AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Central neurofibromatosis or neurofibromatosis type 2 (NF2) is a multisystem genetic disorder associated with bilateral vestibular schwannomas, spinal cord schwannomas, meningiomas, gliomas, and juvenile cataracts with a paucity of cutaneous features, which are seen more consistently in neurofibromatosis type 1 (NF1). Although quite variable in its age of onset and severity of symptoms in affected individuals, NF2 is associated with significant morbidity and decreased life span. Furthermore, diagnosis in childhood is often difficult because of the absence of central nervous system involvement at a young age.

Pathophysiology

The manifestations of NF2 result from mutations in (or rarely deletion of) the NF2 gene located on the long arm of chromosome 22. The gene product known as merlin serves as a tumor suppressor; decreased function or production of this protein results in a predisposition to develop a variety of tumors of the central and peripheral nervous systems. Half of affected individuals have NF2 as a result of a new (de novo) gene mutation.

Frequency

International

The estimated incidence of NF2 is 1 in 37,000 per year, with about half of affected individuals representing first cases in the family as a result of new dominant mutations.

Mortality/Morbidity

• Vestibular schwannomas are the most common and well-recognized feature of NF2 leading to significant morbidity. Symptoms of tinnitus, gradual hearing loss, and even vestibular dysfunction are frequently the initial signs of NF2. Although unilateral hearing loss is the number one presenting symptom, eventually bilateral deafness would be expected in most affected individuals. Untreated vestibular schwannomas can extend locally and may result in brainstem compression, hydrocephalus, and occasionally facial nerve palsy.
• Dumbbell-shaped spinal cord schwannomas are quite common in NF2 and result in significant morbidity; they present a great therapeutic challenge. Spinal cord ependymomas, astrocytomas, and meningiomas also occur but less frequently. Intracranial meningiomas, on the other hand, are a frequent finding and may be asymptomatic or may cause a variety of symptoms and CNS deficits.
• Posterior subcapsular or so-called juvenile cataracts can predate CNS symptomatology. These cataracts may progress over time, leading to decreased visual acuity. A fair percentage of affected individuals are found to have retinal hamartomas or epiretinal membranes that may or may not be visually significant.
• Sensory motor polyneuropathy is seen in some individuals with NF2 who may or may not have identifiable tumors along the length of the peripheral nerve(s) of interest.

Race

All races and ethnic groups are affected equally with NF2.

Sex

Males and females are affected equally with this autosomal dominantly inherited condition.

Age

Although the genetic change causing NF2 is present at conception, the clinical manifestations occur over many years. The typical age of onset of symptoms is in the late teens to early 20s, but the age range covers the entire life span. Some evidence indicates that age of onset of clinical symptoms is lower in maternally transmitted NF2. While NF2 is quite variable in severity from person to person, family studies have shown some intrafamilial consistency in age of onset. Somatic mosaicism for the NF2 mutation in sporadic cases may also complicate the clinical picture, resulting in under or late diagnosis.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Clinical diagnosis of NF2 requires that an individual present with at least 1 of the 3 situations described below. As approximately half of affected persons represent new gene changes, family history is often negative and makes diagnosis all the more difficult.

• Bilateral eighth nerve masses visualized on MRI using thin cuts, with and without gadolinium and on both axial and coronal views
• First-degree relative with documented NF2 for an individual with a unilateral eighth nerve mass imaged as already described
• First-degree relative with documented NF2 for an individual with at least 2 of the following findings:
• • Meningioma
  • Glioma
  • Schwannoma
  • Juvenile cataract

Physical

Unlike NF1, which frequently is associated with a number of cutaneous diagnostic clues, NF2 is accompanied by few external signs.

