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Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of naïve mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1 day, 3 days, and 7 days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with a high glycolytic flux dominate the early injury response and rapidly give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood–nerve barrier, proliferation of endoneurial and perineurial stromal cells, and entry of opsonizing serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1 -/- mice, in which Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1 -/- mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naïve and injured PNS and report on hundreds of ligand–receptor interactions. Our longitudinal analysis represents a new resource for neural tissue regeneration, reveals location- specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/ .

To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age. Severe OBPP was defined as neurotmesis or avulsion of spinal nerves C5 and C6 irrespective of additional C7-T1 lesions, assessed during surgery and confirmed by histopathological examination. We first prospectively studied a derivation group of 48 infants with OBPP with a minimal follow-up of two years. Ten dichotomous items concerning active clinical joint movement and needle electromyography of the deltoid, biceps and triceps muscles were gathered at one week, one month and three months of age. Predictors for a severe lesion were identified using a two-step forward logistic regression analysis. The results were validated in two independent cohorts of OBPP infants of 60 and 13 infants. Prediction of severe OBPP at one month of age was better than at one week and at three months. The presence of elbow extension, elbow flexion and of motor unit potentials in the biceps muscle correctly predicted whether lesions were mild or severe in 93.6% of infants in the derivation group (sensitivity 1.0, specificity 0.88), in 88.3% in the first validation group (sensitivity 0.97, specificity 0.76) and in 84.6% in the second group (sensitivity of 1.0, specificity 0.66). Infants with OBPP with severe lesions can be identified at one month of age by testing elbow extension, elbow flexion and recording motor unit potentials (MUPs) in the biceps muscle. The decision rule implies that children without active elbow extension at one month should be referred to a specialized center, while children with active elbow extension as well as active flexion should not. When there is active elbow extension, but no active elbow flexion an EMG is needed; absence of MUPs in the biceps muscle is an indication for referral.

Case report. The value of movement-based therapy in peripheral nerve injury conditions such as neonatal brachial plexus palsy (NBPP) is unclear. To determine the effectiveness of a home-based movement therapy program in a 17 year old female patient with a right NBPP pan-plexopathy. Home training consisted of arm reaching and object manipulation tasks using devices which recorded performance. Training occurred for 1 h/day, 5 days/week for 6 weeks with periodic webcam supervision. Pre- and post clinical, functional and kinematic assessments were performed in a laboratory setting. Following training, shoulder flexion and elbow extension active range of motion increased by 13° and 9°, respectively, and functional ability also improved. Reach movement duration decreased significantly with a concomitant improvement in movement coordination. These results demonstrate that movement therapy has the potential to improve motor function in NBPP years after the initial insult. 4

Abstract Nerve reconstruction for upper brachial plexus injury consists of nerve repair and/or transfer. Current literature lacks evidence supporting a preferred surgical treatment for adults with such injury involving shoulder and elbow function. We systematically reviewed the literature published from January 1990 to February 2011 using multiple databases to search the following: brachial plexus and graft, repair, reconstruction, nerve transfer, neurotization. Of 1360 articles initially identified, 33 were included in analysis, with 23 nerve transfer (399 patients), 6 nerve repair (99 patients), and 4 nerve transfer + proximal repair (117 patients) citations (mean preoperative interval, 6 ± 1.9 months). For shoulder abduction, no significant difference was found in the rates ratio (comparative probabilities of event occurrence) among the 3 methods to achieve a Medical Research Council (MRC) scale score of 3 or higher or a score of 4 or higher. For elbow flexion, the rates ratio for nerve transfer vs nerve repair to achieve an MRC scale score of 3 was 1.46 (P = .03); for nerve transfer vs nerve transfer + proximal repair to achieve an MRC scale score of 3 was 1.45 (P = .02) and an MRC scale score of 4 was 1.47 (P = .05). Therefore, for elbow flexion recovery, nerve transfer is somewhat more effective than nerve repair; however, no particular reconstruction strategy was found to be superior to recover shoulder abduction. When considering nerve reconstruction strategies, our findings do not support the sole use of nerve transfer in upper brachial plexus injury without operative exploration to provide a clear understanding of the pathoanatomy. Supraclavicular brachial plexus exploration plays an important role in developing individual surgical strategies, and nerve repair (when donor stumps are available) should remain the standard for treatment of upper brachial plexus injury except in isolated cases solely lacking elbow flexion.

