Pediatric Neurofibromatosis Tumors

Isolated optic nerve gliomas (tumors arising only in one eye) usually present with proptosis (sticking out) of the eye, with overlying swelling, retraction, or drooping of the eyelid. The eye may wander and have involuntary movements (nystagmus) ,and, upon testing, decreased vision may be found. Children with NF1 may also have optic nerve gliomas in both eyes.

In the majority of cases, optic nerve gliomas in children with neurofibromatosis are not isolated and involve structures deeper in brain, including the chiasm (where nerves cross to send signals to the brain) and the visual pathways.

Visual pathway gliomas in children are also diagnosed from screening studies, as the tumor may not be symptomatic. In these cases, it may be difficult to determine how long the tumor has been present and whether the child requires treatment.

All newly diagnosed patients with neurofibromatosis type 1 require a careful eye examination. Some in the medical community consider it controversial whether or not all patients require an initial MRI if asymptomatic. Children's National Hospital protocol dictates that doctors obtain MRIs in young children when visual testing is difficult. The finding of optic nerve pallor or other visual problems an MRI scan.

An MRI scan is extremely sensitive in the diagnosis of an optic nerve or visual pathway glioma. In some cases, a CT scan may be done instead but, if possible, a CT scan should be avoided due to concerns over the long-term detrimental effects of radiation.

In children with neurofibromatosis type 1 with an isolated optic nerve tumor, treatment choices at the time of diagnosis include: observation alone, surgery or chemotherapy. Radiotherapy is infrequently used due to concerns over long-term medical complications of such treatment, including the development of secondary tumors.

In children with minimally affected vision, especially in those in which it is unclear if the tumor has been present for a long time, usually the first treatment chosen is observation. Patients need to be followed closely by ophthalmologic, neurologic and neuroimaging (MRI) studies, usually every three months for the first year after diagnosis and at least every six months to one year thereafter for approximately three to five years.

In the cases where vision is completely lost in the eye and there is considerable proptosis (eye-bulging), surgery can be performed in isolated optic nerve gliomas to remove the tumor but spare the globe of the eye.

In situations where the vision is retained but the tumor is progressing, or where there is extensive intracranial disease, chemotherapy is often extremely effective. The chemotherapy regimen, which has been found to be most successful in children with neurofibromatosis type 1 and visual pathway gliomas, is the combination of carboplatin and vincristine (chemotherapy drugs). This approach was first piloted by Roger Packer, MD, at the Children's Hospital of Philadelphia and later at Children's National. This approach is now considered standard of care around the world.

To help cases in which the initial chemotherapy fails, Children's National is evaluating a series of new agents, including biologic agents, which have been chosen to specifically target the tumor while causing fewer medical complications. These are being tested as part of institutional and national clinical trials. Patient eligibility can be determined by contacting the Gilbert Family Neurofibromatosis Institute.

Other than optic nerve and visual pathway gliomas, children with neurofibromatosis are at increased likelihood of developing a variety of different brain tumors. The most common are gliomas in different portions of the brain, including the brain stem, and the cerebral cortex (the area of the brain in charge of language and information processing). Less likely is the development of malignant (cancerous) tumors such as high-grade gliomas, medulloblastomas and ependymomas.

Diagnosis of these lesions is usually made on the basis of an MRI scan done because of central brain problems such as weakness, unsteadiness and seizures. Dependent on the situation, a biopsy may be required to confirm the presence of the tumor, although the majority of low-grade tumors in children with neurofibromatosis are low-grade gliomas (grade 1, pilocytic tumors).

The type of treatment for other types of intracranial (inside the skill) tumors, primarily low-grade gliomas in children with NF1 can be different for each person. The treatment is dependent on the location of the tumor, how fast it is growing, and what symptoms it is causing. In some cases, observation alone is the appropriate first treatment. In other cases, removing the tumor through surgery may work.

In those cases when surgery cannot be performed safely, chemotherapy is often beneficial for children with NF1 and low-grade gliomas. The chemotherapy is the same type that is used in children with visual pathway gliomas; the combination of the carboplatin and vincristine is often quite effective. Children's National is also exploring new biologic-based therapies to treat these conditions for cases in which the tumor does not respond to chemotherapy.