Malformations of Cortical Development

Categories

• group I: abnormal cell proliferation or apoptosis
• group II: abnormal neuronal migration
• group III: abnormal cortical organization

Group	Characteristics	Conditions
Group I	abnormal proliferation of neuronal and glial cells	Microcephaly macrocephaly FCDs without and with balloon cells (Taylor dysplasia types IIa and IIb), hemimegalencephaly, tuberous sclerosis, dysembryoplastic neuroepithelial tumors (DNETs), gangliogliomas, gangliocytomas
Group II	abnormal neuronal migration	Lissencephaly Band Heterotopia
Group III	abnormal cortical organization	Polymicrogyria, schizencephaly, type I FCDs, mild MCDs

Group	Affected step of development	MCDs resulting from the disturbance	Short definition of the MCD
Group I	Progenitor cell proliferation and apoptosis	Microcephaly	Abnormally small head and brain
		Macrocephaly	Abnormally big head and brain
		Hemimegalencephaly	Overgrowth of (part of) a cerebral hemisphere
		Focal cortical dysplasia	Disturbed lamination and dysmorphic neurons
Group II	Neuronal migration	Lissencephaly type I	Absence of normal convolutions/folds
		Periventricular heterotopia (PH)	Neurons accumulating at the ventricles underneath a normal cortex
		Subcortical band heterotopia/double cortex	Band of grey matter located between the lateral ventricular wall and the cortex
Group III	Neuronal organisation	Cobblestone lissencephaly/lissencephaly type II	Overmigration of neurons to localize on the surface of a brain with reduced gyri
		Polymicrogyria	Too many (usually small) folds/convolutions
		Schizencephaly	Fluid-filled cleft from ventricle(s) to pia lined by heterotopic grey matter

Group II - Neuronal migration disorders

(A) Schematics highlighting the cellular basis of NMDs in the adult human cortex, showing the different cortical layers and neuronal migrations. Single ectopic neurons are shown in grey and the affected structures or processes are indicated. (B) Schematic showing the MRI-detectable morphological defects in the adult human brain that are caused by the cellular defects of each NMD. Ectopically located clusters of affected neurons are shown as greyshading. Lissencephaly type I is characterized bya smooth brain surface and a simplified fourlayered cortex (indicated by green shading). In subcortical band heterotopia, the cortex contains an additional band of grey matter underneath the white matter. Periventricular heterotopia is characterized by clusters (nodular) or sheets (laminar) of neurons accumulating at the ventricles underneath a normal cortex. In lissencephaly type II, neuronsovermigrate ontothecorticalsurface. Schematicsareadapted fromMRIimages,seee.g.BizzottoandFrancis,2015;Francisetal., 2006; Guerrini and Parrini, 2010. IKNM, interkinetic nuclear migration; RG, radial glia; RNM, radial neuronal migration; TNM, tangential neuronal migration.