Abnormal myelin and axonal integrity in recently diagnosed patients with obstructive sleep apnea

Abstract

Study objectives: Patients with obstructive sleep apnea (OSA) show significant white matter injury; whether that injury represents myelin or axonal damage is unclear. The objective was to examine myelin and axonal changes in patients with newly diagnosed OSA over control subjects.

Design: Cross-sectional study.

Setting: University-based medical center.

Participants: Twenty-three newly-diagnosed, treatment-naïve OSA and 23 age- and sex-matched control subjects.

Interventions: None.

Measurements and results: Radial and axial diffusivity maps, calculated from diffusion tensor imaging data (3.0 Tesla MRI scanner), indicating diffusion perpendicular (myelin status) or parallel (axonal status) to fibers, respectively, were normalized, smoothed, and compared between groups (analysis of covariance; covariate: age). Global brain radial and axial diffusivity values, and global brain volume with myelin and axonal changes were determined, and region-of-interest analyses performed in areas of significant differences between groups based on voxel-based procedures. Global radial and axial diffusivity values were significantly reduced in OSA versus control subjects (radial, P = 0.004; axial, P = 0.019), with radial (myelin) diffusivity reduced more than axial (axonal), and more left-sided reduction for both measures. Localized declines for myelin and axonal measures appeared in the dorsal and ventral medulla, cerebellar cortex and deep nuclei, basal ganglia, hippocampus, amygdala, corpus callosum, insula, cingulate and medial frontal cortices, and other cortical areas (P < 0.005), all regions mediating functions affected in OSA.

Conclusions: Fiber injury appears in critical medullary respiratory regulatory sites, as well as cognitive and autonomic control areas. Myelin is more affected in newly diagnosed OSA than axons, and primarily on the left side, possibly from the increased myelin sensitivity to hypoxia and asymmetric perfusion.

Keywords: Acute; brain; diffusion; hypoxia; medulla; respiration; tensor imaging.

Figure 1

Brain sites showing significant radial (myelin) and axial (axonal) diffusivity changes in obstructive sleep apnea (OSA) (n = 23), compared to control (n = 23) subjects (uncorrected threshold, P = 0.005), displayed in glass brain mode with three-dimensional representations projected onto two-dimensional axial, sagittal, and coronal sections. (A) Brain areas with significantly reduced radial diffusivity values in OSA over control subjects. (B) Regions with reduced axial diffusivity in OSA compared to control subjects.

Figure 2

Brain regions with significantly reduced radial diffusivity (i.e., primarily myelin changes) in OSA compared to control subjects. Sites with reduced radial diffusivity in OSA included the ventrolateral medulla (a), corpus callosum (b,c), corona radiata (d-f), frontal white matter (g), insular cortices (h, i), ventral hippocampus (j), occipital white matter (k), mid hippocampus extending to the retrolenticular internal capsule (l), amygdala (m), cingulum bundle (o, p), dorsal and posterior thalamus (q, t), putamen and external capsules (s), temporal white matter (u), ventral temporal cortex (v), and cerebellar peduncles (w) and cerebellar cortices (n, r, x, y). All brain images are in neurological convention (L = left, R = right), and the color scale indicates t-statistic values.

Figure 3

Brain areas with reduced axial diffusivity (i.e., largely axonal injury) in obstructive sleep apnea (OSA) over control subjects. Areas with reduced axial diffusivity in OSA compared to control subjects included the corona radiata (a-c), frontal white matter (d), globus pallidus (e), thalamus, extending to the hippocampus (f), ventral medulla (g), temporal white matter (h, i), putamen (j), cingulate cortices (k, l), corpus callosum (m), external capsule (n), and cerebellar cortices (o). Figure conventions are the same as in Figure 2.