Oculomotor Deficits after Chemotherapy in Childhood.

Einar-Jón Einarsson,Christian Moëll,Per-Anders Fransson,Måns Magnusson,Thomas Wiebe,Mitesh Patel,Hannes Petersen,Rossella Rota

doi:10.1371/journal.pone.0147703

Abstract

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological complications following chemotherapy.

Highlights

Recent advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors
The brain itself is given some protection from systemic treatments by the blood-brain barrier, it has been recognized that many chemotherapeutic agents affect central brain function through direct and/or indirect mechanisms [1]
When visual field deficits occur in both eyes and overlap, the corresponding part of the visual cortex may no longer be appropriately stimulated, which can influence the retinotopic organization of the visual cortex [3]

Summary

Introduction

Recent advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. A number of the chemotherapeutic agents used in the treatment of childhood malignancies might cause neurological complications. The brain itself is given some protection from systemic treatments by the blood-brain barrier, it has been recognized that many chemotherapeutic agents affect central brain function through direct and/or indirect mechanisms [1]. Such general damage to key CNS components might result in long-term decline to neurophysiological functions including motor control of the eyes, causing difficulties processing visual information [2]. Most survivors of childhood cancer are not followed-up on a regular basis for the purpose of preventing, detecting and treating long-term neurophysiological deficits [4]

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