Update of surgical treatment of polydactyly.

PURPOSE OF REVIEW: Polydactyly presents with variable extent of duplication and may involve preaxial/radial (hand)/medial (foot), postaxial/ulnar (hand)/lateral (foot) or central duplication. This review will summarize recent advancements in the surgical management of this common entity. RECENT FINDINGS: Modifications to classification systems aim to help guide surgical management of polydactyly. Attempts have been made at quantifying preoperative angulation of the duplicated digits to minimize the chance of residual or recurrent deformity after surgical reconstruction. As a result, consideration should be given to the need for soft tissue correction vs. osteotomy to optimize the clinical outcome. On-top plasty is an option that may be beneficial in 'unequal' preaxial polydactyly, where neither duplicate is preferred on its own. SUMMARY: Polydactyly is one of the most common congenital anomalies in the hands and feet. Determination of surgical intervention often begins with classification systems that exist, which primarily separate these into preaxial, postaxial, and central. Referral for surgical consideration is indicated, given the management is often surgical.

ErbB2 blockade with Herceptin (trastuzumab) enhances peripheral nerve regeneration after repair of acute or chronic peripheral nerve injury.

OBJECTIVE: Attenuation of the growth supportive environment within the distal nerve stump after delayed peripheral nerve repair profoundly limits nerve regeneration. Levels of the potent Schwann cell mitogen neuregulin and its receptor ErbB2 decline during this period, but the regenerative impact of this change is not completely understood. Herein, the ErbB2 receptor pathway is inhibited with the selective monoclonal antibody Herceptin (trastuzumab) to determine its significance in regulating acute and chronic regeneration in a rat hindlimb. METHODS: The common peroneal nerve of Sprague-Dawley rats was transected and repaired immediately or after 4 months of chronic denervation, followed by administration of Herceptin or saline solution. Regenerated motor and sensory neurons were counted using a retrograde tracer 1, 2, or 4, weeks after repair. Distal myelinated axon outgrowth after 4 weeks was quantified using histomorphometry. Immunofluorescent imaging was used to evaluate Schwann cell proliferation and epidermal growth factor receptor (EGFR) activation in the regenerating nerves. RESULTS: Herceptin administration increased the rate of motor and sensory neuron regeneration and the number of proliferating Schwann cells in the distal stump after the first week. Herceptin also increased the number of myelinated axons that regenerated 4 weeks after immediate and delayed repair. Reduced EGFR activation was observed using immunofluorescent imaging. INTERPRETATION: Inhibition of the ErbB2 receptor with Herceptin unexpectedly enhances nerve regeneration after acute and delayed nerve repair. This finding raises the possibility of using targeted molecular therapies to improve outcomes of peripheral nerve injuries. The mechanism may involve a novel inhibitory association between ErbB2 and EGFR. Ann Neurol 2016;80:112-126.

Alternative Nerve Coaptations: End-To-Side and Beyond.

Modern end-to-side (ETS) nerve transfers have undergone several permutations since the early 1990's. Preclinical data have revealed important mechanisms and patterns of donor axon outgrowth into the recipient nerves and target reinnervation. The versatility of ETS nerve transfers can also potentially address several processes that limit functional recovery after nerve injury by babysitting motor end-plates and/or supporting the regenerative environment within the denervated nerve. Further clinical and basic science work is required to clarify the ideal clinical indications, contraindications, and mechanisms of action for these techniques in order to maximize their potential as reconstructive options.

Evaluation of motor and sensory neuron populations in a mouse median nerve injury model.

BACKGROUND: Peripheral nerves can regenerate and restore function after injury but this process is hindered by many factors including chronic denervation, motor end-plate resorption and Schwann cell senescence. Forelimb injury models in rodents are becoming increasingly popular as they more accurately reflect the physiology and biomechanics of upper extremity nerve injuries. However several aspects of this surgical model remain poorly characterized. NEW METHOD: C57Bl/6 mice underwent enumeration of median nerve motor and sensory neuron pools using retrograde labeling with or without nerve transection. Distal histomorphometry of uninjured mouse median nerves was also examined. Baseline reference values of volitional forelimb grip strength measurements were determined and the rate of neural elongation was also estimated. RESULTS: We identified 1363 ± 165 sensory and 216 ± 16 motor neurons within the uninjured dorsal root ganglia (DRG) and ventral spinal cord, respectively. Eight days following injury, approximately 34% of motoneurons had elongated a distance of 5 mm beyond the repair site 8 days following injury. Volitional grip strength decreased 50% with unilateral median nerve transection and was negligible with contralateral flexor tendon tenotomy. COMPARISON WITH EXISTING METHOD: Our spinal cord and DRG harvesting technique presented here was technically straightforward and reliable. Estimates of motor and sensory neuron numbers for the mouse median nerve compared favourably with studies using intramuscular injection of retrograde neurotracer. Histomorphometry data was consistent with and reinforced reference values in the literature. CONCLUSIONS: This study provides data that further develops an increasingly popular surgical model for studying peripheral nerve injury and repair.

