Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

BACKGROUND: Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. METHODS: Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. RESULTS: Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. CONCLUSIONS: The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

Reliable Method for Avoiding Malrotation Deformity After Intramedullary Nailing of Comminuted Femur Fractures: Clinical Validation of a Previously Described Technique.

OBJECTIVES: To evaluate a previously described technique using the inherent anteversion of intramedullary nail (IMN) to avoid malrotation in comminuted femur fractures and describe the use of magnetic resonance imaging (MRI) as an alternative method for assessing postoperative femoral version. DESIGN: Prospective consecutive cohort study. SETTING: Level I trauma center. PATIENT/PARTICIPANTS: Twenty-five consecutive patients with comminuted femur fractures (Winquist III/IV, OTA/AO 32-B/32-C) treated by a single surgeon with IMN between September 1, 2011, and February 28, 2015. INTERVENTION: IMN on a fracture table with intraoperative femoral version set by the inherent version of the implant. All patients received a postoperative computed tomography (CT) or MRI to assess femoral version. MAIN OUTCOME MEASUREMENTS: Mean difference in postoperative femoral anteversion (DFA) between injured limb and uninjured limb as measured by CT or MRI. Mean difference in postoperative femoral version of the injured femur from the inherent version of the implant (12 degrees) was measured with CT or MRI. RESULTS: The mean postoperative DFA was 9.1 ± 5.6 degrees. Postoperative DFA greater than 15 degrees was found in 2 (8.0%) patients. Mean difference in postoperative version of the injured femur from the inherent 12 degrees of the implant was 7.1 ± 5.4 degrees. Patients tolerated MRI studies well. CONCLUSIONS: Our previously described technique using the inherent anteversion of an IMN is effective and leads to a very low rate of malrotation, even in highly comminuted fractures. The technique is particularly useful in treating bilateral femur fractures. MRI can be used safely and effectively to assess anteversion after fixation of femur fractures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Finding Value in Surgical Didactics: Longitudinal Resident Feedback From Case-Based and Traditional Lectures in an Orthopaedic Residency.

OBJECTIVE: To evaluate orthopedic resident perceptions of a didactic curriculum presented in traditional and case-based formats. DESIGN: Prospective cohort study using anonymous web-based survey after each conference evaluating resident perceptions of faculty participation, didactic delivery, content, and overall conference value. Conferences were structured as primarily case-based or traditional lecture. Logistic analysis was performed to determine factors predictive of rating a conference as valuable time spent. SETTING: Orthopedic residency training program at single institution over an academic year. PARTICIPANTS: Orthopedic residents in postgraduate training year 1 to 5 attending mandatory didactic conference. RESULTS: Cased-based conferences received higher Likert ratings on residents' perception of faculty participation, instructor delivery, and improvement in topic understanding when compared to traditional lecture-based conferences (p < 0.0001 for each factor). Residents also were more likely to rate case-based conferences as valuable time spent (p < 0.0001). In our logistic model, factors associated with a negative likelihood of rating a conference as valuable were lecture format (odds ratio [OR] = 0.155, 95% CI: 0.115-0.208), PGY-2 level presenter (OR = 0.288, 95% CI: 0.169-0.490), and PGY-3 level presenter (OR = 0.433, 95% CI: 0.269-0.696). Timing in the year, surgical subspeciality, and conference identity were not significant predictors of conference value rating. CONCLUSIONS: Longitudinal resident feedback demonstrates highly favorable resident perceptions toward case-based formats in didactic sessions. Junior levels residents are not perceived as effective as senior residents and faculty in presenting material in either format. These methods allow for a dynamic approach to identifying strengths and weaknesses in a resident curriculum as a well as a means for more focused and real-time improvements.

Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

INTRODUCTION: Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. METHODS: Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. RESULTS: Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. CONCLUSIONS: Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016.

Spinopelvic dissociation: multidetector computed tomographic evaluation of fracture patterns and associated injuries at a single level 1 trauma center.

The objective of the present study is to evaluate multidetector computed tomographic (MDCT) fracture patterns and associated injuries in patients with spinopelvic dissociation (SPD). Our institutional trauma registry database was reviewed from Jan. 1, 2006, to Sept. 30, 2012, specifically evaluating patients with sacral fractures. MDCT scans of patients with sacral fractures were reviewed to determine the presence of SPD. SPD cases were characterized into the following fracture patterns: U-shaped, Y-shaped, T-shaped, H-shaped, and burst. The following MDCT features were recorded: level of the horizontal fracture, location of vertical fracture, kyphosis between major fracture fragments, displacement of fracture fragment, narrowing of central spinal canal, narrowing of neural foramina, and extension into sacroiliac joints. Quantitative evaluation of the sacral fractures was performed in accordance with the consensus statement by the Spine Trauma Study Group. Medical records were reviewed to determine associated pelvic and non-pelvic fractures, bladder and bowel injuries, nerve injuries, and type of surgical intervention. Twenty-one patients had SPD, of whom 13 were men and eight were women. Mean age was 41.8 years (range 18.8 to 87.7). Five fractures (24 %) were U-shaped, six (29 %) H-shaped, four (19 %) Y-shaped, and six (29 %) burst. Nine patients (43 %) had central canal narrowing, and 19 (90 %) had neural foramina narrowing. Eleven patients (52 %) had kyphotic angulation between major fracture fragments, and seven patients (33 %) had either anterior (24 %) or posterior (10 %) displacement of the proximal fracture fragment. Fourteen patients (67 %) had associated pelvic fractures, and 20 (95 %) had associated non-pelvic fractures. Two patients (10 %) had associated urethral injuries, and one (5 %) had an associated colon injury. Seven patients (33 %) had associated nerve injuries. Six patients (29 %) had surgical fixation while 15 (71 %) were managed non-operatively. On trauma MDCT examinations, patients with SPD have characteristic fracture patterns. It is important to differentiate SPD from other pelvic ring injuries due to high rate of associated injuries. Although all SPD injuries are unstable and need fixation, the decision for operative management in an individual patient depends on the systemic injury pattern, specific fracture pattern, and the ability to attain stable screw fixation.