• Presenting symptoms include hearing loss, ringing in the ears, and balance problems associated with vestibular nerve lesions. Individuals at risk for NF2 should be screened carefully for early signs of hearing loss, motor or sensory changes, and visual deficits.
• Differentiating clinically between the relatively common NF1 and the rare NF2 is occasionally problematic. Patients with NF2 almost never have a large number of cafe-au-lait spots (although rarely 6 or more may be seen), whereas cafe-au-lait spots are numerous and ubiquitous in NF1. Neither axillary nor inguinal freckles are common occurrences in NF2.
• Malignant transformation of benign growths is almost unheard of in NF2, unlike NF1. However, individuals with either NF1 or NF2 can develop multiple subcutaneous lesions that may be clinically indistinguishable (see Images 1-4). In NF2 these lesions most often would be defined histologically as schwannomas or neurilemomas, while in NF1 these would be defined histologically as neurofibromas. Subcutaneous neurofibromas are occasional findings in NF2.
• Posterior subcapsular lenticular opacities, even in childhood, would be suggestive of NF2, whereas Lisch nodules would be diagnostic of NF1.
• Finally, although individuals with either NF1 or NF2 can develop dumbbell-shaped spinal cord tumors, schwannomas are common in NF2, whereas neurofibromas are seen primarily in NF1.

Causes

• NF2 is inherited as an autosomal dominant condition resulting from decreased production of the protein merlin, which has a putative tumor suppressor function. Affected individuals need only 1 mutated or deleted NF2 gene to exhibit signs of the condition.
• The NF2 gene has been localized to the long arm of chromosome 22; numerous mutations in this gene have been identified, most of which are predicted to result in production of a truncated protein with loss of its usual function.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Juvenile cataracts
Multiple meningiomas
Schwannomatosis

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Now that the gene for NF2 has been identified, analysis for disease-causing mutations can be offered in some clinical settings. Detection rates for molecular-based testing approaches 65%; therefore, such testing has some inherent limitations when trying to confirm a diagnosis of NF2. However, for a patient with suspected NF2 who is still young, has a negative family history, and may eventually develop additional criteria, the identification of a specific mutation may be very helpful. In light of the high rate of somatic mosaicism in sporadic cases of NF2 (perhaps as many as 25%), molecular testing of tumor tissue may augment traditional molecular studies when analysis of DNA obtained from blood lymphocytes is nondiagnostic.
• For families with asymptomatic, at-risk members, the application of molecular testing is viewed from a slightly different perspective. Once the clinical diagnosis has been established unequivocally in a given individual, he or she could be offered direct molecular analysis to see if a mutation can be identified. If a mutation is found, then other asymptomatic family members may benefit from presymptomatic testing to see who will and who will not develop NF2. Screening and surveillance recommendations would then be based on the results of this testing and, if a sibling or child of an affected person was found not to carry the mutation, he or she need not be concerned about developing NF2 in the future.
• For families in which no mutation can be identified in a known affected individual, linkage analysis or indirect genetic testing methods may be utilized. However, this requires cooperation on the part of the family as well as DNA samples from multiple affected and unaffected individuals. Even utilizing the best technology available, diagnostic uncertainty may remain depending on the geographical relationship between the genetic markers and the disease-causing gene. On the other hand, with the recent advances in genetic mapping and likelihood of finding informative markers close to or within the gene itself, linkage analysis remains an excellent choice for determining risk from a molecular standpoint.
• For a parent who has NF2, prenatal testing can be done on amniocytes or chorionic villi, either through direct gene mutation analysis when such a change has been identified or through linkage analysis. Prenatal testing may not be possible if the affected parent is the first affected person in the family and a mutation cannot be found. For an affected parent with a known mutation, preimplantation genetic diagnosis may be possible if the couple is willing to undergo in vitro fertilization with transfer of unaffected embryos.
• One note of caution must be made in light of advances in molecular genetic technology. Presymptomatic testing of at-risk family members requires a vigorous informed consent process and might best be done during a genetic counseling session at a cancer, genetic, or neurofibromatosis center that specializes in such matters. This is of even greater concern when considering testing of minors, in whom the potential harm must be weighed against medical benefit. Since aggressive medical surveillance can still be implemented in the absence of a definitive diagnosis and no preventive or curative measures are currently available, the decision whether to undergo presymptomatic testing for this adult-onset disease is a personal one that must be made after a frank and complete discussion with knowledgeable health professionals.

