Gray Matter Heterotopia
Encyclopedia
Gray matter heterotopia is a neurological disorder
caused by clumps of grey matter
being located in the wrong part of the brain
. It is characterized as a type of 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 seizure
s, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered by 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.
is extraordinarily complex and is still not fully understood. Neural matter originates in the outer, ectoderm
ic 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 retina
s of the eye), while the spinal cord develops from the very back end.
Neuron
s 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.
Gray matter heterotopia are common malformations of cortical development. 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 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.
, 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.
Subependymal heterotopia present in a wide array of variations. They can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass.
Symptomatic women with subependymal heterotopia typically present with partial epilepsy
during the second decade of life; development and neurologic examinations up to that point are typically normal. Symptoms in men with subependymal heterotopia vary, depending on whether their disease is linked to their X-chromosome. Men with the X-linked form more commonly have associated anomalies, which can be neurological or more widespread, and they usually suffer from developmental problems. Otherwise (i.e., in non-X-linked cases) the symptomology is similar in both genders.
. Subepedymal heterotopia are frequently accompanied by other structural abnormalities, including an overall decrease in cortical mass. Patients with focal subcortical heterotopia have a variable motor and intellectual disturbance depending on the size and site of the heterotopion.
Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol).
Neurological disorder
A neurological disorder is a disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord, or in the nerves leading to or from them, can result in symptoms such as paralysis, muscle weakness, poor coordination, loss of sensation, seizures,...
caused by clumps of grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...
being located in the wrong part of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
. It is characterized as a type of cortical dysplasia
Cortical dysplasia
Cortical dysplasia is a congenital abnormality where the neurons in an area of the brain failed to migrate in the proper formation in utero. Occasionally neurons will develop that are larger than normal in certain areas. This causes the signals sent through the neurons in these areas to misfire,...
. 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
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
or recurring seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered by 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.
Preliminary Material: Neurological Development of the Human Fetus
The development of the brain in the human fetusFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
is extraordinarily complex and is still not fully understood. Neural matter originates in the outer, ectoderm
Ectoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
ic 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
Neural tube
In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord...
; the front of this tube develops into the brain (and retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
s of the eye), while the spinal cord develops from the very back end.
Neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s 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
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
. 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
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, 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.
Heterotopia
The complexity of neural development makes it fraught with opportunities for error. Grey matter heterotopia is such an error. It is believed grey matter heterotopia is 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. 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 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 or subependymal
Periventricular means beside the ventricleVentricular system
The ventricular system is a set of structures containing cerebrospinal fluid in the brain. It is continuous with the central canal of the spinal cord.-Components:The system comprises four ventricles:* right and left lateral ventricles* third ventricle...
, while subependymal (also spelled subepydymal) means beneath the ependyma
Ependyma
Ependyma is the thin epithelial membrane lining the ventricular system of the brain and the spinal cord. Ependyma is one of the four types of neuroglia in the central nervous system. It is involved in the production of cerebrospinal fluid ....
; 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.
Subependymal heterotopia present in a wide array of variations. They can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass.
Symptomatic women with subependymal heterotopia typically present with partial epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
during the second decade of life; development and neurologic examinations up to that point are typically normal. Symptoms in men with subependymal heterotopia vary, depending on whether their disease is linked to their X-chromosome. Men with the X-linked form more commonly have associated anomalies, which can be neurological or more widespread, and they usually suffer from developmental problems. Otherwise (i.e., in non-X-linked cases) the symptomology is similar in both genders.
Focal Subcortical
Subcortical heterotopia form as distinct nodes in the white matter, "focal" indicating specific area. In general, patients present fixed neurologic deficits and develop partial epilepsy between the ages of 6 and 10. The more extensive the subcortical heterotopia, the greater the deficit; bilateral heterotopia are almost invariably associated with severe developmental delay or mental retardation. The cortex itself often suffers from an absence of gray matter and may be unusually thin or lack deep sulciSulcus (neuroanatomy)
In neuroanatomy, a sulcus is a depression or fissure in the surface of the brain.It surrounds the gyri, creating the characteristic appearance of the brain in humans and other large mammals....
. Subepedymal heterotopia are frequently accompanied by other structural abnormalities, including an overall decrease in cortical mass. Patients with focal subcortical heterotopia have a variable motor and intellectual disturbance depending on the size and site of the heterotopion.
Band form
Like focal subcortical heterotopia, "band" heterotopia form in the white matter beneath the cortex, but the gray matter is more diffuse and is symmetric between the hemispheres. On imaging, band heterotopia appears as bands of gray matter situated between the lateral ventricle and cerebral cortex and separated from both by a layer of normal appearing white matter. Band heterotopia may be complete, surrounded by simple white matter, or partial. The frontal lobes seem to be more frequently involved when it is partial. Patients with band heterotopia may present at any age with variable developmental delay and seizure disorder, which vary widely in severity.Diagnosis
Detection of heterotopia generally occurs when a patient receives brain imaging -- usually an MRI or CAT scan -- to diagnosis seizures that are resistant to medication. Correct diagnosis requires a high degree of radiological skill, due to the heterotopia's resemblance to other masses in the brain.Treatment
When seizures are present in any forms of cortical dysplasia, they are resistant to medication. Frontal lobe resection provides significant relief from seizures to a minority of patients with periventricular lesions.Causes and Prognosis
In general, gray matter heterotopia is fixed in both its occurrence and symptoms; that is, once symptoms occur, it does not tend to progress. Varying results from surgical resection of the affected area have been reported. Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures.Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol).
External links
- GeneReviews/NCBI/NIH/UW entry on X-Linked Periventricular Heterotopia
- http://www.benbest.com/science/anatmind/anatmd4.html