非动脉炎性前部缺血性视神经病变诊疗策略及其脉络膜厚度

非动脉炎性前部缺血性视神经病变(nonarteritic anterior ischemic optic neuropathy,NAION),是一种比较常见视神经疾病,病因、发病机制复杂,治疗效果有限,多年来一直是眼科医生为取得突破性进展而不懈努力的方向。近年来,随着频域相干光断层深度增强成像(enhanced depth imaging spectral-domain optical coherence tomography,EDI-OCT)越来越广泛的应用,为NAION发病机制的研究提供了新的思路:鉴于前部视神经的血供主要来源于睫状后小血管,而这些小血管又构成了脉络膜的主要部分,因此应用EDI-OCT对脉络膜厚度的研究或将为该病发病机制的阐释、治疗效果的评估及预后的随访提供更加便捷的途径。在此,对近年来NAION病因、发病机制、诊断、治疗以及其脉络膜厚度的研究进展进行综述。     

经皮电刺激治疗外伤性外周神经损伤40例的效果分析

目的 本文分析使用经皮神经肌肉电刺激治疗外伤性周围神经损伤的临床疗效,探讨经皮电刺激对神经周围微循环的影响.方法 采用丹迪Keypoint型肌电图仪对40例上肢周围神经不全损伤的患者,行经皮神经肌肉电刺激治疗,配合运动疗法.治疗中使用激光多普勒血流仪(LDF)检测电刺激前、后神经周围微循环血流改变情况,并分析电刺激对微循环的影响.同时在治疗前、后行神经电生理检查对比检测,并对不同病程患者治疗后的效果作对比分析.利用以上分析手段观察受损神经功能的恢复情况.结果 40例臂丛神经、正中神经、桡神经、尺神经不全损伤的患者,经2-10个疗程的治疗后,受损神经功能治愈率达63％ (25/40),有效率为90％ (36/40).LDF检测结果显示电刺激后神经周围微循环血流量较刺激前增加23.36％-26.96％,改善受损神经局部微循环,神经肌电检测结果显示较治疗前有明显好转.在不同病程的患者中进行比较,病程越短者,效果越好.结论 经皮神经肌肉电刺激在外伤性周围神经损伤的治疗中,是一种行之有效的方法,可提高受损神经肌肉的兴奋度,促进受损神经局部的血液循环,有利于周围神经的再生.运动疗法的干预,能改善肌萎缩,增强肌协调力,预防关节僵硬,保持关节活动度,最终取得对外伤性周围神经损伤的满意疗效.应用激光多普勒血流成像技术,测得电刺激前、后神经周围微循环出现明显的血流量增加,证实电刺激能改善受损神经局部微循环.     

视神经疾病与能量代谢及轴浆转运的关系

神经细胞的特化之一是其轴突,长度可达胞体直径的几百甚至几千倍.轴浆转运维系着胞体和轴突终末之间大量的物质交流,保证神经细胞发挥正常功能.轴浆转运障碍可以导致神经细胞功能受损直至凋亡.在一些视神经疾病中,轴浆转运功能的改变是最早出现的症状,因此也可能成为治疗的潜在靶点.在青光眼和视神经缺血的动物模型中,轴浆转运功能的下降是最早出现的变化之一.而Leber's遗传性视神经病变(LHON)和常染色体显性视神经萎缩(ADOA)是已知线粒体功能障碍引起的视神经疾病.不难想象,长距离轴浆转运功能对能量代谢尤其敏感,因此在LHON和ADOA中可能也有不同程度的下降,但似乎并没有受到足够关注.本文首先回顾了微管和马达蛋白在轴浆转运中的作用,比较分析以上所述几种疾病的发病机制、临床表现及治疗手段,试图发现它们之间的共同特点以及这些特点与能量代谢、轴浆转运之间的潜在关系,为其治疗提供新的思路.     

