that spreads beyond the original site of stimulation
    Examination in this group of patients can be difficult due to the exaggerated pain response and possible psychological distress with apprehension. It is helpful to reserve examination of the most sensitive areas of the stump to the end of the examination as once pain is initiated it may make the rest if the examination unreliable even if the patient can tolerate it.
    Gentle tapping in a distal to proximal direction along the courses of the main nerve trunks may elicit a Tinels sign over the neuroma.
    If there is tether pain due to a sensitised nerve end that is stuck in a scarred bed, movement of the residual limb may elicit pain.
    An assessment of the skin quality and scars over the stump must also be made. A tender scar or poorly fashioned amputation stump may contribute to pain after an amputation and the opinion of the patients orthopaedic surgeon and prosthetist should be sought before planning any nerve surgery.
    INVESTIGATIONS
    The principle investigation in this group of patients is a series of ultrasound guided nerve block with pain scores using a visual analogue scale before and after each block. This helps to confirm the distribution of pain within the various transected nerve trunks and helps confirm which trunks have a neuroma that is a significant pain driver. It also helps determine whether more than one nerve is involved in a territory where neighbouring nerves may be contributing to pain together.
    In this particular case the sciatic and saphenous nerve branches were considered to be the main pain drivers.
    Therefore the sciatic, saphenous, posterior cutaneous femoral nerve and femoral nerves were blocked in turn with pain scoring between each individual block. Other candidates for nerve block include the lateral cutaneous nerve of thigh and the obturator nerve but neither correlated clinically with the distribution of pain.
    After blockade in the order above pain was abolished after the saphenous nerve block with minimal contributions from the remaining nerves.
    Ultrasound imaging of the stump may help locate the presence and location an end neuroma which may be lying out of its normal anatomical location particularly after being divided under traction.
    ALTERNATIVE OPERATIVE TREATMENT
    There are a great many alternative surgical treatments for neuroma management with variable results in the published literature. These have include treating the end neuroma with a nerve capping device, burial of the nerve stump into a cortical window, or local muscle. Long grafts to nowhere, recently using Avance allograft have also been described. Comprehensive pain scoring before and after surgical intervention and long term follow up are essential to fully evaluate any technique.
    NON-OPERATIVE MANAGEMENT
    Non surgical modes of treatment have often been exhausted by the time a patient arrives at a peripheral nerve clinic. However a period of desensitisation therapy that includes local soft tissue mobilisation, scar massage and desensitisation is important. Where there is central sensitisation, the patient should see an appropriate occupational therapist for mirror therapy alongside a desensitisation programme.
    Pharmacological treatment may include the use of neuropathic pain agents such as Gabapentin. The full guidance about use of these medications is set out in NICE guideline CG173.
    Psychological therapies are helpful in a subset of patients that demonstrate features of significant psychological distress, but these should be seen as an adjunctive measure alongside treatment of a symptomatic neuroma
    CONTRAINDICATIONS
    Contraindications to surgery include any general concerns about surgery such as poor skin quality or active infection.
    A poor response to the diagnostic blocks would raise concerns about the likely success of surgical intervention. Significant psychological distress in any patient should also raise concerns about the success of a purely surgical approach and an initial psychological assessment is important.

    Setup

    The patient is under a general anaesthetic without muscle relaxant since it is helpful to have reliable nerve stimulation.
    Once the procedure is complete, a local anaesthetic catheter can be left in situ to provide intermittent post operative analgesia for the first 24 hours.
    The patient is positioned supine with the thigh draped off as high into the groin as possible.
    Thrombo-prophylaxis and prophylactic antibiotics are given according to local protocol.
    Both bipolar and unipolar diathermy and suction are be available.
    Once nerves are exposed, a pair of mixter forceps and several sloops will be required. A set of micro-instruments with jewellers forceps and serrated nerve scissors. A neurotomy set can be added to this if available.
    A microscope which should be checked and setup for the correct focal length, inter pupillary distance and working position prior to starting the procedure.
    Nerve coaptation is made using 9/0 nylon and fibrin glue (Tisseal – Baxter).