The adult CNS is an inhibitory environment for axon outgrowth, severely limiting recovery from traumatic injury. This limitation is due, in part, to endogenous axon regeneration inhibitors (ARIs) that accumulate at CNS injury sites. ARIs include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein, and chondroitin sulfate proteoglycans (CSPGs). Some ARIs bind to specific receptors on the axon growth cone to halt outgrowth. Reversing or blocking the actions of ARIs may promote recovery after CNS injury. We report that treatment with sialidase, an enzyme that cleaves one class of axonal receptors for myelinassociated glycoprotein, enhances spinal axon outgrowth into implanted peripheral nerve grafts in a rat model of brachial plexus avulsion, a traumatic injury in which nerve roots are torn from the spinal cord. Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. To model brachial plexus avulsion in the rat, C8 nerve roots were cut flush to the spinal cord and a peroneal nerve graft was inserted into the lateral spinal cord at the lesion site. Infusion of Clostridium perfringens sialidase to the injury site markedly increased the number of spinal axons that grew into the graft (2.6-fold). Chondroitinase ABC, an enzyme that cleaves a different ARI (CSPGs), also enhanced axon outgrowth in this model. In contrast, phosphatidylinositol-specific phospholipase C, which cleaves oligodendrocyte-myelin glycoprotein and Nogo receptors, was without benefit. Molecular therapies targeting sialoglycoconjugates and CSPGs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.

Abstract BACKGROUND: Depression has been associated with poor outcomes in neurosurgical patients, including increased pain, poorer functional recovery, delayed return to work, and decreased patient satisfaction. No reports exist regarding an association of psychiatric diagnoses with outcomes after brachial plexus reconstruction. As outcomes and patient satisfaction become increasingly important to payers and physician reimbursement, assessing modifiable preoperative risk factors for their association with poor outcome and patient satisfaction is imperative. OBJECTIVE: To analyze patients undergoing brachial plexus reconstruction to assess the relationship of depression/anxiety with functional outcome. METHODS: Data were collected retrospectively on all patients who underwent brachial plexus reconstruction to restore elbow flexion between 2005 and 2013. Elbow flexion, graded via the Medical Research Council scale, was assessed at latest follow-up. Multiple variables, including the presence of Axis I psychiatric diagnoses, were assessed for their association with the dichotomous outcome of Medical Research Council scale score ≥3 (antigravity) vs <3 elbow flexion. Standard statistical methods were used. RESULTS: Thirty-seven patients met inclusion criteria. The median postsurgical follow-up time was 21 months. Operations included neurolysis (n = 3), nerve graft repair (n = 6), and nerve transfer (n = 28). Depression was present in 10 of 37 patients (27%). Of variables tested, only depression was associated with poor elbow flexion outcome (odds ratio: 6.038; P = .04). CONCLUSION: Preoperative depression is common after brachial plexus injury. The presence of depression is associated with reduced elbow flexion recovery after reconstruction. Our data suggest assessment and treatment of preoperative mental health is important in designing a comprehensive postoperative management plan to optimize outcomes and patient satisfaction.

Acute peroneal nerve palsy is a well-known complication of total knee arthroplasty (TKA) that causes a neurological deficit typically seen within hours or days postoperatively. Peroneal nerve dysfunction presents more subtlely than peroneal nerve palsy, with decreased knee range of motion, lateral knee pain, or both following TKA. The diagnosis of peroneal nerve dysfunction may not be suspected for weeks, months, or even years after TKA. Electromyography and nerve conduction studies can support the diagnosis. Historically, peroneal nerve palsy following TKA has been treated nonoperatively but has had an unsatisfactory rate of complete recovery. Recently, a few reports have demonstrated that patients with either peroneal nerve palsy or dysfunction after TKA have had excellent results with surgical decompression of the peroneal nerve. The authors describe a 63-year-old woman who reported transient episodes of lateral knee and leg pain for years after undergoing TKA. She eventually underwent electromyography and nerve conduction studies that indicated a diagnosis of peroneal nerve dysfunction. Approximately 10 years after the TKA, she underwent surgical decompression of the peroneal nerve and has done well since, with significant pain relief and an increased activity level. This case supports the recent literature describing peroneal nerve dysfunction as an uncommon but surgically treatable cause of lateral knee pain following TKA. Increased awareness of the condition and its facile treatment via surgical decompression may result in improved outcomes years after TKA.