Imaging Studies

• Radiography
• • Plain films of the spine may be helpful in evaluating scoliosis but are of limited value in looking for spinal cord tumors that may occur in NF2.
  • In general, MRI is the preferred technique for monitoring individuals with NF2 who have symptoms of spinal cord lesions.
• MRI
• • MRI remains the mainstay for diagnosis and screening of CNS and spinal cord tumors (see Images 5-10). At-risk individuals may be monitored for CNS tumors beginning in their teens, with annual MRIs of the head done through their late 50s. Clear molecular diagnosis may help to modify risks for family members and prevent unnecessary testing for asymptomatic individuals who are found not to carry a gene mutation.
  • MRI of the spine is indicated diagnostically when an individual presents with motor or sensory changes suggestive of a spinal cord lesion or lesions. The key point here is early detection, which may result in prompt action and provide a better outcome. However, routine MRI imaging of the spinal cord probably is not indicated for asymptomatic affected or at-risk individuals.

Other Tests

• Hearing evaluations, including brainstem auditory-evoked response (BAER), are important in the identification of early hearing loss and may demonstrate latency abnormalities before a mass is detectable on MRI. In light of this, auditory screening on an annual basis may be quite useful in asymptomatic or presymptomatic individuals. Once a vestibular schwannoma is identified, full audiometry testing, including acoustic reflex testing as well as BAER, is useful as a means of monitoring disease progression. Clinical experience clearly indicates that the size of the vestibular tumor often does not correlate with the degree of hearing loss.

Procedures

• Dilated eye examinations are an important part of the care of affected individuals because they are at a risk for developing visually significant cataracts or retinal lesions. As a diagnostic test, an eye examination for lens opacities, retinal hamartomas, or epiretinal membranes may be quite useful even in a child at risk for NF2. In fact, juvenile cataracts, as the name implies, frequently occur in children and may be seen long before there is any evidence of vestibular schwannomas. For children and adults with NF2, annual eye examinations are recommended since unrecognized visual impairment can further interfere with activities of daily living, especially in an individual with concomitant hearing loss.

Histologic Findings

Unlike the tumors associated with NF1, those found in NF2 are usually of 1 of 3 cell types—Schwann cells, glial cells, or meningeal cells. Although the tumors in NF2 can be locally invasive and cause significant morbidity as a result of their growth properties, they rarely, if ever, undergo malignant transformation. This is somewhat different than NF1, in which plexiform neurofibromas can and occasionally do develop into neurosarcomas; however, both vestibular schwannomas and meningiomas in NF2 tend to be more aggressive than in cases of sporadic (ie, not related to NF2) tumors, with a tendency for more extensive local invasion and histologic evidence of increased mitoses.

TREATMENT

Section 6 of 11  

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• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Medical Care

• For individuals diagnosed with NF2, medical care consists of routine examinations focusing on some of the potential complications related to CNS or spinal cord lesions. Interval history should focus on subtle motor or sensory symptoms such as paresthesias, radiculopathies, weakness, or muscle atrophy. Unless clinical deterioration occurs, MRI of the head on an annual basis would be reasonable, as would annual eye examinations and auditory screening using BAERs.
• Annual neurologic assessment by a trained specialist is most useful in this clinical setting; the neurologist may detect subtle sensory or motor deficits even before the patient is aware of any difficulties.
• For patients with multiple medical problems associated with NF2, management by a team of specialists through a multidisciplinary clinic may provide the most comprehensive and cost-effective care over time. This is especially important with rapid advances in surgical management including such tools as stereotactic radiosurgery and auditory brainstem implants.
• For at-risk individuals who do not carry a diagnosis of NF2, such as siblings and offspring of affected persons, optimal screening recommendations are more difficult to establish. However, since early detection of tumors may improve long-term outcome, many reasons exist to consider a program of surveillance and routine screening. For families in which a specific mutation or linkage has been established, at-risk individuals may choose to know for sure whether they are at risk. Even when diagnostic certainty is not possible, but an individual's chance of having NF2 is at least 50%, annual focused examinations, accompanied by annual head MRIs and hearing evaluations with BAERs, seem to be reasonable screening options.
• Although surgical resection of symptomatic tumors represents the most common approach to clinically significant lesions, in some rare instances, radiation and/or chemotherapy may be recommended to treat disabling ependymomas. However, concerns remain regarding additional risks of radiation therapy in a patient with a germline tumor suppressor gene mutation (ie, someone with NF2) as opposed to an individual with an isolated non–NF2-related tumor.

