The Treatment of Peripheral Nerve Injuries

Background: Nerve lesions often heal incompletely, leading to lifelong functional impairment and high costs for the health care system. The updated German clinical practice guideline is intended to promote the early recognition of nerve lesions and the timely initiation of proper treatment for optimal restoration of function.

Methods: The recommendations are based on an assessment of all the evidence revealed by a systematic search of the literature, as well as on the expertise of the multiprofessional guideline group.

Results: Only a few publications contain high-quality evidence. This version of the guideline contains a more detailed discussion of war injuries, iatrogenic injuries, MR neurography, and specific treatments than the previous version. As for the different methods of nerve replacement, a comparison of autologous transplantation versus the use of conduits and tubes revealed no significant difference between these two methods on the mBMRC scale, and minimal superiority of autologous transplantation with respect to two-point discrimination. As for the use of nerve transfers when nerve reconstruction is not feasible or unlikely to succeed, nerve transfer yielded slightly better results than proximal reconstruction for elbow flexion, but the difference did not reach statistical significance (mBMRC ≥ 3: RR 1.16, 95% confidence interval [1.02; 1.32]). The treatment of neuromas with targeted muscle reinnervation was superior to the classic approach in decreasing both stump pain (MD 2.0 +/- 2.8) and phantom limb pain (MD 3.4 +/- 4.03).

Conclusion: The delayed or improper treatment of peripheral nerve lesions can lead to severe impairment. Timely diagnosis, the use of appropriate treatments in conformity with the guidelines, and interdisciplinary collaboration among specialists are all essential for optimizing the outcome.

Nerve lesions often heal incompletely, leading to lifelong functional impairment, chronic pain, and high costs for the health care system (1, 2). This is due to the pathophysiology of nerve regeneration. After a nerve is transected, the distal nerve end is subject to Wallerian degeneration with loss of axonal structures and the myelin sheath. The axons sprout from the proximal nerve end and grow distally through the remaining basal lamina tubes at a regeneration rate of approximately 1–3 mm/day. If motor axons reach their muscle end organ within 12–18 months, good function can return. Thereafter, the motor end plate degenerates completely, meaning that the possibility of reinneravation is lost. Therefore, the right timing for nerve reconstruction plays a particularly important role in motor nerve damage. Furthermore, since nerve injuries often go unrecognized or are recognized too late, this guideline is intended to promote the early recognition of nerve lesions and the timely initiation of proper treatment for optimal restoration of function.

In terms of diagnosis, advances in imaging using magnetic resonance neurography (MRN) have brought about relevant changes with regard to establishing the indication. From a treatment perspective, nerve transfers, which were not yet available in this form when the previous version of the guideline was developed, have become a firmly established technique for restoring function and treating pain. The major importance of what is often long-term follow-up with occupational therapy and physiotherapy underlines the interdisciplinary aspect here.

The diagnosis and treatment of peripheral nerve injuries are topics much talked about in the literature. However, the numerous publications mostly have low-quality evidence, due to the heterogeneous injury picture, the resulting small number of cases, and ethical problems regarding randomization in health care research, among other factors.

Materials and methods

For the update of the German clinical practice (S3) guideline (eBox 1), areas in which relevant developments have taken place since the publication of the previous version were identified in a first step. In all, seven subject areas were defined, for which a systematic literature search and analysis according to GRADE criteria should be carried out with the aim of presenting aggregated results (eBox 2). The cutoff date for the literature search was 31.07.2023, whereas no start date was specified.

eBox 1

Specialist societies participating in the German clinical practice (S3) guideline on “The treatment of peripheral nerve injuries”

eBox 2

PICO questions for the areas with relevant developments since the publication of the previous version

The methodology was in line with the “Cochrane handbook for systematic reviews of interventions.” The literature search was carried out in MEDLINE with pre-defined medical subject headings (MeSH) terms (3) and in the Cochrane Central Register of Controlled Trials using the terms “nerve trauma“ and “nerve injury” (eFigure). The inclusion criteria are presented in the eMethods.

eFigure

Flowchart of the literature search for the assessment of the patient, intervention, control, outcome (PICO) questions—summarized for the six questions

For all other statements and recommendations, the Oxford levels of evidence used in the previous version (4) have been retained.

Results

Epidemiology

From a collective of 110,667 trauma patients at a European trauma center between 2012 and 2020, 5026 (4.54%) nerve lesions were identified (1). Despite their relative rarity, nerve lesions are of significant medical, social, and health economic relevance, since they predominantly affect people of working age (39.9 years) (1) and the recovery is long and associated with sick leave of 11–1 109 days (2). It is not uncommon for complete recovery not to be achieved—30% of affected individuals with work-related nerve injuries receive a work disability pension of at least 20% (2).

