Neuro-ophthalmic Mechanisms Of Disease

疾病的神经眼科机制

基本信息

批准号：
8938309
负责人：
Edmond J FitzGibbon
金额：
$ 21.82万
依托单位：
NATIONAL EYE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8938309
关键词：
Acoustic Neuroma Affect Anesthesia procedures Anterior Blindness Brain Diseases Brain Part Cataract Characteristics Child Clinic Collaborations Collection Complication Cornea Dental Development Diagnosis Diplopia Disease Disease Progression Dysplasia Endocrine Enrollment Erdheim-Chester Disease Etiology Exophthalmos Eye Eye Movements Facial paralysis Generations Genotype Glioma Goals Hamartoma Hearing Impaired Persons Hereditary Disease Histiocytosis Human Image Incidence Individual Institutes Kidney Laboratories Lead Life Lisch nodules Lung McCune-Albright Syndrome Motion Natural History Neuraxis Neurodegenerative Disorders Neurofibromatoses Neurofibromatosis 1 Neurofibromatosis 2 Neurologic Ocular Motility Disorders Ocular orbit Operative Surgical Procedures Optic Nerve Paper Patients Phenotype Plexiform Neurofibroma Polyostotic fibrous dysplasia Process Protocols documentation Publishing Recommendation Recruitment Activity Reporting Retinal Retroperitoneal Space Risk Somatotrophin increased Somatotropin Sphenoid bone structure Spottings Staging Stimulus Surgical Decompression System Techniques Testing Tissues Universities Vision Visual Motion Visual system structure Wing X-Ray Computed Tomography bone cell motility cohort disease natural history experience eye dryness histiocyte insight long bone oculomotor optic nerve disorder research study response skull base tumor

项目摘要

In this report I will concentrate on studies of various diseases which have characteristic oculomotor abnormalities, and also on diseases that affect vision or have neuro-ophthalmic consequences such as fibrous dysplasia and neurofibromatosis. Oculomotor control is distributed throughout the brain, and diseases differentially affecting parts of the brain can affect eye movements in different, and often specific ways. We have recorded eye movements in patients with neurodegenerative and genetic diseases to characterize their ocular motility disorder, to help make a specific diagnosis, to correlate phenotype to genotype, to stage disease progression, and to give insight into the processes underlying eye movement generation. We are currently analyzing the longitudinally recorded eye movmement of a cohort with Niemann Pick C disease. Fibrous dysplasia (FD) is a disease where normal bone is replaced with fibro-osseous tissue. Patients with McCune Albright syndrome have polyostotic fibrous dysplasia, endocrine abnormalities, and caf au lait spots. In McCune Albright syndrome, the anterior cranial base is frequently involved, including the sphenoid bones. The optic nerve passes through the sphenoid wing and is often found to be encased by FD on CT imaging. The management of fibrous dysplasia encased optic nerves is controversial, as optic neuropathy resulting in vision loss is the most frequently reported neurological complication. In collaboration with Dr. Michael Collins of the Dental Institute, a cohort of more than 90 patients with fibrous dysplasia continue to be followed longitudinally with neuro-ophthalmologic exams to track the natural history of this disease. Our experience in this cohort is that optic neuropathy is unusual and the recommendation is that surgical decompression not be done. Patients with high growth hormone are at risk for optic neuropathy but not if the growth hormone excess can be controlled. We continue to longitudinally follow these patients and recruit new patients with McCune Albright syndrome. Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder. Plexiform neurofibromas develop in about 25% of patients and these are among the most debilitating complication of NF1. There is also a higher incidence of central nervous system gliomas and other neuro-ophthalmic manifestations. In collaboration with Brigitte Wideman of NCI, NF1 patients enrolled in a natural disease study continue to be examined in the eye clinic. Several parameters are followed including Lisch nodules, vision, ocular motility and lid function. Complete neuro-ophthalmic exams and imaging are performed. In collaboration with colleagues at Georgetown University a paper was published on the natural history of orbital plexiform neurofibromas in children. Another ongoing natural history protocol follows patients with neurofibromatosis type 2 (NF2). These patients have acoustic neuromas and compression from these (or from surgical correction of vestibular schwannomas) can lead to facial palsy with poor lid closure, corneal anesthesia, and dry eyes. These complications put their eyes at risk for vision loss which can be devastating in these often deaf individuals. NF2 patients may also present with cataracts and retinal hamartomas. These patients are followed longitudinally for new tumor development. Erdheim Chester disease is a rare histiocytosis typically developing in patient in their 5th decade of life. Collections of histiocytes may be found in the long bones, retroperitoneal space, in the kidneys, lungs and the orbits among other spaces. Presentation in the orbit can lead to proptosis, diplopia, and optic neuropathy. We are longitudinally following a cohort of Erdheim Chester patients with Dr. Juvianee Estrada Veras for neuro-ophthalmic findingss. Orbital involvement is uncommon with less than 20% of our cohort demonstrating orbital masses. In collaboration with Boris Sheliga and Christian Quaia of the NEI, we continue to probe the visual motion system using ocular following response techniques pioneered by Fred Miles of the NEI. These approaches use the machine like eye movements made in response to differing stimuli to help understand the mechanisms underlying motion vision. In the past year experiments demonstrated how ocular following responses are constrained by early stages of the human visual system.

