|
Epilepsy
is a common childhood neurological condition that is associated with many
developmental disorders. This association can occur when epilepsy is a
consequence of a particular brain disorder, or when seizures early in
life interfere with proper brain development and thus lead to further
problems.
The term epilepsy covers a number of conditions that involve disturbed
electrical rhythms in the brain. This abnormal neuronal activity can cause
strange sensations, emotions, and behavior, or sometimes convulsions,
muscle spasms, and loss of consciousness.
There are many possible causes of epilepsy. Anything that disturbs the
normal pattern of neuron activity (e.g., illness, brain damage, abnormal
brain development) can lead to seizures. A person is considered to have
epilepsy when two or more seizures have occurred. Some cases of epilepsy
do result from genetic errors that lead to abnormal brain development,
but there are multiple genes that could be involved in this way, and also
many non-genetic causes of epilepsy. There is much work that still needs
to be done in defining causes and genetic involvement in the occurrence
of epilepsy.
Further understanding of the disease
The following account
will show that there are several different approaches being taken at Baylor
College of Medicine to understand the nature and causes of epilepsy. These
are important studies, not only because epilepsy is a serious and widespread
disorder in itself, but also because study of the biochemical and molecular
mechanisms of epilepsy may contribute toward an overall understanding
of other disorders of the developing nervous system.
Since epileptic seizures result from electrical abnormalities in the brain,
it is logical to study the channels in the outer membranes of brain cells
that are involved in the passage of positively or negatively charged ions
in or out of the cells. Movement of ions through these channels is associated
with normal electrical signals in the brain, so disruption of this normal
activity could result in seizures. Of particular interest are the channels
that transport positively charged calcium and potassium ions.
Some forms of epilepsy are inherited, and thus caused by only one or a
few gene errors that are passed from parent to child. Detailed study of
mutant mouse strains that are defective in the equivalent genes is useful
in determining what is going on in the human condition. The "stargazer,"
"tottering," "lethargic," and "ducky" strains
of mice are all such examples, being defective in genes involved in the
passage of positively charged calcium ions through the cell membrane.
Investigators at Baylor College of Medicine are examining these mice,
and especially the thalamocortical region of their brains, in order to
develop a greater understanding of the mechanism of the seizure activity.
Epileptic symptoms can be induced in animals by the administration of
kainate. Comparison of these animal models of epilepsy with their unaffected
counterparts provides a useful tool for determining anatomical and biochemical
changes that occur in epilepsy.
One area of study in the kainate model of epilepsy is what is called the
"ERK MAPK signaling cascade," which is a chain reaction of biochemical
signals that occurs in the brain, and which has been shown to regulate
channels responsible for the passage of positively charged potassium ions.
This signaling cascade becomes active in the kainate-induced animal model
of epilepsy, and investigators at Baylor College of Medicine are studying
the effects of that activation.
Another animal model of epilepsy is a strain of mice that lacks the "nor-1"
gene, which normally produces its product in the inner ear, hippocampus
and bone. Mice lacking this gene exhibit an abnormal circling behavior
because of an inner ear defect, and have epileptic seizure activity that
results from abnormal hippocampus development. The role of the nor-1 gene
is being further studied.
Researchers at Baylor College of Medicine have found that infusion into
immature hippocampus of a chemical that interferes with the passage of
positively charged sodium ions disrupts neuronal activity in that area
and results in epilepsy. This new animal model of early-onset epilepsy
is being further studied and may provide important clues in understanding
the origin of seizure disorders in infancy.
As the immature brain is developing, there are periods of increased electric
excitability that occur normally at certain stages in development or at
certain times of day. However, excessive excitability during sleep has
been associated with epilepsies in young children. Investigators at Baylor
College of Medicine are studying the regulation of potassium ion channels
in the immature hippocampus, and other processes in this area of the brain
that may be involved in normal and abnormal development.
There is evidence that seizures occurring early in life alter the normal
development of the brain. Indeed, numerous observations suggest that recurrent
seizures in childhood lead to life-long epilepsy that is not easily managed.
An understanding of this process could lead to therapies that would prevent
the development of long-term epilepsy. Other consequences of recurrent
seizures in early life that are currently being investigated at Baylor
College of Medicine include learning deficits and other psycho-social
problems.
Our research also includes investigation of brain anatomy, development,
and function. Defects in the formation of brain synapses (places where
an impulse signal passes from one nerve cell to another), and the ability
of synapses to form new connections, are thought to be at the heart of
many brain development disorders, including epilepsy. Further information
as to what happens in normal and abnormal development could be valuable
for understanding medical conditions and developing treatment strategies.
Work towards therapy
The ongoing research at Baylor College of Medicine into the causes
and mechanisms of epileptic symptoms can potentially lead to information
that is valuable in the development of therapies. The various
genetic and drug-induced animal models of epilepsy that are in
use can be used to test those therapeutic strategies.
Baylor investigators
working on epilepsy:
Baylor MRDDRC projects associated with epilepsy:
Organizations:
Disease information:
Online directory listings:
|