What is the recommended management approach for Neurofibromatosis type 2 (NF2)?

Management of Neurofibromatosis Type 2

For NF2 patients with small vestibular schwannomas (<1.5 cm) and preserved hearing (speech discrimination ≥70%), hearing-sparing microsurgery via retrosigmoid or middle fossa approach is the first-line treatment, while bevacizumab (7.5 mg/kg IV every 3 weeks) should be used for patients with larger tumors and preserved hearing or progressive disease where surgery is not feasible. 1, 2

Initial Assessment and Surveillance Strategy

Establish baseline imaging and monitoring protocol:

• Obtain head MRI at diagnosis, then every 6 months for the first year, followed by annual imaging thereafter 1, 3
• Perform spinal MRI every 3 years to detect meningiomas, schwannomas, and ependymomas 3
• Conduct annual audiological assessment with speech discrimination testing 3
• Use volumetric tumor measurements rather than linear measurements, as they are significantly more sensitive for detecting growth and guiding treatment decisions 2

Key surveillance finding: Vestibular schwannomas in NF2 grow faster than sporadic tumors, requiring closer monitoring than typical acoustic neuromas 2

Treatment Algorithm by Clinical Scenario

For Treatment-Naive Patients with Small Tumors and Good Hearing

Surgical approach is preferred when:

• Tumor diameter is <1.5 cm 2
• Speech discrimination scores are ≥70% in both ears 4, 2
• Tumor incompletely fills the lateral internal auditory canal 4
• Tumor originates from superior vestibular nerve (indicated by reduced caloric response) 4

Surgical technique selection:

• Either retrosigmoid or middle fossa approach can be used, as there is insufficient evidence supporting superiority of either for complete resection and facial nerve preservation 4
• Intraoperative neurophysiological monitoring is mandatory during surgery 2
• For bilateral disease, operate on the more favorable tumor first 4

Critical pitfall: Larger tumor size correlates with greater risk of hearing loss, so counsel patients accordingly before proceeding 4

For Patients with Larger Tumors or Progressive Disease

Bevacizumab is the primary medical therapy:

• Dose: 7.5 mg/kg IV every 3 weeks 2
• Produces hearing improvement in 36% of patients with no hearing deterioration during 12-month treatment 2
• Achieves partial radiographic response (≥20% volume reduction) in 43% of patients 2
• This is the only pharmacological therapy with level II evidence for progressive vestibular schwannomas 2

When to choose bevacizumab over surgery:

• Larger tumors where surgical risk of hearing loss is high 1
• Progressive disease when surgery is not feasible 1
• Patients with multiple tumors who cannot undergo further surgery 4

For Large Tumors Causing Mass Effect

Decompression surgery is mandatory when:

• Tumor causes significant mass effect on brainstem 2
• Patient develops nausea, vomiting, or true vertigo from brainstem compression 5

Post-surgical options:

• Subtotal resection followed by stereotactic radiosurgery or observation is valid for large tumors with residual disease 2
• However, if microsurgical resection becomes necessary after prior stereotactic radiosurgery, counsel patients about increased likelihood of subtotal resection and decreased facial nerve function 4

Management of Associated Tumors

Meningiomas (occur in 50-60% of NF2 patients)

Indications for surgery: 4, 1

• Significant tumor growth on serial imaging
• Parenchymal edema
• Neurologic deficit
• Intractable seizures
• Intracranial hypertension

Surveillance approach:

• Clinical and MRI follow-up at 6 months, then yearly for stable tumors 4
• Very few patients develop new meningiomas during surveillance 4

Special consideration: For cavernous sinus meningiomas, surgery is not recommended; radiosurgery may be helpful for rare symptomatic growing tumors 4

Spinal Tumors (occur in 70% of patients)

Surgical indications:

• Symptomatic tumors with radiological progression 4, 1
• Consider surgery even for asymptomatic tumors showing progression to preserve neurological function and quality of life 6

Important distinction: NF2 ependymomas are usually indolent and rarely require surgery 4, 1

Lower Cranial Nerve Schwannomas

Treatment approach:

• Radiosurgery is more appropriate than surgery for growing tumors with small volume to avoid post-operative swallowing disorders 6

Hearing Rehabilitation Options

When Hearing is Lost

Cochlear implant pathway:

• If hearing is lost after first-side surgery with <60% word discrimination on unoperated side, perform promontory stimulation on operated ear 4
• If positive auditory stimulation, consider cochlear implant with hope for long-term viability and excellent speech discrimination 4
• Preservation of cochlear nerve during surgery allows for future cochlear implantation 2

Auditory brainstem implant (ABI):

• Consider when neither cochlear nerve is stimulated 4, 1
• Provides useful auditory sensations in most deaf NF2 patients 4, 1
• Improves communication ability compared to lip reading alone 4, 1
• Allows detection and recognition of environmental sounds and can offer significant speech understanding without lip reading cues 4

Technical requirement: Patients with cochlear implants or ABIs need device magnet removed for MRI participation 4

Facial Nerve Paralysis Management

Treatment ranges from: 2

• Eye lubrication for mild cases
• Surgical reanastomosis (hypoglossal-facial nerve) for severe cases

Controversial: Radiosurgery and Radiotherapy

The use of radiation therapy in NF2 is highly controversial: 4, 1

Arguments for limited use:

• Stereotactic radiosurgery is valid for growing vestibular schwannomas causing hearing loss 2
• Dose <13 Gy facilitates hearing preservation and minimizes cranial nerve deficits 2
• May be preferred over microsurgery when primary goal is preserving facial nerve function and hearing in small tumors 2

Major concerns:

• May induce malignancy, including secondary meningiomas and multiple small tumors 4, 1
• Patients who fail radiosurgery may become therapy resistant 4, 1
• Lack of thorough data on risks, benefits, and outcomes specific to NF2 4

Clinical reality: There are differences of opinion whether observation, microsurgery, or radiosurgery is more effective for hearing preservation, and insufficient evidence exists to definitively recommend surgical resection as initial treatment in NF2 patients 4

Multidisciplinary Team Requirements

Core team composition: 3

• Medical genetics
• Neurosurgery and neurotology
• Neurology
• Ophthalmology
• Audiology
• Radiology
• Psychology
• Physiotherapy
• Specialist nurses

Additional access needed: 3

• Plastic surgery
• Peripheral nerve surgery
• Adult and pediatric oncology

Delivery model: Weekly multidisciplinary clinics with 6-8 patients, team meeting for management decisions before patient discussion 3

Critical Management Pitfalls to Avoid

Patient burnout: After multiple surgeries and treatments, NF2 patients may suffer from "burnout" and become difficult to engage in further treatment 4, 1

Post-radiation surgery complications: Patients requiring microsurgical resection after stereotactic radiosurgery face increased likelihood of subtotal resection and decreased facial nerve function 4

Exclusion from trials: Patients with multiple prior surgeries or radiation may need exclusion from certain treatments due to malignancy risk and impaired imaging from surgical artifacts 4, 1

Misdiagnosis risk: Facial nerve schwannomas may appear identical to vestibular schwannomas on MRI; suspect this diagnosis when facial palsy is an early symptom during cerebellopontine angle tumor progression 6