    Operation – 1

    A pre-anaesthetic examination is performed to mark out the most prominent Tinel’s points as well as any areas of cutaneous hypersensitivity
    Here the incision has also been marked. The plan is to perfom a targeted muscle reinnervation (TMR) of the saphenous and distal femoral nerves into motor branches into the vastus medialis.
    The incision is planned along the middle third of a line that is drawn from the medial border of the patella to the mid point of the inguinal canal. In an above knee amputation the position of the patella must be estimated, usually be comparing the stump to the contralateral limb.
    This canal is also known as the adductor canal or Hunter’s canal. The contents of the subsartorial canal include the superficial femoral artery and vein and branches of the femoral nerve. The boundaries of the canal are: sartorius anteromedially; adductor longus and magnus posteriorly and , vastus medius laterally.
    Within the canal, both target and recipient nerves run close to one another in the subsartorial canal, separated by a well defined tendinous aponeurosis.

    The thigh is prepped up to the groin crease and draped as proximally as possible
    The hip joint is abducted to improve access to the medial thigh.

    A sandbag may be placed under the contralateral hip to improve the angle of approach to the medial thigh.

    The skin, superficial fascia and fat are incised over the neuroma.The incision is developed towards the deep fascia.
    Traversing vessels are coagulated using the bipolar diathermy.

    The fat is separated to expose the deep fascia over the anterior border of the sartorius in a proximal direction.
    Sartorius runs from the anterior superior iliac spine to the superomedial tibia.IT therefore runs obliquely across the thigh.
    The fibres of sartorius serve to confirm that the incision is centred correctly. These run obliquely from superior and lateral to distal and medial.
    Once sartorius has been identified, the incision can be extended proximally or distally if the initial approach is not quite centred correctly.
    There shuould be easy access to the anterior border of sartorius.

    The process is repeated in a distal direction.

    The fascia over the sartorius is incised and extended over the length of the muscle along its anterior edge.

    The space deep to sartorius is developed with careful blunt dissectionThis image demonstrates blunt dissection into the stripe of fat just under the anterior border of sartorius.
    The saphenous nerve lies in this fatty envelope deep to sartorius and this should be carefully separated to expose the nerve.
    This is the largest sensory branch of the femoral nerve, arising in the proximal thigh.
    After passing through the subsartorial canal, it passes through adductor magnus and into the medial aspect of the leg.

    The saphenous nerve, once identified, is carefully mobilised over its length in the subsartorial canalStaying in the fat under sartorius, the bipolar diathermy is used to coagulate any small traversing vessels to ensure the field is kept clear and dry.
    The saphenous nerve has been identified in the distal part of the exposure. This is always found within a layer of fat. Often an epineural vessel running along the length of the nerve helps to identify it within the fat.
    Deeper and more medially there is a thick aponeurosis which has made its appearance in the upper part of this image.
    Just deep to this thin sheet of tissue lie the femoral nerve and vessels and will be opened to expose these structures in the next few steps.
    S-Saphenous nerve
    M – Sartorius muscle
    A – Aponeurosis

    A mixter forceps is used to pass a sloop around the saphenous nerveAs the mixter is passed around the nerve, it may encounter some resistance, if the nerve is adherent to the surrounding tissue layers. Further mobilisation may be needed.
    It is important not to open and close the jaws of the mixter whilst they are being passed around the nerve as an unseen branch or epineurium may get inadvertently injured.

    Once passed through, the sloop may now be used to aid further dissection along the course of the nerve to mobilise it.
    The nerve continues to lie under cover of sartorius throughout the dissection. As it passes through the canal, it crosses the femoral vessels obliquely to lie on their medial side before passing through the adductor magnus muscle.

    The aponeurosis layer is now formally exposed by retracting the saphenous nerve and fat inferiorly.
    The femoral nerve and vessels can sometimes be seen running just deep to this layer.
    Once the aponeurosis is divided sharply, they will come into view.

    The aponeurosis is now opened along the line of the neurovascular structures.
    This is carefully incised taking care to protect the deeper structures from injury.
    In this image the longitudinal vascular structure that is just visible indicates the position of the femoral artery and vein as well as the nerve to vastus medialis.

