White matter injury in ischemic stroke

Abstract

Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

Keywords: Axonal damage; Demyelination; Ischemic stroke; MRI; Oligodendrogenesis; Therapy; White matter injury.

Figure 1

Transverse images in a 73-year-old man 48 hours after left middle cerebral artery (MCA) occlusion. T1 WI (a) shows mixed areas of abnormal signal intensity in the GM and WM of the temporal lobe. T2 WI (b) and FLAIR (c) images demonstrate high intensity signal in the infarct zone with subtle prominence of WM. WM is traced with a green line and the infarct region is traced with a red line. WM infarct regions are enclosed by both the red and green outlines, whereas GM infarct regions are defined as red regions outside the green outline.

Figure 2

DWI image in the same patient as in Figure 1. a. ADC shows mixed areas of decreased signal intensity in the GM and WM of the temporal lobe. b. DWI demonstrates increased signal intensity in the infarct zone. WM infarct regions are enclosed by both the red and green outlines, whereas GM infarct regions are defined as red regions outside the green outline.

Figure 3

DTI image in an 87-year-old woman 3–4 days after middle cerebral artery occlusion. The region of interest (ROI) in WM was traced as a red line in both ipsilateral and contralateral hemispheres. The infarct regions were outlined with green lines. Infarct WM is enclosed by both the red and green outlines. The regions enclosed by the green outline but outside the red outline are infarct GM (adapted from Radiology 2000, 215:211-220 with permission).

Figure 4

MRS images in a 43-year-old man 5 days after right MCA infarction. Compared with the MRS image in homologous parts of the contralateral hemisphere (b), the MRS image in the infarction area (figure a) shows decreases in N-acetylaspartate (NAA), total creatines (Cr) and total cholines (Cho), and an inversed peak of lactate (lac) appears in the infarction area. I: integral, A: amplitude