Rapid vision loss in a 15-year-old boy

A 15-year-old boy with a recent diagnosis of T-cell acute lymphoblastic leukaemia (ALL) and a history of factor V Leiden heterozygosity presented with a sudden onset of bilateral vision loss over a 24 h period. 2 weeks prior to presentation he received pegaspargase chemotherapy. During the week preceding admission he had noted mild blurred vision and complained of retro-orbital headaches. Ophthalmic examination revealed visual acuity of 20/800 in the right eye and minimal light perception in the left eye. He had sluggish pupillary reactivity to light with a left relative afferent pupillary defect. Dilated fundoscopic examination demonstrated bilateral florid optic disc swelling with peripapillary and dot-blot haemorrhages in the periphery, and macular oedema of the left eye. Neurological examination demonstrated mild left peripheral seventh nerve palsy.

Multiplanar and multisequence MRI of the orbits, face and neck were obtained before and after administration of 20 cc iv contrast (Figures 1–4).

Figure 1.

Pre-contrast T₁ weighted axial MRI of the brain.

Figure 4.

Post-contrast T₁ weighted sagittal MRI.

• What are the abnormalities seen in Figures 1 and 2?

• What do you notice in Figure 3?

• Are there any additional findings in Figure 4?

• What is the diagnosis?

Figure 2.

Post-contrast fat-saturated T₁ weighted axial MRI of the brain.

Figure 3.

Fat-saturated T₂ weighted coronal MRI of the brain.

Findings and diagnosis

Figure 1 shows bilateral enlargement of the optic nerve sheath complexes. Figure 2 shows bilateral circumferential enhancement around the optic nerve sheath complexes. These findings are worrying for leukaemic infiltration. In Figure 3, the cerebrospinal fluid (CSF) surrounding the optic nerve sheath complexes is poorly demonstrated bilaterally. This may indicate bilateral impairment of normal CSF flow to the distal optic nerve sheath complexes. Figure 4 shows leptomeningeal enhancement in the left parietal region, which may represent leukaemic infiltration of the meninges.

The patient was diagnosed with recurrent ALL with central nervous system (CNS) relapse and leukaemic involvement of the optic nerves. He underwent a lumbar puncture that demonstrated an elevated opening pressure of 370 mm of water, but CSF cytology was negative. He underwent emergency radiation therapy, intrathecal and systemic chemotherapy, intravenous steroids and acetazolamide. Within 1 week of treatment, the patient demonstrated improved vision with the ability to detect hand motion in the right eye and light perception in the left eye.

Discussion

The patient's heterozygosity for factor V Leiden and recent pegaspargase chemotherapy placed him at high risk for cerebral venous thrombosis, but his MRI and magnetic resonance venography (MRV) of the brain at the time of presentation excluded this. His risk factors for recurrent ALL within the CNS included receiving prednisone prior to induction chemotherapy and presentation with left facial nerve palsy at the time; ALL was diagnosed a few months earlier.

The differential diagnosis of papilloedema in patients with leukaemia includes central venous sinus thrombosis, prolonged corticosteroid therapy, intracranial bleeding secondary to thrombocytopenia and leukemic infiltration of the optic nerves [1]. The meninges, testicles and ocular structures are the most common extramedullary sites of leukaemic infiltration [2,3]. Infiltration can occur along the optic nerve or the vasculature supplying the orbital structures, resulting in papilloedema [1]. Retinal haemorrhage is the most common finding in leukaemic ophthalmopathy [4]. Other causes of vision loss in patients with leukaemia include vincristine-induced optic atrophy, cortical blindness and radiation retinopathy [5]. In patients with papilloedema, meticulous scrutiny of the CNS is always warranted because leukaemic infiltration of other regions of the brain plays a pivotal role in patient management [1].

MRI remains the ideal imaging study for evaluating leukaemic infiltration of the CNS, and it has been well documented as the study of choice for identifying optic nerve infiltration [2]. Figures 1 and 2 show the typical enlargement and enhancement of leukaemic infiltration of the optic nerve sheaths. Figure 3 demonstrates possible obstruction of CSF flow in the setting of leukaemic infiltration of the optic nerve sheaths. As a result, the optic nerve region can become a pharmacological sanctuary from intrathecal chemotherapy [6]. Early administration of focal radiation is an effective means of reducing the number of leukaemic cells in the optic canal, thereby allowing adequate penetration of chemotherapy into the perineural space of the optic nerve. Our patient received radiation therapy followed by intrathecal chemotherapy.

Leukaemic ophthalmopathy is a known complication of acute leukaemia, with up to 9% of children developing ophthalmic abnormalities and 17% of these children developing infiltration of the optic nerve [3]. Despite aggressive chemotherapy regimens, ophthalmic involvement in ALL has increased in prevalence since the 1970s, probably owing to longer survival rates [2,6]. Prompt treatment must be initiated in order to prevent permanent loss of vision [2].