Lynda J.-S. Yang

Sialic Acid Specificity of Myelin-associated Glycoprotein Binding

Myelin-associated glycoprotein (MAG), a nervous system cell adhesion molecule, is an I-type lectin that binds to sialylated glycoconjugates, including gangliosides bearing characteristic structural determinants (Yang, L. J.-S., Zeller, C. B., Shaper, N. L., Kiso, M., Hasegawa, A., Shapiro, R. E., and Schnaar, R. L. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 814-818). Two cell adhesion systems, COS-1 monkey kidney fibroblasts transiently transfected to express MAG and Chinese hamster ovary (CHO) cells stably transfected to express MAG, were used to probe the structural specificity of MAG-ganglioside binding. Both cell types bound to the same gangliosides: GQ1bα (IV3NeuAc,III6NeuAc,II3(NeuAc)2-Gg4Cer) > GT1b = GD1a > GM3 > GM1, GD1b, and GQ1b (the latter do not support adhesion). Binding was enhanced by pretreatment of MAG-expressing cells with neuraminidase. MAG-expressing Chinese hamster ovary cells bound directly to gangliosides resolved on thin layer chromatograms, allowing detection of MAG binding species in a mixture. The simplest ganglioside ligand for MAG was GM3 bearing N-acetylneuraminic acid, whereas GM3 bearing N-glycolylneuraminic acid did not support adhesion. Chemical modifications of N-acetylneuraminic acid residues (on GD1a) abrogated MAG binding. Mild periodate oxidation of sialic acids to their corresponding seven-carbon (or eight-carbon) sialic acid aldehydes abolished MAG binding, as did further conversion to the corresponding primary alcohols. Eliminating the anionic charge by ethyl esterification, amidation, or reduction also abolished MAG-mediated cell adhesion. These data demonstrate that MAG-ganglioside binding is highly specific and defines key carbohydrate structural determinants for MAG-mediated cell adhesion to gangliosides.

A Systematic Review of Nerve Transfer and Nerve Repair for the Treatment of Adult Upper Brachial Plexus Injury

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.

Entrapment neuropathies I: upper limb (carpal tunnel excluded).

Several entrapment neuropathies of the upper extremity can cause hypoechoic swelling and nerve compression as seen at ultrasound. The ulnar nerve can be compressed at the cubital tunnel of the elbow and Guyons canal at the wrist. The deep branch of the radial nerve can be compressed at the supinator muscle at the elbow, and the superficial radial nerve may be compressed at the dorsal wrist (Wartenbergs syndrome). In addition to compression at the carpal tunnel, the median nerve may be compressed at the elbow, related to a supracondylar process or by the pronator teres. Knowledge of these key anatomical sites of potential nerve compression is essential for accurate diagnosis of entrapment neuropathies.

Diaphragmatic Paralysis Associated With Neonatal Brachial Plexus Palsy

Phrenic nerve palsy can occur in the context of neonatal brachial plexus palsy, yet neither outcomes nor definitive treatment guidelines have been established. Diaphragmatic paralysis alone in the newborn results in significant respiratory sequelae and failure to thrive. Reviewing the available literature revealed little information about the incidence of phrenic nerve palsy associated with neonatal brachial plexus palsy, or whether outcomes are associated with the severity of the brachial plexus palsy. Of patients with brachial plexus palsy evaluated during 2005-2009 (n = 166) at our institution, a minority (2.4%; n = 4) had clinically significant diaphragmatic palsy. Of these, a majority (75%; n = 3) manifested respiratory complications sufficient to warrant diaphragmatic plication. The severity of brachial plexus palsy failed to correlate with severity of respiratory consequences. None of the patients underwent nerve repair or reconstruction. We suggest that diaphragmatic paralysis should not be overlooked during a brachial plexus examination, and diaphragmatic paralysis in the very young may require aggressive intervention before the treatment of brachial plexus palsy.

An outcome study for ulnar neuropathy at the elbow: A multicenter study by the surgery for ulnar nerve (SUN) study group

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.

Longitudinal performance of a surgically implanted neuroprosthesis for lower-extremity exercise, standing, and transfers after spinal cord injury.

OBJECTIVE To investigate the longitudinal performance of a surgically implanted neuroprosthesis for lower-extremity exercise, standing, and transfers after spinal cord injury. DESIGN Case series. SETTING Research or outpatient physical therapy departments of 4 academic hospitals. PARTICIPANTS Subjects (N=15) with thoracic or low cervical level spinal cord injuries who had received the 8-channel neuroprosthesis for exercise and standing. INTERVENTION After completing rehabilitation with the device, the subjects were discharged to unrestricted home use of the system. A series of assessments were performed before discharge and at a follow-up appointment approximately 1 year later. MAIN OUTCOME MEASURES Neuroprosthesis usage, maximum standing time, body weight support, knee strength, knee fatigue index, electrode stability, and component survivability. RESULTS Levels of maximum standing time, body weight support, knee strength, and knee fatigue index were not statistically different from discharge to follow-up (P>.05). Additionally, neuroprosthesis usage was consistent with subjects choosing to use the system on approximately half of the days during each monitoring period. Although the number of hours using the neuroprosthesis remained constant, subjects shifted their usage to more functional standing versus more maintenance exercise, suggesting that the subjects incorporated the neuroprosthesis into their lives. Safety and reliability of the system were demonstrated by electrode stability and a high component survivability rate (>90%). CONCLUSIONS This group of 15 subjects is the largest cohort of implanted lower-extremity neuroprosthetic exercise and standing system users. The safety and efficiency data from this group, and acceptance of the neuroprosthesis as demonstrated by continued usage, indicate that future efforts toward commercialization of a similar device may be warranted.