Surgical Care

• Surgical resection of tumors remains the mainstay of treatment in NF2, with recent advances in surgery permitting preservation of hearing for some affected individuals. For small vestibular schwannomas, both surgical resection and stereotactic radiosurgery have been employed and may preserve both hearing and facial nerve function in selected patients. Larger tumors may require surgical resection despite irreversible hearing loss, especially when there is evidence of brainstem compression, facial nerve palsy or, in extreme cases, early hydrocephalus. Larger tumors may be approached surgically if a patient has a significant decline in hearing, since a debulking procedure may result in preservation of hearing or, at the minimum, prolongation of auditory decompensation.
• In recent years, auditory brainstem implants (ABIs) have been used successfully in some patients with hearing loss secondary to vestibular schwannomas. In many cases, an ABI does not restore hearing, but instead, improves the patient's ability to appreciate environmental sounds and facilitates communication. Prior to surgery, ABI candidates should have a frank discussion about their expectations from this procedure with a careful evaluation of their family support system.
• Unlike the vestibular lesions, intracranial meningiomas, may be quite slow growing; surgical resection should be considered only when such lesions are causing serious, disabling symptoms.
• Resection of spinal cord tumors is often quite difficult and the risks and benefits of surgery must be considered on an individual basis. To maximize operative success, acting promptly is important when neurological symptoms appear, yet complete resection of a spinal cord tumor may not always be possible and in some cases serves primarily a palliative function.
• Surgical resection of cutaneous or subcutaneous growths can be accomplished by any competent surgeon, although plastic surgical consultation is advisable for areas of great cosmetic concern, such as the face.

Consultations

• The neurologist and neurosurgeon work together closely in the management of central and spinal cord lesions in NF2. The neurologist provides valuable information regarding any changes in neurological status over time, whereas the neurosurgeon provides insight into selecting the optimal procedure and makes decisions regarding timing for surgical intervention.
• The otolaryngologist or otologist is an important consultant in the surgical management of vestibular schwannomas, especially if auditory brainstem implants are being considered. Cochlear implants, on the other hand, have not been as effective in treatment of NF2 as originally hoped and generally are reserved for a small subset of patients with vascular compromise of the cochlea without substantial nerve involvement.
• The audiologist serves as an essential member of the management team for individuals with acoustic nerve lesions. After performing annual hearing evaluations by BAER to document disease progression, he or she can provide advice regarding usefulness of amplification. For many patients, augmentation may permit good sound discrimination well into the course of the disease. The audiologist also may make suggestions regarding any additional services such as speech therapy or classes for lip reading or sign language that may be helpful as hearing deficits grow.
• The ophthalmologist is an important team member and can assist in both the diagnosis and care of the patient with NF2. Early detection of juvenile cataracts is quite helpful in making a diagnosis in an at-risk child with minimal symptomatology. Furthermore, annual follow-up for affected individuals permits early detection and possible intervention for visual loss secondary to lenticular lesions.
• Finally, the geneticist may provide both diagnostic and genetic information to affected and at-risk individuals. For family members who are considering molecular testing, an explanation of risks, benefits, and test reliability to all individuals is essential as part of the informed consent process. Issues of potential insurance discrimination, confidentiality, and privacy need to be discussed in addition to personal perspectives on undergoing such testing before an individual can provide consent. For couples considering prenatal diagnosis for NF2, genetic consultation is recommended.

Activity

Activity restriction is not necessary except as recommended by the neurologist or neurosurgeon on the basis of neurological deficits. However, patients with vestibular schwannomas need to be warned about potential balance problems, which may worsen in an underwater situation. Therefore, these individuals should be advised to never swim alone and to have someone with them at all times if they are diving or snorkeling. If disorientation occurs underwater as a result of the acoustic nerve involvement, such activities may need to be curtailed.

MEDICATION

Section 7 of 11  

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• References

No effective medical therapies are known for NF2. However, in rare instances in which surgical resection of symptomatic ependymomas is not possible, chemotherapy with lomustine, vincristine, and prednisone, or carboplatin and vincristine, following radiation therapy may serve a palliative function.

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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• Multimedia
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Further Inpatient Care

• Hospitalization is necessary for neurosurgical procedures as well as ABIs.

