非手术治疗儿童外伤性视神经损伤临床分析

目的分析非手术治疗儿童外伤性视神经损伤的临床特点。方法选取本院2014-11—2015-11收治的43例(45眼)外伤性视神经损伤患儿为本次研究对象,对其临床资料进行回顾性分析,并对其临床表现、发病特征、临床诊断、临床治疗等进行总结。结果本院所收治的外伤性视神经损伤患儿,其发病原因多为车祸,且视力受损严重,在经相应治疗后,多数患儿视力有所恢复。结论针对儿童外伤性视神经损伤,应及早诊断、及早治疗,确保治疗效果,改善其预后。     

大鼠视神经损伤定量模型的建立

目的建立标准化视神经损伤大鼠动物模型，对致伤强度、损伤程度及两者之间的关系进行量化分析。方法在立体定位下，利用微电极毁损视神经颅内段，毁损电压为5V，频率为60kHz，通过改变电毁损的电流强度，造成不同程度视神经损伤。然后进行视网膜切片，计数视神经节细胞层细胞，定量视神经损伤。结果析因方差分析结果显示：视神经节细胞计数存不同刺激时间之间，差异硅著（F=3472，14，P〈0．001）；在不同电流强度组间，差异显著（F=335．83，P〈0．001）；经LSD法多重比较，视神经节细胞计数在刺激电流之间及刺激时间之间差异在α=0．05水平均有显著性意义。刺激强度和刺激时间的单独效应：同一电流组随着刺激时间增加．视神经节细胞计数呈下降趋势；除对照组和90s组外（F=0．79，P=0．548；F=1．54，P=0．242），刺激时间相同时，随电流强度增加．细胞计数也呈下降趋势，刺激电流强度与刺激时间之间交互效廊显著（F=27．30，P〈0．001）：结论立体定向电毁损大鼠颅内段视神经模型可以测定致伤强度和视神经损伤程度，是较理想的视神经损伤模型。     

兔视神经损伤后谷氨酸对视网膜的兴奋毒性损伤作用研究

目的探讨家兔视神经损伤后谷氨酸浓度变化对视网膜的兴奋毒性及其作用机制。方法 40只健康雄性日本大耳白家兔随机分成2组,A组35只,B组5只。A组家兔左眼为实验制备视神经损伤模型,右眼为对照眼。B组家兔双眼同时制备视神经损伤模型。分别于第1、3、7、14及28d随机处死A组7只家兔及B组1只家兔,检测家兔实验眼和对照眼视网膜谷氨酸浓度,并观察B组家兔视网膜病理形态学改变。结果家兔视神经损伤后视网膜内谷氨酸浓度逐渐升高,3d达到高峰,14d时家兔实验眼视网膜谷氨酸浓度仍高于对照眼(p<0.05),28d时其视网膜谷氨酸浓度无统计学差异(p>0.05)。家兔视网膜病理形态学观察:视神经损伤后1d,神经节细胞排列紊乱;3～7d,视网膜节细胞大量空泡化;7d～14d,视网膜厚度变薄,神经节细胞减少;14d后视网膜各层细胞改变逐步趋于稳定。结论家兔视神经损伤后,视网膜谷氨酸浓度升高是视网膜神经节细胞继发损伤的原因之一。     

视神经损伤后再生影响因素的研究

经典理论认为哺乳动物的视神经完全损伤后不能有效再生．只有一些较低等的两栖类和鱼类视神经离断后能完全再生。近20多年来,人们发现哺乳动物视神经本身具有再生潜能,在适宜的微环境条件下能发生轴突侧枝出芽和突触重建;但再生受诸多因素影响,其中既有促进因素,也有抑制因素。本文对影响视神经再生的因素及其研究进展加以综述。     

经颅视神经管减压术与药物综合治疗外伤性视神经损伤对照研究

目的对比经颅视神经管减压术与药物综合治疗外伤性视神经损伤的临床效果。方法选取我院2015-05—2016-05收治的32例外伤性视神经损伤患者为研究对象,随机分为对照组和观察组。对照组选用大剂量激素并进行综合治疗,观察组采用经颅视神经管减压术治疗。观察2组临床效果及并发症情况。结果观察组总有效率(87.50%)显著高于对照组(68.75%),差异有统计学意义(P0.05)。观察组并发症发生率6.25%,明显低于对照组的18.75%,差异有统计学意义(P0.05)。结论对外伤性视神经损伤患者采用经颅视神经管减压术治疗可起到明显效果,术后并发症较少,值得临床推广。     

