Root Avulsion Research Articles

The effect of Puerarin on GAP -43 protein and NGF protein expression of spinal motoneurons following brachial roots avulsion

Objective To study the effects of Puerarin (Pue) on survival rate, expression of GAP-43 and NGF in spinal motoneurons following brachial roots avulsion. Methods From March, 2014 to December, 2015, 192 adult Sprague Dawley rats were divided into four groups: Avulsion, Pue 50 treatment, Pue 100 and Pue 200 groups. The right C5-C7 nerve roots were avulsed through the methods of cervical dorsal approach. Puerarin or normal saline was given immediatedly once daily to the rats respectively by the intraperitoneal injection. The rats were killed at 1, 2, 4 and 6 weeks after injury. The paraffin sections of C7 segment were stained with neutral red. Expression of GAP-43 and NGF were detected by Western blot . Results Compared to the avuled group, the motoneuron survival rates of Pue 100 and Pue 200 dose treatment groups increased on the second week and the sixth week (P < 0.05 or P < 0.01) , and the Pue 200 dose treatment group increased on the fourth week (P < 0.01) . In the anterior horn of all three groups, expression of GAP-43 increased from the 1st week to the 6 week after the operation, and reached the peak at the 4th week, and decreased at the 6th week. Compared to the avuled group, expression of GAP-43 protein increased in the Pue 100 and Pue 200 dose treatment groups at the 1st week and 2nd week, the expression of NGF protein increased in the three Pue treatment groups at four time points (P < 0.05 or P < 0.01) . Conclusion Puerarin can improve the survival rates of spinal motoneurons after the brachial plexus root avulsion, and the expression of GAP-43 and NGF increased, suggesting that Puerarin may play an role in the repair of brachial plexus avulsions by promoting the ex- pression of nerve growth factors. Key words: Puerarin; Brachial plexus injury; Motor neuron; Growth associated protein-43; Nerve growth factor

MiR-137–3p rescue motoneuron death by targeting calpain-2

Brachial plexus root avulsion (BPRA) is a type of injury that leads to motor function loss as a result of motoneurons (MNs) degeneration. Here we identified that the reduced expression of rat miR-137–3p in the ventral horn of spinal cord was associated with MNs death. However, the pathophysiological role of miR-137–3p in root avulsion remains poorly understood. We demonstrated that the calcium-activated neutral protease-2 (calpain-2) was a direct target gene of miR-137–3p with miR-137–3p binding to the 3′-untranslated region of calpain-2. Silencing of calpain-2 suppressed the expression of neuronal nitric oxide synthase (nNOS), a primary source of nitric oxide (NO). After avulsion 2 weeks, up-regulation of miR-137–3p in the spinal cord reduced calpain-2 levels and nNOS expression inside spinal MNs, resulting in an amelioration of the MNs death. These events provide new insight into the mechanism by which upregulation of miR-137–3p can impair MN survival in the BPRA.

Combination Treatment With Exogenous GDNF and Fetal Spinal Cord Cells Results in Better Motoneuron Survival and Functional Recovery After Avulsion Injury With Delayed Root Reimplantation.

When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation. Application of exogenous GDNF to injured spinal cord greatly prevented the motoneuron death and enhanced the regeneration and axonal sprouting, whereas no effect was seen on the functional recovery. In contrast, cell transplantation into the distal nerve did not affect the host motoneurons but instead mitigated the muscle atrophy. The combination of GDNF and cell graft reunited the positive effects resulting in better functional recovery and could therefore be considered as a promising strategy for nerve and spinal cord injuries that involve the avulsion of spinal roots.

Retropharyngeal Contralateral C7 Nerve Transfer to the Lower Trunk for Brachial Plexus Birth Injury: Technique and Results.

