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The following page is adapted from a text written by Pr. Charles Raybaud, neuroradiologist, former chief of the neuradiology unit of La Timone Hospital in Marseilles, currently working at the Hospital for Sick Children, Toronto.
The malformations of cortical development are classified according to their morphological characteristics. It is a classification which was initially proposed by the neuropathologists, and hence is essentially descriptive, but it relies for its major part on the model of cortical development proposed by Sidman and Rakic (1973). This classification is made of four sections : cellular proliferation, cellular differentiation, neuronal migration and cortical organization.
The pool of cerebral stem cells is the result of approximately 35 cycles of symmetrical divisions (one stem cell produces two stem cells). If one cycle is missing, the initial pool is reduced by 50%, if two cycles are missing the initial pool is reduced by 75%. Such perturbations are giving rise to the so-called microlissencephaly (or microcephalia vera or radial microbrain), characterized by a very small brain, disproportionate with respect to the face, with a simplified pattern of gyration but with a cortex which is approximately normal in thickness.
It is the result of asymmetrical divisions : each stem cell gives rise to another stem cell and to a cell which will become either a glial cell or a neuron. Selective alterations of this process lead to cells which have a mixed phenotype of both neuronal and glial cells. Depending on their morphology, they are often described such as « weird » giant neurons, the so-called « balloon cells », or as giant astrocytes (in tuberous sclerosis). This abnormal differentiation is accompanied by a cortical dysplasia (abnormal lamination, abnormal gyration) and an abnormal neuronal migration (transmantle dysplasia). Depending on the volume of the lesion, the following categories are found :
- focal cortical dysplasia (Taylor type).
- its multigyral or lobar form, or hemispheric (hemimegalencephaly).
- very small lesions (microdysgenesis), often not visible using MRI.
- tuberous sclerosis (Bourneville type) is a slightly different conditions since it is associated with numerous other anomalies of body structures (kidney, heart, lung, pancreas).
Nodules of normal neurones can be found in places where they are normally not found. They are responsible for grey matter heterotopias. Depending on their localization, they are described as periventricular or laminar (or double cortex). When there is an abnormal neuronal migration (subcortical laminar heterotopia) associated with an absent cortical gyration, the resulting condition is called lissencephaly (agyria and pachygyria).
They are called polymicrogyria. They are causing an excessively folded cortex which is composed of very tiny circumvolutions
covered by a molecular layer. This cortical anomaly is appearing before the gyri and sulci are organized, hence, the diagnosis is
based on the observation of aberrant sulci associated with multiple small gyri. These anomalies usually have a peri-insular distribution,
unilateral or bilateral (but asymmetric even if they appear roughly symmetric), they are rarely seen in other locations. The affected
portion of the hemisphere is usually atrophied and there is often an abnormal myelinisation.
Schizencephaly is a specific condition in which there is a transcerebral cleft walled with a polymicrogyric cortex, uni- or bilateral
but asymmetric in this latter case. The clefts are very often frontal but they can be found anywhere on the hemisphere.
( Barkovich et al. 2001 , Copp et Harding 1999 , Barkovich et al. 2005)
With the evolution of the concepts related to corticogenesis, and with the enormous improvement of the MRI analysis, it became obvious to many that this classification was somewhat crude. Radiologic subclasses have been described and they sometimes correspond to different etiologies (e.g. lissencephalies/double cortex). The current terminology thus needs to be refined and diversified to better take into account the many different entities that need to be differentiated.
Malformations due to abnormal proliferation of glial and neuronal precursors
- Generalized defect ----------microlissencephaly (thin or normal cortex)
- Localized defect ----------Non neoplasic ..................Tuberous sclerosis ..................Focal cortical dysplasia with « balloon cells » ..................Hemimegalencephaly ----------Neoplasic
Malformations due to abnormal neuronal migration
- Generalized defect ----------Lissencephaly ----------Pachygyria ----------Heterotopia
- Localized defect ----------Agyria or focal pachygyria ----------Polymicrogyria (« unlayered » type) ----------Focal or multifocal heterotopia
Malformations due to abnormal cortical organization
- Generalized defect ----------Polymicrogyria
- Localized defect ----------Bilateral symetrical or asymetrical polymicrogyria ----------Schizencephaly ----------Focal or multifocal cortical dysplasia without « balloon cells »