Treatment of neurological injuries remains complex, but when multidisciplinary treatment is provided quickly, the results are encouraging. Post-surgical follow-up must include particular monitoring to ensure the injury is recognized clinically, diagnosed quickly and assessed for severity of the neurological damage. While muscular and neurological evaluations are an important part of the physical workup, they are not always sufficiently precise to locate the nerve injury or determine its severity.
Workup
When a neurological lesion is identified, a radiological examination is required to rule out luxation of the prosthesis, cement leakage or excessive lengthening. An ENMG can help to locate the injury and identify its mechanism. It can also be useful in
Given that most neurological injuries resolve spontaneously following RSA,23 conservative treatment is often preferable. Time is a treatment in itself. We often propose multidisciplinary care with physiotherapy (neurostimulation and TENS treatments), occupational therapy (desensitization, proprioceptive and sensory
rehabilitation of the limb), local and oral analgesia, but also cryotherapy, acupuncture, etc.…
Analgesic treatments:
Morphine derivatives are widely used in brachial plexus injuries, when mild analgesics are insufficient. If the morphine derivative is also ineffective, neuroleptics such as pregabalin (Lyrica ®), or gabapentin (Neurontin®) can be introduced, or certain antidepressants, notably duloxetine (Cymbalta®). If the side effects are not tolerated, local treatment by anesthetic patch (Neurodol patch®), anti-inflammatory patch (Flector patch®), or an anesthetic spray may be introduced. If the pain remains unbearable, a stellate ganglion block can be proposed, although this is only effective in 50 % of cases, and not without risk (Horner’s Syndrome, worsening of pain…).
Vitamin treatments:
The B vitamins are known for reducing degeneration of the nervous system, which is why they are often prescribed. A B12 (cobalamin) deficit leads to a deficit in methionine, which is necessary for phospholipid and myelin synthesis. Vitamin B12 is also believed to be an antioxidant,110 facilitating the elimination of free radicals, and would appear to be a neuroprotector.111 In patients with alcohol or drug dependencies, and patients with a vitamin B12 deficiency, supplementation should be prescribed immediately. Of course, it is strongly recommended that patients be encouraged to wean of neurotoxic substances such as alcohol.
Corticoid treatments:
Methylprednisolone is thought to prevent the production of free radicals. Applied locally, it offers the advantage of avoiding the side effects of a systemic treatment and, additionally, costs less. It prevents scarring and improves nerve repair following section and suture.112
Physical treatments:
TENS is used to relieve neurogenic pain and electrostimulation helps to preserve denervated muscles. This type of neurostimulation can help to relieve certain neurogenic pains via the "gate control" mechanism. This effect is, unfortunately, often only temporary, but it can sometimes be prescribed to replace, or at least complement, treatments taken per os (especially where their use is a contra-indicated). Maintaining muscle (notably using electrostimulation), during the time it takes for nerve regrowth following a Wallerian degeneration, is essential to avoid the muscle becoming too atrophied by the time the motor unit reaches it. Muscle function can be preserved and functional recovery will be superior. Stretching, used alongside these techniques, will help to reduce musculotendinous retraction.
Complementary therapies:
In order to optimize functional and sensory recovery, it is essential to prescribe a multidisciplinary rehabilitation program, with physiotherapy (muscle reinforcement, neurostimulation and TENS treatments, biofeedback, etc..) and occupational therapy (Mirror therapy, desensitization, and proprioceptive, motor and sensory reintegration of the limb).
Alternative therapies:
Given the complexity of treatment of neurological injuries, other alternative treatments have been developed in both in- and out-patient centers. Acupuncture, cryotherapy (especially auricular therapy), hypnosis and other relaxation therapies, mindfulness and Mirror therapy are increasingly proposed and adopted.
Surgical treatments
If the initial workup detects a prosthesis luxation, cement leakage or excessive lengthening, surgical revision is necessary, and possibly also a nerve suture/graft/neurolysis. Likewise, if an infection or compressive hematoma is found, the collection should be evacuated and the infection treated with antibiotics.
When conservative treatment fails, several possibilities are available, depending on the type of nerve affected:
Neurolysis:
This procedure is used for continuous lesions (conduction block through peritruncular or intraneural, perifascicular fibrosis). Good results are usually obtained, rapidly.
Sutures
Unlike the central nervous system, the peripheral nervous system is capable of repairing damaged axons.113 Schwann cells are essential for such repairs.114 There are various nerve repair techniques (fascicular repair, epineurial repair, grafts…) but the final result depends on various parameters, such as type of lesion, location, extent of the damage, degree and delay in repair, nerve realignment, surgical
technique, but also factors which are personal to the patient.115 Suturing allows the two ends of a nerve to be reconnected, while trying to align the bundles as well as possible for the best results. Tension in the suture zone should be avoided, as it can create a gap between the nerve extremities, which can lead to fibrosis. Such tension can also lead to ischemia, causing an increase in intraneural pressure and relative compression of the microcirculation.
Grafts:
Interfascicular grafts offer a solution to the problem of tension in the event of substance loss, ensuring the nerve retains its elasticity (5 to 25 mmm, depending on the nerve and the author). True fascicular grafting requires an abundance of suture material, given the high number of anatomical fascicles – usually, grafts are performed by matching up fascicle groups. The graft used is generally a free autograft (external saphenous nerve). Revascularization occurs quickly in this type of small graft (3 to 7 days). The best conditions for a graft are: Young patient age, within one year of injury, substance loss of less than 15 cm, presence of good quality surrounding tissue and the possibility of using "multiple roped grafts" (5 to 6 bundles).