Nerve injuries in fractures

Peripheral nerve injuries are more common in certain fractures. According to their anatomical course and critical vascular supply, one sees in particular lesions of the axillary nerve, the radial nerve, and the peroneal nerve resulting directly from fractures (5).

Iatrogenic nerve injuries

In a large case series, 17.4% of peripheral nerve lesions were of iatrogenic origin. In 94% of the cases, a surgical procedure was the cause (6). Major procedures, such as osteosynthesis, herniotomy as well as knee, hip, and shoulder surgery bear the highest risk at 45%. Minor procedures, such as lymph node biopsies from the triangle of the neck and varicose vein surgery, were the cause of nerve lesions in 27% and neurosurgical procedures in 15% of cases. Non-surgical measures such as injections, puncture, positioning, and dressings were responsible for 4% of iatrogenic lesions (7).

Iatrogenic injury is the most common cause of lesions in some nerves. In large collectives of patients, 25.2% of treated sciatic nerve lesions (8), 60% of femoral nerve lesions (9, 10), and 94% of accessory nerve lesions were of iatrogenic origin (11).

Some nerves are more at risk during surgery than others due to their course (12). A large case series showed that the median (21.3%), accessory (18%), radial (15.6%), and peroneal (11.5%) nerves are those most frequently affected (13). The largest German case series to date revealed similar findings (1, 7). Radial nerve palsy is particularly common in humeral osteosynthesis (14). The incidence of radial nerve damage as a result of plate osteosynthesis of the distal humeral shaft was between 5.1 and 16% (15, 16, 17, 18). Iatrogenic nerve injuries are often not noticed immediately (19) (Table).

Table

Risk of iatrogenic nerve injuries in relation to the nerve and type of procedure

Nerve lesions in children

Common causes of nerve injuries in childhood include cuts or lacerations (68.1%), followed by falls (14.6%), road traffic accidents (5.6%), and iatrogenic nerve injuries (1.4%) (1, 20). In the case of traumatic injuries, the finger nerves are most frequently affected at almost 50% (1), followed by the median nerve (14.8%)—mostly as a result of cuts, and less frequently due to supracondylar fractures or elbow dislocation (20, 21). Injuries to the ulnar and radial nerves are also common, usually caused by direct trauma, fractures, or elbow dislocation. Injuries to the lower extremity nerves are significantly less common (20, 22).

Nerve lesions due to combat injuries and gunshot wounds

The extent of an injury from a projectile depends on the body region affected and the kinetic energy delivered to the tissue, which derives from the velocity of the projectile. Therefore, a distinction is made between low- and high-velocity projectiles. On the upper extremity, one can assume that gunshot wounds that cause fractures and vascular injury also cause nerve lesions. Soft tissue damage and tissue contamination are relevant issues in the case of high-speed projectiles. Splintered bone fragments can cause additional nerve damage. Fragment dislocation, swelling, and scarring also contribute to the pattern of injury and are frequently found in the area of the radial nerve on the humerus or the peroneal nerve on the fibula (23, 24, 25, 26, 27, 28). The risk of infection is particularly high in the case of high-velocity projectiles. Infection management involving repeated procedures to clean the wound usually precludes nerve reconstruction in the first instance. The defects caused by debridement may require extensive soft tissue reconstruction—only after this is secondary nerve reconstruction possible (25, 28, 29, 30, 31).

Recommendations on the diagnosis of peripheral nerve injuries

The number of studies on diagnostic issues is largely inadequate and the level of evidence of low. Only for instrument-based diagnostic methods is there a larger number of publications.

Careful history-taking (grade A recommendation) and the earliest possible clinical examination (grade A recommendation) are crucial to distinguishing a peripheral nerve injury from spinal, cerebral, or other functional disorders. The lesion should be comprehensively described (in terms of functional sensitivity, motor function, anatomy/morphology, etiology) and reference made to the current classifications (British Medical Research Council [BMRC] and Seddon/Sunderland) (grade B recommendation). With regard to instrument-based diagnostic methods, neurography yields important information on the pathomechanism (neurapraxia without structural damage to the axons versus axonotmesis involving axonal damage but intact sheath structures) after as little as 1 week and shall be carried out in the first few weeks if there is diagnostic uncertainty (grade A recommendation). To differentiate between neurapraxia and axonotmesis, needle electromyography shall be performed at 2 weeks in the case of uncertainty (grade A recommendation).

