Magnetic resonance imaging pattern recognition in hypomyelinating disorders

Abstract

Hypomyelination is observed in the context of a growing number of genetic disorders that share clinical characteristics. The aim of this study was to determine the possible role of magnetic resonance imaging pattern recognition in distinguishing different hypomyelinating disorders, which would facilitate the diagnostic process. Only patients with hypomyelination of known cause were included in this retrospective study. A total of 112 patients with Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis, Salla disease and fucosidosis were included. The brain scans were rated using a standard scoring list; the raters were blinded to the diagnoses. Grouping of the patients was based on cluster analysis. Ten clusters of patients with similar magnetic resonance imaging abnormalities were identified. The most important discriminating items were early cerebellar atrophy, homogeneity of the white matter signal on T(2)-weighted images, abnormal signal intensity of the basal ganglia, signal abnormalities in the pons and additional T(2) lesions in the deep white matter. Eight clusters each represented mainly a single disorder (i.e. Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, infantile GM1 and GM2 gangliosidosis, Pelizaeus-Merzbacher-like disease and fucosidosis); only two clusters contained multiple diseases. Pelizaeus-Merzbacher-like disease was divided between two clusters and Salla disease did not cluster at all. This study shows that it is possible to separate patients with hypomyelination disorders of known cause in clusters based on magnetic resonance imaging abnormalities alone. In most cases of Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis and fucosidosis, the imaging pattern gives clues for the diagnosis.

Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis

“…The clinical course of these diseases may be similar to that of PMD or sometimes additional signs are present e.g. hypodontia, cataract or atrophy of basal ganglia on MRI [9][10][11][12]. Moreover, world experts in the white matter diseases state that unclassified leukodystrophies with hypomyelination still exist [9,11].…”

Clinical features and management of hereditary spastic paraplegia

“…White matter abnormalities may be found in some AR-HSP, such as SPG 5, SPG 21, SPG 35 or autosomal recessive spastic ataxia with leukoencephalopathy (ARSAL) 47 . In SPG2, white matter abnormalities are also typical; they resemble (but to a lesser extent) the diffuse hypomyelination found in the allelic Pelizaeus-Merzbacher disease 25,48 (Figure 2). …”

Expanded spectrum of Pelizaeus–Merzbacher-like disease: literature revision and description of a novel GJC2 mutation in an unusually severe form

“…The basal ganglia and thalami are normal in most patients. However, Steenweg et al 22 recently described a separate cluster of PMLD patients showing T2 hyperintensity of the subcortical white matter contrasting with a lower T2 signal of the remaining cerebral white matter, associated with hypointensity of the anterolateral part of the thalamus.…”