Review Question - QID 221221

This patient with headaches in the setting of cafe-au-lait spots most likely has neurofibromatosis type 1 (NF1). This patient’s worsening headaches, nausea, vomiting, and papilledema is suggestive of an optic pathway glioma, which can be confirmed with MRI of the head.

NF1 is an autosomal dominant disease caused by a mutation of neurofibromin on chromosome 17. Symptoms of this disease include cutaneous neurofibromas, cafe au lait spots, plexiform neurofibromas, bone abnormalities, pheochromocytoma, cognitive disability, and optic pathway gliomas. Optic pathway gliomas can occur anywhere along the visual pathway. More anterior lesions can present with proptosis, strabismus, disconjugate nystagmus, and unilateral optic nerve atrophy. More posterior gliomas in the optic chiasm, hypothalamus, and anterior third ventricle can present with impaired vision, precocious puberty, and obstructive hydrocephalus, respectively. MRI of the head is the preferred diagnostic modality for optic pathway gliomas because this allows for visualization of the entire course of the optic nerve and a clearer delineation of hypothalamic involvement. Optic pathway gliomas that cause obstructive hydrocephalus can be treated with tumor resection, ventricular shunting, radiotherapy, chemotherapy, and targeted therapies against the MAPK pathway.

Gutmann et al. reviewed the pathophysiology, clinical manifestations, diagnosis, and clinical management of patients with neurofibromatosis type 1. They discuss how nearly all patients with NF1 will develop pigmentary lesions. They recommend that a collaborative and multidisciplinary approach be taken in treating patients with NF1.

Figure/Illustration A is a clinical photograph that demonstrates cafe-au-lait spots (red circles). This finding is classically seen in patients with neurofibromatosis type 1.

Incorrect Answers:
Answer 1: Computed tomography (CT) scan of the head can help delineate bony detail and detect intratumoral calcifications in patients with NF1. CT scans of the head can also be used to rule out intracranial hemorrhage, which are not associated with NF1. MRI allows for better visualization of the entire course of the optic nerve while having a higher sensitivity and specificity for intracranial masses.

Answer 3: Ocular ultrasonography can be used in cases of acute vision changes and suspected elevations in ICP. It can detect retrobulbar hematoma, foreign bodies, lens detachment, retinal detachment, vitreous hemorrhage, and posterior vitreous detachment. In addition, measurement of optic nerve sheath diameter can evaluate for elevated ICP. Ultrasound would be unable to visualize deeper lesions of the optic tract.

Answer 4: Optical coherence tomography of the optic nerves provides information on the optic nerve head topography using interferometry. Optical coherence tomography can be used to identify causes of vision loss, including optic disc edema in acute optic neuritis, non-arteritis ischemic anterior optic neuropathy, and glaucoma. Optical coherence tomography is unable to image extraocular pathologies.

Answer 5: Transcranial Doppler ultrasonography attempts to non-invasively measure ICP by assessing the velocity of blood in the proximal cerebral circulation. Transcranial Doppler ultrasonography is generally a poor predictor of ICP. In addition, transcranial Doppler ultrasonography would not diagnose this patient’s underlying optic pathway glioma.

Bullet Summary:
Optic pathway gliomas are associated with neurofibromatosis type 1 and are most appropriately diagnosed with magnetic resonance imaging.