Pediatric Optic Neuritis: An Isolated Finding, or a Sign of Demyelination?

A 17-year-old young male presented to the emergency department with sudden-onset vision loss in his right eye of 1 week’s duration, associated with intermittent pain with movement of the affected eye. He recalled having an associated frontal headache, dizziness, and 3 episodes of vomiting. He had had an acute viral illness 1 month prior, with vomiting, headache, and dizziness of 1 day’s duration; the symptoms prompted him to seek medical attention, and he had been treated with intravenous fluids and had had a complete recovery.

At presentation, ocular examination of his right eye revealed a visual acuity of 20/200 and a loss of appreciation of light and color vision; motion detection was perceived as a moving shadow. Visual acuity of his left eye was preserved at 20/20. Fundoscopic examination revealed blurry optic disk margins, mostly affecting the left eye. The rest of the neurologic examination findings were remarkable for brisk reflexes on both upper and lower extremities; no neurologic deficits were identified.

The working diagnosis was retrobulbar optic neuritis of the right eye with subclinical optic neuritis of the left eye. Laboratory tests were done to rule out other possible causes, including a syphilis rapid plasma reagin test, Borrelia burgdorferi immunoglobulin M and G antibody testing, and a workup for connective tissue disorders, all of which were negative. Antinuclear antibody (ANA) test results were positive.

T1-weighted magnetic resonance imaging (MRI) revealed multiple low-intensity lesions (Figure 1), and T2-weighted MRI showed hyperintense lesions in the periventricular white matter, the juxtacortical region, and the pons (Figure 2). A diagnosis of multiple sclerosis (MS) was considered.

Figure 1. Brain MRI exhibited numerous periventricular hyperintensities and, to a lesser degree, subcortical hyperintenisities in the cerebrum. Involvement of the corpus callosum is best appreciated on sagittal fluid-attenuated inversion recovery (FLAIR) sequence. The appearance is quite typical of multiple sclerosis.

The patient was treated with intravenous methylprednisolone, 250 mg every 6 hours (1,000 mg/d) for 5 days. Results of an orbital MRI done 3 days after the initiation of treatment with the intravenous corticosteroids were reported as normal. The teenager had a gradual but prompt recovery, and by the time of discharge, he had regained visual acuity to 20/70, normal color vision, and perception of movement. His case was followed at a pediatric MS center.

Figure 2. Brain MRI also showed a number of abnormal signal hyperintensities in the cerebellum, cerebellar peduncles, and the left pons. These are best appreciated on FLAIR sequence and T2-weighted imaging.

Less than 1 month after discharge, the patient developed episodes of generalized extremity numbness, followed by weakness. The diagnosis of MS was reached approximately 6 weeks thereafter based on the McDonald criteria for MS. Brain and spine MRI showed multiple lesions consistent with MS, with 9 supratentorial lesions, 4 brainstem and cerebellar lesions, and a spinal cord lesion. He was started on immunomodulators (interferon beta-1b). The patient had a significant remitting-relapsing course, including subsequent development of internuclear ophthalmoplegia.

Optic neuritis (ON), an inflammatory demyelination of the optic nerve causing acute visual loss, can occur as an isolated finding affecting one or both eyes, or it can be associated with demyelination in other portions of the nervous system,¹ such as neuromyelitis optica, acute disseminated encephalomyelitis, and MS, often as the first manifestation of disease. ON in children most often is self-limited, with a low risk of subsequent central nervous system involvement, as opposed to adults.² The incidence of MS among children with ON is approximately 15%.³ This may be higher in cases with diffuse involvement or if ON recurs within 1 year.³ The incidence also is higher if ON is associated with unilateral retrobulbar optic neuritis, as compared with bilateral affection; it is less common in patients without diffuse involvement as evidenced by MRI findings.³

MRI, visual evoked potential (VEP) tests, and oligoclonal band (OCB) detection in cerebrospinal fluid (CSF) are used for the detection of MS in adults, with MRI the diagnostic test of choice for the diagnosis of MS, showing occult disease in up to 80% of affected individuals at time of initial presentation. Limited data exist about the role of these adjunct studies in predicting the development of MS in children and assessing the risk of progression to MS following an isolated episode of ON.³

ON is fairly rare in childhood. This acute event presents with vision loss that is binocular (more common in children) or monocular, occurring over hours to days, and peaking at 1 to 2 weeks. Loss of color vision, visual field defects (generally central scotoma), and pain that is exacerbated with eye movement tend to accompany this condition.

