Shoulder Traction as a Possible Risk Factor for C5 Palsy in Anterior Cervical Surgery: A Cadaveric Study.

Background and Objectives: Many risk factors for postoperative C5 palsy (PC5P) have been reported regarding a "cord shift" after a posterior approach. However, there are few reports about shoulder traction as a possible risk factor of anterior cervical surgery. Therefore, we assessed the stretched nerve roots when shoulder traction was applied on cadavers. Materials and Methods: Eight cadavers were employed in this study, available based on age and the presence of foramen stenosis. After dissecting the sternocleidomastoid muscle of the cadaver, the shoulder joint was pulled with a force of 2, 5, 8, 10, 15, and 20 kg. Then, the stretched length of the fifth nerve root was measured in the extra-foraminal zone. In addition, the same measurement was performed after cutting the carotid artery to accurately identify the nerve root's origin. After an additional dissection was performed so that the superior trunk of the brachial plexus could be seen, the stretched length of the fifth and sixth nerve roots was measured again. Results: Throughout the entire experiment, the fifth nerve root stretched out for an average of 1.94 mm at 8 kg and an average of 5.03 mm at a maximum force of 20 kg. In three experiments, the elongated lengths of the C5 nerve root at 8 kg and 20 kg were 1.69/4.38 mm, 2.13/5.00 mm, and 0.75/5.31 mm, respectively, and in the third experiment, the elongated length of the C6 nerve root was 1.88/5.44 mm. Conclusions: Although this was a cadaveric experiment, it suggests that shoulder traction could be the risk factors for PC5P after anterior cervical surgery. In addition, for patients with foraminal stenosis and central stenosis, the risk would be higher. Therefore, the surgeon should be aware of this, and the patient would need sufficient explanation.

The prerequisites and clinical outcomes of ipsilateral C7 nerve root transfer to the upper trunk for adult C5-C6 brachial plexus injuries.

PURPOSE: Although ipsilateral C7 nerve transfer is used for the treatment of C5-C6 brachial plexus injuries, accurately evaluating the functional quality of the donor nerve (ipsilateral C7 nerve root) is difficult, especially when the C7 nerve root is slightly injured. The purpose of this study was to determine the indicators to evaluate the quality of the ipsilateral C7 nerve and assess the clinical outcomes of this procedure. METHODS: This study employed the following three indicators to assess the quality of the ipsilateral C7 nerve: (1) the muscle strength and electrophysiological status of the latissimus dorsi, triceps brachii, and extensor digitorum communis; (2) the sensibility of the radial three digits, especially the index finger; and (3) the intraoperative appearance, feel and electrophysiological status of the ipsilateral C7 nerve root. Transfer of the ipsilateral C7 nerve root to the upper trunk was implemented only when the following three tests were conducted, the criteria were met, and the clinical outcomes were assessed in eight patients with C5-C6 brachial plexus injuries. RESULTS: Patients were followed-up for an average of 90 ± 42 months. At the final follow-up, all eight patients achieved recovery of elbow flexion, with five and three patients scoring M4 and M3, respectively, according to the Medical Research Council scoring. The shoulder abduction range of motor recovery averaged 86 ± 47° (range, 30°-170°), whereas the shoulder external rotation averaged 51 ± 26° (range, 15°-90°). CONCLUSION: Ipsilateral C7 nerve transfer is a reliable and effective option for the functional reconstruction of the shoulder and elbow after C5-C6 brachial plexus injuries when the three prerequisites are met.

How to Prevent Nerve Root Injury in Uniportal Full Endoscopic Lumbar Fusion Surgery? Insights From a Cadaveric Anatomic Study With Simulation Surgery.

STUDY DESIGN: The study included 2 fresh-frozen cadavers. OBJECTIVE: To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and full endoscopic facet-resecting (FE fr-TLIF) transforaminal lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots. BACKGROUND: Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery, with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures. PATIENTS AND METHODS: Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Postoperation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined. RESULTS: In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared with FE fs-TLIF (3.30 ± 1.35 vs . 8.58 ± 2.47 mm, respectively; P < 0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared with FE fr-TLIF (3.73 ± 1.97 vs . 6.90 ± 1.36 mm, respectively; P < 0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a 2-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended. CONCLUSION: This study elucidates the anatomic relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques. LEVEL OF EVIDENCE: Level V.

Dorsal root entry zone lesioning for brachial plexus avulsion - technical evolution and long-term follow-up.