Epstein-Barr病毒相关噬血细胞综合征的研究进展

Epstein-Barr病毒相关噬血细胞综合征(EBV-HLH)的病情进展快,病死率高。高细胞因子血症是其发病的重要机制,临床表现多样。诊断需符合HLH诊断标准并存在EBV感染的证据。治疗首选依托泊苷、糖皮质激素、环孢素A联合应用。如化疗效果不佳,可行造血干细胞移植。现就该病的最新研究进展进行综述。     

人巨细胞病毒的定量检验和临床意义

人巨细胞病毒(HCMV)是一种普遍存在的DNA病毒,在免疫系统不成熟或受损的患者中会导致严重的疾病.最近几年,HCMV的定量检测已成为临床上帮助确定抗病毒治疗方案、评估治疗方案疗效和找出耐药性案例的主要方法.这篇综述对HCMV的不同定量方法进行了比较并对如何改善临床诊断做了一些探讨.     

翼状胬肉的发病机制及治疗的现状与进展

翼状胬肉具有较高的发病率,作为眼表疾病之一,如不给予及时有效的治疗会对患者的外貌产生影响,同时造成视力受损。迄今为止,翼状胬肉的具体发病机制尚未完全明确,且治疗方式复杂多样。为了有效提高翼状胬肉的治疗效果,降低复发率,研究学者与临床医师开始针对翼状胬肉的发病机制开展了大量研究,同时对临床治疗方式也进行了诸多改进,且将新型的药物以及医疗器械应用于临床治疗中,为翼状胬肉的防治提供了新的思路。但是其确切的发病机制还有待进一步研究,本文在角膜缘干细胞缺乏、炎性细胞因子、病毒感染细胞凋亡、转化生长因子-β、神经生长因子(NGF)以及血管内皮细胞生长因子(VEGF)方面的研究进行了综述。     

局部亚低温联合血肿清除术治疗外伤性脑内血肿的临床疗效观察

目的:探讨局部亚低温联合血肿清除术治疗外伤性脑内血肿患者的临床疗效。方法:选择我院收治的外伤性脑内血肿患者89例,均给予血肿清除术治疗,其中47例接受血肿清除术联合局部亚低温治疗,评价和比较两组治疗后的临床疗效,术前及术后1天、1周、2周的美国国立卫生研究院卒中量表(NIHSS)评分和血肿体积。结果:治疗组有效率为93.6%,明显高于对照组(P0.05);治疗组术后1天、1周、2周的NIHSS评分明显高于对照组(P0.05),血肿大小明显小于对照组(P0.05)。结论:局部亚低温联合血肿清除术治疗外伤性脑内血肿能有效减轻患者脑部损害,提高患者神经功能。     

胰腺癌发病的分子机制和诊断

胰腺癌是高度恶性肿瘤,起病隐匿,早期诊断困难,临床疗效差,是预后最差的恶性肿瘤之一。目前临床上尚缺乏有效的非 创伤早期筛查手段,多数患者确诊时已失去手术切除的机会。因此探讨胰腺癌发病的分子机制,特别是寻找在胰腺癌组织中高度 特异性表达的基因,对于胰腺癌的早期诊断和治疗具有重要的意义。本文就胰腺癌发病的分子机制和早期诊断进行综述。     

肠道微生态在儿童难治性癫痫发病及治疗中的研究进展CSCD

儿童难治性癫痫是一种常见的儿科神经系统疾病。许多临床前及临床证据表明儿童难治性癫痫患者体内优势菌群与健康人相比存在显著差异;抗癫痫干预后难治性癫痫儿童体内肠道菌群分布发生改变;动物粪菌移植实验进一步证实肠道菌群的改变与癫痫发病及抗癫痫疗效存在因果关系。临床上益生菌的添加可能增强抗癫痫疗效,抗生素的使用往往也影响临床的抗癫痫疗效。肠道微生态可能通过内源性机制(如改变神经递质含量等)及外源性机制(如感染和损伤等)改变儿童难治性癫痫患者的代谢、遗传、免疫和感染等。本综述通过总结近年来国内外肠道微生态与儿童癫痫发病和抗癫痫效果的相关研究,阐述肠道微生态在儿童癫痫发病及治疗中的作用并对其可能的作用机制进行探讨。     

