Pupillary Light Response Deficits in 4-Week-Old Piglets and Adolescent Children after Low-Velocity Head Rotations and Sports-Related Concussions

Abstract

Neurological disorders and traumatic brain injury (TBI) are among the leading causes of death and disability. The pupillary light reflex (PLR) is an emerging diagnostic tool for concussion in humans. We compared PLR obtained with a commercially available pupillometer in the 4 week old piglet model of the adolescent brain subject to rapid nonimpact head rotation (RNR), and in human adolescents with and without sports-related concussion (SRC). The 95% PLR reference ranges (RR, for maximum and minimum pupil diameter, latency, and average and peak constriction velocities) were established in healthy piglets (N = 13), and response reliability was validated in nine additional healthy piglets. PLR assessments were obtained in female piglets allocated to anesthetized sham (N = 10), single (sRNR, N = 13), and repeated (rRNR, N = 14) sagittal low-velocity RNR at pre-injury, as well as days 1, 4, and 7 post injury, and evaluated against RRs. In parallel, we established human PLR RRs in healthy adolescents (both sexes, N = 167) and compared healthy PLR to values obtained <28 days from a SRC (N = 177). In piglets, maximum and minimum diameter deficits were greater in rRNR than sRNR. Alterations peaked on day 1 post sRNR and rRNR, and remained altered at day 4 and 7. In SRC adolescents, the proportion of adolescents within the RR was significantly lower for maximum pupil diameter only (85.8%). We show that PLR deficits may persist in humans and piglets after low-velocity head rotations. Differences in timing of assessment after injury, developmental response to injury, and the number and magnitude of impacts may contribute to the differences observed between species. We conclude that PLR is a feasible, quantifiable involuntary physiological metric of neurological dysfunction in pigs, as well as humans. Healthy PLR porcine and human reference ranges established can be used for neurofunctional assessments after TBI or hypoxic exposures (e.g., stroke, apnea, or cardiac arrest).

Altered Auditory and Visual Evoked Potentials following Single and Repeated Low-Velocity Head Rotations in 4-Week-Old Swine

“…Auditory and visually evoked potentials were captured using methods published previously in healthy piglets [46,47] on each animal before head rotations, to establish a pre-injury baseline, and again at 1, 4, and 7 days after to examine the acute time-course of mild TBI on stimulus processing. Other neurofunctional measures were also collected using this experimental injury paradigm and include piglet gait and pupillary light reflexes, using previously published methods [48,49].…”

Porcine Models of Neurotrauma and Neurological Disorders

“…The Margulies group contributed three primary research articles utilizing rotational acceleration in a pediatric pig model. Oeur et al applied single and repeated low-velocity head rotations in piglets and also gathered data from adolescent humans presenting with concussion, and found that deficits in the pupillary light reflex were altered after injury compared to reference ranges, suggesting that pupillometry could be a valuable tool for neurofunctional assessment [2]. Mull et al reported significant gait alterations in piglets following rotational acceleration that were more severe and longer lasting when multiple rotations were applied, and they also validated reference ranges for assessing gait alterations in piglets [3].…”