A leukodystrophy can be defined as a progressive disorder of the white matter of the brain caused by a genetic defect. MRI is the primary tool to diagnose a leukodystrophy. It is extremely sensitive in visualizing white matter abnormalities. If MRI does not show significant white matter abnormalities in a patient with signs of a progressive encephalopathy, the patient does not have a leukodystrophy and genetic tests for leukodystrophies should not be performed.
If the MRI shows extensive white matter abnormalities, the first question is whether the patient may have a leukodystrophy. Most important clues for the answer come from the clinical picture and the pattern of MRI abnormalities. In the early stages of a leukodystrophy, the clinical picture can, however, be deceptively mild.
If the MRI shows extensive white matter abnormalities compatible with a leukodystrophy, clinicians will usually execute a standard battery of tests, ignoring the information provided by the MRI. However, quantitative MR parameters, including metabolites measured in MR spectroscopy and diffusion tensor as well as magnetization transfer parameters, provide reliable information about the histopathology underlying the white matter abnormalities on MRI (hypomyelination, demyelination, myelin vacuolation, gliosis and cystic degeneration). Secondly, the pattern of selective vulnerability of brain structures as visualized by the distribution of the MRI abnormalities provides important information about the possible genetic cause.
This MR information can be used to guide genetic diagnostics and avoid performance of genetic tests for disorders already excluded by the MRI findings.
The other side of the mirror is that the variability in clinical and MRI phenotype of genetic defects is always wider than initially thought. The fine-tuning of the interplay between MRI interpretation and genetic diagnosis is illustrated by recent findings in Alexander disease.