Brachial plexus birth injuries with multiple nerve root avulsions present a particularly difficult reconstructive challenge because of the limited availability of donor nerves. The contralateral C7 has been described for brachial plexus reconstruction in adults but has not been well-studied in the pediatric population. We present our technique and results for retropharyngeal contralateral C7 nerve transfer to the lower trunk for brachial plexus birth injury. We performed a retrospective review. Any child aged less than 2 years was included. Charts were analyzed for patient demographic data, operative variables, functional outcomes, complications, and length of follow-up. We had a total of 5 patients. Average nerve graft length was 3 cm. All patients had return of hand sensation to the ulnar nerve distribution as evidenced by a pinch test, unprompted use of the recipient limb without mirror movement, and an Active Movement Scale (AMS) of at least 2/7 for finger and thumb flexion; one patient had an AMS of 7/7 for finger and thumb flexion. Only one patient had return of ulnar intrinsic hand function with an AMS of 3/7. Two patients had temporary triceps weakness in the donor limb and one had clinically insignificant temporary phrenic nerve paresis. No complications were related to the retropharyngeal nerve dissection in any patient. Average follow-up was 3.3 years. The retropharyngeal contralateral C7 nerve transfer is a safe way to supply extra axons to the severely injured arm in brachial plexus birth injuries with no permanent donor limb deficits. Early functional recovery in these patients, with regard to hand function and sensation, is promising. Therapeutic V.

Sustained reversal of central neuropathic pain induced by a single intrathecal injection of adenosine A2A receptor agonists

Central neuropathic pain is a debilitating outcome of spinal cord injury (SCI) and current treatments to alleviate this pain condition are ineffective. A growing body of literature suggests that activating adenosine A2A receptors (A2ARs) decreases the production of proinflammatory cytokines and increases the production of anti-inflammatory cytokines. Here, the effect of administering intrathecal A2AR agonists on central neuropathic pain was measured using hindpaw mechanical allodynia in a rat model of SCI termed spinal neuropathic avulsion pain (SNAP). Other models of SCI cause extensive damage to the spinal cord, resulting in paralysis and health problems. SNAP rats with unilateral low thoracic (T13)/high lumbar (L1) dorsal root avulsion develop below-level bilateral allodynia, without concomitant motor or health problems. A single intrathecal injection of the A2AR agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamido adenosine HCl (CGS21680) reversed SCI-induced allodynia for at least 6 weeks. The reversal is likely in part mediated by interleukin (IL)-10, as intrathecally administering neutralizing IL-10 antibodies 1 week after CGS21680 abolished the anti-allodynic effect of CGS21680. Dorsal spinal cord tissue from the ipsilateral site of SCI (T13/L1) was assayed 1 and 6 weeks after CGS21680 for IL-10, CD11b, and tumor necrosis factor (TNF) gene expression. CGS21680 treatment did not change IL-10 gene expression but did significantly decrease CD11b and TNF gene expression at both timepoints. A second A2AR agonist, 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313), was also able to significantly prevent and reverse SCI-induced allodynia for several weeks after a single intrathecal injection, providing converging lines of evidence of A2AR involvement. The enduring pain reversal after a single intrathecal injection of A2AR agonists suggests that A2AR agonists could be exciting new candidates for treating SCI-induced central neuropathic pain.

Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

Early nerve repair in traumatic brachial plexus injuries in adults: treatment algorithm and first experiences.

The object of this study was to assess the advantages and disadvantages of early nerve repair within 2 weeks following adult traumatic brachial plexus injury (ATBPI). From 2009 onwards, the authors have strived to repair as early as possible extended C-5 to C-8 or T-1 lesions or complete loss of C-5 to C-6 or C-7 function in patients in whom there was clinical and radiological suspicion of root avulsion. Among a group of 36 patients surgically treated in the period between 2009 and 2011, surgical findings in those who had undergone treatment within 2 weeks after trauma were retrospectively compared with results in those who had undergone delayed treatment. The result of biceps muscle reanimation was the primary outcome measure. Five of the 36 patients were referred within 2 weeks after trauma and were eligible for early surgery. Nerve ruptures and/or avulsions were found in all early cases of surgery. The advantages of early surgery are as follows: no scar formation, easy anatomical identification, and gap length reduction. Disadvantages include less-clear demarcation of vital nerve tissue and unfamiliarity with the interpretation of frozen-section examination findings. All 5 early-treatment patients recovered a biceps force rated Medical Research Council grade 4. Preliminary results of nerve repair within 2 weeks of ATBPI are encouraging, and the benefits outweigh the drawbacks. The authors propose a decision algorithm to select patients eligible for early surgery. Referral standards for patients with ATBPI must be adapted to enable early surgery.

Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer.

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function (including neuron differentiation and development, axonogenesis, and guidance), microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light (NFL) and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteomic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer.

Novel Model of Somatosensory Nerve Transfer in the Rat.

Nerve transfer (neurotization) is a reconstructive procedure in which the distal denervated nerve is joined with a proximal healthy nerve of a less significant function. Neurotization models described to date are limited to avulsed roots or pure motor nerve transfers, neglecting the clinically significant mixed nerve transfer. Our aim was to determine whether femoral-to-sciatic nerve transfer could be a feasible model of mixed nerve transfer. Three Sprague Dawley rats were subjected to unilateral femoral-to-sciatic nerve transfer. After 50days, functional recovery was evaluated with a prick test. At the same time, axonal tracers were injected into each sciatic nerve distally to the lesion site, to determine nerve fibers' regeneration. In the prick test, the rats retracted their hind limbs after stimulation, although the reaction was moderately weaker on the operated side. Seven days after injection of axonal tracers, dyes were visualized by confocal microscopy in the spinal cord. Innervation of the recipient nerve originated from higher segments of the spinal cord than that on the untreated side. The results imply that the femoral nerve axons, ingrown into the damaged sciatic nerve, reinnervate distal targets with a functional outcome.

Contralateral C7 Nerve Root Transfer for Function Recovery in Adults: A Meta-analysis.

Background:Root avulsion to all 5 roots of the brachial plexus is a common presentation and keeps a major reconstructive challenge. The contralateral C7 (CC7) nerve transfer has been used in treating brachial plexus avulsion injury (BPAI) since 1986. However, the effectiveness of the procedure remains a subject of controversy. The aim of this meta-analysis was to study surgical outcomes regarding motor and sensory recovery after CC7 nerve transfer.Methods:Chinese or English (i.e., “contralateral c-7”, “contralateral c7”, “c7 nerve root”, and “seventh cervical nerve root”) keywords were used for a literature search for articles related to CC7 nerve transfer in several databases (i.e., PubMed, Cochrane, Embase, CNKI, CQVIP, and Wanfang Data). Clinical research articles were screened, and animal studies as well as duplicate publications were excluded. Muscle strength and sensory recovery were considered to be effective only when the scores on the United Kingdom Medical Research Council scale were equal to or higher than M3 and S3, respectively.Results:The overall ipsilateral recipient nerve recovery rates were as follows: the efficiency rate for muscle strength recovery after CC7 nerve transfer was 0.57 (95% confidence interval [CI]: 0.48–0.66) and for sensory recovery was 0.52 (95% CI: 0.46–0.58). When the recipient nerve was the median nerve, the efficiency rate for muscle strength recovery was 0.50 (95% CI: 0.39–0.61) and for sensory was 0.56 (95% CI: 0.50–0.63). When the recipient nerve was the musculocutaneous nerve and the radial nerve, the efficiency rate for muscle strength recovery was 0.74 (95% CI: 0.65–0.82) and 0.50 (95% CI: 0.31–0.70), respectively.Conclusions:Transfer of CC7 nerves to musculocutaneous nerves leads to the best results. CC7 is a reliable donor nerve, which can be safely used for upper limb function reconstruction, especially for entirely BPAI. When modifying procedures, musculocutaneous nerves and median nerve can be combined as recipient nerves.