视神经损伤经颅视神经管减压与视觉诱发电位的临床研究

目的探讨视神经损伤患者经颅视神经管减压治疗的临床疗效。方法回顾性分析经颅视神经管减压治疗的视神经损伤患者35例临床资料,3个月后复查视力及视觉诱发电位(VEP)检查。结果经颅神经管减压术后患者视力大部分改善;术前无光感患者术后视力恢复差;术后患者VEP的P100潜伏期延长、波幅降低,无光感患者波幅下降最明显。结论经颅神经管减压治疗有效,术前无光感患者手术效果差,术后VEP异常明显,VEP评价客观有效,与临床一致。     

不同类型视神经损伤经颅手术治疗临床分析

目的评估不同类型视神经损伤病人经颅视神经减压术的疗效,探讨间接视神经损伤的发病机制与预后。方法回顾性分析163例病人的临床资料,尤其是受力部位和视神经管的CT特点,对间接视神经损伤进行分型,并在术后早期(2周)及中晚期(6￣72个月)对视力恢复进行评估。结果经χ2检验,术后2周与术后半年,眉弓外侧型疗效较眉弓内侧型和颧骨型差(P<0.001),而眉弓内侧型与颧骨型疗效无显著性差异(P>0.05)。结论经颅视神经减压手术是治疗间接视神经损伤的有效方法;眉弓内侧型和颧骨型视神经损伤手术效果优于眉弓外侧型。     

外伤性视神经损伤经颅手术时机选择

目的分析外伤性视神经损伤后影响视力预后的因素，探讨适宜的手术时机。方法回顾性总结分析231例经颅视神经减压手术治疗外伤性视神经损伤患者的临床资料。根据病人术前视力情况分成2组，A组（无光感）171例；B组（光感以上）60例，每组根据伤后手术间隔时间长短再分为≤48h手术组和＞48h手术组。术后随访1个月-6年。结果不同受力部位、术前FVEP检查结果对视力预后有影响（P＜0．001）；视神经管CT有无骨折对视力恢复影响无统计学意义（P=0．571）。A组伤后48h内手术的患者疗效明显高于48h后者（P=0．001），B组伤后48h内手术患者与48h后者的疗效差异无统计学意义（P=0．5047）。结论对颧骨或眉弓前方受力；视觉诱发电位检查P100潜伏期延长但未消失者应该积极考虑手术治疗；对完全失明患者亦不应放弃治疗，并尽可能争取在48h内手术，以挽救其视力；对有残存视力的患者可适当延长受伤至手术的时间。     

Neuronal apoptosis and neurofilament protein expression in the lateral geniculate body of cats following acute optic nerve injuries

