Neurofibromatosis type 2 (NF2) is an autosomal dominant disease with a gene penetrance of over 95%. This disease has a propensity to produce tumors deriving from neural crest elements and is therefore characterized by bilateral vestibular schwannomas, with other presentations including schwannomas of the other cranial and peripheral nerves, meningiomas, and juvenile posterior subcapsular cataract. Rarely, ependymomas and astrocytomas develop. Almost all affected persons develop bilateral vestibular schwannomas by the age of 30 years and the average age of onset of such findings in individuals with NF2 is 18 to 24 years.

Variable expressivity of NF2 among individuals results in varying size, location, and number of tumors. Although these tumors are not malignant, their anatomical location and multiplicity generally lead to high morbidity and early mortality. The average life expectancy is 36 years and actuarial survival from the time of establishment of the correct diagnosis is 15 years. An earlier diagnosis and better-organized treatment in tertiary centers can provide a better chance of survival.

NF2 is not related genetically or phenotypically to neurofibromatosis type 1 (NF1). Individuals with NF2 are unlikely to have the cognitive problems (mental retardation and learning disability) that are usually seen in those with NF1. Patients with NF2 may have “café au lait” spots and cutaneous neurofibromas, but they are fewer and less severe than in NF1 patients; they are not the key features of the condition. Schwannomas almost never undergo malignant transformation to neurofibrosarcoma.

• Tumor growth in patients with NF2 generally presents much earlier in life than in sporadic vestibular schwannoma.

• The growth rate of the schwannomas is usually faster and the tumor may reach a remarkable size and cause severe distortion of the brainstem in NF2. The internal auditory canals are more markedly enlarged and their bony wall can be irregularly eroded. The tumor may even erode through the roof of the internal auditory canal and/or extend into the middle cranial fossa. Additionally, the tumor may invade the cochlear modiolus and extend into the basal turn of the cochlea.

• In many cases, there can be simultaneous schwannomas of other cranial nerves, often at the level of jugular foramen, as well as meningiomas. In some instances, all branches and end organs of the vestibular nerve, selected bundles of the cochlear nerve, the facial nerve, and other cranial and peripheral nerves within the temporal bone are affected by a proliferation of Schwann cells. They can be localized, diffuse, or both, so that decision making and surgical procedures are made extra difficult. Clinically, spinal involvement by the tumor may occasionally make positioning of the patient difficult. Cervical spine involvement may also pose a problem for intubation.

• Histologically, tumors in NF2 are indistinguishable from the conventional vestibular schwannoma. However, in some instances, they may display a conspicuously whorled pattern strongly resembling that of certain meningiomas.

Schwannoma usually affects vestibular nerves bilaterally, although only one side can be affected in certain individuals (mosaicism). Vestibular schwannomas are likely to present simultaneously. More rarely schwannomas can present only unilaterally, with the second tumor revealing itself at a later time. Schwannomas may also develop on other cranial and peripheral nerves. Generally, sensory nerves are more frequently affected than motor nerves.

Spinal tumors are observed in at least two-thirds of individuals with NF2. They often pose the most devastating and difficult aspects of this disease to manage. The most common spinal tumors are schwannomas, which usually originate within the intravertebral canal on the dorsal root and extend both medially and laterally, taking the shape of a “dumbbell.” Intramedullary tumors of the spinal cord such as astrocytoma and ependymoma occur in 5 to 33% of individuals with NF2. Most individuals with spinal cord involvement have multiple tumors, but they tend not to develop corresponding symptoms.

Meningioma develops in approximately half of individuals with NF2. Most are intracranial lesions, though spinal meningiomas can occur. NF2 meningiomas tend to occur less frequently in the skull base and are usually of the fibroblastic variety. Meningiomas in the orbit may compress the optic nerve and result in visual loss. Those at the skull base may cause cranial neuropathy, brainstem compression, and hydrocephalus. Meningioma may be the presenting feature of NF2, particularly in childhood.

Ocular involvement is present in one-third of individuals with NF2. They lose visual acuity in one or both eyes. Posterior subcapsular lens opacity, rarely progressing to a visually significant cataract, is the most common ocular finding. Lens opacities may appear prior to the onset of symptoms from vestibular schwannoma. Retinal hamartoma and epiretinal membrane are seen in up to one-third of individuals. Intracranial and intraorbital tumors may result in diminished visual acuity and diplopia.

Mono/polyneuropathy is an increasingly recognized feature of NF2, occurring particularly in childhood. This is frequently presented as a facial palsy, usually with only partial recovery, a squint (third nerve palsy), or foot or hand drop.

Diagnosis, evaluation, treatment, follow-up, and genetic counseling of patients with NF2 can best be performed in multidisciplinary clinics. The full management is beyond the scope of this book and only the management of intracranial lesions and follow-up are discussed here.