Further Outpatient Care

• Although care of the patient with NF2 theoretically can be done in the primary care setting, the complexity, rarity, and multisystem involvement encountered in this condition suggest that medical care in a disease-specific multidisciplinary clinic may permit optimal management. The following is an outline of reasonable guidelines in the care of the patient with NF2:
• • Annual neurologic examination looking for subtle deficits or changes in neurologic status that might suggest disease progression
  • Annual hearing screening with BAER with referral to an audiologist for amplification, augmentation, or speech therapy recommendations
  • Annual MRI to monitor existing lesions or look for presymptomatic lesions
  • Annual ophthalmologic evaluations to monitor visual acuity

Complications

• Unilateral or, frequently, bilateral vestibular schwannomas leading to tinnitus, hearing loss, and/or problems with balance
• Meningiomas, gliomas, ependymomas, and other cerebral, cerebellar, or spinal cord lesions that may result in neurological deficits, seizures, and/or hydrocephalus
• Peripheral nerve schwannomas, mixed tumors, and occasionally neurofibromas
• Peripheral neuropathies
• Visually significant juvenile cataracts

Prognosis

• The prognosis of NF2 depends upon a number of factors including age of onset of symptoms, degree of hearing deficit, and number and location of various tumors. Although age of onset is relatively similar within families, the age range can vary from 2-70 years. While the tumors themselves are relatively indolent and do not undergo malignant transformation, studies performed in the late 1980s and early 1990s showed clearly that significant rates of mortality as well as morbidity are associated with the diagnosis of NF2. One such study suggested that the survival from the time of actual diagnosis averages 15 years; however, this may be changing for the better with improved diagnosis, surgical techniques, surveillance, screening, and recognition of mild disease due in part to increased physician awareness and availability of molecular diagnostic options.

Patient Education

• Patients and at-risk family members should be made aware of specific symptoms such as tinnitus, hearing deficits, focal weakness, sensory changes, or balance problems that might suggest tumor growth and should prompt immediate medical attention.
• Patients with vestibular schwannomas should be cautioned about diving and underwater activities because of increased risks for disorientation and potential for drowning.
• Patients and their families may be referred to NF-specific regional and national support groups for continuous updates on advances in treatment as well as for emotional support. Neurofibromatosis, Inc. has a toll-free number (1-800-942-6825) and can be reached by e-mail at nfinc1@aol.com. The Children's Tumor Foundation has a toll-free number (1-800-323-7938) for information and to sign up for their newsletter. The NF2 Review, located in Los Angeles, CA, can be reached at 1-213-483-4431 and not only has an NF2-specific newsletter but also has a particular research interest in NF2 with a team of specialists working on auditory brainstem implants and the newest surgical approaches to vestibular schwannomas. Online resources include the NIH Web site and an NF2 person-to-person support group known as the NF2 crew.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
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• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to diagnose vestibular schwannomas early enough to permit intervention that may prolong hearing
• Failure to identify spinal cord lesions early on to permit intervention prior to permanent neurological damage
• Failure to provide appropriate genetic counseling
• Failure to provide complete informed consent prior to undertaking molecular testing

