Selumetinib may alleviate migraine in a patient with neurofibromatosis type 1 (NF1): a case report

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder resulting from loss-of-function mutations in the NF1 gene. Deficiency of neurofibromin leads to hyperactivation of the Ras/MEK/ERK and PI3K/Akt/mTOR pathways, thereby disrupting cellular proliferation and differentiation. In addition to classic manifestations, chronic headache is a recognized complication, potentially attributable to MEK/ERK-mediated neuronal hyperexcitability. Selumetinib, a selective MEK1/2 inhibitor, is approved for paediatric inoperable plexiform neurofibromas, however, its efficacy in treating NF1-associated headaches has not been previously reported. An adolescent female patient, previously diagnosed with NF1 presented with debilitating, daily headaches accompanied by recurrent episodes of projectile vomiting. Comprehensive evaluation excluded alternative organic or psychogenic causes. While neither plexiform neurofibromas nor space-occupying lesions were detected on cranial MRI scans, only NF1-related focal areas of signal intensities (FASIs) were observed, the clinical significance of which is uncertain. Selumetinib treatment was subsequently initiated. The patient demonstrated a rapid and clinically meaningful response, with headache frequency decreasing markedly from daily to approximately once weekly. A corresponding reduction in analgesic use was also observed. This case provides a hypothesis-generating observation of headache improvement during selumetinib treatment in an NF1 patient without plexiform neurofibromas. Further studies are needed to determine whether MEK inhibition has a therapeutic role in NF1-associated headache. Importantly, given the single case nature of the observation, further prospective trials are needed before any therapeutic implications can be considered.