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Neurofibromatosis Type 2 Treatment & Management

  • Author: David T Hsieh, MD, FAAP; Chief Editor: Amy Kao, MD  more...
 
Updated: Oct 27, 2014
 

Approach Considerations

For individuals diagnosed with neurofibromatosis type 2 (NF2), medical care consists of routine examinations focusing on some of the potential complications related to CNS or spinal cord lesions.[3] 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 is reasonable, as is 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 the use of such tools as stereotactic radiosurgery and auditory brainstem implants (ABIs).[4, 18, 19]

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 examination accompanied by annual head MRI scans and hearing evaluations with BAERs seems to be a reasonable screening option.

Treatment setting

Although care of the patient with neurofibromatosis type 2 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.

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Radiation Treatment and Chemotherapy

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.

Therapeutic use of erlotinib has shown promise in the treatment of unresectable, progressive vestibular schwannomas, resulting not only in a decrease in tumor size but also in improvement in auditory function. Further clinical trials are in order before use of this oral chemotherapeutic agent can be recommended on a routine basis.[20] A trial of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, also showed some efficacy in the shrinkage of vestibular schwannomas; the drug improved hearing in some patients with unresectable tumors.[21]

Early in vitro studies have suggested that Gleevec, a tyrosine kinase inhibitor, may be useful in the treatment of vestibular and spinal cord schwannomas in patients with NF2.[22]

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Tumor Resection and Radiosurgery

Surgical resection of tumors remains the mainstay of treatment in neurofibromatosis type 2 (NF2), with recent advances in surgery permitting preservation of hearing for some affected individuals. For small vestibular schwannomas, surgical resection and stereotactic radiosurgery have been used and may preserve hearing and facial nerve function in selected patients.[4]

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. Interestingly, one report indicates that spontaneous regression of one vestibular schwannoma has been seen in several patients following resection of another, contralateral vestibular schwannoma.[23]

Studies have shown efficacy in the surgical treatment of nonvestibular cranial nerve schwannomas using a combination of microsurgery and radiosurgery.[5]

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 neurologic symptoms appear, yet complete resection of a spinal cord tumor may not always be possible and in some cases serves a primarily palliative function. Single fraction radiosurgery may also be used to treat spinal cord schwannomas, either serving as primary therapy or, following surgery, being used if residual tumor or tumor progression occurs.[24]

Surgical resection of cutaneous or subcutaneous growths can be accomplished, although plastic surgical consultation is advisable for areas of great cosmetic concern, such as the face.

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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.[6] ABIs in patients with neurofibromatosis type 2 (NF2), while providing some auditory input, do not enable high levels of speech recognition, presumably because of cochlear nerve damage in these patients.[25] Prior to surgery, ABI candidates should be engaged in a frank discussion about their expectations regarding this procedure, and a careful evaluation should be made of their family support system.[18, 19]

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Activity

Activity restriction is not necessary except as recommended by the neurologist or neurosurgeon on the basis of neurologic 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 acoustic nerve involvement, such activities may need to be curtailed.

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Consultations

The neurologist and neurosurgeon work closely together in the management of central and spinal cord lesions in neurofibromatosis type 2 (NF2). The neurologist provides valuable information regarding any changes in neurologic 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 ABIs are being considered. (Cochlear implants have not been as effective in the 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 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 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, as do personal perspectives on such testing, before an individual can provide consent. For couples considering prenatal diagnosis for NF2, genetic consultation is recommended.

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Long-Term Monitoring

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
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Contributor Information and Disclosures
Author

David T Hsieh, MD, FAAP Assistant Professor of Pediatrics, Assistant Professor of Neurology, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Adjunct Assistant Professor of Pediatrics, Adjunct Assistant Professor of Neurology, University of Texas Health Science Center at San Antonio School of Medicine

David T Hsieh, MD, FAAP is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Acknowledgements

The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of the Air Force, Department of Defense or the U.S. Government.

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience

Disclosure: Nothing to disclose.

Beth A Pletcher, MD Associate Professor, Co-Director of The Neurofibromatosis Center of New Jersey, Department of Pediatrics, University of Medicine and Dentistry of New Jersey

Beth A Pletcher, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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Subcutaneous and cutaneous lesions in a young man with neurofibromatosis type 2; note paucity of cafe-au-lait spots.
Right neck mass in a patient with neurofibromatosis type 2.
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.
Posterior cervical scar from cord lesion resection, thoracic scoliosis, and subcutaneous masses in a young adult with neurofibromatosis type 2.
Meningioma to the left of midline in a patient with neurofibromatosis type 2.
Multiple meningiomas (on the left) on the surface of the brain in a patient with neurofibromatosis type 2.
Bilateral acoustic neuromas in a patient with neurofibromatosis type 2.
Bilateral acoustic neuromas and a left-sided meningioma in a patient with neurofibromatosis type 2.
Small ependymoma in a patient with neurofibromatosis type 2.
Multiple meningiomas in a patient with neurofibromatosis type 2.
 
 
 
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