Subcortical U-fibers

Subcortical uU-fibres, also known as short association fibres, represent connections between adjacent gyri of the brain, located within the cortex or immediately deep to it in the very outer parts of the subcortical white matter ¹. 

They are among the last parts of the brain to myelinate, as late as the third or fourth decade and have very slow myelin turnover. The exception is the perirolandic and occipital poles, which are the same parts which myelinate earliest in infancy (you have to be able to move and see pretty early on I guess) ⁴.

Whether or not they are involved in diseases that primarily affect the white matter depends on the underlying relationship of the pathology myelin metabolism and oligodendroglial cells. 

In diseases in which the abnormality is one of myelin metabolism / turnover, as these fibersfibres have very slow metabolism they tend to be affected last. Note: often the word 'spared' is used, which is correct in so far as at the time one is imaging these patients there is little involvement of these fibersfibres, however, this should not be taken to mean that they cannot be involved; in fact in many instances they are involved eventually. 

In contrast disease in which the damage is directly to oligodendroglial cells, then no such relative sparing will be evident. 

As if this wasn't potentially confusing enough, superimposed up these metabolic differences between subcortical u-fibersU-fibres and deeper white matter, is that merely by their location, subcortical u-fibersU-fibres are relatively protected by from chronic small vessel ischaemic change ⁵. As the hemispheric white matter receives dual blood supply, superficially from penetrating arteries that pass through the cortex as well as deeper vessels that ascend from the perforators, it stands to reason that the white matter closest to either source of blood should be least affected. Indeed this is what is observed, with chronic small vessel ischemic change relatively sparing both the periventricular and subcortical white matter ⁵. It is important to note that this does not apply for large vessel occlusion with will involve the cortex and underlying subcortical white matter. 

Examples of early and late subcortical involvement include ^3,4: 

• subcortical u-fibersU-fibres usually initially spared
  • chronic small vessel ischaemic white matter lesions
  • CADASIL ⁶
  • HIV encephalopathy
  • many toxic leukoencephalopathies
    • heroin smoking -: chasing the dragon
    • radiation / chemotherapy/chemotherapy
  • many leukodystrophies
    • x-linked adrenoleukodystrophy
    • metachromatic leukodystrophy
    • globoid cell leukodystrophy (Krabbe disease)
  • many inborn errors of metabolism
    • phenylketonuria
    • maple syrup urine disease
    • Lowe's disease
    • hypohomocysteinemia
• subcortical u-fibersU-fibres involved relatively early / indiscriminately
  • multiple sclerosis (juxtacortical lesions)
  • progressive multifocal leukoencephalopathy (PML)
  • acute disseminated encephalomyelitis (ADEM)
  • Alexander disease
  • van der Knaap disease 
  • galactosemia
  • Salla disease
  • Pelizaeus-Merzbacher disease