Dysmyelinating Disorders (Leukodystrophies)

Dysmyelinating diseases, or leukodystrophies, are inherited neurodegenerative disorders that affect the integrity of myelin in the brain and peripheral nerves. They can be seen in lysosomal storage diseases, peroxisomal disorders, and diseases caused by mitochondrial dysfunction. The most common of these are presented below.

• Metachromatic leukodystrophy: Late infantile (most common), juvenile, and adult types. Symmetric confluent areas of T2 hyperintensity in the periventricular white matter. Radiating T2-hypointense lines through the demyelinated deep white matter represent sparing of the perivascular white matter and result in the tigroid and leopard skin patterns when imaged in long axis or cross section, respectively. The corpus callosum, internal capsule, corticospinal tracts, and cerebellar white matter may also be involved. Subcortical U fibers are spared.
• X-linked Adrenoleukodystrophy: Affects the white matter of the central nervous system, adrenal cortex, and testes. Early on, there is symmetric white matter demyelination in the peri-trigonal regions extending across the splenium of the corpus callosum, with sparing of the subcortical white matter. Later, demyelination spreads outward and cephalad to involve most of the cerebral white matter and often the subcortical white matter, as well. Three different zones can be defined in the affected white matter:
  • Inner zone: Irreversible gliosis and scarring. Markedly T2-hyperintense and moderately T1-hypointense.
  • Intermediate zone: Active inflammation and breakdown in the blood-brain barrier. T2-isointense to slightly hypointense and enhancing.
  • Outer zone: Leading edge of active demyelination. Moderately T2-hyperintense without enhancement.
• Canavan Disease: Spongiform leukodystrophy (extensive vacuolization of subcortical white matter). Symmetric areas of homogeneous, diffuse T2-hyperintensity and T1-hypointensity are seen throughout the white matter. There is preferential involvement of the subcortical U fibers early on.
• Alexander Disease: Predilection for the frontal lobe white matter early on, with early involvement of the subcortical white matter. Enhancement is seen near the tips of the frontal horns of the lateral ventricles. The disease progresses posteriorly to the parietal white matter and internal and external capsules with cysts in affected regions of the brain.
• MELAS Syndrome: Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes. Patients are usually normal at birth and during early infancy, then show delayed growth, episodic vomiting, seizures, and recurrent cerebral injuries resembling strokes. MRI shows multiple cortical and subcortical infarct-like lesions that cross vascular boundaries. Varying degrees of generalized cerebral and cerebellar atrophy can also be seen. The parietal and occipital lobes and the basal ganglia are frequently involved.

References

Cheon JE, Kim IO, Hwang YS, Kim KJ, Wang KC, Cho BK, Chi JG, Kim CJ, Kim WS, Yeon KM. Leukodystrophy in children: a pictorial review of MR imaging features. Radiographics. 2002 May-Jun;22(3):461-76.