Patients with NF2 usually present in the second and third decades of life, rarely after age 60. Patients' symptoms are attributable to VS, cranial meningiomas, and spinal tumors. The presentation of NF2 can vary considerably, but has been broadly divided into two subtypes based on the severity of disease: Gardner and Wishart NF2 subtypes (Table 63–1). The more severe Wishart type of NF2 is characterized by an early onset of tumors, a more rapid course of disease progression, and the presence of multiple other tumors in addition to bilateral VS. In contrast, the milder Gardner subtype is characterized by a later onset of symptoms, a more benign course of disease, and a tumor burden usually limited to bilateral VS. Many patients with NF2, however, cannot easily be categorized into these subtypes and have many overlapping features.
Table 63–1. Characteristics of Gardner and Wishart NF2 Subtypes. |Favorite Table|Download (.pdf)
Table 63–1. Characteristics of Gardner and Wishart NF2 Subtypes.
- Early onset
- Smaller tumors
- Few tumors
- Slower-growing tumors
- Hearing loss related to tumor size
- Missense mutations
- Later onset
- Larger tumors
- Multiple tumors
- Faster-growing tumors
- Hearing loss not related to tumor size
- Truncation mutations
Hearing impairment is the presenting symptom in nearly 50% of patients. The hearing loss is usually progressive and is associated with poor speech discrimination. Auditory dysfunction is accompanied with tinnitus in 10% of patients. Although the tumors arise from the vestibular nerve, acute vertigo is uncommon since the slow-growth pattern of the tumors allows the central nervous system to compensate. The tumor size at presentation is variable. Generally, younger patients have smaller tumors and older patients harbor larger tumors. VS are larger in patients with the more severe type of NF2 associated with spinal tumors or meningiomas.
Skin tumors are present in nearly two-thirds of patients with NF2. Café-au-lait spots, which are the hallmark of NF1, are also frequently found in patients with NF2. In contrast to patients with NF1, patients with NF2 invariably have fewer than six of these hyperpigmented lesions. Juvenile posterior subcapsular lenticular opacities are common and have been reported in up to 51% of patients with NF2. A proportion of these opacities are thought to be congenital and can be useful in the early diagnosis of NF2 in related family members. Retinal abnormalities are usually associated with the more disruptive protein truncation mutations of the NF2 gene. Muscular weakness or wasting is the initial presenting feature in up to 12% of patients with NF2. Distal, symmetric, sensorimotor neuropathy, though uncommon, may complicate NF2. Because of the heightened awareness of familial risks in individuals diagnosed with NF2, nearly 10–15% of patients diagnosed with NF2 are asymptomatic and are diagnosed as a result of screening.
Magnetic resonance imaging (MRI) with gadolinium-diethylenetriamine pentaacetic acid enhancement is the current gold standard for the radiological investigation of VS and spinal tumors. VS are typically isointense or mildly hypointense to brain on T1-weighted images, but they enhance markedly with gadolinium. As a group, VS enhance far more than any other intracranial tumors, but there is sufficient overlap among tumors of different types that the degree of enhancement alone is not pathognomonic. The enhancement may or may not be homogeneous owing to cystic components in the schwannomas. Intratumoral hemorrhage may cause focal areas of hypointensity or hyperintensity, largely dependent on the age of the hemorrhage. With T2-weighted images, VS have an intensity between that of brain and cerebrospinal fluid.
The resolution of thin-sectioned gadolinium-enhanced MRI scans centered on the internal auditory meatus is such that lesions as small as 1 mm can be picked up. False-negative images are thought to be very rare, but the exact incidence is hard to establish because more sensitive study techniques are currently unavailable. Occasional false-positive gadolinium-enhanced MRI scans have been reported, most commonly as a result of viral mononeuronitis of the seventh or eighth cranial nerves. MRI imaging has an important role in the postoperative evaluation of patients with NF2. It also plays an important role in monitoring tumor growth rates when a nonsurgical approach is undertaken and in screening family members at risk of having NF2. MRI of the cervical spine should be performed on every patient with NF2 to exclude asymptomatic spinal cord lesions, assess therapeutic options in symptomatic patients, and assist in surgical planning.
Patients with NF2, as well as their family members, should undergo complete audiological testing to assess the level of hearing. Although audiological evaluation alone is not sufficient to screen patients or family members for NF2, it can play a valuable role in management. Pure-tone audiometry is useful as a means of monitoring the function in patients diagnosed with NF2, in deciding when function is deteriorating significantly, and in determining the better hearing ear.
It is a commonly held belief that sporadic VS have a more predictable audiological profile when compared with that of NF2-associated vestibular tumors. This is incorrect. The auditory phenotype of a large number of patients with NF2 who were enrolled in an ongoing clinical and genetic study at the National Institutes of Health demonstrated that patients with NF2 had a more predictable audiological profile for a given size tumor than had been previously described with sporadic VS. However, this association between tumor size and auditory findings did not hold true for the subgroup of patients with spinal tumors, meningiomas, or both.
Auditory brainstem response testing has limited usefulness in reliably diagnosing VS in NF2. Interaural latency measurements are not useful in this population because of their bilateral tumors. Auditory brainstem response also is not reliable in detecting small tumors. The bilateral presentation of VS in NF2 means that there is potential for symmetric abnormalities in audiological investigations; therefore, audiometry alone cannot be used to exclude NF2. Pure-tone audiometry, speech audiometry, acoustic reflexes, and brainstem-evoked response audiometry are poor screening modalities for patients with NF2.
Genetic testing for the detection of mutations in the NF2 gene is available at some medical centers and private genetic testing centers. However, it is expensive and its exact role in the management of a patient with NF2 and the identification of family members at risk has not been clearly delineated.
Lalwani AK, Abaza MM, Makariow EV et al. Audiologic presentation of vestibular schwannomas in neurofibromatosis type 2. Am J Otol
. (This paper describes the relationship between the audiological findings, the clinical severity of neurofibromatosis 2, and tumor size.)