Advances in Imaging of Compressive Neuropathies.

Ultrasound and magnetic resonance neurography are useful modalities to aid in the assessment of compressive neuropathies, although they are still limited in their resolution of nerve microstructure and their capacity to monitor postoperative nerve recovery. Optical coherence tomography, a preclinical imaging modality, is promising in its ability to better identify structural and potential physiologic changes to peripheral nerves, but requires additional testing and research prior to widespread clinical implementation. Further advances in nerve imaging may elucidate the ability to visualize the zone of nerve injury intraoperatively, monitor the progression of nerve regeneration, and localize problems during nerve recovery.

Fibular (peroneal) neuropathy.

Fibular neuropathy has variable presenting features depending on the site of the lesion. Anatomical features make it susceptible to injury from extrinsic factors, particularly the superficial location of the nerve at the head of the fibula. There are many mechanisms of compression or other traumatic injury of the fibular nerve, as well as entrapment and intrinsic nerve lesions. Intraneural ganglion cysts are increasingly recognized when the mechanism of neuropathy is not clear from the medical history. Electrodiagnostic testing can contribute to the localization as well as the characterization of the pathologic process affecting the nerve. When the mechanism of injury is unclear from the analysis of the presentation, imaging with MRI and ultrasound may identify nerve lesions that warrant surgical intervention. The differential diagnosis of foot drop includes fibular neuropathy and other neurologic conditions, which can be distinguished through clinical and electrodiagnostic assessment. Rehabilitation measures, including ankle splinting, are important to improve function and safety when foot drop is present. Fibular neuropathy is less frequently painful than many other nerve lesions, but when it is painful, neuropathic medication may be required. Failure to spontaneously recover or the detection of a mass lesion may require surgical management.

Establishing Optic Nerve Diameter Threshold Sensitive and Specific for Optic Atrophy Diagnosis.

PURPOSE: To determine a potential threshold optic nerve diameter (OND) that could reliably differentiate healthy nerves from those affected by optic atrophy (OA) and to determine correlations of OND in OA with retinal nerve fiber layer (RNFL) thickness, visual acuity (VA), and visual field mean deviation (VFMD). METHODS: This was a retrospective case control study. Magnetic resonance (MR) images were reviewed from individuals with OA aged 18 years or older with vision loss for more than 6 months and an OA diagnosis established by a neuro-ophthalmologist. Individuals without OA who underwent MR imaging of the orbit for other purposes were also collected. OND was measured on coronal T2-weighted images in the midorbital section, 1cm posterior to the optic disc. Measurements of mean RNFL thickness, VA and VFMD were also collected. RESULTS: In this study 47 OA subjects (63% women, 78 eyes) and 75 normal subjects (42.7% women, 127 eyes) were assessed. Healthy ONDs (mean 2.73 ± 0.24 mm) were significantly greater than OA nerve diameters (mean 1.94 ± 0.32 mm; P < 0.001). A threshold OND of ≤2.3 mm had a sensitivity of 0.92 and a specificity of 0.93 in predicting OA. Mean RNFL (r = 0.05, p = 0.68), VA (r = 0.17, p = 0.14), and VFMD (r = 0.18, p = 0.16) were not significantly associated with OND. CONCLUSION: ONDs are significantly reduced in patients with OA compared with healthy nerves. A threshold OND of ≤2.3 mm is highly sensitive and specific for a diagnosis of OA. OND was not significantly correlated with RNFL thickness, VA, or VFMD.

Pronator syndrome and anterior interosseous nerve palsy due to neurolymphomatosis: a case report.

Pronator syndrome is a median nerve entrapment neuropathy that can be difficult to diagnose due to its variable presentation and objective findings. Neurolymphomatosis is an uncommon disease in which malignant lymphocytes infiltrate central or peripheral nerve endoneurium and is often missed for prolonged periods prior to diagnosis. We present a rare case of pronator syndrome and anterior interosseous nerve palsy due to neurolymphomatosis that was occult on initial MRI in spite of the presence of a median nerve mass discovered intra-operatively during neurolysis. This case demonstrates the value of ultrasound for the examination of peripheral nerve pathology and illustrates its utility as an adjunct to MRI, in part due to the ability to screen a large region.

