they work to reduce neuronal excitability, the general themes are
interference with voltage-gated sodium, potassium, and calcium
channels; facilitation of the inhibitory action of GABA; and reduction
of the excitatory action of glutamate. The trick is somehow to blunt
excitability enough so that seizures are prevented but not somuch
that the normal functioning of the brain is impaired—it’s a delicate
balance.
Most people with seizure disorders find that a regular regimen of
one or more of the available antiseizure medications will effectively
control their seizures. It is important to do everything possible to
prevent seizures from occurring, especially the more severe seizures.
First off, severe seizures are life-threatening, either from direct effects
on the brain or from the possibility of a fall or other accident while the
seizure is happening. Next, whenever a seizure occurs, it is likely that
at least some of the underlying neural pathways are reinforced and
strengthened, thereby increasing the risk for the occurrence of subse-
quent seizures. Finally, it is likely that seizures, especially severe ones,
result in death of cells in the brain.
How do seizures cause cell death? It turns out that overexcitation
of neurons by glutamate is known to be quite a toxic phenomenon.
It is called excitotoxicity, glutamatergic excitotoxicity, or excito-
toxic cell death. The exact mechanisms of toxicity remain unclear,
but the general scenario is thought to be something like this:
Overexcitation is associated with activation of many ionotropic
glutamate receptors that allow large amounts of Ca** into the cell.
Calcium ions activate many different enzymes, including proteases
(enzymes that break proteins apart), phospholipases (enzymes
that break phospholipids apart), and endonucleases (enzymes thatbreak DNA apart). The activity of enzymes such as these is very