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Exploring the Link Between Dry Eye and Migraine: From Eye to Brain. 探索干眼症与偏头痛之间的联系:从眼睛到大脑
IF 4.4 Q1 Medicine Pub Date : 2021-03-04 eCollection Date: 2021-01-01 DOI: 10.2147/EB.S234073
Brandon S Baksh, Julia Costa Garcia, Anat Galor

Dry eye and migraine are common diseases with large societal and economic burdens that have recently been associated in the literature. This review outlines the link between dry eye and migraine, which may have implications for reducing their respective burdens. We highlight possible shared pathophysiology, including peripheral and central sensitization, as the potential link between dry eye and migraine. Finally, therapies targeting similar pathophysiological mechanisms between dry eye and migraine are discussed.

干眼症和偏头痛是常见疾病,对社会和经济造成巨大负担,最近有文献将两者联系起来。本综述概述了干眼症和偏头痛之间的联系,这可能会对减轻它们各自的负担产生影响。我们强调了干眼症和偏头痛之间可能存在的共同病理生理学,包括外周和中枢敏感化。最后,我们还讨论了针对干眼症和偏头痛之间相似病理生理机制的疗法。
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引用次数: 0
Neuro-Ophthalmological Manifestations of Craniosynostosis: Current Perspectives. 颅畸形的神经眼科表现:当前视角。
IF 4.4 Q1 Medicine Pub Date : 2021-01-29 eCollection Date: 2021-01-01 DOI: 10.2147/EB.S234075
Michael Duan, Jesse Skoch, Brian S Pan, Veeral Shah

Craniosynostosis, a premature fusion of cranial sutures that can be isolated or syndromic, is a congenital defect with a broad, multisystem clinical spectrum. The visual pathway is prone to derangements in patients with craniosynostosis, particularly in syndromic cases, and there is a risk for permanent vision loss when ocular disease complications are not identified and properly treated early in life. Extensive advancements have been made in our understanding of the etiologies underlying vision loss in craniosynostosis over the last 20 years. Children with craniosynostosis are susceptible to interruptions in visual input arising from strabismus, refractive errors, and corneal damage; any of these aberrations can result in understimulation of the visual cortex during childhood neurodevelopment and permanent amblyopia. Elevated intracranial pressure resulting from abnormal cranial shape or volume can lead to papilledema and, ultimately, optic atrophy and vision loss. A pediatric ophthalmologist is a crucial component of the multidisciplinary care team that should be involved in the care of craniosynostosis patients and consistent ophthalmologic follow-up can help minimize the risk to vision posed by such entities as papilledema and amblyopia. This article aims to review the current understanding of neuro-ophthalmological manifestations in craniosynostosis and explore diagnostic and management considerations for the ophthalmologist taking care of these patients.

颅合畸形(Craniosynostosis)是一种颅缝过早融合的疾病,可以是孤立的,也可以是综合征,是一种先天性缺陷,具有广泛的、多系统的临床表现。颅脑发育不全患者的视觉通路很容易发生紊乱,尤其是在综合征病例中,如果不能在生命早期发现眼部疾病并进行适当治疗,就有可能导致永久性视力丧失。在过去的 20 年中,我们对颅突眼视力丧失的病因有了更深入的了解。由于斜视、屈光不正和角膜损伤等原因,颅脑发育不全患儿的视觉输入很容易受到干扰;其中任何一种畸变都可能导致视觉皮层在儿童神经发育期间受到的刺激不足,并造成永久性弱视。颅骨形状或体积异常导致的颅内压升高可引起乳头水肿,最终导致视神经萎缩和视力丧失。小儿眼科医生是多学科护理团队的重要组成部分,应参与颅脑发育异常患者的护理工作,持续的眼科随访有助于将乳头水肿和弱视等疾病对视力造成的风险降至最低。本文旨在回顾目前对颅突症神经眼科表现的认识,并探讨眼科医生在诊断和管理这些患者时应注意的事项。
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引用次数: 0
Glaucoma as Neurodegeneration in the Brain. 青光眼是大脑中的神经变性。
IF 4.4 Q1 Medicine Pub Date : 2021-01-18 eCollection Date: 2021-01-01 DOI: 10.2147/EB.S293765
Jane W Chan, Noel C Y Chan, Alfredo A Sadun

