Ultrasound-based Neuropathy Diagnosis in COVID-19 Patients in Post-intensive Care Rehabilitation Settings: A Retrospective Observational Study

ObjectivesUsing ultrasound (US) scanning to examine the correlation between increase of common fibular nerve's (CFN) cross sectional area (CSA) and functional impairment of foot dorsiflexor muscles as an early sign of peripheral neuropathy.DesignRetrospective observational study.SettingIn-patient rehabilitation unit between November 2020 and July 2021.ParticipantsTwenty-six inpatients who underwent prolonged hospitalization in intensive care units (ICUs) and were diagnosed with critical illness myopathy and polyneuropathy after SARS-COV-2 infection (N=26). Physical examination and US scanning of the CFN and EMG/ENG were carried out on each patient.InterventionsNot applicable.Main Outcome Measure(s)CFN's CSA at the peroneal head.ResultsWe verified a significant increase in the CSA of the CFN measured at the peroneal head in more than 90% of the nerves tested. A cut off value of CFN's CSA of 0.20 cm was used to identify pathologic nerves. No correlations with other variables (body mass index, ICU days) were found.ConclusionUS scanning of the CFN appears to be an early and specific test in the evaluation of CPN's abnormalities in post COVID-19 patients. US scanning is a reproducible, cost effective, safe, and easily administered bedside tool to diagnose a loss of motor function when abnormalities in peripheral nerves are present.     

Birth-related injury to the head and cervical spine in neonates

Birth-related injury is defined as any traumatic or ischemic event sustained during the process of delivery. Perinatally acquired disease processes secondary to birth-related injury can be traumatic or ischemic in nature. In this article, the authors focus on traumatic/mechanical injuries. Other diseases of the perinatal time period, including germinal matrix hemorrhages and hypoxic-ischemic encephalopathy, are beyond the objective of this review.     

The advances in nerve tissue engineering: From fabrication of nerve conduit to in vivo nerve regeneration assays

Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.     

Antioxidant gene therapy against neuronal cell death

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy.     

带蒂筋膜管的耳大神经移植治疗面神经缺失性损伤

Inthepresentstudy，greatauricularnervecoatedbypediculatedfascialtubenearfacialnervetrunkwasusedtotreatdefectivedamageoffacialnerve．Andthefunctionalrecoveryoffacialnervewasmoreapparentthangraftinggreatauricularnervealone．Thestudyisre－portedasfollowing．１Subjectandmethod１．１Subject（１）Threecasesofotogenicfacialparalysis．Case１，male，８yearsold．Hasnecrotizingexternalotitisintherightearandfacialparalysisfor１２months．Case２，female，３６yearsold．Haspa－pillomaofexternalauditorycanal…     

Identification of critical growth factors for peripheral nerve regeneration

Growth factors are essential for the repair and regeneration of tissues and organs, including injured peripheral nerves. However, the expression changes of growth factors during peripheral nerve regeneration have not been fully elucidated. To obtain a global view of alternations of growth factors during the regeneration process, we explored previously achieved sequencing data of rat sciatic nerve stumps at 0 h, 1 d, 4 d, 7 d, and 14 d after nerve crush injury and screened differentially expressed upstream growth factors using Ingenuity Pathway Analysis (IPA) bioinformatic software. Differentially expressed growth factors were then subjected to Gene Ontology (GO) annotation and Kyoto Enrichment of Genes and Genomes (KEGG) pathway analysis. Regulatory networks of the differentially expressed growth factors in axon growth-related biological processes were constructed. Pivotal growth factors involved in axon growth were identified and validated by qRT-PCR. Our current study identified differentially expressed growth factors in the injured nerve stumps after peripheral nerve injury, discovered key growth factors for axon growth and nerve regeneration, and might facilitate the discovery of potential therapeutic targets of peripheral nerve injury.

Growth factors are essential for the repair and regeneration of tissues and organs, including injured peripheral nerves.     