MRI features of benign peripheral nerve sheath tumors: how do sporadic and syndromic tumors differ?

OBJECTIVES: To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas. METHODS: In this retrospective study, our pathology database was searched for "neurofibroma" or "schwannoma" from 2014 to 2019. Exclusion criteria were lack of available MRI and intradural or plexiform tumors. Qualitative and quantitative anatomic (location, size, relationship to nerve, signal, muscle denervation) and functional (arterial enhancement, apparent diffusion-weighted coefficient) MRI features of sporadic and syndrome-related tumors were compared. Statistical significance was assumed for p < 0.05. RESULTS: A total of 80 patients with 64 schwannomas (sporadic: 42 (65.6%) v. syndrome-related: 22 (34.4%)) and 19 neurofibromas (sporadic: 7 (36.8%) v. syndrome-related: 12 (41.7%)) were included. Only signal heterogeneity (T2W p=0.001, post-contrast p=0.03) and a diffused-weighted imaging target sign (p=0.04) were more frequent with schwannomas than neurofibromas. Sporadic schwannomas were similar in size to syndrome-related schwannomas (2.9±1.2cm vs. 3.7±3.2 cm, p = 0.6), but with greater heterogeneity (T2W p = 0.02, post-contrast p = 0.01). Sporadic neurofibromas were larger (4.6±1.5cm vs. 3.4±2.4 cm, p = 0.03) than syndrome-related neurofibromas, also with greater heterogeneity (T2W p=0.03, post-contrast p=0.04). Additional tumors along an affected nerve were only observed with syndrome-related tumors). There was no difference in apparent diffusion coefficient values or presence of early perfusion between sporadic and syndrome-related tumors (p > 0.05). CONCLUSIONS: Although syndrome-related and sporadic schwannomas and neurofibromas overlap in their anatomic, diffusion and perfusion features, signal heterogeneity and presence of multiple lesions along a nerve are differentiating characteristics of syndrome-related tumors.

Multimodality imaging review of ulnar nerve pathologies.

The ulnar nerve is the second most commonly entrapped nerve after the median nerve. Although clinical evaluation and electrodiagnostic studies remain widely used for the evaluation of ulnar neuropathy, advancements in imaging have led to increased utilization of these newer / better imaging techniques in the overall management of ulnar neuropathy. Specifically, high-resolution ultrasonography of peripheral nerves as well as MRI has become quite useful in evaluating the ulnar nerve in order to better guide treatment. The caliber and fascicular pattern identified in the normal ulnar nerves are important distinguishing features from ulnar nerve pathology. The cubital tunnel within the elbow and Guyon's canal within the wrist are important sites to evaluate with respect to ulnar nerve compression. Both acute and chronic conditions resulting in deformity, trauma as well as inflammatory conditions may predispose certain patients to ulnar neuropathy. Granulomatous diseases as well as both neurogenic and non-neurogenic tumors can also potentially result in ulnar neuropathy. Tumors around the ulnar nerve can also lead to mass effect on the nerve, particularly in tight spaces like the aforementioned canals. Although high-resolution ultrasonography is a useful modality initially, particularly as it can be helpful for dynamic evaluation, MRI remains most reliable due to its higher resolution. Newer imaging techniques like sonoelastography and microneurography, as well as nerve-specific contrast agents, are currently being investigated for their usefulness and are not routinely being used currently.

Updates in peripheral nerve surgery of the upper extremity: diagnosis and treatment options.

