New insights into epilepsy
About 1% of the adult population are affected by the seizure disorder epilepsy. This happens when a small cluster of nerve cells in a particular part of the brain become electrically unstable. This abnormal firing pattern can periodically spill over into other brain regions and cause the disabling symptoms that patients display. But what causes this so-called epileptic focus to form in the first place, and how that causes the changes in the surrounding brain tissue which eventually result in seizures wasn’t known. Now we have some new insights, which Chris Smith hears about from Carola Haas…
Carola: The approach we used was to mimic the disease in mice. We can inject a toxin and then observe structural changes occurring similar to the situation in human’s, disease progression so cell death and structural reorganisation of the brain network, until the point that seizures emerge. And we used magnetic resonance imaging to study what's going on after injection of the toxin in the mice’s brain. And we could do that for a period of 3 weeks and this gives us information about structural changes but also, molecular and metabolic changes.
Chris: So just to recap then you’ve got young mice. You expose them to a toxin which causes damage to the right part of the brain so that these animals within about 3 weeks develop a clinical syndrome of seizures a bit like what would happen to a human and you're able then to use imaging to follow how that state evolves in these animals, so you can see what changes happen in the brain upstream of the fully-fledged clinical condition occurring so we can get some insights into what might be happening in the brain of a human who is going to develop these sorts of seizures.
Carola: That’s a reasonable summary. But also, what I would like to point out is that we can study this in periods of weeks which is first of all, impossible in humans because it takes many years and we also cannot put humans in the scanner over many years. So, that was our idea that we try to find early indications of later disease progression.
Chris: Now having made these observations, what changes are happening that appears to pre-date the emergence of the epilepsy and could they be used as a useful predictor in humans, do you think?
Carola: First, I would like to say that we found very early changes, so within 24 hours, which reflect the death of neurons and this predicts the severity of the overall structural changes referred to as “sclerosis”. This sclerosis is also something which we find in humans which are epileptic. So the early changes already predict how severe a sclerosis will develop at the end of the disease. Also, neurotransmitters were severely changed – excitatory transmitters and also inhibitory neurotransmission went down. If we look at a little later, we saw that in other areas, because structural changes were occurring in particular cell types which we hadn’t expected before. So, not only neurons were affected, but also glial cells was severely changed in their structure. These changes, they're also important to predict the severity of the disease outcome at the end.
Chris: Are we only able to diagnose people a bit earlier and just tell them, “you're going to get epilepsy” earlier, or does knowing that a person is at risk of this happening from an early stage give us an alternative therapeutic opportunity, if we intervene with the treatments before the person overtly develops the seizures? Because the seizures can make themselves become worse in the long term, does that mean we have an opportunity to potentially reduce their severity or even stop them altogether if we start therapy sooner?
Carola: Exactly. That’s a big outcome of the study that we have hopefully tools that we can test new anti-epileptic substances with, which are not available at the moment because the substances which are available at the moment, they only treat the symptoms but they don’t cure the epilepsy. So, the big hope we have is that we can use our study to find new medication.