Malignant Optic Glioma of Adulthood
Malignant optic gliomas of adulthood (MOGA), or malignant optic nerve gliomas (MONG), are extremely rare but lethal neoplasms of the anterior visual pathway and optic chiasm and usually spreads beyond visual pathways
Optic gliomas comprise 66% of primary optic nerve tumors, and 0.6-1.2 % of all brain tumors . Ninety percent of optic gliomas occur in children, and most of these are benign. As with malignant gliomas elsewhere intracranially, MOGA/MONG have a 70-100% local recurrence rate, 90% of which appear within 2-3cm of the initial lesion . This entity was first described by Hoyt et al in 1973. Although as many as 89 cases have been reported in the literature, only 57 were pathology-proven           .
The mean age of diagnosis is 62 years. There is no consensus in the literature with regards to gender predilection, with some reports claiming males are more commonly affected, and others claiming both genders are affected equally,.
MOGA/MONG present either as anaplastic astrocytomas (AA; WHO grade III) or glioblastomas (GBM, WHO grade IV). In addition to the optic nerves and chiasm, MOGA/MONG can present in the hypothalamus, temporal lobe, and basal ganglia in 50, 22.5, and 15 percent of patients, respectively.
The glioma destroys adjacent optic nerve tissue, leading to visual field defects corresponding to the damaged area. If the neoplasm spreads to involve the optic chiasm, it may initially cause contralateral superotemporal visual field loss via Wilbrand’s knee, an anatomical phenomenon in which inferonasal crossing optic nerve fibers curve anteriorly into the contralateral optic nerve for 1-2mm before returning to the chiasm and down the optic tract. If untreated, it almost inevitably advances further into the contralateral optic nerve, leading to bilateral visual impairment.
Funduscopic examination revealed papilledema in around 40 percent of patients, hemorrhage in 30 percent, and optic atrophy in 14 percent. These likely occur secondary to the glioma’s compressive, infiltrative, and occlusive vascular tendencies, as well as mass effect.
Presentation can also depend on exact location of the lesion. If it lies in the anterior portion of the optic nerve, funduscopic exam will reveal disc edema. Combined with rapid unilateral vision loss in these cases, this picture mimics anterior ischemic optic neuropathy. Distal portion lesions may be associated with disc pallor secondary to prolonged axoplasmic stasis from compression from the tumor.
Seventy percent of patients present initially with rapidly progressive unilateral visual loss, which spreads to bilateral blindness over the course of 3.3 +/- 2.8 months, usually regardless of treatment. Death typically follows several months later, and almost always within 1-2 years  . Twenty percent of patients report pain as one of their presenting symptoms. Associated neurologic symptoms such as headaches, hemiparesis, and behavioral changes were noted in 39 percent of patients throughout the course of their disease, which may be attributed to satellite lesions in the cerebrum or compressive effects on the adjacent cerebral cortex .
De Paulis et al reported the presence of cerebral aneurysms in 27.5-38 percent of all gliomas. Among the subset of optic nerve gliomas, however, some of these may in fact have been low-grade gliomas (I, II) as opposed to the necessary high grade (III, IV) for MOGA/MONG. In addition, in optic nerve glioma cases, all aneurysms were induced by radiotherapy for the tumor, except for that of the patient in De Paulis’ case, which was an incidental finding.
T1-weighted MRI findings include hypo- to iso-intense heterogenous thickening of the optic nerve, chiasm, or tract, with cystic areas. Diffusion-weighted imaging and diffusion coefficient mapping can also show suggestive results. Serial contrast-enhanced MR images of the orbits can demonstrate an initial focal enhancement with rapid progression and vast extent of nerve enlargement as fairly reliable indicators of this diagnosis. However, thickening and enhancement of the optic nerve are non-specific imaging findings—they can also indicate demyelinating optic neuritis, perioptic neuritis, primary low-grade optic nerve gliomas, lymphoma, leukemia, and metastases. MOGA/MONG appear to remain within the optic nerve sheath as they spread. This is supported by lack of calcification on MRI, a classic finding of optic nerve sheath meningioma. As such, biopsy of the optic nerve itself—not the optic nerve sheath—may be required for establishment of the diagnosis.
Histologically, for a lesion to be considered a MOGA/MONG, it must show necrosis, vascular proliferation, nuclear pleomorphism, and mitoses.
MOGA/MONG presents a significant diagnostic challenge due to its extreme rarity as well as its symptomatologic and image mimicry of far more common conditions. The differential diagnosis is thus broad, and includes optic neuritis, vascular lesions (e.g. cavernoma, ischemic optic neuropathy, CRVO), compressive lesions, neurosarcoidosis, lymphoma, and metastases.
Standard treatment of MOGA/MONG consists of surgical resection or biopsy followed by radiotherapy and/or chemotherapy with temozolomide. A chemoradiation regimen can prolong survival by a median of 2-3 months.
Most patients die within one year of this diagnosis. Seventeen percent of adult intracranial neoplasms are GBM, 20 percent of which metastasize within the central nervous system via cerebrospinal fluid. As such, MOGA/MONG can arise de novo or appear after brain GBM. In the latter case, this appearance predominantly comes five or more years after the initial lesion. Recurrence rates are also high for both de novo and post-cerebral GBM given the highly aggressive nature of the neoplasm, making the case for regular ophthalmic examinations and brain MRI’s after GBM for early diagnosis and treatment of MOGA/MONG. Moreover, screening for intracranial tumors with acute onset unilateral vision loss can preserve vision in the contralateral eye and prolong survival.
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