What is the management of neurofibromatosis (NF)?

Management of Neurofibromatosis

The management of neurofibromatosis requires a multidisciplinary approach with regular monitoring for complications through specialized NF clinics, with specific surveillance protocols based on NF type and patient age. 1

Types of Neurofibromatosis

Neurofibromatosis has distinct types that require different management approaches:

• NF1: Most common (1/2,000-1/3,000 births), autosomal dominant with complete penetrance but variable expressivity 2, 1
• NF2: Characterized by bilateral vestibular schwannomas
• Schwannomatosis: Rarest form with multiple schwannomas

Screening and Surveillance for NF1

Regular Monitoring

• Annual comprehensive medical evaluation 1
• Follow general population age/gender-specific health screening (cholesterol, colonoscopy, cervical cancer) 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

Imaging and Laboratory Studies

• Baseline MRI of known/suspected plexiform neurofibromas 1
• For orbital/periorbital plexiform neurofibromas: MRI brain and orbits with high-resolution sequences every 3-6 months until stability confirmed 1
• Avoid CT scans due to radiation exposure, especially in children 1
• Consider serum vitamin D measurement and supplementation 1
• Dual-energy X-ray absorptiometry for bone density assessment 1

Cancer Surveillance

• Annual mammogram starting at age 30 and breast MRI with contrast between ages 30-50 for women 1
• Monitor for malignant peripheral nerve sheath tumors (MPNSTs) - lifetime risk of 15.8% 1, 2
• Clinical suspicion (pain, rapid growth, neurologic symptoms) is key to early MPNST detection 2
• Monitor for other NF1-associated malignancies (gliomas, gastrointestinal stromal tumors, rhabdomyosarcoma, thyroid cancer) 1

Treatment Approaches for NF1

Pharmacological Management

• Selumetinib: FDA-approved for symptomatic, inoperable plexiform neurofibromas in pediatric patients ≥2 years 1, 3
• MEK inhibitors provide therapeutic options for unresectable plexiform neurofibromas, reducing tumor bulk and improving symptoms 3
• Alternative MEK inhibitors and mixed tyrosine kinase inhibitors may have better efficacy in adults 3

Surgical Management

• Surgery remains the cornerstone of treatment for high-grade MPNST, with the aim of achieving clear margins 2
• For plexiform neurofibromas, complete resection is often impossible due to infiltrative nature 1
• Surgical approaches may be more definitive for adults as tumors are less likely to continue growing 1

Indications for Intervention

• Visual decline
• Progressive tumor growth
• New or worsening functional deficit
• Progressive disfigurement 1

Management of NF2

• VEGF inhibitor bevacizumab can prolong hearing and delay surgery in NF2 patients with bilateral vestibular schwannomas 3
• For vestibular schwannomas, consider early microsurgery when tumors are small to preserve hearing and cranial nerve function 2
• Clinical trials categorize NF2 patients into three groups based on treatment history and morbidity 2:
  1. Treatment naive (0-1 neurosurgical procedures)
  2. Few treatments with some morbidity (2-3 surgeries)
  3. Severe NF2 (multiple surgeries or severe morbidity)

Special Considerations

Pregnancy and Contraception

• Refer pregnant women with NF1 to high-risk obstetrician 1
• Monitor for pregnancy complications (gestational hypertension, preeclampsia, intrauterine growth restriction) 1
• Provide genetic counseling regarding 50% offspring recurrence risk 1
• Discuss prenatal diagnosis and preimplantation genetic diagnosis options 1

Patient Education

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

Prognosis

• NF1 is associated with an 8-15 year reduction in life expectancy, primarily due to malignant neoplasms and cardiovascular causes 1
• MPNSTs contribute significantly to NF1 mortality (standardized mortality ratio >2,000) 1

Care Coordination

• Strong recommendation for evaluation and care coordination through specialized NF clinics 1
• Multidisciplinary team approach essential for managing this complex disorder 1, 4
• Regular communication among various specialties involved in patient care 4

The management of neurofibromatosis requires vigilant monitoring and proactive intervention to minimize morbidity and mortality. Recent advances in targeted therapies offer new hope for patients with previously untreatable manifestations of the disease.