创伤性臂丛神经损伤的磁共振成像3D-FIESTA-C、IDEAL序列特征及诊断价值

目的：探讨创伤性臂丛神经损伤的磁共振成像（MRI）三维循环相位稳态采集快速成像（three-dimensional fast imaging employing steady state acquisition with cycled phases,3D-FIESTA-C）序列和三点法非对称回波水脂分离成像（iterative decomposition of water and fat with echo asymmetry and least squares estimation,IDEAL）序列特征及诊断价值。方法：对32例创伤性臂丛神经损伤患者进行术前MRI 3D-FIESTA-C及IDEAL序列检查后,再行图像后处理及诊断,总结臂丛神经损伤的MRI特征,将诊断结果与手术探查结果进行比较,评价术前MRI 3D-FIESTA-C联合IDEAL序列检查在诊断臂丛神经损伤中的作用。结果：12例患者术后证实共有39条节前神经损伤,3D-FIESTA-C序列显示出38条,其中31条神经根影像提示消失或离断,7条神经根丝减少、迂曲,无法连续追踪至椎间孔,同时可伴有神经根袖变钝、脊膜囊肿形成、硬脊膜增厚及脊髓形态信号异常改变。术前MRI 3D-FIESTA-C序列诊断臂丛神经节前损伤的灵敏度为97.5%,特异度为100%,准确率达98.3%。31例120条节后损伤中共12例45条节后神经断裂,其中7条伴纤维瘤形成,IDEAL序列显示42条节后神经根断裂,其他损伤表现为神经增粗,扭曲,走行僵直,周围结构水肿紊乱等。术前IDEAL序列诊断臂丛节后损伤的灵敏度为96.7%,特异度为100%,准确率为97.1%。结论：MRI 3D-FIESTA-C联合IDEAL序列检查可清晰显示节前及节后臂丛神经损伤情况,对臂丛神经损伤的诊断符合率较高,可作为临床首选的无创性影像学方法。     

Human dermal microvascular endothelial cells produce nerve growth factor: implications for wound repair

Following cutaneous injury, sensory nerves regenerate into the dermis and epidermis. Tissues that are innervated by sensory nerves synthesize neurotrophins such as nerve growth factor (NGF). The close anatomic proximity of nerves and capillaries throughout the skin suggests that mutual regulation may exist between nerve fibers and microvascular endothelial cells (MECs) during wound repair. Release of the neuropeptide substance P by sensory nerves induces endothelial cell rounding, capillary leak, and cytokine upregulation. We propose that dermal endothelial cells produce neurotrophins required for nerve fiber maintenance and regeneration. In this study, we demonstrate that substance P stimulates NGF messenger RNA expression by cultured human dermal MECs. Likewise, enzyme-linked immunosorbant assay demonstrated that conditioned medium from cultured dermal MECs contains NGF. NGF bioactivity in the supemates was verified by conditioned medium-induced clonal rat pheochromocytoma (PC-12) cell differentiation. This activity was inhibited by anti-NGF antibodies. Therefore, we have demonstrated that substance P, an inflammatory neuropeptide released by sensory nerve fibers, induces endothelial cells to produce NGF. Our data suggest that MECs may be unrecognized contributors to nerve regeneration after cutaneous injury.     

Sustained Delivery of VEGF Maintains Innervation and Promotes Reperfusion in Ischemic Skeletal Muscles Via NGF/GDNF Signaling

Tissue reinnervation following trauma, disease, or transplantation often presents a significant challenge. Here, we show that the delivery of vascular endothelial growth factor (VEGF) from alginate hydrogels ameliorates loss of skeletal muscle innervation after ischemic injury by promoting both maintenance and regrowth of damaged axons in mice. Nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) mediated VEGF-induced axonal regeneration, and the expression of both is induced by VEGF presentation. Using both in vitro and in vivo modeling approaches, we demonstrate that the activity of NGF and GDNF regulates VEGF-driven angiogenesis, controlling endothelial cell sprouting and blood vessel maturation. Altogether, these studies produce evidence of new mechanisms of VEGF action, further broaden the understanding of the roles of NGF and GDNF in angiogenesis and axonal regeneration, and suggest approaches to improve axonal and ischemic tissue repair therapies.     

分米波对大鼠再生神经NGF mRNA表达的影响

目的研究分米波对周围神经损伤后再生神经中神经生长因子(NGF)表达的影响。方法选用60只SD大鼠，随机分为实验组和对照组各30只，均于右侧坐骨神经中段切除5mm神经组织，硅胶管桥接神经缺损，形成神经再生室，实验组术后进行局部分米波辐射。于术后1，2，4和8周取材，行大体和光镜观察，并进行免疫组化检测及RT-PCR定量分析。结果实验组NGF阳性染色颗粒及积分光密度值(IOD)明显高于对照组。实验组各时间点再生神经纤维中NGFmRNA的含量均明显高于对照组(P＜0、01)，同一神经纤维中．NGF mRNA表达量近侧明显高于远侧(P＜0．05)。实验组再生神经纤维中NGF mRNA于术后1周即有表达，术后2～4周达到高峰，术后8周后开始下降。结论分米波能增加神经纤维中NGF mRNA的表达，促进周围神经再生。     

