Invited article: an MRI-based approach to the diagnosis of white matter disorders

Abstract

Background: There are many different white matter disorders, both inherited and acquired, and consequently the diagnostic process is difficult. Establishing a specific diagnosis is often delayed at great emotional and financial costs. The pattern of brain structures involved, as visualized by MRI, has proven to often have a high diagnostic specificity.

Methods: We developed a comprehensive practical algorithm that relies mainly on the characteristics of brain MRI.

Results: The initial decision point defines a hypomyelination pattern, in which the cerebral white matter is hyperintense (normal), isointense, or slightly hypointense relative to the cortex on T1-weighted images, vs other pathologies with more prominent hypointensity of the cerebral white matter on T1-weighted images. In all types of pathology, the affected white matter is hyperintense on T2-weighted images, but, as a rule, the T2 hyperintensity is less marked in hypomyelination than in other pathologies. Some hypomyelinating disorders are typically associated with peripheral nerve involvement, while others are not. Lesions in patients with pathologies other than hypomyelination can be either confluent or isolated and multifocal. Among the diseases with confluent lesions, the distribution of the abnormalities is of high diagnostic value. Additional MRI features, such as white matter rarefaction, the presence of cysts, contrast enhancement, and the presence of calcifications, further narrow the diagnostic possibilities.

Conclusion: Application of a systematic decision tree in MRI of white matter disorders facilitates the diagnosis of specific etiologic entities.

Figure 1 MRI algorithm

Figure 2 Normal myelination Normal T2-weighted (A–D) and T1-weighted (E–H) images at term (A, E), and at the ages of 5 months (B, F), 1 year (C, G), and 5 years (D, H). Myelin deposition is represented by a low signal on T2-weighted images and high signal on T1-weighted images. Note that myelination consistently looks more advanced on T1-weighted images than on T2-weighted images.

Figure 3 Variable degrees of hypomyelination The first patient (A, E), 7 years old, has less myelin than a normal neonate; the cause is unknown. The cerebral white matter has a low signal intensity on T1-weighted images (E). The second patient (B, F), 6 years old, diagnosed with Pelizaeus-Merzbacher disease, has somewhat more myelin. The cerebral white matter is isointense with the cortex on T1-weighted images (F). The third patient (C, G), 11 years old, also diagnosed with Pelizaeus-Merzbacher disease, has more myelin. Large areas of the cerebral white matter have a higher signal intensity than the cortex on T1-weighted images (G). The fourth patient (D, H), 4 years old, diagnosed with the 18q⁻ syndrome, has again more myelin. All cerebral white matter has a higher signal intensity than the cortex on T1-weighted images (H), but on the T2-weighted images (D) part of the cerebral white matter still has a slightly higher signal intensity than the cortex.

Figure 4 Predominance of the white matter abnormalities Alexander disease (A) presents in many patients with predominantly frontal white matter abnormalities. Note the additional slight signal abnormalities in the basal ganglia. The most frequent presentation of the cerebral form of X-linked adrenoleukodystrophy (B) is with a lesion in the parieto-occipital white matter. Note that two zones can be distinguished within the lesion. Kearns-Sayre syndrome (C) is one of the disorders characterized by predominantly subcortical white matter abnormalities and relative sparing of the periventricular white matter. The disease also displays signal abnormalities in the thalamus (C). Metachromatic leukodystrophy (D) primarily affects the periventricular and deep cerebral white matter, whereas the U-fibers are relatively spared. The stripes with more normal signal within the abnormal white matter are typically seen in certain lysosomal storage disorders (D). Cortical neuronal degenerative disorders often have an ill-defined, broad, periventricular rim of mildly abnormal signal, as shown here in juvenile neuronal ceroid lipofuscinosis (E). Diffuse cerebral white matter abnormalities are seen in childhood ataxia with central hypomyelination/vanishing white matter (F). In cerebrotendinous xanthomatosis (G), the cerebellar white matter is usually more affected than the cerebral white matter. The cerebellum often also contains areas of low signal (G). In patients with autosomal dominant adult onset leukoencephalopathy related to a duplication of LMNB1 (H), involvement of the middle cerebellar peduncles is frequently seen.