Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Compression of the Ulnar Nerve by the Arcade of Struthers: Look and You Shall Find.

BACKGROUND: The arcade of Struthers was first proposed by Kane et al in 1973. Clinical investigations of this structure have been limited to small case series, focusing on the arcade as an isolated cause of compressive ulnar neuropathy. The purpose of our study was to investigate the incidence of this structure in patients undergoing ulnar nerve transposition. METHODS: A retrospective chart review of prospectively maintained data in a single surgeon's practice was performed. Records of patients undergoing surgery for compressive ulnar neuropathy at the cubital tunnel were evaluated for documentation of a compressive arcade of Struthers. In addition, a scoping review of the literature was undertaken to better characterize current understanding of this structure and its recognition in clinical practice. RESULTS: A total of 197 patients underwent ulnar nerve transposition. The overall incidence of a compressive arcade of Struthers was noted to be 67 out of 197 (34%). All patients with a compressive arcade were noted to have an internal brachial ligament running below the nerve. Patients undergoing revision surgery were found to have a compressive arcade 51% of the time (20/39), whereas 30% of patients undergoing primary surgery were found to have a compressive arcade (47/158). Only 12 clinical studies examining the arcade of Struthers have been published in the last 20 years, the majority being single case reports. CONCLUSIONS: Compression of the ulnar nerve by the arcade of Struthers is a common finding and can contribute to compressive ulnar neuropathy at the elbow both in primary and revision cases.

Patient Outcomes After Peripheral Nerve Injury Depend on Bimanual Dexterity and Preserved Use of the Affected Hand.

BACKGROUND: Little is known about how peripheral nerve injury affects human performance, behavior, and life. Hand use choices are important for rehabilitation after unilateral impairment, but rarely measured, and are not changed by the normal course of rehabilitation and daily life. OBJECTIVE: To identify the relationship between hand use (L/R choices), motor performance, and patient-centered outcomes. METHODS: Participants (n = 48) with unilateral peripheral nerve injury were assessed for hand use via Block Building Task, Motor Activity Log, and Edinburgh Handedness Inventory; dexterity (separately for each hand) via Nine-Hole Peg Test, Jebsen Taylor Hand Function Test, and a precision drawing task; patient-centered outcomes via surveys of disability, activity participation, and health-related quality of life; and injury-related factors including injury cause and affected nerve. Factor Analysis of Mixed Data was used to explore relationships between these variables. The data were analyzed under 2 approaches: comparing dominant hand (DH) versus non-dominant hand (NH), or affected versus unaffected hand. RESULTS: The data were best explained by 5 dimensions. Good patient outcomes were associated with NH performance, DH performance (separately and secondarily to NH performance), and preserved function and use of the affected hand; whereas poor patient outcomes were associated with preserved but unused function of the affected hand. CONCLUSION: After unilateral peripheral nerve injury, hand function, hand usage, and patient life arise from a complex interaction of many factors. To optimize rehabilitation after unilateral impairment, new rehabilitation methods are needed to promote performance and use with the NH, as well as the injured hand.

The Medial Antebrachial Cutaneous Nerve Is a Low-Morbidity Alternative to the Standard Sural Nerve Autograft.

BACKGROUND: Nerve interposition grafting is an important technique in nerve reconstructive surgery that is used when a primary repair is not feasible without significant tension. This study sought to evaluate the long-term morbidity of the medial antebrachial cutaneous (MABC) nerve as an alternative donor nerve in comparison with sural nerve harvest. METHODS: A single surgeon and institution retrospective chart review was performed to identify all patients who underwent nerve autografting using the sural and MABC as donor nerves between January 1, 2000 and December 31, 2019. Surveys assessed overall patient satisfaction with surgery, as well as donor and recipient site morbidity, satisfaction, pain, numbness, and cold sensitivity. RESULTS: Of the 73 patients contacted, 54 agreed to participate, and 43 of 73 (58.9%) ultimately completed the survey: 28 MABC (65.1%) and 15 sural (34.9%). There were no significant differences between the sural and MABC groups in overall satisfaction with surgery, donor and recipient site satisfaction, pain, cold sensitivity, and effect on quality of life. Even though 66.7% of sural donor sites and 75% of MABC donor sites had residual numbness, the effect this had on quality of life was very low (2 and 3, respectively). CONCLUSION: The MABC is a safe alternative to the traditional sural nerve autograft. A small subset of patients undergoing nerve autograft harvest will experience long-term morbidity in the form of pain. Conversely, the more common presence of numbness is not reported as bothersome.

