Using 1.5T MRI the gyral pattern (agyria or pachygyria), thickened cortex and other brain abnormalities can readily be appreciated.75 Several different patterns of LIS arc recognized using MRI, which led to development of a detailed grading system78,79 which considers both the severity of the gyral pattern simplification and the gradient along the anterior to posterior axis. Most patients have a posterior to anterior (P>A) gradient in which the gyral malformation is more severe posteriorly than anteriorly. This pattern is seen most, often as a consequence of a mutation in the LIS1 gene, but

may also occur with mutations of TUBA1A. 80 Others have the reverse anterior to posterior (A>P) gradient, Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical which is seen most commonly as a consequence of mutations in the DCX gene. Figure 4 shows the imaging features of the two main gradients of LIS, and Figure 5 shows different grades of LIS severity. Figure 4. Imaging features of classical lissencephaly contrasting the P>A gradient with the A>P gradient. Axial T1 -weighted MRI scans. The image on the left shows near-complete agyria posteriorly transitioning to pachygyria anteriorly. This is … Figure 5. Imaging features of classical lissencephaly showing the four severity grades. All images are T1 – or T2 -weighted MRI scans. The top row shows axial scans and the

Inhibitors,research,lifescience,medical bottom row coronal scans. Grade 1 is near complete agyria, grade 2 is posterior agyria and … Six genes associated with LIS syndromes have been identified, and in approximately Inhibitors,research,lifescience,medical 80% of cases, a genetic cause can be found, usually an abnormality of the LIS1 or DCX genes.78,81 The six known genes associated with causation of LIS

are LIS1,82 DCX,83 ARX,70 RELN,69 YWHAE,76 and TUBA1A 84 These genes are all known to be required for optimal migration of neurons during brain development. All but the ARX gene are required for normal radial migration of neurons whereas the ARX gene is required for normal tangential migration.85 Inhibitors,research,lifescience,medical Mutations in the LIS1 gene are the most common cause of LIS.81 The LIS1 protein is not only required for INK1197 neuronal migration, but. it is also required for cellular proliferation and intracellular transport (reviewed in ref 86). Subcortical band heterotopia Subcortical band heterotopia (SBH) is alternately known as double cortex87 or subcortical laminar heterotopia.88 The term SBH is preferable to double cortex, as the heterotopic gray matter lacks almost cortical lamination and organization, and does not resemble a cerebral cortex other than being composed of gray matter. SBH is characterized microscopically by bilateral bands of heterotopic gray matter located in the white matter between the lateral ventricular walls and the cortex.65 The overlying cortex appears normal with the exception of mildly shallow sulci. In the most typical forms, the bands are bilateral and symmetric and slightly more prominent anteriorly.