Glaucoma, a group of diseases characterized by progressive optic nerve degeneration that results in irreversible blindness, can be considered a neurodegenerative disorder of both the eye and the brain. Increasing evidence from human and animal studies have shown that glaucoma shares some common neurodegenerative pathways with Alzheimer's disease (AD) and other tauopathies, such as chronic traumatic encephalopathy (CTE) and frontotemporal dementia. This hypothesis is based on the focal adhesion pathway hypothesis and the spreading hypothesis of tau. Not only has the Apolipoprotein E (APOE) gene been shown to be associated with AD, but also with primary open angle glaucoma (POAG). This review will highlight the relevant literature in the past 20 years from PubMed that show the pathogenic overlap between POAG and AD. Neurodegenerative pathways that contribute to transsynaptic neurodegeneration in AD and other tauopathies might also be similar to those in glaucomatous neurodegeneration.

青光眼是一组以视神经进行性变性导致不可逆失明为特征的疾病,可以被认为是眼睛和大脑的神经退行性疾病。来自人类和动物研究的越来越多的证据表明,青光眼与阿尔茨海默病(AD)和其他tau病(如慢性创伤性脑病(CTE)和额颞叶痴呆)有一些共同的神经退行性途径。该假说是基于tau蛋白的黏附途径假说和扩散假说。载脂蛋白E (APOE)基因不仅与AD有关,还与原发性开角型青光眼(POAG)有关。本综述将重点介绍近20年来PubMed中显示POAG与AD致病重叠的相关文献。阿尔茨海默病和其他牛头病中导致经突触神经变性的神经退行性通路也可能与青光眼神经变性相似。
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引用次数: 25
Optical Coherence Tomography in Patients with Alzheimer's Disease: What Can It Tell Us? 阿尔茨海默病患者的光学相干断层扫描:它能告诉我们什么?
IF 4.4 Q1 Medicine Pub Date : 2021-01-08 eCollection Date: 2021-01-01 DOI: 10.2147/EB.S235238
Ailin Song, Nicholas Johnson, Alexandria Ayala, Atalie C Thompson

Purpose: Although Alzheimer's disease (AD) is a leading cause of dementia worldwide, its clinical diagnosis remains a challenge. Optical coherence tomography (OCT) and OCT with angiography (OCTA) are non-invasive ophthalmic imaging tools with the potential to detect retinal structural and microvascular changes in patients with AD, which may serve as biomarkers for the disease. In this systematic review, we evaluate whether certain OCT and OCTA parameters are significantly associated with AD and mild cognitive impairment (MCI).

Methods: PubMed database was searched using a combination of MeSH terms to identify studies for review. Studies were organized by participant diagnostic groups, type of imaging modality, and OCT/OCTA parameters of interest. Participant demographic data was also collected and baseline descriptive statistics were calculated for the included studies.

Results: Seventy-one studies were included for review, representing a total of 6757 patients (2350 AD, 793 MCI, 2902 healthy controls (HC), and 841 others with a range of other neurodegenerative diagnoses). The mean baseline ages were 72.78±3.69, 71.52±2.88, 70.55±3.85 years for AD, MCI and HC groups, respectively. The majority of studies noted significant structural and functional decline in AD patients when compared to HC. Although analysis of MCI groups yielded more mixed results, a similar pattern of decline was often noted amongst patients with MCI relative to HC. OCT and OCTA measurements were also shown to correlate with established measures of AD such as neuropsychological testing or neuroimaging.