BACKGROUND: The visual pathway have 6 parts, involving optic nerve, optic chiasm, optic tract, lateral geniculate body, optic radiation and cortical striatum area. Corresponding changes may be found in these 6 parts following optic nerve injury. At present, studies mainly focus on optic nerve and retina, but studies on lateral geniculate body are few. OBJECTIVE: To prepare models of acute optic nerve injury for observing the changes of neurons in lateral geniculate body, expression of neurofilament protein at different time after injury and cell apoptosis under the optical microscope, and for investigating the changes of neurons in lateral geniculate body following acute optic nerve injury. DESIGN: Completely randomized grouping design, controlled animal experiment. SETTING: Department of Neurosurgery, General Hospital of Ji’nan Military Area Command of Chinese PLA. MATERIALS: Twenty-eight adult healthy cats of either gender and common grade, weighing from 2.0 to 3.5 kg, were provided by the Animal Experimental Center of Fudan University. The involved cats were divided into 2 groups according to table of random digit: normal control group (n =3) and model group (n = 25). Injury 6 hours, 1, 3, 7 and 14 days five time points were set in model group for later observation, 5 cats at each time point. TUNEL kit （Bohringer-Mannheim company）and NF200& Mr 68 000 mouse monoclonal antibody （NeoMarkers Company）were used in this experiment. METHODS: This experiment was carried out in the Department of Neurosurgery, General Hospital of Ji’nan Military Area Command of Chinese PLA between June 2004 and June 2005. ① The cats of model group were developed into cat models of acute intracranial optic nerve injury as follows: The anesthetized cats were placed in lateral position. By imitating operation to human, pterion approach was used. An incision was made at the joint line between outer canthus and tragus, and deepened along cranial base until white optic nerve via optic nerve pore and further to brain tissue. Optic nerve about 3 mm was liberated and occluded by noninvasive vascular clamp for 20 s. After removal of noninvasive vascular clamp, the area compressed by optic nerve was hollowed and narrowed, but non-fractured. Skull was closed when haemorrhage was not found. Bilateral pupillary size, direct and indirect light reflect were observed. Operative side pupil was enlarged as compared with opposite side, direct light reflect disappeared and indirect light reflect existed, which indicated that the models were successful. Animals of control group were not modeled .② The animals in the control group and model group were sacrificed before and 6 hours, 1, 3, 7 and 14 days after modeling respectively. Lateral geniculate body sample was taken and performed haematoxylin & eosin staining. Immunohistochemical staining showed lateral geniculate body neurofilament protein expression, and a comparison of immunohistochemial staining results was made between experimental group and control group. Terminal deoxynucleo-tidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) was used to label apoptotic cells in lateral geniculate body. MAIN OUTCOME MEASURES: Neuronal morphological change, neurofilament protein expression and cell apoptosis in lateral geniculate body following acute optic nerve injury. RESULTS: Twenty-eight involved cats entered the final analysis. ① Histological observation results: In the control group, cell processes were obviously found, which were few or shortening in the model group. ② Neuronal neurofilament protein expression: Cells in lateral geniculate body in the control group and at 6 hours after injury presented clear strip-shaped staining, and those at 7 and 14 days presented irregular distribution without layers and obviously decreasing staining intensity. The positive rate of neurofilament protein in lateral geniculate body in control group and 6 hours, 1, 3, 7 and 14 days after injury was （10.22±0.42）%，（10.03±0.24）%，（9.94±0.14）%，（9.98±0.22）%，（8.18±0.34）% and (6.37±0.18)%, respectively. Positive rate of neurofilament protein in control group, at 6 hours, 1 or 3 days after injury was significantly different from that at 7 days after injury (P < 0.05); Positive rate of neurofilament protein in control group, at 6 hours, 1, 3 or 7 days after injury was significantly different from that at 14 days after injury (P < 0.05). It indicated that neuronal injury in lateral geniculate body was not obvious within short term after optic nerve injury, but obvious at 7 days after injury and progressively aggravated until at 14 days after injury. ③ Neuronal apoptosis: TUNEL staining showed that neuronal apoptosis in lateral geniculate body appeared at 7 days after injury, and a lot of neuronal apoptosis in lateral geniculate body was found at 14 days after injury. It indicated that neuronal injury in lateral geniculate body was related to apoptosis. CONCLUSION: In short term after optic nerve injury (within 7 days), nerve injury of lateral geniculate body is not obvious, then, it will aggravate with the elongation of injury time. The occurrence of neuronal injury of lateral geniculate body is related to the apoptosis of nerve cells.     

Establishing a cat model of acute optic nerve injury

BACKGROUND: In order to investigate the progress in optic nerve injury and the following regeneration and repair, many kinds of animal models of optic nerve injury have been established, such as models of acute and chronic ocular hypertension, compression, amputating wound, ischemia reperfusion or hypoxia, intravitreal injection of excitatory amino acids, etc. However, most of these models are established by squeezing intraorbital optic nerve, and suitable for ophthalmology, and there are fewer models suitable for the acute cranial contusion in neurosurgery. OBJECTIVE: To observe the changes of optic nerve after acute injury, and the characteristics of methods for establishing model of acute optic nerve injury in cats. DESIGN: A complete randomized grouping and controlled animal trial. SETTING: Department of Neurosurgery, General Hospital of Ji’nan Military Area Command of Chinese PLA. MATERIALS: Twenty-eight healthy adult cats, common degree, either sex, weighing 2.0–3.5 kg, were provided by the animal experimental center of Fudan University. The cats were randomly divided into control group (n =3) and model group (n =25), and 5 cats in the model group were observed at 6 hours and 1, 3, 7 and 14 days after injury respectively. JX-2000 biological signal processing system (Department of Physiology, Second Military Medical University of Chinese PLA, Shanghai); Inverted phase contrast microscope (Olympus); Axioplan 2 imaging microgram analytical system (Labsystems). METHODS: The experiments were carried out in the Department of Neurosurgery, General Hospital of Jinan Military Area Command of Chinese PLA from June 2004 to June 2005. The cats in the model groups were made into models of acute optic nerve injury: The cats were anesthetized, then the limbs were fixed in a lateral recumbent position. Pterion approach in human was imitated, the operative incision was made along the line between lateral canthus and tragus, and it could be seen deep along the skull base that white optic nerve (about 3 mm) went through optic foramen and entered into brain tissue. It was squeezed with noninvasive vascular clip for 20 seconds, then the clip was removed, and then the skull was closed after it was examined to be no bleeding. The size of bilateral pupils, direct and indirect light reflexes were observed postoperatively. Successfully established models were judged by larger operated pupil than controlateral one, disappearance of direct light reflex and the existence of indirect light reflex. No model establishment was performed in the control group. Each cat was tested with flash visual evoked potential (F-VEP) to observe the electrophysiological changes before and after experiment. All the cats in the control group and model groups were killed under anesthesia before model establishment and at 6 hours, 1, 3, 7 and 14 days after model establishment respectively, and the pathological changes of the optic nerve after injury were observed under electron microscope and light microscope. MAIN OUTCOME MEASURES: VEP and the ultrastructural changes of optic nerve after acute optic nerve injury in both groups. RESULTS: All the 28 cats were involved in the analysis of results. ① VEP results: The VEP latencies were obviously different between the control group and model group at each time point (P < 0.05), whereas there were no obvious differences among different time points in the model group (P > 0.05). The VEP amplitudes were obviously different between the control group and model group at each time point (P < 0.05), whereas there were no obvious differences among different time points in the model group (P > 0.05). ② Ultrastructural changes of the optic nerve: Under electron microscope, normal optic nerve myelin sheath had complete structure, tramal plates were clear and arranged tightly, axolemma was complete, whereas the structures of endoneurium, myelin sheath, tramal plates, axolemma and axon were in disorders after optic nerve injury. CONCLUSION: Models of acute optic nerve injury established by squeezing intracranial optic nerve with noninvasive vascular clip can be applied in studying intracranial acute optic nerve injury.     