Leber遗传性视神经病变研究进展和挑战

Leber遗传性视神经病变(Leber hereditary optic neuropathy, LHON; MIM535000)是最典型的线粒体遗传病之一, 主要由线粒体DNA (Mitochondrial DNA, mtDNA)3个原发突变(Primary mutation, m.11778G>A、m.3460G> A 和m.14484T>C)引起。患者表现为无痛性双侧视力下降或丧失, 主要易感人群为青壮年男性。不完全外显(Incomplete penetrance)和性别偏好(Gender bias)是该病亟待解决的两大难题, 目前尚无有效的预防及治疗措施。文章对近年来LHON 的分子发病机制、临床症状及特点、体外实验和动物模型研究、预防及治疗等方面的研究进展进行综述, 并集中介绍了我们近期对于我国LHON患者的研究结果。     

创伤性眶尖综合征的诊断与治疗进展

创伤性眶尖综合征是一种少见的颅脑创伤并发症,其主要特点是同时有眶上裂综合征和视神经损伤的表现。其临床症状多样,一般有眼肌麻痹、上睑下垂、瞳孔散大、视力减退等特点。诊断主要依靠临床表现和颅底CT三维重建等影像学检查。创伤性眶尖综合征目前有激素治疗和手术减压治疗等。基因治疗、神经干细胞移植在基础研究中取得了众多成果,但在临床应用上还有限制。手术减压目前认为是有效的,手术方式包括开颅手术和内镜手术,经鼻内镜手术减压具有微创、并发症少等优势。最佳的临床决策和手术治疗尚有待于多中心临床研究的开展和循证医学的支持。     

An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival

Injury to the optic nerve can lead to axonal degeneration, followed by a gradual death of retinal ganglion cells (RGCs), which results in irreversible vision loss. Examples of such diseases in human include traumatic optic neuropathy and optic nerve degeneration in glaucoma. It is characterized by typical changes in the optic nerve head, progressive optic nerve degeneration, and loss of retinal ganglion cells, if uncontrolled, leading to vision loss and blindness.The optic nerve crush (ONC) injury mouse model is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. In this model, the crush injury to the optic nerve leads to gradual retinal ganglion cells apoptosis. This disease model can be used to study the general processes and mechanisms of neuronal death and survival, which is essential for the development of therapeutic measures. In addition, pharmacological and molecular approaches can be used in this model to identify and test potential therapeutic reagents to treat different types of optic neuropathy.Here, we provide a step by step demonstration of (I) Baseline retrograde labeling of retinal ganglion cells (RGCs) at day 1, (II) Optic nerve crush injury at day 4, (III) Harvest the retinae and analyze RGC survival at day 11, and (IV) Representative result.Download video file.^{(53M, mov)}     

Intravitreal Transplantation of Human Umbilical Cord Blood Stem Cells Protects Rats from Traumatic Optic Neuropathy

Objectives

To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process.

Methods

A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR.

Results

After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression.

Conclusion

Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.     

Mononeuropathies of the radial nerve: clinical and neurographic findings in 91 consecutive cases.

Retrospective features of 91 consecutive cases (68 men, 23 women; mean age 44.4 years) of radial mononeuropathy diagnosed over the last 8 years in two electromyography (EMG) services are reported to define the clinical and electrophysiological findings of radial neuropathies in relation to traumatic and non-traumatic causes and site of injury. The occurrence of radial neuropathy was 0.65 x 100 first electromyographic examinations. The most frequent site of damage was the main trunk at the spiral groove of the humerus (36%); the most frequent cause was nerve trauma (70%) due to fracture (36%). In neuropathies of the main trunk and posterior interosseous (PI) nerve, "complete nerve injury" was observed in 36% of cases, conduction motor block in 33% and motor conduction velocity slowing in 46%. At least one of these findings was present in 51%, whereas motor neurography was normal in 13% of cases. Sensory action potential (SAP) anomalies were observed in 51% of cases. In neuropathy of the superficial radial nerve, no SAP was detected in 30% of cases; in all others except one, SAP was reduced in amplitude. Non-traumatic neuropathies showed severer conduction block and less severe anomalies of SAP than traumatic neuropathies. No differences were found between men and women. EMG is essential for confirming the site of injury and neurographic study may be helpful for diagnosis, providing information about lesion type and severity.     