The loss of function resulting from peripheral nerve injuries confers a significant burden to the patient and society. The treatment of peripheral nerve injuries requires an accurate diagnosis and formulation of a functional reconstructive plan. Advances in peripheral nerve imaging complement electrodiagnostic studies, and provide us with detailed information regarding the status of nerve injury, repair, and regeneration in order to prognosticate recovery and determine the need for surgical intervention. When direct nerve repair is not possible, the methods for bridging a nerve gap are the nerve autograft, allograft and conduit. While current research supports the use of conduits and nerve allografts for shorter nerve gaps, the nerve autograft still remains the gold standard for bridging a nerve gap. When direct nerve repair or nerve grafting fails, or is anticipated to be insufficient, nerve transfers are an alternative for reconstruction. Knowledge of axonal counts, upper limb innervation patterns, location and clustering of upper limb peripheral nerves allows for the design of new nerve transfers. The options of nerve transfers for radial, ulnar and median nerve injuries are outlined, as well as their outcomes. Nerve transfers are an attractive option for restoring motor and sensory function while minimizing donor site morbidity. However, one must consider their limitations, and preserve donor sites for secondary tendon transfer options. This article presents the latest information regarding the imaging of peripheral nerves, methods to bridge a nerve gap, and nerve transfers to aid the peripheral nerve surgeon in choosing a reconstructive plan.

7T for clinical imaging of benign peripheral nerve tumors: preliminary results.

PURPOSE: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors. MATERIALS: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil. RESULTS: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI. CONCLUSION: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses.

Nerve-Sparing Gynecologic Surgery Enabled by A Near-Infrared Nerve-Specific Fluorophore Using Existing Clinical Fluorescence Imaging Systems.

Patients undergoing gynecological procedures suffer from lasting side effects due to intraoperative nerve damage. Small, delicate nerves with complex and nonuniform branching patterns in the female pelvic neuroanatomy make nerve-sparing efforts during standard gynecological procedures such as hysterectomy, cystectomy, and colorectal cancer resection difficult, and thus many patients are left with incontinence and sexual dysfunction. Herein, a near-infrared (NIR) fluorescent nerve-specific contrast agent, LGW08-35, that is spectrally compatible with clinical fluorescence guided surgery (FGS) systems is formulated and characterized for rapid implementation for nerve-sparing gynecologic surgeries. The toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) of micelle formulated LGW08-35 are examined, enabling the determination of the optimal imaging doses and time points, blood and tissue uptake parameters, and maximum tolerated dose (MTD). Application of the formulated fluorophore to imaging of female rat and swine pelvic neuroanatomy validates the continued clinical translation and use for real-time identification of important nerves such as the femoral, sciatic, lumbar, iliac, and hypogastric nerves. Further development of LGW08-35 for clinical use will unlock a valuable tool for surgeons in direct visualization of important nerves and contribute to the ongoing characterization of the female pelvic neuroanatomy to eliminate the debilitating side effects of nerve damage during gynecological procedures.

Recurrent motor branch neuropathy in carpal tunnel syndrome: An ultrasound study.

INTRODUCTION/AIMS: The reason for the variable rate of progression of patients with carpal tunnel syndrome (CTS) to thenar muscles impairment is not fully understood. The aim of this study was to evaluate the occurrence of ultrasound signs of recurrent motor branch (RMB) neuropathy in patients with CTS and to correlate imaging findings with clinical and electrophysiological data. METHODS: Two cohorts were recruited, one consisting of CTS patients with electrodiagnostic evidence of prolonged median distal motor latency from wrist to thenar eminence and another consisting of sex- and age-matched healthy controls. Ultrasound reliability of RMB measurement was assessed by the calculation of the interclass correlation coefficient (ICC). Patients were evaluated with electrodiagnostic tests and asked to complete the Boston Carpal Tunnel Questionnaire. The difference between the RMB diameter in patients and controls was analyzed using a t test. Correlations between RMB diameter and other parameters were assessed using linear mixed models. RESULTS: 46 hands from 32 patients with CTS and 50 hands from 50 controls were evaluated. The intra- and interobserver agreements in RMB measurement were very good (ICC = 0.84; 95% confidence interval [CI], 0.75 to 0.90) and good (ICC = 0.79; 95% CI, 0.69 to 0.87). The RMB diameter was significantly larger in patients than in controls (P < .0001). No significant correlation was found between the RMB diameter and other variables, except for BMI and median nerve cross-sectional area. DISCUSSION: Ultrasound is reliable in identifying the RMB and characterizing its abnormalities. In this patient cohort, ultrasound allowed for detection of definite signs of RMB compression neuropathy.