Imagining techniques are gaining in importance. In cases of diagnostic uncertainty, neurosonography should be used preoperatively in order to more precisely define the location and severity of a nerve lesion and to ease decision-making regarding the further surgical procedure (grade B recommendation). MRN is able to visualize nerve lesions at the fascicular level and should be used in equivocal cases to localize and assess cause and severity (grade B recommendation). Compared to sonography, it can show deep and proximal nerve structures as well as patterns of muscular denervation, while nerve structures can also be identified in hematomas and soft tissue injuries. This enables treatment decisions to be made with significant time savings (22) (avoiding disadvantageous watch-and-wait intervals).

Recommendations on the treatment of peripheral nerve injuries

The time aspect takes highest priority in the treatment of peripheral nerve injuries. This is supported not only by a handful of studies with moderate quality of evidence but also, and most importantly, by clinical experience (32, 33). Nerve damage requiring surgical treatment should undergo appropriate microsurgy as soon as possible in order to achieve early and optimal reinnervation (grade B recommendation). Open injuries require immediate treatment, while closed injuries with proven discontinuity should be reconstructed within 1–2 weeks. Closed injuries without discontinuity and for which neurolysis is indicated, as well as adjuvant procedures if necessary, should be operated within 2–6 weeks.

Technical aspects

For all nerve suture or nerve reconstruction procedures, sufficient optical magnification devices and appropriate illumination should be available (microscope or loupes), as well as microsurgical instruments and suture material. Devices for intraoperative neurophysiological testing, such as nerve stimulators to test muscle response to stimuli or to record nerve action potentials, are recommended (grade A recommendation). In the case of primary and secondary nerve sutures, tension-free coaptation of the nerve ends shall be ensured.

If tension-free coaptation is not possible, nerve reconstruction must be performed. In addition to classical autologous transplants, a variety of autologous or alternative conduits are also available. An analysis of the quantitative data (eResults) shows a trend towards autologous transplants, particularly in the case of mixed nerves. For pure sensory nerves, alternative transplants are available as an option.

In the case of partial nerve transection, split repair should be performed under certain conditions and based on strict indication criteria (grade B recommendation).

Various clinical situations

If a nerve shows clinical signs of dysfunction and has an open injury along its course, one can assume in the first instance that it is involved, and immediate exploration shall be undertaken (grade A recommendation). If primary treatment cannot be performed, for example, in the case of gunshot wounds, insufficient experience and equipment, or there are concomitant injuries, secondary treatment (delayed repair) should be carried out within 3–6 weeks, once a non-irritated, non-infected revision area has been achieved and assuming blood supply is good and the diagnosis has been confirmed—if follow-up checks are needed, these should be at the earliest possible time, but within 6 months at the latest (grade B recommendation). In the case of closed/blunt injuries or stretch injuries, a detailed neurological assessment should be carried out if nerve dysfunction is present and, where necessary, nerve exploration performed depending on the clinical, electrophysiological, and/or imaging findings and course (grade B recommendation). In the event that osteosynthesis is required for bony injuries close to the nerve, reliable nerve visualization with corresponding documentation of the findings should be undertaken (grade B recommendation). If regeneration does not occur, the further treatment concept should be determined within 6 months of the trauma, but as early as possible, and surgical nerve exploration should be considered (recommendation grade B). In cases of intraoperative nerve injury, reconstruction shall be performed by an experienced surgeon, ideally during the same procedure or after a few days (grade A recommendation).

The role of the distal nerve transfer

Nerve transfer enables the reinnervation of the affected musculature by transferring sacrificable motor fascicles from a healthy donor nerve near the target muscle to the motor branches of the damaged nerve, thereby converting a proximal lesion into a distal lesion.

The advantages of this method include a shorter reinnervation distance and reduced reinnervation times, while at the same time clearly defining which donor motor (more rarely, sensory) fascicles are assigned to which recipient fascicles. Nerve transfers should be used when nerve reconstruction is not feasible or unlikely to succeed. They can also be used as a complementary end-to-side technique (grade B recommendation). Nerve transfers should be planned in such way that the coaptation site is as close as possible to the target muscle, and timed so that reinnervation of the target muscles—taking into account the time elapsed since the trauma and the distance that still needs to be grown through—can take place within 12 to at most 18 months (grade B recommendation). The donor nerve must be a sacrificable branch and have a largely suitable number of motor axons and function that is as synergistic with the recipient nerve as possible (grade B recommendation). Anatomically narrow areas in the recipient nerve can be decompressed in order to improve reinnervation (grade 0 recommendation). The quality of the evidence is greatly reduced by the quality of the included studies, the considerable variability in follow-up times, and the widely varying group sizes. Therefore, a trend towards better outcomes following nerve transfer can only be reported for the reconstruction of elbow flexion (muscle strength according to the British Medical Research Council [mBMRC] ≥ 3, relative risk [RR] 1.16 [1.02; 1.32] (eResults).