增刊投稿--个性化延续护理对创伤性脊髓损伤伴截瘫患者照顾者照顾负担和生活质量的影响

目的：分析个性化延续护理对创伤性脊髓损伤伴截瘫患者预后效果及患者照顾者照顾负担和生活质量的影响。方法：选择我院自2018年1月至2019年6月收治的180例创伤性脊髓损伤伴截瘫患者作为研究对象,采用随机数字表法将其分成对照组和研究组,每组90例,对照组采用常规出院指导护理干预,研究组采用个性化延续护理干预,对比两组患者护理前后的肢体疼痛评分、功能障碍评分及照顾者护理前后对疾病相关护理知识掌握度评分、照顾负担评分、生活质量评分、对护理工作的总满意率。结果：护理前,两组患者肢体疼痛评分、功能障碍评分及照顾者护理前后对疾病相关护理知识掌握度评分、照顾负担评分、生活质量评分对比均无显著差异(P＞0.05),护理后,研究组患者肢体疼痛评分、功能障碍评分及照顾者照顾负担评分均显著低于对照组,研究组患者照顾者对疾病相关护理知识掌握度评分、生活质量评分及对护理工作的总满意率均显著高于对照组,两组对比具有统计学意义(P＜0.05)。结论：对创伤性脊髓损伤伴截瘫患者实施个性化延续护理干预,不仅能有效提高患者照顾者对疾病相关护理知识的掌握度,同时还能减轻其照顾负担和提高其生活质量,并提高患者预后效果,从而有助于提高其对护理工作的满意度。     

Sutureless nerve repair at the fascicular level using a nerve coupler

Peripheral nerves are transected in many traumatic injuries of the extremities. Satisfactory functional regeneration of such nerves often fails to occur after repair with sutures. Possible reasons for these failures include poor alignment of nerves or fascicles, intrusion of scar tissue into the nerve junction, and outgrowth of nerve tissue from the repair site. This animal study describes an experimental method of sutureless, monofascicular peripheral nerve repair using a resorbable nerve coupler in the rat model. The first version of this coupler shows approximately equal performance to suture repair. Histology and electrophysiology assessments after regeneration showed that the polyglycolic acid (PGA) tube repairs were functionally equal to monofascicular suture junctions as well as being quicker and simpler to perform. Modified coupler designs based on this and other work show greater promise. Collateral studies are using similar versions of the nerve coupler as a vehicle for the insertion of chemical and neuro-electronic factors that may enhance nerve regeneration.     

Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: diagnosis, prognosis, probing mechanisms, and therapeutic decision making

PURPOSE OF REVIEW: Emerging data suggest that biomarkers of brain injury have potential utility as diagnostic, prognostic, and therapeutic adjuncts in the setting of traumatic and ischemic brain injury. Two approaches are being used, namely, assessing markers of structural damage and quantifying mediators of the cellular, biochemical, or molecular cascades in secondary injury or repair. Novel proteomic, multiplex, and lipidomic methods are also being applied. RECENT FINDINGS: Biochemical markers of neuronal, glial, and axonal damage such as neuron-specific enolase, S100B, and myelin basic protein, respectively, are readily detectable in biological samples such as serum or cerebrospinal fluid and are being studied in patients with ischemic and traumatic brain injury. In addition, a number of studies have demonstrated that novel tools to assess simultaneously multiple biomarkers can provide unique insight such as details on specific molecular participants in cell death cascades, inflammation, or oxidative stress. SUMMARY: Multifaceted cellular, biochemical, and molecular monitoring of proteins and lipids is logical as an adjunct to guiding therapies and improving outcomes in traumatic and ischemic brain injury and we appear to be on the verge of a breakthrough with the use of these markers as diagnostic, prognostic, and monitoring adjuncts, in neurointensive care.     

Argon: Neuroprotection in in vitro models of cerebral ischemia and traumatic brain injury

Introduction

Recently, it has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties. In this study we tested the hypothesis that the noble gas argon has a neuroprotective potential as well. Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia.

Methods

Organotypic hippocampal slice cultures from mice pups were subjected to either oxygen-glucose deprivation or to a focal mechanical trauma and subsequently treated with three different concentrations (25, 50 and 74%) of argon immediately after trauma or with a two-or-three-hour delay. After 72 hours of incubation tissue injury assessment was performed using propidium iodide, a staining agent that becomes fluorescent when it diffuses into damaged cells via disintegrated cell membranes.

