Neuro-ophthalmic Mechanisms Of Disease

疾病的神经眼科机制

• 批准号: 8149158
• 负责人: Edmond J FitzGibbon
• 金额: $ 28.09万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 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/8149158
• 关键词: Diagnosis; Disease

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 (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. 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.

在这份报告中，我将集中在各种神经退行性疾病的研究，这些疾病具有特征性的眼部异常和影响视神经的疾病，如纤维结构不良和神经纤维瘤病。 眼动控制分布在整个大脑中，不同影响大脑部分的疾病可以以不同且通常特定的方式影响眼球运动。我们记录了患有神经退行性疾病和遗传性疾病的患者的眼球运动，以表征他们的眼球运动障碍，以帮助做出特定的诊断，将表型与基因型相关联，分期疾病进展，并深入了解眼球运动产生的过程。以下是几个例子。 纤维性发育不良（FD）是一种疾病，其中正常骨被纤维骨组织取代。多骨型常累及前颅底，包括蝶骨。视神经穿过蝶骨翼，在CT成像中经常发现被FD包裹。视神经纤维异常增殖症的治疗是有争议的，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Michael柯林斯博士合作，对80多名纤维性结构不良患者进行了检查，其中许多患者继续接受神经眼科检查纵向随访，以跟踪这种疾病的自然病史。 我们曾报道过，即使视神经管被发育不良的骨质包裹，视觉改变也很少发生。该观察结果的重要性在于阻止预防性椎管减压手术，因为其伤害的可能性更大。 另一个警告是，患有McCune Albright综合征（纤维性发育不良、内分泌病和咖啡Au lait斑的三联征）的患者，如果生长激素水平高且颅骨受累，应密切进行临床随访，因为他们的视神经更容易受到眼眶变化的影响。 1型神经纤维瘤病（NF 1）是一种常见的常染色体显性遗传病。 丛状神经纤维瘤发生在约25%的患者中，这些是NF 1最令人衰弱的并发症。中枢神经系统胶质瘤和其他神经眼科表现的发病率较高。 与NCI的Brigitte Wideman合作，两组NF 1患者正在眼科诊所接受随访。 NF 1患者将入组自然史研究，并纵向随访，记录几个参数，包括Lisch结节、视力和眼球运动。 患有CNS神经胶质瘤的NF 1患者将被纳入聚乙二醇干扰素α-2b（Pegintron）的1期临床试验。两个研究组均将接受完整的神经眼科检查和成像。