The Effectiveness of a Self-Directed e-Learning Module on Trainee Knowledge and Confidence during Plastic Surgery Clinical Rotations.

Background: Exposure to plastic surgery is limited during medical school. This makes rotations for clinical clerks and off-service residents challenging. Available resources are often too detailed and overwhelming. Having an accessible, concise, and interactive plastic surgery e-learning module reviewing core plastic surgery topics could help prepare incoming trainees for their rotations. Methods: An e-learning module was created using text, images, and in-house recorded video recordings. Two cohorts were recruited: control cohort (n = 9), who completed their plastic surgery rotation without use of the module, and an interventional cohort (n = 18), who completed the rotation with use of the module. A demographic survey, a 20-question multiple-choice knowledge test, and self-reported confidence score were completed by both cohorts at the end of their plastic surgery rotations. The intervention cohort also completed the knowledge test at the beginning of their rotation to establish baseline. Knowledge and confidence scores were compared using two-tailed, unpaired, nonparametric analyses (Mann-Whitney test). Results: Learners from the intervention cohort reported a 95% module completion rate and found the resource "extremely helpful" (average Likert of 4.8/5). Learners indicated that they were very likely to recommend the resource to others (average Likert 4.9/5). The intervention cohort scored significantly higher on the knowledge test compared with the control cohort (P = 0.008), and on average reported higher confidence levels; however, this was not statistically significant (P = 0.057). Conclusion: An accessible and concise module on core plastic surgery concepts enhances learner knowledge and confidence during plastic surgery clinical rotations.

Optimizing the Timing of Peripheral Nerve Transfers for Functional Re-Animation in Cervical Spinal Cord Injury: A Conceptual Framework.

Loss of upper extremity function following spinal cord injury (SCI) can have devastating consequences on quality of life. Peripheral nerve transfer surgery aims to restore motor control of upper extremities following cervical SCI and is poised to revolutionize surgical management in this population. The surgery involves dividing an expendable donor nerve above the level of the spinal lesion and coapting it to a recipient nerve arising from the lesional or infralesional segment of the injured cord. In order to maximize outcomes in this complex patient population, refinements in surgical technique need to be integrated with principles of spinal cord medicine and basic science. Deciding on the ideal timing of nerve transfer surgery is one aspect of care that is critical to maximizing recovery and has received very little attention to date in the literature. This complex topic is reviewed, with a focus on expectations for spontaneous recovery within upper motor neuron components of the injury, balanced against the need for expeditious re-innervation for lower motor neuron elements of the injury. The discussion also considers the case of a patient with C6 motor complete SCI in whom myotomes without electrodiagnostic evidence of denervation spontaneously improved by 6 months post-injury, thereby adjusting the surgical plan. The relevant concepts are integrated into a clinical algorithm with recommendations that consider maximal opportunity for spontaneous clinical improvement post-injury while avoiding excessive delays that may adversely affect patient outcomes.

Delayed-Type Hypersensitivity Reaction to Red Tattoo Ink Triggered by Ledipasvir/Sofosbuvir for Hepatitis C: A Case Report.

Tattoos have become increasingly popular worldwide making adverse effects from tattoos a growing concern. In our report, we present a 51-year-old man who developed an unusual allergic reaction to the red ink portions of his tattoos that coincided with the initiation of ledipasvir/sofosbuvir treatment for his hepatitis C. Clinical and histological features were consistent with a delayed-type hypersensitivity reaction to red ink.

Managing Neuroma and Phantom Limb Pain in Ontario: The Status of Targeted Muscle Reinnervation.

Painful neuromas (PN) and phantom limb pain (PLP) are common following amputation and are unreliably treated, which impacts quality of life. Targeted muscle reinnervation (TMR) is a microsurgical technique that repairs the severed proximal nerve end to a redundant motor nerve in the amputated stump. Evidence supports TMR as effective in treating PN and PLP; however, its adoption has been slow. This study aimed to characterize: (1) the populations experiencing post-amputation PN/PLP; (2) current trends in managing PN/PLP; and (3) attitudes toward routine use of TMR to manage PN/PLP. METHODS: A cross-sectional survey was distributed to all orthopedic surgeons, plastic surgeons, and physiatrists practicing in Ontario, via publicly available emails and specialty associations. Data were collected on demographics, experience with amputation, managing post-amputation pain, and attitudes toward routine use of TMR. RESULTS: Sixty-six of 698 eligible participants submitted complete surveys (9.5% response rate). Respondents had a greater experience with surgical management of PN (71% PN versus 10% PLP). However, surgery was considered a 3rd-line option for PN and not an option for PLP in 57% and 59% of respondents, respectively. Thirty participants (45%) were unaware of TMR as an option, and only 8 respondents have currently incorporated TMR into their practice. Many (76%) would be willing to incorporate TMR into their practice as either an immediate or delayed surgical technique. CONCLUSIONS: Despite its promise in managing post-amputation pain, awareness of TMR as a surgical option is generally poor. Several barriers to the widespread adoption of this technique are defined.