Results

We could show argon's neuroprotective effects at different concentrations when applied directly after oxygen-glucose deprivation or trauma. Even three hours after application, argon was still neuroprotective.

Conclusions

Argon showed a neuroprotective effect in both in vitro models of oxygen-glucose deprivation and traumatic brain injury. Our promising results justify further in vivo animal research.     

Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice

Peripheral nerves have the capacity for regeneration, but the rate of regeneration is so slow that many nerve injuries lead to incomplete recovery and permanent disability for patients. Macrophages play a critical role in the peripheral nerve response to injury, contributing to both Wallerian degeneration and nerve regeneration, and their function has recently been shown to be dependent on intracellular metabolism. To date, the impact of their intracellular metabolism on peripheral nerve regeneration has not been studied. We examined conditional transgenic mice with selective ablation in macrophages of solute carrier family 16, member 1 (Slc16a1), which encodes monocarboxylate transporter 1 (MCT1), and found that MCT1 contributed to macrophage metabolism, phenotype, and function, specifically in regard to phagocytosis and peripheral nerve regeneration. Adoptive cell transfer of wild-type macrophages ameliorated the impaired nerve regeneration in macrophage-selective MCT1-null mice. We also developed a mouse model that overexpressed MCT1 in macrophages and found that peripheral nerves in these mice regenerated more rapidly than in control mice. Our study provides further evidence that MCT1 has an important biological role in macrophages and that manipulations of macrophage metabolism can enhance recovery from peripheral nerve injuries, for which there are currently no approved medical therapies.     

Onodi气房骨折外伤性视神经病鼻内镜下视神经减压术7例报告

目的探讨Onodi气房骨折所致视神经损伤的特点及手术和辅助用药的经验。方法 7例影像学检查判断Onodi气房骨折致视神经损伤患者,术前6例无光感,1例眼前手动,均为单眼外伤,伤后1至7天行鼻内镜下视神经减压术,术中发现骨折片碎裂成角压迫神经严重,术前后给予大剂量激素及神经营养剂治疗。结果随访3~9个月,6例患者视力无改善,1例患者视力有提高。结论 Onodi气房骨折较蝶窦骨折形成的骨折片碎裂成角压迫视神经损伤更为严重,术前视力更差,术后恢复也较差。     

周围神经损伤后不同时间的修复比较

背景:大量实验证明,Bungner带-许旺细胞-基底膜结构是神经再生理想的微环境.这一结构在神经损伤两三周后形成.而在神经损伤数小时后,近断端的神经纤维就开始发芽再生神经纤维开始再生与所需微环境的形成并不同步.目的:观察周围神经损伤后不同时间进行修复的最佳效果.设计、时间及地点:随机对照动物实验,于2007-06/2008-06在哈尔滨医科大学动物实验中心完成.材料:新西兰大白兔20只,随机数字表法分为4组:2周后神经修复组、4周后神经修复组、3个月后神经修复组、即时神经修复组.方法:建立成年新西兰大白兔周围神经损伤模型,即时修复组立即缝合伤口,2周后神经修复组、4周后神经修复组、3个月后神经修复组采用神经两断端分别固定于肌膜上,逐层缝合伤口,2周,4周,3个月后重新打开伤口,在手术显微镜下用10-0无损伤尼龙针线进行外膜缝合修复坐骨神经,缝合伤口.主要观察指标:各组缝合神经段的神经电生理、轴突数、光镜及电镜观察结果.结果:2周后神经修复组神经传导速度慢于4周后神经修复组、3个月后神经修复组(P＜0.01);即时神经修复组与2周后神经修复组差异无显著性意义(P＞0.05).2周后神经修复组效果最好,神经纤维走行正常、排列完好,神经纤维可见血管增生,髓鞘结构较好,许旺细胞功能活跃,新生轴突内微缝密集排列.4周后神经修复组最差,神经纤维数量少、排列紊乱,髓鞘轴突变性明显,大部分神经纤维脱髓鞘崩解,轴突消失,未见再生神经纤维.3个月后神经修复组效果较差,可见较多神经纤维结构破坏,捧列略紊乱,髓鞘和轴突变性较明显,仅见少量再生神经纤维,许旺细胞略少,胞质不发达.即时进行神经修复组效果较好,神经纤维结构破坏不明显,排列整齐,髓鞘和轴突变性轻,神经纤维内见有大量再生髓鞘,许旺细胞明显增多,胞质较发达.2周后神经修复组轴突计数优于其他3组(P＜0.05),4周后神经修复组最少.结论:神经损伤2周后进行神经修复效果优于其他时间点,是周围神经损伤后修复的最佳时机.     

