Faculty Bibliography

Idiopathic sclerosing inflammation of the orbit is a distinct form of orbital inflammatory disease characterized by slow and relentless involvement of orbital structures. It is this insidious and relentless course that makes distinction from neoplastic lesions clinically difficult. We report the case of a patient with a several-week history of headache and decreased vision that was originally thought to represent an optic nerve sheath meningioma, based on clinical and radiographic evaluation. Subsequent histopathology from an optic nerve biopsy, however, was more consistent with optic nerve glioma. Eventually, pathologic examination of whole sections through the optic nerve was required to establish and confirm the actual diagnosis of sclerosing orbital inflammation.

The Controlled High Risk Avonex Multiple Sclerosis Study (CHAMPS) tested whether interferon beta la (Avonex) treatment would benefit patients who had experienced a first acute demyelinating event involving the optic nerve, brain stem/cerebellum, or spinal cord, and who displayed MRI brain signal abnormalities that have previously predicted a high likelihood of future MS-like events. The study randomized 383 patients into an Avonex-treated and a placebo-treated group; both groups received intravenous methylprednisolone 1 gm/d followed by prednisone 1 mg/kg for 11 days. The Avonex-treated group demonstrated a 44% reduction in the 3-year cumulative probability of developing clinically definite multiple sclerosis (rate ratio 0.56, 95% confidence interval 0.38 to 0.8; P = 0.002). At 18 months, treatment with Avonex was associated with a significant reduction of new T2 lesions, gadolinium enhanced lesions and T2 lesion volume. Among placebo-treated patients, 82% had developed a new subclinical MRI signal abnormality by the eighteenth month after study entry. Treatment benefit was observed irrespective of the qualifying event. The findings of this study support the efficacy of Avonex therapy in significantly reducing the 3-year likelihood of future neurologic events and worsening of the brain MRI in patients with a first acute CNS demyelinating event.

A 33-year-old man developed a complete third nerve palsy in the setting of acute bacterial endocarditis. MRI revealed an ischemic stroke in the cerebral peduncle involving the third nerve fascicle. Subsequently, he was observed to have paradoxic elevation of the eyelid on adduction and downgaze. To the authors' knowledge, this is the first demonstration of oculomotor synkinesis after an acquired, ischemic CNS lesion.

The authors report three patients with acute, chronic, and recurrent neuropathy associated with varicella zoster virus (VZV) infection but without zoster rash. CSF of all three patients contained VZV immunoglobulin G antibody, but not herpes simplex virus. In two patients, serum/CSF ratios of VZV immunoglobulin G were reduced compared to normal ratios for immunoglobulin G and albumin, and one patient also had VZV immunoglobulin M in CSF. All three patients received antiviral therapy and improved. The diagnosis of nervous system infection by VZV may be confirmed by the presence of antibody to VZV in CSF even without detectable VZV DNA.

Treatment decisions for ocular myasthenia gravis (OMG) should be based on symptomatology. Local, nonpharmacologic treatment of ptosis or diplopia is successful in relatively few patients, and the majority of patients require drug therapy for satisfactory resolution of their symptoms. Response to anticholinesterase agents is variable, but should always be used as the first-line agent or adjunctive therapy in the treatment of OMG. It is unknown whether early treatment of OMG with corticosteroids or other immunosuppressive agents prevents or delays the development of generalized myasthenia, although some observations support this speculation. Corticosteroids are usually necessary for adequate improvement of ophthalmoplegia or ptosis. Surgical correction of ptosis or ocular motility deficits is not recommended for most patients with OMG, because of the fluctuating nature of the deficits and the high rate of recurrent deficits following surgery. All patients with OMG should be screened for the presence of thymus tumors, and thymectomy is recommended for all patients with a thymoma. Some patients with OMG who do not harbor a thymus tumor may also benefit from thymectomy.

We report two patients who developed isolated visual symptoms and signs as initial manifestations of Creutzfeldt-Jakob disease (CJD). Both patients had normal conventional T1- and T2-weighted brain magnetic resonance (MR) images; in one patient, early cortical abnormalities were detected by diffusion-weighted and fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Results from the cerebrospinal fluid assay for the 14-3-3 brain protein were also negative in one patient, despite pathologic confirmation of CJD at autopsy. The Heidenhain variant of CJD should be considered in all patients who present with isolated visual manifestations, including homonymous hemianopsia and normal conventional brain MRI. Diffusion-weighted and FLAIR MRI may demonstrate early cortical abnormalities in patients with CJD. The CSF assay for the 14-3-3 protein may be normal, even in pathologically confirmed cases.

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.