Conclusion: OCT and OCTA show great potential as non-invasive technologies for the diagnosis of AD. However, further research is needed to determine whether there are AD-specific patterns of structural or microvascular change in the retina and optic nerve that distinguish AD from other neurodegenerative diseases. Development of sensitive and specific OCT/OCTA parameters will be necessary before they can be used to detect AD in clinical settings.

目的:虽然阿尔茨海默病(AD)是世界范围内痴呆症的主要原因,但其临床诊断仍然是一个挑战。光学相干断层扫描(OCT)和OCT血管造影(OCTA)是一种非侵入性眼科成像工具,具有检测AD患者视网膜结构和微血管变化的潜力,可作为该疾病的生物标志物。在这篇系统综述中,我们评估了某些OCT和OCTA参数是否与AD和轻度认知障碍(MCI)显著相关。方法:使用MeSH术语组合检索PubMed数据库,以确定需要审查的研究。研究按参与者诊断组、成像方式类型和感兴趣的OCT/OCTA参数进行组织。还收集了参与者的人口统计数据,并计算了纳入研究的基线描述性统计。结果:纳入71项研究,共6757例患者(2350例AD, 793例MCI, 2902例健康对照(HC)和841例其他神经退行性诊断)。AD组、MCI组和HC组的平均基线年龄分别为72.78±3.69岁、71.52±2.88岁、70.55±3.85岁。大多数研究表明,与HC相比,AD患者的结构和功能明显下降。虽然对轻度认知损伤组的分析得出的结果比较复杂,但在轻度认知损伤患者中,与HC患者相比,出现了相似的下降模式。OCT和OCTA测量也被证明与阿尔茨海默病的既定测量方法相关,如神经心理测试或神经影像学。结论:OCT和OCTA在AD的无创诊断中具有很大的应用潜力。然而,需要进一步的研究来确定视网膜和视神经中是否存在AD特异性的结构或微血管改变模式,以区分AD与其他神经退行性疾病。开发敏感和特定的OCT/OCTA参数是必要的,然后才能在临床环境中用于检测AD。
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引用次数: 24
Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review. 免疫检查点抑制剂的神经眼科并发症:系统综述。
IF 4.4 Q1 Medicine Pub Date : 2020-11-03 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S277760
Caberry W Yu, Matthew Yau, Natalie Mezey, Ishraq Joarder, Jonathan A Micieli

Objective: Immune checkpoint inhibitors (ICIs) are novel cancer therapies that may be associated with immune-related adverse events (IRAEs) and come to the attention of neuro-ophthalmologists. This systematic review aims to synthesize the reported ICI-associated IRAEs relevant to neuro-ophthalmologists to help in the diagnosis and management of these conditions.

Methods: A systematic review of the literature indexed by MEDLINE, Embase, CENTRAL, and Web of Science databases was searched from inception to May 2020. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Primary studies on ICIs and neuro-ophthalmic complications were included. Outcomes included number of cases and incidence of neuro-ophthalmic IRAEs.

Results: Neuro-ophthalmic complications of ICIs occurred in 0.46% of patients undergoing ICI and may affect the afferent and efferent visual systems. Afferent complications include optic neuritis (12.8%), neuroretinitis (0.9%), and giant cell arteritis (3.7%). Efferent complications include myasthenia gravis (MG) (45.0%), thyroid-like eye disease (11.9%), orbital myositis (13.8%), general myositis with ptosis (7.3%), internuclear ophthalmoplegia (0.9%), opsoclonus-myoclonus-ataxia syndrome (0.9%), and oculomotor nerve palsy (0.9%). Pembrolizumab was the most common causative agent for neuro-ophthalmic complications (32.1%). Mortality was highest for MG (19.8%). Most patients (79.8%) experienced improvement or complete resolution of neuro-ophthalmic symptoms due to cessation of ICI and immunosuppression with systemic corticosteroids.

Conclusion: While incidence of neuro-ophthalmic IRAEs is low, clinicians involved in the care of cancer patients must be aware of their presentation to facilitate prompt recognition and management. Collaboration between oncology and neuro-ophthalmology teams is required to effectively manage patients and reduce morbidity and mortality.