Background: Biceps recovery is a critical determinant for treatment decision-making in patients with neonatal brachial plexus palsy (NBPP). One treatment intervention used by therapists is neuromuscular electrical stimulation (NMES), but its use remains controversial. This study's aim was to determine the effect and safety of NMES on biceps function in infants with NBPP compared to standard therapy. Methods: In this pilot, randomized controlled study, patients were randomized to the NMES treatment or control/sham group. Inclusion criteria were infants 3 to 9 months of age with a confirmed diagnosis of NBPP and biceps weakness, without other comorbidities. The parents administered the NMES (treatment or control) 30 min daily. Outcomes of active range of motion (AROM), muscle strength, and morphometric measurements were assessed by one of two blinded therapists at enrollment and 1 -, 2-, and 3-month follow-up intervals. Results: Seventeen patients (10 NMES, seven control) participated in the study. Despite equal group demographics, the treatment group demonstrated significant improvement in elbow flexion AROM after the first month of NMES compared to the control group (improvement 31[degrees] vs. -3[degrees], P =.047). No adverse effects were reported. Conclusion: Use of NMES can be beneficial and should be considered in the early rehabilitation protocol for infants with NBPP. Keywords elbow flexion, electrical stimulation, Erb's palsy, biceps, therapy, treatment

Background Ultrasound has been utilized in the evaluation of compressive and traumatic peripheral nerve pathology. Objective To determine whether US can provide comprehensive evaluation of the post-ganglionic brachial plexus in the setting of neonatal brachial plexus palsy and whether this information can be used to guide preoperative nerve reconstruction strategies. Materials and methods In this retrospective cohort study, preoperative brachial plexus ultrasonography was performed in 52 children with neonatal brachial plexus palsy who were being considered for surgery. The 33 children who had surgery compose the patient cohort. The presence and location of post-ganglionic neuromas were evaluated by US and compared to the surgical findings. US evaluation of shoulder muscle atrophy was conducted as an indirect way to assess the integrity of nerves. Finally, we correlated glenohumeral joint laxity to surgical and clinical management. Results Ultrasound correctly identified 21 of 25 cases of upper trunk and middle trunk neuroma involvement (84% sensitivity for each). It was 68% sensitive and 40% specific in detection of lower trunk involvement. US identified shoulder muscle atrophy in 11 of 21 children evaluated; 8 of these 11 went on to nerve transfer procedures based upon the imaging findings. US identified 3 cases of shoulder joint laxity of the 13 children evaluated. All 3 cases were referred for orthopedic evaluation, with 1 child undergoing shoulder surgery and another requiring casting. Conclusion Ultrasound can provide useful preoperative evaluation of the post-ganglionic brachial plexus in children with neonatal brachial plexus palsy.

Abstract BACKGROUND: Many instruments have been developed to measure upper extremity disability, but few have been applied to ulnar neuropathy at the elbow (UNE). OBJECTIVE: We measured patient outcomes following ulnar nerve decompression to (1) identify the most appropriate outcomes tools for UNE and (2) to describe outcomes following ulnar nerve decompression. METHODS: Thirty-nine patients from 5 centers were followed prospectively after nerve decompression. Outcomes were measured preoperatively and at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Each patient completed the Michigan Hand Questionnaire (MHQ), Carpal Tunnel Questionnaire (CTQ), and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires. Grip, key-pinch strength, Semmes-Weinstein monofilament, and 2-point discrimination were measured. Construct validity was calculated by using Spearman correlation coefficients between questionnaire scores and physical and sensory measures. Responsiveness was assessed by standardized response means. RESULTS: Key-pinch (P = .008) and Semmes-Weinstein monofilament testing of the ulnar ring (P < .001) and small finger (radial: P = .004; ulnar: P < .001) improved following decompression. Two-point discrimination improved significantly across the radial (P = .009) and ulnar (P = .007) small finger. Improved symptoms and function were noted by the CTQ (preoperative CTQ symptom score 2.73 vs 1.90 postoperatively, P < .001), DASH (P < .001), and MHQ: function (P < .001), activities of daily living (P = .003), work (P = .006), pain (P < .001), and satisfaction (P < .001). All surveys demonstrated strong construct validity, defined by correlation with functional outcomes, but MHQ and CTQ symptom instruments demonstrated the highest responsiveness. CONCLUSION: Patient-reported outcomes improve following ulnar nerve decompression, including pain, function, and satisfaction. The MHQ and CTQ are more responsive than the DASH for isolated UNE treated with decompression.