Abstract
Background
Treatment of peripheral nerve injury remains one of the most challenging aspects of reconstructive surgery. Functional outcomes remain inconsistent, high-quality evidence is limited, and major knowledge gaps persist.
Where are we now?
When evaluating patients for peripheral nerve injury, the treating physician must ascertain several critical factors to help inform decision-making, including the timing, mechanism, localization, and severity of the injury. Current algorithms rely on history, physical examination, electrodiagnostic studies, imaging, and occasionally operative exploration to establish a diagnosis. The surgeon must decide if the injury will recover spontaneously or if further operative intervention is indicated to achieve the best possible functional outcome. Accurate prognostication remains challenging secondary to the difficulty grouping patients into homogenous cohorts based on patient and injury characteristics, as well as heterogenous outcome measures. Intraoperatively, determining both the severity and zone of injury remains challenging. Surgical treatment strategies include neurolysis, primary repair, nerve grafting, nerve transfer, or tendon transfers. Functional outcomes assessment is currently performed using Medical Research Council muscle grading, range of motion measures, and various sensory measures, which remain subjective with inconsistent intraobserver and interobserver reliability. Nerve-specific patient reported outcomes measures remain limited.
Where do we need to go?
Diagnostic improvements are needed to more quickly and accurately define injury severity and determine which patients will benefit from surgical intervention. Intraoperatively, accurate determination of both the zone of injury and the functional status of the proximal nerve is also needed. Reproducible outcome measures that can be easily adopted across multiple institutions are needed to facilitate high-quality evidence that can help guide treatment decisions.
How do we get there?
Multicenter collaborative efforts are needed to focus clinical research priorities using reproducible diagnostic criteria to accurately define injury severity, establish consistency in surgical techniques and treatment algorithms, and accurately and reproducibly measure outcomes. Further translational efforts in imaging, biomaterials, and basic science research are also needed. By aligning research priorities with patient-centered outcomes, the field can begin to close the gap between surgical innovation and functional recovery.
Key words: Brachial plexus, Lower extremity, Nerve surgery, Outcomes, Peripheral nerve injury, Upper extremity
Peripheral nerve injuries remain among the most challenging conditions in reconstructive surgery. Despite decades of progress in microsurgical technique, nerve transfers, grafting strategies, and biologic adjuncts, there remains limited high-quality evidence, heterogeneous outcome reporting, and disagreement about diagnostic and treatment algorithms. Patients with upper-extremity (UE) nerve injury, lower-extremity (LE) nerve injury, and brachial plexus injuries (BPI) face profound functional disability, pain, and psychosocial burden.
UE Nerve Injuries
Where are we now?
UE nerve injuries occur in 2.6% of all UE trauma and have a significant impact on UE function, productivity, and quality of life.1 In contrast to the LE, which functions to provide a stable platform for ambulation, the UE relies on a combination of high-resolution sensory afferent and motor efferent pathways to perform complex functions and fine motor tasks that are critical for independence and activities of daily living. Functional deficits following LE nerve injury have historically been treated well with bracing, arthrodesis, or amputation with prosthetic fitting. Meanwhile, bracing and arthrodesis in UE nerve injuries frequently result in disappointing functional outcomes because these modalities poorly substitute for the complex functional deficits, including sensory deficits, that occur in UE nerve injury.2 Although tendon transfers have historically been used extensively in the treatment of isolated UE nerve injuries, they inevitably result in incomplete restoration of strength and anatomic function and rely on basic tendon transfer principles, including adequate function of adjacent muscle groups, which may not be available in cases of multinerve involvement or BPI.3 Despite advances in UE prosthetics, sensory feedback, cost, and durability remain major challenges. As a result, indications for elective UE amputation in the treatment of UE nerve injury remain narrow, and functional outcomes remain modest. The advent of direct nerve repair techniques, nerve grafting, and nerve transfers has allowed surgeons an opportunity for early intervention and potential for functional recovery. As a result, there has been increased emphasis on early recognition and appropriate treatment of UE nerve injury.4 However, although UE nerve injuries are some of the most extensively studied, major gaps in evidence and knowledge persist. Prognostication remains limited, especially in partial axonotmetic injuries, where electrodiagnostic and imaging modalities have not yet achieved sufficient resolution to distinguish between injuries that will recover clinically meaningful function.5 Diffusion tensor imaging and other advanced MRI techniques show potential but remain specialized and not widely used for routine evaluation.6 At a biological level, our understanding of axonal regeneration, Schwann cell dynamics, and cortical plasticity remains incomplete, complicating efforts to develop predictive models.7
Timing of surgery remains controversial, largely because of the lack of early diagnostic modalities that can accurately characterize the severity of injury and accurately predict long-term functional recovery. As a result, nerve injuries are often treated with a period of initial observation, typically lasting 2–4 months, to ascertain whether spontaneous recovery will occur to a degree sufficient to warrant definitive nonsurgical treatment.8 However, studies consistently demonstrate that for those injuries that do require surgery, early intervention results in improved functional outcomes. Therefore, for patients who do eventually require operative intervention, this initial period of observation wastes valuable time that may improve functional recovery if the diagnosis of unrecoverable injury could be made sooner. Although traditional teaching favors intervention within 6 months, contemporary data suggest that some transfers retain efficacy even after a year, particularly in select patient populations.9, 10, 11 However, prolonged denervation is clearly associated with poorer outcomes, and the optimal threshold for timing remains undefined.
