Malformations of cortical development related to the neuronal proliferation can be represented by cortical dysplasia, a focal cortical thickening with radial hyperintense bands on T2 images.

Focal cortical dysplasia (FCD) is  a localized area of cortical thickening with an indistinct gray-white matter junction. There is macrogyria and abnormally widened or deep sulci and a subcortical focus of abnormal signal intensity extending from the gray-white matter junction to the superolateral margin of the lateral ventricle (figure 3). Some forms of FCD may show increased signal on FLAIR and T2 -weighted images which has been thought to represent the presence of “balloon cells”.

Fig. 3: Transmantal dysplasia – Coronal (A) and axial (B) MRI weighted FLAIR demonstrating linear hight signal intensity (arrows) that expands from cortex to the ventricle.

Tuberous sclerosis complex (TSC), an autosomal dominant syndrome with hight penetrance with genes related to the codes of hamartin (TSC1 on 9q34) and tuberin (TSC2 on 16pl3), is a multisystem syndrome characterized by hamartomata in multiple organ, most frequently the brain, including abnormal proliferation of neurons and glia in the central nervous system. Typical brain abnormalities include cortical tubers (figure 4), subependymal nodules, and subependymal giant cell astrocytoma. The pathological features of cortical tubers may be indistinguishable from those of some forms of focal cortical dysplasia, witch have no particular dysmorphic, neurocutaneous, or multiple congenital anomaly syndromes associated. 

Fig. 4: Tuberous sclerosis - Axial MRI images weighted T2 (A) and FLAIR (B) showing cortical tubers, represented by the red arrows, more evident on FLAIR.

Changes in neuronal migrations can result in ectopic position of the gray matter with heterotopias, demonstrated as ectopic substance with the same signal of cortex in all sequences (figure 5) and classified according to their location.

Based on MRI, there are three types of heterotopia : periventricular nodular (associated with mutations in the FLNA gene, related to efficient cell motility), focal subcortical (with volume reduction of white matter and thinning of the overlying cortex) and in-band (where tracks of gray matter are separated from the cortex by a thin layer of white substance). Other genes, such as ARFGEF2, DCX and LIS1 may also be related with heterotopy. 

Fig. 5: Periventricular heterotopia – Axial MRI images weighted T2 (A), FLAIR (B) and T1 (C), showing heterotopic tissue isointense to gray substance, represented by the arrows.

When cortical organization is incorrect, MRI can detect polymicrogyria (PMG), many small prominent convolutions separated by shallow sulci with an irregular appearance of the cortical surface and cortical white matter (figure 6).  

Fig. 6: FLAIR sequence shows bilateral perisylvian polymicrogyria (arrows).

Most frequently affecting the perisylvian cortex, PMG can be unilateral or bilateral, symmetric or asymmetric. It can be an isolated finding or can be associated with multiple different syndromes.

The affected Sylvian fissures may appear extended and superiorly orientated posteriorly.

Injury during cortical organization may also cause schizenchephaly (SCZ), represented by a cleft lined with gray matter that connects the subarachnoid space with the ventricular system. The clefts of SCZ can be unilateral or bilateral and of the “open-lip” (figure 7) or “closed-lip” (figure 8) subtype.

Fig. 7: Schizencephaly “open-lip” – Computed tomography (CT) axial (A) image and MRI axial weighted T1 (B) - Transcortical cleft extending from the surface of the right lateral ventricle to the subarachnoid periencefalic space.

Fig. 8: Schizencephaly “closed-lip”. Axial MRI image weighted T1 that shows indentation in the ependymal surface, called “nipple” (red arrow) lined by polymicrogyria (green arrow).

The etiology of SCZ remains highly controversial, and there are likely both genetic and non-genetic causes. Congenital CMV infection and in utero ischemic insults are associated with SCZ.

It is important to differentiate open-lip schizencephaly and porencephaly because both lesions show similar signal intensity. The presence of tissue with signal intensity similar to that of gray matter lining the cavity formed by the pathology makes the diagnosis of schizencephaly more likely.

Another rare malformation of cortical development is lissencephaly, which can cause epilepsy, mental retardation and early death. Despite the severity, many patients survive until adulthood. In this condition, migration of neurons is affected, leaving a smooth brain surface with cortical disorganization and volume reduction of white matter.

Lissencephaly may be complete (agyria, figure 9), with complete absence of surface gyri in the cerebral surface, or incomplete (pachygiria, figure 10) with few  thick convolutions. This cortical malformation is related to mutations in the DCX and L1S1 genes and may appear alone or as part of other syndromes.

Fig. 9: Lissencephaly – axial MRI image, weighted T2 smooth surface, with absence of sulci and gyri

Fig. 10: Pachygiria – MRI axial (A) and sagittal (B) images weighted T1, showing a few poorly formed gyri (red arrows).