Neuronal migration defect of the developing cerebellar vermis in substrains of C57BL/6 mice: cytoarchitecture and prevalence of molecular layer heterotopia.

Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. In the present report we describe the prevalence and cytoarchitecture of molecular-layer heterotopia, a malformation of neuronal migration, in the cerebellar vermis of C57BL/6 mice and closely-related strains. In particular, we found a diverse number of cell-types affected by these malformations including Purkinje cells, granule cells, inhibitory interneurons (GABAergic and glycinergic), and glia. Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.

Congenital cytomegalovirus infection: the impact of cerebral cortical malformations.

AIM: Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. METHODS: Twenty-six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. RESULTS: CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. CONCLUSION: In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2-0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.

[Neurocristopathies: a high incidence of cerebral dysgenesis in patients with Hirschsprung's disease]. / Neurocrestopatías: alta frecuencia de disgenesias cerebrales en pacientes con enfermedad de Hirschsprung.

INTRODUCTION: Hirschsprung's disease (HD), or aganglionic megacolon, is a congenital disorder that is characterised by the absence of ganglion cells in the submucosal and myenteric plexuses of the intestine, which is caused by the failure of these cells to migrate from the neural crest (neurocristopathy). Cerebral dysgenesis and polymalformation syndromes have been reported in association with HD, thus suggesting an abnormal morphogenesis. AIM: To study the frequency of cerebral malformations in patients with HD in our environment. PATIENTS AND METHODS: We conducted a retrospective study of 41,666 live newborn infants, over the period 1993-2003, and 17 cases of HD where identified. RESULTS: The incidence of HD in the health district of the province of Albacete is 1.68 per 5,000 live newborn infants. Of the 17 patients with HD who were studied, 10 were isolated (58.8%) and seven (41.1%) were associated to other structural abnormalities and psychomotor retardation. Three of the cases in this latter group were due to chromosome pathology (trisomy 21, Down syndrome), two were caused by specific polymalformation syndromes (one Mowat-Wilson syndrome and one possible FG syndrome), one was due to a pattern of abnormalities that did not fit any known syndrome, and one had a normal phenotype and isolated cerebral dysgenesis. In all of cases the neuroimaging studies identified cerebral dysgenesis that was compatible with neuronal migration disorders. CONCLUSIONS: The frequency of association of HD, either isolated or within the context of a specific malformation syndrome, with neuronal migration disorders is high (23.5%). We suggest a full genetic and neurological evaluation should be carried out in patients with HD, together with brain imaging studies in order to rule out the possibility of cerebral dysgenesis.