A Truncated 14-Amino-Acid Myelin Protein-Zero-Targeting Peptide for Fluorescence-Guided Nerve-Preserving Surgery.

BACKGROUND: The occurrence of accidental nerve damage during surgery and the increasing application of image guidance during head-and-neck surgery have highlighted the need for molecular targeted nerve-sparing interventions. The implementation of such interventions relies on the availability of nerve-specific tracers. In this paper, we describe the development of a truncated peptide that has an optimized affinity for protein zero (P0), the most abundant protein in myelin. METHODS AND MATERIALS: Further C- and N-terminal truncation was performed on the lead peptide Cy5-P0101-125. The resulting nine Cy5-labelled peptides were characterized based on their photophysical properties, P0 affinity, and in vitro staining. These characterizations were combined with evaluation of the crystal structure of P0, which resulted in the selection of the optimized tracer Cy5-P0112-125. A near-infrared Cy7-functionalized derivative (Cy7-P0112-125) was used to perform an initial evaluation of fluorescence-guided surgery in a porcine model. RESULTS: Methodological truncation of the 26-amino-acid lead compound Cy5-P0101-125 resulted in a size reduction of 53.8% for the optimized peptide Cy5-P0112-125. The peptide design and the 1.5-fold affinity gain obtained after truncation could be linked to interactions observed in the crystal structure of the extracellular portion of P0. The near-infrared analogue Cy7-P0112-125 supported nerve illumination during fluorescence-guided surgery in the head-and-neck region in a porcine model. CONCLUSIONS: Methodological truncation yielded a second-generation P0-specific peptide. Initial surgical evaluation suggests that the peptide can support molecular targeted nerve imaging.

A scoping review of current and emerging techniques for evaluation of peripheral nerve health, degeneration and regeneration: part 2, non-invasive imaging.

Peripheral neuroregenerative research and therapeutic options are expanding exponentially. With this expansion comes an increasing need to reliably evaluate and quantify nerve health. Valid and responsive measures of the nerve status are essential for both clinical and research purposes for diagnosis, longitudinal follow-up, and monitoring the impact of any intervention. Furthermore, novel biomarkers can elucidate regenerative mechanisms and open new avenues for research. Without such measures, clinical decision-making is impaired, and research becomes more costly, time-consuming, and sometimes infeasible. Part 1 of this two-part scoping review focused on neurophysiology. In part 2, we identify and critically examine many current and emerging non-invasive imaging techniques that have the potential to evaluate peripheral nerve health, particularly from the perspective of regenerative therapies and research.

Current and Future Applications of Fluorescence Guidance in Orthopaedic Surgery.

Fluorescence-guided surgery (FGS) is an evolving field that seeks to identify important anatomic structures or physiologic phenomena with helpful relevance to the execution of surgical procedures. Fluorescence labeling occurs generally via the administration of fluorescent reporters that may be molecularly targeted, enzyme-activated, or untargeted, vascular probes. Fluorescence guidance has substantially changed care strategies in numerous surgical fields; however, investigation and adoption in orthopaedic surgery have lagged. FGS shows the potential for improving patient care in orthopaedics via several applications including disease diagnosis, perfusion-based tissue healing capacity assessment, infection/tumor eradication, and anatomic structure identification. This review highlights current and future applications of fluorescence guidance in orthopaedics and identifies key challenges to translation and potential solutions.

Repeatability, Reproducibility and Sources of Variability in the Assessment of Backscatter Coefficient and Texture Parameters from High-Frequency Ultrasound Acquisitions in Human Median Nerve.