视神经损伤与经颅视神经管减压术

通过对近年来的19篇文献进行分析发现外伤性视神经经损伤主要发生在眉额部受到外力打击后,不一定伴有视神经管骨折,以伤后立即失明和伴有骨折者损伤较重,且疗效不理想。及时的颅视神经管减压是良好的选择,要求打开视神经管顶的全宽和全长,最好在伤后10天内尽早手术,早期大剂量的糖皮质激素的作用也日益受到关注。对于视神经管段的视神经损伤,经颅视神经管减压术是值得大力提倡的。     

Ultrastructural changes in the optic nerve and capillary vessels during early stages of optic nerve injury★

BACKGROUND: Capillaries are the only blood supply for optic nerves, which makes the system more vulnerable to impaired blood circulation. OBJECTIVE: To observe the ultrastructural changes in the optic nerves and capillaries in rabbits following intracanalicular segment injury to the optic nerve. DESIGN, TIME AND SETTING: Comparative, observational, pathological morphology was performed at the Department of Anatomy, Weifang Medical College from September to November 2007. MATERIALS: Models of intracanalicular segment injury to the optic nerve were induced in the right eye of thirty healthy, adult rabbits by a flee-falling metal cylinder. The H-7500 transmission electron microscope was provided by Hitachi, Japan. METHODS: All rabbits were randomly assigned into experimental (n = 25) and control (n = 5) groups. Optic nerve specimens were obtained from the experimental group at 0.5, 6, 12, 48, and 96 hours, respectively, following injury. Uitrastructural changes to the optic nerves and their capillaries were observed by electron microscopy. Optic nerve injury was not established in the control group, but optic nerve specimens were collected similarly to the experimental group. MAIN OUTCOME MEASURES: Ultrastructural changes in the injured optic nerves and their capillaries. RESULTS: Thirty rabbits were included in the final analysis. In the control group, cross-sections of the optic nerves exhibited varied thicknesses with regularly arranged fibers. The axons appeared to be smooth with condensed myelin sheaths and oval mitochondria. The microtubules and mierofilaments were clearly seen. The lumens of the capillaries were regular with densely arranged endothelial cells and visible mitochondria. In the experimental group, 30 minutes after injury to the optic nerves, swollen axons, sparse myelin sheath, disordered microtubules and microfilaments, swollen mitochondria, and a decreased number of pinocytosis vesicles and microfilaments in endothelial cells of the capillaries were observed. At 6 hours, medullary and vacuolar degeneration in the mitochondria, and swollen endothelial cells in the capillary, were visible. At 12 hours, these changes were more obvious. At 48 hours, granular dissolution of microtubules, micro filaments, and mitochondria, as well as diffuse degeneration of mitochondria in the endothelial cells, were observed. At 96 hours, axonal disintegration, vacuolar degeneration, and dilated capillaries were observed. CONCLUSION: During early stages, the injured intracanalicular optic nerve exhibited swollen axons with vacuolar degeneration, swollen and degenerated mitochondria, decreased number of microtubules and microfilaments, and dilated capillaries with increased permeability.     

