Subcortical U-Fibers: Signposts to the Diagnosis of White Matter Disease

White matter diseases can be broadly separated into 3 main categories: diseases that affect myelin metabolism, diseases that result in direct damage to myelin and/or oligodendrocytes, and vascular diseases. Disorders of myelin metabolism (dysmyelinating disorders), including many inherited leukodystrophies, will generally spare the subcortical U-fibers, with their relatively slower rate of myelin turnover. However, conditions in which direct damage to previously normal myelin and/or oligodendrocytes predominates (demyelinating disorders), including multiple sclerosis and progressive multifocal leukoencephalopathy, typically demonstrate early U-fiber involvement. The purpose of this article is to demonstrate how recognizing the presence or absence of subcortical U-fiber involvement as a visible manifestation of the underlying pathophysiology in white matter disease can be extremely helpful in more confidently narrowing what may otherwise be a very broad differential diagnosis.

Learning Objective: To recognize how the presence or absence of subcortical U-fiber involvement in white matter disease can help narrow what may otherwise be a very broad differential diagnosis.