Neurofibromatosis Type 2 (NF2)

Neurofibromatosis type 2 (NF2) is a genetic disorder primarily characterized by the development of tumors along the nerves, most notably bilateral vestibular schwannomas (also known as acoustic neuromas). These tumors grow on the nerves that control hearing and balance, located in the inner ear. While vestibular schwannomas are the hallmark of NF2, individuals with the condition are also at risk of developing other types of tumors in the nervous system, including meningiomas, ependymomas, and other schwannomas on cranial and spinal nerves. NF2 is less common than NF1, affecting approximately 1 in 25,000 to 33,000 people.

Diagnosis

Diagnosing NF2 typically involves a combination of clinical evaluation, imaging studies, and genetic testing. The diagnostic criteria for NF2 generally include:

• Bilateral vestibular schwannomas (acoustic neuromas): The presence of tumors on both hearing and balance nerves is the most definitive sign of NF2.
• A first-degree relative with NF2 and either a unilateral vestibular schwannoma or any two of the following: meningioma, glioma, schwannoma (other than vestibular), juvenile posterior subcapsular lenticular opacities (a type of cataract).
• In the absence of a family history, meeting one of the following criteria:
  
  • Unilateral vestibular schwannoma and any two of the following: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacities.
  • Multiple meningiomas (two or more) any two of the following: glioma, schwannoma, juvenile posterior subcapsular lenticular opacities.

Imaging studies, particularly magnetic resonance imaging (MRI) of the brain and spine, are essential for identifying vestibular schwannomas and other potential tumors. Audiometry (hearing tests) and balance studies are also important parts of the diagnostic process. Genetic testing to identify a mutation in the NF2 gene can confirm the diagnosis and is particularly helpful in individuals who meet some but not all of the clinical criteria, or for family planning purposes.

Treatment

There is currently no cure for NF2, and treatment focuses on managing the growth of tumors and the associated symptoms to preserve neurological function and improve quality of life. Due to the potential for tumors to develop in various locations, a multidisciplinary team approach is crucial, involving neurosurgeons, otolaryngologists (ENTs) or neuro-otologists, and neurologists.

Treatment strategies are highly individualized and depend on the type, size, location, and growth rate of the tumors, as well as the patient's overall health and symptoms. Options may include:

• Watchful Waiting: For small, slow-growing, or asymptomatic tumors, regular monitoring with MRI scans and audiology tests may be recommended.
• Surgery: Surgical removal of tumors is a common treatment, particularly for vestibular schwannomas that are growing or causing significant symptoms like hearing loss, balance problems, or pressure on the brainstem. Surgery aims to remove as much of the tumor as possible while preserving nerve function. However, complete removal can be challenging, and there is a risk of damaging surrounding nerves, potentially leading to hearing loss, facial weakness, or other neurological deficits. Surgery may also be performed for symptomatic meningiomas, ependymomas, or other schwannomas.
• Radiation Therapy: Stereotactic radiosurgery (a precise form of radiation therapy) or fractionated radiotherapy may be used to control the growth of vestibular schwannomas and other tumors. Radiation can be an alternative to surgery, especially for smaller tumors or in cases where surgery is high-risk. While it can help control tumor growth, it may not eliminate the tumor and can have potential long-term side effects.
• Medications:
  
  • Bevacizumab (Avastin): This targeted therapy drug has shown some success in shrinking vestibular schwannomas and improving hearing in some individuals with NF2. It works by inhibiting the growth of new blood vessels that tumors need to survive. Research into other targeted therapies for NF2 is ongoing.
  • Medications for symptom management: Medications may be used to manage symptoms such as pain, seizures (though less common in NF2 than NF1), or hydrocephalus (build-up of fluid in the brain) if it occurs.
• Rehabilitation and Supportive Care: Audiological rehabilitation (e.g., hearing aids, auditory brainstem implants) and vestibular rehabilitation can help manage hearing and balance issues. Physical therapy, occupational therapy, and speech therapy may be beneficial depending on the neurological deficits. Psychological support and counseling are also important for individuals and families living with the challenges of NF2.

