Clinical and neuroimaging findings in patients with lissencephaly/subcortical band heterotopia spectrum: a magnetic resonance conventional and diffusion tensor study

Abstract

Purpose To clarify brain abnormalities on magnetic resonance imaging (MRI) and its clinical implications in lissencephaly/ subcortical band heterotopia (LIS/SBH) spectrum patients. Methods The clinical severity and classification according to Di Donato were retrospectively reviewed in 23 LIS/SBH spectrum patients. The morphological and signal abnormalities of the brainstem, corpus callosum, and basal ganglia were also assessed. The brainstem distribution pattern of the corticospinal tract (CST) was analyzed by diffusion tensor imaging (DTI) and categorized into two types: normal pattern, in which the CST and medial lemniscus (ML) are separated by the dorsal portion of the transverse pontine fiber, and the abnormal pattern, in which the CST and ML are juxtaposed on the dorsal portion of a single transverse pontine fiber. Correlations between MR grading score and potential additional malformative findings of the brain and clinical symptoms were investigated. Results All patients with grade 3 (n = 5) showed brainstem deformities, signal abnormalities of pontine surface and had a tendency of basal ganglia deformity and callosal hypoplasia whereas those abnormalities were rarely seen in patients with grade 1 and 2 (n = 18). For DTI analysis, the patients with grade 3 LIS/SBH had typically abnormal CST, whereas the patients with grade 1 and 2 LIS/SBH had normal CST. The classification was well correlated with CST and brainstem abnormalities and clinical severity. Conclusion MR assessment including DTI analysis may be useful in assessing the clinical severity in LIS/BH spectrum and may provide insight into its developmental pathology.

Brain Pathways in LIS1-Associated Lissencephaly Revealed by Diffusion MRI Tractography

“…The disorganized fibers of the association pathways seen in our specimens might be a good example of histopathological findings in the white matter of LIS, where heterotopic neurons are scattered, and axons are randomly oriented due to axonal guidance defects [34]. Abnormalities of white matter tracts have been previously reported [2,27], as well as hypoplasia, disorganization, or the complete absence of the corticospinal tract (CST) in patients with LIS [35][36][37][38].…”

“…Mutations in lissencephaly 1 (LIS1) and doublecortin (DCX) were the first two genes found to be associated with type I LIS. With advances in molecular genetic analysis, more than 20 LIS/SBH-related genes have been identified, and the number of newly associated genes continues to grow [27]. In addition to impaired neuronal migration processes, disturbed neurogenesis may also be involved in the smooth brain [28].…”