What are the management options for Neurofibromatosis (NF), including NF1 (Neurofibromatosis type 1) and NF2 (Neurofibromatosis type 2)?

Management of Neurofibromatosis (NF1 and NF2)

The management of neurofibromatosis requires a specialized multidisciplinary approach with different strategies for NF1 and NF2, with surgical intervention for symptomatic tumors and MEK inhibitors like selumetinib for inoperable plexiform neurofibromas in NF1 patients. 1

Neurofibromatosis Type 1 (NF1) Management

Plexiform Neurofibromas

• First-line treatment: Selumetinib (FDA-approved MEK inhibitor) for symptomatic, inoperable plexiform neurofibromas in pediatric patients ≥2 years 1, 2
• Surgical approach: Consider for accessible tumors causing symptoms, but complete resection is often impossible due to infiltrative nature 1
• Monitoring: Newly diagnosed plexiform neurofibromas require close observation with serial evaluations 1
• Indications for intervention:
  • Visual decline
  • Progressive tumor growth
  • New or worsening functional deficit
  • Progressive disfigurement

Orbital/Periorbital Plexiform Neurofibromas

• Perform MRI brain and orbits with high-resolution sequences 3
• Imaging frequency based on clinical progression (at least every 3-6 months until stability confirmed) 1
• Avoid CT scans due to radiation exposure, especially in children 1

Malignant Peripheral Nerve Sheath Tumors (MPNSTs)

• Monitor for MPNSTs (lifetime risk: 15.8%) 1
• Key warning signs: pain, rapid growth, neurologic symptoms 1
• Surgery remains cornerstone of treatment, aiming for clear margins 1

Screening and Monitoring

• Annual general medical evaluation 1
• Blood pressure measurement to detect hypertension, pheochromocytoma, and renal artery stenosis 1
• Clinical evaluation for scoliosis using Adam's forward bend test 1
• Thorough skin examination for café-au-lait spots and neurofibromas 1
• For women: Annual mammogram starting at age 30 and breast MRI with contrast between ages 30-50 1

Neurofibromatosis Type 2 (NF2) Management

Vestibular Schwannomas

• Early microsurgery: Consider when tumors are small to preserve hearing and cranial nerve function 1
• Patient categorization for treatment planning 3:
  1. Treatment naive: 0-1 neurosurgical CNS procedure, no major complications except hearing loss or minor mononeuropathy
  2. Few treatments/some morbidity: 2-3 CNS surgeries, ambulant with no more than one major complication
  3. Severe NF2: Multiple surgeries or severe morbidity

Hearing Preservation Strategies

• Cochlear preservation surgery for patients with VS ≤1.5-cm and speech discrimination scores ≥70% 3
• Hearing monitoring: 4-frequency pure-tone average (significant change: >5 dB) or speech discrimination (significant change: 15% difference) 3

Other NF2 Tumors

• Intracranial meningiomas (occur in 50% of NF2 patients): Surgery for growing tumors 4
• Spinal tumors (occur in ~50% of NF2 patients): Surgery when radiological progression is demonstrated, even if asymptomatic 4
• Lower cranial nerve schwannomas: Radiosurgery for small growing tumors to avoid swallowing disorders 4
• Facial nerve schwannomas: Suspect when facial palsy is an early symptom during cerebello-pontine tumor progression 4

Monitoring

• Regular MRI surveillance of all known tumors 5
• Quality of life assessments using structured validated questionnaires 3
• Video assessment of facial nerve function 3

General Management for Both NF1 and NF2

Genetic Counseling

• Provide counseling regarding 50% offspring recurrence risk 1
• Discuss prenatal diagnosis and preimplantation genetic diagnosis options 1
• Discuss limitations of PGD for individuals with de novo mutations, somatic mosaicism, and large genomic rearrangements 1

Pregnancy Considerations

• Refer pregnant women with NF to high-risk obstetrician 1
• Monitor for pregnancy complications (gestational hypertension, preeclampsia, intrauterine growth restriction) 1

Patient Education

• Educate about concerning symptoms requiring immediate attention:
  • Progressive severe pain
  • Changes in tumor volume
  • New unexplained neurologic symptoms
  • Diaphoresis/palpitations 1

Important Caveats and Pitfalls

1. Misdiagnosis: NF1 and NF2 are distinct disorders with different management approaches but are often confused 6

2. Delayed diagnosis: Many patients identify expert care too late to save the cochlear nerve in NF2 3

3. Incomplete tumor removal: Complete resection of plexiform neurofibromas is often impossible due to their infiltrative nature 1

4. Radiation exposure: Avoid CT scans, especially in children, due to increased cancer risk in NF patients 1

5. Surgical complications: VS surgery frequently leads to deafness and loss of facial nerve function, infections, and headaches 3

6. Tumor progression monitoring: There is no correlation between tumor size and hearing loss in NF2 3

7. Life expectancy impact: NF1 is associated with an 8-15 year reduction in life expectancy 1