Brachial Gunshot Wounds: Injury Patterns and Considerations for Managing the Abnormal Neurological Examination.

BACKGROUND: Nerve injuries from gunshot wounds (GSWs) to the upper arm can cause significant morbidity and loss of function. However, indications for surgical exploration and nerve reconstruction remain unclear as both low- and high-grade injuries can present with an abnormal neurological examination. METHODS: Adult patients presenting with a history of isolated GSW to the upper arm between 2010 and 2019 at a single urban level 1 trauma center were screened for inclusion in this retrospective study. Patient demographics, neurological examination findings, concurrent injuries, and intraoperative findings were gathered. Bivariate analysis was performed to characterize factors associated with nerve injuries. RESULTS: There were 139 adult patients with isolated brachial GSWs, and 49 patients (35%) presented with an abnormal neurological examination and significantly associated with concurrent humerus fractures (39% vs 21%, P = .026) and brachial artery injuries (31% vs 2%, P < .001). Thirty of these 49 patients were operatively explored. Fifteen patients were found to have observed nerve injuries during operative exploration including 8 patients with nerve transections. The radial nerve was the most commonly transected nerve (6), and among the 16 contused nerves, the median (8) was most common. CONCLUSION: Nerve injury from upper arm GSWs is common with directly traumatized nerves confirmed in at least 39% and nerve transection in at least 16% of patients with an abnormal neurological examination. Timely referral to a hand and/or peripheral nerve surgeon for close clinical follow-up, appropriate diagnosis, and any necessary surgical reconstruction with nerve grafts, tendon transfers, and nerve transfers is recommended.

The Yearly Periodicity of Operative Upper Extremity Trauma: A Retrospective Study of "Trauma Season".

BACKGROUND: Upper extremity (UE) trauma requiring operative care increases during the summer and fall months, which the authors colloquially refer to as "trauma season." METHODS: CPT databases were queried for codes related to acute UE trauma at a single level-1 trauma center. Monthly CPT code volume was tabulated for 120 consecutive months and average monthly volume was calculated. Raw data were plotted as a time series and transformed as a ratio to the moving average. Autocorrelation was applied to the transformed data set to detect yearly periodicity. Multivariable modeling quantified the proportion of volume variability attributable to yearly periodicity. Subanalysis assessed presence and strength of periodicity in four age groups. RESULTS: A total of 11,084 CPT codes were included. Monthly trauma-related CPT volume was highest in July through October and lowest in December through February. Time-series analysis revealed yearly oscillation in addition to a growth trend. Autocorrelation revealed statistically significant positive and negative peaks at a lag of 12 and 6 months, respectively, confirming yearly periodicity. Multivariable modeling revealed R 2 attributable to periodicity of 0.53 ( P < 0.01). Periodicity was strongest in younger populations and weaker in older populations. R 2 was 0.44 for ages 0 to 17, 0.35 for ages 18 to 44, 0.26 for ages 45 to 64, and 0.11 for ages 65 and older. CONCLUSIONS: Operative UE trauma volumes peak in the summer and early fall and reach a winter nadir. Periodicity accounts for 53% of trauma volume variability. The authors' findings have implications for allocation of operative block time and personnel and expectation management over the course of the year.

A feasibility study transplanting macrophages to a segmental nerve injury.