Locally-applied corticoids
Dexamethasone applied locally can improve functional recovery and nerve morphology.116 It would appear to offer better efficacy than when administered systemically.117 One of the mechanisms which may explain this advantage would be an upregulation of the expression of brain-derived neurotrophic factor (BDNF).
Neuro-active steroids are capable of reversing the degenerative effects of ageing on
the myelinated fibers, as well as on the number of myelin anomalies.118,119 A neuroprotective effect of steroids has also been noted on neuron degeneration following physical trauma of a peripheral nerve. The data available strongly suggest that a therapeutic approach to peripheral neuropathies using neuroactive steroids is possible, or even using molecules capable of interacting with their receptors, or of inducing their synthesis directly in situ.
Treatments currently in development
In addition to these important factors for regenerating damaged nerves, certain molecules can be applied locally to the site of the injury, with a positive effect. It is now established that the peripheral nervous system (and particularly Schwann cells) is not only capable of synthesizing neuroactive steroids, but that it is also a target for them. Schwann cells respond to different neuroactive steroids (such as progesterone, testosterone and its derivatives, estrogens…) by altering their proliferation and their cellular products (membranes and myelin proteins …). Certain studies have shown that applying Tacrolimus (FK506), hyaluronic acid and its derivatives, melatonin and methylprednisolone, help to suppress fibroblastic proliferation on the site of the injury, thus reducing nerve scarring.111
Tacrolimus, which is generally used to prevent graft rejections, has a powerful effect on axon regeneration via its immunosuppressive and neurotrophic action.120,121,122 Peripheral nerves are repaired by reducing the scar tissue formed, thus allowing the damaged nerve to function better.
Hyaluronic acid is known as an agent which reduces scarring by preventing lymphocyte migration, degranulation and phagocytosis, as well as macrophagic motility. The exact mechanism is not fully understood, but this substance presents numerous benefits (chondroprotection, improves healing…). Exogenic hyaluronic acid reduces the reproduction and activity of pro-inflammatory mediators and matrixial metalloproteinases, and modifies immune cell behaviors. Thus, when a hyaluronic acid gel comes into contact with an injured nerve, the gel significantly reduces adherences to the nerve.123
Melatonin could prevent the formation of free radicals and neuromas. Melatonin is a neurohormone, synthesized by the hypophysis, which plays numerous roles, most notably its well-known role in the circadian rhythm. Various in vitro and in vivo studies have shown that melatonin is a powerful "eliminator" of free radicals. It is as effective as other antioxidants (mannitol, glutathione, vitamin E) in protecting cells from oxidative damage. However, these antioxidant effects only occur at doses much higher than those found at the maximum nocturnal peak.124 When a peripheral nerve injury occurs, free radicals are produced, alongside an ischemic and inflammatory process. High concentrations of melatonin could reduce these elements, thereby encouraging neurological recovery. Melatonin has an effect on the morphological characteristics of nerve tissue, suggesting that it may be a neuroprotector, fighting free radicals, antioxidants and analgesics in peripheral neurological degenerative diseases. Several studies have proven that melatonin has a positive effect on axon length and regrowth following peripheral nerve injuries.125,126 Peripheral nerve recovery depends on the balance between Schwann cell regeneration and scar
reduce scar formation on the stump and prevent the production of collagen in the granulation tissue of a peripheral nerve in animals which had undergone a pinealectomy.125,129,130 Another recent study show that melatonin stimulates the proliferation of Schwann cells both in vitro and in vivo, following peripheral neurological lesions, and improves nerve regeneration.131 It is thought that the main reason why there is only slight functional recovery following peripheral neurological lesions is that axon regrowth occurs on the wrong muscles. Chang et al.131 recently demonstrated that motor plates re-innervated following a peripheral neurological lesion were much larger in animals treated with melatonin. Melatonin is capable of reducing not only apoptotic cells in the central nervous system, but also the demise of rat motor neurons following transection of the sciatic nerve in neonate rats.132 There is currently no consensus regarding therapeutic dose. Certain studies have shown that doses of 50mg/kg can almost completely neutralize the ultrastructural modifications following a sciatic nerve lesion.133 These results suggest, therefore, that melatonin has a strong neuroprotective effect at doses over 50 mg/kg and that it can preserve peripheral nerve fibers from oxidative damage following sciatic nerve injuries.134 It should, however, be noted that, depending on the dose administered, the effects can be the complete opposite – while a dose between 1 and 50 mg/kg reduces neuron demise, when administered subcutaneously in rats, doses between 50 and 100 mg/kg can lead to epileptic fits, growth retardation or even death.111,132 Further studies are required to evaluate adequate dosage, limit the risk of side effects and explore the risks of this type of treatment. It would also appear that there can be dangerous drug interactions with ZoloftÒ (Sertraline), where toxic neuropathy of the optic nerve has been described.134,135
Type of lesion Treatment Level of evidence
therapy)
Cryotherapy (especially auricular
Table 6: Treatment recommended according to the type of nerve lesion.