Early neuroaxonal injury is seen in the acute phase of pediatric optic neuritis

Colin Wilbur; Y Arun Reginald; Giulia Longoni; Stephanie A Grover; Agnes M Wong; Donald J Mabbott; Douglas L Arnold; Ruth Ann Marrie; Amit Bar-Or; Brenda Banwell; Fiona Costello; E Ann Yeh; Canadian Pediatric Demyelinating Disease Network.

doi:10.1016/j.msard.2019.101387

Early neuroaxonal injury is seen in the acute phase of pediatric optic neuritis

Mult Scler Relat Disord. 2019 Nov:36:101387. doi: 10.1016/j.msard.2019.101387. Epub 2019 Sep 7.

Affiliations

¹ Division of Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada; Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
³ Division of Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
⁴ Program in Neurosciences and Mental Health, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
⁵ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
⁶ Departments of Medicine and Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
⁸ Division of Child Neurology, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
⁹ Departments of Clinical Neurosciences and Surgery, University of Calgary, Calgary, Alberta, Canada.
¹⁰ Division of Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada; Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics (Neurology), University of Toronto, Toronto, Ontario, Canada. Electronic address: ann.yeh@sickkids.ca.

PMID: 31539739
DOI: 10.1016/j.msard.2019.101387

Abstract

Background: Thinning of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) occur in the chronic phase after optic neuritis (ON) in children and reflect neuroaxonal injury. The objective of this study was to describe changes in RNFL and GCIPL thickness in the acute phase following pediatric ON.

Methods: Data were collected prospectively from consecutive children presenting with ON as part of an incident acquired demyelinating event. Children with a final diagnosis of multiple sclerosis (n = 9, 10 ON-affected eyes) or monophasic demyelination (n = 16, 25 ON-affected eyes) who underwent spectral-domain optical coherence tomography (OCT) testing within 30 days of symptom onset were included. Standardized visual assessment was performed at presentation and 6-18 months follow-up. OCT measures were compared to those of healthy controls (n = 25, 50 eyes).

Results: Median (interquartile range [IQR]) global RNFL thickness was increased in ON-affected eyes (155 μm [114-199 μm]) compared to control eyes (104 μm [98.5-107.5 μm]; p < 0.0001). Compared to controls, fellow eyes demonstrated a reduced temporal quadrant RNFL thickness (59 μm [53-72 μm] versus 71.5 μm [65-81 μm]; p = 0.013) and lower GCIPL thickness (80.5 μm [74-88 μm] versus 87 μm [85-89 μm]; p = 0.003). The ON-affected eyes of children with monophasic demyelination demonstrated a greater global RNFL thickness (183.5 μm [146.5-206 μm]) compared to the ON-affected eyes of children with multiple sclerosis (108.5 μm [95-124 μm]; p = 0.01). OCT measures at presentation did not predict low-contrast visual acuity nor color vision at 6-18 months follow-up.

Conclusion: Children with multiple sclerosis show less RNFL swelling in their ON-affected eyes at onset compared to children with monophasic demyelination. Lower GCIPL and temporal RNFL thickness in the clinically unaffected eyes of those children with unilateral ON suggests the presence of pre-existing neuroaxonal injury in children presenting with a first episode of ON. This finding may be driven by the subset of children with multiple sclerosis.

Keywords: Acquired demyelinating syndrome; Multiple sclerosis; Optic neuritis; Optical coherence tomography.

MeSH terms

Acute Disease
Adolescent
Axons / pathology*
Child
Female
Follow-Up Studies
Humans
Male
Multiple Sclerosis / pathology*
Optic Neuritis / pathology*
Retinal Ganglion Cells / pathology
Retinal Neurons / pathology*
Tomography, Optical Coherence