Pasol, Joshua MD; Sternau, Linda MD; Luetmer, Patrick MD; Giannini, Caterina MD, PhD
Bascom Palmer Eye Institute (JP), University of Miami Miller School of Medicine, Miami, Florida; Department of Neurosurgery (LS), Mount Sinai Medical Center, Miami Beach, Florida; Department of Neuroradiology (PL), and Department of Neuropathology (CG), Mayo Clinic, Rochester, Minnesota.
A 75-year-old man experienced sudden loss of vision in his right eye. His past medical history was significant for non-insulin-dependent diabetes, hypertension, hypercholesterolemia, and an abdominal liposarcoma. He was receiving treatment for glaucoma with pressure-lowering drops and had been noted to have normal visual fields prior to the onset of visual loss. He denied any symptoms of temporal arteritis.
An examination at an outside facility 3 weeks after the onset of visual loss revealed vision of counting fingers in the right eye and 20/30 vision in the left eye, a right relative afferent pupillary defect, and a swollen right optic disc associated with peripapillary hemorrhages. The left eye had normal visual function with a normal fundus appearance except for a 0.6 cup-to-disc ratio. The patient was diagnosed with presumed anterior ischemic optic neuropathy (AION). Over the next several months, the vision in the right eye deteriorated to no light perception.
The patient presented at our institution about 4 months after the onset of visual loss. At that time, his visual acuity was no light perception in the right eye and 20/25 in the left eye. Color vision with the left eye was normal using Ishihara plates. Confrontation field testing in the left eye showed a full field; automated static perimetry using a Humphrey perimeter resulted in unreliable responses. Eye movements were full. Slit-lamp biomicroscopy revealed a mild cataract in both eyes. The right optic disc was swollen superiorly and nasally, with pallor temporally. The fellow optic disc was normal (Fig. 1). Mild diabetic retinopathy was present in the periphery of both fundi.
The patient underwent an evaluation that revealed an erythrocyte sedimentation rate (ESR) of 38 mm/hr and a C-reactive protein (CRP) level of 1.72 mg/dL. Prednisone 60mg was started and an immediate biopsy of the temporal artery was performed and revealed mild atherosclerosis. Steroids were therefore discontinued. Other laboratories were either negative or normal including: ACE, RPR, ANA, ANCA, Myeloperoxidase, dsDNA, NMO IgG antibody assay, and vitamin B12 level. Neuroimaging was obtained.
Magnetic resonance imaging (MRI) of the orbits reveals enhancement and mild enlargement of the right optic nerve extending from the orbit to the optic chiasm. (Figs. 2a-e).
A diagnosis of possible optic neuritis was made, and the patient was given a 5-day course of intravenous methylprednisolone 1000 mg without improvement. An optic nerve biopsy was recommended but declined by the patient. He was therefore examined both clinically and with neuroimaging at regular intervals over the next several months. During this time, the right eye remained blind. Repeat MRI was performed.
The repeat MRI shows progression of the enhancement and an increase in the size of the optic nerve, particularly within the orbit (Figs. 3a-c).
Approximately 1 year after onset of visual loss, the patient underwent a biopsy of the right optic nerve via a right lateral craniotomy. At the time of surgery, the intracranial segment of the right optic nerve was noted to be enlarged and appeared grey in color (Fig. 4). Pathologic specimens were obtained and sent for further evaluation (Figures 5a-d).
The pathology specimen shows disorganized tissue with microcyst formation (Fig. 5a), dense fibrillary tissue and elongated spindle cells (Figs. 5b and 5c), and degenerating axons (Rosenthal fibers, Fig. 5d). The appearance is that of a typical benign pilocytic astrocytoma involving the optic nerve.
Pilocytic astrocytoma (WHO grade I) of the optic nerve.
There are numerous causes of acute visual loss. A complete history and physical examination and, in many cases, the course of the visual loss (i.e., progressive, stable, or improvement) are fundamental in reaching the correct diagnosis. This patient was first diagnosed with presumed anterior ischemic optic neuropathy (AION) because of the acute presentation and the ophthalmic findings of optic disc swelling with peripapillary hemorrhages. The vision, however, proceeded to deteriorate to no light perception, which is not typical of non-arteritic AION but that can occur with arteritic AION. Thus, after the ESR and CRP were found to be slightly elevated and despite the lack of constitutional symptoms typically experienced by patients with giant-cell (temporal) arteritis, the patient was placed on a short course of systemic steroids and a temporal artery biopsy was performed. Red flags were also raised when the optic disc remained swollen months after the onset of loss of vision, thus raising the suspicion of another process causing the loss of vision. The finding on MRI of enlargement and enhancement of the right optic nerve suggested an inflammatory process such as sarcoidosis or an infiltrative tumor such as a lymphoma or glioma. Accordingly, the patient was treated with a short course of high-dose steroids. When the MRI appearance of the nerve did not improve, an optic nerve biopsy was performed, revealing a low-grade pilocytic astrocytoma.