目的:免疫检查点抑制剂(ICIs)是一种新型癌症疗法,可能与免疫相关不良事件(IRAEs)有关,并引起神经眼科医生的注意。本系统综述旨在总结与神经眼科医生相关的 ICI 相关 IRAE 报告,以帮助诊断和管理这些病症:方法:对 MEDLINE、Embase、CENTRAL 和 Web of Science 等数据库收录的文献进行了系统性检索。报告遵循《系统综述和荟萃分析首选报告项目》(PRISMA)指南。纳入了有关 ICIs 和神经眼科并发症的主要研究。结果包括病例数和神经眼科 IRAE 的发生率:结果:接受 ICI 的患者中有 0.46% 出现了 ICI 神经眼科并发症,这些并发症可能会影响传入和传出视觉系统。传入并发症包括视神经炎(12.8%)、神经视网膜炎(0.9%)和巨细胞动脉炎(3.7%)。传出并发症包括重症肌无力(MG)(45.0%)、甲状腺样眼病(11.9%)、眼眶肌炎(13.8%)、伴有上睑下垂的全身肌炎(7.3%)、核间性眼肌麻痹(0.9%)、肌阵挛-肌阵挛-共济失调综合征(0.9%)和眼运动神经麻痹(0.9%)。Pembrolizumab是神经眼科并发症最常见的致病因子(32.1%)。MG的死亡率最高(19.8%)。大多数患者(79.8%)在停止使用ICI和全身皮质类固醇免疫抑制后,神经眼科症状得到改善或完全缓解:结论:虽然神经眼科 IRAE 的发病率较低,但参与癌症患者护理的临床医生必须了解其表现形式,以便及时识别和处理。肿瘤科和神经眼科团队必须通力合作,才能有效管理患者,降低发病率和死亡率。
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引用次数: 0
A Review of Neuro-Ophthalmological Manifestations of Human Coronavirus Infection. 人冠状病毒感染的神经眼科表现综述
IF 4.4 Q1 Medicine Pub Date : 2020-10-30 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S268828
Maria Elisa Luís, Diogo Hipólito-Fernandes, Catarina Mota, Diogo Maleita, Catarina Xavier, Tiago Maio, João Paulo Cunha, Joana Tavares Ferreira

Introduction: Human coronavirus (HCoVs) are a group of viruses with recognized neurotropic and neuroinvasive capabilities. The reports on the neurological and ocular findings are increasing day after day and several central and peripheral neurological manifestations are already described. However, none specifically describes the neuro-ophthalmological manifestation of HCoVs. This is the first article specifically reviewing neuro-ophthalmological manifestations of HCoVs infection.

Methods: PubMed and Google Scholar databases were searched using the keywords: coronaviridae, coronavirus, COVID-19, SARS-CoV-2, SARS-CoV-1, MERS, ocular, ophthalmology, ophthalmological, neuro-ophthalmology, neurological, manifestations. A manual search through the reference lists of relevant articles was also performed. There were no restrictions concerning language or study type and publications not yet printed but available online were considered.

Results: Coronavirus eye involvement is not frequent and includes mostly a typical viral follicular conjunctivitis. Recently, retinal anatomical alterations were described using optic coherence tomography. Neuro-ophthalmological symptoms and signs can appear isolated or associated with neurological syndromes. The manifestations include headache, ocular pain, visual impairment, diplopia, and cranial nerve palsies secondary to Miller Fisher syndrome, Guillain-Barré syndrome, or encephalitis, and nystagmus.

Conclusion: Neurological and neuro-ophthalmological syndromes, symptoms, and signs should not be neglected and a complete ophthalmological examination of these patients should be performed to fully describe ocular manifestations related to HCoVs. We believe that major ocular and neuro-ophthalmological manifestations reports lack due to safety issues concerning detailed ophthalmological examination; on the other hand, in a large number of cases, the presence of life-threatening coronavirus disease hinders ocular examination and ophthalmologist's visit to the intensive care unit.