Neurofilament-histomorphometry comparison in the evaluation of unmyelinated axon regeneration following peripheral nerve injury: An alternative to electron microscopy.

BACKGROUND: Currently, assessment of unmyelinated axon regeneration is limited to electron microscopy (EM), which is expensive, time consuming and not universally available. This study presents a protocol to estimate the number of unmyelinated axons in a regenerating peripheral nerve without the need for electron microscopy. NEW METHOD: The common peroneal nerve of Sprague-Dawley rats was transected, repaired and regenerated for 4 weeks. Two distal adjacent segments of the regenerating nerve were then processed for either conventional histomorphometry using toluidine blue or immunolabeling of neurofilament protein. Myelinated axon and total axon counts were obtained, respectively, to generate estimates of unmyelinated axon numbers, which were then compared to unmyelinated axon counts using EM from the same specimens. For comparison, unmyelinated axons were counted in an uninjured rat laryngeal nerve. RESULTS: After 4 weeks of regeneration, the estimated number of regenerating unmyelinated axons was 4044 ± 232 using this technique, representing 81.3% of the total axonal population. By comparison, the proportion of unmyelinated axons in the uninjured laryngeal nerve was 55% of the total axonal population. COMPARISON WITH EXISTING METHOD: These estimates correlate with electron microscopy measurements, both in terms of the proportion of unmyelinated axons and also by linear regression analysis. CONCLUSIONS: The neurofilament staining method correlates with electron microscopy estimates of the same nerve sections. It is useful for the efficient counting of unmyelinated axons in the regenerating peripheral nerve and can be used by laboratories that do not have access to EM facilities.

Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

BACKGROUND: Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. OBJECTIVE: To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. METHODS: In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. RESULTS: Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. CONCLUSION: This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

Enhancement of facial nerve motoneuron regeneration through cross-face nerve grafts by adding end-to-side sensory axons.

BACKGROUND: In unilateral facial palsy, cross-face nerve grafts are used for emotional facial reanimation. Facial nerve regeneration through the grafts takes several months, and the functional results are sometimes inadequate. Chronic denervation of the cross-face nerve graft results in incomplete nerve regeneration. The authors hypothesize that donor axons from regional sensory nerves will enhance facial motoneuron regeneration, improve axon regeneration, and improve the amplitude of facial muscle movement. METHODS: In the rat model, a 30-mm nerve graft (right common peroneal nerve) was used as a cross-face nerve graft. The graft was coapted to the proximal stump of the transected right buccal branch of the facial nerve and the distal stumps of the transected left buccal and marginal mandibular branches. In one group, sensory occipital nerves were coapted end-to-side to the cross-face nerve graft. Regeneration of green fluorescent protein-positive axons was imaged in vivo in transgenic Thy1-green fluorescent protein rats, in which all neurons express green fluorescence. After 16 weeks, retrograde labeling of regenerated neurons and histomorphometric analysis of myelinated axons was performed. Functional outcomes were assessed with video analysis of whisker motion. RESULTS: "Pathway protection" with sensory axons significantly enhanced motoneuron regeneration, as assessed by retrograde labeling, in vivo fluorescence imaging, and histomorphometry, and significantly improved whisker motion during video analysis. CONCLUSION: Sensory pathway protection of cross-face nerve grafts counteracts chronic denervation in nerve grafts and improves regeneration and functional outcomes.

The ErbB2 inhibitor Herceptin (Trastuzumab) promotes axonal outgrowth four weeks after acute nerve transection and repair.

Accumulating evidence suggests that neuregulin, a potent Schwann cell mitogen, and its receptor, ErbB2, have an important role in regulating peripheral nerve regeneration. We hypothesized that Herceptin (Trastuzumab), a monoclonal antibody that binds ErbB2, would disrupt ErbB2 signaling, allowing us to evaluate ErbB2's importance in peripheral nerve regeneration. In this study, the extent of peripheral motor and sensory nerve regeneration and distal axonal outgrowth was analyzed two and four weeks after common peroneal (CP) nerve injury in rats. Outcomes analyzed included neuron counts after retrograde labeling, histomorphometry, and protein analysis. The data analysis revealed that there was no impact of Herceptin administration on either the numbers of motor or sensory neurons that regenerated their axons but histomorphometry revealed that Herceptin significantly increased the number of regenerated axons in the distal repaired nerve after 4 weeks. Protein analysis with Western blotting revealed no difference in either expression levels of ErbB2 or the amount of activated, phosphorylated ErbB2 in injured nerves. In conclusion, administration of the ErbB2 receptor inhibitor after nerve transection and surgical repair did not alter the number of regenerating neurons but markedly increased the number of regenerated axons per neuron in the distal nerve stump. Enhanced axon outgrowth in the presence of this ErbB2 inhibitor indicates that ErbB2 signaling may limit the numbers of axons that are emitted from each regenerating neuron.