Optic nerve gliomas are rare in adults. These tumors can range from low-grade tumors as in this case to infiltrating tumors such an anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). Pilocytic astrocytomas are usually seen in children and young adults and are present in 15% to 20% of patients with neurofibromatosis type 1 (1). Wulc et al. reported seven cases of optic nerve pilocytic astrocytoma in patients ranging from 18 to 61 (2). One of their cases had NF1. Other cases have been reported in adults (3-4), but none appear to have been as old as ours. Unlike benign optic nerve gliomas, malignant optic nerve gliomas (MONGs) are most often reported in older individuals. Wabbels et al. reviewed 45 cases of MONG in the literature (12). The mean age of diagnosis was 54 with a mean survival time of just over 8 months.
The typical presentation of adult optic nerve PAs is progressive loss of vision and variable proptosis (2-4). The vision can range from 20/30 to no light perception. Most cases are associated with slowly progressive visual loss. Sudden visual loss, as seen in our patient, may occur from acute hemorrhage within the infiltrated nerve or from ischemia in the region of maximum compression. Sudden visual loss can also occur in patients with other types of optic nerve tumors such as optic nerve sheath meningioma (5) and malignant optic nerve gliomas (6). Other ocular findings in both children and adults with optic nerve PAs include an ipsilateral relative afferent pupillary defect, optic disc swelling or pallor, peripapillary hemorrhages, and retinochoroidal (shunt) vessels (2).
The diagnosis of a PA is based on a combination of clinical findings, neuroimaging, and, ultimately, pathologic findings. The pathology is characteristic of a low-grade astrocytoma (WHO grade I), including spindle-shaped (hair-like) cells, a fibrillary background (see Figs. 5a-c), degenerating axons (Rosenthal fibers; see Fig. 5d), eosinophilic granular bodies, and, in some cases, areas of cystic degeneration (7). Mitotic figures and necrosis are absent, thus differentiating these tumors from higher grade gliomas, although the cellular proliferation rate as evidenced by the Ki67 index, is somewhat variable. Although some authors consider these tumors to be “hamartomas,” they are, in fact, true tumors and should be considered as such with respect to assessment and management.
Both computed tomographic (CT) scanning and MRI can detect these tumors. Both typically reveal enlargement and enhancement of the nerve; however, of the two, MRI is the study of choice due to its ability to delineate the extent of involvement. CT is useful to evaluate the size of the optic canal and to assess the presence of neural calcification that might be associated with an optic nerve sheath meningioma. In our case, the initial MRI 4 months after symptom onset demonstrated uniform high T2 signal and uniform enhancement confined to the optic nerve with mild associated mass effect. The imaging differential diagnosis of this appearance includes both inflammatory and neoplastic conditions. Sarcoidosis and, rarely, tuberculosis and syphilis can present with this picture. Wegener granulomatosis also can involve the optic nerve, but rarely in isolation. Within the neoplastic category, lymphoma can present as an isolated optic neuropathy with this imaging appearance (11). In our patient, a meningioma could be excluded based on the imaging appearance, as meningiomas typically demonstrate low T2 signal and a “tram-track” or “doughnut” enhancement of the optic nerve sheath with no enhancement of the nerve.
The management of optic nerve pilocytic astrocytomas is somewhat controversial. For children, most authors recommend observation alone with radiation therapy, chemotherapy, or surgical resection used in cases of progressive visual loss not due to amblyopia, an increase in the size of the tumor by neuroimaging, or disfiguring proptosis. The number of cases of PAs reported in adults is too small to warrant a definitive recommendation; however, the cases reported suggest that the visual and systemic prognoses generally are good, and thus are similar to the prognoses in children. Thus, treatment is used when necessary to protect the fellow eye from being affected by extension of the tumor to the optic chiasm and, hopefully, improve vision in the affected eye. Radiation, chemotherapy or surgery may be used in selected cases (8). In adults more than children, careful monitoring by clinical examination and neuroimaging is essential to identify the rare cases of malignant transformation that can be occur spontaneously or following radiation (9,10,13). It has been recommended that our patient receive radiation to protect the vision in his fellow eye from chiasmal involvement.
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