Normal neuronal migration
Normal neuronal migration involves the development of six cortical layers, each one performing distinct functions.Normal cerebral development occurs in three dynamic and overlapping stages:
first stage: stem cells proliferate and differentiate into neurons or glial cells within the forebrain and the ventricular and subventricular zones lining the cerebral cavity;
in humans this stage lasts from gestational weeks 5-6 to 16-20;
second stage: migration away from the origin in a radial fashion along the glial fibers from the periventricular region of the ganglionic eminences towards the pial surface;
the generations settle into a pattern within the cortical plate during this stage;
in humans this stage lasts from gestational weeks 6-7 to 20-24;
third stage: apoptosis and synaptogenesis within the six cortical layers to develop correct cortical organization;
in humans this stage lasts from gestational week 16 until long after birth.Most types of incomplete neuronal migration to the cortex occur during the third and fourth gestational months. The abnormal migration of the neurons causes them to not reach their proper final destinations, which results in failure of the sulci and gyri to form.The stage of cortical development at which migration is arrested is directly related to the level of structural malposition.One of the most critical stages in brain development is when the post-mitotic neurons migrate from the ventricular zone to form the cortical plate. Migration arrested toward the latter part of development usually restricts the abnormal cell position to the cortex level. Neuronal migration disorder caused by genetic mutations
Several genetic mutations have been isolated and linked to specific malformations of the cerebral cortex.
Some children with quadriplegia also have hemiparetic tremors, an uncontrollable shaking that affects the limbs on one side of the body and impairs normal movement. Occasionally, terms such as monoplegia, paraplegia, triplegia, and pentaplegia may also be used to refer to specific manifestations of the spasticity. Pathogenesis
Pachygyria, lissencephaly (smooth brain), and polymicrogyria (multiple small gyri) are all the results of abnormal cell migration. The abnormal migration is typically associated with a disorganized cellular architecture, failure to form six layers of cortical neurons (a four-layer cortex is common), and functional problems. The abnormal formation of the brain may be associated with seizures, developmental delay, and mental dysfunctions.Normally, the brain cells begin to develop in the periventricular region (germinal matrix) and then migrate from medial to lateral, to form the cerebral cortex. Diagnosis
Different imaging modalities are commonly used for diagnosis. While computed tomography (CT) provides higher spatial resolution imaging of the brain, cerebral cortex malformations are more easily visualized in vivo and classified using magnetic resonance imaging (MRI) which provides higher contrast imaging and better delineation of white and gray matter.Diffuse pachygyria (a mild form of lissencephaly) can be seen on an MRI as thickened cerebral cortices with few and large gyri and incomplete development of the Sylvian fissures. severe epilepsy
reduced longevity
varying degrees of mental retardation
intractable epilepsy
spasticityCognitive ability correlates with the thickness of any subcortical band present and the degree of pachygyria.