Influence of Strategic Cortical Infarctions on Pupillary Function

Abstract

Objective: Cortical activity, including cognitive and emotional processes, may influence pupillary function. The exact pathways and the site of cortical pupillary innervation remain elusive, however. We investigated the effects of select cortical strokes, i.e. ischemic infarcts affecting the insular cortex and prefrontal eye field, on pupillary function. Methods: Seventy-four patients with acute ischemic stroke, consecutively admitted to our institution from March to July 2018, were assessed 24 h after endovascular recanalization therapy (i.e., day 2 after the stroke), using automated pupillometry. Stroke location and volume and clinical severity (estimated by the Alberta Stroke Program Early CT Score and National Institute of Health Stroke Scale) were recorded. We excluded patients with posterior circulation stroke, intracranial pathology other than ischemic stroke, midline shift on computed tomography exceeding 5 millimeters or a history of eye disease. Pupillometry data from 25 neurologically normal patients with acute myocardial infarction were acquired for control. Results: Fifty stroke patients after thrombectomy were included for analysis. Twenty-five patients (50%) had insular cortex or prefrontal eye field involvement (group 1, strategic infarcts); 25 patients had infarcts located in other cerebral areas (group 2, other infarcts). The pupillary light reflex, as measured by constriction velocity and maximal/minimal pupillary diameters, was within physiological limits in all patients, including controls. However, while pupillary size and constriction velocities were correlated in all subjects, the correlation of size and dilatation velocity was absent in right-hemispheric infarcts (left hemisphere infarcts, group 1 (r ² = 0.15, p = 0.04), group 2 (r ² = 0.41, p = 0.0007); right hemisphere infarcts, group 1 (r ² = 0.008, p = 0.69); group 2 (r ² = 0.12, p = 0.08); controls (r ² = 0.29, p ≤ 0.0001). Conclusions: Cortical infarcts of the prefrontal eye field or insula do not impair the pupillary light reflex in humans. However, subtle changes may occur when the pupils dilate back to baseline, probably due to autonomic dysfunction. Replication is needed to explore the possible influence of hemispheric lateralization. We suggest that endovascular therapy for acute ischemic stroke may serve as a clinical research model for the study of acquired cortical lesions in humans.

Keywords: endovascular stroke therapy; insula; mechanical thrombectomy; prefrontal eye field; pupillary light reflex; pupillometry; pupils; stroke.

Figure 1

We performed a clinical practice study investigating the cortical modulation of pupillary function following strategic cerebral strokes. This figure depicts CT of the brain from 2 exemplary stroke patients 24 h following endovascular therapy for large vessel occlusive stroke. Strategic ischemic infarctions are seen in the left prefrontal eye field (Left) and right insular cortex (Central). Using automated pupillometry [(Right); courtesy of https://commons.wikimedia.org/wiki/Main_Page], we collected pupillometry data of patients with strategic infarcts in the prefrontal eye field and/or insular cortex (group 1) and compared them to data from stroke patients without infarcts in these areas (group 2) and to data from patients with myocardial infarcts but without clinical evidence of brain injury (control group).

Figure 2

Pupillometry data from patients with strategic cerebral infarcts and controls: Maximal pupillary diameters and constriction velocities. Solid lines denote the best fit from linear regression analysis. (Left) Relationship between maximum diameter and constriction velocity of the left eye, group 1 in green (Y = 0.5945X+2.2, r² = 0.38, p = 0.0009); controls in red (Y = 0.8142X + 1.772, r² = 0.69, p < 0.0001). (Right) Relationship between maximum diameter and constriction velocity of the right eye, group 1 in green (Y = 0.6748X + 1.975, r² = 0.57, p < 0.0001); controls in red (Y = 0.9028X +1.671, r² = 0.72, p < 0.0001).

Figure 3

Pupillometry data from patients with strategic cerebral infarcts and controls: Minimal pupillary diameters and dilatation velocities. Solid lines denote the best fit from linear regression analysis. (Left) Relationship between minimum diameter and dilatation velocity of the left eye, group 1 in green (Y = 0.3976X + 1.977, r² = 0.063, p = 0.23); controls in red (Y = 0.5857X + 1.83, r² = 0.22, p = 0.018, adjusted p = 0.054). (Right) Relationship between minimum diameter and dilation velocity of the right eye, group 1 in green (Y = 0.07548X + 2.263, r² = 0.004, p = 0.75); controls in red (Y = 0.6646X + 1.738, r² = 0.37, p = 0.0013, adjusted p = 0.005).

Figure 4

Pupillometry data from patients with left, respectively, right hemisphere cerebral infarcts (plotted against pupillometry data from controls without hemispheric strokes): Maximal pupillary diameters and constriction velocities. Solid lines denote the best fit from linear regression analysis. (Left) Left hemisphere infarcts, group 1 in green (Y = 0.9538X + 1.322, r² = 0.67, p ≤ 0.0001); group 2 in blue (Y = 0.9257 X + 1.428, r² = 0.7, p < 0.0001); controls in red (Y = 0.8583X + 1.721, r² = 0.7, p ≤ 0.0001). (Right) Right hemisphere infarcts, group 1 in green (Y = 0.3189X + 2.861, r² = 0.3, p = 0.0077); group 2 in blue (Y = 0.6064X + 2.086, r² = 0.4, p = 0.0005), controls in red (identical values as above).

Figure 5

Pupillometry data from patients with left, respectively, right hemisphere cerebral infarcts (plotted against pupillometry data from controls without hemispheric strokes): Minimal pupillary diameters and dilatation velocities. Solid lines denote the best fit from linear regression analysis, showing the relationship between minimum diameter and dilation velocity. (Left) Left hemisphere infarcts, group 1 in green (Y = 0.5528X + 1.705, r² = 0.15, p = 0.04); group 2 in blue (Y = 0.8756X + 1.538, r² = 0.41, p = 0.0007); controls in red (Y = 0.6312 X 1.78, r² = 0.3, p ≤ 0.0001). (Right) Right hemisphere infarcts, group 1 in green (Y = −0.1018 X+2.549, r² = 0.008, p = 0.69); group 2 in blue (Y = 0.5222X + 2.023, r² = 0.12, p = 0.0821), controls in red (identical values as above).