engleski

Neuronal migration and cortical migratory disorders

In this review we outline the neurobiological basis for classification of cortical migratory disorders. Neurons of the human cortex are born in the ventricular and subventricular zone and migrate for a long distance to reach their final point of destination in the cortex, using two types of migratory routes and mechanisms: (1) radial migration along radial glia and (2) tangential, presumably “ neurophilic” migration. The process of migration is complex and may be disturbed by various genetic and extrinsic factors. The disturbances of proliferation in the ventricular zone result in major malformations such as schizencephaly, while the failure of onset of migration results in periventricular nodular heterotopia with characteristic abnormalities in magnetic resonance imaging (MRI) and with genetic aberration in the background (FILAMIN1 gene mutation). The typical migratory disorder is lissencephaly type I caused by defect of ongoing migration. The lissencephaly type I is currently included in agyria-pachigyria band spectrum disorders. This group of disorders is caused by mutations of LIS1 and DCX (XLIS) gene mutations associated with Miller-Dieker syndrome, Lennox-Gastaut syndrome and epilepsy. The defects of late phases of migration cause lissencephaly type II, cobblestone complex, which is associated with Walker-Warburg syndrome, macrocephaly, retinal malformation, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy. Zellweger syndrome is morphologically characterized by polymicrogyria and biochemically by defects of the mitochondrial desaturation pathway. The disorders with later migration failure show abnormal MRI restricted to the cortex. Another migratory disorder, focal cortical dysplasia, is a frequent cause of drug resistant epilepsy. An especially helpful diagnostic tool for migratory disorders is high resolution (3T) MRI. Genetic testing together with detailed MRI of migratory disorders opens new perspectives for early detection and improved treatment of migratory disorders.

epilepsy; 3T magnetic resonance imaging; radial unit hypothesis; GABA-ergic interneurons; glutamatergic neurons; heterotopia

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