The other intracranial, cranial nerve, or spinal nerve tumors are very slow growing and surgical intervention for these tumors may cause disability years before it would occur naturally. Radiation therapy of NF2-associated tumors should be considered carefully because radiation exposure may induce, accelerate, or transform tumors in an individual with an inactive tumor-suppressor gene.

• At-risk asymptomatic individuals. Individuals, especially children who are at risk of developing NF2, are closely monitored. Early recognition of NF2 may allow for earlier intervention and consequently better final outcome. This can be done with DNA-based testing.

• At-risk asymptomatic individuals testing positive for the mutant genes. Individuals belonging to this category need regular annual MRI scanning from the teenage years until at least the fifth decade because some individuals with NF2 do not have any symptoms until they reach their sixth decade.

• Individuals with tumor. Patients in this group need follow-up and regular annual (at least) MRI scanning for life. Even patients who have undergone complete surgical removal of bilateral vestibular schwannoma still need long follow-up, because vestibular schwannomas still have a chance of regrowing and, more importantly, existing or new occurrences of meningiomas and/or other cranial nerve schwannomas should be monitored.

• When the tumor is larger than 1.5 cm, with contralateral hearing present, we will attempt surgical removal by the enlarged translabyrinthine approach with concomitant cochlear or ABI implantation.

• If the tumor is less than 1.5 cm or is positioned intracanalicularly, the options are dependent on hearing.

• No hearing: surgery with intention of cochlear nerve preservation and concomitant CI placement if applicable.

• Hearing present: an attempt at hearing preservation technique with auditory implant (CI or ABI) in the same stage if unsuccessful, or close observation with regular MRI scans and hearing evaluation.

If the ear is the only hearing ear, there are two possible options. One is to monitor the hearing closely and to offer surgical treatment when the hearing starts to deteriorate. The second option is to attempt a hearing preservation approach with possible cochlear implantation if necessary. Counseling of the patient plays a role in which decision is taken.

Any patient with neurological complications related to the vestibular schwannoma may also need surgical intervention, regardless of the size of tumor.

If the tumor is greater than 1.5 cm, we tend to approach the tumor via the extended translabyrinthine transapical approach with concomitant placement of a hearing implant. We may place either a CI or an ABI depending on the cochlear nerve viability.

Unfortunately, at the time of writing, no reliable test is available to gain information intraoperatively on the functionality of a preserved cochlear nerve to guide the choice between a CI or an ABI. The ideal tool to provide this information would be a temporary intracochlear electrode, but no such tool or implant is on the market at present.

If the patient presents with bilateral vestibular schwannomas, the convention is always to remove the larger tumor. This decision is usually made easier because the larger tumor very often corresponds to the worse-hearing ear. If the tumors are of similar size, the tumor on the side with the worse-hearing ear should be removed first.

If the larger tumor corresponds to the better-hearing ear, careful individualized management is necessary. We could remove the larger tumor, taking care to preserve the cochlear nerve for the coming CI. In case of failure, an ABI can be placed. One could also argue that we should take out the smaller tumor on the worse-hearing ear, because the risk of injuring the cochlear and facial nerves during removal of smaller tumors is usually lower. In this case a CI may be more strongly indicated. Both arguments are legitimate and should be explored with the patient and family at length. Ultimately, in such situations, the patient may have to decide.

Patients with NF2 who are 12 years old or older and who also have reasonable expectations and motivation and strong family support are indicated for ABIs. They may have or will have profound bilateral hearing loss after a natural history of tumors or unsuccessful preservation of the cochlear nerve during tumor removal.

The only absolute contraindication to the placement of an ABI is in a patient with an active purulent infection in the middle ear or a very short life expectancy. Relative contraindications may include patients who meet the formal criteria but who lack adequate support or motivation, as outlined above. Additionally, when the cochlear nerve can be preserved intact after resection of the vestibular schwannoma, placement of a CI is indicated.

Promontory testing is the direct stimulation of the cochlear promontory via an electrode placed surgically in the middle ear. A negative result of promontory testing—when pitch is not perceived—implies a retrocochlear cause of deafness. A positive result—when pitch is perceived in response to stimulation—indicates that the cochlear nerve is capable of transmitting tonal information centrally, thus making the patient an ideal candidate for cochlear implantation. Hence, in certain situations, when the anatomical integrity of the cochlear nerve has been preserved after tumor removal performed years before, promontory testing is used to assess whether the patient is a good candidate for a cochlear implant. Newer strategies/devices are being developed to provide more reliable measurements during surgery to test the functionality and feasibility of a cochlear implant after removal of the tumor.