Faculty Bibliography

PURPOSE: To examine the potential for visual acuity loss, and its relation to extent and location of optic pathway gliomas in a cohort of children with neurofibromatosis type 1 studied with magnetic resonance imaging. METHODS: We reviewed the neuro-ophthalmologic records and brain/orbital magnetic resonance imaging scans for 43 consecutive pediatric patients with neurofibromatosis type 1 and optic pathway gliomas who were followed at the Children's Hospital of Philadelphia. The presence of visual loss, defined as abnormal visual acuity for age in one or both eyes, was determined. Optic pathway gliomas were classified by tumor extent and location according to involvement of the optic nerves, chiasm, and postchiasmal structures by magnetic resonance imaging. RESULTS: Involvement of the optic tracts and other postchiasmal structures at tumor diagnosis was associated with a significantly higher probability of visual acuity loss (P =.048, chi-square test). Visual loss was noted in 20 of 43 patients (47%) at a median age of 4 years; however, three patients developed visual acuity loss for the first time during adolescence. CONCLUSIONS: In pediatric patients with neurofibromatosis type 1 and optic pathway gliomas, the likelihood of visual loss is dependent on the extent and location of the tumor by magnetic resonance imaging and is particularly associated with involvement of postchiasmal structures. Furthermore, older age during childhood (adolescence) does not preclude the occurrence of visual loss. Close follow-up beyond the early childhood years, particularly for those with postchiasmal tumor, is recommended.

Ophthalmologic practice requires a solid foundation in the principles and interpretation of the neuro-ophthalmologic examination. This article reviews the techniques used in the neuro-ophthalmologic examination to assess visual acuity, ocular motility, visual fields, the pupils, the eyelids, and the fundus. The neuro-ophthalmological examination in comatose patients is also reviewed. Neuro-ophthalmic techniques are paramount in the assessment of comatose patients, especially with regard to brainstem localization and diagnosis.

We describe a 45-year-old man with biopsy proven cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This patient demonstrated unique retinal findings, including arteriole narrowing and sheathing, irregular choroidal filling on fluorescein angiography, and patchy visual field loss. CADASIL is a hereditary, nonamyloid, nonathersclerotic microangiopathy. This disorder has been mapped to chromosome 19 with mutations in the Notch 3 gene. Deposits of granular osmiophilic material in the basal lamina of the smooth muscle cells of small vessels are considered pathognomonic for CADASIL and are typically seen only on electron microscopy. Although CADASIL is a systemic vascular disease affecting the entire arteriole tree, we are unaware of other reports describing the retinal findings observed in our patient.

The clinical characteristics, differential diagnosis, and treatment options are presented for five different categories of neuro-ophthalmic disease. Nystagmus, optic neuritis, diplopia, pseudotumor cerebri, and temporal arteritis, are frequently encountered in neuro-ophthalmic practice. This article focuses on current therapies for these neuro-ophthalmic disorders. Potential differences in approach to pediatric versus adult patients are emphasized.

BACKGROUND: Ross syndrome is an uncommon disorder characterized by the triad of segmental anhidrosis, hyporeflexia, and tonic pupils. METHODS: The authors describe the clinical findings of five patients with Ross syndrome and detail the results of their pharmacologic and autonomic testing. RESULTS: In four patients, the classic findings of Ross syndrome were accompanied by Horner's syndrome. Other symptoms of dysautonomia were also common. CONCLUSIONS: These findings suggest that Ross syndrome is a dysautonomic condition of varying expression resulting from a generalized injury to ganglion cells or their projections.

Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon beta-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n= 118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.

Multiple myeloma and plasmacytoma are rare causes of mass lesions at the skull base and cavernous sinus. Sixth nerve palsy, in isolation or in combination with other cranial neuropathies, may occur rarely as the initial presenting feature of multiple myeloma. We report the neuro-ophthalmologic, radiologic, and pathologic findings for two patients who developed sixth nerve palsies as an initial manifestation of intracranial plasmacytoma and multiple myeloma. One patient presented with an isolated sixth nerve palsy in the setting of multiple vasculopathic risk factors. Treatable skull base lesions, including plasmacytoma and multiple myeloma, must be considered in patients with sixth nerve palsies, especially among those who demonstrate a progressive course or multiple cranial neuropathies.

A patient presented with symptoms of limbic and brainstem encephalitis, motor and sensory neuronopathy, cerebellar dysfunction, and highly positive anti-Hu antibodies. He also harbored P/Q-type calcium channel antibodies and manifested the Lambert-Eaton myasthenic syndrome (LEMS). Small-cell lung cancer was found, and he received both antineoplastic therapy and intravenous immunoglobulin (IVIg). Remission of the malignancy was achieved. Although the anti-Hu-related manifestations improved after therapy, LEMS has persisted, leading to IVIg dependency.

OBJECTIVE: To investigate the ability of a portable, personal computer-driven, pupillometer to record the pupillary response curve during the swinging flashlight test. Also, to determine whether these response curves can be used to identify and quantify relative asymmetry in the pupillary light reflex between eyes in healthy volunteers with simulated afferent pupil defects (APDs) and patients with optic neuropathies. DESIGN: Comparative, observational case series and instrument validation. PARTICIPANTS: Healthy volunteers with no known ocular disease and patients (n = 20) with various optic neuropathies noted to have relative APDs on examination. METHODS: Pupillary response curves of the right eye were recorded with a portable, electronic, infrared pupillometer from healthy volunteers (with and without simulated APDs) and patients with APDs while the light stimulus alternated between eyes, simulating the swinging flashlight test. Simulated APDs in healthy volunteers were created with increasingly dense neutral density filters in front of the left eye. MAIN OUTCOME MEASURES: Differences in constriction amplitude, latency, and constriction velocity of the pupillary response with right eye stimulation versus left eye stimulation in both groups of subjects. RESULTS: A significant correlation between neutral density filter strength and intereye differences was seen for all measurement parameters in volunteers with simulated APDs. Depending on the measurement parameter and stimulus intensity, simulated APDs of 0.6 log units or more could be distinguished from normal responses. Clinically graded true APDs had intereye differences similar to simulated APDs of the same density. Those with real and simulated APDs of 0.9 log units or more could be distinguished from healthy volunteers with 80% sensitivity and 92% specificity. Responses from those with real and simulated small APDs of 0.3 to 0.6 log units could not be distinguished reliably. CONCLUSIONS: Portable, personal-computer driven, electronic, infrared pupillography can record the swinging flashlight test accurately and identify large afferent pupillary defects. An affordable, portable, reliable device for identifying relative APDs would be useful in the identification and follow-up of patients with neurogenic vision loss.