在本报告中，我将集中研究各种具有特征性眼动异常的疾病，以及影响视力或具有神经性后果的疾病，例如纤维发育异常和神经纤维瘤病。动眼控制分布在整个大脑中，对大脑的一部分有差异化的疾病会以不同的，通常特定的方式影响眼睛运动。我们记录了神经退行性和遗传疾病的患者的眼球运动，以表征其眼运动障碍，以帮助做出特定的诊断，将表型与基因型相关，以阶段疾病的进展并深入了解眼动运动产生的过程。我们目前正在分析与Niemann Pick C疾病的纵向记录的眼睛移动。纤维发育不良（FD）是一种疾病，正常骨被纤维骨组织代替。 McCune Albright综合征患者患有多质体纤维发育不良，内分泌异常和CAF AU LAIT斑点。在麦考纳·奥尔布赖特综合症中，经常涉及前颅骨，包括蝶骨骨骼。视神经穿过蝶翅，通常被发现被CT成像上的FD包裹。纤维发育不良包裹的视神经的管理是有争议的，因为导致视力丧失的视神经病变是最常见的神经系统并发症。与牙科研究所的迈克尔·柯林斯（Michael Collins）博士合作，由90多名纤维发育不良患者进行了纵向遵循神经莫科学检查，以跟踪这种疾病的自然历史。我们在该队列中的经验是，视神经病变是不寻常的，建议不进行手术减压。高生长激素的患者有视力神经病的风险，但如果可以控制生长激素过量的患者。我们继续纵向关注这些患者，并招募新患有麦康纳·奥尔布赖特综合症的患者。神经纤维瘤病1型（NF1）是常见的常染色体显性遗传疾病。大约25％的患者发育于大约25％的神经纤维瘤，这是NF1最令人衰弱的并发症之一。中枢神经系统神经胶质瘤和其他神经恐怖表现也更高。与NCI的Brigitte Wideman合作，在眼科诊所继续检查参加自然疾病研究的NF1患者。遵循了几个参数，包括Lisch结节，视觉，眼动和盖子功能。进行完整的神经性检查和成像。与乔治敦大学的同事合作，一篇论文发表了有关儿童轨道上的神经纤维瘤的自然史。另一种正在进行的自然历史方案是遵循2型神经纤维瘤病患者（NF2）。这些患者具有声学神经瘤和来自这些患者的压缩（或者是手术校正的前庭schwannomas）会导致面部麻痹，盖子闭合，角膜麻醉和干眼睛。这些并发症使他们的视力丧失风险在这些经常聋哑人中可能造成毁灭性。 NF2患者也可能出现白内障和视网膜瘤。这些患者纵向遵循新的肿瘤发育。埃德海姆·切斯特（Erdheim Chester）疾病是一种罕见的组织细胞增多症，通常在患者的第五个生命中发育。在长骨，腹膜后空间，肾脏，肺和轨道中，可以在其他空间中发现组织形成细胞的集合。轨道上的介绍会导致肝病，复视和视神经病变。我们正在纵向遵循欧德海姆·切斯特（Erdheim Chester）的同伴，尤维亚·埃斯特拉达（Juvianee Estrada Veras）进行神经性发现的发现。轨道涉及少于我们的队列占轨道质量的少于20％。在与NEI的Boris Sheliga和Christian Quaia的合作中，我们继续使用NEI的Fred Miles开创的眼部响应技术来探测视觉运动系统。这些方法使用机器就像对不同刺激的响应的眼动动作，以帮助了解运动视觉的基础机制。在过去的一年中，实验证明了眼睛以后的反应如何受到人类视觉系统的早期阶段的约束。