Gray Matter Heterotopias and Cortical Organizational Abnormalities

Gray matter migration and organization disorders constitute a large group of abnormalities. Examples of these anomalies consist of gray matter heterotopias, polymicrogyria, pachygyria, agyria, lissencephaly, schizencephaly, unilateral hemimegalencephaly, and other processes.

This case illustrates two main concepts, heterotopic gray matter, and abnormalities in cortical organization, namely polymicrogyria. Severe cases manifest in infants. Mild cases can be seen in people who live to an old age, and are only identified during autopsy. Lissencephaly cases, especially when severe, can be associated with early demise. Clinically, these patients present with seizures, development delay, and possibly, disorders of movement. Treatment consists of medical management of seizures, and surgery such as corpus callosotomy.

Gray matter originates in the periventricular germinal matrix. It normally migrates in an organized fashion along special fiber tracts toward the cortex. After migrating into the cortex, gray matter organizes itself into a six layer cortex.

Gray Matter Migration Abnormalities: If gray matter migration is disrupted, a patient can get heterotopic gray matter in the periventricular, deep, or subcortical locations. This can be seen as structures that follow gray matter signal on all sequences, without enhancement. Heterotopic gray matter can result from acquired causes such as maternal trauma, infection, or toxemia. Heterotopic gray matter can also be inherited. The most common location for heterotopic gray matter is subependymal. In this case, gray matter nodules are located adjacent to the ventricular surface. In band heterotopia, a thin gray matter band is located deep to a thin, abnormal cortex. This produces the "double cortex" sign. In subcortical heterotopia, nodular gray matter areas are visualized underneath a thin and dysplastic appearing cortex. In this disorder, the gray matter nodules can be quite large. These findings sometimes confuse the inexperienced observer, who may refer to the large nodules as neoplasm. Sometimes, in subcortical heterotopia, a curvilinear gray matter structure is continuous with both the cortex and underlying ventricular surface.

In classic lissencephaly, which is sometimes included under the heading of gray matter migration abnormalities, there lies a thick inner band of gray matter, a cell sparse zone, and a thin outer layer of gray matter. This is associated with a "hour glass" configuration. There can be some gyral formation, as part of a pachygyria/agyria complex.

In cobblestone cortex, neurons migrate more than normal, and produce a pebbled surface of the brain. This is associated with congenital muscular dystrophies.

Gray Matter Organization Abnormalities: If gray matter organization is disrupted, a patient can get polymicrogyria. In polymicrogyria, problems occur in late neuronal migration and cortical organization. Neurons reach the cortical destination, but do not distribute normally. This results in small convoluted gyri. On MRI, there is irregularity of the gray white junction. This most commonly occurs in the perisylvian locations. The cortex can be normal or above normal in thickness. Sulci are shallow or absent. Polymicrogyria can be associated with CMV infection. This contrasts with pachygyria where the cortex and white matter junction remains smooth.

There is not much else in the differential diagnosis of this case. Possibilities in the differential include tuberous sclerosis with sub-ependymal nodules, or some kind of a neoplastic/metastatic process. Subependymal nodules associated with tuberous sclerosis can be calcified, and calcifications are easily visualized on CT. Subependymal nodules generally follow white matter characteristics, not characteristics of gray matter. Subcortical lesions in tuberous sclerosis generally, but not always, demonstrate abnormal T2-bright signal. Metastatic disease generally enhances and carries a different clinical presentation compared to gray matter migration disorders.

Agyrica, and pachygyria demonstrate a four layer cortex. Complete agyria is referred to as lissencephaly. Pachygyria shows broad, fat, and shallow gyri. Schizencephaly describes a cleft in the brain parenchyma that extends from the ventricle to the surface of the cortex. This is lined by dysplastic gray matter.

Hemimegalencephaly refers to hamartoma type growth of a cerebral hemisphere. In megalencephaly, the cortex is thick, with a pachygyria pattern, polygyria pattern, or fused/shallow gyri. In megalencephaly, gray matter heterotopias are present. Myelination is abnormal in the affected cerebral hemisphere.