Neuro-ophthalmic Mechanisms Of Disease

在这份报告中，我将集中研究各种神经退行性疾病，这些疾病具有特征性的动眼神经异常，以及影响视神经的疾病，如纤维结构不良和神经纤维瘤病。 眼球运动控制分布在整个大脑中，而影响大脑不同部位的疾病可以以不同的、往往是特定的方式影响眼球运动。我们记录了神经退行性和遗传性疾病患者的眼球运动，以表征他们的眼球运动障碍，帮助做出特定的诊断，将表型与基因、疾病进展阶段相关联，并深入了解眼球运动产生的潜在过程。下面是几个例子。 纤维异常增殖症(FD)是一种正常骨骼被纤维骨组织取代的疾病。在多发性骨型中，前颅底经常受累，包括蝶骨。视神经穿过蝶骨翼，在CT影像上常可见其被FD包裹。由于视神经病变导致视力丧失是最常见的神经系统并发症，对包绕视神经的纤维异常增殖症的处理是有争议的。与牙科研究所的迈克尔·柯林斯博士合作，对80多名纤维发育不良患者进行了检查，其中许多患者继续进行纵向神经眼科检查，以追踪这种疾病的自然病史。我们已经报道过，即使视神经管被发育不良的骨包裹，视觉变化也很少发生。这一观察的重要性是为了阻止预防性的椎管减压手术，因为它们更有可能造成伤害。另一个警告是，麦库恩-奥尔布赖特综合征(纤维发育不良、内分泌疾病和咖啡馆斑点三合一)患者生长激素水平高，颅骨受累，临床应密切关注，因为他们的视神经更有可能受到眼眶变化的影响。 神经纤维瘤病1型(NF1)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大约25%的患者中，这是NF1最令人虚弱的并发症之一。中枢神经系统胶质瘤和其他神经眼科症状的发生率较高。与NCI的Brigitte Wideman合作，两组NF1患者正在眼科诊所接受跟踪。NF1患者将参加一项自然病史研究，并纵向记录几项参数，包括利施结节、视力和眼球运动。患有CNS胶质瘤的NF1患者将参加聚乙二醇干扰素α-2b(PEGINTRON)的1期临床试验。两个研究组都将接受全面的神经眼科检查和成像。

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.