INTRODUCTION/AIMS: Promoting regeneration after segmental nerve injury repair is a challenge, but improving angiogenesis could be beneficial. Macrophages facilitate regeneration after injury by promoting angiogenesis. Our aim in this study was to evaluate the feasibility and effects of transplanting exogenous macrophages to a segmental nerve injury. METHODS: Bone marrow-derived cells were harvested from donor mice and differentiated to macrophages (BMDM), then suspended within fibrin hydrogels to facilitate BMDM transplantation. BMDM survival was characterized in vitro. The effect of this BMDM fibrin hydrogel construct at a nerve injury site was assessed using a mouse sciatic nerve gap injury. Mice were equally distributed to "fibrin+Mφ" (fibrin hydrogels containing culture medium and BMDM) or "fibrin" hydrogel control (fibrin hydrogels containing culture medium alone) groups. Flow cytometry (n = 3/group/endpoint) and immunohistochemical analysis (n = 5/group/endpoint) of the nerve gap region were performed at days 3, 5, and 7 after repair. RESULTS: Incorporating macrophage colony-stimulating factor (M-CSF) improved BMDM survival and expansion. Transplanted BMDM survived for at least 7 days in a nerve gap (~40% retained at day 3 and ~15% retained at day 7). From transplantation, macrophage quantities within the nerve gap were elevated when comparing fibrin+Mφ with fibrin control (~25% vs. 3% at day 3 and ~14% vs. 6% at day 7). Endothelial cells increased by about fivefold within the nerve gap, and axonal extension into the nerve gap increased almost twofold for fibrin+Mφ compared with fibrin control. DISCUSSION: BMDM suspended within fibrin hydrogels at a nerve gap do not impair regeneration.

Improving the Care of Our Patients: Twenty-Three Years of the James Barrett Brown Resident Research Day.

BACKGROUND: James Barrett Brown was one of the founders of Plastic and Reconstructive Surgery as a specialty in the United States. Susan Mackinnon started the James Barrett Brown Resident Research Day in 1997 in his honor to serve as an annual opportunity for trainees to present their research to the Division and a visiting contemporary leader in plastic surgery. We sought to determine the proportion of Resident Research Day projects that have progressed to publication. METHODS: Available internal records from 1998 to 2019 were used to identify presenters and projects. Academic productivity of presenters was estimated with the h-index from the Scopus database. RESULTS: One hundred forty-five students, residents, and fellows presented 276 projects at Resident Research Day from 1998 to 2019. These presentations were associated with 144 unique peer-reviewed publications, representing 52% of the presented projects. They were published an average of 1.8 years after presentation, and the presenter was the first or last author on 67% of them. The current average h-index of trainees who published at least 1 project (8.3) is significantly higher than the h-index of those who did not (5.0, P < 0.001). CONCLUSIONS: The James Barrett Brown Resident Research Day not only honors the legacy of Brown but also enhances scholarly activity of trainees. The opportunity to present and publish research teaches project planning, implementation, and data analysis, followed by manuscript preparation and the publication process. This important skill set can provide the foundation for the academic careers of future leaders in plastic surgery.

Rapid Functional Recovery After Thoracic Outlet Decompression in a Series of Adolescent Athletes With Chronic Atraumatic Shoulder-Girdle Pain, Scapular Winging/Dyskinesis, and Normal Electrodiagnostic Studies.

BACKGROUND: Spontaneous shoulder-girdle pain and scapular winging/dyskinesis can be caused by several neuromuscular disorders identifiable by electrodiagnostic studies (EDX). We describe a group of adolescent athletes with this clinical presentation but normal EDX, followed by later development of neurogenic thoracic outlet syndrome (NTOS). METHODS: We identified patients referred for evaluation of NTOS that had a history of chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX. Each was refractory to conservative management and underwent supraclavicular decompression and brachial plexus neurolysis for NTOS. Functional disability was quantified by Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores. RESULTS: There were 5 female patients with a mean age at symptom onset of 14.2 ± 0.4 years, including spontaneous severe pain in the shoulder, scapula, and arm, along with prominent scapular winging/dyskinesis, and normal EDX. Symptoms had persisted for 18.9 ± 4.0 months prior to referral, with pronounced upper extremity disability (mean QuickDASH, 54.6 ± 6.9). By 3 months after surgical treatment for NTOS, all 5 patients experienced near-complete symptom resolution, including scapular winging/dyskinesis, with markedly improved function (mean QuickDASH, 2.2 ± 1.3) and a return to normal activity. CONCLUSIONS: A subset of patients with chronic atraumatic shoulder-girdle pain, scapular winging/dyskinesis, and normal EDX may develop dynamic brachial plexus compression characteristic of NTOS, exhibiting an ischemic "Sunderland-zero" nerve conduction block for which surgical decompression can result in rapid and substantial clinical improvement. The presence of surgically treatable NTOS should be considered for selected patients with long-standing scapular winging/dyskinesis who fail conservative management.

