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6-year-old boy presents with intermittent headaches
Funduscopic examination revealed bilateral circumferential optic nerve elevation.
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A 6-year-old boy was referred to the New England Eye Center with symptoms of intermittent headaches for the last 3 months. The patient and his mother described the headaches as occurring three to four times per week, located primarily frontal and “on top of the head,” that would become progressively severe, lasting 1 to 2 hours, occasionally associated with nausea. Initially, it was thought the headaches may be related to concentrated activities such as reading. However, the pain was now occurring more often without any notable aggravating factors.
The patient was seen by his primary care provider for these headaches 4 weeks prior, and he was started on as-needed ibuprofen and an antacid for the occasional nausea and gastrointestinal prophylaxis. After minimal improvement, he was referred to Tufts Neurology for further work-up. Before any additional work-up for the headaches, the neurologist asked that he have a baseline eye exam performed. The patient denied any diplopia, acuity changes or eye pain. The patient lives with both of his parents in suburban Massachusetts and has no significant medical or family medical history.
The patient’s uncorrected visual acuity was 20/25 in both eyes, and his cycloplegic refraction was +0.75 +0.50 × 175 in the right eye and +1.00 +0.50 × 120 in the left eye. His external examination was normal, with no ptosis, lid retraction, exophthalmos or palpable preauricular nodes. His pupillary exam, extraocular movements, confrontation fields, color vision and IOPs were also within normal limits. Slit lamp biomicroscopy was unremarkable with no evidence of corneal disease or inflammation. The funduscopic exam revealed bilateral circumferential optic nerve elevation without any signs of hypoplasia, shunt vessels, significant hemorrhages or exudates (Figure 1). The remainder of the fundus exam, including retinal vasculature, macula and retinal periphery, was within normal limits.
Figure 1. Color fundus photographs demonstrating bilateral circumferential optic nerve elevation with mild hyperemia and vessel obscuration.
Images: Hansen BA, Strominger MB
Figure 2. Retinal nerve fiber layer OCT confirming bilateral nerve swelling.
The patient was unable to cooperate with a formal visual field exam but did have a retinal nerve fiber layer OCT that confirmed acute bilateral optic nerve swelling (Figure 2).
What is your diagnosis?
Intermittent headaches
Given the potentially ominous implications, the discovery of optic nerve elevation in the pediatric patient should prompt an urgent evaluation. In this unique younger population, it is important to maintain a broad differential diagnosis.
A differential for the pediatric patient with optic nerve elevation includes pseudopapilledema (optic nerve drusen, anatomic variability), infectious or post-infectious causes (Lyme, syphilis, toxoplasmosis, toxocariasis, tuberculosis, Bartonella henselae, herpes simplex virus, cytomegalovirus, paramyxovirus), inflammatory (sarcoidosis, juvenile idiopathic arthritis), infiltrative neoplastic (leukemia, lymphoma, astrocytic hamartoma), increased intracranial pressure (intracranial or nerve sheath tumors, hemorrhage, hydrocephalus, venous sinus thrombosis, idiopathic intracranial hypertension, choroid plexus tumor), optic neuritis, hypertensive crisis (pheochromocytoma), toxic/medication related (tetracyclines, sulfonamides, vitamin A analogs, ethylene glycol, methanol, lead, mercury, thallium, nutritional deficiency-thiamine, B12, B2, B3, B6), and genetic anomalies (mucopolysaccharidosis, craniosynostosis syndromes).
The potential etiology may be guided by carefully obtaining a patient history. Recent travel, current living situation (particularly assessing toxic/nutritional risks), recent fevers, chills, rashes, joint paints, lymphadenopathy, and recent or current medications are important inquiries. Headaches are a common complaint, and specific characteristics need to be elicited. Headaches from elevated intracranial pressure are often described as frontotemporal, pulsatile with slowly increasing intensity, worse in the mornings or awakening at night and often associated with nausea and vomiting (more common in children). Headache associated with refractive error (often hyperopia) is an entity classified by the International Headache Society but should be a diagnosis of exclusion only. Asymptomatic disc margin blurring found incidentally on exam is not uncommon and often signifies pseudopapilledema. Examination of parents or siblings can help to identify familial anatomic optic nerve abnormalities. Vision loss is an important finding that often signifies optic neuritis in the setting of acute disc elevation. Acute papilledema often has no visual symptoms or may have only transient visual obscurations.
