Managing Plexiform Neurofibroma and Other Complications of Neurofibromatosis Type 1 in the Adult Neurology Clinic: A Review.

PURPOSE OF REVIEW: Loss-of-function variants in the NF1 gene result in the development of neurofibromatosis type 1 (NF1), a neurogenetic disease and multisystem disorder that includes a predilection for benign and malignant tumors of the central and peripheral nervous systems. Patients with NF1 experience a wide variety of comorbidities, such as chronic pain conditions, learning disabilities, and signs and symptoms that include migraines and NF1-associated plexiform neurofibromas (PNs), which can cause disfigurement and pain. All of these factors can severely affect health-related quality of life (HRQoL). Although treatment options are limited, advances in targeted therapies have led to the approval of the mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) inhibitors selumetinib and mirdametinib, which reduce target PN volume and improve HRQoL in patients with NF1-PNs.

RECENT FINDINGS: A multidisciplinary team is necessary to evaluate patients and determine appropriate treatments that may reduce the burden of NF1. For adult patients with NF1, neurologists or neuro-oncologists may determine individual patient imaging and serial monitoring needs based on clinical evaluations and patient history. Imaging is useful to identify and determine the extent of potentially concerning tumors, although the specific imaging methods available depend on individual institutional capabilities. Biopsies may be conducted on areas of clinical or radiologic concern to determine the presence of malignant peripheral nerve sheath tumors or atypical neurofibromatous neoplasm of uncertain biological potential. Systemic treatment or surgical debulking may be recommended to reduce PN symptoms caused by tumor size, inflammation, and compression of vital organs. However, in patients with inoperable symptomatic NF1-PN, systemic MEK inhibitors may be considered to target PN volume reductions. Currently, 2 MEK1/2 inhibitors (selumetinib and mirdametinib) are approved by the US Food and Drug Administration and European Commission for the treatment of NF1-PN.

SUMMARY: Because of the complexity of how and when to administer treatment and the impact of symptoms on HRQoL, a multidisciplinary team is essential to manage the manifestations of NF1, including PN, to achieve the greatest benefit from currently available therapies.