BACKGROUND: Brachial plexus avulsion (BPA) injuries can cause severe deafferentation pain. This has been successfully treated with dorsal root entry zone (DREZ) lesioning. Distortions in anatomy following a BPA injury can make identifying neural structures challenging. We describe a modification to the operative technique that improves the surgical view and the advanced intraoperative neuromonitoring (IONM) employed to identify DREZ. We have analysed the long-term outcomes for pain, quality of life, and complications in patients undergoing DREZ lesioning. METHODS: This is a single-centre retrospective case series including patients who underwent DREZ lesioning with IONM for brachial plexus avulsion between 2012 and 2022. Analysed data included pre- and postoperative pain (VAS), quality of life score for chronic pain, and complications. The evolution of the surgical approach is discussed. RESULTS: 44 consecutive patients underwent a DREZ lesioning procedure with intraoperative monitoring and mapping. In these patients the mean VAS score improved from 8.9 (7-10) to 1.87 (0-6) (p < 0.0001) at the time of discharge. 31 patients were followed-up for more than 12 months with a mean duration of follow-up of 41 months and their results were as follows: the mean VAS improved from 9.0 (7-10) to 4.1 (0-9) (p < 0.0001) at the last follow-up and the mean QOL values improved from 3.7 (2-6) to 7.4 (4-10) (p < 0.0001). The long-term outcomes were 'good' in 39%, 'fair' in 29% and 'poor' in 32% of patients. 55% of the patients were able to stop or reduce pain medications. CONCLUSIONS: Modifications of surgical technique provide better exposure of DREZ, and IONM aids in identifying DREZ in the presence of severe intra-dural changes. Long-term outcomes of DREZ lesioning indicate not only a reduction in pain but also a significant improvement in quality of life.

Anatomical damages in the spinal nerve roots and the spinal cord after brachial plexus injury: descriptive study from a cohort of consecutive patients who underwent DREZ-lesioning for pain-practical implications.

BACKGROUND: Systematic descriptions of anatomical damage after brachial plexus injury (BPI) at the intradural level have been scarcely reported in detail. However, considering these damages, not only in the spinal nerve roots but also in the spinal cord itself, is crucial in determining the appropriate surgical approach to restore upper limb function and address refractory pain. Therefore, the authors present a descriptive study focusing on intradural findings observed during microsurgical DREZ-lesioning. METHODS: This study enrolled 19 consecutive patients under the same protocol. Microsurgical observation through exposure of C4 to Th1 medullary segments allowed to describe the lesions in spinal nerve roots, meninges, and spinal cord. Electrical stimulation of the ventral roots checked the muscle responses. RESULTS: Extensive damage was observed among the 114 explored roots (six roots per patient), with only 21 (18.4%) ventral (VR) and 17 (14.9%) dorsal (DR) roots retaining all rootlets intact. Damage distribution varied, with the most frequent impairments in C6 VRs (18 patients) and the least in Th1 VRs (14 patients), while in all the 19 patients for the C6 DRs (the most frequently impaired) and in 14 patients for Th1 DRs (the less impaired). C4 roots were found damaged in 12 patients. Total or partial avulsions affected 63.3% and 69.8% of DRs and VRs, respectively, while 15.8% and 14.0% of the 114 DRs and VRs were atrophic, maintaining muscle responses to stimulation in half of those VRs. Pseudomeningoceles were present in 11 patients but absent in 46% of avulsed roots. Adhesive arachnoiditis was noted in 12 patients, and dorsal horn parenchymal alterations in 10. CONCLUSIONS: Knowledge of intradural lesions post-BPI helps in guiding surgical indications for repair and functional neurosurgery for pain control.

Boundary cap neural crest stem cells promote angiogenesis after transplantation to avulsed dorsal roots in mice and induce migration of endothelial cells in 3D printed scaffolds.