A chronically-denervated versus a freshly-harvested autograft for nerve repair in rats.

OBJECTIVES: Autologous nerve grafting remains the gold standard for repair of peripheral nerve injuries. Its use, however, is limited by donor nerve availability and donor site morbidity. This is especially problematic after failure of an initial autograft that requires a repeat nerve graft, resulting in a second surgical site with associated morbidity. Based on the molecular differences in nerve degeneration in the proximal and distal segments after transection, we hypothesized that a chronically-denervated proximal stump may be viable for autologous nerve repair. METHODS: 20 Sprague-Dawley rats underwent right sciatic nerve excision and sural nerve transection. After 8 weeks, nerve repair was performed by harvesting the proximal segment of the sural nerve (n=10) or a fresh sural nerve (n=10) from the contralateral hind limb. Electrophysiological changes were analyzed to compare the fresh and denervated grafts. RESULTS: Electrophysiological testing demonstrated higher compound motor action potential in the denervated group compared to the fresh autograft group, however this difference was not statistically significant (p=0.117). CONCLUSION: The proximal segment of a chronically-denervated sural nerve can be as effective as a fresh sural nerve for autologous repair of peripheral nerve injuries in a rodent model.

A human hair keratin hydrogel scaffold enhances median nerve regeneration in nonhuman primates: an electrophysiological and histological study.

A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve conduit luminal filler following median nerve transection injury in 10 Macaca fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a NeuraGen® collagen conduit filled with either saline or keratin hydrogel and nerve regeneration was evaluated by electrophysiology for a period of 12 months. The keratin hydrogel-grafted nerves showed significant improvement in return of compound motor action potential (CMAP) latency and recovery of baseline nerve conduction velocity (NCV) compared with the saline-treated nerves. Histological evaluation was performed on retrieved median nerves and abductor pollicis brevis (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger nerve area in the keratin group compared with the saline group and the keratin APB muscles had a significantly higher myofiber density than the saline group. This is the first published study to show that an acellular biomaterial hydrogel conduit filler can be used to enhance peripheral nerve regeneration and motor recovery in an NHP model.

Computer simulation of nerve transfer strategies for restoring shoulder function after adult C5 and C6 root avulsion injuries.

PURPOSE: Functional ability after nerve transfer for upper brachial plexus injuries relies on both the function and magnitude of force recovery of targeted muscles. Following nerve transfers targeting either the axillary nerve, suprascapular nerve, or both, it is unclear whether functional ability is restored in the face of limited muscle force recovery. METHODS: We used a computer model to simulate flexing the elbow while maintaining a functional shoulder posture for 3 nerve transfer scenarios. We assessed the minimum restored force capacity necessary to perform the task, the associated compensations by neighboring muscles, and the effect of altered muscle coordination on movement effort. RESULTS: The minimum force restored by the axillary, suprascapular, and combined nerve transfers that was required for the model to simulate the desired movement was 25%, 40%, and 15% of the unimpaired muscle force capacity, respectively. When the deltoid was paralyzed, the infraspinatus and subscapularis muscles generated higher shoulder abduction moments to compensate for deltoid weakness. For all scenarios, movement effort increased as restored force capacity decreased. CONCLUSIONS: Combined axillary and suprascapular nerve transfer required the least restored force capacity to perform the desired elbow flexion task, whereas single suprascapular nerve transfer required the most restored force capacity to perform the same task. Although compensation mechanisms allowed all scenarios to perform the desired movement despite weakened shoulder muscles, compensation increased movement effort. Dynamic simulations allowed independent evaluation of the effect of restored force capacity on functional outcome in a way that is not possible experimentally. CLINICAL RELEVANCE: Simultaneous nerve transfer to suprascapular and axillary nerves yields the best simulated biomechanical outcome for lower magnitudes of muscle force recovery in this computer model. Axillary nerve transfer performs nearly as well as the combined transfer, whereas suprascapular nerve transfer is more sensitive to the magnitude of reinnervation and is therefore avoided.

An ulnar intraneural ganglion arising from the pisotriquetral joint: case report.

Intraneural ganglions of the hand are rare and remain poorly understood. We report a case of an intraneural ganglion arising from the pisotriquetral joint that penetrated the ulnar nerve at Guyon's canal. Although rare, these ganglions should be considered in the differential diagnosis of any neoplasms causing compression neuropathy.