Optic glioma in childhood

The majority of patients with optic nerve glioma present before the age of 10 (1). Childhood cases are often seen in patients with neurofibromatosis type 1 (NF-1) (2). Optic nerve gliomas that arise in childhood are usually relatively benign, low-grade tumors, such as pilocytic or fibrillary astrocytoma (3).

Patients with optic nerve gliomas can be asymptomatic or may present with symptoms that depend on the location of the tumor. Among symptomatic patients, the most common symptoms are diminished vision and proptosis, in cases when glioma is confined to the optic nerve (3). Treatment is reserved for patients with documented worsening of symptoms and is required in approximately 30% of patients. Progression of gliomas after the age of 12 is uncommon (1).

Diagnosis is confirmed with imaging methods and biopsy is not necessary for lesions that have characteristic clinical or imaging findings (3). Although optic gliomas can be seen on CT, MRI is the preferred imaging method for confirming the diagnosis and monitoring the progression or treatment response.  

Optic glioma in adulthood

Late-onset of optic gliomas is a rare entity that is less well characterized given that the optic gliomas occur mostly during childhood.

Adult patients with optic glioma can be divided into two groups. The first group are the patients who have been diagnosed with optic glioma in childhood and whose condition is continously followed-up. The second group consists of patients whose glioma was first diagnosed in adulthood (4). Given that the optic gliomas are largely asymptomatic, especially in patients with NF-1, a proportion of patients  diagnosed in the adulthood might also actually belong to the first group, but were either undiagnosed during childhood or their condition was not recognized until adulthood (4).

Malignant optic nerve glioma

A special group of optic gliomas in adulthood are malignant optic gliomas. These tumors are extremely rare with only several dozens of described cases in the literature (5). They were first described and reviewed in 1973 by Hoyt et al who identified their several characteristic features, such as the middle-age group occurence, imitation of optic neuritis symptoms in the early stage, fast progression to blindness and lethal outcome in a short time frame (6).

Besides the optic nerve and the chiasm, the malignant optic glioma can occur in the hypothalamus, temporal lobe, basal ganglia and other intracranial structures (5). Histologically, these tumors are classified as an anaplastic astrocytoma (WHO grade III) or a glioblastoma (WHO grade IV), both being high-grade astrocytomas that are characterized by cellular pleomorphism, high mitotic activity, necrosis and hemorrhage (8). Histological diagnosis of the malignant glioma is made by the biopsy, which is a mandatory procedure in order to confirm the diagnosis (9).

Imaging of malignant optic nerve glioma

MRI is the imaging modality of choice. CT does not have an important role in making the diagnosis of malignant optic glioma. CT may show well-demarcated enlargement of the nerve which is usually isodense to the brain with variable contrast enhancement. It may detect subtle erosions and enlargement of the optic canal, a feature typical for slow-growing optic nerve glioma in childhood. MRI is superior to computerized tomography in the assessment of the intracanalicular and intracranial extent of the tumor. However, neuroradiologic imaging features of the malignant optic nerve glioma may be non-specific in the early stage (7, 11).

On MRI, malignant optic nerve glioma can be seen as a hypointense or an isointense signal on native T1-weighted images, while on postcontrast T1-weighted images signal enhancement and expansion of the optic nerve, chiasm and optic tract can be seen.

 T2-weighted image hyperintensity of the affected visual pathway is a matter of debate. It has been suggested that T2-weighted image hyperintensity is a possible discriminating factor of malignant optic nerve glioma versus sarcoidosis, with the latter having a tendency of being hypointense on T2-weighted images. However, T2-weighted image intensity is variable in sarcoidosis, and T2-weighted image hyperintensity of malignant optic nerve glioma was not reported by all authors (3, 7, 11).

Clinical presentation and differential diagnosis

Unlike the optic glioma in childhood, which presents by slowly decreasing visual acuity and proptosis, malignant optic gliomas present with sudden acute visual loss, while proptosis is exceptionally rare (2). With the sudden visual loss as an initial symptom, patients might be misdiagnosed with optic neuritis, anterior ischemic optic neuropathy or retinal vascular occlusion (7).

The initial clinical presentation and pattern of visual loss depend on the location of the tumor. Gliomas that are located in the optic nerve will initially disrupt the uniocular vision and cause ipsilateral fundoscopic changes (10). If the tumor is located more proximally in the chiasm, bilateral visual disturbances with a normal-appearing fundus will occur. However, due to the aggressive nature of the malignant glioma, complete blindness occurs in a time range from several weeks to several months, regardless of the initial location of the tumor (11). Blindness is caused by encasement of the optic nerve below pia mater by the tumor cells, causing impairment of perfusion with progressive vascular occlusion and demyelination (12). With further expansion of tumor, hypothalamic dysfunction, hemiparesis and other neurologic deficits arise, and are followed by the fatal outcome.

With regard to imaging features, differential diagnosis of a suspected malignant optic nerve glioma includes infectious, demyelinating, vascular and infiltrative neuropathies. Differential diagnosis also includes possible causes of optic nerve enlargement, such as optic nerve meningioma, sarcoidosis, orbital lymphoma, orbital pseudotumor and others (7, 13).

Treatment

Standard therapy for patients diagnosed with malignant optic nerve glioma consists of surgery, followed by radiotherapy or chemo-radiotherapy. Unfortunately, although medicine has advanced dramatically in the last few decades, the course of the disease has not changed considerably, with lethal outcome in one or two years after the diagnosis (7).