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Subcutaneous and cutaneous lesions in a young man with neurofibromatosis type 2; note paucity of cafe-au-lait spots.
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Media file 2:  Right neck mass in a patient with neurofibromatosis type 2.
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Media file 3:  Facial asymmetry, OS proptosis, and exotropia as well as several subcutaneous lesions on the forehead and face in a 20-year-old man with neurofibromatosis type 2.
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Media file 4:  Posterior cervical scar from cord lesion resection, thoracic scoliosis, and subcutaneous masses in a young adult with neurofibromatosis type 2.
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Media file 5:  Meningioma to the left of midline in a patient with neurofibromatosis type 2.
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Media file 6:  Multiple meningiomas (on the left) on the surface of brain in a patient with neurofibromatosis type 2.
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Media file 7:  Bilateral acoustic neuromas in a patient with neurofibromatosis type 2.
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Media file 8:  Bilateral acoustic neuromas and a left-sided meningioma in a patient with neurofibromatosis type 2.
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Media file 9:  Small ependymoma in a patient with neurofibromatosis type 2.
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Media file 10:  Multiple meningiomas in a patient with neurofibromatosis type 2.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Aguiar PH, Tatagiba M, Samii M. The comparison between the growth fraction of bilateral vestibular schwannomas in neurofibromatosis 2 (NF2) and unilateral vestibular schwannomas using the monoclonal antibody MIB 1. Acta Neurochir (Wien). 1995;134(1-2):40-5. [Medline].
• Baser M, MacCollin M, Sujansky E, et al. Malignant nervous system tumors in patients with neurofibromatosis 2. FASEB Summer Research Conference on Neurofibromatosis. 1996.
• Briggs RJ, Brackmann DE, Baser ME. Comprehensive management of bilateral acoustic neuromas. Current perspectives. Arch Otolaryngol Head Neck Surg. Dec 1994;120(12):1307-14. [Medline].
• Epstein FJ, Farmer JP, Freed D. Adult intramedullary spinal cord ependymomas: the result of surgery in 38 patients. J Neurosurg. Aug 1993;79(2):204-9. [Medline].
• Evans DG, Huson SM, Donnai D. A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet. Dec 1992;29(12):841-6. [Medline].
• Evans DG, Huson SM, Donnai D. A clinical study of type 2 neurofibromatosis. Q J Med. Aug 1992;84(304):603-18. [Medline].
• Hagel C, Lindenau M, Lamszus K, et al. Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens. Acta Neuropathol (Berl). Aug 2002;104(2):179-87. [Medline].
• Hoffman RA, Kohan D, Cohen NL. Cochlear implants in the management of bilateral acoustic neuromas. Am J Otol. Nov 1992;13(6):525-8. [Medline].
• Kanowitz SJ, Shapiro WH, Golfinos JG, et al. Auditory brainstem implantation in patients with neurofibromatosis type 2. Laryngoscope. Dec 2004;114(12):2135-46. [Medline].
• Kanter WR, Eldridge R, Fabricant R. Central neurofibromatosis with bilateral acoustic neuroma: genetic, clinical and biochemical distinctions from peripheral neurofibromatosis. Neurology. Aug 1980;30(8):851-9. [Medline].
• Kluwe L, Mautner V, Heinrich B, et al. Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet. Feb 2003;40(2):109-14. [Medline].
• Laszig R, Sollmann WP, Marangos N. The restoration of hearing in neurofibromatosis type 2. J Laryngol Otol. May 1995;109(5):385-9. [Medline].
• Mautner VF, Tatagiba M, Guthoff R. Neurofibromatosis 2 in the pediatric age group. Neurosurgery. Jul 1993;33(1):92-6. [Medline].
• Mautner VF, Lindenau M, Baser ME. Skin abnormalities in neurofibromatosis 2. Arch Dermatol. Dec 1997;133(12):1539-43. [Medline].
• McCormick PC, Torres R, Post KD. Intramedullary ependymoma of the spinal cord. J Neurosurg. Apr 1990;72(4):523-32. [Medline].
• Ojemann RG. Management of acoustic neuromas (vestibular schwannomas) (honored guest presentation). Clin Neurosurg. 1993;40:498-535. [Medline].
• Otto SR, Brackmann DE, Hitselberger W. Auditory brainstem implantation in 12- to 18-year-olds. Arch Otolaryngol Head Neck Surg. May 2004;130(5):656-9. [Medline].
• Parry DM, Eldridge R, Kaiser-Kupfer MI. Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet. Oct 1 1994;52(4):450-61. [Medline].
• Samii M, Matthies C. Management of 1000 vestibular schwannomas (acoustic neuromas): hearing function in 1000 tumor resections. Neurosurgery. Feb 1997;40(2):248-60. [Medline].
• Selch MT, Pedroso A, Lee SP, et al. Stereotactic radiotherapy for the treatment of acoustic neuromas. J Neurosurg. Nov 2004;101 Suppl 3:362-72. [Medline].
• Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol. Mar 1993;52(2):106-13. [Medline].
• Thomassin JM, Epron JP, Regis J. Preservation of hearing in acoustic neuromas treated by gamma knife surgery. Stereotact Funct Neurosurg. Oct 1998;70 Suppl 1:74-9. [Medline].

Article Last Updated: Mar 13, 2006