Calibration and standardisation of graded optic nerve injuries in rats

Abstract

Objectives:

To calibrate and standardise an animal model of graded optic nerve injury (ONI) in rats to facilitate future inter-laboratory data comparisons, focussing on quantification of injury intensity, injury severity, and the correlation between them.

Methods:

A pair of cross-action forceps or a pair of artery clips was used to induce optic nerve (ON) crush injuries. A lever principle and a simplified method were used to measure the crushing force. The simplified method directly measured weights as an external force exerted on the tip of the forceps or clips, which was just sufficient to maintain a gap and was equivalent to the closing (crush) force. The impulse and averaged impulse were explored as physical quantities to compare injury intensities. Graded ONIs were made by crushing the ON for 3, 6, 12, 30 or 60 seconds by the cross-action forceps, or 5, 10 or 15 seconds by the artery clips. The injury severity was evaluated by counting surviving retinal ganglion cell (RGC) through applied FluoroGold to the superior colliculus and lateral geniculate body before ON crush, intact RGC counting by applied FluoroGold after ON crush, and ON axon counting.

Results:

Similar results were obtained by the lever principle method and the simplified method. The crushing force of the cross-action forceps and the artery clips was 148.0 gram force (gf) and 32.4?gf, respectively. The graded ONI animal models were successfully created in rats without retinal ischaemia post-trauma. The averaged impulse produced by the artery clips for 15 seconds was equal to that produced by a 3-second crush of the cross-action forceps. The correlation between injury intensity and injury severity was fitted for a power function.

Discussion:

Our results provide a simplified and effective means to quantify and analyse data from ON crush studies compared with previously reported animal models.     

Efficacy of nerve growth factor on the treatment of optic nerve contusion Evaluation with visual evoked potential

BACKGROUND: Pattern- visual evoked potential (PVEP) can reflect the functional status of retinal ganglial cells (RGC) and visual cortex, and is an objective examination for visual pathway function. It is a unique method for objectively examining the optic nerve function of optic ganglion cells. OBJECTIVE: To observe the effects of nerve growth factor (NGF) on PVEF in the treatment of optic nerve contusion, evaluate the clinical efficacy of NGF, and make an efficacy comparison with vitamin B12. DESIGN: A randomly grouping, controlled observation. SETTING: Department of Ophthalmology, Tangshan Gongren Hospital Affiliated to Hebei Medical University. PARTICIPANTS: Forty patients with optic nerve contusion caused by eye trauma, who received the treatment in the Tangshan Worker Hospital Affiliated to Hebei Medical University between January 2006 and June 2007, were recruited in this study. The involved 40 patients, including 34 males and 6 females, were aged 14–59 years. They were confirmed to have optic nerve contusion by ophthalmologic consultation combined with history of disease and orbital CT examination. Informed consents of treatments and detected items were obtained from all the patients. The patients were randomly divided into 2 groups with 20 in each: NGF group and vitamin B12 group. METHODS: Conservative treatment was used in the two groups. In addition, patients in the NGF group were intramuscularly injected with NGF solution 18 μg /time, once a day. Those in the vitamin B12 group were injected by the same method with common vitamin B12 of 500 μg combined with vitamin B1 of 100 mg, once a day. MAIN OUTCOME MEASURES: PVEP examination was conducted in all the patients before, one and two weeks after treatment, and latency and amplitude at P100 were detected. RESULTS: Forty patients with optic nerve contusion participated in the final analysis. Before treatment, significant differences in the latency and amplitude at P100 were not found in patients between two groups (P > 0.05). For each patient in the NGF group, the latency of PVEP at P100 was significantly shortened, and the amplitude was significantly increased one and two weeks after treatment as compared with vitamin B12 group（t =2.06–2.34, P < 0.05）. CONCLUSION: NGF treatment can obviously improve the visual function of patients with optic nerve contusion. The curative effect of NGF is superior to vitamin B12.     

改良翼点入路手术减压治疗视神经损伤

目的 探讨颅脑损伤合并视神经损伤手术入路及减压的范围。方法 改良翼点入路开颅手术治疗22例颅损伤合并视神经损伤患者，术中磨除骨性视神经管周径1／2，切开视神经鞘膜、总腱环及镰状韧带，视神经充分减压。视力恢复评价标准：黑矇、光感、眼前手动、眼前数指和能见标字视力表符号5个级别，术后视力提高2个级别以上者为有效。结果 术后3～6月随访，有效率为81．8％。结论 改良翼点入路手术减压治疗视神经损伤效果良好，术后视力恢复与伤后手术时间、手术方法及减压范围有关，亦与其原发损伤程度密切相关。