Adult peripheral nerve disorders: nerve entrapment, repair, transfer, and brachial plexus disorders

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Describe the pathophysiologic bases for nerve injury and how they apply to patient evaluation and management. 2. Recognize the wide variety of injury patterns and associated patient complaints and physical findings associated with peripheral nerve pathology. 3. Evaluate and recommend further tests to aid in defining the diagnosis. 4. Specify treatment options and potential risks and benefits. SUMMARY: Peripheral nerve disorders comprise a gamut of problems, ranging from entrapment neuropathy to direct open traumatic injury and closed brachial plexus injury. The pathophysiology of injury defines the patient's symptoms, examination findings, and treatment options and is critical to accurate diagnosis and treatment. The goals of treatment include management of the often associated pain and improvement of sensory and motor function. Understanding peripheral nerve anatomy is critical to adopting novel nerve transfer procedures, which may provide superior options for a variety of injury patterns.     

A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration

Unlike in mammals, fish retinal ganglion cells (RGCs) have a capacity to repair their axons even after optic nerve transection. In our previous study, we isolated a tissue type transglutaminase (TG) from axotomized goldfish retina. The levels of retinal TG (TG(R)) mRNA increased in RGCs 1-6weeks after nerve injury to promote optic nerve regeneration both in vitro and in vivo. In the present study, we screened other types of TG using specific FITC-labeled substrate peptides to elucidate the implications for optic nerve regeneration. This screening showed that the activity of only cellular coagulation factor XIII (cFXIII) was increased in goldfish optic nerves just after nerve injury. We therefore cloned a full-length cDNA clone of FXIII A subunit (FXIII-A) and studied temporal changes of FXIII-A expression in goldfish optic nerve and retina during regeneration. FXIII-A mRNA was initially detected at the crush site of the optic nerve 1h after injury; it was further observed in the optic nerve and achieved sustained long-term expression (1-40days after nerve injury). The cells producing FXIII-A were astrocytes/microglial cells in the optic nerve. By contrast, the expression of FXIII-A mRNA and protein was upregulated in RGCs for a shorter time (3-10days after nerve injury). Overexpression of FXIII-A in RGCs achieved by lipofection induced significant neurite outgrowth from unprimed retina, but not from primed retina with pretreatment of nerve injury. Addition of extracts of optic nerves with injury induced significant neurite outgrowth from primed retina, but not from unprimed retina without pretreatment of nerve injury. The transient increase of cFXIII in RGCs promotes neurite sprouting from injured RGCs, whereas the sustained increase of cFXIII in optic nerves facilitates neurite elongation from regrowing axons.     

Anti-semaphorin 3A antibodies rescue retinal ganglion cells from cell death following optic nerve axotomy

Damage to the optic nerve in mammals induces retrograde degeneration and apoptosis of the retinal ganglion cell (RGC) bodies. The mechanisms that mediate the response of the neuronal cells to the axonal injury are still unknown. We have previously shown that semaphorins, axon guidance molecules with repulsive cues, are capable of mediating apoptosis in cultured neuronal cells (Shirvan, A., Ziv, I., Fleminger, G., Shina, R., He, Z., Brudo, I., Melamed, E., and Brazilai, A. (1999) J. Neurochem. 73, 961-971). In this study, we examined the involvement of semaphorins in an in vivo experimental animal model of complete axotomy of the rat optic nerve. We demonstrate that a marked induction of type III semaphorin proteins takes place in ipsilateral retinas at early stages following axotomy, well before any morphological signs of RGC apoptosis can be detected. Time course analysis revealed that a peak of expression occurred after 2-3 days and then declined. A small conserved peptide derived from semaphorin 3A that was previously shown to induce neuronal death in culture was capable of inducing RGC loss upon its intravitreous injection into the rat eye. Moreover, we demonstrate a marked inhibition of RGC loss when axotomized eyes were co-treated by intravitreous injection of function-blocking antibodies against the semaphorin 3A-derived peptide. Marked neuronal protection from degeneration was also observed when the antibodies were applied 24 h post-injury. We therefore suggest that semaphorins are key proteins that modulate the cell fate of axotomized RGC. Neutralization of the semaphorin repulsive function may serve as a promising new approach for treatment of traumatic injury in the adult mammalian central nervous system or of ophthalmologic diseases such as glaucoma and ischemic optic neuropathy that induce apoptotic RGC death.     