Following a Surgical Paradigm Shift Through the Adoption of Nerve Transfers Among Board-Eligible and Practicing Plastic Surgeons.

BACKGROUND: Nerve transfers represent a new paradigm in the treatment of nerve injuries. Their current level of adoption among surgeons is unknown. This study evaluates the incidence of nerve transfers on case logs of board-eligible plastic surgeons over the past 14 years and surveys practicing nerve surgeons regarding their use of this technique. METHODS: We queried the American Board of Plastic Surgery case log database for all nerve reconstruction Current Procedural Terminology codes from 2008 to 2021 and assessed trends and relationships between geographic region, examination year, and nerve transfer use. We surveyed nerve surgery professional societies to assess trends in practice, compared with a 2017 survey. RESULTS: A total of 1959 nerve reconstruction cases were logged by 738 candidates from 2008 to 2021. Twelve percent of cases included nerve transfers. The proportion of nerve transfer codes (Z = -11.57; P < .0001) and the proportion of candidates performing nerve transfers (Z = -9.21, P < .0001) increased over the study period. Nerve transfers were associated with geographic region (χ2 = 25.826, P = .0002), with most cases performed in the Midwest (26.4%). A higher proportion of practicing nerve surgeons reported performing nerve transfers in this survey than in our 2017 survey (χ2 = 16.7, P < .001). CONCLUSIONS: There has been an increase in nerve transfers logged in the past 14 years by board-eligible plastic surgeons, as well as increased use among currently practicing nerve surgeons. Although nerve transfer use is increasing among both plastic and orthopedic surgeons, a greater proportion of nerve reconstructions include nerve transfers in the plastic surgery cohort.

Calling on Sponsorship: Analysis of Speaker Gender Representation at Hand Society Meetings.

BACKGROUND: The paucity of leadership diversity in surgical specialties is well documented. Unequal opportunities for participation at scientific meetings may impact future promotions within academic infrastructures. This study evaluated gender representation of surgeon speakers at hand surgery meetings. METHODS: Data were retrieved from the 2010 and 2020 meetings of the American Association for Hand Surgery (AAHS) and American Society for Surgery of the Hand (ASSH). Programs were evaluated for invited and peer-reviewed speakers excluding keynote speakers and poster presentations. Gender was determined from publicly available sources. Bibliometric data (Hirsch index) for invited speakers were analyzed. RESULTS: In 2010 at the AAHS ( n = 142) and ASSH meetings ( n = 180), female surgeons represented 4% of the invited speakers and in 2020 increased to 15% at AAHS ( n = 193) and 19% at ASSH ( n = 439). From 2010 to 2020, female surgeon invited speakers had a 3.75-fold increase at AAHS and 4.75-fold increase at ASSH. Representation of female surgeon peer-reviewed presenters at these meetings was similar (2010 AAHS, 26%; and 2010 ASSH, 22%; 2020 AAHS, 23%; 2020 ASSH, 22%). The academic rank of women speakers was significantly lower ( P < 0.001) than for male speakers. At the assistant professor level, the mean Hirsch index was significantly lower ( P < 0.05) for female invited speakers. CONCLUSIONS: Although there was a significant improvement in gender diversity in invited speakers at the 2020 meetings compared with 2010, female surgeons remain underrepresented. Gender diversity is lacking at national hand surgery meetings, and continued effort and sponsorship of speaker diversity is imperative to curate an inclusive hand society experience.

A Surgical Framework for the Management of Incomplete Axillary Nerve Injuries.

