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Legends to supplemental figures
Figure e-1: Hypomyelination plus
In a 3-year-old patient with hypomyelination with atrophy of the basal ganglia and cerebellum (HABC), the MRI reveals hypomyelination in combination with a small caudate nucleus and absence of the putamen (A, E). In a 21-month-old patient with infantile neuronal ceroid lipofuscinosis, the MRI shows hypomyelination in combination with global cerebral atrophy and dark thalami on T2-weighted images (B, F). In a 13-month-old patient with infantile onset GM1 gangliosidosis, MRI demonstrates hypomyelination in combination with a slightly elevated signal of the basal ganglia on T2-weighted images and white thalami on T1-weighted images (C, G). In a 4-year-old patient with fucosidosis, MRI reveals hypomyelination in combination with an abnormally low signal of the globus pallidus and thalamus on T2-weighted images and abnormally high signal of those structures on T1-weighted images (D, H).
Figure e-2: Multifocal cerebral white matter abnormalities
The first patient (A, B) has a proven congenital cytomegalovirus infection. The largest lesions, seen in the deep parietal white matter, are divided into two by a narrow band of more normal signal intensity (A). The sagittal image shows an anterior temporal cyst (B). The second patient (C, D) has been diagnosed with acute disseminated encephalomyelitis. Note the small areas of contrast enhancement on the coronal T1-weighted image (D). Multiple sclerosis (E-H) leads to multifocal lesions in an early stage (E), but may ultimately become completely confluent (G), simulating a leukodystrophy. Assessment of previous MRIs (E) and the presence of multifocal contrast enhancement (F, H) help to establish the correct diagnosis.
Micro-angiopathies (I-L) typically lead to multifocal and more confluent lesions in the periventricular and deep cerebral white matter, as a rule in combination with lesions in the brain stem and basal ganglia (I, K). Gradient echo images tend to show evidence of micro-bleeds (J). In defects in collagen IV A1 (I, J), porencephaly is frequently observed (J). A white pulvinar on T1-weighted images (L) is a sign of Fabry disease (K, L).
Genetic disorders may also present with multifocal lesions. Leukoencephalopathy with brain stem and spinal cord involvement and elevated white matter lactate (LBSL) may present with confluent or multifocal (M) cerebral white matter abnormalities. The typical involvement of certain brain stem tracts (N) leads to the correct diagnosis. Chromosomal abnormalities, such as 6p- (O, P), may be associated with multifocal cerebral white matter abnormalities and enlarged perivascular spaces (P).
Figure e-3: predominance of the white matter abnormalities
Alexander disease (A, B) presents in many patients with predominantly frontal white matter abnormalities (A), often associated with brain stem lesions (B). Note the additional slight signal abnormalities in the basal ganglia (A). Contrast enhancement of certain structures (B) is also a feature of the disease. The most frequent presentation of the cerebral form of X-linked adrenoleukodystrophy (C, D) is with a lesion in the parieto-occipital white matter. Note that two zones can be distinguished within the lesion (C). Enhancement of a rim within the lesions is a characteristic finding (D). Metachromatic leukodystrophy (E) 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 (E). Cortical neuronal degenerative disorders often have an ill-defined, broad, periventricular rim of mildly abnormal signal, as shown here in juvenile neuronal ceroid lipofuscinosis (F). Kearns-Sayre syndrome (G, H) is one of the disorders characterized by predominantly subcortical white matter abnormalities and relative sparing of the periventricular white matter (G). The disease displays also signal abnormalities in the thalamus (G) and brain stem (H). Diffuse cerebral white matter abnormalities are seen in childhood ataxia with central hypomyelination / vanishing white matter (CACH/VWM) (I, J). FLAIR images show evidence of white matter rarefaction and cystic degeneration (J). In cerebrotendinous xanthomatosis (CTX) (K, L), the cerebellar white matter is usually more affected than the cerebral white matter. The cerebellum often also contains areas of low signal (L). Alexander disease almost invariably leads to brain stem abnormalities, with focal lesions (M) or atrophy of the medulla oblongata (N). The cerebellar white matter may also be affected (N). In patients with autosomal dominant adult onset leukoencephalopathy related to a duplication of LMNB1 (O, P), involvement of the middle cerebellar peduncles is frequently seen (P), in addition to prominent supratentorial white matter abnormalities (O).