Dorsal root avulsion injuries lead to loss of sensation and to reorganization of blood vessels (BVs) in the injured area. The inability of injured sensory axons to re-enter the spinal cord results in permanent loss of sensation, and often also leads to the development of neuropathic pain. Approaches that restore connection between peripheral sensory axons and their CNS targets are thus urgently need. Previous research has shown that sensory axons from peripherally grafted human sensory neurons are able to enter the spinal cord by growing along BVs which penetrate the CNS from the spinal cord surface. In this study we analysed the distribution of BVs after avulsion injury and how their pattern is affected by implantation at the injury site of boundary cap neural crest stem cells (bNCSCs), a transient cluster of cells, which are located at the boundary between the spinal cord and peripheral nervous system and assist the growth of sensory axons from periphery into the spinal cord during development. The superficial dorsal spinal cord vasculature was examined using intravital microscopy and intravascular BV labelling. bNCSC transplantation increased vascular volume in a non-dose responsive manner, whereas dorsal root avulsion alone did not decrease the vascular volume. To determine whether bNCSC are endowed with angiogenic properties we prepared 3D printed scaffolds, containing bNCSCs together with rings prepared from mouse aorta. We show that bNCSC do induce migration and assembly of endothelial cells in this system. These findings suggest that bNCSC transplant can promote vascularization in vivo and contribute to BV formation in 3D printed scaffolds.

Riluzole treatment modulates KCC2 and EAAT-2 receptor expression and Ca2+ accumulation following ventral root avulsion injury.

Avulsion injury results in motoneuron death due to the increased excitotoxicity developing in the affected spinal segments. This study focused on possible short and long term molecular and receptor expression alterations which are thought to be linked to the excitotoxic events in the ventral horn with or without the anti-excitotoxic riluzole treatment. In our experimental model the left lumbar 4 and 5 (L4, 5) ventral roots of the spinal cord were avulsed. Treated animals received riluzole for 2 weeks. Riluzole is a compound that acts to block voltage-activated Na+ and Ca2+ channels. In control animals the L4, 5 ventral roots were avulsed without riluzole treatment. Expression of astrocytic EAAT-2 and that of KCC2 in motoneurons on the affected side of the L4 spinal segment were detected after the injury by confocal and dSTORM imaging, intracellular Ca2+ levels in motoneurons were quantified by electron microscopy. The KCC2 labeling in the lateral and ventrolateral parts of the L4 ventral horn was weaker compared with the medial part of L4 ventral horn in both groups. Riluzole treatment dramatically enhanced motoneuron survival but was not able to prevent the down-regulation of KCC2 expression in injured motoneurons. In contrast, riluzole successfully obviated the increase of intracellular calcium level and the decrease of EAAT-2 expression in astrocytes compared with untreated injured animals. We conclude that KCC2 may not be an essential component for survival of injured motoneurons and riluzole is able to modulate the intracellular level of calcium and expression of EAAT-2.

Is dorsal root entry zone lesioning effective and safe for managing continuous versus paroxysmal pains post-brachial plexus avulsion?

OBJECTIVE: Patients with brachial plexus avulsion (BPA) experience chronic deafferentation pain characterized by two patterns: continuous background pain and electrical shooting paroxysmal attacks. The authors' aim was to report the effectiveness and safety of dorsal root entry zone (DREZ) lesioning in relieving the two forms of pain over short and long periods. METHODS: All patients who underwent DREZ lesioning performed by the senior author for medically refractory BPA-related pain between July 1, 2016, and June 30, 2020, in Johns Hopkins Hospital were followed up. The intensity levels for continuous and paroxysmal pains were evaluated using the numeric rating scale (NRS) preoperatively and at 4 time points postsurgery, including the day of discharge, with a mean hospital stay of 5.6 ± 1.8 days; first postoperative clinic visit (33.0 ± 15.7 days); short-term follow-up (4.0 ± 1.4 months); and long-term follow-up (3.1 ± 1.3 years). The percent of pain relief according to the NRS was categorized into excellent (≥ 75%), fair (25%-74%), and poor (< 25%). RESULTS: A total of 19 patients were included, with 4 (21.1%) lost to long-term follow-up. The mean age was 52.7 ± 13.6 years; 16 (84.2%) were men, and 10 (52.6%) had left-sided injuries. A motor vehicle accident was the most common etiology of BPA (n = 16, 84.2%). Preoperatively, all patients had motor deficits, and 8 (42.1%) experienced somatosensory deficits. The greatest pain relief was observed at the first postoperative and short-term follow-up visits, with the lowest proportions of patients having continuous pain (26.3% and 23.5%, respectively) and paroxysmal pain (5.3% and 5.9%, respectively). Also, the highest reductions in mean NRS scores were observed for first postoperative and short-term follow-up visits (continuous 1.1 ± 2.1 and 1.1 ± 2.3; paroxysms 0.4 ± 1.4 and 0.5 ± 1.7, respectively) compared to the preoperative symptomatology (continuous 6.7 ± 3.0; paroxysms 7.9 ± 4.3) (p < 0.001). Most patients had excellent relief of continuous pain (82.4% and 81.3%) and of paroxysms (90.9% and 90.0%) at the first postoperative visit and short-term follow-up visit, respectively. The pain relief benefits had diminished by 3 years after surgery but remained significantly better than in the preoperative assessment. At the last evaluation, the proportion of patients achieving excellent relief of paroxysmal pain (66.7%) was double that for continuous pain (35.7%) (p < 0.001). New sensory phenomena were observed among 10 patients (52.6%), and 1 patient developed a motor deficit. CONCLUSIONS: DREZ lesioning is an effective and safe option for relieving BPA-associated pain, with good long-term outcomes and better benefits for paroxysmal pain than for the continuous pain component.