Ultrasound (US) is an increasingly prevalent and effective diagnostic modality for neuromuscular imaging. Gray-scale B-mode imaging has been the dominant US approach to evaluating nerves qualitatively or making morphometric measurements of nerves, providing important insights into pathological changes for conditions such as carpal tunnel syndrome. Among more recent ultrasound strategies, high-frequency ultrasound (often defined as >15 MHz for clinical applications), quantitative ultrasound and image textural analysis offer promising enhancements for improved and more objective approaches to nerve imaging. In this study, we evaluated the repeatability and reproducibility of backscatter coefficient (BSC) and imaging texture features extracted by gray-level co-occurrence matrices (GLCMs) in homogeneous tissue-mimicking reference phantoms and in median nerves in the wrists of healthy participants. We also investigated several practical sources of variability in the assessment of quantitative parameters, including influences of operators, and participant-to-participant variability. Overall, BSC- and GLCM-based outcomes are highly repeatable and reproducible after operator training, based on measurement of descriptive statistics, repeatability coefficient (RC) and reproducibility coefficient recommended by Quantitative Imaging Biomarker Alliance (QIBA RDC). GLCM parameters appear more reproducible and repeatable than BSC-based parameters in healthy participants in vivo. However, such variability noted here must be compared with the value ranges and variability of the results in pathological nerves, including median nerves afflicted by trauma, overuse syndromes such as carpal tunnel syndrome and after surgical repair.

Functional recovery and muscle atrophy in pre-clinical models of peripheral nerve transection and gap-grafting in mice: effects of 4-aminopyridine.

We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve transection, gap, and grafting models. To evaluate and compare the functional recovery, nerve morphology, and muscle atrophy, we used a novel stepwise nerve transection with gluing (STG), as well as 7-mm irreparable nerve gap (G-7/0) and 7-mm isografting in 5-mm gap (G-5/7) models in the absence and presence of 4-AP treatment. Following surgery, sciatic functional index was determined weekly to evaluate the direct in vivo global motor functional recovery. After 12 weeks, nerves were processed for whole-mount immunofluorescence imaging, and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber cross-sectional area and minimal Feret's diameter. Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model. 4-AP did not affect the sciatic functional index recovery in any model. Compared to STG, nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting. While muscle weight, cross-sectional area, and minimal Feret's diameter were significantly smaller in G-7/0 model compared with STG and G-5/7, 4-AP treatment significantly increased right TA muscle mass, cross-sectional area, and minimal Feret's diameter in G-7/0 model. These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap, and 4-AP exerts differential effects on functional recovery and muscle atrophy.

High-resolution ultrasound of peripheral neuropathies in rheumatological patients: An overview of clinical applications and imaging findings.

Peripheral neuropathies are surprisingly common and can be associated with a number of conditions, including rheumatological diseases. Whether the co-existence of peripheral neuropathies with rheumatological disorders is coincidental or related to a common pathogenic mechanism, these disabling conditions can affect the outcome of rheumatological patients and should be targeted with specific treatment. The clinical presentation of peripheral neuropathy can be multifaceted and difficult to recognize in polysymptomatic patients. However, physicians adopting state-of-art diagnostic strategies, including nerve imaging, may improve the detection rate and management of neuropathies. In particular, a diagnostic approach relying exclusively on clinical history and nerve conduction studies may not be sufficient to disclose the etiology of the nerve damage and its anatomical location and thus requires integration with morphological studies. High-Resolution Ultrasound (HRUS) is increasingly adopted to support the diagnosis and follow-up of both joint disorders in rheumatology and peripheral neuropathies of different etiologies. In this review, the different types of nerve disorders associated with the most common syndromes of rheumatological interest are discussed, focusing on the distinctive sonographic features.

Long-Duration and Non-Invasive Photoacoustic Imaging of Multiple Anatomical Structures in a Live Mouse Using a Single Contrast Agent.