Intraoperatively, assessment of the zone of injury currently relies on direct visual inspection of the nerve under both loupe and microscope magnification, as well as tactile changes within the nerve on direct palpation following exposure. When resecting neuroma or preparing nerve ends for grafting, some studies have suggested that serial frozen sections be sent to pathology to evaluate for the degree of scarring versus normal fascicular structure. However, histological evaluation may not directly correlate with the functional status of the nerve.12 For nerves that remain in continuity, electrical stimulation can give an indication of functional status, but exact thresholds correlating the amplitude of nerve stimulation with muscle contraction and ultimate functional recovery have not been established.13
Postoperative outcomes measures remain largely subjective. Additionally, functional outcomes as measured by surgeons do not always agree with patient-centered metrics. Outcome reporting continues to represent a central weakness. Most studies rely on surgeon-graded Medical Research Council (MRC) strength, despite mounting evidence that these measures correlate poorly with patient experience.14 A recent systematic review highlighted marked heterogeneity in outcome measures across UE nerve injury studies, further limiting comparison and meta-analysis.15 Quality-of-life instruments and validated patient-reported outcome measures (PROMs) remain rarely incorporated. Variability across centers persists in the choice of nerve transfer, repair technique, and timing, reflecting the absence of consensus guidelines.5
Where do we need to go?
To move forward, the field requires validated diagnostic tools for partial injury, clearer evidence defining optimal timing for intervention, and widespread adoption of standardized PROMs. Greater consistency across centers in the choice of reconstructive strategy and outcome reporting is needed to allow meaningful comparison.5
How do we get there?
Integrating advanced imaging, biomarkers, and electrophysiology into prognostic models may improve diagnostic precision and provide earlier definitive diagnosis for partial injuries that will not recover spontaneously, allowing for earlier operative intervention. Multicenter, prospective studies will be essential to establish timing thresholds and build consensus on surgical strategy. Adoption of validated PROMs, along with integration of wearable devices, motion analysis, and digital phenotyping, could supplement traditional outcomes and better capture real-world recovery.5
LE Nerve Injuries
Where are we now?
LE nerve injuries remain comparatively underrepresented in the literature despite profound functional and psychosocial consequences. Published work is heavily skewed toward the common peroneal and sciatic nerves, with notably fewer series on tibial, femoral, obturator, and lumbosacral plexus injuries; this imbalance limits generalizable guidance on timing, reconstruction strategy, and rehabilitation pathways.16 The biology and biomechanics of the LE compound these evidence gaps: axons must traverse longer distances to reach downstream muscle targets, LE muscle function must recover sufficient strength to support an individual’s entire body and move the leg which weighs considerably more than the arm, restoration of muscle spindle input may be critical for proprioception and gait coordination, and differences in muscle fiber length and cross-sectional area affect muscle excursion and maximal muscle force in the lower compared to the UE—factors that likely make even minor delays in treatment more costly than in the upper limb.16, 17, 18
Outcome definition is a central problem. Many reports still anchor “success” to MRC grades, yet patients and clinicians increasingly prioritize outcomes that reflect real-world function: independence from an ankle-foot orthosis, fall frequency, gait symmetry and endurance, return to work, and pain reduction.19, 20, 21 Specifically, there is a need to integrate performance-based testing, motion analysis, and wearable sensor data with validated PROMs to capture recovery more completely.16
Recent studies on UE nerves also highlight the influence of patient-specific factors on recovery, particularly body mass index (BMI). Higher BMI is associated with inferior motor outcomes after nerve transfer. If extrapolated to the LE, elevated BMI may contribute to impaired donor activation, reduced efficiency of reinnervation, and increased rehabilitation demands.22, 23, 24 These findings suggest that body composition should be systematically recorded and incorporated into prognostic models and multicenter registries.