人类冠状病毒(HCoVs)是一类公认的嗜神经性和侵袭性病毒。关于神经学和眼学发现的报告日复一日地增加,并且已经描述了几种中枢和周围神经学表现。然而,没有一个专门描述hcov的神经-眼科表现。这是第一篇专门回顾hcov感染的神经-眼科表现的文章。方法:以冠状病毒科、冠状病毒、COVID-19、SARS-CoV-2、SARS-CoV-1、MERS、眼科、眼科、神经眼科、神经学、表现为关键词检索PubMed和Google Scholar数据库。还对相关文章的参考书目进行了人工检索。对语言或研究类型没有限制,并考虑了尚未印刷但可在网上获得的出版物。结果:冠状病毒累及眼部并不常见,主要包括典型的病毒性滤泡性结膜炎。最近,视网膜解剖改变被描述使用光学相干断层扫描。神经眼科症状和体征可单独出现或与神经系统综合征相关。其表现包括头痛、眼痛、视力损害、复视、继发于米勒-费雪综合征、格林-巴-罗综合征或脑炎和眼球震颤的脑神经麻痹。结论:不应忽视神经和神经眼科综合征、症状和体征,应对这些患者进行完整的眼科检查,以充分描述与hcov相关的眼部表现。我们认为,由于详细眼科检查的安全性问题,主要的眼部和神经眼科表现报告不足;另一方面,在大量病例中,危及生命的冠状病毒的存在阻碍了眼科检查和眼科医生前往重症监护病房。
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引用次数: 2
Neurofibromatosis Type 1: Ocular Electrophysiological and Perimetric Anomalies. 神经纤维瘤病 1 型:眼电生理学和周边异常。
IF 3.1 Q1 OPHTHALMOLOGY Pub Date : 2020-10-21 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S255184
Marcella Nebbioso, Antonietta Moramarco, Alessandro Lambiase, Sandra Giustini, Marco Marenco, Emanuele Miraglia, Pasquale Fino, Chiara Iacovino, Ludovico Alisi

Introduction: Neurofibromatosis type 1 (NF1) is a multisystemic disease caused by the mutation of Nf1 gene located on chromosome 17q11.2. The mutation determines the loss of function of the protein neurofibromin with consequent uncontrolled cellular proliferation. Patients are characterized by a wide range of dermatological, neurological, and ophthalmological symptoms.

Purpose: The aim of the study was to evaluate, through pattern visual evoked potentials (p-VEPs) and frequency doubling technology (FDT) Matrix perimetry, the objective and psychophysical functionality of the optic pathways in a group of NF1 patient.

Methods: The study group consisted of 26 patients affected by NF1 and 17 healthy controls. Each patient underwent a complete ophthalmological examination, p-VEPs with the evaluation of amplitude and latency of the P100 wave, and FDT perimetry, with the evaluation of central sensitivity (CS), mean deviation (MD), pattern standard deviation (PSD) and glaucoma hemifield test (GHT).

Results: NF1 patients showed a statistically significant alteration in the transmission of visual impulse. P-VEPs results highlighted a reduced amplitude and an increased latency of the P100 wave, suggesting an involvement of the visual pathway. Visual field analysis showed a significant reduction in all the observed parameters as well (CS, MD, PSD, and GHT).

Conclusion: The present study showed, in NF1 patients, a qualitative and quantitative alteration in the conduction of stimuli through the visual pathways. The observed alterations are present, although, only at a subclinical level. None of the patients included in the study showed any manifest visual deficit nor had any concomitant pathology that might have affected the outcome of the study. In conclusion, electrophysiological exams and computer perimetry may take part, alongside a wider array of exams, in the differential diagnosis and later monitoring of NF1.

