pathology of epilepsy

F. Frank LeFever flefever at
Sat Sep 19 10:22:12 EST 1998

I appreciate Matt's elaboration, and his referencer to Kapur &
MacDonald, which I intend to look into: my own special interest is in
long-term consequences of MILD head injury, which raises seizure risk
only very slightly, compared to severe injury.  Interestingly, data
I've seen suggest a dichotomy rather than smooth "dose-response"
progression: i.e., not much difference between "mild" and "moderate" in
this regard, but big difference between them and "severe".  Possibly
just an artifact of classification rules, but maybe---??  Any ideas?

Also appreciate his putting LTP in this context.  MUCH work has gone
into relating LTP to memory, but perhaps this is not such a good model;
better one might be "primed burst" potentiation, which has only
recently come too my attention.  (Ironically, one of my speakers at the
NYNG spring conference, Monika Fleshner, has been involved in studies
of the effect of stress on PBP compared to effect on LTP)

F. Frank LeFever, Ph.D.
New York Neuropsychology Group

In <6tu5gj$8ps$1 at> Matt Jones <jonesmat at>
>In article <6tsmjt$rgh at> F. Frank LeFever,
>flefever at writes:
>>Well....Where to begin?  "Crossing the synapse ineffectively"?  Well,
>>no; one might say TOO effectively--or more to the point, there is an
>>imbalance between excitatory synapses (e.g. NMDA glutaminergic) and
>>inhibitory ones (e.g. GABA).  Crudely, think of a runaway engine with
>>no governor, no brakes, etc.
>I'm no expert, but Mr. LeFever is right. An imbalance between
>(both NMDA and non-NMDA) and GABAergic inhibition within a circuit is
>probably at the root of a lot of seizure disorders. There are a lot of
>ways that such an imbalance might develop. Injury, heredity, fever,
>A lot of the time, "epilepsy" which is a term that describes a
>_tendency_ to experience seizures rather than just having a seizure,
>be traced back to a single seizure event. For example, say a person is
>a car accident and sustains a head injury. That injury might cause a
>seizure (perhaps right then, perhaps later). Since the person doesn't
>have epilepsy at the time, they and their families aren't aware that
>seizure is going to occur, and therefore don't take various
>When the seizure occurs, the person isn't in a hospital, and doesn't
>access to antiepileptic drugs, etc. So this initial seizure may be
>severe and last for a long time (i.e., the person may be in "status
>epilepticus" for tens of minutes before it subsides or can be
>Seizures can result from damage, but more importantly they also cause
>damage themselves. So this initial severe seizure can set up a "chain
>reaction" of biochemical and physiological events that will predispose
>the person to experience further seizures later in life. Some of these
>changes might involve the expression of new neuronal genes that favor
>increased excitability, or the suppression of genes that favor
>(see a recent J. Neuroscience paper by Kapur and Macdonald). Some of
>changes seem to involve an actual outgrowth of excitatory axons, so
>the density of excitatory synapses is greatly increased ("sprouting").
>Why does the brain respond like this to an injury? It would seem that
>rational brain would do exactly the opposite. I suppose its because
>brain didn't really evolve to cope with head trauma, but rather to be
>very flexible, very plastic organ that accomodates itself to make the
>best of new input. In the healthy brain, there are all sorts of
>mechanisms for _increasing_  the strength of excitatory connections in
>response to various events. For example, there's a thing called Long
>Potentiation (LTP), where a strong stimulus causes the excitatory
>synapses to get stronger, and to stay stronger for a really long time.
>There's also a bunch of mechanisms for downregulating inhibition
>strong stimuli (autoinhibition of GABA release via GABA-B receptors,
>postsynaptic GABA-A receptor desensitization, downregulation of GABA
>receptor density, etc.). So the brain appears to be poised and ready
>rev itself up at the drop of a hat. Given that, it's no surprise that
>epilepsy is such an insidious problem.
>Matt Jones
>The Vollum Institute
>Portland, OR

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