Neurofibromatosis Type 1 – ch. 5. th

Neurofibromatosis Type 1 – ch. 5. th

Medical Care

For individuals diagnosed with neurofibromatosis type 1 (NF1), routine examinations should focus on the potential complications.

  • Annual examinations permit early detection of problems, decreasing morbidity and improving quality of life.
  • Annual eye examinations are important in early detection of optic nerve lesions.

Cutaneous examination performed at each visit should look for new neurofibromas or progression of preexisting lesions. Plexiform neurofibromas may be locally invasive, therefore clinical evaluation should be directed at determining the extent of involvement and detecting evidence of bony erosion or nerve entrapment.

Skeletal involvement, including scoliosis, hemihypertrophy, or long-bone modeling defects, should be documented.

Blood pressure should be checked at each visit and hypertension treated promptly if detected. Hypertension workup should include evaluation for pheochromocytoma (ie, measurement of urinary catecholamines and metanephrines) and testing for renal artery stenosis. Percutaneous transluminal renal artery angioplasty may, in some cases, effectively treat renal artery stenosis secondary to fibromuscular dysplasia.

Interval history should focus on subtle sensory or motor symptoms such as paresthesia, radiculopathy, weakness, or muscle atrophy.

  • Patients should be asked about incontinence. At each visit, minor changes in the sensory or motor examination should be documented carefully.
  • Symptoms of spinal cord neurofibromas may be subtle and slowly progressive; prompt identification and early surgical intervention allow for optimal outcome.

Removal of neurofibromas for medical or cosmetic indications is one of the most common procedures on individuals with NF1.

  • Recent advances in laser technology have permitted nonsurgical removal of small, cutaneous neurofibromas.
  • However, careful surgical resection of small or large neurofibromas may leave an even smaller, less prominent scar.

Although laser treatment has been used for various cutaneous, hyperpigmented lesions (eg, port-wine stains, tattoos), it has not yet proven successful in permanent removal of café-au-lait spots.

Use of chemotherapy to treat malignant peripheral nerve sheath tumors (MPNSTs) that are unresectable or metastatic has been debated for a number of years, with less than optimal outcomes using a variety of combinations of agents. More recently, in vitro studies looking at a broader range of agents targeting the Ras and/or other relevant pathways have shown some promising results.

  • Farnesyl transferases used in combination with lovastatin have shown synergistic effects in growth inhibition of MPNST cell lines in vitro.
  • Sorafenib also appears to inhibit MPNST cell growth in vitro.
  • A rapamycin complex 1 inhibitor (RAD001) demonstrated decreased tumor cell growth when used alone, and, when used in combination with erlotinib (an epidermal growth factor receptor tyrosine kinase inhibitor), showed even further growth inhibition and tumor cell apoptosis.
  • Hyaluronan oligomers, another promising agent, has shown efficacy in slowing growth of MPNSTs in animal models. These small molecules, when used in combination with a traditional chemotherapy agent (doxorubicin), substantially inhibit tumor growth.
  • In the near future, studies such as these will likely lead to preclinical and then clinical trials for patients with unresectable MPNSTs.
  • The use of chemotherapy, especially with carboplatin and vincristine have been shown to be effective in controlling the progression of optic nerve gliomas.

Surgical Care

Surgical resection of neurofibromas can be accomplished, but plastic surgery consultation is advisable for areas of great cosmetic concern such as the face. Resection is the treatment of choice for pheochromocytomas.

Neurofibromas that press on vital structures, obstruct vision, or grow rapidly deserve immediate attention.

Plexiform neurofibromas may be difficult to approach surgically, often recurring after resection because of residual tumor cell collections deep in soft tissues. Surgeons must realize that removing some of these lesions can result in substantial blood loss and must plan accordingly.

Symptomatic peripheral nerve sheath tumors located along the nerves of the brachial or pelvic plexus sometimes require surgical intervention with the very real potential for postoperative nerve dysfunction. Added to this is the risk for malignant transformation that carries with it a very poor prognosis; the decision to operate requires much thought and careful consideration. One should always weigh the potential diagnostic benefits taking into account one’s index of suspicion for malignancy, against the potential risks for long-term neurologic sequelae.

For many patients, neurofibromas on the scalp, along the hairline, or around the waist where clothes rub can cause great irritation and discomfort. Therefore, removing these should not be considered cosmetic but a necessary medical procedure.

Resection of spinal cord tumors is difficult but often necessary to prevent progressive paraplegia or quadriplegia.

  • Acting promptly when neurological symptoms appear is important to maximize operative success.
  • Surgical intervention may not guarantee a complete resection of the tumor, but it may serve a palliative function in some cases.
  • Single fraction radiosurgery has been used in some centers to treat benign intradural extramedullary spinal cord tumors. This technique may be used as a primary therapeutic approach or in cases of postsurgical progression or when residual tumor is a concern after a subtotal surgical resection.

Orthopedic intervention is indicated for rapidly progressive scoliosis and for some severe bony defects.

  • Following patients with NF1 when scoliosis is first detected is advisable, so that nonsurgical approaches may be used in an attempt to obviate the need for a future spinal fusion procedure.
  • Limb-sparing procedures in addition to new bracing and casting technologies have decreased the need for amputation in patients with a pseudarthrosis. See the image below. Below-the-knee amputation for tibial pseudarthrosis.
  • Patients with long-bone defects are best served by ongoing orthopedic care.

Some hypertensive patients with renal artery stenosis require surgical resection and repair instead of or following angioplasty.

Resection of a pheochromocytoma requires preoperative treatment with an alpha-blocker (preferably a selective postsynaptic alpha1-receptor antagonist) to offset the effects of catecholamine release during surgical manipulation of the tumor.

Medication Summary

No known medical therapies are beneficial to patients with NF1. Several drug trials have been initiated, looking for medications that slow or halt the growth of neurofibromas. Thus far, none of these medications have demonstrated significant benefit, although various research trials involving chemotherapeutic and other agents are underway in an attempt to slow the growth of plexiform neurofibromas.

For a small subset of patients with pruritus due to cutaneous neurofibromas, diphenhydramine may provide some temporary relief. Such patients also are encouraged to avoid hot showers and baths, since hot temperatures may exacerbate itching.

Treatment with carboplatin shows efficacy in controlling the growth of visually significant optic gliomas.

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