Long-duration in vivo simultaneous imaging of multiple anatomical structures is useful for understanding physiological aspects of diseases, informative for molecular optimization in preclinical models, and has potential applications in surgical settings to improve clinical outcomes. Previous studies involving simultaneous imaging of multiple anatomical structures, for example, blood and lymphatic vessels as well as peripheral nerves and sebaceous glands, have used genetically engineered mice, which require expensive and time-consuming methods. Here, an IgG4 isotype control antibody is labeled with a near-infrared dye and injected into a mouse ear to enable simultaneous visualization of blood and lymphatic vessels, peripheral nerves, and sebaceous glands for up to 3 h using photoacoustic microscopy. For multiple anatomical structure imaging, peripheral nerves and sebaceous glands are imaged inside the injected dye-labeled antibody mass while the lymphatic vessels are visualized outside the mass. The efficacy of the contrast agent to label and localize deep medial lymphatic vessels and lymph nodes using photoacoustic computed tomography is demonstrated. The capability of a single injectable contrast agent to image multiple structures for several hours will potentially improve preclinical therapeutic optimization, shorten discovery timelines, and enable clinical treatments.

Feasibility of simultaneous high-resolution anatomical and quantitative magnetic resonance imaging of sciatic nerves in patients with Charcot-Marie-Tooth type 1A (CMT1A) at 7T.

INTRODUCTION/AIMS: Magnetic resonance imaging (MRI) of peripheral nerves can provide image-based anatomical information and quantitative measurement. The aim of this pilot study was to investigate the feasibility of high-resolution anatomical and quantitative MRI assessment of sciatic nerve fascicles in patients with Charcot-Marie-Tooth (CMT) 1A using 7T field strength. METHODS: Six patients with CMT1A underwent imaging on a high-gradient 7T MRI scanner using a 28-channel knee coil. Two high-resolution axial images were simultaneously acquired using a quantitative double-echo in steady-state (DESS) sequence. By comparing the two DESS echoes, T2 and apparent diffusion coefficient (ADC) maps were calculated. The cross-sectional areas and mean T2 and ADC were measured in individual fascicles of the tibial and fibular (peroneal) portions of the sciatic nerve at its bifurcation and 10 mm distally. Disease severity was measured using Charcot-Marie-Tooth Examination Score (CMTES) version 2 and compared to imaging findings. RESULTS: We demonstrated the feasibility of 7T MRI of the proximal sciatic nerve in patients with CMT1A. Using the higher field, it was possible to measure individual bundles in the tibial and fibular divisions of the sciatic nerve. There was no apparent correlation between diffusion measures and disease severity in this small cohort. DISCUSSION: This pilot study indicated that high-resolution MRI that allows for combined anatomical and quantitative imaging in one scan is feasible at 7T field strengths and can be used to investigate the microstructure of individual nerve fascicles.

Neurosurgery for the Neurologist: Peripheral Nerve Injury and Compression (What can be Fixed?).

This chapter will review the current management of patients with peripheral nerve injuries and nerve compression syndromes that result in favorable surgical outcomes when appropriately evaluated and referred in a timely fashion. Given the fact that neurologists frequently evaluate patients with these conditions and refer patients to neurosurgeons, it is important for them to be aware of the indications for, types and timing of surgical procedures, and expected outcomes with the various types of interventions.

Neural tissue engineering: From bioactive scaffolds and in situ monitoring to regeneration.

Peripheral nerve injury is a large-scale problem that annually affects more than several millions of people all over the world. It remains a great challenge to effectively repair nerve defects. Tissue engineered nerve guidance conduits (NGCs) provide a promising platform for peripheral nerve repair through the integration of bioactive scaffolds, biological effectors, and cellular components. Herein, we firstly describe the pathogenesis of peripheral nerve injuries at different orders of severity to clarify their microenvironments and discuss the clinical treatment methods and challenges. Then, we discuss the recent progress on the design and construction of NGCs in combination with biological effectors and cellular components for nerve repair. Afterward, we give perspectives on imaging the nerve and/or the conduit to allow for the in situ monitoring of the nerve regeneration process. We also cover the applications of different postoperative intervention treatments, such as electric field, magnetic field, light, and ultrasound, to the well-designed conduit and/or the nerve for improving the repair efficacy. Finally, we explore the prospects of multifunctional platforms to promote the repair of peripheral nerve injury.