BACKGROUND: Axillary nerve injury is the most common nerve injury affecting shoulder function. Nerve repair, grafting, and/or end-to-end nerve transfers are used to reconstruct complete neurotmetic axillary nerve injuries. While many incomplete axillary nerve injuries self-resolve, axonotmetic injuries are unpredictable, and incomplete recovery occurs. Similarly, recovery may be further inhibited by superimposed compression neuropathy at the quadrangular space. The current framework for managing incomplete axillary injuries typically does not include surgery. METHODS: This study is a retrospective analysis of 23 consecutive patients with incomplete axillary nerve palsy who underwent quadrangular space decompression with additional selective medial triceps to axillary end-to-side nerve transfers in 7 patients between 2015 and 2019. Primary outcome variables included the proportion of patients with shoulder abduction M3 or greater as measured on the Medical Research Council (MRC) scale, and shoulder pain measured on a Visual Analogue Scale (VAS). Secondary outcome variables included pre- and postoperative Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) scores. RESULTS: A total of 23 patients met the inclusion criteria and underwent nerve surgery a mean 10.7 months after injury. Nineteen (83%) patients achieved MRC grade 3 shoulder abduction or greater after intervention, compared with only 4 (17%) patients preoperatively (p = 0.001). There was a significant decrease in VAS shoulder pain scores of 4.2 ± 2.5 preoperatively to 1.9 ± 2.4 postoperatively (p < 0.001). The DASH scores also decreased significantly from 48.8 ± 19.0 preoperatively to 30.7 ± 20.4 postoperatively (p < 0.001). Total follow-up was 17.3 ± 4.3 months. CONCLUSION: A surgical framework is presented for the appropriate diagnosis and surgical management of incomplete axillary nerve injury. Quadrangular space decompression with or without selective medial triceps to axillary end-to-side nerve transfers is associated with improvement in shoulder abduction strength, pain, and DASH scores in patients with incomplete axillary nerve palsy.

Expectant Management, Tendon Transfer, or Nerve Transfer Surgery for Radial Nerve Injury: A Qualitative Study Exploring Patient Expectations, Goals, and Treatment Experiences.

BACKGROUND: After a radial nerve injury, patients must weigh a complicated set of advantages and disadvantages to observation or surgery. We conducted semistructured interviews to characterize the decision-making process that these patients undertake. METHODS: We recruited participants who were treated with expectant management (nonoperatively), received only a tendon transfer, or received a nerve transfer. Participants completed a semistructured interview that was transcribed and coded to identify recurring themes, to describe the influence of qualitative findings on treatment decision-making. RESULTS: We interviewed 15 participants (5 expectant management, 5 tendon transfer only, and 5 nerve transfer). Participants' primary concerns were returning to work, hand appearance, regaining motion, resuming activities of daily living, and enjoying hobbies. Delayed diagnosis and/or insurance coverage led 3 participants to change treatment from nerve transfer to isolated tendon transfer. Interactions with providers early in diagnosis and treatment had strong effects on how members of the care team were perceived. The hand therapist was the primary person who shaped expectations, provided encouragement, and prompted referral to the treating surgeon. Participants valued debate among the care team members regarding treatment, provided that medical terminology was explained. CONCLUSIONS: This study highlights the importance of initial, collaborative care in setting expectations for patients with radial nerve injuries. Many participants named returning to work and hand appearance as primary concerns. Hand therapists were the primary source of support and information during recovery. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abductor Digiti Minimi and Anterior Interosseous to Ulnar Motor Nerve Transfer: The Super Turbocharge End-to-Side Transfer.

SUMMARY: Anterior interosseous nerve to ulnar motor nerve supercharged end-to-side (SETS) nerve transfer to restore intrinsic function is a recently adopted nerve transfer in severe ulnar neuropathy. Its success is predicated on the critical threshold number of axons innervating the intrinsic muscles. Given the relative expendability of the abductor digiti minimi (ADM) muscle and the critical function of the other intrinsic muscles, the authors modified their SETS transfer to redirect axons from the ADM to turbocharge the ulnar motor nerve to innervate the more critical intrinsic muscles. They refer to this procedure as a super turbocharged end-to-side (STETS) procedure. The ADM has been used previously as a muscle/tendon transfer for thumb opposition and more recently as a nerve transfer to reinnervate the thenar branch of the median nerve. Although current methods of assessment of reinnervation are likely unable to differentiate between contributions from the anterior interosseous nerve SETS versus ADM STETS transfer, this technique follows the fundamentals of modern nerve surgery, where directing the maximum number of nerve fibers in a timely fashion to the most critical target is paramount for the best functional recovery. The authors suggest that the STETS technique may optimize outcomes in ulnar neuropathy without additional patient morbidity.