Although ON is a clinical diagnosis, confirmatory testing often is required in children, including a full neuro-ophthalmologic evaluation. Orbital MRI scans can show optic nerve inflammation with a bright T2 signal, but they also may appear normal; thus, a normal orbital MRI finding does not rule out ON.

Brain MRI is important for determining the prognosis.¹ A positive MRI at onset of ON is a strong predictor for the development of MS, as is relapsing ON, although limited data exist about the implication in children. The role of lumbar puncture in isolated ON is controversial; however, if brain parenchymal lesions are present, the presence of OCBs in CSF can help stratify the risk of MS, whereas VEP is considered if the diagnosis is not clear.

In the 10 years following an initial episode of ON, adults have a 38% chance of developing MS.² Up to 50% of patients with an initial isolated episode of ON have brain lesions, implying a further increased risk when brain MRI demonstrates white matter lesions at the time of presentation; 17% to 36% of patients receive a diagnosis of MS by 24 months. In children, this risk is unclear, and the natural history of childhood optic neuritis remains relatively unreported. Studies have yielded rates from 4% to 36%.¹ Acute ON in children differs from the typical adult form; most pediatric cases are bilateral with severe loss of visual acuity, but with a significantly high recovery rate.

MS may be the suspected diagnosis at the time of the first attack, but definitive diagnosis requires recurrence to establish a polyphasic course, as was the case with our patient.

Visual recovery is reached in up to 80% of cases, with visual acuity returning to 20/40 or better gradually over the course of weeks. Good prognostic factors in the pediatric population include an age of ON onset younger than 10 years (3% to 10% of patients with MS have symptoms before age 18),¹ the presence of papilledema, and normal brain MRI, with the latter being the strongest predictor.

It is important to establish predictive factors for MS in children, since they tend to have lower disability scores and longer disease duration compared with adults; however, they reach comparable disability 10 years earlier than do adult patients. Studies have shown that treating children with MS with immunomodulators (interferon beta-1a, interferon beta-1b, and glatiramer acetate) can reduce the relapse rate, with comparable safety and tolerability as in the adult population.⁴

Massiel Sarmiento, MD, is a resident in the Department of Pediatrics at Lincoln Medical and Mental Health Center in the Bronx, New York.

Virginia Kaldas, MD, is a resident in the Department of Pediatrics at Lincoln Medical and Mental Health Center in the Bronx, New York.

Sergey Prokhorov, MD, is an attending physician and pediatric neurologist in the Department of Pediatric Neurology at Lincoln Medical and Mental Health Center in the Bronx, New York.

References

1. Benson LA, Bove E, Gorman M. Pediatric neuroimmunology. In: Sims KB, ed. Handbook of Pediatric Neurology. Philadelphia, PA: Lippincott Williams & Wilkins; 2014:383-404.
2. Heussinger N, Kontopantelis E, Rompel O, Paulides M, Trollmann R. Predicting multiple sclerosis following isolated optic neuritis in children. Eur J Neurol. 2013;20(9):1292-1296.
3. Piña-Garza JE. Disorders of the visual system. In: Piña-Garza JE. Fenichel’s Clinical Pediatric Neurology. Philadelphia, PA: Elsevier; 2013:313-326.
4. Bonhomme GR, Waldman AT, Balcer LJ, et al. Pediatric optic neuritis: brain MRI abnormalities and risk of multiple sclerosis. Neurology. 2009;72(10):881-885.