Leukodystrophy Imaging: Insights for Diagnostic Dilemmas

Abstract

Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific, and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns which can be used as differentiating tools. In this review, we talk about these MRI study findings for each leukodystrophy, associated genetics, blood work that can help in differentiation, emerging diagnostics, and a follow-up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease, Pelizaeus-Merzbacher disease, Alexander's disease, Canavan disease, and Aicardi-Goutières Syndrome.

Keywords: demyelinating disorders; leukodystrophies; magnetic resonance imaging; myelin imaging; white matter disorders.

Figure 1

Major MRI findings, CSF/blood markers, and other key features in leukodystrophies.

Figure 2

Pathophysiology of X-Linked Adrenoleukodystrophy: Mutations in the ABCD1 gene on the X chromosome result in the prevention of very long chain fatty acids (VLCFAs) into the peroxisome, resulting in the clinical phenotype due to VLCFA accumulation throughout the body.

Figure 3

MRI findings found in metachromatic leukodystrophy. (A) Hypointense radial stripes resembling tiger skin. (B) Hypointense dots resembling leopard skin. Reprinted/adapted with permission from Ref. [35].

Figure 4

The three-step process for infant screening for KD.

Figure 5

T2 (left) and T1 (right) imaging of a patient with Pelizaeus–Merzbacher disease showing lack of myelination in internal capsule, proximal corona radiata, and the optic radiation. Reprinted/adapted with permission from Ref. [57].

Figure 6

MRIs characteristic of Alexander Disease; the right image demonstrates an increased signal of T2, the middle image demonstrates a decreased signal of T1, and the right image is a T2 midline sagittal section demonstrating atrophy. Reprinted/adapted with permission from Ref. [66].