Is it possible to regenerate nerve damage

What grows back, what doesn't?

Peripheral nerve injuries occur most frequently in connection with accidents, but also iatrogenically, especially during surgery. The prognosis depends crucially on the extent of the peripheral nerve injury: Incomplete lesions or injuries in which the connective tissue covering structures of the nerve are preserved usually have a good prognosis and can primarily be treated conservatively, whereas complete lesions with a complete interruption of continuity without surgery Therapy is not expected to provide sufficient regeneration. If there is no nerve regeneration despite exhausting all therapeutic options, replacement operations can at least partially restore the function.

In the case of peripheral nerve lesions, a distinction can be made between primary and secondary nerve injuries. Primary nerve injuries arise directly as part of the trauma through complete or partial severance (pointed trauma) or pressure or tensile damage (blunt trauma), whereas secondary nerve lesions occur with a time latency to the trauma. These secondary nerve lesions are usually caused by complications such as increasing hematomas, excessive callus formation during fracture healing, a developing compartment syndrome or an aneurysm spurium with accompanying vascular damage, which can lead to pressure damage to the nerve. While primary nerve lesions are usually already noticed during the primary surgical treatment of the accident injury, secondary nerve injuries can certainly only occur when the patient is undergoing follow-up care by the general practitioner.

A secondary nerve injury is an indication of a developing complication after trauma (e.g. increasing hematoma formation) and must be diagnosed immediately.

Symptoms of peripheral nerve injury

Motor, sensory and autonomic disorders typically occur after a peripheral nerve injury. The anatomical distribution pattern is based on the muscles or skin areas innervated by the damaged peripheral nerve (Fig. 1). The motor symptoms are typically flaccid paresis, which after a period of three weeks are also associated with increasing atrophy of the corresponding muscles. The reflexes connected to the corresponding nerves are weakened or extinguished (e.g. missing patellar tendon reflex when the femoral nerve is damaged). In the skin area innervated by the nerve concerned, not only sensory disorders occur, which typically affect all sensitive qualities (touch, pain, temperature), but also autonomic disorders with reduced sweat secretion. Clinically important is the distinction between a complete nerve lesion (with complete paralysis of the muscles innervated by the respective nerve and anesthesia in the autonomous, sensitive supply area) and an incomplete nerve lesion in which the corresponding functions are partially preserved. Especially after accidental injuries, this differentiation can cause difficulties due to the limited examination conditions due to open wounds, bandages and movement inhibition due to swelling and pain. Additional neurophysiological (electromyography (EMG), electroneurography (ENG; Fig. 2), evoked potentials) and additional imaging examinations (nerve ultrasonography, MRT) can provide valuable services here.

Classification of nerve injuries

In order to understand the classification of the severity of a peripheral nerve injury, knowledge of the fine structure of a peripheral nerve is essential (Fig. 3): The individual medullary and medullary nerve fibers are surrounded by a delicate connective tissue layer, the endoneurium. Within a peripheral nerve there are nerve fiber bundles (fascicles) in which many individual nerve fibers are combined and surrounded by a further layer of connective tissue, the perineurium. These nerve fiber bundles as well as accompanying blood vessels and fat tissue are located in a tough connective tissue covering, the epineurium, which encloses the peripheral nerves.

The classification of the degree of severity is now based on the extent of damage to axons, myelin sheaths and connective tissue sheaths, the classifications according to Seddon [3] and Sunderland [6] being the most common (Table 1). The prognosis of nerve damage depends crucially on the severity: In the mildest form of nerve damage, neurapraxia, in which only a circumscribed medullary sheath lesion is present and both axons and connective tissue covering structures are preserved, the prognosis is very good and the symptoms regress within days to expect weeks. In all other forms of damage in which there is damage to the axons, Waller's degeneration of the axon distal to the lesion site occurs within approx. 14 days and the axon stump located proximal to the lesion site sprouts again at a speed of approx. 1 mm / Day 1]. So that the newly sprouting axon can reach its destination (endplate region of the muscle or skin area), intact connective tissue nerve sheaths are essential as guide structures. If the continuity of these nerve sheaths is completely interrupted, sprouting with neuroma formation and a lack of reinnervation is to be expected (Table 1).