Indications and Technique for the Use of Intraoperative Neuromonitoring in Brachial Plexus Surgery.

Confirming the presence or absence of a functioning nerve root in traumatic brachial plexus injuries is vital in the surgical decision-making process. Intraoperative neuromonitoring can confirm intact rootlets with the use of motor evoked potentials and somatosensory evoked potentials. The purpose of this article is to describe the rationale and details of intraoperative neuromonitoring to provide a basic understanding of its role in decision-making in patients with brachial plexus injuries.

Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats.

Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFß) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury.

Neuroprotection and gliosis attenuation by intravenous application of human mesenchymal stem cells (hMSC) following ventral root crush in mice.

Rupture and stretching of spinal roots are common incidents that take place in high-energy accidents. The proximal axotomy of motoneurons by crushing of ventral roots is directly related to the degeneration of half of the lesioned population within the first two weeks. Moreover, only a small percentage of surviving motoneurons can successfully achieve regeneration after such a proximal lesion, and new treatments are necessary to improve this scenario. In this sense, mesenchymal stem cells (MSC) are of great interest once they secrete a broad spectrum of bioactive molecules that are immunomodulatory and can restore the environment after a lesion. The present work aimed at studying the effects of human mesenchymal stem cells (hMSC) therapy after ventral root crush (VRC) in mice. We evaluated motoneuron survival, glial reaction, and synapse preservation at the ventral horn. For this purpose, C57BL/6 J were submitted to a crush procedure of L4 to L6 ventral roots and treated with a single intravenous injection of adipose-derived hMSC. Evaluation of the results was carried out at 7, 14, and 28 days after injury. Analysis of motoneuron survival and astrogliosis showed that hMSC treatment resulted in higher motoneuron preservation (motoneuron survival ipsi/contralateral ratio: VRC group = 53%, VRC + hMSC group = 66%; p < 0.01), combined with reduction of astrogliosis (ipsi/contralateral GFAP immunolabeling: VRC group = 470%, VRC + hMSC group = 250%; p < 0.001). The morphological classification and Sholl analysis of microglial activation revealed that hMSC treatment reduced type V and increased type II profiles, indicating an enhancement of surveying over activated microglial cells. The glial reactivity modulation directly influenced synaptic inputs in apposition to axotomized motoneurons. In the hMSC-treated group, synaptic maintenance was increased (ipsi/contralateral synaptophysin immunolabeling: VRC group = 53%, VRC + hMSC group = 64%; p < 0.05). Overall, the present data show that intravenous injection of hMSC has neuroprotective and anti-inflammatory effects, decreasing reactive astrogliosis, and microglial reaction. Also, such cell therapy results in motoneuron preservation, combined with significant maintenance of spinal cord circuits, in particular those related to the ventral horn.

Peptide ligands targeting FGF receptors promote recovery from dorsal root crush injury via AKT/mTOR signaling.

