Advances in MR Imaging of Leukodystrophies

Leukodystrophies are hereditary disorders of white matter that impair brain that is initially normally formed and developed (1, 2). They can affect brain myelin throughout life. The disorders are commonly progressive in nature and ultimately fatal. First manifestations are often cognitive deterioration and neuropsychological problems. Motor and balance difficulties occur, as do visual abnormalities. Classic leukodystrophies lead to a vegetative state or death within months to years. In general, the earlier the onset of symptoms, the more progressive the disease course. Most leukodystrophies are monogenetic disorders. The mutant gene often encodes an enzyme or protein that maintains neuronal and/or glial health and is responsible for regulation of brain metabolism. Many enzymes involved play a role in lipid metabolism. The inability to degrade or synthesize substrate leads to an upstream excess or downstream lack of vital lipids. This can cause a wide range of pathology, from inflammatory demyelination to axonal degeneration and microglial activation. Hence, the often cited prominent demyelination is only one manifestation in leukodystrophies, and myelinforming oligodendrocytes are not the only cells affected in these disorders. Yet, there are some common characteristics that distinguish the pathology in leukodystrophies from that of other disorders. MRI has played a seminal role in visualization of the lesion pattern. (3). The demyelinating lesions are usually confluent and symmetric. Many of the classic disorders, such as X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD) and Krabbe, show relative sparing of subcortical fibers. Yet again, other disorders have early involvement of the U fibers and other unique characteristics, such as cystic rarefaction and degeneration. Hereditary disorders that do not show demyelination but rather hypomyelination have come to increasing attention (4). Common neurological features in hypomyelinating disorders are developmental delay, nystagmus, cerebellar ataxia and spasticity. One of the better characterized hypomyelinating disorders is Pelizaeus Merzbacher disease (PMD). Beyond this classic disorder, a multitude of other hypomyelinating disorders exist. Only about half of the patients with evidence of hypomyelination on MRI come to a definitive diagnosis. Yet, specific clinical and MRI features can be pathognomonic and lead to diagnosis.