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.
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