Common surgical techniques to address LE nerve injuries include neurolysis, direct repair, autograft or allograft reconstruction, and strategic tendon transfer. Large historical experiences, particularly in peroneal neuropathy, show substantial heterogeneity in motor recovery and gait outcomes, reflecting variable injury mechanisms, denervation intervals, and end-organ condition.25 Published literature on techniques as well as outcomes of LE nerve transfers is significantly lacking, particularly compared to the UE; furthermore, many LE studies focus on acute flaccid myelitis in the pediatric population, which may limit its application to adult traumatic etiologies of LE nerve injury.26, 27, 28 For foot drop, targeted nerve transfers to reinnervate tibialis anterior and secondary ankle dorsiflexors such as peroneus brevis and toe extensors can yield ≥M4 ankle dorsiflexion in carefully selected patients, but durability, patient selection criteria, and comparative effectiveness versus tendon transfer remain incompletely defined.16,29,30 For long-gap reconstructions (eg, sciatic), vascularized nerve grafts and meticulous attention to tension-free coaptation are advocated in select cases, yet high-level evidence is lacking and long-term function is inconsistently reported.16 Rehabilitation, particularly donor activation–focused re-education and progressive gait retraining, likely mediates a large share of outcome variability, but protocols are not standardized and are understudied in LE cohorts.16,31
Where do we need to go?
The field must move toward more standardized outcome frameworks that incorporate both performance-based and patient-reported measures. Prognostic models should account for patient-specific factors such as BMI and comorbidities. Comparative effectiveness studies of nerve reconstruction, tendon transfer, and hybrid strategies are especially needed, as practice remains highly variable and largely center dependent.16
How do we get there?
Dedicated multicenter registries are required to systematically record mechanism, timing, reconstruction details, and standardized outcomes across PROMs, performance testing, and gait/wearable metrics. Prospective comparative studies such as nerve reconstruction versus tendon transfer and hybrid strategies will be essential to refine indications and provide evidence-based algorithms for LE nerve injuries.16
Adult Traumatic Brachial Plexus Injury
Where are we now?
Adult traumatic BPI are among the most devastating peripheral nerve conditions, producing severe motor and sensory loss, chronic pain, and long-term psychosocial consequences. Surgical management strategies include direct repair, autografting, nerve transfers, and free functional muscle transfer, each with variable results. Despite decades of clinical research, the literature remains dominated by level IV case series, limiting the strength of available evidence.32
Several critical gaps persist. Pain management remains one of the most underexplored domains. Data from the multicenter PLANeT study demonstrate that pain interference remains unchanged at one year after surgery, despite technically successful reconstruction, and that pain correlates strongly with depression, anxiety, and functional limitations.33 Traditional surgeon-reported outcomes, such as MRC strength, do not align with patient experiences of recovery.34
Delivery of care is inconsistent: registry data show that nearly one-third of patients in the United States undergo surgery more than a year after injury, with delays often attributable to lack of referral pathways and insufficient awareness among community providers.35,36 Even among experienced centers, substantial variability exists in surgical algorithms, underscoring the absence of consensus on optimal timing, choice of nerve transfers, and role of adjunctive procedures.37
Where do we need to go?
Outcome measurement must move beyond surgeon-graded strength to systematically include patient-reported and quality-of-life outcomes. Pain requires far greater attention, both as a primary research end point and as an integrated component of rehabilitation. At the systems level, improved referral pathways and dissemination of expertise are needed to reduce delays in surgical intervention. An international consensus on timing and surgical strategy would improve comparability and standardize care.32
How do we get there?
Future directions must prioritize multicenter collaboration and standardized outcome frameworks. International registries and NIH-funded prospective cohorts provide models for higher-level evidence. Integration of rehabilitation science, mental health support, and patient education will be essential to deliver holistic care. Advances in digital and biologic technologies may further refine prognostication and tracking of recovery.32
Conclusion
Across UE, LE, and brachial plexus nerve injuries, substantial evidence gaps persist. Despite decades of surgical innovation, most of the literature remains single-center, retrospective, and methodologically heterogeneous. Prognostication remains unreliable, the timing of intervention unresolved, and outcome reporting inconsistent.
The common themes identified at Nerve SPACE underscore the need for coordinated efforts to standardize diagnosis, classification, treatment algorithms, and outcome measures to facilitate multicenter studies and thereby improve the quality of evidence that can help guide future decision-making and research focus.
Moving forward, the nerve surgery community must prioritize international registries, prospective multicenter trials, and adoption of standardized outcome measures that incorporate patient-centered domains. Collaboration across surgery, rehabilitation, engineering, and basic science will be essential to deliver consistent, evidence-based, and patient-centered care.
Conflicts of Interest
Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R13AR085496. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Dy declares research support from the National Institutes of Health, Orthopaedic Research and Education Foundation, American Foundation for Surgery of the Hand, and Checkpoint Surgical. Dr Dy receives fees for speaking engagements from Johnson & Johnson/DePuy Synthes and Checkpoint Surgical and is on the medical advisory board for OrthoCell. The other authors have no other relevant conflicts to disclose.
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