White Matter Lesions

Excerpt

The brain's white matter (WM) constitutes a network of nerve fibers that allows the exchange of information and communication between different areas of the gray matter (GM). WM lies beneath the GM in the brain and superficial to GM in the spinal cord and has evolved more than GM and occupies almost half of the brain. The size of white matter varies depending on the extent of central GM in different regions of spinal cord cross-sections. In particular, the GM to WM ratio grows from the cervical region to the lumbar region as the WM decreases when it proceeds towards the terminal portion of the spinal cord.

The WM contains neural networks formed by bundles of axons to mediate essential connectivity between different key motor and cognitive cortical regions. The white matter comprises myelinated and unmyelinated axons and glial cells, including myelin-producing oligodendrocytes, microglia, astrocytes, and oligodendrocyte progenitor cells. Myelin acts as electrical insulation for axons, is responsible for rapid saltatory impulse propagation, and protects the nerve fibers from injury. Myelin has a water content of about 40%. The remaining dry mass (60%) is mainly composed of proteins (15% to 30%) and lipids (70% to 85%), with phospholipids, cholesterol, galactolipids, and plasmalogens in a molar ratio of 2:2:1:1, respectively.

WM lesions or leukoaraiosis encompasses small vessel vascular brain diseases and non-vascular conditions. Any process leading to a change in chemical composition, damage, or ischemia of myelinated fibers can present as white matter lesions on magnetic resonance imaging (MRI), representing the gold standard for lesion investigation. WM hyperintensity (WMH) is quite a descriptive expression used on MRI. These lesions are best seen as hyperintensities on T2 weighted and FLAIR (fluid-attenuated inversion recovery) sequences of MRI. FLAIR sequences are particularly important in assessing white matter lesions near the ventricular margin by nullifying the cerebrospinal fluid signal.

While the WMHs are well-described on MRI, the lesions were first illustrated based on brain computed tomography (CT). In 1985, Hachinski 1985 described "leukoaraiosis" as "diminished density of white matter that is seen on brain computed tomography." Concerning small vessel vascular brain processes, white matter lesions are commonly present in MRI of asymptomatic elderly individuals, typically located in periventricular (PV-WMH) and deep subcortical regions (DS-WMH). For instance, white matter lesions are frequently detected in people with untreated chronic hypertension. The volume of white matter lesions increases with age from small punctate lesions to large confluent lesions. Nevertheless, although white matter lesions were initially considered a normal, age-related finding, recent investigations proved that large areas of disease in the brain's WM must be considered neuroimaging markers of brain frailty. Of note, various longitudinal studies described white matter lesions as a predictor for future risk of stroke, cognitive decline, depression, disability, and mortality in the general population. The clinical significance of the lesions is confirmed by the results of a meta-analysis that demonstrated a 3-fold increased risk of dementia and stroke and a doubled risk of death in people with white matter lesions. For instance, ischemic microvascular disease, a vascular cause of white matter lesions, may cause about 45% of dementia cases and 20% of strokes. Again, white matter lesions are associated with poor post-stroke outcomes and increased risk of parenchymal hematoma following mechanical thrombectomy.

Apart from white matter lesions secondary to small vessel disease, these lesions are also common features of demyelinating inflammatory disorders, leukodystrophies, and degenerative disorders. Clinical aspects, prognosis, and management vary according to the distribution and spread of the WM damage. Therefore, this group of lesions and diseases includes very different clinical conditions regarding etiology, pathogenesis, pathological features, clinical presentations, imaging, and therapy.