简介神经纤维瘤病 1 型(NF1)是一种多系统疾病,由位于染色体 17q11.2 上的 Nf1 基因突变引起。该基因突变决定了神经纤维瘤蛋白功能的丧失,从而导致细胞增殖失控。目的:本研究的目的是通过模式视觉诱发电位(p-VEPs)和频率倍增技术(FDT)矩阵测周法,评估一组 NF1 患者视通路的客观和心理物理功能:研究小组由 26 名 NF1 患者和 17 名健康对照者组成。每位患者都接受了全面的眼科检查、p-VEPs(评估 P100 波的振幅和潜伏期)和 FDT 视觉测定(评估中心灵敏度 (CS)、平均偏差 (MD)、模式标准偏差 (PSD) 和青光眼半视野测试 (GHT)):结果:NF1 患者的视觉冲动传输发生了统计学意义上的显著变化。P-VEPs结果显示,P100波的振幅减小,潜伏期延长,这表明视觉通路受到了影响。视野分析表明,所有观察到的参数(CS、MD、PSD 和 GHT)均明显减少:本研究显示,NF1 患者通过视觉通路传导刺激的质和量都发生了改变。所观察到的改变仅存在于亚临床水平。研究中没有任何患者出现明显的视觉障碍,也没有任何可能影响研究结果的并发病症。总之,电生理检查和计算机视力检查可与更广泛的检查一起,参与 NF1 的鉴别诊断和后期监测。
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引用次数: 0
Spaceflight Associated Neuro-Ocular Syndrome (SANS): A Systematic Review and Future Directions. 航天相关的神经-眼综合征(SANS):系统回顾和未来方向。
IF 4.4 Q1 Medicine Pub Date : 2020-10-19 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S234076
Yosbelkys Martin Paez, Lucy I Mudie, Prem S Subramanian

Purpose: To present a systematic review of the current body of literature surrounding spaceflight associated neuro-ocular syndrome (SANS) and highlight priorities for future research.

Methods: Three major biomedical databases were searched with the following terms: ((neuro ocular) OR ((brain) AND (eye))) AND ((spaceflight) OR (astronaut) OR (microgravity)) AND (ENGLISH[Language]). Once duplicates were removed, 283 papers were left. Articles were excluded if they were not written in English or conference abstracts only. We avoided including review papers which did not provide any new information; however, two reviews on the pathophysiology of SANS were included for completeness. No limitations on date of publication were used. All included entries were then summarized for their contribution to knowledge about SANS.

Results: Four main themes among the publications emerged: papers defining the clinical entity of SANS, its pathophysiology, technology used to study SANS, and publications on possible prevention of SANS. The key clinical features of SANS include optic nerve head elevation, hyperopic shifts, globe flattening, choroidal folds, and increased cerebrospinal fluid (CSF) volume in optic nerve sheaths. Two main hypotheses are proposed for the pathophysiology of SANS. The first being elevated intracranial pressure and the second compartmentalization of CSF to the globe. These hypotheses are not mutually exclusive, and our understanding of the pathophysiology of SANS is still evolving. The use of optical coherence tomography (OCT) has greatly furthered our knowledge about SANS, and with the deployment of OCT to the International Space Station, we now have ability to collect intraflight data. No effective prevention for SANS has been found, although fortunately, even with persistent anatomic and physiologic neuro-ocular changes, any functional impact has been correctable with spectacles.

Conclusion: This is the first systematic review of SANS. Despite the limitations of studying a syndrome that can only occur in a small, discrete population, we present a thorough overview of the literature surrounding SANS and several key areas important for future research are identified.