Salvage options

Motor replacement surgery by means of tendon transfer can be performed if reinnervation of the affected muscle is not feasible or has been unsuccessful (grade B recommendation) (see eResults).

Neuromas: prevention and treatment

Symptomatic neuromas can be treated surgically using various reconstructive or ablative strategies. Decisions in this regard need to be made on a case-by-case basis (grade 0 recommendation).

For macro-amputations, a special form of nerve transfer has been established whereby the blind-ending nerve stumps are placed on a motor nerve branch leading to a muscle that is still intact (targeted muscle reinnervation). This enables highly selective reinnervation of individual areas of the muscle and increases the number of signals that can be individually controlled and captured for prosthetic fitting. Lower neuroma rates and a reduction in phantom pain have been observed as a secondary effect (eSupplement).

Postoperative follow-up care

Pharmacological treatment to improve nerve regeneration cannot be recommended (grade 0 recommendation). Electrotherapy and (laser-)photostimulation can be used as a complementary treatment option for nerve lesions with axonal damage (axonotmesis or neurotmesis) (grade 0 recommendation). For neuropathic pain, guideline-compliant pain medicine treatment shall be given (grade A recommendation). Pain-relieving components of occupational therapy and physiotherapy should be used (mirror therapy, transcutaneous electrical nerve stimulation [TENS]; grade B recommendation).

In the case of nerve injuries and following nerve reconstruction, concomitant occupational therapy and physiotherapy shall be provided as soon as possible after trauma or surgical reconstruction (recommendation grade A). This includes targeted sensory re-education (mirror therapy, graded motor imagery program, sensitivity training; grade B recommendation) and interventions to improve motor functions (mirror therapy, electrical muscle stimulation, motor function training; grade B recommendation).

Discussion

The frequently problematic or incomplete healing of peripheral nerve injuries can only be reduced by a guideline-compliant combination of early diagnosis and correct treatment measures. An interdisciplinary collaboration between all specialist areas is of paramount importance for the best possible restoration of function. This literature analysis shows that the need for research remains high.

Acknowledgments

The authors would like to thank all participating specialist societies and, in particular, the authors that participated on the guideline (eBox 1): Susanne Rein, Elisabeth Haas-Lützenberger, Frank Siemers, Johannes Frank, Clemens Dumont, Jonas Kolbenschlag, Johannes Heinzel, Michael Schädel-Höpfner, Maria T. Pedro, Peter Pöschl, Rezvan Ahmadi, Sascha Tafelski, Hannelore Wendt, Natalie Winter, Ingela Henningsen, Thomas Kretschmer, Christian Heinen, Christian Bischoff, Alexander Grimm, Wilhelm Schulte-Mattler, Katrin Hahn, Daniel Schwarz, Martin Bendszus, Holm Thieme, Reinhard Meier as well as Ms. Lena-Marie Marter and Ms. Diana Schoppe from the Guidelines Office of the German Society for Orthopaedics and Trauma Surgery (Deutsche Gesellschaft für Orthopädie und Unfallchirurgie, DGOU) for the constructive collaboration.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 29 January 2024, revised version accepted on

9 April 2024.

Clinical guidelines in the Deutsche Ärzteblatt, as in numerous other specialist journals, are not subject to a peer review procedure, since S3 guidelines represent texts that have already been evaluated, discussed, and broadly agreed upon multiple times by experts (peers).

Translated from the original German by Christine Rye.

Corresponding author
Prof. Dr. med. Leila Harhaus

Abteilung für Handchirurgie, Periphere Nervenchirurgie und Rehabilitation, Klinik für Hand- und Plastische Chirurgie der Universität Heidelberg, BG-Klinik Ludwigshafen

Ludwig-Guttmann-Straße 13, 67071 Ludwigshafen, Germany

Cite this as:
Harhaus L, Dengler NF, Schwerdtfeger K, Stolle A: Clinical practice guideline: The treatment of peripheral nerve injuries. Dtsch Arztebl Int 2024; 121: 534–8. DOI: 10.3238/arztebl.m2024.0071

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