    The opening is developed and extended proximally and distally along the course of the femoral arterySpreading the Jamiesons scissors along the artery improves the exposure in this area.
    The branch of the femoral nerve with its segmental supply into vastus medialis will be running alongside the artery.

    The nerve to vastus medialis is found and then a sloop is passed around it.A mixter is used to pass the sloop around the nerve.
    Once held in the sloop, the Jamiesons scissors are used to improve exposure and to demonstrate the multiple branches from the main trunk that run into the vastus medialis.
    The sloop allows the nerve to be safely held and mobilised whilst the dissection proceeds.

    The main femoral nerve and any branches identified are stimulated using the nerve stimulatorThe saphenous nerve is a sensory nerve and the lack of any motor activity upon stimulation confirms its identity.
    The branches into vastus medialis arise segmentally from the main trunk. Both the main trunk and any branches seen arising from it are also stimulated at a 1.5mA and demonstrate contraction of the muscle.
    In this procedure two such motor branches will be required to enable the saphenous nerve and the terminal femoral nerve to be redirected into them.

    The nerve to vastus medialis is exposed proximally to find a second segmental branch.The aponeurosis is opened proximally to enable access.
    It must be divided sharply whilst ensuring the neurovascular structures just deep to it are protected.
    Dissecting along the nerve in a distal to proximal direction carries the risk of inadvertent avulsion of a nerve branch at its point of take off. Antegrade dissection along the main nerve trunk is always safer.

    The saphenous nerve is prepared for divisionTMR is a form of nerve transfer surgery and the principle of transecting the donor nerve as distally as possible applies.
    The saphenous nerve is being mobilised distally to maximise length.
    Its most distal portion is tethered to scar within the stump.

    The saphenous nerve is divided distally.One technique for ensuring a clean, single cut through the nerve with minimal handling is demonstrated here. A sharp size 15 blade is used whilst the nerve rests over a saline soaked gauze. This serves to allow a controlled transection with minimal movement of the nerve.
    An alternative is to use a set of Victor Meyer neurotomes and a neurotomy blade, described elsewhere on Orthoracle.

    This image demonstrates the divided proximal end of the saphenous nerve. It is examined to ensure there is a normal fascicle structure and that the nerve has been sectioned proximal to the distal neuroma.

    The branches arising from the main trunk of the nerve to vastus medialis are now slooped and stimulated.
    Two such motor branches are slooped.

    Each branch is now divided as proximally as possible. Here the nerve is being divided at its point of take off from the main vastus medialis nerve trunk, which is as proximal as one can go. This ensures that the length of the recipient nerve is maximised and ensures that the donor and recipient nerves are able to undergo coaptation without tension.
    The same technique described above is used, with a small damp swab used to stabilise the nerve which is divided sharply.

    The rest of the nerve to vastus medialis runs distally into the stump. Since there is a risk that this nerve end may also be a potential a pain driver.
    The nerve is exposed further distally.
    The distal end of this nerve can also be used as a donor nerve to coapt into one of its own motor branches. Although this is not essential, the distal stump of this nerve is redundant and has already been exposed. Performing a second TMR using this nerve removes its cut end from the amputation stump and may increase the chances of a successful outcome.
    It is dividing as distally as possible to provide a second donor nerve with comfortable reach into one of its own proximal branches.

    Both the saphenous nerve and the remaining vastus medialis nerve are lined up to be transferred into the two proximal vastus medialis motor branches.The nerve ends are placed upon two pieces of background material to improve visualisation under the microscope.
    The two recipient motor branches are seen at A
    B is the proxinal end of the saphenous nerve.
    C is the rest of the nerve to vastus medialis
    Th microinstruments should be available for manipulation of the nerve ends and for the next steps which will include neurorrhaphy.

    The microscope is broought into the field. a 9/0 nylon suture is used to perform two separate coaptations.Both the saphenous and distal femoral nerve to vastus medialis are coapted to the two motor branches into vastus medialis.
    Three to four epineurial sutures are placed at even points around the circumference of the nerve ends to bring them together and allow the fascicles to face each other.