A novel rat model of brachial plexus injury with nerve root stumps

BackgroundThe C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and thus can be used as donors for nerve grafting. To date, there are no appropriate animal models to evaluate spared nerve root stumps. Hence, the aim of this study was to establish and evaluate a rat model with spared nerve root stumps in BPI. New methodIn rupture group, the proximal parts of C5-T1 nerve roots were held with the surrounding muscles and the distal parts were pulled by a sudden force after the brachial plexus was fully exposed, and the results were compared with those of sham group. To validate the model, the lengths of C5-T1 spared nerve root stumps were measured and the histologies of the shortest one and the corresponding spinal cord were evaluated. ResultsC5 nerve root stump was found to be the shortest. Histology findings demonstrated that the nerve fibers became more irregular and the continuity decreased; numbers and diameters of myelinated axons and thickness of myelin sheaths significantly decreased over time. The survival of motoneurons was reduced, and the death of motoneurons may be related to the apoptotic process. Comparison with existing method(s)Our model could successfully create BPI model with nerve root stumps by traction, which could simulate injury mechanisms. While other models involve root avulsion or rupturing by distal nerve transection. ConclusionsThis model would be suitable for evaluating nerve root stumps and testing new therapeutic strategies for neuroprotection through nerve root stumps in the future.

Nerve transfer to relieve pain in upper brachial plexus injuries: Does it work?

ObjectivesPatients with C5 and C6 nerve root avulsion may complain from pain. For these patients, end-to-side nerve transfer of the superficial radial nerve into the median nerve is suggested to relieve pain. Patients and MethodsEleven patients (with a primary brachial plexus reconstruction) undergoing end-to-side nerve transfer of the superficial radial nerve into the ulnovolar part of the median nerve were assessed. Pain before surgery was compared to that at 6-month follow-up using visual analog scale (VAS) scores. ResultsA significant difference was seen between the mean VAS before (8.5) and after surgery (0.7) (P=0.0). After the six-month follow-up, 6 patients felt no pain according to VAS, notwithstanding 5 patients with a mild pain. ConclusionThe evidence from the present study suggests that end-to-side nerve transfer of the superficial radial nerve into the ulnovolar part of the median nerve is an effective technique in reducing pain in patients with C5 and C6 nerve root avulsion.

Efficacy and factors determining the outcome of dorsal root entry zone lesioning procedure (DREZotomy) in the treatment of intractable pain syndrome.

Chronic pain is a disabling condition that adversely affects patient quality of life. The dorsal root entry zone lesioning procedure (DREZotomy) is a modality used to treat intractable pain caused by insults to neural structures. This study aimed to investigate the efficacy of and the factors that determine the outcome of microsurgical DREZotomy (MDT). All consecutive patients who underwent MDT for treatment of intractable pain during September 2008 to December 2016 were enrolled. Demographic data, clinical characteristics, intraoperative findings, and postoperative outcomes were analyzed. The 40 included patients underwent MDT for relief of intractable pain caused by 27 brachial plexus injuries (BPIs), 6 spinal cord injuries, 3 neoplasms, and 4 other causes. A significant reduction in pain was observed post-MDT for both average (p<0.001) and maximal pain (p<0.001). Favorable outcome (≥50% pain reduction) was observed in 67.5% of patients, with the best outcome in BPI-related pain. In multivariate analysis, injury of the spinal nerve root (root avulsion or injury) was significantly associated with good average pain relief (OR, 5.8; 95% CI, 1.2-27.5; p=0.026) and pain freedom (OR, 5.0; 95% CI, 1.12-22.30; p=0.035). Electrical pain (OR, 6.49; 95% CI, 1.20-35.19; p=0.030) and lower number of painful dermatomes (OR, 1.30; 95% CI, 1.01-1.67; p=0.039) were significantly associated with good maximal pain relief. MDT is an effective procedure for treatment of intractable pain in well-selected patients, particularly in cases with brachial plexus avulsion pain. Injury of the spinal nerve root (brachial plexus avulsion and cauda equina injury) was associated with good average pain relief and pain freedom, and electrical pain and lower number of painful dermatomes were associated with good maximal pain relief. The results are useful in the selection of candidates for DREZotomy and prediction of surgical outcome.