Background: Fibroblast growth factor receptors (FGFRs) are key targets for nerve regeneration and repair. The therapeutic effect of exogenous recombinant FGFs in vivo is limited due to their high molecular weight. Small peptides with low molecular weight, easy diffusion, low immunogenicity, and nontoxic metabolite formation are potential candidates. The present study aimed to develop a novel low-molecular-weight peptide agonist of FGFR to promote nerve injury repair. Methods: Phage display technology was employed to screen peptide ligands targeting FGFR2. The peptide ligand affinity for FGFRs was detected by isothermal titration calorimetry. Structural biology-based computer virtual analysis was used to characterize the interaction between the peptide ligand and FGFR2. The peptide ligand effect on axon growth, regeneration, and behavioral recovery of sensory neurons was determined in the primary culture of sensory neurons and dorsal root ganglia (DRG) explants in vitro and a rat spinal dorsal root injury (DRI) model in vivo. The peptide ligand binding to other membrane receptors was characterized by surface plasmon resonance (SPR) and liquid chromatography-mass spectrometry (LC-MS)/MS. Intracellular signaling pathways primarily affected by the peptide ligand were characterized by phosphoproteomics, and related pathways were verified using specific inhibitors. Results: We identified a novel FGFR-targeting small peptide, CH02, with seven amino acid residues. CH02 activated FGFR signaling through high-affinity binding with the extracellular segment of FGFRs and also had an affinity for several receptor tyrosine kinase (RTK) family members, including VEGFR2. In sensory neurons cultured in vitro, CH02 maintained the survival of neurons and promoted axon growth. Simultaneously, CH02 robustly enhanced nerve regeneration and sensory-motor behavioral recovery after DRI in rats. CH02-induced activation of FGFR signaling promoted nerve regeneration primarily via AKT and ERK signaling downstream of FGFRs. Activation of mTOR downstream of AKT signaling augmented axon growth potential in response to CH02. Conclusion: Our study revealed the significant therapeutic effect of CH02 on strengthening nerve regeneration and suggested a strategy for treating peripheral and central nervous system injuries.

Dorsal Root Entry Zone Lesioning: Systematic Review

Introduction Dorsal root entry zone (DREZ) leasioning (DREZ-otomy) is considered an effective treatment for chronic pain due to spinal cord injuries, brachial and lumbosacral plexus injuries, postherpetic neuralgia, spasticity, and other conditions. The objective of the technique is to cause a selective destruction of the afferent pain fibers located in the dorsal region of the spinal cord. Objective To identify and review the effectiveness and the main aspects related to DREZ-otomy, as well as the etiologies that can be treated with it. Methods The PubMed, MEDLINE and LILACS databases were used as bases for this systematic review, having the impact factor as the selection criteria. The 23 selected publications, totalizing 1,099 patients, were organized in a table for systematic analysis. Results Satisfactory pain control was observed in 70.1% of the cases, with the best results being found in patients with brachial/lumbosacral plexus injury (70.8%) and the worst, in patients with trigeminal pain (40% to 67%). Discussion Most of the published articles observed excellent results in the control of chronic pain, especially in cases of plexus injuries. Complications are rare, and can be minimized with the use of new technologies for intraoperative monitoring and imaging. Conclusion DREZ-otomy can be considered a great alternative for the treatment of chronic pain, especially in patients who do not tolerate the side effects of the medications used in the clinical management or have refractory pain.

Does the L5 spinal nerve move? Anatomical evaluation with implications for postoperative L5 nerve palsy.

PURPOSE: While palsy of the L5 nerve root due to stretch injury is a known complication in complex lumbosacral spine surgery, the underlying pathophysiology remains unclear. The goal of this cadaveric study was to quantify movement of the L5 nerve root during flexion/extension of the hip and lower lumbar spine. METHODS: Five fresh-frozen human cadavers were dissected on both sides to expose the lumbar vertebral bodies and the L5 nerve roots. Movement of the L5 nerve root was tested during flexion and extension of the hip and lower lumbar spine. Four steps were undertaken to characterize these movements: (1) removal of the bilateral psoas muscles, (2) removal of the lumbar vertebral bodies including the transforaminal ligaments from L3 to L5, (3) opening and removing the dura mater laterally to visualize the rootlets, and (4) removal of remaining soft tissue surrounding the L5 nerve root. Two metal bars were inserted into the sacral body at the level of S1 as fixed landmarks. The tips of these bars were connected to make a line for the ruler that was used to measure movement of the L5 nerve roots. Movement was regarded as measurable when there was an L5 nerve excursion of at least 1 mm. RESULTS: The mean age at death was 86.6 years (range 68-89 years). None of the four steps revealed any measurable movement after flexion/extension of the hip and lower lumbar spine on either side (< 1 mm). Flexion of the hip and lower lumbar spine revealed lax L5 nerve roots. Extension of the hip and lower lumbar spine showed taut ones. CONCLUSION: Significant movement or displacement of the L5 nerve root could not be quantified in this study. No mechanical cause for L5 nerve palsy could be identified so the etiology of the condition remains unclear.

Calving-related intradural avulsion injuries of the thoracolumbar spinal nerve roots in a calf.