    Operation – 2

    The saphenous nerve coaptation is checked to ensure all fascicles are contained.There are no gaps, but equally the coaptation is not too tight to cause overlapping of fascicles.

    The second coaptation is completed
    There is a slight size mismatch here but the donor nerve fascicles are all facing the recipient. There is no tension on either neurorrhaphy.

    Fibrin glue is now used to augment the repairs, firstly with a small amount placed around the epineurial repairThis will seal it off and support the existing sutures.

    This is repeated for both repairs.
    The background material helps to contain the glue around the repair site.

    The background material is now wrapped, rather like a cigar, around the repair to allow the glue to set in a cylindrical form around the entire repair.This is repeated for each site.

    An optional step is to take a small cuff of surrounding muscle to wrap the neurorrhaphy site.Wrapping the neurorrhaphy is local muscle is described by numerous authors for TMR.
    This is recommended when there is a large size mismatch between the donor and recipient nerve
    This commonly occurs in TMR where an entire distal nerve trunk is coapted onto a small muscle branch. In such cases muscle wrapping serves to contain any escaping fascicles as regeneration progresses into the recipient motor nerve.
    Although the size match is actually quite reasonable here, this image demonstrates the technique of mobilising a few fibres of sartorius to enable them to sit around the neurorrhaphy site.

    A 4/0 vicryl suture secures the muscle around the nerve repair.It is vital not to introduce tension or compression during this step. The cuff of muscle merely acts as an extra layer, wrapping the epineurial sutures to ensure that any repair site neuroma is contained.

    In this case a nerve catheter will be left in the surgical bed to allow delivery of local anaesthetic around the nerves for post operative pain relief. This may be removed if the patient is comfortable after 12-24 hours but can be very useful if the patient experiences nerve pain in the early post operative period.

    The wound is washed out with normal saline and a layered closure is performed with monocryl suture

    Steristrips support the wound edges.
    A non adherent sealed dressing is then placed over this.

    The stump is wrapped with velband and crepe.
    The nerve catheter is secured and placed over the dressings with clear labelling and instructions about its use and removal for the nursing staff.

    Post Operative

    Once recovered from the general anaesthetic the patient is returned to the ward. If pain is well controlled the patient can mobilise safely with input from the ward physiotherapists.
    The patient is typically discharged the next morning after removal of the nerve catheter on the ward.
    The first follow up clinic appointment is in one week, when the dressings are removed and an initial post operative pain score is recorded.
    At two weeks the wound is sealed and the dressings can be reduced.
    Prosthetic fitting, or resumed prothetic use may be commenced once the wound is resilient after 6- 8 weeks provided the wound is well healed and the patient feels ready to do so.
    Liaison with the patients prosthetist throughout is essential to ensure satisfactory outcomes.
    Further follow up with repeat pain scoring is scheduled for 3 months, 6 months and 1 year postoperatively.

    Recommended Reading

    1. Targeted Muscle Reinnervation for the Upper and Lower Extremity. Kuiken TA, Barlow AK, Hargrove L, Dumanian GA.
    Tech Orthop. 2017 Jun;32(2):109-116.
    An overview of the use of targetted muscle reinnervation and its role in both prosthetic control and neuroma prevention.
    2. Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation. Valerio IL, Dumanian GA, Jordan SW, Mioton LM, Bowen JB, West JM, Porter K, Ko JH, Souza JM, Potter BK.
    J Am Coll Surg. 2019 Mar;228(3):217-226.
    There is an increasing recognition that TMR performed at the same time as a limb amputation may prevent the onset of neuropathic pain.
    In this cohort study fifty one patients were compared with a larger historical control group showing significant reductions in neuropathic pain in the TMR group.
    3.Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial.
    Dumanian GA, et al. Apkarian AV, Porter K, Jordan SW.Ann Surg. 2019 Aug;270(2):238-246.
    This RCT compared conventional neurectomy with TMR for the treatment of chronic post amputation pain showed significantly greater improvements in pain scores in the TMR group.

    Reference

    • orthoracle.com

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