Visual pathway lesions in neurofibromatosis type 1: diagnostic and treatment options

Optic pathway gliomas occur frequently in children with neurofibromatosis 1 (NF1). As not all patients with these tumors are symptomatic, regular examination of NF1 patients is important, and a nonsurgical treatment algorithm should be followed if a tumor is found.

Key Points

New Orleans-Children with neurofibromatosis type 1 (NF1) have a high rate of optic pathway gliomas (OPGs). Since not all affected children are symptomatic, every patient with NF1 should have an annual examination, even if OPG is not present. In cases where OPG is present, a treatment algorithm has been devised based on the age of the child and the occurrence or lack of progression.

R. Nick Hogan, MD, PhD, associate professor of ophthalmology, University of Texas Southwestern Medical Center, Dallas, provided an overview of OPG in a presentation at the annual meeting of the American Academy of Ophthalmology.

Noting statistics on childhood tumors of the central nervous system, Dr. Hogan said that 5% are in the optic pathway. Of these, 65% are optic gliomas, and 30% to 70% of OPGs occur in patients with NF1.

The incidence of NF1 is 1:3,500 worldwide. The disorder is autosomal dominant and due to a mutation on chromosome 17, in the gene that encodes neurofibromin, a tumor suppressor protein. Lack of this protein results in uncontrolled astrocytic proliferation.

Optic pathway gliomas can occur in various locations, such as the optic nerve, optic chiasm, and the optic tract. However, 84% of those gliomas are found in the anterior visual pathway, generally in the chiasm or the nerves.

Under gross examination, an OPG looks like a sausage-shaped fusiform expansion. There is some meningeal hyperplasia, which is reactive. Astrocytic proliferation compresses the optic nerve and thickens the septae, and islands of neoplastic astrocytes can be found between nerve fibers. The immature astrocytic proliferation forms a hair-like pattern, from which their name, pilocytic astrocytoma, is derived, Dr. Hogan said. Most astrocytomas are of this type and are classified as World Health Organization (WHO) grade 1.

Astrocytomas can have microcystic degeneration and mucin within the cavities. Rosenthal fibers are often seen as well; these are formed by eosinophilic condensation of intermediate filaments. Fibrillary astrocytomas are another type of low-grade glioma (WHO grade II), but they are found mostly in the brainstem.

Describing the epidemiology of OPGs in NF1, Dr. Hogan noted that the mean age at presentation is 4.5 years; the incidence is similar in males and females, and only about 10% of cases occur after the age of 19.

About 40% of patients will present with ocular complaints. Vision loss occurs in 35% to 50% of cases; it is more likely in tumors affecting the chiasm and most likely in postchiasmal tumors, Dr. Hogan said. In most cases (72%), the presenting ocular problem is decreased visual acuity, manifested as abnormal pupil function or decreased color vision. Proptosis (31%), strabismus or diplopia (6%), or nystagmus (2%) may also occur.

Nonophthalmic symptoms usually occur with intracranial tumors; these typically include precocious puberty or increased intracranial pressure. However, 60% to 70% of patients have no symptoms at diagnosis, largely due to a high rate of surveillance.

"That brings up some controversial issues, such as should all children with NF1 undergo imaging, what eye exam components are important, what exam should be used for preverbal patients with NF1, and at what interval should vision evaluation occur," Dr. Hogan said.

Screening recommendations

In 1997, an NF1 OPG task force tackled the question of who should be screened and concluded that there was no evidence that early detection reduced the degree of vision loss. The group also found that OPG was rarely identified before the age of 1 year, and that if OPG is found it may never be symptomatic and may never progress. Despite this lack of endorsement for early screening, many medical institutions include magnetic resonance imaging (MRI) screening in the initial evaluation of children of known NF1 carriers.

The eye examination should include age-appropriate visual acuity and color vision testing, Dr. Hogan said, but visual field testing is unreliable in children under age 10. An iris and pupil exam and fundus exam may also be performed.

Visual evoked potential (VEP) testing is indicated for preverbal children and others with an unreliable eye exam. It is objective, rarely requires sedation, can be performed at any age, and is considered to be 93% sensitive and 75% specific for optic nerve glioma in children with NF1.