Periventricular Nodular Heterotopia

Gray matter heterotopias are neurological disorders caused by clumps of gray matter (nodules of neurons) located in the wrong part of the brain. A grey matter heterotopia is characterized as a type of focal cortical dysplasia. The neurons in heterotopia appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered as an incidentaloma when brain imaging performed for an unrelated problem and has no apparent ill effect on the patient. At the other extreme, heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation. Fatalities are practically unknown, other than the death of unborn male fetuses with a specific genetic defect. Gray matter heterotopias are neurological disorders caused by clumps of gray matter (nodules of neurons) located in the wrong part of the brain. A grey matter heterotopia is characterized as a type of focal cortical dysplasia. The neurons in heterotopia appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered as an incidentaloma when brain imaging performed for an unrelated problem and has no apparent ill effect on the patient. At the other extreme, heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation. Fatalities are practically unknown, other than the death of unborn male fetuses with a specific genetic defect. The development of the brain in the human fetus is extraordinarily complex and is still not fully understood. Neural matter originates in the outer, ectodermic layer of the gastrula; thus, it originates from the cell layer primarily responsible for skin, hair, nails, etc., rather than from the layers that develop into other internal organs. The nervous system originates as a tiny, simple open tube called the neural tube; the front of this tube develops into the brain (and retinas of the eye), while the spinal cord develops from the very back end. Neurons begin to form early, but most of them become structural rather than active nerve cells. The brain generally forms from the inside-out, especially in the case of the neocortex. The difficulties arising from this are readily apparent, as each successive layer of cells must travel through the previous layer to reach its destination. Therefore, nervous tissue develops ladders made of radial glial cells that neurons climb, through the previous layers, to reach their proper destination. Some destinations, such as the cerebral cortex, even have 'placeholder' neurons that travel up the ladder to form a structure; when the final neurons germinate, they find a correct placeholder and then the placeholder cell dies. The complexity of neural development makes it fraught with opportunities for error. Grey matter heterotopia is such an example. It is believed that gray matter heterotopia are caused by arrested migration of neurons to the cerebral cortex; that is, when neurons that are supposed to form part of the cerebral cortex. fail to climb to the end of their ladder correctly and are permanently situated in the wrong location. Gray matter heterotopia are common malformations of cortical development classed as neuronal migration disorders. Heterotopias are classed in two groups: nodular and diffuse. Nodular types are subependymal and subcortical; diffuse types are termed band heterotopias. Affected patients are generally divided into three groups, depending on the location of the formation: subependymal, subcortical, and band heterotopia. In addition, especially with heterotopia that are genetically linked, there are gender differences, men suffering more severe symptoms than women with similar formations. In general, band heterotopia, also known as double cortex syndrome, are seen exclusively in women; men with a mutation of the related gene (called XLIS or DCX) usually die in utero or have a much more severe brain anomaly. Symptoms in affected women vary from normal to severe developmental delay or mental retardation; the severity of the syndrome is related to the thickness of the band of arrested neurons. Nearly all affected patients that come to medical attention have epilepsy, with partial complex and atypical absence epilepsy being the most common syndromes. Some of the more severely affected patients develop drop attacks. Periventricular means beside the ventricle, while subependymal (also spelled subepydymal) means beneath the ependyma; because the ependyma is the thin epithelial sheet lining the ventricles of the brain, these two terms are used to define heterotopia occurring directly next to a ventricle. This is by far the most common location for heterotopia. Patients with isolated subependymal heterotopia usually present with a seizure disorder in the second decade of life.