Calving difficulty may lead to traumatic peripheral nerve injury. A male, 8-mo-old, Japanese Black calf with a history of secondary dystocia as a result of fetal gigantism had lameness and gait disturbance. At autopsy, multifocal dural thickening with adhesions to the adjacent spinal cord was observed at T12-13 and L4-5 vertebral levels. Microscopically, numerous traumatic neuroma-like fascicles of nerve twigs were embedded in the dura mater with abundant collagenous connective tissue. By immunohistochemistry, axons and Schwann cells were confirmed in each nerve fascicle. Our observations suggest that avulsion injuries in the preganglionic fibers of the spinal nerve roots, and secondary spinal cord compression, resulted in the development of neurologic signs.

Neuroprotection by dimethyl fumarate following ventral root crush in C57BL/6J mice.

CNS lesions usually result in permanent loss of function and are an important problem in the medical field. In order to investigate neuroprotection/degeneration mechanisms and the synaptic plasticity of motoneurons, in addition to the potential for a variety of treatments, different experimental models of axonal injury have been proposed. Recent studies have tested the immunomodulatory drug dimethyl fumarate (DMF) for the treatment of neurodegenerative diseases and have shown promising outcomes. Therefore, in this work, we investigated the effects of DMF with regard to neuroprotection and its influence on the glial response in C57BL/6J animals subjected to crushing of the motor roots in the lumbar intumescence of the spinal cord. The animals were divided into a vehicle-treated injury group (0.08 % methylcellulose solution control group, n = 7) and injured groups treated with DMF at different doses (15, 30, 45, 90 and 180 mg/kg; n = 6-7 per dose). The 90 mg/kg dose showed the best neuroprotective results, so it was used for treatment over a period of eight weeks. Neuronal survival was assessed through Nissl staining, and functional recovery was evaluated with the CatWalk system (walking track test) and the von Frey test (mechanoreception). Immunohistochemistry was used to assess synaptic coverage and astroglial and microglial reactivity using the primary antibodies anti-synaptophysin (pre-synaptic terminal pan marker), GAD65 (GABAergic pre-synaptic terminations - inhibitory), and VGLUT1 (glutamatergic pre-synaptic terminations - excitatory). Glial reactions were evaluated with anti-IBA1 (microglia) and GFAP (astrocytes). Gene transcript levels of IL-3, IL-4, TNF-α, IL-6, TGF-ß, iNOS-M1, and arginase-M2 were quantified by RT-qPCR. The results indicated that treatment with DMF, at a dose of 90 mg/kg, promoted neuroprotection and immunomodulation towards an anti-inflammatory response. It also resulted in greater preservation of inhibitory synapses and reduced astroglial reactivity, providing a more favorable environment for sensorimotor recovery.

C5 Palsy After Cervical Spine Decompression: Topographic Correlation With C6 Chassaignac Tubercle?: A Fresh-Cadaveric Study of the Cervical Spine and Rediscussion of Etiological Hypotheses.

STUDY DESIGN: Cadaveric study on fresh unprocessed, nonpreserved, undyed specimens, which has not previously been reported. OBJECTIVE: Our aim was to explore the possible topographic correlation of the C5 nerve root with regards to its course and regional relation to C6 Chassaignac tubercle. SUMMARY OF BACKGROUND DATA: C5 palsy is reported amongst the most frequent postoperative complications of cervical spinal procedures. We hypothesized that etiologic mechanisms proposed thus far in the current literature, although with some plausible explanation, still cannot explain why the C5 nerve root and not any other level suffer a postoperative palsy. METHODS: Six fresh cadavers had extensive layer by layer dissection performed by two surgeons (one of whom has experience as an anatomy demonstrator and dissector). Roots of brachial plexus were exposed in relation to cervical transverse processes. Photographs were taken at each stage of the exposure. RESULTS: We observed a close relation of the path of the C5 nerve root with the C6 tubercle bilaterally. Moreover, we noted a steeper descent of C5 in comparison with the other adjacent roots. CONCLUSION: Steeper angle of the C5 nerve root and close proximity to C6 Chassaignac tubercle may play a role in predisposing it to neuropraxia. Detailed anatomical photographs on fresh unprocessed cadaveric specimens are novel. Peculiar anatomical features and recent experimental evidence discussed do highlight a postganglionic extraforaminal etiology corresponding well to the demographic meta-analysis data on clinical features of postoperative C5 palsy. Exploring an alternative unified "neurophysiologic stress and critical tipping point" etiological model that encompasses current theories and correlates known metanalyses observations, we believe further studies would be prudent to ascertain/refute these findings. LEVEL OF EVIDENCE: 3.