目的:对目前有关航天相关神经-眼综合征(SANS)的文献进行系统综述,并指出未来研究的重点。方法:检索三个主要生物医学数据库,检索词为:((神经眼)OR(脑)AND(眼))AND(航天)OR(宇航员)OR(微重力)AND(英语[语言])。除去重复的文件后,还剩下283份。非英文或会议摘要的文章被排除在外。我们避免纳入没有提供任何新信息的综述论文;然而,为了完整起见,我们纳入了两篇关于SANS病理生理学的综述。没有使用出版日期限制。然后总结所有包含的条目对SANS知识的贡献。结果:在出版物中出现了四个主题:定义SANS临床实体的论文,其病理生理学,用于研究SANS的技术,以及关于SANS可能预防的出版物。SANS的主要临床特征包括视神经头抬高、远视移位、球体变平、脉络膜褶皱和视神经鞘内脑脊液(CSF)体积增加。对SANS的病理生理机制提出了两种主要假设。第一种是颅内压升高,第二种是脑脊液向全球区隔化。这些假设并不相互排斥,我们对SANS病理生理学的理解仍在发展。光学相干层析成像(OCT)的使用极大地促进了我们对SANS的了解,并且随着OCT在国际空间站的部署,我们现在有能力收集飞行内部数据。虽然没有发现有效的预防SANS的方法,但幸运的是,即使有持续的解剖和生理性神经-眼改变,任何功能影响都可以通过眼镜矫正。结论:这是首次对SANS进行系统评价。尽管研究一种只能发生在小而离散的人群中的综合征存在局限性,但我们对围绕SANS的文献进行了全面概述,并确定了对未来研究重要的几个关键领域。
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引用次数: 20
Etiology of Retinal and Cerebellar Pathology in Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex. 西太平洋肌萎缩性侧索硬化症和帕金森-痴呆综合症视网膜和小脑病理的病因学。
IF 4.4 Q1 Medicine Pub Date : 2020-07-16 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S260823
Peter S Spencer

Purpose: To reexamine the etiology of a unique retinal pathology (linear and vermiform sub-retinal tubular structures) described among subjects with and without neurodegenerative disease in former high-incidence foci of Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in Guam (USA) and the Kii peninsula of Honshu island (Japan).

Methods: Analysis of published and unpublished reports of 1) ALS/PDC and the retinal and cerebellar pathology associated therewith and 2) exogenous neurotoxic factors associated with ALS/PDC and the developing retina and cerebellum.

Results: ALS/PDC retinal and cerebellar pathology matches persistent retinal and cerebellar dysplasia found in laboratory animals given single in utero or postnatal systemic treatment with cycasin, the principal neurotoxic component in the seed of cycad plants traditionally used for food (Guam) or oral medicine (Kii-Japan), both of which have been linked to the human neurodegenerative disease.

Conclusion: ALS/PDC-associated retinal and cerebellar dysplasia could arise from in utero exposure to methylazoxymethanol, the genotoxic metabolite of cycasin that results from maternal ingestion of this azoxyglucoside. These results support the environmental toxic etiology of retinal and brain pathology in ALS/PDC.

目的:重新检查一种独特的视网膜病理(线状和蚓状视网膜下管状结构)的病因,在美国关岛和日本本州岛Kii半岛的西太平洋肌萎缩性侧索硬化症和帕金森-痴呆复发症(ALS/PDC)的前高发灶中,有和没有神经退行性疾病的受试者中描述。方法:对已发表和未发表的ALS/PDC及其相关视网膜和小脑病理报告和与ALS/PDC及发育中的视网膜和小脑相关的外源性神经毒性因子进行分析。结果:ALS/PDC视网膜和小脑病理与在实验室动物中发现的持续性视网膜和小脑发育不良相吻合,实验动物在子宫内或出生后接受单一的苏铁素系统治疗,苏铁素是苏铁植物种子中的主要神经毒性成分,传统上用于食物(关岛)或口服药物(Kii-Japan),这两种植物都与人类神经退行性疾病有关。结论:ALS/ pdc相关的视网膜和小脑发育不良可能由子宫内暴露于甲基甲氧基甲醇引起,甲基甲氧基甲醇是苏铁素的遗传毒性代谢物,由母体摄入这种偶氮氧基糖苷引起。这些结果支持ALS/PDC患者视网膜和脑病理的环境毒性病因学。
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引用次数: 11
Clinical Prediction Score for Early Neuroimaging in Acquired Isolated Oculomotor Nerve Palsy. 获得性孤立性动眼神经麻痹早期神经影像学预测评分。
IF 4.4 Q1 Medicine Pub Date : 2020-07-14 eCollection Date: 2020-01-01 DOI: 10.2147/EB.S253305
Juthamat Witthayaweerasak, Natchada Tansuebchueasai, Nipat Aui-Aree