Decompression with Brachioradialis Tenotomy Improves Pain and Quality of Life in Patients with Radial Sensory Nerve Compression.

BACKGROUND: Decompression of the superficial sensory branch of the radial nerve (SBRN) with complete brachioradialis tenotomy may treat pain in both simple and complex cases of SBRN compression neuropathy. METHODS: A retrospective chart review was performed of consecutive patients undergoing this procedure between 2008 and 2020 including postoperative outcomes within 90 days. Data were collected and analyzed, including patient and injury demographics, pain descriptors, and patient-reported pain questionnaire, including reported pain severity and impact on quality of life using visual analogue scale (VAS) instruments. Within-group presurgical and postsurgical analyses and between-group statistical analyses were performed. RESULTS: Thirty-three of 58 patients met inclusion criteria. Median time from symptom onset to surgery was 300 days, and median postoperative follow-up time was 37 days. Twenty-five percent of patients ( n = 8) underwent isolated SBRN decompression. The remainder had concomitant decompression of another radial [ n = 16 (48%) or peripheral [ n = 12 (36%)] entrapment point. Ten of 33 patients (30%) had resolution of pain at final follow-up ( P = 0.004). Median change in worst pain over the previous week was -4 ( P < 0.001), and average pain over the last month was -2.75 ( P < 0.001) on the VAS. The impact of pain on quality of life showed a median change of -3 ( P < 0.001) on the VAS. CONCLUSION: Decompression of the sensory branch of the radial nerve including a complete brachioradialis tenotomy improves pain and quality-of-life VAS scores in patients with both simple compression neuropathy syndrome and complex nerve compression syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Loss of Gata1 decreased eosinophils, macrophages, and type 2 cytokines in regenerating nerve and delayed axon regeneration after a segmental nerve injury.

The immune system has garnered attention for its role in peripheral nerve regeneration, particularly as it pertains to regeneration across segmental injuries. Previous work demonstrated that eosinophils are recruited to regenerating nerve and express interleukin-4, amongst potential cytokines. These results suggest a direct role for eosinophils in promoting nerve regeneration. Therefore, we further considered eosinophils roles in nerve regeneration using a segmental nerve injury and Gata1 knockout (KO) mice, which are severely eosinophil deficient, compared to wild-type BALB/c mice (WT). Mice receiving a sciatic nerve gap injury demonstrated distinct cytokine expression and leukocytes within regenerating nerve. Compared to controls, Gata1 KO regenerated nerves contained decreased expression of type 2 cytokines, including Il-5 and Il-13, and decreased recruitment of eosinophils and macrophages. At this early time point during ongoing regeneration, the macrophages within Gata1 KO nerves also demonstrated significantly less M2 polarization compared to controls. Subsequently, motor and sensory axon regeneration across the gap injury was decreased in Gata1 KO compared to WT during ongoing nerve regeneration. Over longer observation to allow for more complete nerve regeneration, behavioral recovery measured by grid-walk assessment was not different comparing groups but modestly delayed in Gata1 KO compared to WT. The extent of final axon regeneration was not different amongst groups. Our data provide additional evidence suggesting eosinophils contribute to nerve regeneration across a nerve gap injury, but are not essential to regeneration in this context. Our evidence also suggests eosinophils may regulate cytokines that promote distinct macrophage phenotypes and axon regeneration.

What is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, and Phantom Nerve Pain.

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for optimal management of each. Further, we delineate the reasons why compression neuropathy and neuroma are amenable to surgery, while painful hyperalgesia and phantom nerve pain are not.