Determination of the severity

Determining the severity of a nerve lesion is the job of the neurologist. In the case of clinically complete peripheral nerve lesions, EMG / ENG can only be used to reliably differentiate between neurapraxia with preserved axons and axonotmesis or neurotmesis with damaged axons on the other hand only after Wallerian degeneration of the axon sections distal to the lesion site [5]. Nerve sonography or MRI can help to differentiate between axonotmesis and neurotmesis. However, if the continuity of the nerve is macroscopically preserved and the imaging is unremarkable, the axonotmesis / neurotmesis can only be distinguished on the basis of the course, with the lack of timely reinnervation of the affected muscles suggesting neurotmesis.

The time to reinnervation can be estimated from the distance between the muscle and the lesion site and the sprouting speed of the axon of 1 mm / day. Clinically, a Hoffmann-Tinel sign that moves from proximal to distal (uncomfortable, electrifying sensation when percussing the nerve course) can indicate the increasing sprouting of the axons [1].

Therapeutic approach

The therapeutic approach depends on the type and extent of the nerve lesion. In the case of a primarily open, complete nerve lesion (e.g. stab or saw injury), there is a high probability of neurotmesis / Sunderland grade V injury with poor regeneration prognosis. Here a primary or secondary surgical treatment with exposure of the nerves and, if necessary, removal of a continuity interruption is justified. However, if the lesions are primarily closed and continuity is maintained by imaging, the prognosis is usually much better. In this case, a wait-and-see approach with conservative therapy is justified [2]. This consists primarily of occupational and physiotherapy. However, regular clinical and electrophysiological follow-up controls are essential for this procedure. In the event of secondary deterioration or the lack of timely reinnervation, an operative revision should also be sought in these cases. If you decide to have a surgical revision, this should ideally take place three to four months, at the latest six months after the trauma, as irreversible endplate degeneration in the target muscle must be assumed after nine to twelve months, which even then no longer expects successful reinnervation lets when sprouting axons reach the target muscle.

Whenever a peripheral nerve injury is suspected, a neurological presentation should be carried out in order to confirm the diagnosis and to determine the severity of the nerve damage, which is very important for the prognosis and further therapy.

In the case of incomplete peripheral nerve lesions, the prognosis is significantly better than in the case of complete lesions, so that a wait-and-see approach with conservative therapy makes sense in any case [2]. Only if there is no improvement in the course and / or sonographic evidence of the neuroma should an operative revision be considered in these cases, taking into account the above. Time window.

If, despite all therapeutic measures, there is no nerve regeneration and functionally relevant restrictions remain, a replacement operation can be carried out to at least partially restore the lost function. As a rule, this should only be done after a period of at least twelve months after the trauma, when nerve regeneration is definitely no longer to be expected. The principle of replacement surgery is the transposition of the tendon of an intact muscle onto the tendon of a paralytic muscle. One of the most frequently performed replacement operations is the so-called "stapes plasty" to restore the elevation of the foot in the event of irreversible damage to the peroneal nerve. The tendon of the functioning M. tibialis posterior (supplied by the N. tibialis) is pulled forward through the interosseous membrane and connected to the tendons of the M. tibialis anterior and M. peroneus longus (both supplied by the N. peroneus) [4] . The prerequisite for this operation, however, is an intact tibial nerve.


1. Müller-Vahl H, Mumenthaler M, Stöhr M, Tegenthoff M (2014) Lesions of peripheral nerves and radicular syndromes. 10th edition, Georg Thieme Verlag, Stuttgart - New York
2. Pöschl P, Schulte-Mattler WJ (2012) Neurophysiological diagnosis of traumatic nerve lesions. Klin Neurophysiol 43: 1-9
3. Seddon HJ (1943) Three types of nerve injury. Brain 66: 237-288
4. Steinau HU, Tofaute A, Huellmann K, Goertz O, Lehnhardt M, Kammler J, Steinstraesser L, Daigeler A (2011) Tendon transfers for drop foot correction: long-term results including quality of life assessment, and dynamometric and pedobarographic measurements . Arch Orthop Trauma Surg 131: 903-910
5. Stöhr M (2005) Clinical Electromyography and Neurography - Textbook and Atlas. 5th edition, Kohlhammer, Stuttgart
6. Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74: 491-516




Bergmannsheil University Hospital of the Employers' Liability Insurance Association

Conflicts of Interest: The author has not declared any.