Associated Meningioma Treatment

Meningiomas are common in individuals with NF2 and can occur in multiple locations on the membranes covering the brain and spinal cord. Treatment for meningiomas in NF2 depends on their size, location, growth rate, and whether they are causing symptoms.

• Observation: Many meningiomas in NF2 are slow-growing and asymptomatic. In these cases, a "watch and wait" approach with regular MRI monitoring is often recommended.
• Surgery: Surgical removal is the primary treatment for symptomatic or growing meningiomas. The goal is to remove the tumor completely while preserving neurological function. The complexity of surgery depends on the tumor's size and location. Multiple meningiomas or those in critical areas can make surgical management challenging.
• Radiation Therapy: Radiation therapy, including stereotactic radiosurgery or fractionated radiotherapy, may be used for meningiomas that are inoperable, not completely removed surgically, or that continue to grow after surgery. Radiation aims to control tumor growth but does not typically eliminate the tumor.

The decision regarding the best treatment approach for meningiomas in NF2 is made by a multidisciplinary team, considering the individual's overall NF2 presentation and the potential impact of treatment on their neurological function.

Associated Ependymoma Treatment

Ependymomas are another type of tumor that can occur in individuals with NF2. These tumors arise from the ependymal cells lining the ventricles of the brain and the central canal of the spinal cord. Treatment for ependymomas in NF2 is similar to the approach for sporadic ependymomas, with considerations for the individual's NF2 diagnosis and other tumor burden.

• Surgery: Maximal safe surgical resection is the primary treatment for ependymomas. The goal is to remove as much of the tumor as possible to relieve symptoms and potentially improve outcomes. The feasibility and extent of surgical removal depend on the tumor's location and size.
• Radiation Therapy: Radiation therapy is often used after surgery, especially if the tumor could not be completely removed or if the ependymoma is a higher grade. Radiation helps to control any remaining tumor cells and reduce the risk of recurrence. The type and dose of radiation are carefully planned based on the tumor's characteristics and location.
• Chemotherapy: Chemotherapy is generally less effective for ependymomas compared to other brain tumors, but it may be considered in certain situations, such as for recurrent tumors or those that have spread.

The management of ependymomas in NF2 requires careful consideration within the broader context of the individual's other NF2-related tumors and neurological function. A multidisciplinary team, including neurosurgeons, neuro-oncologists, and radiation oncologists, collaborates to determine the most appropriate treatment plan.

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Outcomes

The outcome for individuals with NF2 is variable and depends largely on the number, location, and growth rate of tumors, as well as the effectiveness of treatments. NF2 can significantly impact quality of life due to the potential for hearing loss, balance problems, facial weakness, vision problems (from cataracts or optic nerve involvement), and other neurological deficits resulting from tumor growth or treatment.

Potential outcomes and complications of NF2 include:

• Hearing Loss and Deafness: This is a very common outcome due to vestibular schwannomas.
• Balance Problems: Damage to the vestibular nerves can cause chronic dizziness and difficulty with balance.
• Facial Weakness or Paralysis: This can occur if facial nerves are affected by tumors or damaged during surgery.
• Vision Problems: Cataracts are common, and tumors affecting the optic nerve are possible, potentially leading to vision loss.
• Other Neurological Deficits: Depending on the location of other schwannomas, meningiomas, or ependymomas, individuals may experience pain, weakness, numbness, or problems with motor skills.
• Hydrocephalus: Tumors can sometimes block the flow of cerebrospinal fluid, leading to hydrocephalus, which requires intervention.
• Spinal Cord Compression: Tumors on the spinal cord can cause pain, weakness, and sensory changes.

While NF2 is a chronic and potentially debilitating condition, ongoing research is improving our understanding of the disease and leading to the development of new diagnostic tools and therapeutic strategies. Regular monitoring, timely intervention, and comprehensive supportive care are essential for managing the challenges of NF2 and optimizing outcomes for affected individuals.

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