Super-selective cervical nerve root stimulation in contralateral C7 transfer: An intraoperative study

ObjectiveWe designed this study using super-selective intraoperative cervical nerve root stimulation aiming to support decision making about complete or partial contralateral C7 (cC7) nerve root transfer in patients with multiple cervical root avulsion injury. MethodsSuper-selective intraoperative stimulations of anterior, lateral, medial and posterior aspect of C5–C8 nerve roots were performed. Compound muscle action potentials (CMAP) were recorded in the lateral part of the deltoid (DM), long head of biceps brachii (BCM), brachioradial (BRM), long head of triceps brachii (TCM), and extensor digitorum communis (EDC) muscle. Muscle strength was documented immediately after cC7 transfer procedures and on scheduled follow-up visits according to the Medical Research Council (MRC) scale. ResultsIn the DM, stimulation of the posterior aspect of C5 resulted in the largest CMAP amplitudes (2.0 mV ± 1.9; 80% ± 28.3). The BCM CMAPs induced by the different aspects of C6 all revealed homogenous stimulation results. Stimulation of the lateral aspect of C7 induced the largest amplitude of TCM CMAPs (1.3 mV ± 1.0; 67.1% ± 43.3). CMAP amplitudes of individual muscles and individual contributions of cervical nerve roots to the TCM varied between subjects. Overall donor side morbidity was low, no permanent motor deficit occurred. ConclusionA super-selective intraoperative cervical nerve root stimulation may help minimize donor side morbidity in transfer procedures. Individual differences of cervical nerve root innervation pattern need to be addressed in future electrophysiological studies. SignificanceOur study outlines individual differences of cervical nerve root innervation pattern.

Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation

The “gold standard” treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

The diagnostic accuracy of 1.5T magnetic resonance imaging for detecting root avulsions in traumatic adult brachial plexus injuries.

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S109 Magnetoencephalographic-based brain–machine interface robotic hand for controlling sensorimotor cortical plasticity and phantom limb pain

Objectives Phantom limb pain is neuropathic pain after amputation of a limb and partial or complete deafferentation such as brachial plexus root avulsion. The underlying cause of this pain has been attributed to maladaptive plasticity of the sensorimotor cortex. It has been suggested that experimental reorganization would affect pain, especially if it results in functional restoration. We tested the hypothesis that restoration of hand motor function using a brain–machine interface (BMI) based on magnetoencephalographic (MEG) signals will normalize maladapted cortical representation and relieve pain. Methods This study included 10 phantom limb patients (9 brachial plexus root avulsion and 1 amputee). MEG signals during movements of the phantom hand or intact hand were used to train the decoder inferring movements of each hand. The robotic hand was controlled by the decoder. Patients controlled the robotic hand by moving the phantom hand. The training effects were compared among trainings with the phantom decoder, real hand decoder, and random decoder in a randomized cross-over trial. Results BMI training with the phantom decoder increased the decoding accuracy of phantom hand movements and pain. In contrast, BMI training with the intact hand decoder reduced accuracy and pain. Discussion It was suggested that BMI training to modulate the motor representation of phantom hand controlled pain. The sensorimotor cortical plasticity might induce pain. Conclusions and Significance Phantom limb pain was controlled by BMI training to induce sensorimotor cortical plasticity.

Leptin is essential for microglial activation and neuropathic pain after preganglionic cervical root avulsion

AimsPreganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown. Main methodsPreganglionic avulsion of the left 6th–8th cervical roots was performed in C57B/6J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal and supraspinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity. Key findingsLeptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis in the dorsal horn and brainstem. Furthermore, increase in the expression of CD86 and iNOS, and Wallerian degeneration were noted in the spinal cord. The administration of exogenous leptin to leptin-deficient mice reversed these effects. SignificanceWe concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.

Plasticity of Select Primary Afferent Projections to the Dorsal Horn after a Lumbosacral Ventral Root Avulsion Injury and Root Replantation in Rats.

