Neuro-ophthalmic Mechanisms Of Disease

疾病的神经眼科机制

基本信息

批准号：
8339766
负责人：
Edmond J FitzGibbon
金额：
$ 29.5万
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/8339766
关键词：
Acoustic Neuroma Affect Anesthesia procedures Anterior Blindness Brain Diseases Brain Part Cafe-au-Lait Spot Cataract Characteristics Clinic Collaborations Complication Cornea Degenerative Disorder Dental Diagnosis Disease Disease Progression Dysplasia Enrollment Etiology Eye Eye Movements Facial paralysis Generations Genotype Glioma Goals Hamartoma Hereditary Disease Image Incidence Institutes Laboratories Lead Lisch nodules McCune-Albright Syndrome Measures Natural History Neuraxis Neurodegenerative Disorders Neurofibromatoses Neurofibromatosis 1 Neurofibromatosis 2 Neurologic Ocular Motility Disorders Operative Surgical Procedures Optic Nerve Optics Patients Phase I Clinical Trials Phenotype Plexiform Neurofibroma Process Protocols documentation Publishing Reporting Retinal Risk Saccades Somatotrophin increased Somatotropin Sphenoid bone structure Staging Subacute Neuronopathic Gaucher Disease Testing Thick Tissues Triad Acrylic Resin ViraferonPeg Vision Visual Wing bone cell motility cohort cranium disease natural history eye dryness insight oculomotor optic nerve disorder peginterferon alfa-2b prophylactic skull base tomography

项目摘要

In this report I will concentrate on studies of various neuro-degenerative diseases which have characteristic oculomotor abnormalities and in diseases that affect the optic nerve 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, correlate phenotype to genotype, stage disease progression, and to give insight into the processes underlying eye movement generation. Several examples appear below. Fibrous dysplasia (FD) is a disease where normal bone is replaced with fibro-osseous tissue. In the polyostotic form, 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 80 patients with fibrous dysplasia have been examined and many of these patients continue to be followed longitudinally with neuro-ophthalmologic exams to track the natural history of this disease. We have reported that even when the optic canal is encased with dysplastic bone,visual changes rarely occur. The importance of this observation is to discourage prophylactic canal decompression surgery since their is a greater likelihood of harm. Another caveat is that patients with McCune Albright syndrome (MAS - the triad of fibrous dysplasia, endocrinopathies and cafe au lait spots) who have high growth hormone levels and skull involvement should be clinically followed closely, since their optic nerves are more likely to be affected by orbital changes. Indeed, a preliminary report suggests that controlling excess growth hormone reduces the risk of optic neuropathy. Ocular coherence tomography of the optic nerve (NFL thickness) is proving to be a useful measure to follow MAS patients for the early occurrence of optic neuropathy. 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 a higher incidence of central nervous system gliomas and other neuro-ophthalmic manifestations. In collaboration with Brigitte Wideman of NCI, two groups of patients with NF1 are being followed in the eye clinic. NF1 patients will be enrolled in a natural history study and followed longitudinally noting several parameters including Lisch nodules, vision, and ocular motility. NF1 patients with CNS glioma will be enrolled in a phase 1 clinical trial of peginterferon alfa-2b (Pegintron). Both study groups will be followed with complete neuro-ophthalmic exams and imaging. 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) can lead to facial palsy and poor lid closure, corneal anesthesia, and dry eyes. NF2 patients also present with posterior cataracts and retinal hamartomas. We recently published the results of following a cohort of 15 patients with Gaucher type 3 disease. Significant findings include vertical saccade slowing with downward saccades more affected and evidence of slow progression of the disease as noted by saccadic recordings.

在本报告中，我将集中研究具有特征性眼动异常的各种神经差异疾病以及影响视神经的疾病，例如纤维性发育不良和神经瘤病。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，阶段疾病进展，并深入了解眼动运动产生的过程。下面显示了几个示例。纤维发育不良（FD）是一种疾病，正常骨被纤维骨组织代替。在多质体形式中，颅底碱经常涉及包括蝶骨骨头。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）合作，已经检查了80多名纤维发育不全患者的队列，其中许多患者继续接受神经莫科检查的纵向跟踪，以跟踪这种疾病的自然史。我们报告说，即使视管用发育不良的骨头包裹，视觉变化也很少发生。这种观察的重要性是劝阻预防性的运河减压手术，因为它们的可能性更大。另一个警告是，患有麦金纳·奥尔布赖特综合征的患者（MAS-纤维发育不全的三合会，内分泌病和咖啡馆的患者）患有高生长激素水平和颅骨受累的患者应在临床上紧随其后，因为其光学神经更有可能受到眶性变化的影响。实际上，初步报告表明，控制多余的生长激素会降低视力神经病的风险。事实证明，视神经（NFL厚度）的眼相干断层扫描是跟随MAS患者早期发生视觉神经病的有用措施。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性恐怖表现的发生率更高。与NCI的Brigitte Wideman合作，在Eye Clinic中遵循两组NF1患者。 NF1患者将参加一项自然历史研究，并遵循纵向注意的几个参数，包括Lisch结节，视力和眼动。 NF1 CNS神经胶质瘤患者将参加PEGINTERFERON ALFA-2B（PEGINTRON）的1期临床试验。两个研究组都将进行完整的神经性检查和成像。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，这些患者（或手术校正）的压缩会导致面部麻痹和盖子闭合，角膜麻醉和干眼睛。 NF2患者还出现后白内障和视网膜瘤瘤。我们最近发表了遵循15例Gaucher 3型疾病患者队列的结果。重大发现包括垂直扫视放缓，下向下扫视更受影响和疾病进展缓慢的证据。