White matter lesions (WMLs), also called white matter hyperintensities, are a common finding on T2 and fluid-attenuated inversion recovery (FLAIR) sequences on brain magnetic resonance imaging (MRI). WMLs are most often due to small vessel ischemia, though may also occur with demyelinating or other inflammatory diseases and a variety of more obscure pathologies. In population-based studies enrolling midlife subjects, the prevalence of at least one WML on MRI is approximately 40%. Prevalence increases with older age, hypertension, smoking, and diabetes. In those older than 70 years, prevalence of WML of presumed vascular etiology exceeds 90%. Although at times symptomatic, more often WMLs are incidentally discovered and not directly related to current active focal neurologic symptoms. An example is the patient with migraine or nonspecific neurologic symptoms who undergoes MRI. Radiographic pattern and location, along with clinical features of the patient, help to identify the most likely underlying etiology of WML.
When WMLs are accompanied by restricted diffusion on diffusion weighted imaging, acute infarction is by far the most likely explanation. Rarely, acute demyelinating lesions may mimic infarction in this setting, but the clinical presentation is usually one of gradually evolving (as opposed to abrupt onset) symptoms, allowing differentiation.
The vast majority of clinically silent lesions in the subcortical white matter represent the consequences of small vessel ischemia ( Fig. 116.1 ). Hypertension is the most important risk factor. Migraine, particularly with aura, is associated with an increased prevalence of WML and is an important consideration in younger patients without vascular risk factors found to have WML. Lesions tend to be juxtacortical or periventricular and usually spare the callosal and subcallosal regions. Infectious and inflammatory disease can be associated with WML; suggestive systemic symptoms or focal neurologic symptoms are almost always present in these cases. In the immunocompromised patient, rare causes of WML include progressive multifocal leukoencephalopathy (caused by the JC virus), primary human immunodeficiency virus (HIV) encephalopathy, and central nervous system (CNS) lymphoma, among others. The characteristic radiographic appearance of these conditions may be variable in the immunocompromised. For instance, CNS lymphoma typically enhances homogenously but can demonstrate a rim of enhancement in immunocompromised patients. Progressive multifocal leukoencephalopathy usually does not enhance in markedly immunocompromised patients but can enhance in patients with milder immunosuppression or during immune reconstitution.
Demyelinating disease (i.e., multiple sclerosis) causes WMLs that tend to be periventricular and extend perpendicular to the corpus callosum (“Dawson’s fingers”) as shown in Fig. 116.2 . Lesions are often associated with the “central vein sign” on T2* weighted imaging.