Important findings on exam include bilaterality of the optic nerve elevation, nerve hyperemia vs. pallor, opacification of the peripapillary retinal nerve fiber layer, microvascular abnormalities on the disc surface (telangiectasias or flame hemorrhages), and loss of spontaneous venous pulsations (although absent in 20% of the general population).
Supplemental testing such as Humphrey visual field and fluorescein angiography may be difficult to obtain in children, but acute papilledema will classically show an enlarged blind spot and disc leakage. OCT has been proposed as one method of helping to differentiate among papilledema, optic neuritis and nonarteritic anterior ischemic neuropathy by looking for an inward deflection of the peripapillary retinal pigment epithelium and Bruch’s membrane. These findings, however, have not been verified in the pediatric population. Autofluorescence or B-scan may be helpful to rule out pseudopapilledema secondary to optic nerve drusen.
Our patient was an otherwise healthy individual from a good living situation on no medications. Although from a highly endemic area for Lyme disease, he had no other concerning history or findings consistent with an infectious or post-infectious etiology. His intermittent headaches for 3 months associated with occasional nausea and bilateral symmetric optic nerve elevation were concerning for papilledema. He was sent for laboratory work-up and MRI imaging of the brain and orbits (Figures 3 and 4), which showed a 4.6 cm by 4.8 cm heterogeneously enhancing mass arising from the posterior aspect of the fourth ventricle with significant mass effect and secondary hydrocephalus. The patient was then referred urgently to neurosurgery.
Discussion
Medulloblastomas are primary embryonal tumors of the central nervous system and make up the most common malignant brain tumors of childhood. They are thought to arise infratentorially from disruptions in cerebellar neurogenesis. They account for 16% to 25% of primary central nervous system neoplasms and approximately 40% of all posterior fossa tumors.
The most common presenting symptoms are related to elevated intracranial pressure typically from compression of the fourth ventricle and secondary hydrocephalus. These symptoms commonly include morning headaches, vomiting, personality changes and lethargy. Infants may present only with irritability, anorexia and developmental delay. Unfortunately, these symptoms are often intermittent and subtle. Thus, duration for months before diagnosis is common. Visual symptoms may also be a presenting feature in up to 60% of patients. These symptoms are thought to be related to compression, hemorrhage or arachnoiditis. A case series of 24 patients reviewed by Cassidy and colleagues reported that preoperative ocular symptoms included nystagmus (62%), sixth nerve palsy (50%), gaze palsy (8%), fourth nerve palsy (4%) and internuclear ophthalmoplegia (4%). There have also been reports of patients presenting with direct optic nerve compression or orbital metastasis leading to acute vision loss.
Diagnosis of medulloblastoma can be guided by careful ophthalmologic and neurologic exam along with central nervous system imaging (preferably MRI of the brain with and without contrast), biopsy and cerebrospinal fluid cytology. After histopathologic diagnosis, patients are risk stratified based on disease extension at diagnosis, residual tumor on postoperative imaging, age and tumor histological subtype. Molecular markers are also playing an increasingly important role in further risk stratification.
Treatment of medulloblastoma requires a multispecialty and multimodality approach with surgical resection, craniospinal irradiation and chemotherapy. It is important to recognize the role of the ophthalmologist in the continued care of these patients. Although many of the ophthalmic complications resolve after debulking surgery, 40% to 50% of patients may have long-term ocular sequelae requiring orthoptic treatment with prisms, occlusion or strabismus surgery. After treatment, patients are also at a high risk for neuropsychological sequelae with decreased IQ scoring, below average perceptual motor task performance and impaired motor dexterity. Thus, maximizing each patient’s quality of life through optimal vision correction is essential. Careful collaboration among neurosurgery, neurology, radiation and medical oncology, ophthalmology and pediatrics becomes increasingly important as patient long-term survival continues to improve.
Follow-up
Within 24 hours of the initial brain MRI, our patient began having symptoms of progressive ataxia. He underwent emergent suboccipital craniotomy for bulk resection of the tumor. Postoperatively, his ataxia had resolved with no new neurologic deficits. However, repeat imaging revealed a rim of residual tumor along the posterior resection cavity of more than 1.5 cm. This prompted a repeat craniotomy with additional surgical resection. After this surgery, the patient received low-dose craniospinal radiation plus chemotherapy with vincristine, followed by reduced radiation field treatment to the posterior fossa. He presently has no ocular symptoms and stable vision.
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For more information:
Bradley A. Hansen, MD, and Mitchell B. Strominger, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.