Bilateral 8th cranial nerve tumors, also known as vestibular schwannomas or acoustic neuromas (see figure), are pathognomonic of a fascinating syndrome called central neurofibromatosis or neurofibromatosis type 2 (NF-2). NF-2 is a rare, autosomal-dominant disease with an incidence of 1 in 30,000 live births. The mechanism by which the genetic changes underlying NF-2 produce these tumors of a cranial nerve remains a mystery. Interestingly, two other associations are also sufficient to make a diagnosis of NF-2. These are unilateral VS at early age (< 30 years) plus two other specific lesions (meningioma, schwannoma other than VS, glioma or pre-senile cataract), and unilateral VS at early age with an affected first-degree parent, sibling or child. Patients with NF-2 usually present between the ages of 18 and 24 years with tinnitus, hearing loss and balance difficulties. Symptoms of unilateral tinnitus, asymmetric hearing loss or unresolving vertigo or imbalance warrant a gadolinium-enhanced MRI with a neurotological consultation to rule out brainstem pathology.
NF-2 is caused by inactivation of the NF-2 tumor suppressor gene on chromosome 22 (22q12.2) which encodes the "Merlin" protein. Like a double negative, inactivation of a tumor suppressor gene produces an autosomal-dominant inheritance pattern identical to classical activating mutations.
When a diagnosis of NF-2 is entertained, evaluation should include a complete family history; a detailed head and neck and neurological examination with attention to cranial nerve deficits, and an MRI of the brain with dedicated images to detect bilateral VS, meningiomas and optic gliomas. Spinal MRI with gadolinium should be performed to look for spinal meningiomas or schwannomas, and ophthalmologic evaluation should be obtained in cases with visual loss or with suspicion of juvenile cataracts.
Unilateral VS and NF-2
The features of NF-2 (e.g., bilateral VS) are 100 percent penetrant by age 60, but bilateral VS are usually already present by age 30. Therefore, patients older than age 30 with unilateral VS are at low risk for NF-2, because unilateral VS are sporadic in the vast majority of these individuals.
A definitive diagnosis of NF-2 can be made in a patient with bilateral VS at any age, but a more difficult diagnostic situation arises in the relatively young person with unilateral VS in whom the second tumor might not yet be detectable. Annual MRI scans can be performed to observe for the second tumor, or the NF-2 gene can be screened for mutations to select those patients who need to be followed over time.
Genetic testing can be confirmatory or predictive in young adults and children. NF-2 presents as an autosomal-dominant mutation in 50 percent of cases. The other fifty percent of cases are due to a spontaneous mutation and one-third of these will present as somatic mosaics, making the mutation undetectable to standard testing methods. If a patient with somatic mosaicism has a mutation detected in his tumor but that mutation is not present in the child’s leukocyte DNA, then the child has less than a 5 percent chance of developing NF-2. Prenatal diagnosis using amniocentesis can only be performed if the mutation in the parent is known. Children of patients with unilateral VS and no family history of NF-2 have no increased risk of NF-2 over the general population and, therefore, do not need genetic screening.
Management of these complex patients requires a team which includes a neurotologist, an audiologist, a neurosurgeon and radiation oncologist with experience in treating VS, and a neuroradiologist. Decisions about intervention with surgery or radiosurgery are individualized for each patient. Smaller tumors can be surgically removed with a hearing preservation approach (middle cranial fossa or retrosigmoid approach). The use of radiotherapy in cases of NF-2 remains controversial due to the potential of limitations with hearing restoration caused by fibrosis at targeted areas.
Developments in cochlear implants and auditory brainstem implants (ABI) have opened the door for more aggressive tumor removal with improved chances of hearing restoration, depending on the damage to the auditory nerve and brainstem nuclei. A cochlear implant is useful if the auditory nerve is intact after treatment. If cranial nerve VIII is damaged and cannot be stimulated, ABI is the best choice for hearing rehabilitation
For more information about management of VS and other skull base tumors at the Swedish Hearing and Skull Base Center at Swedish Neuroscience Institute, please call at 206-320-2832.