Leber Hereditary Optic Neuropathy: How Do Mitochondrial DNA Mutations Cause Degeneration of the Optic Nerve?

Leber hereditary optic neuropathy (LHON) is an inherited form of bilateral optic atrophy in which the primary etiological event is a mutation in the mitochondrial genome. The optic neuropathy involves a loss of central vision due to degeneration of the retinal ganglion cells and optic nerve axons that subserve central vision. The primary mitochondrial mutation is necessary—but not sufficient—for development of the optic neuropathy, and secondary genetic and/or epigenetic risk factors must also be present although they are poorly defined at the present time. There is broad agreement that mutations at nucleotides 3460, 11778, and 14484 are primary LHON mutations, but there may also be other rare primary mutations. It appears that the three primary LHON mutations are associated with respiratory chain dysfunction, but the derangements may be relatively subtle. There is also debate on whether there are mitochondrial mutations that have a secondary etiological or pathogenic role in LHON. The specific pattern of the optic neuropathy may arise from a chokepoint in the optic nerve in the region of the nerve head and lamina cribosa, and which may be more severe in those LHON family members who become visually affected. It is hypothesized that the respiratory chain dysfunction leads to axoplasmic stasis and swelling, thereby blocking ganglion cell function and causing loss of vision. In some LHON patients, this loss of function is reversible in a substantial number of ganglion cells, but in others, a cell death pathway (probably apoptotic) is activated with subsequent extensive degeneration of the retinal ganglion cell layer and optic nerve.     

Ocular neuroprotection by siRNA targeting caspase-2

Retinal ganglion cell (RGC) loss after optic nerve damage is a hallmark of certain human ophthalmic diseases including ischemic optic neuropathy (ION) and glaucoma. In a rat model of optic nerve transection, in which 80% of RGCs are eliminated within 14 days, caspase-2 was found to be expressed and cleaved (activated) predominantly in RGC. Inhibition of caspase-2 expression by a chemically modified synthetic short interfering ribonucleic acid (siRNA) delivered by intravitreal administration significantly enhanced RGC survival over a period of at least 30 days. This exogenously delivered siRNA could be found in RGC and other types of retinal cells, persisted inside the retina for at least 1 month and mediated sequence-specific RNA interference without inducing an interferon response. Our results indicate that RGC apoptosis induced by optic nerve injury involves activation of caspase-2, and that synthetic siRNAs designed to inhibit expression of caspase-2 represent potential neuroprotective agents for intervention in human diseases involving RGC loss.     

Early downregulation of IGF-I decides the fate of rat retinal ganglion cells after optic nerve injury

Retinal ganglion cells (RGCs) die by apoptosis after optic nerve injury. A number of reports have separately shown changes in pro-apoptotic proteins such as the Bcl-2 family members following optic nerve injury. However, induction time of these apoptotic signals has not been identified due to different treatments of the optic nerve, and insufficient time intervals for measurements. Therefore, the stream of cell death signals is not well understood. In the present study, we systematically reinvestigated a detailed time course of these cell death/survival signals in the rat retina after optic nerve crush, to determine the signal cascade leading to RGC apoptosis. The most conspicuous changes detected in the retina were the rapid inactivation of phospho-Akt and phospho-Bad proteins 2-3 days after optic nerve damage, and the subsequent gradual activation of Bax protein and caspase-3 activity accompanied by cell loss of RGCs 6 days after nerve injury. Cellular localization of these molecular changes was limited to RGCs. Furthermore, amount of insulin-like growth factor-I (IGF-I), an activator of the phosphatidyl inositol-3-kinase (PI3K)/Akt system, was initially decreased from RGCs 1-2 days just prior to the inactivation of phospho-Akt by optic nerve crush. Conversely, supplementation with IGF-I into the rat retina induced upregulation of phospho-Akt expression and cell survival of RGCs both in vitro and in vivo. Thus, injury to the optic nerve might induce early changes in cellular homeostasis with a plausible loss of trophic support for injured RGCs. Actually, IGF-I drastically enhanced neurite outgrowth from adult rat RGCs via a wortmannin-dependent mechanism in a retinal explant culture. Our data strongly indicate that IGF-I is a key molecule that induces RGC apoptosis or RGC survival and regeneration in the retina during the early stage of optic nerve injury.