Developmental Differences of the Major Forebrain Commissures in Lissencephalies

Abstract

Background and purpose Changes of the major forebrain commissures in lissencephaly have not been systematically studied. This study investigated the developmental differences of the commissures in patients with varying types of lissencephaly to determine whether specific commissural features may help in distinguishing among lissencephaly phenotypes. Materials and methods MRI of 124 patients were retrospectively reviewed. Patients were classified as classic(cLIS), variant(vLIS) and Cobblestone lissencephaly(CBSC) according to cortical phenotype; few patients had genetic diagnoses. Abnormalities of the corpus callosum, anterior (AC), and hippocampal commissures (HC) were recorded, and the overall shape was regarded as hypogenetic, hypoplastic, dysmorphic, angled splenium and convex corpus compared with ge matched controls. Correlations between commissural characteristics and cortical patterns were analyzed using Monte Carlo simulation of chi-square, ‘extention to mxn table’, and Fisher’s exact tests as appropriate (p<0.05). Results Patients were classified as cLIS (57.4%), vLIS (38.4%) or CBSC (4.2%). The most common callosal developmental anomaly was hypogenesis with absent rostrum, small inferior genu and small splenium. An angled (90°) splenium was found to be significantly associated with cLIS; and excessively convex corpus callosum with VLDLR mutations. ACC with enlarged anterior commissure was found in all ARX mutations. Conclusion Specific patterns of the commissure anomalies were associated with certain types of lissencephaly. Callosal anomalies were more common than those of AC or HC. Developmental differences of commissures may be useful as an imaging criterion in differentiating the groups of lissencephalies and may give insight into the processes causing these malformations.

Clinical, genetic and imaging findings identify new causes for corpus callosum development syndromes

“…In the majority of patients with ACC, the anterior and hippocampal commissures are absent or small, which is consistent with common processes of commissure development (Hetts et al, 2006). In a smaller subset of patients with ACC, but in all cases with ACC with an identified ARX mutation (Hetts et al, 2006;Kara et al, 2010), the anterior commissure is enlarged, and limited evidence suggests that this may represent a compensatory mechanism to maintain inter-cerebral transfer of information (Fischer et al, 1992;Barr and Corballis, 2002). A similar increase in anterior commissure size has been well established in multiple inbred mouse strains, and is accounted for by an increase in unmyelinated axons (Livy et al, 1997).…”

Location of Periventricular Nodular Heterotopia Is Related to the Malformation Phenotype on MRI

“…It is known that some migration disorders, such as lissencephalies, have additional defects in axonal connectivity, 21 and it has been postulated that causative genes are implicated in both neuronal migration and axon outgrowth. 22 We may hypothesize, by extension, that this may also be valid for heterotopia and that those phenotypes that have greater association with cortical (neuronal) disorders (eg, pPNH) will show a greater frequency of connectivity abnormalities and, thus, diminished WM.…”

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

“…We used the GMFM 88 items version (GMFM-88), which includes several simple tasks performed in five dimensions: 1) lying-rolling, 2) sitting, 3) creeping-kneeling, 4) standing, 5) walking-running-jumping. The GMFM-88 has been already reported to be valid measures in patients with AS syndrome [ 30 , 31 ]. Quantification is based on how much of the task the patient can realize independently, without any reference to the quality of the performance.…”