Injuries to the conus medullaris and cauda equina portions of the spinal cord result in neurological impairments, including paralysis, autonomic dysfunction, and pain. In experimental studies, earlier investigations have shown that a lumbosacral ventral root avulsion (VRA) injury results in allodynia, which may be ameliorated by surgical replantation of the avulsed ventral roots. Here, we investigated the long-term effects of an L6 + S1 VRA injury on the plasticity of three populations of afferent projections to the dorsal horn in rats. At 8 weeks after a unilateral L6 + S1 VRA injury, quantitative morphological studies of the adjacent L5 dorsal horn showed reduced immunoreactivity (IR) for the vesicular glutamate transporter, VGLUT1 and isolectin B4 (IB4) binding, whereas IR for calcitonin gene-related peptide (CGRP) was unchanged. The IR for VGLUT1 and CGRP as well as IB4 binding was at control levels in the L5 dorsal horn at 8 weeks following an acute surgical replantation of the avulsed L6 + S1 ventral roots. Quantitative morphological studies of the L5 dorsal root ganglia (DRGs) showed unchanged neuronal numbers for both the VRA and replanted series compared to shams. The portions of L5 DRG neurons expressing IR for VGLUT1 and CGRP, and IB4 binding were also the same between the VRA, replanted, and sham-operated groups. We conclude that the L5 dorsal horn shows selective plasticity for VGLUT1 and IB4 primary afferent projections after an L6 + S1 VRA injury and surgical repair.

Contralateral C-7 transfer: is direct repair really superior to grafting?

It is not uncommon for a severe traumatic brachial plexus injury to involve all 5 roots, resulting in a flail upper limb. In such cases, surgical reconstruction is often palliative, providing only rudimentary function. Nerve transfers are the mainstay of reconstructive strategies due to the predominance of root avulsions. Consistent results are obtained only for restoration of shoulder stability and elbow flexion, whereas restoring useful hand function remains a challenge. The transfer of the contralateral C-7 (cC-7) is commonly used in an attempt to restore basic hand function, but results are notoriously unreliable and inconsistent. Shu-feng Wang and colleagues recently proposed a potentially more successful permutation of this procedure. They advocated direct approximation of the cC-7 to the lower trunk on the paralyzed side, thus avoiding the interposition of nerve grafts. This technique involves a lengthy dissection of the cC-7 transfer across the midline via a prespinal route, as well as extensive mobilization of the ipsilateral lower trunk by cutting a subset of its branches, adducting the arm, and (if necessary) shortening the humerus. Each of these steps is indispensable to achieve direct approximation of the nerve ends. Many surgeons have tried to emulate Wang's strategy. However, the technical difficulties involved have forced recourse to interposition of nerve grafts once again. The authors report their observations in the first 22 patients in whom they performed this procedure. Direct cC-7 repair via the prespinal route was performed in 12 patients. Shortening of the humerus was necessary in 9 of these 12 patients. In 10 patients, a direct repair was not feasible and nerve grafting was performed. The median follow-up period was 26 months for the direct coaptation group and 28.5 months for the nerve graft group. In the direct repair group, 10 of the 12 patients regained Medical Research Council Grade 3 flexion of the wrist and of the middle, ring, and little fingers, while the remaining 2 patients had Grade 2 function. Flexion appeared 12-14 months after the operation. At the latest follow-up, these patients could activate the wrist and hand without requiring significant augmentation maneuvers in the donor limb. In contrast, repair requiring interposition grafts resulted in Grade 3 strength in only 2 of 10 patients, while 7 had Grade 2 strength, and 1 experienced failure. In all grafted cases, the patient had to forcibly contract the contralateral pectoralis major and triceps muscles to produce the weak movements on the reconstructed side. In this small series, the authors demonstrated a distinct advantage associated with the avoidance of grafts when transferring the cC-7 to restore hand function. The authors conclude that efforts to achieve direct approximation of the donor C-7 and the recipient lower trunk are necessary and justified.