Severe Obstetric Brachial Plexus Palsies Can Be Identified at One Month of Age

Objective To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age. Methods 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. Results 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). Interpretation 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.

Axon regeneration inhibitors

Abstract Objective: To increase awareness of the advancements in nerve regeneration. Methods: Review of the literature regarding inhibitors of nerve outgrowth and presentation of potential agents that reverse the inhibition, thereby promoting nerve regeneration. Results: The injured adult central nervous system (CNS) inhibits axon outgrowth, thereby limiting recovery from traumatic injury. Axon regeneration inhibitors (ARIs) that contribute to inhibition of recovery include myelin-associated glycoprotein, Nogo, oligodendrocyte-myelin glycoprotein and chondroitin sulfate proteoglycans. The ARIs bind to specific receptors on the axon growth cone to halt outgrowth; consequently, reversing or blocking the actions of ARIs may promote recovery after CNS injury. Sialidase, an enzyme that cleaves one class of axonal receptors for myelin-associated 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. Conclusion: Repair using peripheral nerve grafts is a promising restorative surgical treatment in humans, although functional improvement remains limited. Molecular therapies targeting ARIs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.

Utility of electrodiagnostic testing and computed tomography myelography in the preoperative evaluation of neonatal brachial plexus palsy

OBJECT The rate of neonatal brachial plexus palsy (NBPP) remains 0.4%-4% despite improvements in perinatal care. Among affected children, the extent of brachial plexus palsy differs greatly, as does the prognosis. Controversial elements in management include indications and timing of nerve repair as well as type of reconstruction in patients in whom function will ultimately not be recovered without surgical intervention. Differentiating preganglionic (avulsion) from postganglionic (rupture) lesions is critical because preganglionic lesions cannot spontaneously recover motor function. Distinguishing between these lesions at initial presentation based on clinical examination alone can be difficult in infants. The purpose of the present study was to determine the sensitivity of preoperative electrodiagnostic studies (EDSs) and CT myelography (CTM) in determining the presence of nerve root rupture and avulsions in infants with NBPP. METHODS After receiving institutional review board approval, the authors conducted a retrospective review of patients referred to the Neonatal Brachial Plexus Program between 2007 and 2010. Inclusion criteria included children who underwent brachial plexus exploration following preoperative EDSs and CTM. The CTM scans were interpreted by a staff neuroradiologist, EDSs were conducted by a single physiatrist, and intraoperative findings were recorded by the operating neurosurgeon. The findings from the preoperative EDSs and CTM were then compared with intraoperative findings. The sensitivities and 95% confidence intervals were determined to evaluate performance accuracy of each preoperative measure. RESULTS Twenty-one patients (8 male amd 13 female) met inclusion criteria for this study. The sensitivity of EDSs and CTM for detecting a postganglionic rupture was 92.8% (CI 0.841-0.969) and 58.3% (CI 0.420-0.729), respectively. The sensitivity for EDSs and CTM for preganglionic nerve root avulsion was 27.8% (CI 0.125-0.509) and 72.2% (CI 0.491-0.875), respectively. In cases in which both CTM and EDSs gave concordant results, the sensitivity for both modalities combined was 50.0% (CI 0.237-0.763) for avulsion and 80.8% (CI 0.621-0.915) for rupture. Overall, EDSs were most useful in identifying ruptures, particularly in the upper plexus, whereas CTM was most sensitive in identifying avulsions in the lower plexus. CONCLUSIONS Knowledge of the spinal nerve integrity is critical for early management of patients with NBPP. Surgical management, in the form of nerve repair/reconstruction, and optimal prognostication of NBPP depend on the accurate diagnosis of the level and type of lesion. Both EDSs and CTM scans must always be interpreted in the context of a comprehensive evaluation of the patient. They provide supplemental information (in addition to the physical examination) for early detection of nerve root rupture and avulsion injuries, aiding surgical decision making and preoperative planning for NBPP. Continued advances in imaging, EDSs, and microsurgical nerve repair techniques will allow surgeons to achieve greater success for functional recovery in management of NBPP.

High-Resolution MRI Evaluation of Neonatal Brachial Plexus Palsy: A Promising Alternative to Traditional CT Myelography

BACKGROUND AND PURPOSE: Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy remains relatively common. CT myelography is currently considered to be the optimal imaging technique for evaluating nerve root integrity. Recent improvements in MR imaging techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries). We aim to demonstrate utility of MR imaging in the evaluation of normal and avulsed spinal nerve roots. MATERIALS AND METHODS: All study patients with clinically diagnosed neonatal brachial plexus palsy underwent MR imaging by use of a high-resolution, heavily T2-weighted (driven equilibrium) sequence. MR imaging findings were reviewed for presence of nerve root avulsion from C5–T1 and for presence of pseudomeningocele. The intraoperative findings were reviewed and compared with the preoperative MR imaging findings. RESULTS: Thirteen patients (9 male, 4 female) underwent MR imaging; 6 patients underwent nerve reconstruction surgery, during which a total of 19 nerve roots were evaluated. Eight avulsions were noted at surgery and in the remainder, the nerve injury was more distal (rupture/postganglionic injury). Six of the 8 nerve root avulsions identified at surgery were at C5–6 level, whereas 1 nerve root avulsion was identified at C7 and C8 levels, respectively. The overall sensitivity and specificity of MR imaging for nerve root avulsions was 75% and 82%, respectively. CONCLUSIONS: Our preliminary results demonstrate that high-resolution MR imaging offers an excellent alternative to CT myelography for the evaluation of neonatal brachial plexus palsy with similar sensitivity compared with CT myelography.