Purpose: An immediate neuroimaging investigation in patients with isolated oculomotor nerve palsy (ONP) remains controversial. We aimed to develop a clinical prediction score to determine whether or not acquired isolated ONP patients require prompt imaging.

Methods: A retrospective study was performed. Demographic data and clinical presentations were collected to determine predictive factors favored for early brain imaging using multivariate logistic regression analysis.

Results: Ninety-seven eyes of 96 patients diagnosed with isolated ONP were included. Forty-one eyes (42.3%) were caused by ischemia, while the other 56 eyes (57.7%) were caused by non-ischemic etiologies, namely aneurysm (n = 22), trauma (n = 18), inflammation (n = 5), tumor (n = 4), and others (n = 7). Eighty-two eyes (84.5%) had undergone neuroimaging study due to initially suspected non-ischemic causes. Only 36 (43.9%) revealed concordant diagnosis. The potential clinical predictors favored for neuroimaging using multivariate logistic regression analysis were age 10‒50 years (adjusted odds ratio [aOR] 9.01, 95% CI: 1.25‒64.8), age 51‒70 years (aOR 1.71, 95% CI: 0.46‒6.35), history of head trauma (aOR 7.14, 95% CI: 1.19‒42.9), absence of vascular risk factors (aOR 3.85, 95% CI: 1.23‒12.1), and poor pupillary response (aOR 6.96, 95% CI: 1.99‒24.3). The predictor scores with an area under the ROC curve of 0.852 were 4, 1, 4, 3, and 4, respectively. The optimum cut-point was 3 for a sensitivity of 96% and specificity of 44%.

Conclusion: Patients with acquired isolated ONP should be considered early neuroimaging studies when they are younger than 50 years old, have a history of head trauma, have no history of vascular risk factors, or have poor pupillary reaction.

目的:孤立性动眼神经麻痹(ONP)患者的即时神经影像学调查仍然存在争议。我们的目的是建立一个临床预测评分,以确定获得性孤立性ONP患者是否需要及时影像学检查。方法:回顾性研究。收集人口统计数据和临床表现,利用多变量logistic回归分析确定有利于早期脑成像的预测因素。结果:96例确诊为孤立性ONP的患者中97只眼入选。41只眼(42.3%)为缺血所致,56只眼(57.7%)为非缺血性病因所致,分别为动脉瘤(22只)、外伤(18只)、炎症(5只)、肿瘤(4只)及其他(7只)。82只眼(84.5%)因初步怀疑非缺血性病因而行神经影像学检查。只有36例(43.9%)诊断一致。多因素logistic回归分析支持神经影像学的潜在临床预测因子为10-50岁(调整比值比[aOR] 9.01, 95% CI: 1.25-64.8)、51-70岁(aOR 1.71, 95% CI: 0.46-6.35)、头部外伤史(aOR 7.14, 95% CI: 1.19-42.9)、无血管危险因素(aOR 3.85, 95% CI: 1.23-12.1)和瞳孔反应差(aOR 6.96, 95% CI: 1.99-24.3)。ROC曲线下面积为0.852的预测因子得分分别为4、1、4、3、4。最佳切割点为3,灵敏度为96%,特异性为44%。结论:获得性孤立性ONP患者年龄小于50岁、有头部外伤史、无血管危险因素史或瞳孔反应差者应考虑早期神经影像学检查。
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引用次数: 2
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Eye and Brain
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