The brain has its own thermostat – study shows epilepsy may interfere with it

David Henshall, Annamaria Vezzani, Rossella Di Sapia, RCSI University of Medicine and Health Sciences

Doctors have long known that changes in body temperature can affect seizure activity. Fever can trigger seizures in some young children, while in rare forms of epilepsy, bathing in hot water can bring on a seizure. Raised body temperature can also trigger seizures in Dravet syndrome, a rare form of epilepsy that usually begins in infancy and is particularly sensitive to fever and overheating.

Temperature may also move in the other direction. Earlier animal studies found that epilepsy can alter daily temperature rhythms and affect nerve cells in the hypothalamus, the part of the brain that helps regulate body temperature.

In our new research, our team, based in Italy, Ireland, the UK and the Netherlands, investigated how early these changes begin, what might be happening in the brain’s temperature-control centres and whether similar changes can be seen in people with epilepsy.

The brain has its own thermostat. The brain is metabolically active and can be slightly warmer than the rest of the body, although the difference varies between brain regions and over the course of the day. Deep in the brain, the hypothalamus coordinates many of the body’s responses to heat and cold. Different parts of the hypothalamus help balance heat loss and heat production to keep temperature within a narrow range.

Using mice in which we had induced a condition resembling temporal lobe epilepsy in humans, we combined specialised MRI measurements of temperature in the hippocampus with continuous recordings of body temperature and electrical activity in the brain. Temporal lobe epilepsy is a common form of the condition that begins in the temporal lobe.

Temperature changes begin early

We found that temperature in the hippocampus was already higher three days after the initial brain injury used to produce epilepsy in the mice. Crucially, this happened before the first seizures appeared. The higher temperature then persisted after epilepsy was established.

That timing suggests the change cannot simply be explained by the heat generated by repeated seizures. We also found that body temperature rose around individual seizures, with the increase beginning before the seizure itself.

These observations show that temperature and seizure activity are closely linked, but they cannot tell us what is causing what. Rising temperature might make a seizure more likely, developing seizure activity might itself raise temperature, or both could reflect changes in the same brain networks.

When we examined the hypothalamus in mice with epilepsy, we found fewer nerve cells in two regions involved in temperature regulation. The reduction was roughly one-fifth when compared with mice without epilepsy. We also saw inflammation, altered activity in surviving cells and reduced volume in part of the hypothalamus.

We then looked for related changes in people. In brain scans from hundreds of people with epilepsy, corresponding parts of the hypothalamus were smaller than in people without the condition. The differences were most marked in people whose epilepsy was associated with visible damage or other changes in the brain.

The human scans cannot show whether the same cell loss or inflammation seen in mice is present in people, and smaller brain regions do not by themselves prove that temperature regulation is impaired. But finding changes in similar regions in mice and people gives us a reason to investigate the connection further.

We also found changes in thyroid hormones in the mice. The pattern suggested disruption somewhere along the chain of hormonal signals running from the brain to the thyroid gland, rather than allowing us to pinpoint the problem in one particular part of the system.

Taken together, the findings raise the possibility that epilepsy that develops after injury or other changes in the brain can affect some of the networks involved in keeping temperature stable. They do not yet show that disrupted temperature control causes seizures, or that seizures progressively damage these brain regions.

What could this mean in hotter weather?

Our study did not expose people with epilepsy to extreme heat or test whether hot weather increases their seizure risk. So it cannot tell us whether people with epilepsy as a group are less able to cope with heat.

There are, however, reasons to investigate the question. In a small 2024 London study, researchers compared brain recordings from nine people with drug-resistant epilepsy during heatwaves and cooler periods. During heatwaves, three participants had significantly more abnormal electrical discharges between seizures. Five had more seizures, and seizure numbers were higher across the group overall. Other research has also reported associations between environmental heat and epilepsy-related outcomes, although the evidence is still limited.

Our results offer one possible explanation to test. If the brain’s temperature-control system is altered in some forms of epilepsy, hot weather could potentially make seizures more likely in people whose ability to regulate temperature is already affected. That has not yet been shown.

By looking at which genes were more or less active in the affected brain regions, we also found changes involving inflammation and tissue repair. We then used computer analysis to identify existing medicines that might act on some of those biological processes. These are only leads for future research. They now need to be tested in experiments before we know whether they could affect seizures or temperature control.

For now, the findings suggest that changes in temperature regulation may be an overlooked feature of epilepsy.. The next step is to find out whether the changes seen in the brain affect how people with epilepsy regulate temperature and respond to heat. With climate change increasing concern about the effects of extreme temperatures on people with conditions affecting the brain and nervous system, that is an increasingly important question to answer.

This article is republished from The Conversation under a Creative Commons license. Read the original article.