Increased cytochrome c in rat cerebrospinal fluid after cardiac arrest and its effects on hypoxic neuronal survival

Cerebrospinal fluid (CSF) proteins may be useful biomarkers of neuronal death and ultimate prognosis after hypoxic–ischemic brain injury. Cytochrome c has been identified in the CSF of children following traumatic brain injury. Cytochrome c is required for cellular respiration but it is also a central component of the intrinsic pathway of apoptosis. Thus, in addition to serving as a biomarker, cytochrome c release into CSF may have an effect upon survival of adjacent neurons. In this study, we use Western blot and ELISA to show that cytochrome c is elevated in CSF obtained from pediatric rats following resuscitation from cardiac arrest. Using biotinylated human cytochrome c in culture media we show that cytochrome c crosses the cell membrane and is incorporated into mitochondria of neurons exposed to anoxia. Lastly, we show that addition of human cytochrome c to primary neuronal culture exposed to anoxia improves survival. To our knowledge, this is the first study to show cytochrome c is elevated in CSF following hypoxic ischemic brain injury. Results from primary neuronal culture suggest that extracellular cytochrome c is able to cross the cell membrane of injured neurons, incorporate into mitochondria, and promote survival following anoxia.     

Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury.

Neurotrophins have been shown to promote axonal growth and regeneration after spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by using a controlled delivery system to increase the duration of neurotrophin availability following injury. Such a delivery system can be incorporated into a bioactive scaffold to serve as a physical bridge for regeneration. This study assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin scaffolds implanted in spinal cord lesions immediately following 2-mm ablation injury in adult rats. Nine days after injury, fibrin scaffolds containing the delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth into the lesion than did control scaffolds or saline (1.5- to 3-fold increase). Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar formation at the white matter border of the lesion. Hindlimb motor function of treated animals did not improve relative to controls at 12 weeks post-injury. Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial regenerative response by increasing neuronal fiber sprouting and cell migration into the lesion, while functional motor recovery was not observed in this model.     

Cognitive and behavioural post-traumatic impairments: What is the specificity of a brain injury ? A study within the ESPARR cohort

ObjectiveThe variety and extent of impairments occurring after traumatic brain injury vary according to the nature and severity of the lesions. In order to better understand their interactions and long-term outcome, we have studied and compared the cognitive and neurobehavioral profile one year post onset of patients with and without traumatic brain injury in a cohort of motor vehicle accident victims.MethodThe study population is composed of 207 seriously injured persons from the ESPARR cohort. This cohort, which has been followed up in time, consists in 1168 motor vehicle accident victims (aged 16 years or more) with injuries with all degrees of severity. Inclusion criteria were: living in Rhone county, victim of a traffic accident having involved at least one wheel-conducted vehicle and having occurred in Rhone county, alive at the time of arrival in hospital and having presented in one of the different ER facilities of the county. The cohort's representativeness regarding social and geographic criteria and the specificities of the accidents were ensured by the specific targeting of recruitment. Deficits and impairments were assessed one year after the accident using the Neurobehavioral Rating Scale - Revised and the Trail-Making Test. Within our seriously injured group, based on the Glasgow Score, the presence of neurological deficits, aggravation of neurological condition in the first 72 hours and/or abnormal cerebral imaging, we identified three categories: (i) moderate/severe traumatic brain injury (n = 48), (ii) mild traumatic brain injury (n = 89), and (iii) severely injured but without traumatic brain injury (n = 70).ResultsThe most frequently observed symptoms were anxiety, irritability, memory and attention impairments, depressive mood and emotional lability. While depressive mood and irritability were observed with similar frequency in all three groups, memory and attention impairments, anxiety and reduced initiative were more specific to traumatic brain injury whereas executive disorders were associated with moderate/severe traumatic brain injury.Discussion-ConclusionThe presence and the initial severity of a traumatic brain injury condition the nature and frequency of residual effects after one year. Some impairments such as irritability, which is generally associated with traumatic brain injury, do not appear to be specific to this population, nor does depressive mood. Substantial interactions between cognitive, affective and neurobehavioral disorders have been highlighted.