Case Report
An 8 year-old African American female with severe sickle cell (HgSS) disease diagnosed at birth was confirmed to have NF1 at 13 months of age with > 6 cafe au lait macules over 5mm in diameter, freckling in the axillary regions (Crowe’s sign) and significant family history as the mother of child has 6 other children, 3 of whom have NF1 including herself.  The patient’s SCD course was complicated by splenic sequestration necessitating splenectomy at 3 years of age.  She was started on Hydroxyurea at 5 years of age and since has had a good hematologic and clinical response in that she did not require hospitalizations or emergency intervention for a severe vaso-occlusive crisis. She followed with ophthalmology annually to screen for ophthalmologic associations with SCD and NF1 beginning at age 6 years. She was also seen by neurology to evaluate for possible brain vasculopathies as well as learning delays associated with NF1.  Routine brain imaging surveillance with MRI/MRA had been normal except for a T2 hyperintensity in the right frontal lobe periventricular white matter related to a remote infarct and slightly prominent lenticulostriate vessels noted initially when she was 5 years of age (Supplemental Fig. S1). She has been neurologically asymptomatic.
When she was 7 years of age, she was noted to have incidental papilledema. Subsequent work up revealed MRI/MRA brain w/wo contrast and MRI orbits w/wo showed no masses or new changes compared to prior imaging. A lumbar puncture was then performed showing an opening pressure of 34cm H2O confirming the clinical suspicion of IH. She was asymptomatic at the time, but was started on 250 mg PO BID of acetazolamide orally while at the same time the hydroxyurea was discontinued, as reports had shown high fetal hemoglobin could cause intracranial hypertension. Her fetal hemoglobin was 30.5% which was otherwise an ideal response to the disease modifying agent in a patient with severe SCD.
Papilledema was noted to persist several weeks after starting acetazolamide, so the dose was titrated up and the patient was referred for pediatric neuro-ophthalmic evaluation. Ancillary testing performed 3 months later during pediatric neuro-ophthalmic evaluation confirmed normal retinal nerve fiber layer (RNFL) analysis with mild peripapillary hyperreflective ovoid mass-like structures (PHOMS) at the present dose of acetazolamide 425 mg PO BID (Fig. 1). The patient was then tapered off acetazolamide over the period of 1 month, and repeat testing performed 7 months later confirmed presence of normal RNFL analysis in both eyes with congenital anomaly of both optic nerves (Supplemental Fig. S2). Since optical coherence tomography (OCT) RNFL was normal and the patient continued to have no symptoms, hydroxyurea was restarted 5 months after initial diagnosis of IH and her fetal hemoglobin at that time was 15.7%. Table 1 shows her hemoglobin electrophoresis trend. She has been feeling well with no worsening in the ophthalmological exam while off acetazolamide.