Linear growth of corpus callosum and cerebellar vermis in very-low-birth-weight preterm infants.

BACKGROUND/PURPOSE: Impaired growth of the corpus callosum (CC) and cerebellar vermis (CV) is associated with poorer neurodevelopmental outcomes in preterm infants. However, references on the postnatal growth rate of the CC and CV by sonography are limited. The aim of this study is to assess the normal linear growth of CC and CV using a serial cranial ultrasound. METHODS: We prospectively enrolled preterm infants with very low birth weight from September 2008 to December 2009 after excluding those with congenital anomalies or diseases affecting the brain parenchyma. Serial sonographic measurements of the CC and CV were performed according to the standard protocol. Scheduled comprehensive neurodevelopmental evaluations were performed till the corrected age of 2 years. We excluded those with significant brain damages or poor neurodevelopmental outcomes in the final analysis. The growth rate was estimated using the loess smoothing curve and linear regression analysis. RESULTS: Among the 86 enrolled neonates, 14 with significant brain damage and 8 with poor neurodevelopmental outcomes were excluded from the final analysis. The growth rate of the CC length was 1.72 (95% confidence interval [CI]: 1.24-2.20) and 0.57 (95% CI: 0.33-0.80) mm per week before and after the postmenstrual age of 30.5 weeks, respectively. The growth rate of the CV length was 0.78 (95% CI: 0.68-0.89) mm per week. CONCLUSION: We proposed reference values of the normal linear growth rate of the CC and CV lengths in very-low-birth-weight preterm infants using the serial cranial ultrasound.

Sox2 conditional mutation in mouse causes ataxic symptoms, cerebellar vermis hypoplasia, and postnatal defects of Bergmann glia.

Sox2 is a transcription factor active in the nervous system, within different cell types, ranging from radial glia neural stem cells to a few specific types of differentiated glia and neurons. Mutations in the human SOX2 transcription factor gene cause various central nervous system (CNS) abnormalities, involving hippocampus and eye defects, as well as ataxia. Conditional Sox2 mutation in mouse, with different Cre transgenes, previously recapitulated different essential features of the disease, such as hippocampus and eye defects. In the cerebellum, Sox2 is active from early embryogenesis in the neural progenitors of the cerebellar primordium; Sox2 expression is maintained, postnatally, within Bergmann glia (BG), a differentiated cell type essential for Purkinje neurons functionality and correct motor control. By performing Sox2 Cre-mediated ablation in the developing and postnatal mouse cerebellum, we reproduced ataxia features. Embryonic Sox2 deletion (with Wnt1Cre) leads to reduction of the cerebellar vermis, known to be commonly related to ataxia, preceded by deregulation of Otx2 and Gbx2, critical regulators of vermis development. Postnatally, BG is progressively disorganized, mislocalized, and reduced in mutants. Sox2 postnatal deletion, specifically induced in glia (with GLAST-CreERT2), reproduces the BG defect, and causes (milder) ataxic features. Our results define a role for Sox2 in cerebellar function and development, and identify a functional requirement for Sox2 within postnatal BG, of potential relevance for ataxia in mouse mutants, and in human patients.

Eye movements, sensorimotor adaptation and cerebellar-dependent learning in autism: toward potential biomarkers and subphenotypes.

Because of the wide range of symptoms expressed in individuals with autism spectrum disorder (ASD) and their idiosyncratic severity, it is unlikely that a single remedial approach will be universally effective. Resolution of this dilemma requires identifying subgroups within the autism spectrum, based on symptom set and severity, on an underlying neuro-structural difference, and on specific behavioral dysfunction. This will provide critical insight into the disorder and may lead to better diagnoses, and more targeted remediation in these subphenotypes of people with ASD. In this review, we discuss findings that appear to link the structure of the cerebellar vermis and plasticity of the saccadic eye-movement system in people with an autism spectrum disorder (ASD). Differences in cerebellar vermis structure in ASD could critically impact visuo-sensorimotor development in early infancy, which may in turn manifest as the visual orienting, communication and social interaction differences often seen in this population. It may be possible to distinguish a subpopulation of children with vermal hypoplasia, to establish whether this group manifests more severe deficits in visual orienting and in adaptation to persistent visual errors, and to establish whether this putative subphenotype of ASD is associated with a specific and distinct clinical symptom profile.

Spontaneous malformations of the cerebellar vermis: Prevalence, inheritance, and relationship to lobule/fissure organization in the C57BL/6 lineage.

The complex neuronal circuitry of the cerebellum is embedded within its lamina, folia, and lobules, which together play an important role in sensory and motor function. Studies in mouse models have demonstrated that both cerebellar lamination and lobule/fissure development are under genetic control. The cerebellar vermis of C57BL/6 mice exhibits spontaneous malformations of neuronal migration of posterior lobules (VIII-IX; molecular layer heterotopia); however, the extent to which other inbred mice also exhibit these malformations is unknown. Using seven different inbred mouse strains and two first filial generation (F1) hybrids, we show that only the C57BL/6 strain exhibits heterotopia. Furthermore, we observed heterotopia in consomic and recombinant inbred strains. These data indicate that heterotopia formation is a weakly penetrant trait requiring homozygosity of one or more C57BL/6 alleles outside of chromosome 1 and the sex chromosomes. Additional morphological analyses showed no relationship between heterotopia formation and other features of lobule/fissure organization. These data are relevant toward understanding normal cerebellar development and disorders affecting cerebellar foliation and lamination.