This is a slice of brain from a patient who had Alexander disease. In this disease, there is diffuse loss of white matter. In this image, note how dark the demyelinated white matter appears, especially in contrast to the relatively spared region indicated by the unnecessarily large red arrow. Note also that the subcortical U-fibers (outlined in green) are also demyelinated. This finding can be of diagnostic value when trying to differentiate different leukodystrophies.